MRI patterns in prolonged low response states following traumatic brain injury in children and adolescents.

Science.gov (United States)

Patrick, Peter D; Mabry, Jennifer L; Gurka, Matthew J; Buck, Marcia L; Boatwright, Evelyn; Blackman, James A

2007-01-01

To explore the relationship between location and pattern of brain injury identified on MRI and prolonged low response state in children post-traumatic brain injury (TBI). This observational study compared 15 children who spontaneously recovered within 30 days post-TBI to 17 who remained in a prolonged low response state. 92.9% of children with brain stem injury were in the low response group. The predicted probability was 0.81 for brain stem injury alone, increasing to 0.95 with a regional pattern of injury to the brain stem, basal ganglia, and thalamus. Low response state in children post-TBI is strongly correlated with two distinctive regions of injury: the brain stem alone, and an injury pattern to the brain stem, basal ganglia, and thalamus. This study demonstrates the need for large-scale clinical studies using MRI as a tool for outcome assessment in children and adolescents following severe TBI.

Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.

Science.gov (United States)

Dolinay, Tamas; Himes, Blanca E; Shumyatcher, Maya; Lawrence, Gladys Gray; Margulies, Susan S

2017-08-01

Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a modest benefit in preventing VILI because they cannot impede alveolar overdistension and concomitant epithelial barrier dysfunction in the inflamed lung regions. There are currently no effective biochemical therapies to mitigate injury to the alveolar epithelium. We hypothesize that alveolar stretch activates the integrated stress response (ISR) pathway and that the chemical inhibition of this pathway mitigates alveolar barrier disruption during stretch and mechanical ventilation. Using our established rat primary type I-like alveolar epithelial cell monolayer stretch model and in vivo rat mechanical ventilation that mimics the alveolar overdistension seen in acute respiratory distress syndrome, we studied epithelial responses to mechanical stress. Our studies revealed that the ISR signaling pathway is a key modulator of epithelial permeability. We show that prolonged epithelial stretch and injurious mechanical ventilation activate the ISR, leading to increased alveolar permeability, cell death, and proinflammatory signaling. Chemical inhibition of protein kinase RNA-like endoplasmic reticulum kinase, an upstream regulator of the pathway, resulted in decreased injury signaling and improved barrier function after prolonged cyclic stretch and injurious mechanical ventilation. Our results provide new evidence that therapeutic targeting of the ISR can mitigate VILI.

Wallerian degeneration: the innate-immune response to traumatic nerve injury

Directory of Open Access Journals (Sweden)

Rotshenker Shlomo

2011-08-01

Full Text Available Abstract Traumatic injury to peripheral nerves results in the loss of neural functions. Recovery by regeneration depends on the cellular and molecular events of Wallerian degeneration that injury induces distal to the lesion site, the domain through which severed axons regenerate back to their target tissues. Innate-immunity is central to Wallerian degeneration since innate-immune cells, functions and molecules that are produced by immune and non-immune cells are involved. The innate-immune response helps to turn the peripheral nerve tissue into an environment that supports regeneration by removing inhibitory myelin and by upregulating neurotrophic properties. The characteristics of an efficient innate-immune response are rapid onset and conclusion, and the orchestrated interplay between Schwann cells, fibroblasts, macrophages, endothelial cells, and molecules they produce. Wallerian degeneration serves as a prelude for successful repair when these requirements are met. In contrast, functional recovery is poor when injury fails to produce the efficient innate-immune response of Wallerian degeneration.

The synthetic NCAM-derived peptide, FGL, modulates the transcriptional response to traumatic brain injury

DEFF Research Database (Denmark)

Pedersen, Martin Volmer; Helweg-Larsen, Rehannah Borup; Nielsen, Finn Cilius

2008-01-01

Cerebral responses to traumatic brain injury (TBI) include up- and downregulation of a vast number of proteins involved in endogenous inflammatory responses and defense mechanisms developing postinjury. The present study analyzed the global gene expression profile in response to cryo-induced TBI...... at various time-points postlesion (6 h, 1 day and 4 days). The effects of injury, treatment, and injury-treatment interaction were observed. TBI alone rendered a large number of genes affected. Analysis of lesion and treatment interactions resulted in a clear effect of the interaction between injury and FGL......-treatment compared to injury and placebo-treatment. Genes affected by TBI alone included inflammation markers, protein kinases, ion channel members and growth factors. Genes encoding regulators of apoptosis, signal transduction and metabolism were altered by the interaction between FGL-treatment and TBI. FGL...

Clinically Relevant Levels of 4-Aminopyridine Strengthen Physiological Responses in Intact Motor Circuits in Rats, Especially After Pyramidal Tract Injury.

Science.gov (United States)

Sindhurakar, Anil; Mishra, Asht M; Gupta, Disha; Iaci, Jennifer F; Parry, Tom J; Carmel, Jason B

2017-04-01

4-Aminopyridine (4-AP) is a Food and Drug Administration-approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. To determine if 4-AP at clinically relevant levels alters the excitability of intact motor circuits. In anesthetized rats, electrodes were placed over motor cortex and the dorsal cervical spinal cord for electrical stimulation, and electromyogram electrodes were inserted into biceps muscle to measure responses. The motor responses to brain and spinal cord stimulation were measured before and for 5 hours after 4-AP administration both in uninjured rats and rats with a cut lesion of the pyramidal tract. Blood was collected at the same time as electrophysiology to determine drug plasma concentration with a goal of 20 to 100 ng/mL. We first determined that a bolus infusion of 0.32 mg/kg 4-AP was optimal: it produced on average 61.5 ± 1.8 ng/mL over the 5 hours after infusion. This dose of 4-AP increased responses to spinal cord stimulation by 1.3-fold in uninjured rats and 3-fold in rats with pyramidal tract lesion. Responses to cortical stimulation also increased by 2-fold in uninjured rats and up to 4-fold in the injured. Clinically relevant levels of 4-AP strongly augment physiological responses in intact circuits, an effect that was more robust after partial injury, demonstrating its broad potential in treating central nervous system injuries.

Brain injury and discrimination: Two competing models-perceptions of responsibility and dangerousness.

Science.gov (United States)

Foster, Lynette A; Leathem, Janet M; Humphries, Steve

2016-01-01

(1) To examine whether the willingness of people to socialize with adolescents with brain injury is influenced by gender, visibility of injury and/or knowing how to interact with people with brain injury; and (2) To consider two models: the responsibility model (attributions about the cause of a condition) and the danger appraisal model (perceptions of dangerousness due to anger/aggression) for their effect on willingness to socialize and to understand how these perceptions lead to avoidant behaviour. Participants were recruited either by personal approach or via Facebook advertising and completed a survey after reading a brief vignette and seeing a photo of an adolescent male or female, with or without a head scar. Vignettes for some participants were varied to represent perceptions of responsibility and dangerousness Main outcomes and results: ANOVAs and structural equation modelling revealed that participants were more willing to socialize with the adolescents with a scar than with no scar. Knowledge about how to interact with survivors impacted willingness to socialize, but familiarity did not. The full danger appraisal model was supported, but only some aspects of the responsibility model were supported. The results provide useful information for rehabilitation health professionals working with survivors of brain injury. The implications of these findings are discussed with regards to assisting adolescents' re-entry into society post-injury.

Retinal ganglion cell survival and axon regeneration after optic nerve injury in naked mole-rats.

Science.gov (United States)

Park, Kevin K; Luo, Xueting; Mooney, Skyler J; Yungher, Benjamin J; Belin, Stephane; Wang, Chen; Holmes, Melissa M; He, Zhigang

2017-02-01

In the adult mammalian central nervous system (CNS), axonal damage often triggers neuronal cell death and glial activation, with very limited spontaneous axon regeneration. In this study, we performed optic nerve injury in adult naked mole-rats, the longest living rodent, with a maximum life span exceeding 30 years, and found that injury responses in this species are quite distinct from those in other mammalian species. In contrast to what is seen in other mammals, the majority of injured retinal ganglion cells (RGCs) survive with relatively high spontaneous axon regeneration. Furthermore, injured RGCs display activated signal transducer and activator of transcription-3 (STAT3), whereas astrocytes in the optic nerve robustly occupy and fill the lesion area days after injury. These neuron-intrinsic and -extrinsic injury responses are reminiscent of those in "cold-blooded" animals, such as fish and amphibians, suggesting that the naked mole-rat is a powerful model for exploring the mechanisms of neuronal injury responses and axon regeneration in mammals. J. Comp. Neurol. 525:380-388, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Smooth Muscle Specific Overexpression of p22phox Potentiates Carotid Artery Wall Thickening in Response to Injury

Directory of Open Access Journals (Sweden)

Michael R. Manogue

2015-01-01

Full Text Available We hypothesized that transgenic mice overexpressing the p22phox subunit of the NADPH oxidase selectively in smooth muscle (Tgp22smc would exhibit an exacerbated response to transluminal carotid injury compared to wild-type mice. To examine the role of reactive oxygen species (ROS as a mediator of vascular injury, the injury response was quantified by measuring wall thickness (WT and cross-sectional wall area (CSWA of the injured and noninjured arteries in both Tgp22smc and wild-type animals at days 3, 7, and 14 after injury. Akt, p38 MAPK, and Src activation were evaluated at the same time points using Western blotting. WT and CSWA following injury were significantly greater in Tgp22smc mice at both 7 and 14 days after injury while noninjured contralateral carotids were similar between groups. Apocynin treatment attenuated the injury response in both groups and rendered the response similar between Tgp22smc mice and wild-type mice. Following injury, carotid arteries from Tgp22smc mice demonstrated elevated activation of Akt at day 3, while p38 MAPK and Src activation was elevated at day 7 compared to wild-type mice. Both increased activation and temporal regulation of these signaling pathways may contribute to enhanced vascular growth in response to injury in this transgenic model of elevated vascular ROS.

Role of contact inhibition of locomotion and junctional mechanics in epithelial collective responses to injury

Science.gov (United States)

Coburn, Luke; Lopez, Hender; Schouwenaar, Irin-Maya; Yap, Alpha S.; Lobaskin, Vladimir; Gomez, Guillermo A.

2018-03-01

Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond to injuries by reorganizing their cell-cell junctions and migrating directionally towards the sites of damage. Notwithstanding, the mechanisms that drive collective responses in epithelial aggregates remain poorly understood. In this work, we develop a minimal mechanistic model that is able to capture the essential features of epithelial collective responses to injuries. We show that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interfaces as well as contact inhibition of locomotion (CIL) correctly predicts two key properties of epithelial response to injury as: (1) local relaxation of the tissue and (2) collective reorganization involving the extension of cryptic lamellipodia that extend, on average, up to 3 cell diameters from the site of injury and morphometric changes in the basal regions. Our model also suggests that active responses (like the actomyosin purse string and softening of cell-cell junctions) are needed to drive morphometric changes in the apical region. Therefore, our results highlight the importance of the crosstalk between junctional biomechanics, cell substrate adhesion, and CIL, as well as active responses, in guiding the collective rearrangements that are required to preserve the epithelial barrier in response to injury.

Dynamics robustness of cascading systems.

Directory of Open Access Journals (Sweden)

Jonathan T Young

2017-03-01

Full Text Available A most important property of biochemical systems is robustness. Static robustness, e.g., homeostasis, is the insensitivity of a state against perturbations, whereas dynamics robustness, e.g., homeorhesis, is the insensitivity of a dynamic process. In contrast to the extensively studied static robustness, dynamics robustness, i.e., how a system creates an invariant temporal profile against perturbations, is little explored despite transient dynamics being crucial for cellular fates and are reported to be robust experimentally. For example, the duration of a stimulus elicits different phenotypic responses, and signaling networks process and encode temporal information. Hence, robustness in time courses will be necessary for functional biochemical networks. Based on dynamical systems theory, we uncovered a general mechanism to achieve dynamics robustness. Using a three-stage linear signaling cascade as an example, we found that the temporal profiles and response duration post-stimulus is robust to perturbations against certain parameters. Then analyzing the linearized model, we elucidated the criteria of when signaling cascades will display dynamics robustness. We found that changes in the upstream modules are masked in the cascade, and that the response duration is mainly controlled by the rate-limiting module and organization of the cascade's kinetics. Specifically, we found two necessary conditions for dynamics robustness in signaling cascades: 1 Constraint on the rate-limiting process: The phosphatase activity in the perturbed module is not the slowest. 2 Constraints on the initial conditions: The kinase activity needs to be fast enough such that each module is saturated even with fast phosphatase activity and upstream changes are attenuated. We discussed the relevance of such robustness to several biological examples and the validity of the above conditions therein. Given the applicability of dynamics robustness to a variety of systems, it

Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

Directory of Open Access Journals (Sweden)

Nathalie Le Clef

Full Text Available Acute kidney injury (AKI is an underestimated, yet important risk factor for development of chronic kidney disease (CKD. Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD. Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

Neural Responses to Injury: Prevention, Protection and Repair; Volume 7: Role Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury

National Research Council Canada - National Science Library

Bazan, Nicolas

1996-01-01

...: Prevention, Protection, and Repair, Subproject: Role of Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury, are as follows: Species Rat(Albino Wistar), Number Allowed...

Epigenetic modulation of gene expression governs the brain's response to injury.

Science.gov (United States)

Simon, Roger P

2016-06-20

Mild stress from ischemia, seizure, hypothermia, or infection can produce a transient neuroprotected state in the brain. In the neuroprotected state, the brain responds differently to a severe stress and sustains less injury. At the genomic level, the response of the neuroprotected brain to a severe stress is characterized by widespread differential regulation of genes with diverse functions. This reprogramming of gene expression observed in the neuroprotected brain in response to a stress is consistent with an epigenetic model of regulation mediated by changes in DNA methylation and histone modification. Here, we summarize our evolving understanding of the molecular basis for endogenous neuroprotection and review recent findings that implicate DNA methylation and protein mediators of histone modification as epigenetic regulators of the brain's response to injury. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mesenchymal stem cells induce dermal fibroblast responses to injury

International Nuclear Information System (INIS)

Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

2010-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.

MW151 Inhibited IL-1β Levels after Traumatic Brain Injury with No Effect on Microglia Physiological Responses.

Directory of Open Access Journals (Sweden)

Adam D Bachstetter

Full Text Available A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI. In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS-penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a closed head injury model of mild TBI suppressed acute cytokine up-regulation and downstream cognitive impairment. Here, we report results from a diffuse brain injury model in mice using midline fluid percussion. Low dose (0.5-5.0 mg/kg administration of MW151 suppresses interleukin-1 beta (IL-1β levels in the cortex while sparing reactive microglia and astrocyte responses. To probe molecular mechanisms, we used live cell imaging of the BV-2 microglia cell line to demonstrate that MW151 does not affect proliferation, migration, or phagocytosis of the cells. Our results provide insight into the roles of glial responses to brain injury and indicate the feasibility of using appropriate dosing for selective therapeutic modulation of injurious IL-1β increases while sparing other glial responses to injury.

Impact and injury response of long track speed skaters

NARCIS (Netherlands)

Forbes, P.A.; Swartjes, F.H.M.; Ruimerman, R.; Willems, J.W.M.

2009-01-01

The following study presents a combined numerical-experimental investigation into the impact and injury response of long track speed skaters when impacting the protective boarding around the track. The high speeds common within the sport combined with the inherent slipperiness of the ice create a

Sphere-forming cells from peripheral cornea demonstrate a wound-healing response to injury.

Science.gov (United States)

Huang, Stephanie U; Yoon, Jinny J; Ismail, Salim; McGhee, Jennifer J; Sherwin, Trevor

2015-11-01

The cornea is the initial refractive interface of the eye. Its transparency is critical for clear vision and is maintained by stem cells which also act to repair injury inflicted by external insults, such as chemical and thermal burns. Damage to the epithelium compromises its clarity and can reduce or eliminate the stem cell population, diminishing the ability for self-repair. This condition has been termed "limbal stem cell deficiency"; severe cases can lead to corneal blindness. Sphere-forming cells isolated from peripheral cornea are a potential source of stem and progenitor cells for corneal repair. When provided with appropriate substrate, these spheres have the ability to adhere and for cells to migrate outwards akin to that of their natural environment. Direct compression injury and remote scratch injury experiments were conducted on the sphere cells to gauge their wound healing capacity. Measures of proliferation, differentiation, and migration were assessed by immunohistochemical detection of EdU incorporation, α-smooth muscle actin expression and confocal image analysis, respectively. Both modes of injury were observed to draw responses from the spheres indicating wound healing processes. Direct wounding induced a rapid, but transient increase in expression of α-SMA, a marker of corneal myofibroblasts, followed by a proliferative and increasing migratory response. The spheres were observed to respond to remote injury as entire units, with no directional response seen for targeted repair over the scratch injury area. These results give strength to the future use of these peripheral corneal spheres as transplantable units for the regeneration of corneal tissue. © 2015 International Federation for Cell Biology.

Isoliquiritigenin protects against sepsis-induced lung and liver injury by reducing inflammatory responses.

Science.gov (United States)

Chen, Xiong; Cai, Xueding; Le, Rongrong; Zhang, Man; Gu, Xuemei; Shen, Feixia; Hong, Guangliang; Chen, Zimiao

2018-02-05

Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries. Copyright © 2017. Published by Elsevier Inc.

Determining the Most Robust Dimensional Structure of Categories from the International Classification of Functioning, Disability and Health Across Subgroups of Persons With Spinal Cord Injury to Build the Basis for Future Clinical Measures

DEFF Research Database (Denmark)

Ballert, Carolina S; Stucki, Gerold; Biering-Sørensen, Fin

2014-01-01

OBJECTIVE: To determine the most robust dimensional structure of the International Classification of Functioning, Disability and Health (ICF) categories relevant to spinal cord injury (SCI) across subgroups of lesion level, health care context, sex, age, and resources of the country. DESIGN......: A multidimensional between-item response Rasch model was used. The choice of the dimensions was conceptually driven using the ICF components from the functioning chapters and splits of the activity and participation component described in the ICF. SETTING: Secondary analysis of data from an international, cross....... The model fit improvement from the unidimensional to the 2-dimensional and from the 2-dimensional to the 3-dimensional model was significant in all groups (P

Differential effects of voluntary and forced exercise on stress responses after traumatic brain injury.

Science.gov (United States)

Griesbach, Grace S; Tio, Delia L; Vincelli, Jennifer; McArthur, David L; Taylor, Anna N

2012-05-01

Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. Moreover, recent work from our laboratory showed that there is a heightened stress response after fluid percussion injury (FPI). In order to determine if a heightened stress response is also observed with acute exercise, at post-injury days 0-4 and 7-11, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) release were measured in rats running voluntarily or exposed to two daily 20-min periods of forced running wheel exercise. Forced, but not voluntary exercise, continuously elevated CORT. ACTH levels were initially elevated with forced exercise, but decreased by post-injury day 7 in the control, but not the FPI animals. As previously reported, voluntary exercise did not increase BDNF in the FPI group as it did in the control animals. Forced exercise did not increase levels of BDNF in any group. It did, however, decrease hippocampal glucocorticoid receptors in the control group. The results suggest that exercise regimens with strong stress responses may not be beneficial during the early post-injury period.

Heterogeneity of existing research relating to sexual violence, sexual assault and rape precludes meta-analysis of injury data.

LENUS (Irish Health Repository)

Kennedy, Kieran M

2013-07-01

In order for medical practitioners to adequately explain to the court the findings of their clinical examinations of victims of sexual violence, they must have access to research data which will place their findings in to context. Unfortunately, existing research has reported a very wide range of injury prevalence data. This papers aims to provide an explanation for this wide variation in results and, furthermore, this paper aims to establish if it is possible to carry out a meta-analysis of existing research data, pertaining to the prevalence of injury after sexual assault. It is suggested that pooling of individual study results may allow statistically robust determination of the true prevalence of injury in victims of sexual violence. It is concluded that heterogeneity in research methodology, between existing research studies, is responsible for the broad range of reported prevalence rates. Finally, this heterogeneity is seen to preclude robust meta-analysis.

The optimization model for multi-type customers assisting wind power consumptive considering uncertainty and demand response based on robust stochastic theory

International Nuclear Information System (INIS)

Tan, Zhongfu; Ju, Liwei; Reed, Brent; Rao, Rao; Peng, Daoxin; Li, Huanhuan; Pan, Ge

2015-01-01

Highlights: • Our research focuses on demand response behaviors of multi-type customers. • A wind power simulation method is proposed based on the Brownian motion theory. • Demand response revenue functions are proposed for multi-type customers. • A robust stochastic optimization model is proposed for wind power consumptive. • Models are built to measure the impacts of demand response on wind power consumptive. - Abstract: In order to relieve the influence of wind power uncertainty on power system operation, demand response and robust stochastic theory are introduced to build a stochastic scheduling optimization model. Firstly, this paper presents a simulation method for wind power considering external environment based on Brownian motion theory. Secondly, price-based demand response and incentive-based demand response are introduced to build demand response model. Thirdly, the paper constructs the demand response revenue functions for electric vehicle customers, business customers, industry customers and residential customers. Furthermore, robust stochastic optimization theory is introduced to build a wind power consumption stochastic optimization model. Finally, simulation analysis is taken in the IEEE 36 nodes 10 units system connected with 650 MW wind farms. The results show the robust stochastic optimization theory is better to overcome wind power uncertainty. Demand response can improve system wind power consumption capability. Besides, price-based demand response could transform customers’ load demand distribution, but its load curtailment capacity is not as obvious as incentive-based demand response. Since price-based demand response cannot transfer customer’s load demand as the same as incentive-based demand response, the comprehensive optimization effect will reach best when incentive-based demand response and price-based demand response are both introduced.

Attention to affective pictures in closed head injury: event-related brain potentials and cardiac responses.

Science.gov (United States)

Solbakk, Anne-Kristin; Reinvang, Ivar; Svebak, Sven; Nielsen, Christopher S; Sundet, Kjetil

2005-02-01

We examined whether closed head injury patients show altered patterns of selective attention to stimulus categories that naturally evoke differential responses in healthy people. Self-reported rating and electrophysiological (event-related potentials [ERPs], heart rate [HR]) responses to affective pictures were studied in patients with mild head injury (n = 20; CT/MRI negative), in patients with predominantly frontal brain lesions (n = 12; CT/MRI confirmed), and in healthy controls (n = 20). Affective valence similarly modulated HR and ERP responses in all groups, but group differences occurred that were independent of picture valence. The attenuation of P3-slow wave amplitudes in the mild head injury group indicates a reduction in the engagement of attentional resources to the task. In contrast, the general enhancement of ERP amplitudes at occipital sites in the group with primarily frontal brain injury may reflect disinhibition of input at sensory receptive areas, possibly due to a deficit in top-down modulation performed by anterior control systems.

Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury

Directory of Open Access Journals (Sweden)

Popovich Phillip G

2011-08-01

Full Text Available Abstract In this review, we first provide a brief historical perspective, discussing how peripheral nerve injury (PNI may have caused World War I. We then consider the initiation, progression, and resolution of the cellular inflammatory response after PNI, before comparing the PNI inflammatory response with that induced by spinal cord injury (SCI. In contrast with central nervous system (CNS axons, those in the periphery have the remarkable ability to regenerate after injury. Nevertheless, peripheral nervous system (PNS axon regrowth is hampered by nerve gaps created by injury. In addition, the growth-supportive milieu of PNS axons is not sustained over time, precluding long-distance regeneration. Therefore, studying PNI could be instructive for both improving PNS regeneration and recovery after CNS injury. In addition to requiring a robust regenerative response from the injured neuron itself, successful axon regeneration is dependent on the coordinated efforts of non-neuronal cells which release extracellular matrix molecules, cytokines, and growth factors that support axon regrowth. The inflammatory response is initiated by axonal disintegration in the distal nerve stump: this causes blood-nerve barrier permeabilization and activates nearby Schwann cells and resident macrophages via receptors sensitive to tissue damage. Denervated Schwann cells respond to injury by shedding myelin, proliferating, phagocytosing debris, and releasing cytokines that recruit blood-borne monocytes/macrophages. Macrophages take over the bulk of phagocytosis within days of PNI, before exiting the nerve by the circulation once remyelination has occurred. The efficacy of the PNS inflammatory response (although transient stands in stark contrast with that of the CNS, where the response of nearby cells is associated with inhibitory scar formation, quiescence, and degeneration/apoptosis. Rather than efficiently removing debris before resolving the inflammatory response as

Three-dimensional dose-response models of risk for radiation injury carcinogenesis

International Nuclear Information System (INIS)

Raabe, O.G.

1988-01-01

The use of computer graphics in conjunction with three-dimensional models of dose-response relationships for chronic exposure to ionizing radiation dramaticly clarifies the separate and interactive roles of competing risks. The three dimensions are average dose rate, exposure time, and risk. As an example, the functionally injurious and carcinogenic responses after systemic uptake of Ra-226 by beagles, mice and people with consequent alpha particle irradiation of the bone are represented by three-dimensional dose-rate/time/response surfaces that demonstrate the contributions with the passage of time of the competing deleterious responses. These relationships are further evaluated by mathematical stripping with three-dimensional illustrations that graphically show the resultant separate contribution of each effect. Radiation bone injury predominates at high dose rates and bone cancer at intermediate dose rates. Low dose rates result in spontaneous deaths from natural aging, yielding a type of practical threshold for bone cancer induction. Risk assessment is benefited by the insights that become apparent with these three-dimensional models. The improved conceptualization afforded by them contributes to planning and evaluating epidemiological analyses and experimental studies

Epigenetic modulation of gene expression governs the brain’s response to injury

Science.gov (United States)

Simon, Roger P.

2016-01-01

Mild stress from ischemia, seizure, hypothermia, or infection can produce a transient neuroprotected state in the brain. In the neuroprotected state, the brain responds differently to a severe stress and sustains less injury. At the genomic level, the response of the neuroprotected brain to a severe stress is characterized by widespread differential regulation of genes with diverse functions. This reprogramming of gene expression observed in the neuroprotected brain in response to a stress is consistent with an epigenetic model of regulation mediated by changes in DNA methylation and histone modification. Here, we summarize our evolving understanding of the molecular basis for endogenous neuroprotection and review recent findings that implicate DNA methylation and protein mediators of histone modification as epigenetic regulators of the brain’s response to injury. PMID:26739198

Kinematic responses and injuries of pedestrian in car-pedestrian collisions

Science.gov (United States)

Teng, T. L.; Liang, C. C.; Hsu, C. Y.; Tai, S. F.

2017-10-01

How to protect pedestrians and reduce the collision injury has gradually become the new field of automotive safety research and focus in the world. Many engineering studies have appeared and their purpose is trying to reduce the pedestrian injuries caused by traffic accident. The physical model involving impactor model and full scale pedestrian model are costly when taking the impact test. This study constructs a vehicle-pedestrian collision model by using the MADYMO. To verify the accuracy of the proposed vehicle-pedestrian collision model, the experimental data are used in the pedestrian model test. The proposed model also will be applied to analyze the kinematic responses and injuries of pedestrian in collisions in this study. The modeled results can help assess the pedestrian friendliness of vehicles and assist in the future development of pedestrian friendliness vehicle technologies.

Pre-injury beta blocker use does not affect the hyperdynamic response in older trauma patients

Directory of Open Access Journals (Sweden)

David C Evans

2014-01-01

Full Text Available Purpose: Trauma dogma dictates that the physiologic response to injury is blunted by beta-blockers and other cardiac medications. We sought to determine how the pre-injury cardiac medication profile influences admission physiology and post-injury outcomes. Materials and Methods: Trauma patients older than 45 evaluated at our center were retrospectively studied. Pre-injury medication profiles were evaluated for angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACE-I/ARB, beta-blockers, calcium channel blockers, amiodarone, or a combination of the above mentioned agents. Multivariable logistic regression or linear regression analyses were used to identify relationships between pre-injury medications, vital signs on presentation, post-injury complications, length of hospital stay, and mortality. Results: Records of 645 patients were reviewed (mean age 62.9 years, Injury Severity Score >10, 23%. Our analysis demonstrated no effect on systolic and diastolic blood pressures from beta-blocker, ACE-I/ARB, calcium channel blocker, and amiodarone use. The triple therapy (combined beta-blocker, calcium channel blocker, and ACE-I/ARB patient group had significantly lower heart rate than the no cardiac medication group. No other groups were statistically different for heart rate, systolic, and diastolic blood pressure. Conclusions: Pre-injury use of cardiac medication lowered heart rate in the triple-agent group (beta-blocker, calcium channel blocker, and ACEi/ARB when compared the no cardiac medication group. While most combinations of cardiac medications do not blunt the hyperdynamic response in trauma cases, patients on combined beta-blocker, calcium channel blocker, and ACE-I/ARB therapy had higher mortality and more in-hospital complications despite only mild attenuation of the hyperdynamic response.

Differential Effects of Voluntary and Forced Exercise on Stress Responses after Traumatic Brain Injury

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Griesbach, Grace S.; Tio, Delia L.; Vincelli, Jennifer; McArthur, David L.; Taylor, Anna N.

2012-01-01

Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. Moreover, recent work from our laboratory showed that there is a heightened stress response after fluid percussion injury (FPI). In order to determine if a heightened stress response is also observed ...

Sirtuin 1 Agonist Minimizes Injury and Improves the Immune Response Following Traumatic Shock.

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Luciano, Jason A; Kautza, Benjamin; Darwiche, Sophie; Martinez, Silvia; Stratimirovic, Sladjana; Waltz, Paul; Sperry, Jason; Rosengart, Matthew; Shiva, Sruti; Zuckerbraun, Brian S

2015-08-01

Survival from traumatic injury requires a coordinated and controlled inflammatory and immune response. Mitochondrial and metabolic responses to stress have been shown to play a role in these inflammatory and immune responses. We hypothesized that increases in mitochondrial biogenesis via a sirtuin 1 agonist would decrease tissue injury and partially ameliorate the immunosuppression seen following trauma. C57Bl/6 mice were subjected to a multiple trauma model. Mice were pretreated with either 100 mg/kg per day of the sirtuin 1 agonist, Srt1720, via oral gavage for 2 days prior to trauma and extended until the day the animals were killed, or they were pretreated with peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) siRNA via hydrodynamic tail vein injection 48 h prior to trauma. Markers for mitochondrial function and biogenesis were measured in addition to splenocyte proliferative capacity and bacterial clearance. Srt1720 was noted to improve mitochondrial biogenesis, mitochondrial function, and complex IV activity following traumatic injury (P hepatic injury with significant reductions in serum alanine aminotransferase levels seen in mice treated with srt1720. Splenocyte proliferative capacity and intraperitoneal bacterial clearance were evaluated as markers for overall immune function following trauma-hemorrhage. Treatment with Srt1720 minimized the trauma-induced decreases in splenocyte proliferation (P clearance. The PGC1α signaling pathway is an important regulator of mitochondrial function and biogenesis, which can potentially be harnessed to protect against hepatic injury and minimize the immunosuppression that is seen following trauma-hemorrhage.

Robustness Beamforming Algorithms

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Sajad Dehghani

2014-04-01

Full Text Available Adaptive beamforming methods are known to degrade in the presence of steering vector and covariance matrix uncertinity. In this paper, a new approach is presented to robust adaptive minimum variance distortionless response beamforming make robust against both uncertainties in steering vector and covariance matrix. This method minimize a optimization problem that contains a quadratic objective function and a quadratic constraint. The optimization problem is nonconvex but is converted to a convex optimization problem in this paper. It is solved by the interior-point method and optimum weight vector to robust beamforming is achieved.

Injury-Induced Type I IFN Signaling Regulates Inflammatory Responses in the Central Nervous System

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Khorooshi, Reza; Owens, Trevor

2010-01-01

Innate glial response is critical for the induction of inflammatory mediators and recruitment of leukocytes to sites of the injury in the CNS. We have examined the involvement of type I IFN signaling in the mouse hippocampus following sterile injury (transection of entorhinal afferents). Type I I...

Acute injury in the peripheral nervous system triggers an alternative macrophage response

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Ydens Elke

2012-07-01

Full Text Available Abstract Background The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. Methods To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative using real-time quantitative polymerase chain reaction (RT-qPCR, western blot, and immunohistochemistry. Results Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40, and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2. The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. Conclusions We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the

The psychological response to injury in student athletes: a narrative review with a focus on mental health.

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Putukian, Margot

2016-02-01

Injury is a major stressor for athletes and one that can pose significant challenges. Student athletes must handle rigorous academic as well as athletic demands that require time as well as significant physical requirements. Trying to perform and succeed in the classroom and on the playing field has become more difficult as the demands and expectations have increased. If an athlete is injured, these stressors increase. Stress is an important antecedent to injuries and can play a role in the response to, rehabilitation and return to play after injury. The psychological response to injury can trigger and/or unmask mental health issues including depression and suicidal ideation, anxiety, disordered eating, and substance use/abuse. There are barriers to mental health treatment in athletes. They often consider seeking help as a sign of weakness, feeling that they should be able to 'push through' psychological obstacles as they do physical ones. Athletes may not have developed healthy coping behaviours making response to injury especially challenging. I discuss the current state of knowledge regarding the psychological response to injury and delineate resources necessary to direct the injured athlete to a mental health care provider if appropriate. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Frontal White Matter Damage Impairs Response Inhibition in Children Following Traumatic Brain Injury

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Lipszyc, Jonathan; Levin, Harvey; Hanten, Gerri; Hunter, Jill; Dennis, Maureen; Schachar, Russell

2014-01-01

Inhibition, the ability to suppress inappropriate cognitions or behaviors, can be measured using computer tasks and questionnaires. Inhibition depends on the frontal cortex, but the role of the underlying white matter (WM) is unclear. We assessed the specific impact of frontal WM damage on inhibition in 29 children with moderate-to-severe traumatic brain injury (15 with and 14 without frontal WM damage), 21 children with orthopedic injury, and 29 population controls. We used the Stop Signal Task to measure response inhibition, the Behavior Rating Inventory of Executive Function to assess everyday inhibition, and T2 fluid-attenuated inversion recovery magnetic resonance imaging to identify lesions. Children with frontal WM damage had impaired response inhibition compared with all other groups and poorer everyday inhibition than the orthopedic injury group. Frontal WM lesions most often affected the superior frontal gyrus. These results provide evidence for the critical role of frontal WM in inhibition. PMID:24618405

Dose - response relationship between noise exposure and the risk of occupational injury

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Jin-Ha Yoon

2015-01-01

Full Text Available Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers′ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively. Workplace dust exposure was classified as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals derived from a logistic regression model were 1.68 (1.27-2.24 and 3.42 (2.26-5.17 at 80-89 dB and ≥90 dB versus <80 dB. These associations remained significant when in a separate analysis according to high or low dust exposure level. Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.

Dose — response relationship between noise exposure and the risk of occupational injury

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Yoon, Jin-Ha; Hong, Jeong-Suk; Roh, Jaehoon; Kim, Chi-Nyon; Won, Jong-Uk

2015-01-01

Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers’ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively). Workplace dust exposure was classified as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals) derived from a logistic regression model were 1.68 (1.27-2.24) and 3.42 (2.26-5.17) at 80-89 dB and ≥90 dB versus occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury. PMID:25599757

Host responses to concurrent combined injuries in non-human primates.

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Bradley, Matthew J; Vicente, Diego A; Bograd, Benjamin A; Sanders, Erin M; Leonhardt, Crystal L; Elster, Eric A; Davis, Thomas A

2017-01-01

Multi-organ failure (MOF) following trauma remains a significant cause of morbidity and mortality related to a poorly understood abnormal inflammatory response. We characterized the inflammatory response in a non-human primate soft tissue injury and closed abdomen hemorrhage and sepsis model developed to assess realistic injury patterns and induce MOF. Adult male Mauritan Cynomolgus Macaques underwent laparoscopy to create a cecal perforation and non-anatomic liver resection along with a full-thickness flank soft tissue injury. Treatment consisted of a pre-hospital phase followed by a hospital phase after 120 minutes. Blood counts, chemistries, and cytokines/chemokines were measured throughout the study. Lung tissue inflammation/apoptosis was confirmed by mRNA quantitative real-time PCR (qPCR), H&E, myeloperoxidase (MPO) and TUNEL staining was performed comparing age-matched uninjured controls to experimental animals. Twenty-one animals underwent the protocol. Mean percent hepatectomy was 64.4 ± 5.6; percent blood loss was 69.0 ± 12.1. Clinical evidence of end-organ damage was reflected by a significant elevation in creatinine (1.1 ± 0.03 vs. 1.9 ± 0.4, p=0.026). Significant increases in systemic levels of IL-10, IL-1ra, IL-6, G-CSF, and MCP-1 occurred (11-2986-fold) by 240 minutes. Excessive pulmonary inflammation was evidenced by alveolar edema, congestion, and wall thickening (H&E staining). Concordantly, amplified accumulation of MPO leukocytes and significant pulmonary inflammation and pneumocyte apoptosis (TUNEL) was confirmed using qRT-PCR. We created a clinically relevant large animal multi-trauma model using laparoscopy that resulted in a significant systemic inflammatory response and MOF. With this model, we anticipate studying systemic inflammation and testing innovative therapeutic options.

Host responses to concurrent combined injuries in non-human primates

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Matthew J. Bradley

2017-11-01

Full Text Available Abstract Background Multi-organ failure (MOF following trauma remains a significant cause of morbidity and mortality related to a poorly understood abnormal inflammatory response. We characterized the inflammatory response in a non-human primate soft tissue injury and closed abdomen hemorrhage and sepsis model developed to assess realistic injury patterns and induce MOF. Methods Adult male Mauritan Cynomolgus Macaques underwent laparoscopy to create a cecal perforation and non-anatomic liver resection along with a full-thickness flank soft tissue injury. Treatment consisted of a pre-hospital phase followed by a hospital phase after 120 minutes. Blood counts, chemistries, and cytokines/chemokines were measured throughout the study. Lung tissue inflammation/apoptosis was confirmed by mRNA quantitative real-time PCR (qPCR, H&E, myeloperoxidase (MPO and TUNEL staining was performed comparing age-matched uninjured controls to experimental animals. Results Twenty-one animals underwent the protocol. Mean percent hepatectomy was 64.4 ± 5.6; percent blood loss was 69.0 ± 12.1. Clinical evidence of end-organ damage was reflected by a significant elevation in creatinine (1.1 ± 0.03 vs. 1.9 ± 0.4, p=0.026. Significant increases in systemic levels of IL-10, IL-1ra, IL-6, G-CSF, and MCP-1 occurred (11-2986-fold by 240 minutes. Excessive pulmonary inflammation was evidenced by alveolar edema, congestion, and wall thickening (H&E staining. Concordantly, amplified accumulation of MPO leukocytes and significant pulmonary inflammation and pneumocyte apoptosis (TUNEL was confirmed using qRT-PCR. Conclusion We created a clinically relevant large animal multi-trauma model using laparoscopy that resulted in a significant systemic inflammatory response and MOF. With this model, we anticipate studying systemic inflammation and testing innovative therapeutic options.

Endogenous Tim-1 (Kim-1) promotes T-cell responses and cell-mediated injury in experimental crescentic glomerulonephritis.

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Nozaki, Yuji; Nikolic-Paterson, David J; Snelgrove, Sarah L; Akiba, Hisaya; Yagita, Hideo; Holdsworth, Stephen R; Kitching, A Richard

2012-05-01

The T-cell immunoglobulin mucin 1 (Tim-1) modulates CD4(+) T-cell responses and is also expressed by damaged proximal tubules in the kidney where it is known as kidney injury molecule-1 (Kim-1). We sought to define the role of endogenous Tim-1 in experimental T-cell-mediated glomerulonephritis induced by sheep anti-mouse glomerular basement membrane globulin acting as a planted foreign antigen. Tim-1 is expressed by infiltrating activated CD4(+) cells in this model, and we studied the effects of an inhibitory anti-Tim-1 antibody (RMT1-10) on immune responses and glomerular disease. Crescentic glomerulonephritis, proliferative injury, and leukocyte accumulation were attenuated following treatment with anti-Tim-1 antibodies, but interstitial foxp3(+) cell accumulation and interleukin-10 mRNA were increased. T-cell proliferation and apoptosis decreased in the immune system along with a selective reduction in Th1 and Th17 cellular responses both in the immune system and within the kidney. The urinary excretion and renal expression of Kim-1 was reduced by anti-Tim-1 antibodies reflecting diminished interstitial injury. The effects of anti-Tim-1 antibodies were not apparent in the early phase of renal injury, when the immune response to sheep globulin was developing. Thus, endogenous Tim-1 promotes Th1 and Th17 nephritogenic immune responses and its neutralization reduces renal injury while limiting inflammation in cell-mediated glomerulonephritis.

A Robust Response of Precipitation to Global Warming from CMIP5 Models

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Lau, K. -M.; Wu, H. -T.; Kim, K. -M.

2012-01-01

How precipitation responds to global warming is a major concern to society and a challenge to climate change research. Based on analyses of rainfall probability distribution functions of 14 state-of-the-art climate models, we find a robust, canonical global rainfall response to a triple CO2 warming scenario, featuring 100 250% more heavy rain, 5-10% less moderate rain, and 10-15% more very light or no-rain events. Regionally, a majority of the models project a consistent response with more heavy rain events over climatologically wet regions of the deep tropics, and more dry events over subtropical and tropical land areas. Results suggest that increased CO2 emissions induce basic structural changes in global rain systems, increasing risks of severe floods and droughts in preferred geographic locations worldwide.

Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

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Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei

2017-03-01

The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

Area and depth of surfactant-induced corneal injury predicts extent of subsequent ocular responses.

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Jester, J V; Petroll, W M; Bean, J; Parker, R D; Carr, G J; Cavanagh, H D; Maurer, J K

1998-12-01

To correlate area and depth of initial corneal injury induced by surfactants of differing type and irritant properties with corneal responses and outcome in the same animals over time by using in vivo confocal microscopy (CM). Six groups of six adult rabbits were treated with anionic, cationic, and nonionic surfactants that caused different levels of ocular irritation. Test materials included slight irritants: 5% sodium lauryl sulfate (SLS), polyoxyethylene glycol monoalkyl ether (POE), and 5% 3-isotridecyloxypropyl-bis(polyoxyethylene) ammonium chloride (ITDOP); mild irritants: 5% 3-decyloxypropyl-bis(polyoxyethylene) amine (DOP) and sodium linear alkylbenzene sulfonate (LAS); and a moderate irritant: a proprietary detergent (DTRGT). Ten microliters surfactant were directly applied to the cornea of one eye of each rabbit. Ten untreated rabbits served as control subjects. Area and depth of initial injury was determined by using in vivo CM to measure epithelial thickness, epithelial cell size, corneal thickness, and depth of stromal injury in four corneal regions at 3 hours and at day 1. Area and depth of corneal responses to injury were evaluated at various times from days 3 through 35 by macroscopic grading and quantitative confocal microscopy through-focusing (CMTF). In vivo CM revealed corneal injury with slight irritants to be restricted to the epithelium, whereas the mild and moderate irritants caused complete epithelial cell loss with increasing anterior stromal damage: DOP < LAS < DTRGT. With the slight ocular irritants there was little or no change in corneal thickness or the CMTF intensity profiles. Three hours after treatment, mild and moderate ocular irritants caused a significant increase in corneal thickness, which peaked at day 1 with DOP (483.3+/-80.1 microm) and LAS (572.3+/-60.0 microm) and day 3 with DTRGT (601.4+/-68.7 microm); returning to normal (similar to control values) by day 7 with DOP and day 35 with LAS and DTRGT. The CMTF intensity

Placebo response in neuropathic pain after spinal cord injury: a meta-analysis of individual participant data

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Jutzeler CR

2018-04-01

Full Text Available Catherine R Jutzeler,1–3 Freda M Warner,1,2 Jacquelyn J Cragg,1,3 Jenny Haefeli,4 J Scott Richards,5 Sven R Andresen,6 Nanna B Finnerup,7,8 Catherine Mercier,9 John LK Kramer1,2 1Faculty of Medicine, ICORD, University of British Columbia, Vancouver, BC, Canada; 2Faculty of Education, School of Kinesiology, University of BC, Vancouver, BC, Canada; 3Faculty of Medicine, Spinal Cord Injury Center, University Hospital Balgrist, University of Zurich, Zurich, Switzerland; 4Weill Institute for Neurosciences, Department of Neurological Surgery, Brain and Spinal Injury Center, University of California, San Francisco, CA, USA; 5Department of Physical Medicine and Rehabilitation, University of Alabama at Birmingham, Birmingham, AL, USA; 6Spinal Cord Injury Centre of Western Denmark, Department of Neurology, Regional Hospital of Viborg, Viborg, Denmark; 7Danish Pain Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 8Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; 9Center for Interdisciplinary Research in Rehabilitation and Social Integration, Québec, QC, Canada Background: Understanding factors associated with high placebo responses in clinical trials increases the likelihood of detecting a meaningful treatment effect. The aim of the present study was to identify subject-level factors that contribute to placebo variability in patients with neuropathic pain due to spinal cord injury (SCI.Methods: Multiple regression analysis of patient data from randomized, double-blind, placebo-controlled trials (duration >4 weeks involving individuals with SCI was performed. Patient demographics, as well as injury and pain characteristics were examined for their association with changes in pain rating from baseline to the end of the trial (i.e., placebo response. The overall effect of individual predictors was quantified with meta-analysis statistics.Results: A total of 276 patients with SCI from six studies were

UNC5B receptor deletion exacerbates tissue injury in response to AKI.

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Ranganathan, Punithavathi; Jayakumar, Calpurnia; Navankasattusas, Sutip; Li, Dean Y; Kim, Il-man; Ramesh, Ganesan

2014-02-01

Netrin-1 regulates cell survival and apoptosis by activation of its receptors, including UNC5B. However, the in vivo role of UNC5B in cell survival during cellular stress and tissue injury is unknown. We investigated the role of UNC5B in cell survival in response to stress using mice heterozygously expressing the UNC5B gene (UNC5B(-/flox)) and mice with targeted homozygous deletion of UNC5B in kidney epithelial cells (UNC5B(-/flox/GGT-cre)). Mice were subjected to two different models of organ injury: ischemia reperfusion injury of the kidney and cisplatin-induced nephrotoxicity. Both mouse models of UNC5B depletion had normal organ function and histology under basal conditions. After AKI, however, UNC5B(-/flox/GGT-cre) mice exhibited significantly worse renal function and damage, increased tubular apoptosis, enhanced p53 activation, and exacerbated inflammation compared with UNC5B(-/flox) and wild-type mice. shRNA-mediated suppression of UNC5B expression in cultured tubular epithelial cells exacerbated cisplatin-induced cell death in a p53-dependent manner and blunted Akt phosphorylation. Inhibition of PI3 kinase similarly exacerbated cisplatin-induced apoptosis; in contrast, overexpression of UNC5B reduced cisplatin-induced apoptosis in these cells. Taken together, these results show that the netrin-1 receptor UNC5B plays a critical role in cell survival and kidney injury through Akt-mediated inactivation of p53 in response to stress.

Expression and cellular distribution of ubiquitin in response to injury in the developing spinal cord of Monodelphis domestica.

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Natassya M Noor

Full Text Available Ubiquitin, an 8.5 kDa protein associated with the proteasome degradation pathway has been recently identified as differentially expressed in segment of cord caudal to site of injury in developing spinal cord. Here we describe ubiquitin expression and cellular distribution in spinal cord up to postnatal day P35 in control opossums (Monodelphis domestica and in response to complete spinal transection (T10 at P7, when axonal growth through site of injury occurs, and P28 when this is no longer possible. Cords were collected 1 or 7 days after injury, with age-matched controls and segments rostral to lesion were studied. Following spinal injury ubiquitin levels (western blotting appeared reduced compared to controls especially one day after injury at P28. In contrast, after injury mRNA expression (qRT-PCR was slightly increased at P7 but decreased at P28. Changes in isoelectric point of separated ubiquitin indicated possible post-translational modifications. Cellular distribution demonstrated a developmental shift between earliest (P8 and latest (P35 ages examined, from a predominantly cytoplasmic immunoreactivity to a nuclear expression; staining level and shift to nuclear staining was more pronounced following injury, except 7 days after transection at P28. After injury at P7 immunostaining increased in neurons and additionally in oligodendrocytes at P28. Mass spectrometry showed two ubiquitin bands; the heavier was identified as a fusion product, likely to be an ubiquitin precursor. Apparent changes in ubiquitin expression and cellular distribution in development and response to spinal injury suggest an intricate regulatory system that modulates these responses which, when better understood, may lead to potential therapeutic targets.

Self-Awareness of the Male Sexual Response after Spinal Cord Injury

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Cardoso, Fernando Luiz; Savall, Ana Carolina R.; Mendes, Aline K.

2009-01-01

The aim of this study was to assess the impact of spinal cord injury on men's sexual motivation, through the sexual desire self-assessment, and the sexual arousal and orgasm physiological responses. This research consisted of a descriptive, nonprobabilistic and comparative study, designed to outline the target population characteristics to compare…

Esophageal cancer related gene-4 is a choroid plexus-derived injury response gene: evidence for a biphasic response in early and late brain injury.

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Sonia Podvin

Full Text Available By virtue of its ability to regulate the composition of cerebrospinal fluid (CSF, the choroid plexus (CP is ideally suited to instigate a rapid response to traumatic brain injury (TBI by producing growth regulatory proteins. For example, Esophageal Cancer Related Gene-4 (Ecrg4 is a tumor suppressor gene that encodes a hormone-like peptide called augurin that is present in large concentrations in CP epithelia (CPe. Because augurin is thought to regulate senescence, neuroprogenitor cell growth and differentiation in the CNS, we evaluated the kinetics of Ecrg4 expression and augurin immunoreactivity in CPe after CNS injury. Adult rats were injured with a penetrating cortical lesion and alterations in augurin immunoreactivity were examined by immunohistochemistry. Ecrg4 gene expression was characterized by in situ hybridization. Cell surface augurin was identified histologically by confocal microscopy and biochemically by sub-cellular fractionation. Both Ecrg4 gene expression and augurin protein levels were decreased 24-72 hrs post-injury but restored to uninjured levels by day 7 post-injury. Protein staining in the supraoptic nucleus of the hypothalamus, used as a control brain region, did not show a decrease of auguin immunoreactivity. Ecrg4 gene expression localized to CPe cells, and augurin protein to the CPe ventricular face. Extracellular cell surface tethering of 14 kDa augurin was confirmed by cell surface fractionation of primary human CPe cells in vitro while a 6-8 kDa fragment of augurin was detected in conditioned media, indicating release from the cell surface by proteolytic processing. In rat CSF however, 14 kDa augurin was detected. We hypothesize the initial release and proteolytic processing of augurin participates in the activation phase of injury while sustained Ecrg4 down-regulation is dysinhibitory during the proliferative phase. Accordingly, augurin would play a constitutive inhibitory function in normal CNS while down

Comparison of isolated and concomitant liver injuries: is hepatic trauma entirely responsible for the outcome?

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Yazici, P; Aydin, U; Sozbilen, M

2010-01-01

This study was undertaken to examine both isolated and concomitant liver injuries to clarify the role of liver trauma on outcome. This retrospective study was a review of all abdominal trauma patients who presented with liver injuries, with or without concomitant injury at Ege University School of Medicine over a 3-year period. Presentation, injury grade, management, and outcomes were analyzed. Patients with isolated hepatic injury (Group A) were compared with patients who had concomitant hepatic injury (liver and spleen/small bowel) (Group B). Significance was set at 95% confidence intervals. Of 368 patients, 80 (21%) presented with liver injury. Of these, the aetiology was as follows: 53 (66.2%) blunt injury, 19 (23%) penetrating injury, and 8 (10%) gun shot trauma. There were 38 patients in Group A and 42 in Group B. Of these 42 patients, 19 were diagnosed with serious types of injury ; eight thoracic, three open long bone fracture, one intra-cardiac, one intracranial. Six additional patients were observed with injuries to large abdominal vessels. Eleven patients (28.9%) with isolated hepatic injury were managed non-operatively. Mortality, intensive care unit and hospital length of stay, and transfusion requirements were significantly higher in Group B. Only the number of transfused blood units and the grade of liver injury were found to be effective on outcome whereas stepwise regression analysis revealed that injury type (penetrating) and blood transfusion were predictive for mortality. This study highlighted that although isolated liver injury results in good outcome with non-operative management, concomitant injuries to the liver lead to a higher failure and mortality rate. However, liver injury itself is rarely responsible for death.

Long descending cervical propriospinal neurons differ from thoracic propriospinal neurons in response to low thoracic spinal injury

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Stelzner Dennis J

2010-11-01

Full Text Available Abstract Background Propriospinal neurons, with axonal projections intrinsic to the spinal cord, have shown a greater regenerative response than supraspinal neurons after axotomy due to spinal cord injury (SCI. Our previous work focused on the response of axotomized short thoracic propriospinal (TPS neurons following a low thoracic SCI (T9 spinal transection or moderate spinal contusion injury in the rat. The present investigation analyzes the intrinsic response of cervical propriospinal neurons having long descending axons which project into the lumbosacral enlargement, long descending propriospinal tract (LDPT axons. These neurons also were axotomized by T9 spinal injury in the same animals used in our previous study. Results Utilizing laser microdissection (LMD, qRT-PCR, and immunohistochemistry, we studied LDPT neurons (located in the C5-C6 spinal segments between 3-days, and 1-month following a low thoracic (T9 spinal cord injury. We examined the response of 89 genes related to growth factors, cell surface receptors, apoptosis, axonal regeneration, and neuroprotection/cell survival. We found a strong and significant down-regulation of ~25% of the genes analyzed early after injury (3-days post-injury with a sustained down-regulation in most instances. In the few genes that were up-regulated (Actb, Atf3, Frs2, Hspb1, Nrap, Stat1 post-axotomy, the expression for all but one was down-regulated by 2-weeks post-injury. We also compared the uninjured TPS control neurons to the uninjured LDPT neurons used in this experiment for phenotypic differences between these two subpopulations of propriospinal neurons. We found significant differences in expression in 37 of the 84 genes examined between these two subpopulations of propriospinal neurons with LDPT neurons exhibiting a significantly higher base line expression for all but 3 of these genes compared to TPS neurons. Conclusions Taken collectively these data indicate a broad overall down

Burn injury triggered dysfunction in dendritic cell response to TLR9 activation and resulted in skewed T cell functions.

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Haitao Shen

Full Text Available Severe trauma such as burn injury is often associated with a systemic inflammatory syndrome characterized by a hyperactive innate immune response and suppressed adaptive immune function. Dendritic cells (DCs, which sense pathogens via their Toll-like receptors (TLRs, play a pivotal role in protecting the host against infections. The effect of burn injury on TLR-mediated DC function is a debated topic and the mechanism controlling the purported immunosuppressive response remains to be elucidated. Here we examined the effects of burn injury on splenic conventional DC (cDC and plasmacytoid DC (pDC responses to TLR9 activation. We demonstrate that, following burn trauma, splenic cDCs' cytokine production profile in response to TLR9 activation became anti-inflammatory dominant, with high production of IL-10 (>50% increase and low production of IL-6, TNF-α and IL-12p70 (∼25-60% reduction. CD4+ T cells activated by these cDCs were defective in producing Th1 and Th17 cytokines. Furthermore, burn injury had a more accentuated effect on pDCs than on cDCs. Following TLR9 activation, pDCs displayed an immature phenotype with an impaired ability to secrete pro-inflammatory cytokines (IFN-α, IL-6 and TNF-α and to activate T cell proliferation. Moreover, cDCs and pDCs from burn-injured mice had low transcript levels of TLR9 and several key molecules of the TLR signaling pathway. Although hyperactive innate immune response has been associated with severe injury, our data show to the contrary that DCs, as a key player in the innate immune system, had impaired TLR9 reactivity, an anti-inflammatory phenotype, and a dysfunctional T cell-priming ability. We conclude that burn injury induced impairments in DC immunobiology resulting in suppression of adaptive immune response. Targeted DC immunotherapies to promote their ability in triggering T cell immunity may represent a strategy to improve immune defenses against infection following burn injury.

Design principles for robust oscillatory behavior.

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Castillo-Hair, Sebastian M; Villota, Elizabeth R; Coronado, Alberto M

2015-09-01

Oscillatory responses are ubiquitous in regulatory networks of living organisms, a fact that has led to extensive efforts to study and replicate the circuits involved. However, to date, design principles that underlie the robustness of natural oscillators are not completely known. Here we study a three-component enzymatic network model in order to determine the topological requirements for robust oscillation. First, by simulating every possible topological arrangement and varying their parameter values, we demonstrate that robust oscillators can be obtained by augmenting the number of both negative feedback loops and positive autoregulations while maintaining an appropriate balance of positive and negative interactions. We then identify network motifs, whose presence in more complex topologies is a necessary condition for obtaining oscillatory responses. Finally, we pinpoint a series of simple architectural patterns that progressively render more robust oscillators. Together, these findings can help in the design of more reliable synthetic biomolecular networks and may also have implications in the understanding of other oscillatory systems.

Brain response to traumatic brain injury in wild-type and interleukin-6 knockout mice: a microarray analysis

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Poulsen, Christian Bjørn; Penkowa, Milena; Borup, Rehannah

2005-01-01

Traumatic injury to the brain is one of the leading causes of injury-related death or disability. Brain response to injury is orchestrated by cytokines, such as interleukin (IL)-6, but the full repertoire of responses involved is not well known. We here report the results obtained with microarrays...... in wild-type and IL-6 knockout mice subjected to a cryolesion of the somatosensorial cortex and killed at 0, 1, 4, 8 and 16 days post-lesion. Overall gene expression was analyzed by using Affymetrix genechips/oligonucleotide arrays with approximately 12,400 probe sets corresponding to approximately 10...... in the initial tissue injury and later regeneration of the parenchyma. IL-6 deficiency showed a dramatic effect in the expression of many genes, especially in the 1 day post-lesion timing, which presumably underlies the poor capacity of IL-6 knockout mice to cope with brain damage. The results highlight...

NF-kappaB-driven STAT2 and CCL2 expression in astrocytes in response to brain injury

DEFF Research Database (Denmark)

Khorooshi, Reza; Babcock, Alicia A; Owens, Trevor

2008-01-01

Tissue response to injury includes expression of genes encoding cytokines and chemokines. These regulate entry of immune cells to the injured tissue. The synthesis of many cytokines and chemokines involves NF-kappaB and signal transducers and activators of transcription (STAT). Injury to the CNS ...

Fusion of Color and Depth Camera Data for Robust Fall Detection

NARCIS (Netherlands)

Josemans, W.; Englebienne, G.; Kröse, B.; Battiato, S.; Braz, J.

2013-01-01

The availability of cheap imaging sensors makes it possible to increase the robustness of vision-based alarm systems. This paper explores the benefit of data fusion in the application of fall detection. Falls are a common source of injury for elderly people and automatic fall detection is,

Interleukin-1 and acute brain injury

Directory of Open Access Journals (Sweden)

Katie N Murray

2015-02-01

Full Text Available Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review.

Model System for Live Imaging of Neuronal Responses to Injury and Repair

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Mathieu Gravel

2011-11-01

Full Text Available Although it has been well established that induction of growth-associated protein-43 (GAP-43 during development coincides with axonal outgrowth and early synapse formation, the existence of neuronal plasticity and neurite outgrowth in the adult central nervous system after injuries is more controversial. To visualize the processes of neuronal injury and repair in living animals, we generated reporter mice for bioluminescence and fluorescence imaging bearing the luc (luciferase and gfp (green fluorescent protein reporter genes under the control of the murine GAP-43 promoter. Reporter functionality was first observed during the development of transgenic embryos. Using in vivo bioluminescence and fluorescence imaging, we visualized induction of the GAP-43 signals from live embryos starting at E10.5, as well as neuronal responses to brain and peripheral nerve injuries (the signals peaked at 14 days postinjury. Moreover, three-dimensional analysis of the GAP-43 bioluminescent signal confirmed that it originated from brain structures affected by ischemic injury. The analysis of fluorescence signal at cellular level revealed colocalization between endogenous protein and the GAP-43-driven gfp transgene. Taken together, our results suggest that the GAP-43-luc/gfp reporter mouse represents a valid model system for real-time analysis of neurite outgrowth and the capacity of the adult nervous system to regenerate after injuries.

A novel vaccine p846 encoding Rv3615c, Mtb10.4, and Rv2660c elicits robust immune response and alleviates lung injury induced by Mycobacterium infection.

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Kong, Hongmei; Dong, Chunsheng; Xiong, Sidong

2014-01-01

Development of effective anti-tuberculosis (TB) vaccines is one of the important steps to improve control of TB. Cell-mediated immune response significantly affects the control of M. tuberculosis infection. Thus, vaccines able to elicit strong cellular immune response hold special advantages against TB. In this study, three well-defined mycobacterial antigens (Rv3615c, Mtb10.4 [Rv0228], and Rv2660c) were engineered as a novel triple-antigen fusion DNA vaccine p846. The p846 vaccine consists of a high density of CD4(+) and CD8(+) T-cell epitopes. Intramuscular immunization of p846 induced robust T cells mediated immune response comparable to that of bacillus Calmette-Guérin (BCG) vaccination but more effective than that of individual antigen vaccination. After mycobacterial challenge, p846 immunization decreased bacterial burden at least 15-fold compared with individual antigen-based vaccination. Notably, the lungs of mice immunized with p846 exhibited fewer inflammatory cell infiltrates and less damage than those of control group mice. Our data demonstrate that the potential of p846 vaccine to protect against TB and the feasibility of this design strategy for further TB vaccine development.

A robust direct-integration method for rotorcraft maneuver and periodic response

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Panda, Brahmananda

1992-01-01

The Newmark-Beta method and the Newton-Raphson iteration scheme are combined to develop a direct-integration method for evaluating the maneuver and periodic-response expressions for rotorcraft. The method requires the generation of Jacobians and includes higher derivatives in the formulation of the geometric stiffness matrix to enhance the convergence of the system. The method leads to effective convergence with nonlinear structural dynamics and aerodynamic terms. Singularities in the matrices can be addressed with the method as they arise from a Lagrange multiplier approach for coupling equations with nonlinear constraints. The method is also shown to be general enough to handle singularities from quasisteady control-system models. The method is shown to be more general and robust than the similar 2GCHAS method for analyzing rotorcraft dynamics.

Biomechanical Analysis of Human Abdominal Impact Responses and Injuries through Finite Element Simulations of a Full Human Body Model.

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Ruan, Jesse S; El-Jawahri, Raed; Barbat, Saeed; Prasad, Priya

2005-11-01

Human abdominal response and injury in blunt impacts was investigated through finite element simulations of cadaver tests using a full human body model of an average-sized adult male. The model was validated at various impact speeds by comparing model responses with available experimental cadaver test data in pendulum side impacts and frontal rigid bar impacts from various sources. Results of various abdominal impact simulations are presented in this paper. Model-predicted abdominal dynamic responses such as force-time and force-deflection characteristics, and injury severities, measured by organ pressures, for the simulated impact conditions are presented. Quantitative results such as impact forces, abdominal deflections, internal organ stresses have shown that the abdomen responded differently to left and right side impacts, especially in low speed impact. Results also indicated that the model exhibited speed sensitive response characteristics and the compressibility of the abdomen significantly influenced the overall impact response in the simulated impact conditions. This study demonstrates that the development of a validated finite element human body model can be useful for abdominal injury assessment. Internal organ injuries, which are difficult to detect in experimental studies with human cadavers due to the difficulty of instrumentation, may be more easily identified with a validated finite element model through stress-strain analysis.

Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats

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Marta Rocha Araujo

2016-06-01

Full Text Available Traumatic spinal cord injury results in severe neurological deficits, mostly irreversible. The cell therapy represents a strategy for treatment particularly with the use of stem cells with satisfactory results in several experimental models. The aim of the study was to compare the treatment of spinal cord injury (SCI with and without mesenchymal stem cells (MSC, to investigate whether MSCs migrate and/or remain at the site of injury, and to analyze the effects of MSCs on inflammation, astrocytic reactivity and activation of endogenous stem cells. Three hours after SCI, animals received bone marrow-derived MSCs (1×107 in 1mL PBS, IV. Animals were euthanized 24 hours, 7 and 21 days post-injury. The MSC were not present in the site of the lesion and the immunofluorescent evaluation showed significant attenuation of inflammatory response with reduction in macrophages labeled with anti-CD68 antibody (ED1, decreased immunoreactivity of astrocytes (GFAP+ and greater activation of endogenous stem cells (nestin+ in the treated groups. Therefore, cell transplantation have a positive effect on recovery from traumatic spinal cord injury possibly due to the potential of MSCs to attenuate the immune response.

Robustness of intratumour 18F-FDG PET uptake heterogeneity quantification for therapy response prediction in oesophageal carcinoma

International Nuclear Information System (INIS)

Hatt, Mathieu; Tixier, Florent; Visvikis, Dimitris; Cheze Le Rest, Catherine; Pradier, Olivier

2013-01-01

Intratumour uptake heterogeneity in PET quantified in terms of textural features for response to therapy has been investigated in several studies, including assessment of their robustness for reconstruction and physiological reproducibility. However, there has been no thorough assessment of the potential impact of preprocessing steps on the resulting quantification and its predictive value. The goal of this work was to assess the robustness of PET heterogeneity in textural features for delineation of functional volumes and partial volume correction (PVC). This retrospective analysis included 50 patients with oesophageal cancer. PVC of each PET image was performed. Tumour volumes were determined using fixed and adaptive thresholding, and the fuzzy locally adaptive Bayesian algorithm, and heterogeneity was quantified using local and regional textural features. Differences in the absolute values of the image-derived parameters considered were assessed using Bland-Altman analysis. The impact on their predictive value for the identification of patient nonresponders was assessed by comparing areas under the receiver operating characteristic curves. Heterogeneity parameters were more dependent on delineation than on PVC. The parameters most sensitive to delineation and PVC were regional ones (intensity variability and size zone variability), whereas local parameters such as entropy and homogeneity were the most robust. Despite the large differences in absolute values obtained from different delineation methods or after PVC, these differences did not necessarily translate into a significant impact on their predictive value. Parameters such as entropy, homogeneity, dissimilarity (for local heterogeneity characterization) and zone percentage (for regional characterization) should be preferred. This selection is based on a demonstrated high differentiation power in terms of predicting response, as well as a significant robustness with respect to the delineation method used

Prediction and analysis of human thoracic impact responses and injuries in cadaver impacts using a full human body finite element model.

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Ruan, Jesse; El-Jawahri, Raed; Chai, Li; Barbat, Saeed; Prasad, Priya

2003-10-01

Human thoracic dynamic responses and injuries associated with frontal impact, side impact, and belt loading were investigated and predicted using a complete human body finite element model for an average adult male. The human body model was developed to study the impact biomechanics of a vehicular occupant. Its geometry was based on the Visible Human Project (National Library of Medicine) and the topographies from human body anatomical texts. The data was then scaled to an average adult male according to available biomechanical data from the literature. The model includes details of the head, neck, ribcage, abdomen, thoracic and lumbar spine, internal organs of the chest and abdomen, pelvis, and the upper and lower extremities. The present study is focused on the dynamic response and injuries of the thorax. The model was validated at various impact speeds by comparing predicted responses with available experimental cadaver data in frontal and side pendulum impacts, as well as belt loading. Model responses were compared with similar individual cadaver tests instead of using cadaver corridors because the large differences between the upper and lower bounds of the corridors may confound the model validation. The validated model was then used to study thorax dynamic responses and injuries in various simulated impact conditions. Parameters that could induce injuries such as force, deflection, and stress were computed from model simulations and were compared with previously proposed thoracic injury criteria to assess injury potential for the thorax. It has been shown that the model exhibited speed sensitive impact characteristics, and the compressibility of the internal organs significantly influenced the overall impact response in the simulated impact conditions. This study demonstrates that the development of a validated FE human body model could be useful for injury assessment in various cadaveric impacts reported in the literature. Internal organ injuries, which are

Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

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An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

2014-01-01

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice

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Andrés-Hernando, Ana; Altmann, Christopher; Ahuja, Nilesh; Lanaspa, Miguel A.; Nemenoff, Raphael; He, Zhibin; Ishimoto, Takuji; Simpson, Pete A.; Weiser-Evans, Mary C.; Bacalja, Jasna

2011-01-01

Patients with acute kidney injury (AKI) have increased serum proinflammatory cytokines and an increased occurrence of respiratory complications. The aim of the present study was to examine the effect of renal and extrarenal cytokine production on AKI-mediated lung injury in mice. C57Bl/6 mice underwent sham surgery, splenectomy, ischemic AKI, or ischemic AKI with splenectomy and kidney, spleen, and liver cytokine mRNA, serum cytokines, and lung injury were examined. The proinflammatory cytokines IL-6, CXCL1, IL-1β, and TNF-α were increased in the kidney, spleen, and liver within 6 h of ischemic AKI. Since splenic proinflammatory cytokines were increased, we hypothesized that splenectomy would protect against AKI-mediated lung injury. On the contrary, splenectomy with AKI resulted in increased serum IL-6 and worse lung injury as judged by increased lung capillary leak, higher lung myeloperoxidase activity, and higher lung CXCL1 vs. AKI alone. Splenectomy itself was not associated with increased serum IL-6 or lung injury vs. sham. To investigate the mechanism of the increased proinflammatory response, splenic production of the anti-inflammatory cytokine IL-10 was determined and was markedly upregulated. To confirm that splenic IL-10 downregulates the proinflammatory response of AKI, IL-10 was administered to splenectomized mice with AKI, which reduced serum IL-6 and improved lung injury. Our data demonstrate that AKI in the absence of a counter anti-inflammatory response by splenic IL-10 production results in an exuberant proinflammatory response and lung injury. PMID:21677145

Active muscle response contributes to increased injury risk of lower extremity in occupant-knee airbag interaction.

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Nie, Bingbing; Sathyanarayan, Deepak; Ye, Xin; Crandall, Jeff R; Panzer, Matthew B

2018-02-28

Recent field data analysis has demonstrated that knee airbags (KABs) can reduce occupant femur and pelvis injuries but may be insufficient to decrease leg injuries in motor vehicle crashes. An enhanced understanding of the associated injury mechanisms requires accurate assessment of physiological-based occupant parameters, some of which are difficult or impossible to obtain from experiments. This study sought to explore how active muscle response can influence the injury risk of lower extremities during KAB deployment using computational biomechanical analysis. A full-factorial matrix, consisting of 48 finite element simulations of a 50th percentile occupant human model in a simplified vehicle interior, was designed. The matrix included 32 new cases in combination with 16 previously reported cases. The following influencing factors were taken into account: muscle activation, KAB use, KAB design, pre-impact seating position, and crash mode. Responses of 32 lower extremity muscles during emergency braking were replicated using one-dimensional elements of a Hill-type constitutive model, with the activation level determined from inverse dynamics and validated by existing volunteer tests. Dynamics of unfolding and inflating of the KABs were represented using the state-of-the-art corpuscular particle method. Abbreviated Injury Scale (AIS) 2+ injury risks of the knee-thigh-hip (KTH) complex and the tibia were assessed using axial force and resultant bending moments. With all simulation cases being taken together, a general linear model was used to assess factor significance (P systems. Future efforts are recommended on realistic vehicle and restraint environment and advanced modeling strategies toward a full understanding of KAB efficacy.

Characterization of chemically induced liver injuries using gene co-expression modules.

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Gregory J Tawa

Full Text Available Liver injuries due to ingestion or exposure to chemicals and industrial toxicants pose a serious health risk that may be hard to assess due to a lack of non-invasive diagnostic tests. Mapping chemical injuries to organ-specific damage and clinical outcomes via biomarkers or biomarker panels will provide the foundation for highly specific and robust diagnostic tests. Here, we have used DrugMatrix, a toxicogenomics database containing organ-specific gene expression data matched to dose-dependent chemical exposures and adverse clinical pathology assessments in Sprague Dawley rats, to identify groups of co-expressed genes (modules specific to injury endpoints in the liver. We identified 78 such gene co-expression modules associated with 25 diverse injury endpoints categorized from clinical pathology, organ weight changes, and histopathology. Using gene expression data associated with an injury condition, we showed that these modules exhibited different patterns of activation characteristic of each injury. We further showed that specific module genes mapped to 1 known biochemical pathways associated with liver injuries and 2 clinically used diagnostic tests for liver fibrosis. As such, the gene modules have characteristics of both generalized and specific toxic response pathways. Using these results, we proposed three gene signature sets characteristic of liver fibrosis, steatosis, and general liver injury based on genes from the co-expression modules. Out of all 92 identified genes, 18 (20% genes have well-documented relationships with liver disease, whereas the rest are novel and have not previously been associated with liver disease. In conclusion, identifying gene co-expression modules associated with chemically induced liver injuries aids in generating testable hypotheses and has the potential to identify putative biomarkers of adverse health effects.

The systems approach to error reduction: factors influencing inoculation injury reporting in the operating theatre.

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Cutter, Jayne; Jordan, Sue

2013-11-01

To examine the frequency of, and factors influencing, reporting of mucocutaneous and percutaneous injuries in operating theatres. Surgeons and peri-operative nurses risk acquiring blood-borne viral infections during surgical procedures. Appropriate first-aid and prophylactic treatment after an injury can significantly reduce the risk of infection. However, studies indicate that injuries often go unreported. The 'systems approach' to error reduction relies on reporting incidents and near misses. Failure to report will compromise safety. A postal survey of all surgeons and peri-operative nurses engaged in exposure prone procedures in nine Welsh hospitals, face-to-face interviews with selected participants and telephone interviews with Infection Control Nurses. The response rate was 51.47% (315/612). Most respondents reported one or more percutaneous (183/315, 58.1%) and/or mucocutaneous injuries (68/315, 21.6%) in the 5 years preceding the study. Only 54.9% (112/204) reported every injury. Surgeons were poorer at reporting: 70/133 (52.6%) reported all or >50% of their injuries compared with 65/71 nurses (91.5%). Injuries are frequently under-reported, possibly compromising safety in operating theatres. A significant number of inoculation injuries are not reported. Factors influencing under-reporting were identified. This knowledge can assist managers in improving reporting and encouraging a robust safety culture within operating departments. © 2012 John Wiley & Sons Ltd.

Loss of the inducible Hsp70 delays the inflammatory response to skeletal muscle injury and severely impairs muscle regeneration.

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Sarah M Senf

Full Text Available Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecular mechanisms which coordinate these events are only beginning to be defined. In the current study we demonstrate that Heat shock protein 70 (Hsp70 is increased following muscle injury, and is necessary for the normal sequence of events following severe injury induced by cardiotoxin, and physiological injury induced by modified muscle use. Indeed, Hsp70 ablated mice showed a significantly delayed inflammatory response to muscle injury induced by cardiotoxin, with nearly undetected levels of both neutrophil and macrophage markers 24 hours post-injury. At later time points, Hsp70 ablated mice showed sustained muscle inflammation and necrosis, calcium deposition and impaired fiber regeneration that persisted several weeks post-injury. Through rescue experiments reintroducing Hsp70 intracellular expression plasmids into muscles of Hsp70 ablated mice either prior to injury or post-injury, we confirm that Hsp70 optimally promotes muscle regeneration when expressed during both the inflammatory phase that predominates in the first four days following severe injury and the regenerative phase that predominates thereafter. Additional rescue experiments reintroducing Hsp70 protein into the extracellular microenvironment of injured muscles at the onset of injury provides further evidence that Hsp70 released from damaged muscle may drive the early inflammatory response to injury. Importantly, following induction of physiological injury through muscle reloading following a period of muscle disuse, reduced inflammation in 3-day reloaded muscles of Hsp70 ablated mice was associated with preservation of myofibers, and increased muscle force production at later time points compared to WT. Collectively our

Robustness of intratumour {sup 18}F-FDG PET uptake heterogeneity quantification for therapy response prediction in oesophageal carcinoma

Energy Technology Data Exchange (ETDEWEB)

Hatt, Mathieu; Tixier, Florent; Visvikis, Dimitris [CHRU Morvan, INSERM, UMR 1101, LaTIM, Brest (France); Cheze Le Rest, Catherine [CHU Miletrie, Nuclear Medicine, Poitiers (France); Pradier, Olivier [CHRU Morvan, Radiotherapy, Brest (France)

2013-10-15

Intratumour uptake heterogeneity in PET quantified in terms of textural features for response to therapy has been investigated in several studies, including assessment of their robustness for reconstruction and physiological reproducibility. However, there has been no thorough assessment of the potential impact of preprocessing steps on the resulting quantification and its predictive value. The goal of this work was to assess the robustness of PET heterogeneity in textural features for delineation of functional volumes and partial volume correction (PVC). This retrospective analysis included 50 patients with oesophageal cancer. PVC of each PET image was performed. Tumour volumes were determined using fixed and adaptive thresholding, and the fuzzy locally adaptive Bayesian algorithm, and heterogeneity was quantified using local and regional textural features. Differences in the absolute values of the image-derived parameters considered were assessed using Bland-Altman analysis. The impact on their predictive value for the identification of patient nonresponders was assessed by comparing areas under the receiver operating characteristic curves. Heterogeneity parameters were more dependent on delineation than on PVC. The parameters most sensitive to delineation and PVC were regional ones (intensity variability and size zone variability), whereas local parameters such as entropy and homogeneity were the most robust. Despite the large differences in absolute values obtained from different delineation methods or after PVC, these differences did not necessarily translate into a significant impact on their predictive value. Parameters such as entropy, homogeneity, dissimilarity (for local heterogeneity characterization) and zone percentage (for regional characterization) should be preferred. This selection is based on a demonstrated high differentiation power in terms of predicting response, as well as a significant robustness with respect to the delineation method used

Toll-like receptor 2 signaling in response to brain injury: an innate bridge to neuroinflammation

DEFF Research Database (Denmark)

Babcock, Alicia; Wirenfeldt, Martin; Holm, Thomas

2006-01-01

-mutant mice. Consistent with the fact that responses in knock-out mice had all returned to wild-type levels by 8 d, there was no evidence for effects on neuronal plasticity at 20 d. These results identify a role for TLR2 signaling in the early glial response to brain injury, acting as an innate bridge...

Leaf age affects the responses of foliar injury and gas exchange to tropospheric ozone in Prunus serotina seedlings

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Zhang Jianwei, E-mail: jianweizhang@fs.fed.u [Environmental Resources Research Institute, Pennsylvania State University, University Park, PA 16802 (United States); School of Forest Resources, Pennsylvania State University, University Park, PA 16802 (United States); Schaub, Marcus; Ferdinand, Jonathan A. [Environmental Resources Research Institute, Pennsylvania State University, University Park, PA 16802 (United States); Skelly, John M. [Department of Plant Pathology, Pennsylvania State University, University Park, PA 16802 (United States); Steiner, Kim C. [School of Forest Resources, Pennsylvania State University, University Park, PA 16802 (United States); Savage, James E. [Department of Plant Pathology, Pennsylvania State University, University Park, PA 16802 (United States)

2010-08-15

We investigated the effect of leaf age on the response of net photosynthesis (A), stomatal conductance (g{sub wv}), foliar injury, and leaf nitrogen concentration (N{sub L}) to tropospheric ozone (O{sub 3}) on Prunus serotina seedlings grown in open-plots (AA) and open-top chambers, supplied with either carbon-filtered or non-filtered air. We found significant variation in A, g{sub wv}, foliar injury, and N{sub L} (P < 0.05) among O{sub 3} treatments. Seedlings in AA showed the highest A and g{sub wv} due to relatively low vapor pressure deficit (VPD). Older leaves showed significantly lower A, g{sub wv}, N{sub L}, and higher foliar injury (P < 0.001) than younger leaves. Leaf age affected the response of A, g{sub wv}, and foliar injury to O{sub 3}. Both VPD and N{sub L} had a strong influence on leaf gas exchange. Foliar O{sub 3}-induced injury appeared when cumulative O{sub 3} uptake reached 8-12 mmol m{sup -2}, depending on soil water availability. The mechanistic assessment of O{sub 3}-induced injury is a valuable approach for a biologically relevant O{sub 3} risk assessment for forest trees. - Ozone effects on symptom development and leaf gas exchange interacted with leaf age and N-content on black cherry seedlings.

Mediators' Emotional Responses to Self-Injurious Behavior: An Experimental Study.

Science.gov (United States)

Mossman, Dominique A.; Hastings, Richard P.; Brown, Tony

2002-01-01

Sixty mediators from British schools for children with mental retardation watched one of five matched videos depicting no self-injury, self-injury maintained by positive reinforcement, self-injury maintained by negative reinforcement, and self-injury unrelated to social events. Self-injury maintained by negative reinforcement was associated with…

Sodium 4-Phenylbutyrate Attenuates Myocardial Reperfusion Injury by Reducing the Unfolded Protein Response.

Science.gov (United States)

Takatori, Osamu; Usui, Soichiro; Okajima, Masaki; Kaneko, Shuichi; Ootsuji, Hiroshi; Takashima, Shin-Ichiro; Kobayashi, Daisuke; Murai, Hisayoshi; Furusho, Hiroshi; Takamura, Masayuki

2017-05-01

The unfolded protein response (UPR) plays a pivotal role in ischemia-reperfusion (I/R) injury in various organs such as heart, brain, and liver. Sodium 4-phenylbutyrate (PBA) reportedly acts as a chemical chaperone that reduces UPR. In the present study, we evaluated the effect of PBA on reducing the UPR and protecting against myocardial I/R injury in mice. Male C57BL/6 mice were subjected to 30-minute myocardial I/R, and were treated with phosphate-buffered saline (as a vehicle) or PBA. At 4 hours after reperfusion, mice treated with PBA had reduced serum cardiac troponin I levels and numbers of apoptotic cells in left ventricles (LVs) in myocardial I/R. Infarct size had also reduced in mice treated with PBA at 48 hours after reperfusion. At 2 hours after reperfusion, UPR markers, including eukaryotic initiation of the factor 2α-subunit, activating transcription factor-6, inositol-requiring enzyme-1, glucose-regulated protein 78, CCAAT/enhancer-binding protein (C/EBP) homologous protein, and caspase-12, were significantly increased in mice treated with vehicle compared to sham-operated mice. Administration of PBA significantly reduced the I/R-induced increases of these markers. Cardiac function and dimensions were assessed at 21 days after I/R. Sodium 4-phenylbutyrate dedicated to the improvement of cardiac parameters deterioration including LV end-diastolic diameter and LV fractional shortening. Consistently, PBA reduced messenger RNA expression levels of cardiac remodeling markers such as collagen type 1α1, brain natriuretic peptide, and α skeletal muscle actin in LV at 21 days after I/R. Unfolded protein response mediates myocardial I/R injury. Administration of PBA reduces the UPR, apoptosis, infarct size, and preserved cardiac function. Hence, PBA may be a therapeutic option to attenuate myocardial I/R injury in clinical practice.

Intrinsic response of thoracic propriospinal neurons to axotomy

Directory of Open Access Journals (Sweden)

Stelzner Dennis J

2010-06-01

Full Text Available Abstract Background Central nervous system axons lack a robust regenerative response following spinal cord injury (SCI and regeneration is usually abortive. Supraspinal pathways, which are the most commonly studied for their regenerative potential, demonstrate a limited regenerative ability. On the other hand, propriospinal (PS neurons, with axons intrinsic to the spinal cord, have shown a greater regenerative response than their supraspinal counterparts, but remain relatively understudied in regards to spinal cord injury. Results Utilizing laser microdissection, gene-microarray, qRT-PCR, and immunohistochemistry, we focused on the intrinsic post-axotomy response of specifically labelled thoracic propriospinal neurons at periods from 3-days to 1-month following T9 spinal cord injury. We found a strong and early (3-days post injury, p.i upregulation in the expression of genes involved in the immune/inflammatory response that returned towards normal by 1-week p.i. In addition, several regeneration associated and cell survival/neuroprotective genes were significantly up-regulated at the earliest p.i. period studied. Significant upregulation of several growth factor receptor genes (GFRa1, Ret, Lifr also occurred only during the initial period examined. The expression of a number of pro-apoptotic genes up-regulated at 3-days p.i. suggest that changes in gene expression after this period may have resulted from analyzing surviving TPS neurons after the cell death of the remainder of the axotomized TPS neuronal population. Conclusions Taken collectively these data demonstrate that thoracic propriospinal (TPS neurons mount a very dynamic response following low thoracic axotomy that includes a strong regenerative response, but also results in the cell death of many axotomized TPS neurons in the first week after spinal cord injury. These data also suggest that the immune/inflammatory response may have an important role in mediating the early strong

Molecular mechanisms governing differential robustness of development and environmental responses in plants

DEFF Research Database (Denmark)

Lachowiec, Jennifer; Queitsch, Christine; Kliebenstein, Daniel James

2016-01-01

-genome duplications, tandem gene duplication and hybridization are emerging as major regulators of robustness in development. Despite their obvious implications for plant evolution and plant breeding, the mechanistic underpinnings by which plants modulate precise levels of robustness, plasticity and evolvability...

Are Men With a History of Head Injury Less Responsive to Cognitive Behavioral Therapy for Intimate Partner Violence?

Science.gov (United States)

Akerele, Felicia A; Murphy, Christopher M; Williams, Megan R

2017-06-01

Head injury is highly prevalent among intimate partner violence (IPV) offenders. This study investigates responsiveness to cognitive behavioral therapy (CBT) for partnerviolent men with and without a history of head injury using archival data on 310 males seeking IPV counseling at a community domestic violence agency. Participants reported on their history of head injury, age at injury, and length of time unconscious in a structured interview at program intake. Criminal justice outcomes were assessed for the 2-year period after scheduled completion of treatment using a publicly available state database. A significantly greater percentage of men with a history of head injury (N = 84) than those without (N = 226) had criminal involvement for incidents of partner abuse during the follow-up period. In addition, men with a history of moderate-to-severe head injury (n = 25) had more criminal involvement for general violence than those with no history of head injury. The findings highlight the need to screen partner-violent men for head injury and to develop and investigate intervention enhancements for those individuals.

Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

Science.gov (United States)

An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A; Leak, Rehana K; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

2014-04-01

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

Practical applications of injury surveillance: a brief 25-year history of the Connecticut Injury Prevention Center.

Science.gov (United States)

Lapidus, Garry; Borrup, Kevin; DiVietro, Susan; Campbell, Brendan T; Beebe, Rebecca; Grasso, Damion; Rogers, Steven; Joseph, D'Andrea; Banco, Leonard

2016-04-01

The mission of the Connecticut Injury Prevention Center (CIPC), jointly housed in Connecticut Children's Medical Center and Hartford Hospital, is to reduce unintentional injury and violence among Connecticut residents, with a special focus on translating research into injury prevention programmes and policy. The CIPC engages in four core activities: research, education and training, community outreach programmes and public policy. As surveillance is an essential element of injury prevention, the CIPC has developed a robust statewide fatal and non-fatal injury surveillance system that has guided our prior work and continues to inform our current projects. The purpose of this article is to review the projects, programmes, and collaborative relationships that have made the CIPC successful in reducing unintentional injury and violence in Connecticut throughout the course of its 25 years history. Retrospective review of the application of injury surveillance. We believe that the application of our surveillance system can serve as a model for others who wish to engage in collaborative, community-based, data-driven injury prevention programmes in their own communities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Inflammatory responses are not sufficient to cause delayed neuronal death in ATP-induced acute brain injury.

Directory of Open Access Journals (Sweden)

Hey-Kyeong Jeong

Full Text Available BACKGROUND: Brain inflammation is accompanied by brain injury. However, it is controversial whether inflammatory responses are harmful or beneficial to neurons. Because many studies have been performed using cultured microglia and neurons, it has not been possible to assess the influence of multiple cell types and diverse factors that dynamically and continuously change in vivo. Furthermore, behavior of microglia and other inflammatory cells could have been overlooked since most studies have focused on neuronal death. Therefore, it is essential to analyze the precise roles of microglia and brain inflammation in the injured brain, and determine their contribution to neuronal damage in vivo from the onset of injury. METHODS AND FINDINGS: Acute neuronal damage was induced by stereotaxic injection of ATP into the substantia nigra pars compacta (SNpc and the cortex of the rat brain. Inflammatory responses and their effects on neuronal damage were investigated by immunohistochemistry, electron microscopy, quantitative RT-PCR, and stereological counting, etc. ATP acutely caused death of microglia as well as neurons in a similar area within 3 h. We defined as the core region the area where both TH(+ and Iba-1(+ cells acutely died, and as the penumbra the area surrounding the core where Iba-1(+ cells showed activated morphology. In the penumbra region, morphologically activated microglia arranged around the injury sites. Monocytes filled the damaged core after neurons and microglia died. Interestingly, neither activated microglia nor monocytes expressed iNOS, a major neurotoxic inflammatory mediator. Monocytes rather expressed CD68, a marker of phagocytic activity. Importantly, the total number of dopaminergic neurons in the SNpc at 3 h (∼80% of that in the contralateral side did not decrease further at 7 d. Similarly, in the cortex, ATP-induced neuron-damage area detected at 3 h did not increase for up to 7 d. CONCLUSIONS: Different cellular

Assessment of abdominal muscle function in individuals with motor-complete spinal cord injury above T6 in response to transcranial magnetic stimulation.

Science.gov (United States)

Bjerkefors, Anna; Squair, Jordan W; Chua, Romeo; Lam, Tania; Chen, Zhen; Carpenter, Mark G

2015-02-01

To use transcranial magnetic stimulation and electromyography to assess the potential for preserved function in the abdominal muscles in individuals classified with motor-complete spinal cord injury above T6. Five individuals with spinal cord injury (C5-T3) and 5 able-bodied individuals. Transcranial magnetic stimulation was delivered over the abdominal region of primary motor cortex during resting and sub-maximal (or attempted) contractions. Surface electromyography was used to record motor-evoked potentials as well as maximal voluntary (or attempted) contractions in the abdominal muscles and the diaphragm. Responses to transcranial magnetic stimulation in the abdominal muscles occurred in all spinal cord injury subjects. Latencies of muscle response onsets were similar in both groups; however, peak-to-peak amplitudes were smaller in the spinal cord injury group. During maximal voluntary (or attempted) contractions all spinal cord injury subjects were able to elicit electromyography activity above resting levels in more than one abdominal muscle across tasks. Individuals with motor-complete spinal cord injury above T6 were able to activate abdominal muscles in response to transcranial magnetic stimulation and during maximal voluntary (or attempted) contractions. The activation was induced directly through corticospinal pathways, and not indirectly by stretch reflex activations of the diaphragm. Transcranial magnetic stimulation and electromyography measurements provide a useful method to assess motor preservation of abdominal muscles in persons with spinal cord injury.

Burden of injury of serious road injuries in six EU countries.

Science.gov (United States)

Weijermars, Wendy; Bos, Niels; Filtness, Ashleigh; Brown, Laurie; Bauer, Robert; Dupont, Emmanuelle; Martin, Jean Louis; Perez, Katherine; Thomas, Pete

2018-02-01

Information about the burden of (non-fatal) road traffic injury is very useful to further improve road safety policy. Previous studies calculated the burden of injury in individual countries. This paper estimates and compares the burden of non-fatal serious road traffic injuries in six EU countries/regions: Austria, Belgium, England, The Netherlands, the Rhône region in France and Spain. It is a cross-sectional study based on hospital discharge databases. of study are patients hospitalized with MAIS3+ due to road traffic injuries. The burden of injury (expressed in years lived with disability (YLD)) is calculated applying a method that is developed within the INTEGRIS study. The method assigns estimated disability information to the casualties using the EUROCOST injury classification. The average burden per MAIS3+ casualty varies between 2.4 YLD and 3.2 YLD per casualty. About 90% of the total burden of injury of MAIS3+ casualties is due to lifelong consequences that are experienced by 19% to 33% of the MAIS3+ casualties. Head injuries, spinal cord injuries and injuries to the lower extremities are responsible for more than 90% of the total burden of MAIS3+ road traffic injuries. Results per transport mode differ between the countries. Differences between countries are mainly due to differences in age distribution and in the distribution over EUROCOST injury groups of the casualties. The analyses presented in this paper can support further improvement of road safety policy. Countermeasures could for example be focused at reducing skull and brain injuries, spinal cord injuries and injuries to the lower extremities, as these injuries are responsible for more than 90% of the total burden of injury of MAIS3+ casualties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Injury Response of Resected Human Brain Tissue In Vitro

NARCIS (Netherlands)

Verwer, Ronald W. H.; Sluiter, Arja A.; Balesar, Rawien A.; Baaijen, Johannes C.; de Witt Hamer, Philip C.; Speijer, Dave; Li, Yichen; Swaab, Dick F.

2015-01-01

Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by

Epigenetic modulation of gene expression governs the brain���s response to injury

OpenAIRE

Simon, Roger P.

2015-01-01

Mild stress from ischemia, seizure, hypothermia, or infection can produce a transient neuroprotected state in the brain. In the neuroprotected state, the brain responds differently to a severe stress and sustains less injury. At the genomic level, the response of the neuroprotected brain to a severe stress is characterized by widespread differential regulation of genes with diverse functions. This reprogramming of gene expression observed in the neuroprotected brain in response to a stress is...

Designing robust control-based HIV-treatment

Directory of Open Access Journals (Sweden)

Fredy Andrés Olarte Dussán

2008-05-01

Full Text Available Designing a robust control-based treatment for human immunodeficiency virus (HIV-infected patients was studied. The dynamics of the immune system’s response to infection was modelled using a 5th order nonlinear model with separate efficacy coefficients for protease inhibitor (PIs and reverse transcriptase inhibitors (RTIs. The immune res-ponse has been represented as an uncertain system due to errors in parameter estimation and the existence of un-modelled dynamics. A polytopic system was constructed incorporating all possible system parameter values. A con-trol system was designed using robust pole location techniques stabilising the polytopic system around an equilibrium point having a low viral load. Numerical simulation results (including the organism’s pharmacokinetical response to anti-retroviral drugs showed that the control law could lead to long-term stable conditions, even in extreme cases.

The immunological consequences of injury.

LENUS (Irish Health Repository)

Ni Choileain, N

2012-02-03

Immediate and early trauma death rates are determined by "first hits" such as hypoxia, hypotension and organ injury, while late mortality correlates closely with "second hits" such as infection. An imbalance between the early systemic inflammatory response (SIRS), and the later compensatory counter-inflammatory response (CARS), is considered to be responsible for much post-traumatic morbidity and mortality. From a clinical perspective, this remains a significant healthcare problem, which has stimulated decades of experimental and clinical research aimed at understanding the functional effects of injury on the immune system. This review describes the impact of injury on the innate and adaptive immune systems. Though it is worth noting that the features of the immune response to injury overlap in many areas with immune dysregulation in sepsis, we attempt here to elucidate the mechanism by which injury predisposes to infection rather than to describe the alterations in host immunity consequent to established sepsis.

Robust Optimization in Simulation : Taguchi and Response Surface Methodology

NARCIS (Netherlands)

Dellino, G.; Kleijnen, J.P.C.; Meloni, C.

2008-01-01

Optimization of simulated systems is tackled by many methods, but most methods assume known environments. This article, however, develops a 'robust' methodology for uncertain environments. This methodology uses Taguchi's view of the uncertain world, but replaces his statistical techniques by

A robust metric for screening outliers from analogue product manufacturing tests responses

NARCIS (Netherlands)

Krishnan, S.; Kerkhoff, H.G.

2011-01-01

Mahalanobis distance is one of the commonly used multivariate metrics for finely segregating defective devices from non-defective ones. An associated problem with this approach is the estimation of a robust mean and a covariance matrix. In the absence of such robust estimates, especially in the

A Robust Metric for Screening Outliers from Analogue Product Manufacturing Tests Responses

NARCIS (Netherlands)

Krishnan, Shaji; Krishnan, Shaji; Kerkhoff, Hans G.

2011-01-01

Mahalanobis distance is one of the commonly used multivariate metrics for finely segregating defective devices from non-defective ones. An associated problem with this approach is the estimation of a robust mean and a covariance matrix. In the absence of such robust estimates, especially in the

Activated Α7nachr Improves Postoperative Cognitive Dysfunction and Intestinal Injury Induced by Cardiopulmonary Bypass in Rats: Inhibition of the Proinflammatory Response Through the Th17 Immune Response

Directory of Open Access Journals (Sweden)

Keyan Chen

2018-04-01

Full Text Available Backgrund/Aims: To investigate the effects of activated α7 nicotinic acetylcholine receptor (α7nAChR on postoperative cognitive dysfunction (POCD and intestinal injury induced by cardiopulmonary bypass (CPB and its relationship with the Th17 response in order to provide a theoretical basis for organ protection and targeted drug therapy during the perioperative period. Methods: Sprague-Dawley rat models of CPB were established. Rat intestinal and brain injuries were observed after CPB using hematoxylin and eosin staining. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. Inflammatory factors and markers of brain injury in rat serum were measured using enzyme-linked immunosorbent assay. The expression levels of Bcl-2, Bax, caspase-3, ZO-1, occludin, AQP4, RORγT, and α7nAchR were examined using western blotting. Transcription factor RORγT expression was determined using real-time fluorescent quantitative polymerase chain reaction. Th17 cells in the peripheral blood and spleen were determined using flow cytometry. α7nAchR knockout rats were established. The Th17 response in the peripheral blood and spleen of α7nAchR knockout rats was further verified using flow cytometry. Results: CPB can induce POCD and intestinal injury in rats. α7nAchR activation markedly reduced intestinal injury, POCD, neuronal apoptosis, proinflammatory factor expression, and number of CD4+IL-17+ cells. α7nAchR knockout significantly increased serum D-lactic acid, FABP2, S-100β, NSE, TNF-α, IL-6, and IL-17 secretion. The number of CD4+IL-17+ cells was also significantly increased. Conclusion: α7nAchR activation markedly ameliorates the intestinal injury and POCD induced by CPB. Inhibition of the Th17 immune response can reduce the proinflammatory response, which could provide a new method for clinical perioperative organ protection and targeted drug therapy.

Protection for Thorax Injury Severity in 90° Lateral Collision

Directory of Open Access Journals (Sweden)

Dimitrios Kallieris

1996-01-01

Full Text Available The thoracic trauma index (TTI and the viscous criterion (VC are injury criteria intended for the prediction of torso injury severity. The criteria were assessed in two series of experiments: 90° (lateral car to car collisions and controlled left trunk impacts against either a rigid or padded wall. Forty-two belt restrained human cadavers in the age range 18–65 years, located in the near-side front passenger seat, were used. The impact velocity was between 40 and 60 km/h. Left and right side impacts were simulated using standard or modified car side structures. With the second series of experiments, the left side of each subject was impacted under one of two different test conditions: 24 km/h rigid wall or 32 km/h padded wall. The thorax deformation was evaluated through the double integration of the accelerated difference at the fourth and eight ribs, near and far side. Deformation maxima of 6–138 mm (mean 69 mm, VC values of 0.3–4.7 m/s (mean 1.6 m/s, and TTI values of 85–252 (mean 63 occurred. Torso abbreviated injury severity (AIS values were between 0 and 5. Statistical analyses showed a stronger influence of age on injury severity than the injury criteria or biomechanical responses in the two series of experiments. The TTI showed the highest correlation with thoracic AIS and the number of rib fractures, while VC was the better predictor of abdominal AIS. The results are discussed critically and the strength and robustness of the injury criteria analyzed.

Investigating Robustness of Item Response Theory Proficiency Estimators to Atypical Response Behaviors under Two-Stage Multistage Testing. ETS GRE® Board Research Report. ETS GRE®-16-03. ETS Research Report No. RR-16-22

Science.gov (United States)

Kim, Sooyeon; Moses, Tim

2016-01-01

The purpose of this study is to evaluate the extent to which item response theory (IRT) proficiency estimation methods are robust to the presence of aberrant responses under the "GRE"® General Test multistage adaptive testing (MST) design. To that end, a wide range of atypical response behaviors affecting as much as 10% of the test items…

Brain Cholinergic Function and Response to Rivastigmine in Patients With Chronic Sequels of Traumatic Brain Injury

DEFF Research Database (Denmark)

Östberg, Anna; Virta, Jere; Rinne, Juha O

2018-01-01

subjects for more than 1 year after at least moderate traumatic brain injury. Ten of the subjects were respondents and 7 nonrespondents to cholinergic medication. DESIGN:: Cholinergic function was assessed with [methyl-C] N-methylpiperidyl-4-acetate-PET (C-MP4A-PET), which reflects the activity...... was notably lower throughout the cortex in both respondents and nonrespondents, without significant differences between them. CONCLUSION:: Our study suggests that frontal cholinergic dysfunction is associated with the clinical response to cholinergic stimulation in patients with traumatic brain injury....

Environmental Subconcussive Injury, Axonal Injury, and Chronic Traumatic Encephalopathy

Directory of Open Access Journals (Sweden)

Wendy A. Morley

2018-03-01

Full Text Available Brain injury occurs in two phases: the initial injury itself and a secondary cascade of precise immune-based neurochemical events. The secondary phase is typically functional in nature and characterized by delayed axonal injury with more axonal disconnections occurring than in the initial phase. Axonal injury occurs across the spectrum of disease severity, with subconcussive injury, especially when repetitive, now considered capable of producing significant neurological damage consistent with axonal injury seen in clinically evident concussion, despite no observable symptoms. This review is the first to introduce the concept of environmental subconcussive injury (ESCI and sets out how secondary brain damage from ESCI once past the juncture of microglial activation appears to follow the same neuron-damaging pathway as secondary brain damage from conventional brain injury. The immune response associated with ESCI is strikingly similar to that mounted after conventional concussion. Specifically, microglial activation is followed closely by glutamate and calcium flux, excitotoxicity, reactive oxygen species and reactive nitrogen species (RNS generation, lipid peroxidation, and mitochondrial dysfunction and energy crisis. ESCI damage also occurs in two phases, with the primary damage coming from microbiome injury (due to microbiome-altering events and secondary damage (axonal injury from progressive secondary neurochemical events. The concept of ESCI and the underlying mechanisms have profound implications for the understanding of chronic traumatic encephalopathy (CTE etiology because it has previously been suggested that repetitive axonal injury may be the primary CTE pathogenesis in susceptible individuals and it is best correlated with lifetime brain trauma load. Taken together, it appears that susceptibility to brain injury and downstream neurodegenerative diseases, such as CTE, can be conceptualized as a continuum of brain resilience. At one end

Seawater immersion aggravates burn-associated lung injury and inflammatory and oxidative-stress responses.

Science.gov (United States)

Ma, Jun; Wang, Ying; Wu, Qi; Chen, Xiaowei; Wang, Jiahan; Yang, Lei

2017-08-01

With the increasing frequency of marine development activities and local wars at sea, the incidence of scald burns in marine accidents or wars has been increasing yearly. Various studies have indicated that immersion in seawater has a systemic impact on some organs of animals or humans with burn. Thus, for burn/scald injuries after immersion in seawater, it is desirable to study the effects and mechanisms of action on important organs. In the present study, we aimed to investigate the effect of immersion in seawater on lung injury, inflammatory and oxidative-stress responses in scalded rats. The structural damage to lungs was detected by hematoxylin and eosin staining and the results showed that seawater immersion aggravated structural lung injury in scalded rats. The expression of HMGB1 in lung tissues was detected by immunohistochemical analysis and the results showed that seawater immersion increased HMGB1 expression in lung tissues of scalded rats. Apoptosis in lung tissues was detected by terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) staining and the results showed that seawater immersion increased apoptosis rate in lung tissues of scalded rats. In addition, the expression levels of TNF-α, IL-6, IL-8, SOD, and MDA in serum were analyzed by enzyme-linked immunosorbent assays (ELISAs) and the results showed that seawater immersion induced secretion of proinflammatory factors (TNF-α, IL-6, and IL-8), increased MDA protein level, and suppressed SOD activity in the serum of scalded rats. Furthermore, measurement of plasma volume and pH showed that seawater immersion decreased plasma volume and pH value. Overall, the results indicated that all effects induced by immersion in seawater in scalded rats are more pronounced than those induced by freshwater. In conclusion, seawater immersion may aggravate lung injury and enhance inflammatory and oxidative-stress responses after burn. Copyright © 2017 Elsevier Ltd and ISBI. All rights

Robustness Metrics: Consolidating the multiple approaches to quantify Robustness

DEFF Research Database (Denmark)

Göhler, Simon Moritz; Eifler, Tobias; Howard, Thomas J.

2016-01-01

robustness metrics; 3) Functional expectancy and dispersion robustness metrics; and 4) Probability of conformance robustness metrics. The goal was to give a comprehensive overview of robustness metrics and guidance to scholars and practitioners to understand the different types of robustness metrics...

Changes in emotional empathy, affective responsivity, and behavior following severe traumatic brain injury.

Science.gov (United States)

de Sousa, Arielle; McDonald, Skye; Rushby, Jacqueline

2012-01-01

This study was designed to examine the relationship between deficits in empathy, emotional responsivity, and social behavior in adults with severe traumatic brain injury (TBI). A total of 21 patients with severe TBI and 25 control participants viewed six film clips containing pleasant, unpleasant, and neutral content whilst facial muscle responses, skin conductance, and valence and arousal ratings were measured. Emotional empathy (the Balanced Emotional Empathy Scale, BEES: self-report) and changes in drive and control in social situations (The Current Behaviour Scale, CBS: relative report) were also assessed. In comparison to control participants, those in the TBI group reported less ability to empathize emotionally and had reduced facial responding to both pleasant and unpleasant films. They also exhibited lowered autonomic arousal, as well as abnormal ratings of valence and arousal, particularly to unpleasant films. Relative reported loss of emotional control was significantly associated with heightened empathy, while there was a trend to suggest that impaired drive (or motivation) may be related to lower levels of emotional empathy. The results represent the first to suggest that level of emotional empathy post traumatic brain injury may be associated with behavioral manifestations of disorders of drive and control.

RUNNING INJURY DEVELOPMENT

DEFF Research Database (Denmark)

Johansen, Karen Krogh; Hulme, Adam; Damsted, Camma

2017-01-01

BACKGROUND: Behavioral science methods have rarely been used in running injury research. Therefore, the attitudes amongst runners and their coaches regarding factors leading to running injuries warrants formal investigation. PURPOSE: To investigate the attitudes of middle- and long-distance runners...... able to compete in national championships and their coaches about factors associated with running injury development. METHODS: A link to an online survey was distributed to middle- and long-distance runners and their coaches across 25 Danish Athletics Clubs. The main research question was: "Which...... factors do you believe influence the risk of running injuries?". In response to this question, the athletes and coaches had to click "Yes" or "No" to 19 predefined factors. In addition, they had the possibility to submit a free-text response. RESULTS: A total of 68 athletes and 19 coaches were included...

Running Injury Development

DEFF Research Database (Denmark)

Krogh Johansen, Karen; Hulme, Adam; Damsted, Camma

2017-01-01

Background: Behavioral science methods have rarely been used in running injury research. Therefore, the attitudes amongst runners and their coaches regarding factors leading to running injuries warrants formal investigation. Purpose: To investigate the attitudes of middle- and long-distance runners...... able to compete in national championships and their coaches about factors associated with running injury development. Methods: A link to an online survey was distributed to middle- and long-distance runners and their coaches across 25 Danish Athletics Clubs. The main research question was: “Which...... factors do you believe influence the risk of running injuries?”. In response to this question, the athletes and coaches had to click “Yes” or “No” to 19 predefined factors. In addition, they had the possibility to submit a free-text response. Results: A total of 68 athletes and 19 coaches were included...

How robust is the atmospheric circulation response to Arctic sea-ice loss in isolation?

Science.gov (United States)

Kushner, P. J.; Hay, S. E.; Blackport, R.; McCusker, K. E.; Oudar, T.

2017-12-01

It is now apparent that active dynamical coupling between the ocean and atmosphere determines a good deal of how Arctic sea-ice loss changes the large-scale atmospheric circulation. In coupled ocean-atmosphere models, Arctic sea-ice loss indirectly induces a 'mini' global warming and circulation changes that extend into the tropics and the Southern Hemisphere. Ocean-atmosphere coupling also amplifies by about 50% Arctic free-tropospheric warming arising from sea-ice loss (Deser et al. 2015, 2016). The mechanisms at work and how to separate the response to sea-ice loss from the rest of the global warming process remain poorly understood. Different studies have used distinctive numerical approaches and coupled ocean-atmosphere models to address this problem. We put these studies on comparable footing using pattern scaling (Blackport and Kushner 2017) to separately estimate the part of the circulation response that scales with sea-ice loss in the absence of low-latitude warming from the part that scales with low-latitude warming in the absence of sea-ice loss. We consider well-sampled simulations from three different coupled ocean-atmosphere models (CESM1, CanESM2, CNRM-CM5), in which greenhouse warming and sea-ice loss are driven in different ways (sea ice albedo reduction/transient RCP8.5 forcing for CESM1, nudged sea ice/CO2 doubling for CanESM2, heat-flux forcing/constant RCP8.5-derived forcing for CNRM-CM5). Across these different simulations, surprisingly robust influences of Arctic sea-ice loss on atmospheric circulation can be diagnosed using pattern scaling. For boreal winter, the isolated sea-ice loss effect acts to increase warming in the North American Sub-Arctic, decrease warming of the Eurasian continent, enhance precipitation over the west coast of North America, and strengthen the Aleutian Low and the Siberian High. We will also discuss how Arctic free tropospheric warming might be enhanced via midlatitude ocean surface warming induced by sea-ice loss

A novel radiation responsive cis-acting element regulates gene induction and mediates tissue injury

International Nuclear Information System (INIS)

Hallahan, Dennis E.; Virudachalam, Subbulakshmi; Kuchibahtla, Jaya

1997-01-01

containing binding domains for the transcription factors AP-1 and Ets. This DNA sequence (TGCCTCAGTTTCCC) is similar to antioxidant responsive element. X-ray- mediated transcriptional activation of the 5' regulatory region of ICAM-1 required the antioxidant responsive element (ARE). Electrophoretic mobility shift analysis of nuclear proteins from irradiated endothelial cells incubated with the ARE binding domain (5'-GCTGCTGCCTCAGTTTCCC-3') showed increased protein-DNA complexes at 60 and 120 minutes after irradiation. Conclusions: 1) ICAM induction in irradiated tissue occurs in the microvascular endothelium. 2) ICAM expression contributes to the pathogenesis of radiation-mediated tissue injury and the ICAM knockout serves as a model for the study of the pathogenesis of tissue injury. 3) ICAM expression is regulated by a novel radiation-inducible cis-acting element that has homology to previously identified antioxidant responsive elements

Acute alcohol response phenotype in heavy social drinkers is robust and reproducible.

Science.gov (United States)

Roche, Daniel J O; Palmeri, Michael D; King, Andrea C

2014-03-01

-tracking and psychomotor performance, which is not affected by FH status. This acute alcohol response phenotype in heavy, frequent binge drinkers appears to be robust and reproducible. Copyright © 2013 by the Research Society on Alcoholism.

DNA damage response in nephrotoxic and ischemic kidney injury

Energy Technology Data Exchange (ETDEWEB)

Yan, Mingjuan; Tang, Chengyuan [Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 (China); Ma, Zhengwei [Department of Cellular Biology & Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA 30912 (United States); Huang, Shuang [Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL (United States); Dong, Zheng, E-mail: zdong@augusta.edu [Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 (China); Department of Cellular Biology & Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, GA 30912 (United States)

2016-12-15

DNA damage activates specific cell signaling cascades for DNA repair, cell cycle arrest, senescence, and/or cell death. Recent studies have demonstrated DNA damage response (DDR) in experimental models of acute kidney injury (AKI). In cisplatin-induced AKI or nephrotoxicity, the DDR pathway of ATR/Chk2/p53 is activated and contributes to renal tubular cell apoptosis. In ischemic AKI, DDR seems more complex and involves at least the ataxia telangiectasia mutated (ATM), a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, and p53; however, while ATM may promote DNA repair, p53 may trigger cell death. Targeting DDR for kidney protection in AKI therefore relies on a thorough elucidation of the DDR pathways in various forms of AKI.

Nationwide Study of Humidifier Disinfectant Lung Injury in South Korea, 1994-2011. Incidence and Dose-Response Relationships.

Science.gov (United States)

Paek, Domyung; Koh, Younsuck; Park, Dong-Uk; Cheong, Hae-Kwan; Do, Kyung-Hyun; Lim, Chae-Man; Hong, Soo-Jong; Kim, Yong-Hwa; Leem, Jong-Han; Chung, Kyu Hyuck; Choi, Ye-Yong; Lee, Jong-Hyeon; Lim, Sin-Ye; Chung, Eun-Hee; Cho, Young Ah; Chae, Eun Jin; Joh, Joon-Sung; Yoon, Yup; Lee, Kyu-Hong; Choi, Bo Youl; Gwack, Jin

2015-12-01

Humidifier disinfectant lung injury is an acute lung disease attributed to recurrent inhalation of certain disinfectant aerosols emitted from room humidifiers. An outbreak of this toxic lung injury occurred in South Korea from 1995 until all humidifier disinfectant products were recalled from the consumer market by the government in 2011. A nationwide study was conducted to ascertain and classify all potential cases of humidifier disinfectant lung injury in Korea and to assess dose-response relationships. By several mechanisms, clinicians and the general public were invited to report all suspected cases of humidifier disinfectant lung injury to public health officials in South Korea. A committee was convened to define diagnostic criteria based on pathologic, radiologic, and clinical findings for index cases, combined with assessment of environmental exposure to humidifier disinfectants. Clinical review and environmental assessments were performed and later combined to determine overall likelihood of disease for each study participant, classified as definite, probable, possible, or unlikely. Survival time from exposure to onset of symptoms was analyzed to assess dose-response relationships. Three broad categories of risk factors were examined: (1) biological susceptibility, (2) temporal cycle of exposure and recovery, and (3) spatial conditions and density of disinfectant. Of 374 possible cases identified and reviewed, 329 were unanimously classified by the diagnostic committee, as follows: 117 definite, 34 probable, 38 possible and 140 unlikely cases. A total of 62 individuals with definite or probable disease died. Risk factors examined for polyhexamethyleneguanidine phosphate exposure that were found to be significant in shortening survival included age 4 years or younger at onset, use of disinfectant for 7 days per week, airborne density of 800 μg/m(3) or more of disinfectant, and daily exposure 11 or more hours in duration. Dose-response analysis indicated

Competition improves robustness against loss of information

Directory of Open Access Journals (Sweden)

Arash eKermani Kolankeh

2015-03-01

Full Text Available A substantial number of works aimed at modeling the receptive field properties of the primary visual cortex (V1. Their evaluation criterion is usually the similarity of the model response properties to the recorded responses from biological organisms. However, as several algorithms were able to demonstrate some degree of similarity to biological data based on the existing criteria, we focus on the robustness against loss of information in the form of occlusions as an additional constraint for better understanding the algorithmic level of early vision in the brain. We try to investigate the influence of competition mechanisms on the robustness. Therefore, we compared four methods employing different competition mechanisms, namely, independent component analysis, non-negative matrix factorization with sparseness constraint, predictive coding/biased competition, and a Hebbian neural network with lateral inhibitory connections. Each of those methods is known to be capable of developing receptive fields comparable to those of V1 simple-cells. Since measuring the robustness of methods having simple-cell like receptive fields against occlusion is difficult, we measure the robustness using the classification accuracy on the MNIST hand written digit dataset. For this we trained all methods on the training set of the MNIST hand written digits dataset and tested them on a MNIST test set with different levels of occlusions. We observe that methods which employ competitive mechanisms have higher robustness against loss of information. Also the kind of the competition mechanisms plays an important role in robustness. Global feedback inhibition as employed in predictive coding/biased competition has an advantage compared to local lateral inhibition learned by an anti-Hebb rule.

Incentive-Compatible Robust Line Planning

Science.gov (United States)

Bessas, Apostolos; Kontogiannis, Spyros; Zaroliagis, Christos

The problem of robust line planning requests for a set of origin-destination paths (lines) along with their frequencies in an underlying railway network infrastructure, which are robust to fluctuations of real-time parameters of the solution. In this work, we investigate a variant of robust line planning stemming from recent regulations in the railway sector that introduce competition and free railway markets, and set up a new application scenario: there is a (potentially large) number of line operators that have their lines fixed and operate as competing entities issuing frequency requests, while the management of the infrastructure itself remains the responsibility of a single entity, the network operator. The line operators are typically unwilling to reveal their true incentives, while the network operator strives to ensure a fair (or socially optimal) usage of the infrastructure, e.g., by maximizing the (unknown to him) aggregate incentives of the line operators.

AFFECTIVE RESPONSES AFTER DIFFERENT INTENSITIES OF EXERCISE IN PATIENTS WITH TRAUMATIC BRAIN INJURY

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Patricia eRzezak

2015-06-01

Full Text Available BACKGROUND: Patients with traumatic brain injury (TBI usually have mood and anxiety symptoms secondary to their brain injury. Exercise may be a cost-effective intervention for the regulation of the affective responses of this population. However, there are no studies evaluating the effects of exercise or the optimal intensity of exercise for this clinical group. METHODS: Twelve male patients with moderate or severe TBI [mean age of 31.83 and SD of 9.53] and 12 age- and gender-matched healthy volunteers [mean age of 30.58 and SD of 9.53] participated in two sessions of exercise of high and moderate intensity. Anxiety and mood was evaluated, and subjective assessment of experience pre- and post-exercise was assessed. A mixed between and within-subjects GLM analysis was conducted to compare groups [TBI, control] over condition [baseline, session 1, session 2] allowing for group by condition interaction to be determined. Planned comparisons were also conducted to test study hypotheses.RESULTS: Although no group by condition interaction was observed, planned comparisons indicated that baseline differences between patients and controls in anxiety (Cohens’ d=1.80, tension (d=1.31, depression (d=1.18, anger (d=1.08, confusion (d=1.70, psychological distress (d=1.28 and physical symptoms (d=1.42 disappear after one session of exercise, independently of the intensity of exercise. CONCLUSIONS: A single-section of exercise, regardless of exercise intensity, had a positive effect on the affective responses of patients with TBI both by increasing positive valence feelings and decreasing negative ones. Exercise can be an easily accessible intervention that may alleviate depressive symptoms related to brain injury.

Exposure to Experimental Preeclampsia in Mice Enhances the Vascular Response to Future Injury

Science.gov (United States)

Pruthi, Dafina; Khankin, Eliyahu V.; Blanton, Robert M.; Aronovitz, Mark; Burke, Suzanne D.; McCurley, Amy; Karumanchi, S. Ananth; Jaffe, Iris Z.

2015-01-01

Cardiovascular disease (CVD) remains the leading killer of women in developed nations. One gender-specific risk factor is preeclampsia (PE), a syndrome of hypertension and proteinuria that complicates 5% of pregnancies. Although PE resolves after delivery, exposed women are at increased long term risk of premature CVD and mortality. Preexisting CVD risk factors are associated with increased risk of developing PE but whether PE merely uncovers risk or contributes directly to future CVD remains a critical unanswered question. A mouse PE model was used to test the hypothesis that PE causes an enhanced vascular response to future vessel injury. A PE-like state was induced in pregnant CD1 mice by overexpressing soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein that induces hypertension and glomerular disease resembling human PE. Two months post-partum, sFlt-1 levels and blood pressure normalized and cardiac size and function by echocardiography and renal histology were indistinguishable in PE-exposed compared to control mice. Mice were then challenged with unilateral carotid injury. PE-exposed mice had significantly enhanced vascular remodeling with increased vascular smooth muscle cell proliferation (180% increase, P<0.01) and vessel fibrosis (216% increase, P<0.001) compared to control pregnancy. In the contralateral uninjured vessel, there was no difference in remodeling after exposure to PE. These data support a new model in which vessels exposed to PE retain a persistently enhanced vascular response to injury despite resolution of PE after delivery. This new paradigm may contribute to the substantially increased risk of CVD in woman exposed to PE. PMID:25712723

Lung Surfactant Protein D (SP-D) Response and Regulation During Acute and Chronic Lung Injury

DEFF Research Database (Denmark)

Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F.

2013-01-01

in three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. METHODS: Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. RESULTS: In lipopolysaccharide-challenged mice, the level of SP...... injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized systemically....... The study also confirms the concept of using increased SP-D serum levels as a biomarker of especially chronic airway inflammation....

Robust fast controller design via nonlinear fractional differential equations.

Science.gov (United States)

Zhou, Xi; Wei, Yiheng; Liang, Shu; Wang, Yong

2017-07-01

A new method for linear system controller design is proposed whereby the closed-loop system achieves both robustness and fast response. The robustness performance considered here means the damping ratio of closed-loop system can keep its desired value under system parameter perturbation, while the fast response, represented by rise time of system output, can be improved by tuning the controller parameter. We exploit techniques from both the nonlinear systems control and the fractional order systems control to derive a novel nonlinear fractional order controller. For theoretical analysis of the closed-loop system performance, two comparison theorems are developed for a class of fractional differential equations. Moreover, the rise time of the closed-loop system can be estimated, which facilitates our controller design to satisfy the fast response performance and maintain the robustness. Finally, numerical examples are given to illustrate the effectiveness of our methods. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury.

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Kerui Gong

Full Text Available Glutamate in the peripheral nervous system is involved in neuropathic pain, yet we know little how nerve injury alters responses to this neurotransmitter in primary sensory neurons. We recorded neuronal responses from the ex-vivo preparations of the dorsal root ganglia (DRG one week following a chronic constriction injury (CCI of the sciatic nerve in adult rats. We found that small diameter DRG neurons (30 µm were unaffected. Puff application of either glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA and kainic acid (KA, or the group I metabotropic receptor (mGluR agonist (S-3,5-dihydroxyphenylglycine (DHPG, induced larger inward currents in CCI DRGs compared to those from uninjured rats. N-methyl-D-aspartate (NMDA-induced currents were unchanged. In addition to larger inward currents following CCI, a greater number of neurons responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a 60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured controls. mGluR1 receptor expression increased by 60% in the membrane fraction, whereas mGluR5 receptor subunit expression remained unchanged after CCI. These results show that following nerve injury, small diameter DRG neurons, many of which are nociceptive, have increased excitability and an increased response to glutamate that is associated with changes in receptor expression at the neuronal membrane. Our findings provide further evidence that glutamatergic transmission in the periphery plays a role in nociception.

Cutaneous microvascular perfusion responses to insulin iontophoresis are differentially affected by insulin resistance after spinal cord injury.

Science.gov (United States)

La Fountaine, Michael F; Cirnigliaro, Christopher M; Azarelo, Frank; Hobson, Joshua C; Tascione, Oriana; Swonger, Kirsten N; Dyson-Hudson, Trevor; Bauman, William A

2017-09-01

What is the central question of this study? What impact does insulin resistance have on cutaneous perfusion responses to insulin iontophoresis in vascular beds with markedly reduced or functionally ablated sympathetic nervous system vasomotor function resulting from spinal cord injury? What is the main finding and its importance? Persons with spinal cord injury have sublesional microvascular endothelial dysfunction, as indicated by a blunted cutaneous perfusion response to acetylcholine iontophoresis, and the presence of insulin resistance has a further confounding effect on endothelium-mediated changes to cutaneous perfusion in the lower extremities. Endothelium-mediated mechanisms that regulate skin blood flow might play an integral role in optimizing skin perfusion in vascular beds with sympathetic nervous system vasomotor impairment, such as in spinal cord injury (SCI). Insulin is a vasoactive hormone and second messenger of nitric oxide that facilitates endothelium-mediated dilatation. The effects of insulin resistance (IR) on sublesional cutaneous perfusion responses to insulin provocation have yet to be described in persons with SCI. Persons with SCI and an able-bodied (AB) cohort were divided into subgroups based upon fasting plasma insulin concentration cut-offs for IR (≥13.13 mIU ml -1 ) or insulin sensitivity (IS; insulin, acetylcholine or placebo iontophoresis in the lower extremities; BPU responses were log 10 transformed to facilitate comparisons, and the net insulin response (NetIns) BPU response was calculated (insulin minus placebo BPU response). The NetIns was significantly greater in both IS groups compared with their corresponding IR group. The acetylcholine-mediated BPU responses in the SCI subgroups were significantly lower than those in the ABIS group. The proportional BPU responses of NetIns to acetylcholine in the IS cohorts (i.e. ABIS and SCIS) were significantly greater (P < 0.05) than that of each IR subgroup. The presence of IR

Improving Hybrid III injury assessment in steering wheel rim to chest impacts using responses from finite element Hybrid III and human body model.

Science.gov (United States)

Holmqvist, Kristian; Davidsson, Johan; Mendoza-Vazquez, Manuel; Rundberget, Peter; Svensson, Mats Y; Thorn, Stefan; Törnvall, Fredrik

2014-01-01

The main aim of this study was to improve the quality of injury risk assessments in steering wheel rim to chest impacts when using the Hybrid III crash test dummy in frontal heavy goods vehicle (HGV) collision tests. Correction factors for chest injury criteria were calculated as the model chest injury parameter ratios between finite element (FE) Hybrid III, evaluated in relevant load cases, and the Total Human Model for Safety (THUMS). This is proposed to be used to compensate Hybrid III measurements in crash tests where steering wheel rim to chest impacts occur. The study was conducted in an FE environment using an FE-Hybrid III model and the THUMS. Two impactor shapes were used, a circular hub and a long, thin horizontal bar. Chest impacts at velocities ranging from 3.0 to 6.0 m/s were simulated at 3 impact height levels. A ratio between FE-Hybrid III and THUMS chest injury parameters, maximum chest compression C max, and maximum viscous criterion VC max, were calculated for the different chest impact conditions to form a set of correction factors. The definition of the correction factor is based on the assumption that the response from a circular hub impact to the middle of the chest is well characterized and that injury risk measures are independent of impact height. The current limits for these chest injury criteria were used as a basis to develop correction factors that compensate for the limitations in biofidelity of the Hybrid III in steering wheel rim to chest impacts. The hub and bar impactors produced considerably higher C max and VC max responses in the THUMS compared to the FE-Hybrid III. The correction factor for the responses of the FE-Hybrid III showed that the criteria responses for the bar impactor were consistently overestimated. Ratios based on Hybrid III and THUMS responses provided correction factors for the Hybrid III responses ranging from 0.84 to 0.93. These factors can be used to estimate C max and VC max values when the Hybrid III is

Regulator of G-protein signaling-5 is a marker of hepatic stellate cells and expression mediates response to liver injury.

Directory of Open Access Journals (Sweden)

Arya J Bahrami

Full Text Available Liver fibrosis is mediated by hepatic stellate cells (HSCs, which respond to a variety of cytokine and growth factors to moderate the response to injury and create extracellular matrix at the site of injury. G-protein coupled receptor (GPCR-mediated signaling, via endothelin-1 (ET-1 and angiotensin II (AngII, increases HSC contraction, migration and fibrogenesis. Regulator of G-protein signaling-5 (RGS5, an inhibitor of vasoactive GPCR agonists, functions to control GPCR-mediated contraction and hypertrophy in pericytes and smooth muscle cells (SMCs. Therefore we hypothesized that RGS5 controls GPCR signaling in activated HSCs in the context of liver injury. In this study, we localize RGS5 to the HSCs and demonstrate that Rgs5 expression is regulated during carbon tetrachloride (CCl4-induced acute and chronic liver injury in Rgs5LacZ/LacZ reporter mice. Furthermore, CCl4 treated RGS5-null mice develop increased hepatocyte damage and fibrosis in response to CCl4 and have increased expression of markers of HSC activation. Knockdown of Rgs5 enhances ET-1-mediated signaling in HSCs in vitro. Taken together, we demonstrate that RGS5 is a critical regulator of GPCR signaling in HSCs and regulates HSC activation and fibrogenesis in liver injury.

IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

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Xiaorong Hu

2016-05-01

Full Text Available Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO group, ischemia and reperfusion (I/R group, (IL-23 + I/R group and (anti-IL-23 + I/R group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH, creatine kinase (CK and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P 0.05. All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

Neuroimaging Cerebrovascular Function and Diffuse Axonal Injury after Traumatic Brain Injury and Response to Sildenafil Treatment

Science.gov (United States)

2016-04-05

n=4, FPI+sildenafil n=3). No significant main effect of either injury or treatment was observed (data not shown). Water Maze Animals in all groups...spent in prior quadrant on trial one of test day revealed no significant main effect of either injury or treatment . 41 Figure 15. Water ...injury with sildenafil treatment (each pɘ.0001). Error bars represent SEM. 50 Analysis of mean diffusivity in grey matter ROIs

Safety climate and injuries: an examination of theoretical and empirical relationships.

Science.gov (United States)

Beus, Jeremy M; Payne, Stephanie C; Bergman, Mindy E; Arthur, Winfred

2010-07-01

Our purpose in this study was to meta-analytically address several theoretical and empirical issues regarding the relationships between safety climate and injuries. First, we distinguished between extant safety climate-->injury and injury-->safety climate relationships for both organizational and psychological safety climates. Second, we examined several potential moderators of these relationships. Meta-analyses revealed that injuries were more predictive of organizational safety climate than safety climate was predictive of injuries. Additionally, the injury-->safety climate relationship was stronger for organizational climate than for psychological climate. Moderator analyses revealed that the degree of content contamination in safety climate measures inflated effects, whereas measurement deficiency attenuated effects. Additionally, moderator analyses showed that as the time period over which injuries were assessed lengthened, the safety climate-->injury relationship was attenuated. Supplemental meta-analyses of specific safety climate dimensions also revealed that perceived management commitment to safety is the most robust predictor of occupational injuries. Contrary to expectations, the operationalization of injuries did not meaningfully moderate safety climate-injury relationships. Implications and recommendations for future research and practice are discussed.

Depletion of macrophages in CD11b diphtheria toxin receptor mice induces brain inflammation and enhances inflammatory signaling during traumatic brain injury.

Science.gov (United States)

Frieler, Ryan A; Nadimpalli, Sameera; Boland, Lauren K; Xie, Angela; Kooistra, Laura J; Song, Jianrui; Chung, Yutein; Cho, Kae W; Lumeng, Carey N; Wang, Michael M; Mortensen, Richard M

2015-10-22

Immune cells have important roles during disease and are known to contribute to secondary, inflammation-induced injury after traumatic brain injury. To delineate the functional role of macrophages during traumatic brain injury, we depleted macrophages using transgenic CD11b-DTR mice and subjected them to controlled cortical impact. We found that macrophage depletion had no effect on lesion size assessed by T2-weighted MRI scans 28 days after injury. Macrophage depletion resulted in a robust increase in proinflammatory gene expression in both the ipsilateral and contralateral hemispheres after controlled cortical impact. Interestingly, this sizeable increase in inflammation did not affect lesion development. We also showed that macrophage depletion resulted in increased proinflammatory gene expression in the brain and kidney in the absence of injury. These data demonstrate that depletion of macrophages in CD11b-DTR mice can significantly modulate the inflammatory response during brain injury without affecting lesion formation. These data also reveal a potentially confounding inflammatory effect in CD11b-DTR mice that must be considered when interpreting the effects of macrophage depletion in disease models. Copyright © 2015 Elsevier B.V. All rights reserved.

Responses and Injuries to PMHS in Side-Facing and Oblique Seats in Horizontal Longitudinal Sled Tests per FAA Emergency Landing Conditions.

Science.gov (United States)

Humm, John R; Yoganandan, Narayan; Pintar, Frank A; DeWeese, Richard L; Moorcroft, David M; Taylor, Amanda M; Peterson, Brian

2016-11-01

The objective of the present exploratory study is to understand occupant responses in oblique and side-facing seats in the aviation environment, which are increasingly installed in modern aircrafts. Sled tests were conducted using intact Post Mortem Human Surrogates (PMHS) seated in custom seats approximating standard aircraft geometry. End conditions were selected to represent candidate aviation seat and restraint configurations. Three-dimensional head center-of-gravity linear accelerations, head angular velocities, and linear accelerations of the T1, T6, and T12 spinous processes, and sacrum were obtained. Three-dimensional kinematics relative to the seat were obtained from retroreflective targets attached to the head, T1, T6, T12, and sacrum. All specimens sustained spinal injuries, although variations existed by vertebral level. While the tension mechanism was associated with cervical spine injuries, complex distraction-coupled with bending and tension was attributed to thoracolumbar spine injuries. Skeletal fractures to the ribcage were attributed to compression induced by the restraint from the seatbelt, the presence of the armrest, and/or severe motions of the unconstrained torso. Pelvic injuries were also attributed to restraint offered by the lap belt on the accelerating torso-pelvis complex in the absence of the armrest. Lower extremity injuries occurred due to the unconstrained motion (flailing mechanism). These results serve as an initial dataset to understand the kinematics of different body regions, injuries and patterns, and potential injury mechanisms describing PMHS responses in the aviation environment.

Depth-weighted robust multivariate regression with application to sparse data

KAUST Repository

Dutta, Subhajit; Genton, Marc G.

2017-01-01

A robust method for multivariate regression is developed based on robust estimators of the joint location and scatter matrix of the explanatory and response variables using the notion of data depth. The multivariate regression estimator possesses desirable affine equivariance properties, achieves the best breakdown point of any affine equivariant estimator, and has an influence function which is bounded in both the response as well as the predictor variable. To increase the efficiency of this estimator, a re-weighted estimator based on robust Mahalanobis distances of the residual vectors is proposed. In practice, the method is more stable than existing methods that are constructed using subsamples of the data. The resulting multivariate regression technique is computationally feasible, and turns out to perform better than several popular robust multivariate regression methods when applied to various simulated data as well as a real benchmark data set. When the data dimension is quite high compared to the sample size it is still possible to use meaningful notions of data depth along with the corresponding depth values to construct a robust estimator in a sparse setting.

Depth-weighted robust multivariate regression with application to sparse data

KAUST Repository

Dutta, Subhajit

2017-04-05

A robust method for multivariate regression is developed based on robust estimators of the joint location and scatter matrix of the explanatory and response variables using the notion of data depth. The multivariate regression estimator possesses desirable affine equivariance properties, achieves the best breakdown point of any affine equivariant estimator, and has an influence function which is bounded in both the response as well as the predictor variable. To increase the efficiency of this estimator, a re-weighted estimator based on robust Mahalanobis distances of the residual vectors is proposed. In practice, the method is more stable than existing methods that are constructed using subsamples of the data. The resulting multivariate regression technique is computationally feasible, and turns out to perform better than several popular robust multivariate regression methods when applied to various simulated data as well as a real benchmark data set. When the data dimension is quite high compared to the sample size it is still possible to use meaningful notions of data depth along with the corresponding depth values to construct a robust estimator in a sparse setting.

Blast Injuries: What Clinicians Need to Know

Centers for Disease Control (CDC) Podcasts

2008-11-05

In this podcast, Dr. Richard C. Hunt, Director of the CDC’s Division of Injury Response, National Center for Injury Prevention and Control provides a brief overview for health care providers on how to respond and care for persons injured by an explosion or blast event.  Created: 11/5/2008 by National Center for Injury Prevention and Control (NCIPC), Division of Injury Response (DIR).   Date Released: 11/6/2008.

Effect of PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction

Directory of Open Access Journals (Sweden)

Li-Jun Deng

2017-10-01

Full Text Available Objective: To study the effect of probucol + aspirin + atorvastatin (PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction. Methods: Patients with acute cerebral infarction who were treated in Affiliated Hospital of Jianghan University between February 2015 and January 2015 were selected and randomly divided into the PAS group who received probucol + aspirin + atorvastatin triple therapy and the control group who received aspirin + atorvastatin double therapy. The markers of nerve injury, oxidative stress and inflammatory response were determined before treatment and 15 d after treatment. Results: 15 d after treatment, peripheral blood Keap-1 expression and serum GPX1 contents of both groups of patients were significantly higher than those before treatment while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those before treatment, and peripheral blood Keap-1 expression and serum GPX1 content of PAS group were significantly higher than those of control group while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those of control group. Conclusion: PAS triple therapy can reduce the nerve injury as well as oxidative stress response and inflammatory response in patients with cerebral infarction.

Leaf age affects the responses of foliar injury and gas exchange to tropospheric ozone in Prunus serotina seedlings

International Nuclear Information System (INIS)

Zhang Jianwei; Schaub, Marcus; Ferdinand, Jonathan A.; Skelly, John M.; Steiner, Kim C.; Savage, James E.

2010-01-01

We investigated the effect of leaf age on the response of net photosynthesis (A), stomatal conductance (g wv ), foliar injury, and leaf nitrogen concentration (N L ) to tropospheric ozone (O 3 ) on Prunus serotina seedlings grown in open-plots (AA) and open-top chambers, supplied with either carbon-filtered or non-filtered air. We found significant variation in A, g wv , foliar injury, and N L (P 3 treatments. Seedlings in AA showed the highest A and g wv due to relatively low vapor pressure deficit (VPD). Older leaves showed significantly lower A, g wv , N L , and higher foliar injury (P wv , and foliar injury to O 3 . Both VPD and N L had a strong influence on leaf gas exchange. Foliar O 3 -induced injury appeared when cumulative O 3 uptake reached 8-12 mmol m -2 , depending on soil water availability. The mechanistic assessment of O 3 -induced injury is a valuable approach for a biologically relevant O 3 risk assessment for forest trees. - Ozone effects on symptom development and leaf gas exchange interacted with leaf age and N-content on black cherry seedlings.

Role of alveolar epithelial Early growth response-1 (Egr-1) in CD8+ T Cell mediated Lung Injury

OpenAIRE

Ramana, Chilakamarti V.; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung- Joo; Enelow, Richard I.

2009-01-01

Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8+ T cells in this injury, and have found that the critical effector molecule is TNF-α expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory c...

Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat

Science.gov (United States)

Zheng, Lingxing; Walls, Michael; Allette, Yohance M.; White, Fletcher A.; Shi, Riyi

2013-01-01

Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound’s pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggests that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. PMID:24147766

Response to Intervention: The Functional Assessment of Children Returning to School with Traumatic Brain Injury

Science.gov (United States)

Dykeman, Bruce F.

2009-01-01

Children with Traumatic Brain Injury (TBI) face many demands when completing their rehabilitation and returning to school. Although the prognosis can be favorable for many children, the course of recovery poses unique challenges for children and staff alike. To this end, a functional assessment of TBI children within a Response-to-Intervention…

Mechanisms of motor recovery after subtotal spinal cord injury: insights from the study of mice carrying a mutation (WldS) that delays cellular responses to injury.

Science.gov (United States)

Zhang, Z; Guth, L; Steward, O

1998-01-01

Partial lesions of the mammalian spinal cord result in an immediate motor impairment that recovers gradually over time; however, the cellular mechanisms responsible for the transient nature of this paralysis have not been defined. A unique opportunity to identify those injury-induced cellular responses that mediate the recovery of function has arisen from the discovery of a unique mutant strain of mice in which the onset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated WldS for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We have used this experimental animal model to evaluate possible causal relationships between these delayed cellular responses and the onset of functional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in WldS (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor function at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) was substantially delayed in mice carrying the WldS mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor function until 16 days postoperatively. (a) The rapid return of locomotor function in the C57BL/6 mice suggests that the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) The marked delay in the return of locomotor function in WldS mice indicates that the processes of neuroplasticity are induced by degenerative changes in the damaged neurons. (c) These strains of mice can be effectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional plasticity and restoring locomotor function after spinal cord injury.

Inflammatory and apoptotic alterations in serum and injured tissue after experimental polytrauma in mice: distinct early response compared with single trauma or "double-hit" injury.

Science.gov (United States)

Weckbach, Sebastian; Hohmann, Christoph; Braumueller, Sonja; Denk, Stephanie; Klohs, Bettina; Stahel, Philip F; Gebhard, Florian; Huber-Lang, Markus S; Perl, Mario

2013-02-01

The exact alterations of the immune system after polytrauma leading to sepsis and multiple-organ failure are poorly understood. Thus, the early local and systemic inflammatory and apoptotic response was characterized in a new polytrauma model and compared with the alterations seen after single or combined injuries. Anesthetized C57BL/6 mice were subjected to either blunt bilateral chest trauma (Tx), closed head injury, right femur fracture including contralateral soft tissue injury, or a combination of injuries (PTx). After 2 hours or 6 hours, animals were sacrificed, and the systemic as well as the local pulmonary immune response (bronchoalveolar lavage [BAL]/plasma cytokines, lung myeloperoxidase [MPO] activity, and alveolocapillary barrier dysfunction) were evaluated along with lung/brain apoptosis (lung caspase 3 Western blotting, immunohistochemistry, and polymorphonuclear leukocytes [PMN] Annexin V). Hemoglobin, PO2 saturation, and pH did not differ between the experimental groups. Local BAL cytokines/chemokines were significantly increased in almost all groups, which included Tx. There was no further enhancement of this local inflammatory response in the lungs in case of PTx. At 2 hours, all groups except sham and closed head injury alone revealed an increased activity of lung MPO. However, 6 hours after injury, lung MPO remained increased only in the PTx group. Increased BAL protein levels were found, reflecting enhanced lung leakage in all groups with Tx 6 hours after trauma. Only after PTx was neutrophil apoptosis significantly decreased, whereas lung caspase 3 and plasma interleukin 6/keratinocyte chemoattractant (KC) were substantially increased. The combination of different injuries leads to an earlier systemic inflammatory response when compared with the single insults. Interestingly, only after PTx but not after single or double hits was lung apoptosis increased, and PMN apoptosis was decreased along with a prolonged presence of neutrophils in the

The contribution of staff call light response time to fall and injurious fall rates: an exploratory study in four US hospitals using archived hospital data

Directory of Open Access Journals (Sweden)

Tzeng Huey-Ming

2012-03-01

Full Text Available Abstract Background Fall prevention programs for hospitalized patients have had limited success, and the effect of programs on decreasing total falls and fall-related injuries is still inconclusive. This exploratory multi-hospital study examined the unique contribution of call light response time to predicting total fall rates and injurious fall rates in inpatient acute care settings. The conceptual model was based on Donabedian's framework of structure, process, and health-care outcomes. The covariates included the hospital, unit type, total nursing hours per patient-day (HPPDs, percentage of the total nursing HPPDs supplied by registered nurses, percentage of patients aged 65 years or older, average case mix index, percentage of patients with altered mental status, percentage of patients with hearing problems, and call light use rate per patient-day. Methods We analyzed data from 28 units from 4 Michigan hospitals, using archived data and chart reviews from January 2004 to May 2009. The patient care unit-month, defined as data aggregated by month for each patient care unit, was the unit of analysis (N = 1063. Hierarchical multiple regression analyses were used. Results Faster call light response time was associated with lower total fall and injurious fall rates. Units with a higher call light use rate had lower total fall and injurious fall rates. A higher percentage of productive nursing hours provided by registered nurses was associated with lower total fall and injurious fall rates. A higher percentage of patients with altered mental status was associated with a higher total fall rate but not a higher injurious fall rate. Units with a higher percentage of patients aged 65 years or older had lower injurious fall rates. Conclusions Faster call light response time appeared to contribute to lower total fall and injurious fall rates, after controlling for the covariates. For practical relevance, hospital and nursing executives should consider

Within-session responses to high-intensity interval training in spinal cord injury.

Science.gov (United States)

Astorino, Todd Anthony; Thum, Jacob S

2018-02-01

Completion of high-intensity interval training (HIIT) increases maximal oxygen uptake and health status, yet its feasibility in persons with spinal cord injury is unknown. To compare changes in cardiorespiratory and metabolic variables between two interval training regimes and moderate intensity exercise. Nine adults with spinal cord injury (duration = 6.8 ± 6.2 year) initially underwent determination of peak oxygen uptake. During subsequent sessions, they completed moderate intensity exercise, HIIT, or sprint interval training. Oxygen uptake, heart rate, and blood lactate concentration were measured. Oxygen uptake and heart rate increased (p  0.05) to moderate intensity exercise. Peak oxygen uptake and heart rate were higher (p HIIT (90% peak oxygen uptake and 99% peak heart rate) and sprint interval training (80% peak oxygen uptake and 96% peak heart rate) versus moderate intensity exercise. Despite a higher intensity and peak cardiorespiratory strain, all participants preferred interval training versus moderate exercise. Examining long-term efficacy and feasibility of interval training in this population is merited, considering that exercise intensity is recognized as the most important variable factor of exercise programming to optimize maximal oxygen uptake. Implications for Rehabilitation Spinal cord injury (SCI) reduces locomotion which impairs voluntary physical activity, typically resulting in a reduction in peak oxygen uptake and enhanced chronic disease risk. In various able-bodied populations, completion of high-intensity interval training (HIIT) has been consistently reported to improve cardiorespiratory fitness and other health-related outcomes, although its efficacy in persons with SCI is poorly understood. Data from this study in 9 men and women with SCI show similar changes in oxygen uptake and heart in response to HIIT compared to a prolonged bout of aerobic exercise, although peak values were higher in response to HIIT. Due to

Information theory perspective on network robustness

International Nuclear Information System (INIS)

Schieber, Tiago A.; Carpi, Laura; Frery, Alejandro C.; Rosso, Osvaldo A.; Pardalos, Panos M.; Ravetti, Martín G.

2016-01-01

A crucial challenge in network theory is the study of the robustness of a network when facing a sequence of failures. In this work, we propose a dynamical definition of network robustness based on Information Theory, that considers measurements of the structural changes caused by failures of the network's components. Failures are defined here as a temporal process defined in a sequence. Robustness is then evaluated by measuring dissimilarities between topologies after each time step of the sequence, providing a dynamical information about the topological damage. We thoroughly analyze the efficiency of the method in capturing small perturbations by considering different probability distributions on networks. In particular, we find that distributions based on distances are more consistent in capturing network structural deviations, as better reflect the consequences of the failures. Theoretical examples and real networks are used to study the performance of this methodology. - Highlights: • A novel methodology to measure the robustness of a network to component failure or targeted attacks is proposed. • The use of the network's distance PDF allows a precise analysis. • The method provides a dynamic robustness profile showing the response of the topology to each failure event. • The measure is capable to detect network's critical elements.

Suprathreshold Heat Pain Response Predicts Activity-Related Pain, but Not Rest-Related Pain, in an Exercise-Induced Injury Model

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Coronado, Rogelio A.; Simon, Corey B.; Valencia, Carolina; Parr, Jeffrey J.; Borsa, Paul A.; George, Steven Z.

2014-01-01

Exercise-induced injury models are advantageous for studying pain since the onset of pain is controlled and both pre-injury and post-injury factors can be utilized as explanatory variables or predictors. In these studies, rest-related pain is often considered the primary dependent variable or outcome, as opposed to a measure of activity-related pain. Additionally, few studies include pain sensitivity measures as predictors. In this study, we examined the influence of pre-injury and post-injury factors, including pain sensitivity, for induced rest and activity-related pain following exercise induced muscle injury. The overall goal of this investigation was to determine if there were convergent or divergent predictors of rest and activity-related pain. One hundred forty-three participants provided demographic, psychological, and pain sensitivity information and underwent a standard fatigue trial of resistance exercise to induce injury of the dominant shoulder. Pain at rest and during active and resisted shoulder motion were measured at 48- and 96-hours post-injury. Separate hierarchical models were generated for assessing the influence of pre-injury and post-injury factors on 48- and 96-hour rest-related and activity-related pain. Overall, we did not find a universal predictor of pain across all models. However, pre-injury and post-injury suprathreshold heat pain response (SHPR), a pain sensitivity measure, was a consistent predictor of activity-related pain, even after controlling for known psychological factors. These results suggest there is differential prediction of pain. A measure of pain sensitivity such as SHPR appears more influential for activity-related pain, but not rest-related pain, and may reflect different underlying processes involved during pain appraisal. PMID:25265560

Arthroscopic knee surgery does not modify hyperalgesic responses to heat injury

DEFF Research Database (Denmark)

Werner, Mads U; Duun, Preben; Kraemer, Otto

2003-01-01

contralateral to the surgical side. Ibuprofen and acetaminophen were given for 2 days before the first burn injury and again from the time of surgery. In the controls, the two burn injuries were separated by 7 days. Sensory variables included cumulated pain score during induction of the burn (visual analog...... scale), secondary hyperalgesia area, and mechanical and thermal pain perception and pain thresholds assessed before and 1 h after the burn injury. RESULTS: The heat injuries induced significant increases in pain perception (P pain thresholds (P pain...... thresholds were higher during the second burn injury in patients (P pain to heat injury (P > 0.8), secondary hyperalgesia areas (P > 0.1), mechanical and thermal pain perception (P > 0.1), or mechanical and thermal pain...

The extent of soft tissue and musculoskeletal injuries after earthquakes; describing a role for reconstructive surgeons in an emergency response.

Science.gov (United States)

Clover, A J P; Jemec, B; Redmond, A D

2014-10-01

Earthquakes are the leading cause of natural disaster-related mortality and morbidity. Soft tissue and musculoskeletal injuries are the predominant type of injury seen after these events and a major reason for admission to hospital. Open fractures are relatively common; however, they are resource-intense to manage. Appropriate management is important in minimising amputation rates and preserving function. This review describes the pattern of musculoskeletal and soft-tissue injuries seen after earthquakes and explores the manpower and resource implications involved in their management. A Medline search was performed, including terms "injury pattern" and "earthquake," "epidemiology injuries" and "earthquakes," "plastic surgery," "reconstructive surgery," "limb salvage" and "earthquake." Papers published between December 1992 and December 2012 were included, with no initial language restriction. Limb injuries are the commonest injuries seen accounting for 60 % of all injuries, with fractures in more than 50 % of those admitted to hospital, with between 8 and 13 % of these fractures open. After the first few days and once the immediate lifesaving phase is over, the management of these musculoskeletal and soft-tissue injuries are the commonest procedures required. Due to the predominance of soft-tissue and musculoskeletal injuries, plastic surgeons as specialists in soft-tissue reconstruction should be mobilised in the early stages of a disaster response as part of a multidisciplinary team with a focus on limb salvage.

Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury

DEFF Research Database (Denmark)

Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

2005-01-01

Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via intracell......Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via...... intracellular signaling. This cytokine exerts its functions via interaction with two receptors: type-1 receptor (TNFR1) and type-2 receptor (TNFR2). In this work, the inflammatory response after a freeze injury (cryolesion) in the cortex was studied in wild-type (WT) animals and in mice lacking TNFR1 (TNFR1 KO...... signaling also affected the expression of apoptosis/cell death-related genes (Fas, Rip, p53), matrix metalloproteinases (MMP3, MMP9, MMP12), and their inhibitors (TIMP1), suggesting a role of TNFR1 in extracellular matrix remodeling after injury. However, GDNF, NGF, and BDNF expression were not affected...

An adenoviral vector expressing lipoprotein A, a major antigen of Mycoplasma mycoides subspecies mycoides, elicits robust immune responses in mice.

Science.gov (United States)

Carozza, Marlène; Rodrigues, Valérie; Unterfinger, Yves; Galea, Sandra; Coulpier, Muriel; Klonjkowski, Bernard; Thiaucourt, François; Totté, Philippe; Richardson, Jennifer

2015-01-01

Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides small colony type (MmmSC), is a devastating respiratory disease of cattle. In sub-Saharan Africa, where CBPP is enzootic, live attenuated vaccines are deployed but afford only short-lived protection. In cattle, recovery from experimental MmmSC infection has been associated with the presence of CD4(+) T lymphocytes that secrete interferon gamma in response to MmmSC, and in particular to the lipoprotein A (LppA) antigen. In an effort to develop a better vaccine against CBPP, a viral vector (Ad5-LppA) that expressed LppA was generated from human adenovirus type 5. The LppA-specific immune responses elicited by the Ad5-LppA vector were evaluated in mice, and compared to those elicited by recombinant LppA formulated with a potent adjuvant. Notably, a single administration of Ad5-LppA, but not recombinant protein, sufficed to elicit a robust LppA-specific humoral response. After a booster administration, both vector and recombinant protein elicited strong LppA-specific humoral and cell-mediated responses. Ex vivo stimulation of splenocytes induced extensive proliferation of CD4(+) T cells for mice immunized with vector or protein, and secretion of T helper 1-associated and proinflammatory cytokines for mice immunized with Ad5-LppA. Our study - by demonstrating the potential of a viral-vectored prototypic vaccine to elicit prompt and robust immune responses against a major antigen of MmmSC - represents a first step in developing a recombinant vaccine against CBPP. Copyright © 2014 Elsevier Ltd. All rights reserved.

Robust design optimization using the price of robustness, robust least squares and regularization methods

Science.gov (United States)

Bukhari, Hassan J.

2017-12-01

In this paper a framework for robust optimization of mechanical design problems and process systems that have parametric uncertainty is presented using three different approaches. Robust optimization problems are formulated so that the optimal solution is robust which means it is minimally sensitive to any perturbations in parameters. The first method uses the price of robustness approach which assumes the uncertain parameters to be symmetric and bounded. The robustness for the design can be controlled by limiting the parameters that can perturb.The second method uses the robust least squares method to determine the optimal parameters when data itself is subjected to perturbations instead of the parameters. The last method manages uncertainty by restricting the perturbation on parameters to improve sensitivity similar to Tikhonov regularization. The methods are implemented on two sets of problems; one linear and the other non-linear. This methodology will be compared with a prior method using multiple Monte Carlo simulation runs which shows that the approach being presented in this paper results in better performance.

Response actions to difficulties in using everyday technology after acquired brain injury.

Science.gov (United States)

Larsson Lund, Maria; Lövgren Engström, Ann-Louice; Lexell, Jan

2012-03-01

People with acquired brain injury (ABI) have difficulties using everyday technology (ET) in daily tasks at home and in society. To support them in managing the demands imposed by using ET, knowledge is needed concerning their response actions to the difficulties. The aim of this study was to explore and describe what characterizes response actions to difficulties using ET, their conditions, and how they influence the experiences of tasks in daily life among people with ABI. Interviews and observations were undertaken with 13 persons with an ABI. Data were analysed qualitatively using the constant comparative method. The participants' response actions were categorized as (i) deliberate and organized planning, (ii) random and inflexible repeating (iii), re-evaluating tasks, (iv) explaining difficulties related to others, and (iv) proving and protecting capability. Certain conditions were decisive for the different response actions to be applied and also for their effectiveness in enabling engagement in tasks in daily life. Each participant used several types of response actions and the same action could be applied in several situations. To support people with an ABI to manage the demands imposed by using ET, it is important to identify the uniqueness of each client and his or her response actions to difficulties using ET and thereafter adjust the interventions accordingly.

Robust Measurement via A Fused Latent and Graphical Item Response Theory Model.

Science.gov (United States)

Chen, Yunxiao; Li, Xiaoou; Liu, Jingchen; Ying, Zhiliang

2018-03-12

Item response theory (IRT) plays an important role in psychological and educational measurement. Unlike the classical testing theory, IRT models aggregate the item level information, yielding more accurate measurements. Most IRT models assume local independence, an assumption not likely to be satisfied in practice, especially when the number of items is large. Results in the literature and simulation studies in this paper reveal that misspecifying the local independence assumption may result in inaccurate measurements and differential item functioning. To provide more robust measurements, we propose an integrated approach by adding a graphical component to a multidimensional IRT model that can offset the effect of unknown local dependence. The new model contains a confirmatory latent variable component, which measures the targeted latent traits, and a graphical component, which captures the local dependence. An efficient proximal algorithm is proposed for the parameter estimation and structure learning of the local dependence. This approach can substantially improve the measurement, given no prior information on the local dependence structure. The model can be applied to measure both a unidimensional latent trait and multidimensional latent traits.

Stimulation of 5-HT2A receptors recovers sensory responsiveness in acute spinal neonatal rats.

Science.gov (United States)

Swann, Hillary E; Kauer, Sierra D; Allmond, Jacob T; Brumley, Michele R

2017-02-01

Quipazine is a 5-HT 2A -receptor agonist that has been used to induce motor activity and promote recovery of function after spinal cord injury in neonatal and adult rodents. Sensory stimulation also activates sensory and motor circuits and promotes recovery after spinal cord injury. In rats, tail pinching is an effective and robust method of sacrocaudal sensory afferent stimulation that induces motor activity, including alternating stepping. In this study, responsiveness to a tail pinch following treatment with quipazine (or saline vehicle control) was examined in spinal cord transected (at midthoracic level) and intact neonatal rats. Rat pups were secured in the supine posture with limbs unrestricted. Quipazine or saline was administered intraperitoneally and after a 10-min period, a tail pinch was administered. A 1-min baseline period prior to tail-pinch administration and a 1-min response period postpinch was observed and hind-limb motor activity, including locomotor-like stepping behavior, was recorded and analyzed. Neonatal rats showed an immediate and robust response to sensory stimulation induced by the tail pinch. Quipazine recovered hind-limb movement and step frequency in spinal rats back to intact levels, suggesting a synergistic, additive effect of 5-HT-receptor and sensory stimulation in spinal rats. Although levels of activity in spinal rats were restored with quipazine, movement quality (high vs. low amplitude) was only partially restored. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Gustatory tissue injury in man: radiation dose response relationships and mechanisms of taste loss

International Nuclear Information System (INIS)

Mossman, K.L.

1986-01-01

In this report dose response data for gustatory tissue damage in patients given total radiation doses ranging from 3000 to 6000 cGy are presented. In order to evaluate direct radiation injury to gustatory tissues as a mechanism of taste loss, measurements of damage to specific taste structures in bovine and murine systems following radiation exposure in the clinical range are correlated to taste impairment observed in radiotherapy patients. (author)

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology

Science.gov (United States)

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental

Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.

Science.gov (United States)

Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

2014-10-01

Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial

Human-derived nanoparticles and vascular response to injury in rabbit carotid arteries: Proof of principle

Directory of Open Access Journals (Sweden)

Maria A K Schwartz

2008-06-01

Full Text Available Maria A K Schwartz1, John C Lieske2, Vivek Kumar2, Gerard Farell-Baril2, Virginia M Miller1,31Departments of Physiology and Biomedical Engineering, Internal Medicine; 2Division of Nephrology, and 3Surgery, Mayo Clinic College of Medicine, Rochester, MN, USAAbstract: Self-calcifying, self-replicating nanoparticles have been isolated from calcified human tissues. However, it is unclear if these nanoparticles participate in disease processes. Therefore, this study was designed to preliminarily test the hypothesis that human-derived nanoparticles are causal to arterial disease processes. One carotid artery of 3 kg male rabbits was denuded of endothelium; the contralateral artery remained unoperated as a control. Each rabbit was injected intravenously with either saline, calcified, or decalcified nanoparticles cultured from calcified human arteries or kidney stones. After 35 days, both injured and control arteries were removed for histological examination. Injured arteries from rabbits injected with saline showed minimal, eccentric intimal hyperplasia. Injured arteries from rabbits injected with calcified kidney stone- and arterial-derived nanoparticles occluded, sometimes with canalization. The calcified kidney stone-derived nanoparticles caused calcifications within the occlusion. Responses to injury in rabbits injected with decalcified kidney stone-derived nanoparticles were similar to those observed in saline-injected animals. However, decalcified arterial-derived nanoparticles produced intimal hyperplasia that varied from moderate to occlusion with canalization and calcifi cation. This study offers the first evidence that there may be a causal relationship between human-derived nanoparticles and response to injury including calcification in arteries with damaged endothelium.Keywords: arterial calcification, endothelial injury, intimal hyperplasia

Robustness studies on coal gasification process variables

African Journals Online (AJOL)

coal before feeding to the gasification process [1]. .... to-control variables will make up the terms in the response surface model for the ... Montgomery (1999) explained that all the Taguchi engineering objectives for a robust ..... software [3].

Foliar injury responses of eleven plant species to ozone/sulfur dioxide mixtures

Energy Technology Data Exchange (ETDEWEB)

Tingey, D T; Reinert, R A; Dunning, J A; Heck, W W

1973-01-01

Eleven plant species were exposed to ozone and/or sulfur dioxide to determine if a mixture of the two gases enhanced foliar injury. Tobacco, radish, and alfalfa developed more injury that the additive injury of the single gases. In other species, such as cabbage, broccoli, and tomato, the foliar injury from mixed-gas exposures was additive or less than additive. Leaf injury from the ozone/sulfur dioxide mixture appeared as upper surface flecking, stipple, bifacial necrosis, and lower surface glazing and, in general, appeared similar to injury from oxidant or ozone. The concentrations of ozone and sulfur dioxide that caused plant injury were similar to those found in urban areas. These concentrations may result in yield losses to plants grown under field conditions.

Psychological impact of injuries in athletes.

Science.gov (United States)

Smith, A M

1996-12-01

Although research on the psychological impact of injury is in its infancy, this article reviews relevant literature focusing on post-injury emotional response, self-esteem, and the effect of mood disturbance on rehabilitation from sport injury. Injury is often accompanied by depression, tension, anger and low self-esteem, particularly in competitive, seriously injured athletes. Mood disturbance seems to relate to the athlete's perceived progress in rehabilitation and has been shown to negatively relate to attendance at rehabilitation sessions. This article also describes how the Emotional Responses of Athletes to Injury Questionnaire (ERAIQ) serves as a guide for the initial interview of an injured athlete. Interventions such as positive self-talk, relaxation, goal setting and healing imagery, all used by a faster healing group of athletes, and although not well researched, seem appropriate to assist athletes in coping with injury. Modelling interventions during injury rehabilitation have also been shown to have a positive effect on rehabilitation and should be used. These relationships are described in more depth and in the context of a theoretical model. Directions for future research are suggested.

Hepatic injury induces contrasting response in liver and kidney to chemicals that are metabolically activated: Role of male sex hormone

International Nuclear Information System (INIS)

Kim, Young C.; Yim, Hye K.; Jung, Young S.; Park, Jae H.; Kim, Sung Y.

2007-01-01

Injury to liver, resulting in loss of its normal physiological/biochemical functions, may adversely affect a secondary organ. We examined the response of the liver and kidney to chemical substances that require metabolic activation for their toxicities in mice with a preceding liver injury. Carbon tetrachloride treatment 24 h prior to a challenging dose of carbon tetrachloride or acetaminophen decreased the resulting hepatotoxicity both in male and female mice as determined by histopathological examination and increases in serum enzyme activities. In contrast, the renal toxicity of the challenging toxicants was elevated markedly in male, but not in female mice. Partial hepatectomy also induced similar changes in the hepatotoxicity and nephrotoxicity of a challenging toxicant, suggesting that the contrasting response of male liver and kidney was associated with the reduction of the hepatic metabolizing capacity. Carbon tetrachloride pretreatment or partial hepatectomy decreased the hepatic xenobiotic-metabolizing enzyme activities in both sexes but elevated the renal p-nitrophenol hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase activities significantly only in male mice. Increases in Cyp2e1 and Cyp2b expression were also evident in male kidney. Castration of males or testosterone administration to females diminished the sex-related differences in the renal response to an acute liver injury. The results indicate that reduction of the hepatic metabolizing capacity induced by liver injury may render secondary target organs susceptible to chemical substances activated in these organs. This effect may be sex-specific. It is also suggested that an integrated approach should be taken for proper assessment of chemical hazards

Perceptual Robust Design

DEFF Research Database (Denmark)

Pedersen, Søren Nygaard

The research presented in this PhD thesis has focused on a perceptual approach to robust design. The results of the research and the original contribution to knowledge is a preliminary framework for understanding, positioning, and applying perceptual robust design. Product quality is a topic...... been presented. Therefore, this study set out to contribute to the understanding and application of perceptual robust design. To achieve this, a state-of-the-art and current practice review was performed. From the review two main research problems were identified. Firstly, a lack of tools...... for perceptual robustness was found to overlap with the optimum for functional robustness and at most approximately 2.2% out of the 14.74% could be ascribed solely to the perceptual robustness optimisation. In conclusion, the thesis have offered a new perspective on robust design by merging robust design...

Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.

Directory of Open Access Journals (Sweden)

Manoj Bhasin

Full Text Available Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC and medial smooth muscle cells (SMC from canine vein grafts, 2 hours (H to 30 days (D following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12-24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1 signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1, a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention.

Injuries in Slow-Pitch Softball.

Science.gov (United States)

Loosli, Alvin R.; And Others

1988-01-01

Review of sports medicine records of 285 softball players and responses of 200 adult softball players to a questionnaire regarding injuries leads to suggestions about ways to prevent softball injuries, including preseason conditioning and strengthening. (Author/CB)

Interleukin-1 Receptor in Seizure Susceptibility after Traumatic Injury to the Pediatric Brain.

Science.gov (United States)

Semple, Bridgette D; O'Brien, Terence J; Gimlin, Kayleen; Wright, David K; Kim, Shi Eun; Casillas-Espinosa, Pablo M; Webster, Kyria M; Petrou, Steven; Noble-Haeusslein, Linda J

2017-08-16

Epilepsy after pediatric traumatic brain injury (TBI) is associated with poor quality of life. This study aimed to characterize post-traumatic epilepsy in a mouse model of pediatric brain injury, and to evaluate the role of interleukin-1 (IL-1) signaling as a target for pharmacological intervention. Male mice received a controlled cortical impact or sham surgery at postnatal day 21, approximating a toddler-aged child. Mice were treated acutely with an IL-1 receptor antagonist (IL-1Ra; 100 mg/kg, s.c.) or vehicle. Spontaneous and evoked seizures were evaluated from video-EEG recordings. Behavioral assays tested for functional outcomes, postmortem analyses assessed neuropathology, and brain atrophy was detected by ex vivo magnetic resonance imaging. At 2 weeks and 3 months post-injury, TBI mice showed an elevated seizure response to the convulsant pentylenetetrazol compared with sham mice, associated with abnormal hippocampal mossy fiber sprouting. A robust increase in IL-1β and IL-1 receptor were detected after TBI. IL-1Ra treatment reduced seizure susceptibility 2 weeks after TBI compared with vehicle, and a reduction in hippocampal astrogliosis. In a chronic study, IL-1Ra-TBI mice showed improved spatial memory at 4 months post-injury. At 5 months, most TBI mice exhibited spontaneous seizures during a 7 d video-EEG recording period. At 6 months, IL-1Ra-TBI mice had fewer evoked seizures compared with vehicle controls, coinciding with greater preservation of cortical tissue. Findings demonstrate this model's utility to delineate mechanisms underlying epileptogenesis after pediatric brain injury, and provide evidence of IL-1 signaling as a mediator of post-traumatic astrogliosis and seizure susceptibility. SIGNIFICANCE STATEMENT Epilepsy is a common cause of morbidity after traumatic brain injury in early childhood. However, a limited understanding of how epilepsy develops, particularly in the immature brain, likely contributes to the lack of efficacious treatments

Leaf age affects the responses of foliar injury and gas exchange to tropospheric ozone in Prunus serotina seedlings

Science.gov (United States)

Jianwei Zhang; Marcus Schaub; Jonathan A. Ferdinand; John M. Skelly; Kim C. Steiner; James E. Savage

2010-01-01

We investigated the effect of leaf age on the response of net photosynthesis (A), stomatal conductance (gwv), foliar injury, and leaf nitrogen concentration (NL) to tropospheric ozone (O3) on Prunus serotina seedlings grown in open-plots (AA) and open-top...

The role and dynamics of β-catenin in precondition induced neuroprotection after traumatic brain injury.

Directory of Open Access Journals (Sweden)

Gali Umschweif

Full Text Available Preconditioning via heat acclimation (34°C 30 d results in neuroprotection from traumatic brain injury due to constitutive as well as dynamic changes triggered by the trauma. Among these changes is Akt phosphorylation, which decreases apoptosis and induces HIF1α. In the present study we investigated the Akt downstream GSK3β/β-catenin pathway and focused on post injury alternations of β catenin and its impact on the cellular response in preconditioned heat acclimated mice. We found that the reduction in motor disability is accompanied with attenuation of depressive like behavior in heat acclimated mice that correlates with the GSK3β phosphorylation state. Concomitantly, a robust β catenin phosphorylation is not followed by its degradation, or by reduced nuclear accumulation. Enhanced tyrosine phosphorylation of β catenin in the injured area weakens the β catenin-N cadherin complex. Membrane β catenin is transiently reduced in heat acclimated mice and its recovery 7 days post TBI is accompanied by induction of the synaptic marker synaptophysin. We suggest a set of cellular events following traumatic brain injury in heat acclimated mice that causes β catenin to participate in cell-cell adhesion alternations rather than in Wnt signaling. These events may contribute to synaptogenesis and the improved motor and cognitive abilities seen heat acclimated mice after traumatic brain injury.

Using Dynamic Response Index (DRI) as a spinal injury predictor

CSIR Research Space (South Africa)

Ahmed, Rayeesa

2014-09-01

Full Text Available , moments and accelerations on an occupant are measured using an Anthropomorphic Testing Device (ATD). These measurements are then correlated to injury criteria which determine the probability of injury. Seats are typically evaluated in terms of probability...

Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus.

Directory of Open Access Journals (Sweden)

Taisheng Li

2006-12-01

Full Text Available Most of the individuals infected with SARS coronavirus (SARS-CoV spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.

“It's Just a Matter of Time:” Lessons from Agency and Community Responses to Polar Bear-inflicted Human Injury

OpenAIRE

Aimee L Schmidt; Douglas A Clark

2018-01-01

Bear-inflicted human injuries or deaths are often widely publicised, controversial, and evoke substantial social responses that articulate public expectations about bear management. In this paper, we examine how local people and management agencies (i.e. Manitoba Conservation, Parks Canada, and the Town of Churchill) responded to a polar bear-inflicted human injury in Churchill, Manitoba, Canada. On November 1st, 2013, two people in Churchill were badly mauled by a polar bear. The incident sh...

Data-driven quantification of the robustness and sensitivity of cell signaling networks

International Nuclear Information System (INIS)

Mukherjee, Sayak; Seok, Sang-Cheol; Vieland, Veronica J; Das, Jayajit

2013-01-01

Robustness and sensitivity of responses generated by cell signaling networks has been associated with survival and evolvability of organisms. However, existing methods analyzing robustness and sensitivity of signaling networks ignore the experimentally observed cell-to-cell variations of protein abundances and cell functions or contain ad hoc assumptions. We propose and apply a data-driven maximum entropy based method to quantify robustness and sensitivity of Escherichia coli (E. coli) chemotaxis signaling network. Our analysis correctly rank orders different models of E. coli chemotaxis based on their robustness and suggests that parameters regulating cell signaling are evolutionary selected to vary in individual cells according to their abilities to perturb cell functions. Furthermore, predictions from our approach regarding distribution of protein abundances and properties of chemotactic responses in individual cells based on cell population averaged data are in excellent agreement with their experimental counterparts. Our approach is general and can be used to evaluate robustness as well as generate predictions of single cell properties based on population averaged experimental data in a wide range of cell signaling systems. (paper)

The early IL-6 and IL-10 response in trauma is correlated with injury severity and mortality

DEFF Research Database (Denmark)

Stensballe, J; Christiansen, M; Tønnesen, E

2009-01-01

BACKGROUND: Trauma has previously been shown to influence interleukin (IL)-6 and IL-10 levels, but the association of injury severity and mortality with IL-6 and IL-10 responses in the early phase of accidental trauma remains to be investigated. We wished to describe serum levels of IL-6 and IL-10...... in the first 24 h after trauma and to assess the relationship with severity of injury and mortality. METHODS: Prospective, descriptive cohort study in a Level 1 trauma centre, Copenhagen, Denmark. We included 265 consecutive adult trauma patients admitted directly from the accident scene during an 18-month...... period. Serum levels of IL-6 and IL-10 were measured upon arrival and at 6, 12, and 24 h after admittance using an enzyme-linked immunosorbent assay. Correlation analysis was used to assess the relationship between Injury Severity Score (ISS) and levels of IL-6 and IL-10. Analysis of variance was used...

Application of Multivariate Modeling for Radiation Injury Assessment: A Proof of Concept

Directory of Open Access Journals (Sweden)

David L. Bolduc

2014-01-01

Full Text Available Multivariate radiation injury estimation algorithms were formulated for estimating severe hematopoietic acute radiation syndrome (H-ARS injury (i.e., response category three or RC3 in a rhesus monkey total-body irradiation (TBI model. Classical CBC and serum chemistry blood parameters were examined prior to irradiation (d 0 and on d 7, 10, 14, 21, and 25 after irradiation involving 24 nonhuman primates (NHP (Macaca mulatta given 6.5-Gy 60Co Υ-rays (0.4 Gy min−1 TBI. A correlation matrix was formulated with the RC3 severity level designated as the “dependent variable” and independent variables down selected based on their radioresponsiveness and relatively low multicollinearity using stepwise-linear regression analyses. Final candidate independent variables included CBC counts (absolute number of neutrophils, lymphocytes, and platelets in formulating the “CBC” RC3 estimation algorithm. Additionally, the formulation of a diagnostic CBC and serum chemistry “CBC-SCHEM” RC3 algorithm expanded upon the CBC algorithm model with the addition of hematocrit and the serum enzyme levels of aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. Both algorithms estimated RC3 with over 90% predictive power. Only the CBC-SCHEM RC3 algorithm, however, met the critical three assumptions of linear least squares demonstrating slightly greater precision for radiation injury estimation, but with significantly decreased prediction error indicating increased statistical robustness.

NLRP3-inflammasome activating DAMPs stimulate an inflammatory response in glia in the absence of priming which contributes to brain inflammation after injury

Directory of Open Access Journals (Sweden)

Catherine Diane Savage

2012-09-01

Full Text Available Inflammation in the absence of infection (sterile inflammation contributes to acute injury and chronic disease. Cerebral ischaemia is a devastating condition in which the primary injury is caused by reduced blood supply and is therefore sterile. The cytokine interleukin-1β (IL-1β is a key contributor to ischaemic brain injury and central inflammatory responses. The release of IL-1β is regulated by the protease caspase-1, and its activating complex, the inflammasome. Of the known inflammasomes the best characterised, and one that is perceived to sense sterile injury is formed by a pattern recognition receptor called NLRP3. A key feature of NLRP3-inflammasome dependent responses in vitro in macrophages is the requirement of an initial priming stimulus by a pathogen (PAMP, or damage associated molecular pattern (DAMP respectively. We sought to determine the inflammatory responses of NLRP3-activating DAMPs on brain derived mixed glial cells in the absence of an initial priming stimulus in vitro. In cultured mouse mixed glia the DAMPs ATP, MSU and CPPD crystals had no effect on the expression of IL-1α or IL-1β and induced release only when the cells were primed with a PAMP. In the absence of priming, these DAMPs did however induce inflammation via the production of IL-6 and CXCL1, and the release of the lysosomal protease cathepsin B. Furthermore, the acute phase protein serum amyloid A (SAA acted as a priming stimulus on glial cells resulting in levels of IL-1 expression comparable to those induced by the PAMP LPS. In vivo, after cerebral ischaemia, IL-1 production contributed to increased IL-6 and CXCL1 since these cytokines were profoundly reduced in the ischaemic hemispheres from IL-1α/β double KO mice, although injury-induced cytokine responses were not abolished. Thus, DAMPs augment brain inflammation by directly stimulating production of glial derived inflammatory mediators. This is markedly enhanced by DAMP-induced IL-1-release

Patterns of Storm Injury and Tree Response

Science.gov (United States)

Kevin Smith; Walter Shortle; Kenneth Dudzik

2001-01-01

The ice storm of January 1998 in the northeastern United States and adjacent Canada was an extreme example of severe weather that injures trees every year. Broken branches, split branch forks, and snapped stems are all examples of storm injury.

Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat.

Science.gov (United States)

Due, Michael R; Park, Jonghyuck; Zheng, Lingxing; Walls, Michael; Allette, Yohance M; White, Fletcher A; Shi, Riyi

2014-03-01

Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here, we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound's pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggest that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. Following spinal cord injury (SCI), acrolein involvement in neuropathic pain is likely through direct activation and elevated levels of pro-nociceptive channel TRPA1. While acrolein elevation correlates with neuropathic pain, suppression of this aldehyde by hydralazine leads to an analgesic effect. Acrolein may serve as a novel therapeutic target for preclinical and clinical SCI to relieve both acute and chronic post-SCI neuropathic pain. © 2013 International Society for Neurochemistry.

Functional role of monocytes and macrophages for the inflammatory response in acute liver injury

Directory of Open Access Journals (Sweden)

Henning W Zimmermann

2012-10-01

Full Text Available Different etiologies such as drug toxicity, acute viral hepatitis B or acetaminophen poisoning can cause acute liver injury (ALI or even acute liver failure (ALF. Excessive cell death of hepatocytes in the liver is known to result in a strong hepatic inflammation. Experimental murine models of liver injury highlighted the importance of hepatic macrophages, so-called Kupffer cells, for initiating and driving this inflammatory response by releasing proinflammatory cytokines and chemokines including tumor necrosis factor (TNF, interleukin-6 (IL-6, IL-1-beta or monocyte chemoattractant protein 1 (MCP-1, CCL2 as well as activating other non-parenchymal liver cells, e.g. endothelial or hepatic stellate cells (HSC. Many of these proinflammatory mediators can trigger hepatocytic cell death pathways, e.g. via caspase activation, but also activate protective signaling pathways, e.g. via nuclear factor kappa B (NF-kB. Recent studies in mice demonstrated that these macrophage actions largely depend on the recruitment of monocytes into the liver, namely of the inflammatory Ly6c+ (Gr1+ monocyte subset as precursors of tissue macrophages. The chemokine receptor CCR2 and its ligand MCP-1/CCL2 promote monocyte subset infiltration upon liver injury. In contrast, the chemokine receptor CX3CR1 and its ligand fractalkine (CX3CL1 are important negative regulators of monocyte infiltration by controlling their survival and differentiation into functionally diverse macrophage subsets upon injury. The recently identified cellular and molecular pathways for monocyte subset recruitment, macrophage differentiation and interactions with other hepatic cell types in the injured liver may therefore represent interesting novel targets for future therapeutic approaches in ALF.

Activation of bradykinin B2 receptor induced the inflammatory responses of cytosolic phospholipase A2 after the early traumatic brain injury.

Science.gov (United States)

Chao, Honglu; Liu, Yinlong; Lin, Chao; Xu, Xiupeng; Li, Zheng; Bao, Zhongyuan; Fan, Liang; Tao, Chao; Zhao, Lin; Liu, Yan; Wang, Xiaoming; You, Yongping; Liu, Ning; Ji, Jing

2018-06-09

Phospholipase A 2 is a known aggravator of inflammation and deteriorates neurological outcomes after traumatic brain injury (TBI), however the exact inflammatory mechanisms remain unknown. This study investigated the role of bradykinin and its receptor, which are known initial mediators within inflammation activation, as well as the mechanisms of the cytosolic phospholipase A 2 (cPLA 2 )-related inflammatory responses after TBI. We found that cPLA 2 and bradykinin B2 receptor were upregulated after a TBI. Rats treated with the bradykinin B2 receptor inhibitor LF 16-0687 exhibited significantly less cPLA 2 expression and related inflammatory responses in the brain cortex after sustaining a controlled cortical impact (CCI) injury. Both the cPLA 2 inhibitor and the LF16-0687 improved CCI rat outcomes by decreasing neuron death and reducing brain edema. The following TBI model utilized both primary astrocytes and primary neurons in order to gain further understanding of the inflammation mechanisms of the B2 bradykinin receptor and the cPLA 2 in the central nervous system. There was a stronger reaction from the astrocytes as well as a protective effect of LF16-0687 after the stretch injury and bradykinin treatment. The protein kinase C pathway was thought to be involved in the B2 bradykinin receptor as well as the cPLA 2 -related inflammatory responses. Rottlerin, a Protein Kinase C (PKC) δ inhibitor, decreased the activity of the cPLA 2 activity post-injury, and LF16-0687 suppressed both the PKC pathway and the cPLA 2 activity within the astrocytes. These results indicated that the bradykinin B2 receptor-mediated pathway is involved in the cPLA 2 -related inflammatory response from the PKC pathway. Copyright © 2018. Published by Elsevier B.V.

Development of a Finite Element Model of the Human Shoulder to Investigate the Mechanical Responses and Injuries in Side Impact

Science.gov (United States)

Iwamoto, Masami; Miki, Kazuo; Yang, King H.

Previous studies in both fields of automotive safety and orthopedic surgery have hypothesized that immobilization of the shoulder caused by the shoulder injury could be related to multiple rib fractures, which are frequently life threatening. Therefore, for more effective occupant protection, it is important to understand the relationship between shoulder injury and multiple rib fractures in side impact. The purpose of this study is to develop a finite element model of the human shoulder in order to understand this relationship. The shoulder model included three bones (the humerus, scapula and clavicle) and major ligaments and muscles around the shoulder. The model also included approaches to represent bone fractures and joint dislocations. The relationships between shoulder injury and immobilization of the shoulder are discussed using model responses for lateral shoulder impact. It is also discussed how the injury can be related to multiple rib fractures.

Loud preimpact tones reduce the cervical multifidus muscle response during rear-end collisions: a potential method for reducing whiplash injuries.

Science.gov (United States)

Mang, Daniel W H; Siegmund, Gunter P; Brown, Harrison J; Goonetilleke, Samanthi C; Blouin, Jean-Sébastien

2015-01-01

Neck muscle responses after unexpected rear-end collisions consist of a stereotypical combination of postural and startle responses. Prior work using surface electromyography (EMG) has shown that the superficial neck muscle responses can be attenuated when a loud tone (105 dB) is presented 250 milliseconds before impact, but the accompanying response of the deeper multifidus muscles remains unknown. Quantifying this response in multifidus is important because this muscle attaches directly to the cervical facet capsule and can potentially increase the strain in the capsule during an impact and contribute to whiplash injury. To investigate if a loud preimpact tone decreases the cervical multifidus muscle response during rear-end perturbations. After approval by the University Clinical Ethics Review Board, human volunteers experienced a series of three whiplash-like perturbations. Twelve subjects with no history of neurologic disorders or whiplash injury were recruited to participate in this experiment. Bilateral indwelling EMG of multifidus at the C4 and C6 levels, surface EMG of sternocleidomastoid (SCM) and C4 paraspinals (PARAs), and kinematics of the head/neck were measured. Subjects experienced three whiplash-like perturbations (peak acceleration of 19.5 m/s(2)) preceded by either no tone or a loud tone (105 dB) presented 250 milliseconds before sled acceleration onset. The loud tone decreased the muscle activity of C6 multifidus (42%) and C4 PARAs (30%), but did not affect the C4 multifidus or SCM activity. Peak head kinematic responses (extension angle: 6%, retraction: 9%, linear forward acceleration: 9%, and angular acceleration in extension: 13%) were also decreased by the loud preimpact tone. The attenuation of peak C6 multifidus activity and head kinematic responses suggests that a loud preimpact tone may reduce the strain in the cervical facet capsule, which may reduce the risk of whiplash injury during rear-end collisions. Copyright © 2015 Elsevier Inc

Robust mislabel logistic regression without modeling mislabel probabilities.

Science.gov (United States)

Hung, Hung; Jou, Zhi-Yu; Huang, Su-Yun

2018-03-01

Logistic regression is among the most widely used statistical methods for linear discriminant analysis. In many applications, we only observe possibly mislabeled responses. Fitting a conventional logistic regression can then lead to biased estimation. One common resolution is to fit a mislabel logistic regression model, which takes into consideration of mislabeled responses. Another common method is to adopt a robust M-estimation by down-weighting suspected instances. In this work, we propose a new robust mislabel logistic regression based on γ-divergence. Our proposal possesses two advantageous features: (1) It does not need to model the mislabel probabilities. (2) The minimum γ-divergence estimation leads to a weighted estimating equation without the need to include any bias correction term, that is, it is automatically bias-corrected. These features make the proposed γ-logistic regression more robust in model fitting and more intuitive for model interpretation through a simple weighting scheme. Our method is also easy to implement, and two types of algorithms are included. Simulation studies and the Pima data application are presented to demonstrate the performance of γ-logistic regression. © 2017, The International Biometric Society.

Novel robust cellulose-based foam with pH and light dual-response for oil recovery

Science.gov (United States)

Wang, Qian; Meng, Guihua; Wu, Jianning; Wang, Yixi; Liu, Zhiyong; Guo, Xuhong

2018-05-01

We fabricated pH and light dual-responsive adsorption materials which could induce the transition of surface wettability between hydrophobicity and hydrophilicity by using ATRP. The structure and morphology of adsorption materials were confirmed by ATR-FTIR, XPS, TGA and SEM. It showed that the modified cellulose (CE)-based foam was hydrophobic, which can adsorb a range of oils and organic solvents in water under pH = 7.0 or visible light irradiation (λ > 500 nm). Meanwhile, the wettability of robust CE-based foam can convert hydrophobicity into hydrophilicity and underwater oleophobicity under pH = 3.0 or UV irradiation (λ = 365 nm), giving rise to release oils and organic solvents. Most important of all, the adsorption and desorption processes of the modified CE-based foam could be switched by external stimuli. Furthermore, the modified CE-based foam was not damaged and still retained original performance after reversible cycle repeated for many times with variation of surface wettability. In short, it indicates that CE-based foam materials with switchable surface wettability are new responsive absorbent materials and have owned potential application in the treatment of oil recovery.

A theoretical framework for understanding neuromuscular response to lower extremity joint injury.

Science.gov (United States)

Pietrosimone, Brian G; McLeod, Michelle M; Lepley, Adam S

2012-01-01

Neuromuscular alterations are common following lower extremity joint injury and often lead to decreased function and disability. These neuromuscular alterations manifest in inhibition or abnormal facilitation of the uninjured musculature surrounding an injured joint. Unfortunately, these neural alterations are poorly understood, which may affect clinical recognition and treatment of these injuries. Understanding how these neural alterations affect physical function may be important for proper clinical management of lower extremity joint injuries. Pertinent articles focusing on neuromuscular consequences and treatment of knee and ankle injuries were collected from peer-reviewed sources available on the Web of Science and Medline databases from 1975 through 2010. A theoretical model to illustrate potential relationships between neural alterations and clinical impairments was constructed from the current literature. Lower extremity joint injury affects upstream cortical and spinal reflexive excitability pathways as well as downstream muscle function and overall physical performance. Treatment targeting the central nervous system provides an alternate means of treating joint injury that may be effective for patients with neuromuscular alterations. Disability is common following joint injury. There is mounting evidence that alterations in the central nervous system may relate to clinical changes in biomechanics that may predispose patients to further injury, and novel clinical interventions that target neural alterations may improve therapeutic outcomes.

Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood

International Nuclear Information System (INIS)

Ordonhez Rigato, Paula; Maciel, Milton; Goldoni, Adriana Leticia; Piubelli, Orlando; Alves de Brito, Cyro; Fusaro, Ana Elisa; Eurico de Alencar, Liciana Xavier; August, Thomas; Torres Azevedo Marques, Ernesto; Silva Duarte, Alberto Jose da; Sato, Maria Notomi

2010-01-01

Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-γ, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric LAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory.

Robust multivariate analysis

CERN Document Server

J Olive, David

2017-01-01

This text presents methods that are robust to the assumption of a multivariate normal distribution or methods that are robust to certain types of outliers. Instead of using exact theory based on the multivariate normal distribution, the simpler and more applicable large sample theory is given.  The text develops among the first practical robust regression and robust multivariate location and dispersion estimators backed by theory.   The robust techniques  are illustrated for methods such as principal component analysis, canonical correlation analysis, and factor analysis.  A simple way to bootstrap confidence regions is also provided. Much of the research on robust multivariate analysis in this book is being published for the first time. The text is suitable for a first course in Multivariate Statistical Analysis or a first course in Robust Statistics. This graduate text is also useful for people who are familiar with the traditional multivariate topics, but want to know more about handling data sets with...

Constitutive Activity of the Arabidopsis MAP Kinase 3 Confers Resistance to Pseudomonas syringae and Drives Robust Immune Responses

KAUST Repository

Lang, Julien

2017-08-02

Mitogen Activated Protein Kinases (MAPKs) are known to be important mediators of plant responses to biotic and abiotic stresses. In a recent report, we enlarged the understanding of the Arabidopsis thaliana MPK3 functions showing that the expression of a constitutively active (CA) form of the protein led to auto-immune phenotypes. CA-MPK3 plants are dwarf and display defense responses that are characterized by the accumulation of salicylic acid and phytoalexins as well as by the upregulation of several defense genes. Consistently with these data, we present here results demonstrating that, compared to wild type controls, CA-MPK3 plants are more resistant to the hemibiotrophic pathogen Pseudomonas syringae DC3000. Based on our previous work, we also discuss the mechanisms of robust plant immunity controlled by sustained MPK3 activity, focusing especially on the roles of disease resistance proteins.

Cardiovascular response during urodynamics in individuals with spinal cord injury

DEFF Research Database (Denmark)

Liu, N; Zhou, M-W; Biering-Sørensen, F

2017-01-01

STUDY DESIGN: Retrospective chart review. OBJECTIVES: To establish the frequency and severity of autonomic dysreflexia (AD) during urodynamics among individuals with chronic spinal cord injury (SCI) and to investigate the possible effect of the number of years since SCI on the severity of AD...... was more severe in individuals with complete (American Spinal Cord Association (ASIA) impairment scale (AIS) A) injuries, worse with greater time after SCI. CONCLUSION: Individuals with cervical SCI, DSD, poor bladder compliance or >2 years after SCI were associated with a higher possibility of developing...... AD during urodynamics. Furthermore, AD was more severe in complete (AIS A) individuals and was exacerbated with time after injury....

Robust optimization of the billet for isothermal local loading transitional region of a Ti-alloy rib-web component based on dual-response surface method

Science.gov (United States)

Wei, Ke; Fan, Xiaoguang; Zhan, Mei; Meng, Miao

2018-03-01

Billet optimization can greatly improve the forming quality of the transitional region in the isothermal local loading forming (ILLF) of large-scale Ti-alloy ribweb components. However, the final quality of the transitional region may be deteriorated by uncontrollable factors, such as the manufacturing tolerance of the preforming billet, fluctuation of the stroke length, and friction factor. Thus, a dual-response surface method (RSM)-based robust optimization of the billet was proposed to address the uncontrollable factors in transitional region of the ILLF. Given that the die underfilling and folding defect are two key factors that influence the forming quality of the transitional region, minimizing the mean and standard deviation of the die underfilling rate and avoiding folding defect were defined as the objective function and constraint condition in robust optimization. Then, the cross array design was constructed, a dual-RSM model was established for the mean and standard deviation of the die underfilling rate by considering the size parameters of the billet and uncontrollable factors. Subsequently, an optimum solution was derived to achieve the robust optimization of the billet. A case study on robust optimization was conducted. Good results were attained for improving the die filling and avoiding folding defect, suggesting that the robust optimization of the billet in the transitional region of the ILLF was efficient and reliable.

Negative psychological responses of injury and rehabilitation adherence effects on return to play in competitive athletes: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Ivarsson A

2017-03-01

Full Text Available Andreas Ivarsson,1 Ulrika Tranaeus,2,3 Urban Johnson,1 Andreas Stenling 4 1Center of Research on Welfare, Health and Sport, School of Health and Welfare, Halmstad University, Halmstad, 2Performance and Training Unit, The Swedish School of Sport and Health Sciences (GIH, 3Musculoskeletal & Sports Injury Epidemiology Center, IMM, Karolinska Institutet, Stockholm, 4Department of Psychology, Umeå University, Umeå, Sweden Abstract: Previous research offers evidence that psychological factors influence an injured athlete during the rehabilitation process. Our first objective was to conduct a systematic review and meta-analysis of the results from all published studies that examined the relationships among negative affective responses after sport injuries, rehabilitation adherence, and return to play (RTP. The second objective was to use a meta-analytic path analysis to investigate whether an indirect effect existed between negative affective responses and RTP through rehabilitation adherence. This literature review resulted in seven studies providing 14 effect sizes. The results from the meta-analysis showed that negative affective responses had a negative effect on successful RTP, whereas rehabilitation adherence had a positive effect on RTP. The results from the meta-analytic path analysis showed a weak and nonsignificant indirect effect of negative affective responses on RTP via rehabilitation adherence. These results underline the importance of providing supportive environments for injured athletes to increase the chances of successful RTP via a decrease in negative affective responses and increase in rehabilitation adherence. Keywords: affective responses, rehabilitation behaviors, return to play, sport injuries

Robustness Analysis of Real Network Topologies Under Multiple Failure Scenarios

DEFF Research Database (Denmark)

Manzano, M.; Marzo, J. L.; Calle, E.

2012-01-01

on topological characteristics. Recently approaches also consider the services supported by such networks. In this paper we carry out a robustness analysis of five real backbone telecommunication networks under defined multiple failure scenarios, taking into account the consequences of the loss of established......Nowadays the ubiquity of telecommunication networks, which underpin and fulfill key aspects of modern day living, is taken for granted. Significant large-scale failures have occurred in the last years affecting telecommunication networks. Traditionally, network robustness analysis has been focused...... connections. Results show which networks are more robust in response to a specific type of failure....

Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.

Directory of Open Access Journals (Sweden)

Masami Watabe-Rudolph

Full Text Available Atrophy of the olfactory epithelium (OE associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc(-/- with short telomeres compared to wild type mice (mTerc(+/+ with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc(-/- mice compared to mTerc(+/+ mice. Seven days after chemical induced damage, G3 mTerc(-/- mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc(+/+ mice (p = 0.031. Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21 rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people.

Robustness of Structures

DEFF Research Database (Denmark)

Faber, Michael Havbro; Vrouwenvelder, A.C.W.M.; Sørensen, John Dalsgaard

2011-01-01

In 2005, the Joint Committee on Structural Safety (JCSS) together with Working Commission (WC) 1 of the International Association of Bridge and Structural Engineering (IABSE) organized a workshop on robustness of structures. Two important decisions resulted from this workshop, namely...... ‘COST TU0601: Robustness of Structures’ was initiated in February 2007, aiming to provide a platform for exchanging and promoting research in the area of structural robustness and to provide a basic framework, together with methods, strategies and guidelines enhancing robustness of structures...... the development of a joint European project on structural robustness under the COST (European Cooperation in Science and Technology) programme and the decision to develop a more elaborate document on structural robustness in collaboration between experts from the JCSS and the IABSE. Accordingly, a project titled...

Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.

Directory of Open Access Journals (Sweden)

Laila Elsherif

Full Text Available Mice expressing the tetracycline transactivator (tTA transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between α-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the α-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.

Does naloxone reinstate secondary hyperalgesia in humans after resolution of a burn injury?

DEFF Research Database (Denmark)

Pereira, Manuel P; Werner, Mads U; Ringsted, Thomas K

2013-01-01

Development of secondary hyperalgesia following a cutaneous injury is a centrally mediated, robust phenomenon. The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear. Recent animal studies, carried out after the resolution of inflammatory pain...

Role of alveolar epithelial Early growth response-1 (Egr-1) in CD8+ T Cell mediated Lung Injury

Science.gov (United States)

Ramana, Chilakamarti V.; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung- Joo; Enelow, Richard I.

2009-01-01

Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8+ T cells in this injury, and have found that the critical effector molecule is TNF-α expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8+ T cell recognition, and demonstrate that the Early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-α– dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection. PMID:19786304

Role of alveolar epithelial early growth response-1 (Egr-1) in CD8+ T cell-mediated lung injury.

Science.gov (United States)

Ramana, Chilakamarti V; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung-Joo; Enelow, Richard I

2009-12-01

Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8(+) T cells in this injury, and have found that the critical effector molecule is TNF-alpha expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8(+) T cell recognition, and demonstrate that the early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-alpha-dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection.

Hybrid Robust Control Law with Disturbance Observer for High-Frequency Response Electro-Hydraulic Servo Loading System

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Zhiqing Sheng

2016-04-01

Full Text Available Addressing the simulating issue of the helicopter-manipulating booster aerodynamic load with high-frequency dynamic load superimposed on a large static load, this paper studies the design of the robust controller for the electro-hydraulic loading system to realize the simulation of this kind of load. Firstly, the equivalent linear model of the electro-hydraulic loading system under assumed parameter uncertainty is established. Then, a hybrid control scheme is proposed for the loading system. This control scheme consists of a constant velocity feed-forward compensator, a robust inner loop compensator based on disturbance observer and a robust outer loop feedback controller. The constant velocity compensator eliminates most of the extraneous force at first, and then the double-loop cascade composition control strategy is employed to design the compensated system. The disturbance observer–based inner loop compensator further restrains the disturbances including the remaining extraneous force, and makes the actual plant tracking a nominal model approximately in a certain frequency range. The robust outer loop controller achieves the desired force-tracking performance, and guarantees system robustness in the high frequency region. The optimized low-pass filter Q(s is designed by using the H∞ mixed sensitivity optimization method. The simulation results show that the proposed hybrid control scheme and controller can effectively suppress the extraneous force and improve the robustness of the electro-hydraulic loading system.

Real-Time Continuous Response Spectra Exceedance Calculation Displayed in a Web-Browser Enables Rapid and Robust Damage Evaluation by First Responders

Science.gov (United States)

Franke, M.; Skolnik, D. A.; Harvey, D.; Lindquist, K.

2014-12-01

A novel and robust approach is presented that provides near real-time earthquake alarms for critical structures at distributed locations and large facilities using real-time estimation of response spectra obtained from near free-field motions. Influential studies dating back to the 1980s identified spectral response acceleration as a key ground motion characteristic that correlates well with observed damage in structures. Thus, monitoring and reporting on exceedance of spectra-based thresholds are useful tools for assessing the potential for damage to facilities or multi-structure campuses based on input ground motions only. With as little as one strong-motion station per site, this scalable approach can provide rapid alarms on the damage status of remote towns, critical infrastructure (e.g., hospitals, schools) and points of interests (e.g., bridges) for a very large number of locations enabling better rapid decision making during critical and difficult immediate post-earthquake response actions. Details on the novel approach are presented along with an example implementation for a large energy company. Real-time calculation of PSA exceedance and alarm dissemination are enabled with Bighorn, an extension module based on the Antelope software package that combines real-time spectral monitoring and alarm capabilities with a robust built-in web display server. Antelope is an environmental data collection software package from Boulder Real Time Technologies (BRTT) typically used for very large seismic networks and real-time seismic data analyses. The primary processing engine produces continuous time-dependent response spectra for incoming acceleration streams. It utilizes expanded floating-point data representations within object ring-buffer packets and waveform files in a relational database. This leads to a very fast method for computing response spectra for a large number of channels. A Python script evaluates these response spectra for exceedance of one or more

Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury: potential insight into the mechanism of isomorphic and isotopic responses.

Science.gov (United States)

Martires, Kathryn J; Baird, Kristin; Citrin, Deborah E; Hakim, Fran T; Pavletic, Steven Z; Cowen, Edward W

2011-09-01

The mechanisms responsible for the variable manifestations of chronic cutaneous graft-vs-host disease (cGVHD) are poorly understood. Localization of sclerotic-type chronic graft-vs-host disease to sites of skin injury (isomorphic and isotopic responses), a recognized phenomenon in morphea, suggests a potential common pathway between cGVHD and other sclerotic skin conditions. Four cases of sclerotic-type cGVHD developed at the site of disparate skin injuries (ionizing radiotherapy, repeated needle sticks, central catheter site, and varicella-zoster virus infection). We review the spectrum of previously reported cases of sclerotic and nonsclerotic cGVHD relating to external forces on the skin. Localization of sclerotic-type cGVHD may occur after many types of skin injury, including UV and ionizing radiotherapy, needle sticks, viral infection, and pressure or friction. Recognition of this phenomenon may be helpful for the early diagnosis of sclerotic disease. Recent insights into the immunological consequences of minor skin injury may provide important clues to the underlying pathogenesis of cGVHD-mediated skin disease.

Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response.

Science.gov (United States)

Ogryzko, Nikolay V; Hoggett, Emily E; Solaymani-Kohal, Sara; Tazzyman, Simon; Chico, Timothy J A; Renshaw, Stephen A; Wilson, Heather L

2014-02-01

Interleukin-1 (IL-1), the 'gatekeeper' of inflammation, is the apical cytokine in a signalling cascade that drives the early response to injury or infection. Expression, processing and secretion of IL-1 are tightly controlled, and dysregulated IL-1 signalling has been implicated in a number of pathologies ranging from atherosclerosis to complications of infection. Our understanding of these processes comes from in vitro monocytic cell culture models as lines or primary isolates, in which a range and spectra of IL-1 secretion mechanisms have been described. We therefore investigated whether zebrafish embryos provide a suitable in vivo model for studying IL-1-mediated inflammation. Structurally, zebrafish IL-1β shares a β-sheet-rich trefoil structure with its human counterpart. Functionally, leukocyte expression of IL-1β was detectable only following injury, which activated leukocytes throughout zebrafish embryos. Migration of macrophages and neutrophils was attenuated by inhibitors of either caspase-1 or P2X7, which similarly inhibited the activation of NF-κB at the site of injury. Zebrafish offer a new and versatile model to study the IL-1β pathway in inflammatory disease and should offer unique insights into IL-1 biology in vivo.

Reactive microglia after taste nerve injury: comparison to nerve injury models of chronic pain [v1; ref status: indexed, http://f1000r.es/wh

Directory of Open Access Journals (Sweden)

Dianna L Bartel

2013-02-01

Full Text Available The chorda tympani (CT, which innervates taste buds on the anterior portion of the tongue, is susceptible to damage during inner ear surgeries. Injury to the CT causes a disappearance of taste buds, which is concurrent with significant microglial responses at central nerve terminals in the nucleus of the solitary tract (nTS. The resulting taste disturbances that can occur may persist for months or years, long after the nerve and taste buds have regenerated. These persistent changes in taste sensation suggest alterations in central functioning and may be related to the microglial responses. This is reminiscent of nerve injuries that result in chronic pain, where microglial reactivity is essential in maintaining the altered sensation (i.e., pain. In these models, methods that diminish microglial responses also diminish the corresponding pain behavior. Although the CT nerve does not contain nociceptive pain fibers, the microglial reactivity after CT damage is similar to that described in pain models. Therefore, methods that decrease microglial responses in pain models were used here to test if they could also affect microglial reactivity after CT injury. Treatment with minocycline, an antibiotic that dampens pain responsive microglia, was largely ineffective in diminishing microglial responses after CT injury. In addition, signaling through the toll-like 4 receptor (TLR4 does not seem to be required after CT injury as blocking or deleting TLR4 had no effect on microglial reactivity. These results suggest that microglial responses following CT injury rely on different signaling mechanisms than those described in nerve injuries resulting in chronic pain.

Sensory and Motor Responses to Spinal Cord Injury

National Research Council Canada - National Science Library

Yezierski, Robert P

1999-01-01

The goal of Dr. Yezierski's research was to gain a better understanding of the anatomical, neurochemical and functional changes that occur within the central nervous system following spinal cord injury...

Rat models of spinal cord injury: from pathology to potential therapies

Science.gov (United States)

2016-01-01

ABSTRACT A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials. PMID:27736748

Preliminary Evidence of Reduced Urge to Cough and Cough Response in Four Individuals following Remote Traumatic Brain Injury with Tracheostomy

Directory of Open Access Journals (Sweden)

Erin Silverman

2016-01-01

Full Text Available Cough and swallow protect the lungs and are frequently impaired following traumatic brain injury (TBI. This project examined cough response to inhaled capsaicin solution challenge in a cohort of four young adults with a history of TBI within the preceding five years. All participants had a history of tracheostomy with subsequent decannulation and dysphagia after their injuries (resolved for all but one participant. Urge to cough (UTC and cough response were measured and compared to an existing database of normative cough response data obtained from 32 healthy controls (HCs. Participants displayed decreased UTC and cough responses compared to HCs. It is unknown if these preliminary results manifest as a consequence of disrupted sensory (afferent projections, an inability to perceive or discriminate cough stimuli, disrupted motor (efferent response, peripheral weakness, or any combination of these factors. Future work should attempt to clarify if the observed phenomena are borne out in a larger sample of individuals with TBI, determine the relative contributions of central versus peripheral nervous system structures to cough sensory perceptual changes following TBI (should they exist, and formulate recommendations for systematic screening and assessment of cough sensory perception in order to facilitate rehabilitative efforts. This project is identified with the National Clinical Trials NCT02240329.

Swiss national community survey on functioning after spinal cord injury : Protocol, characteristics of participants and determinants of non-response

NARCIS (Netherlands)

Brinkhof, Martin W G; Fekete, Christine; Chamberlain, Jonviea D; Post, Marcel W M; Gemperli, Armin

2016-01-01

OBJECTIVE: To detail the protocol, recruitment, study population, response, and data quality of the first population-based community survey of the Swiss Spinal Cord Injury (SwiSCI) Cohort Study. DESIGN: The survey consisted of 3 successive modules administered between September 2011 and March 2013.

Swiss national community survey on functioning after spinal cord injury : Protocol, characteristics of participants and determinants of non-response

NARCIS (Netherlands)

Brinkhof, Martin W. G.; Fekete, Christine; Chamberlain, Jonviea D.; Post, Marcel W. M.; Gemperli, Armin

Objective: To detail the protocol, recruitment, study population, response, and data quality of the first population-based community survey of the Swiss Spinal Cord Injury (SwiSCI) Cohort Study. Design: The survey consisted of 3 successive modules administered between September 2011 and March 2013.

Defining robustness protocols: a method to include and evaluate robustness in clinical plans

International Nuclear Information System (INIS)

McGowan, S E; Albertini, F; Lomax, A J; Thomas, S J

2015-01-01

We aim to define a site-specific robustness protocol to be used during the clinical plan evaluation process. Plan robustness of 16 skull base IMPT plans to systematic range and random set-up errors have been retrospectively and systematically analysed. This was determined by calculating the error-bar dose distribution (ebDD) for all the plans and by defining some metrics used to define protocols aiding the plan assessment. Additionally, an example of how to clinically use the defined robustness database is given whereby a plan with sub-optimal brainstem robustness was identified. The advantage of using different beam arrangements to improve the plan robustness was analysed. Using the ebDD it was found range errors had a smaller effect on dose distribution than the corresponding set-up error in a single fraction, and that organs at risk were most robust to the range errors, whereas the target was more robust to set-up errors. A database was created to aid planners in terms of plan robustness aims in these volumes. This resulted in the definition of site-specific robustness protocols. The use of robustness constraints allowed for the identification of a specific patient that may have benefited from a treatment of greater individuality. A new beam arrangement showed to be preferential when balancing conformality and robustness for this case. The ebDD and error-bar volume histogram proved effective in analysing plan robustness. The process of retrospective analysis could be used to establish site-specific robustness planning protocols in proton therapy. These protocols allow the planner to determine plans that, although delivering a dosimetrically adequate dose distribution, have resulted in sub-optimal robustness to these uncertainties. For these cases the use of different beam start conditions may improve the plan robustness to set-up and range uncertainties. (paper)

Defining robustness protocols: a method to include and evaluate robustness in clinical plans

Science.gov (United States)

McGowan, S. E.; Albertini, F.; Thomas, S. J.; Lomax, A. J.

2015-04-01

We aim to define a site-specific robustness protocol to be used during the clinical plan evaluation process. Plan robustness of 16 skull base IMPT plans to systematic range and random set-up errors have been retrospectively and systematically analysed. This was determined by calculating the error-bar dose distribution (ebDD) for all the plans and by defining some metrics used to define protocols aiding the plan assessment. Additionally, an example of how to clinically use the defined robustness database is given whereby a plan with sub-optimal brainstem robustness was identified. The advantage of using different beam arrangements to improve the plan robustness was analysed. Using the ebDD it was found range errors had a smaller effect on dose distribution than the corresponding set-up error in a single fraction, and that organs at risk were most robust to the range errors, whereas the target was more robust to set-up errors. A database was created to aid planners in terms of plan robustness aims in these volumes. This resulted in the definition of site-specific robustness protocols. The use of robustness constraints allowed for the identification of a specific patient that may have benefited from a treatment of greater individuality. A new beam arrangement showed to be preferential when balancing conformality and robustness for this case. The ebDD and error-bar volume histogram proved effective in analysing plan robustness. The process of retrospective analysis could be used to establish site-specific robustness planning protocols in proton therapy. These protocols allow the planner to determine plans that, although delivering a dosimetrically adequate dose distribution, have resulted in sub-optimal robustness to these uncertainties. For these cases the use of different beam start conditions may improve the plan robustness to set-up and range uncertainties.

Injury prevention and public health

Directory of Open Access Journals (Sweden)

David A. Sleet

2010-06-01

Full Text Available Injuries are one of the most under-recognized public health problems facing the world today. With more than 5 million deaths every year, violence and injuries account for 9% of global mortality, as many deaths as from HIV, Malaria and Tuberculosis combined. Eight of the 15 leading causes of death for people ages 15 to 29 years are injury-related: road traffic injuries, suicides, homicides, drowning, burns, war injuries, poisonings and falls. For every death due to war, there are three deaths due to homicide and five deaths due to suicide. However, most violence happens to people behind closed doors and results not in death, but often in years of physical and emotional suffering [1]. Injuries can be classified by intent: unintentional or intentional. Traffic injuries, fire-related injuries, falls, drowning, and poisonings are most often classified as unintentional injuries; injuries due to assault, selfinflicted violence such as suicide, and war are classified as intentional injuries, or violence. Worldwide, governments and public and private partners are increasingly aware of the strains that unintentional injuries and violence place on societies. In response they are strengthening data collection systems, improving services for victims and survivors, and increasing prevention efforts [1].

On the possible role of robustness in the evolution of infectious diseases

Science.gov (United States)

Ogbunugafor, C. Brandon; Pease, James B.; Turner, Paul E.

2010-06-01

Robustness describes the capacity for a biological system to remain canalized despite perturbation. Genetic robustness affords maintenance of phenotype despite mutational input, necessarily involving the role of epistasis. Environmental robustness is phenotypic constancy in the face of environmental variation, where epistasis may be uninvolved. Here we discuss genetic and environmental robustness, from the standpoint of infectious disease evolution, and suggest that robustness may be a unifying principle for understanding how different disease agents evolve. We focus especially on viruses with RNA genomes due to their importance in the evolution of emerging diseases and as model systems to test robustness theory. We present new data on adaptive constraints for a model RNA virus challenged to evolve in response to UV radiation. We also draw attention to other infectious disease systems where robustness theory may prove useful for bridging evolutionary biology and biomedicine, especially the evolution of antibiotic resistance in bacteria, immune evasion by influenza, and malaria parasite infections.

Divergent forms of endoplasmic reticulum stress trigger a robust unfolded protein response in honey bees.

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Johnston, Brittany A; Hooks, Katarzyna B; McKinstry, Mia; Snow, Jonathan W

2016-03-01

Honey bee colonies in the United States have suffered from an increased rate of die-off in recent years, stemming from a complex set of interacting stresses that remain poorly described. While we have some understanding of the physiological stress responses in the honey bee, our molecular understanding of honey bee cellular stress responses is incomplete. Thus, we sought to identify and began functional characterization of the components of the UPR in honey bees. The IRE1-dependent splicing of the mRNA for the transcription factor Xbp1, leading to translation of an isoform with more transactivation potential, represents the most conserved of the UPR pathways. Honey bees and other Apoidea possess unique features in the Xbp1 mRNA splice site, which we reasoned could have functional consequences for the IRE1 pathway. However, we find robust induction of target genes upon UPR stimulation. In addition, the IRE1 pathway activation, as assessed by splicing of Xbp1 mRNA upon UPR, is conserved. By providing foundational knowledge about the UPR in the honey bee and the relative sensitivity of this species to divergent stresses, this work stands to improve our understanding of the mechanistic underpinnings of honey bee health and disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Robust-BD Estimation and Inference for General Partially Linear Models

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Chunming Zhang

2017-11-01

Full Text Available The classical quadratic loss for the partially linear model (PLM and the likelihood function for the generalized PLM are not resistant to outliers. This inspires us to propose a class of “robust-Bregman divergence (BD” estimators of both the parametric and nonparametric components in the general partially linear model (GPLM, which allows the distribution of the response variable to be partially specified, without being fully known. Using the local-polynomial function estimation method, we propose a computationally-efficient procedure for obtaining “robust-BD” estimators and establish the consistency and asymptotic normality of the “robust-BD” estimator of the parametric component β o . For inference procedures of β o in the GPLM, we show that the Wald-type test statistic W n constructed from the “robust-BD” estimators is asymptotically distribution free under the null, whereas the likelihood ratio-type test statistic Λ n is not. This provides an insight into the distinction from the asymptotic equivalence (Fan and Huang 2005 between W n and Λ n in the PLM constructed from profile least-squares estimators using the non-robust quadratic loss. Numerical examples illustrate the computational effectiveness of the proposed “robust-BD” estimators and robust Wald-type test in the appearance of outlying observations.

Major Peripheral Nerve Injuries After Elbow Arthroscopy.

Science.gov (United States)

Desai, Mihir J; Mithani, Suhail K; Lodha, Sameer J; Richard, Marc J; Leversedge, Fraser J; Ruch, David S

2016-06-01

To survey the American Society for Surgery of the Hand membership to determine the nature and distribution of nerve injuries treated after elbow arthroscopy. An online survey was sent to all members of the American Society for Surgery of the Hand under an institutional review board-approved protocol. Collected data included the number of nerve injuries observed over a 5-year period, the nature of treatment required for the injuries, and the outcomes observed after any intervention. Responses were anonymous, and results were securely compiled. We obtained 372 responses. A total of 222 nerve injuries were reported. The most injured nerves reported were ulnar, radial, and posterior interosseous (38%, 22%, and 19%, respectively). Nearly half of all patients with injuries required operative intervention, including nerve graft, tendon transfer, nerve repair, or nerve transfer. Of the patients who sustained major injuries, those requiring intervention, 77% had partial or no motor recovery. All minor injuries resolved completely. Our results suggest that major nerve injuries after elbow arthroscopy are not rare occurrences and the risk of these injuries is likely under-reported in the literature. Furthermore, patients should be counseled on this risk because most nerve injuries show only partial or no functional recovery. With the more widespread practice of elbow arthroscopy, understanding the nature and sequelae of significant complications is critically important in ensuring patient safety and improving outcomes. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Shift in U.S. payer responsibility for the acute care of violent injuries after the Affordable Care Act: Implications for prevention.

Science.gov (United States)

Coupet, Edouard; Karp, David; Wiebe, Douglas J; Kit Delgado, M

2018-03-28

Investment in violence prevention programs is hampered by lack of clearly identifiable stakeholders with a financial stake in prevention. We determined the total annual charges for the acute care of injuries from interpersonal violence and the shift in financial responsibility for these charges after the Medicaid expansion from the Affordable Care Act in 2014. We analyzed all emergency department (ED) visits from 2009 to 2014 with diagnosis codes for violent injury in the Nationwide Emergency Department Sample (NEDS). We used sample weights to estimate total charges with adjusted generalized linear models to estimate charges for the 15% of ED visits with missing charge data. We then calculated the share attributable by payer and determined the difference in proportion by payer from 2013 to 2014. Between 2009 and 2013, the uninsured accounted for 28.2-31.3% of annual charges for the acute care of violent injury, while Medicaid was responsible for a similar amount (29.0-31.0%). In 2014, there were $10.7 billion in total charges for violent injury. Medicaid assumed the greatest share, 39.8% (95% CI: 38.0-41.5%, $3.5-5.1 billion), while the uninsured accounted for 23.6% (95% CI: 22.2-24.9%, $2.0-3.0 billion), and Medicare accounted for 7.8% (95% CI: 7.7-8.0%, $0.7-1.0 billion). After Medicaid expansion, taxpayers are now accountable for nearly half of the $10.7 billion in annual charges for the acute care of violent injury in the U.S. These findings highlight the benefit to state Medicaid programs of preventing interpersonal violence. Published by Elsevier Inc.

CSF proteomics of secondary phase spinal cord injury in human subjects: perturbed molecular pathways post injury.

Directory of Open Access Journals (Sweden)

Mohor Biplab Sengupta

Full Text Available Recovery of sensory and motor functions following traumatic spinal cord injury (SCI is dependent on injury severity. Here we identified 49 proteins from cerebrospinal fluid (CSF of SCI patients, eight of which were differentially abundant among two severity groups of SCI. It was observed that the abundance profiles of these proteins change over a time period of days to months post SCI. Statistical analysis revealed that these proteins take part in several molecular pathways including DNA repair, protein phosphorylation, tRNA transcription, iron transport, mRNA metabolism, immune response and lipid and ATP catabolism. These pathways reflect a set of mechanisms that the system may adopt to cope up with the assault depending on the injury severity, thus leading to observed physiological responses. Apart from putting forward a picture of the molecular scenario at the injury site in a human study, this finding further delineates consequent pathways and molecules that may be altered by external intervention to restrict neural degeneration.

Local membrane deformation and micro-injury lead to qualitatively different responses in osteoblasts [v1; ref status: indexed, http://f1000r.es/3o7

Directory of Open Access Journals (Sweden)

G. Monserratt Lopez-Ayon

2014-07-01

Full Text Available Micro-damage of bone tissue is known to regulate bone turnover. However, it is unknown if individual bone cells can differentiate between membrane deformation and micro-injury. We generated osteoblasts from mouse bone marrow or bone morphogenetic protein 2-transfected C2C12 cells. Single cells were mechanically stimulated by indentation with the atomic force microscopy probe with variable force load either resulting in membrane deformation only, or leading to membrane penetration and micro-injury. Changes in the cytosolic free calcium concentration ([Ca2+]i in fluo4-AM loaded cells were analyzed. When deformation only was induced, it resulted in an immediate elevation of [Ca2+]i which was localized to the probe periphery. Multiple consecutive local Ca2+ responses were induced by sequential application of low level forces, with characteristic recovery time of ~2 s. The duration of [Ca2+]i elevations was directly proportional to the tip-cell contact time. In contrast, cell micro-injury resulted in transient global elevations of [Ca2+]i, the magnitude of which was independent of the tip-cell contact time. Sequential micro-injury of the same cell did not induce Ca2+ response within 30 s of the first stimulation. Both local and global Ca2+elevations were blocked in Ca2+-free media or in the presence of stretch-activated channel blocker Gd3+. In addition, amount of Ca2+ released during global responses was significantly reduced in the presence of PLC inhibitor Et-18-OCH3. Thus, we found qualitative differences in calcium responses to mechanical forces inducing only membrane deformation or deformation leading to micro-injury.

Acute stress response and recovery after whiplash injuries. A one-year prospective study.

Science.gov (United States)

Kongsted, Alice; Bendix, Tom; Qerama, Erisela; Kasch, Helge; Bach, Flemming W; Korsholm, Lars; Jensen, Troels S

2008-05-01

Chronic whiplash-associated disorder (WAD) represents a major medical and psycho-social problem. The typical symptomatology presented in WAD is to some extent similar to symptoms of post traumatic stress disorder. In this study we examined if the acute stress reaction following a whiplash injury predicted long-term sequelae. Participants with acute whiplash-associated symptoms after a motor vehicle accident were recruited from emergency units and general practitioners. The predictor variable was the sum score of the impact of event scale (IES) completed within 10 days after the accident. The main outcome-measures were neck pain and headache, neck disability, general health, and working ability one year after the accident. A total of 737 participants were included and completed the IES, and 668 (91%) participated in the 1-year follow-up. A baseline IES-score denoting a moderate to severe stress response was obtained by 13% of the participants. This was associated with increased risk of considerable persistent pain (OR=3.3; 1.8-5.9), neck disability (OR=3.2; 1.7-6.0), reduced working ability (OR=2.8; 1.6-4.9), and lowered self-reported general health one year after the accident. These associations were modified by baseline neck pain intensity. It was not possible to distinguish between participants who recovered and those who did not by means of the IES (AUC=0.6). In conclusion, the association between the acute stress reaction and persistent WAD suggests that post traumatic stress reaction may be important to consider in the early management of whiplash injury. However, the emotional response did not predict chronicity in individuals.

Methods for robustness programming

NARCIS (Netherlands)

Olieman, N.J.

2008-01-01

Robustness of an object is defined as the probability that an object will have properties as required. Robustness Programming (RP) is a mathematical approach for Robustness estimation and Robustness optimisation. An example in the context of designing a food product, is finding the best composition

UNIX-based operating systems robustness evaluation

Science.gov (United States)

Chang, Yu-Ming

1996-01-01

Robust operating systems are required for reliable computing. Techniques for robustness evaluation of operating systems not only enhance the understanding of the reliability of computer systems, but also provide valuable feed- back to system designers. This thesis presents results from robustness evaluation experiments on five UNIX-based operating systems, which include Digital Equipment's OSF/l, Hewlett Packard's HP-UX, Sun Microsystems' Solaris and SunOS, and Silicon Graphics' IRIX. Three sets of experiments were performed. The methodology for evaluation tested (1) the exception handling mechanism, (2) system resource management, and (3) system capacity under high workload stress. An exception generator was used to evaluate the exception handling mechanism of the operating systems. Results included exit status of the exception generator and the system state. Resource management techniques used by individual operating systems were tested using programs designed to usurp system resources such as physical memory and process slots. Finally, the workload stress testing evaluated the effect of the workload on system performance by running a synthetic workload and recording the response time of local and remote user requests. Moderate to severe performance degradations were observed on the systems under stress.

The systemic immune response to trauma: an overview of pathophysiology and treatment.

Science.gov (United States)

Lord, Janet M; Midwinter, Mark J; Chen, Yen-Fu; Belli, Antonio; Brohi, Karim; Kovacs, Elizabeth J; Koenderman, Leo; Kubes, Paul; Lilford, Richard J

2014-10-18

Improvements in the control of haemorrhage after trauma have resulted in the survival of many people who would otherwise have died from the initial loss of blood. However, the danger is not over once bleeding has been arrested and blood pressure restored. Two-thirds of patients who die following major trauma now do so as a result of causes other than exsanguination. Trauma evokes a systemic reaction that includes an acute, non-specific, immune response associated, paradoxically, with reduced resistance to infection. The result is damage to multiple organs caused by the initial cascade of inflammation aggravated by subsequent sepsis to which the body has become susceptible. This Series examines the biological mechanisms and clinical implications of the cascade of events caused by large-scale trauma that leads to multiorgan failure and death, despite the stemming of blood loss. Furthermore, the stark and robust epidemiological finding--namely, that age has a profound influence on the chances of surviving trauma irrespective of the nature and severity of the injury--will be explored. Advances in our understanding of the inflammatory response to trauma, the impact of ageing on this response, and how this information has led to new and emerging treatments aimed at combating immune dysregulation and reduced immunity after injury will also be discussed.

Robust Distributed Model Predictive Load Frequency Control of Interconnected Power System

Directory of Open Access Journals (Sweden)

Xiangjie Liu

2013-01-01

Full Text Available Considering the load frequency control (LFC of large-scale power system, a robust distributed model predictive control (RDMPC is presented. The system uncertainty according to power system parameter variation alone with the generation rate constraints (GRC is included in the synthesis procedure. The entire power system is composed of several control areas, and the problem is formulated as convex optimization problem with linear matrix inequalities (LMI that can be solved efficiently. It minimizes an upper bound on a robust performance objective for each subsystem. Simulation results show good dynamic response and robustness in the presence of power system dynamic uncertainties.

The Role of Negative Affect on Headache-Related Disability Following Traumatic Physical Injury.

Science.gov (United States)

Pacella, Maria L; Hruska, Bryce; George, Richard L; Delahanty, Douglas L

2018-03-01

Acute postinjury negative affect (NA) may contribute to headache pain following physical injury. Early psychiatric-headache comorbidity conveys increased vulnerability to chronic headache-related disability and impairment. Yet, it is unknown whether NA is involved in the transition to chronic headache related-disability after injury. This prospective observational study examined the role of acute postinjury NA on subacute and chronic headache-related disability above and beyond nonpsychiatric factors. Eighty adult survivors of single-incident traumatic physical injury were assessed for negative affect (NA): a composite of depression and anxiety symptoms, and symptoms of posttraumatic stress disorder (PTSS) during the acute 2-week postinjury phase. NA was examined as the primary predictor of subacute (6-week) and chronic (3-month) headache-related disability; secondary analyses examined whether the individual NA components differentially impacted the outcomes. Hierarchical linear regression confirmed NA as a unique predictor of subacute (Cohen's f  2  = 0.130; P = .005) and chronic headache related-disability (Cohen's f  2  = 0.160; P = .004) beyond demographic and injury-related factors (sex, prior headaches, and closed head injury). Upon further analysis, PTSS uniquely predicted greater subacute (Cohen's f  2  = 0.105; P = .012) and chronic headache-related disability (Cohen's f  2  = 0.103; P = .022) above and beyond demographic and injury-related factors, depression, and anxiety. Avoidance was a robust predictor of subacute headache impairment (explaining 15% of the variance) and hyperarousal was a robust predictor of chronic headache impairment (10% of the variance). Although NA consistently predicted headache-related disability, PTSS alone was a unique predictor above and beyond nonpsychiatric factors, depression, and anxiety. These results are suggestive that early treatment of acute postinjury PTSS may correlate with

Cerebral Vascular Injury in Traumatic Brain Injury.

Science.gov (United States)

Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon

2016-01-01

Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI. Published by Elsevier Inc.

Robustness of Structural Systems

DEFF Research Database (Denmark)

Canisius, T.D.G.; Sørensen, John Dalsgaard; Baker, J.W.

2007-01-01

The importance of robustness as a property of structural systems has been recognised following several structural failures, such as that at Ronan Point in 1968,where the consequenceswere deemed unacceptable relative to the initiating damage. A variety of research efforts in the past decades have...... attempted to quantify aspects of robustness such as redundancy and identify design principles that can improve robustness. This paper outlines the progress of recent work by the Joint Committee on Structural Safety (JCSS) to develop comprehensive guidance on assessing and providing robustness in structural...... systems. Guidance is provided regarding the assessment of robustness in a framework that considers potential hazards to the system, vulnerability of system components, and failure consequences. Several proposed methods for quantifying robustness are reviewed, and guidelines for robust design...

Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority of vaccinated cancer patients.

Science.gov (United States)

Widenmeyer, Melanie; Griesemann, Heinrich; Stevanović, Stefan; Feyerabend, Susan; Klein, Reinhild; Attig, Sebastian; Hennenlotter, Jörg; Wernet, Dorothee; Kuprash, Dmitri V; Sazykin, Alexei Y; Pascolo, Steve; Stenzl, Arnulf; Gouttefangeas, Cécile; Rammensee, Hans-Georg

2012-07-01

CD4(+) T cells have been shown to be crucial for the induction and maintenance of cytotoxic T cell responses and to be also capable of mediating direct tumor rejection. Therefore, the anticancer therapeutic efficacy of peptide-based vaccines may be improved by addition of HLA class II epitopes to stimulate T helper cells. Survivin is an apoptosis inhibiting protein frequently overexpressed in tumors. Here we describe the first immunological evaluation of a survivin-derived CD4(+) T cell epitope in a multipeptide immunotherapy trial for prostate carcinoma patients. The survivin peptide is promiscuously presented by several human HLA-DRB1 molecules and, most importantly, is naturally processed by dendritic cells. In vaccinated patients, it was able to induce frequent, robust and multifunctional CD4(+) T cell responses, as monitored by IFN-γ ELISPOT and intracellular cytokine staining. Thus, this HLA-DR restricted epitope is broadly immunogenic and should be valuable for stimulating T helper cells in patients suffering from a wide range of tumors. Copyright © 2011 UICC.

Robust D-optimal designs under correlated error, applicable invariantly for some lifetime distributions

International Nuclear Information System (INIS)

Das, Rabindra Nath; Kim, Jinseog; Park, Jeong-Soo

2015-01-01

In quality engineering, the most commonly used lifetime distributions are log-normal, exponential, gamma and Weibull. Experimental designs are useful for predicting the optimal operating conditions of the process in lifetime improvement experiments. In the present article, invariant robust first-order D-optimal designs are derived for correlated lifetime responses having the above four distributions. Robust designs are developed for some correlated error structures. It is shown that robust first-order D-optimal designs for these lifetime distributions are always robust rotatable but the converse is not true. Moreover, it is observed that these designs depend on the respective error covariance structure but are invariant to the above four lifetime distributions. This article generalizes the results of Das and Lin [7] for the above four lifetime distributions with general (intra-class, inter-class, compound symmetry, and tri-diagonal) correlated error structures. - Highlights: • This paper presents invariant robust first-order D-optimal designs under correlated lifetime responses. • The results of Das and Lin [7] are extended for the four lifetime (log-normal, exponential, gamma and Weibull) distributions. • This paper also generalizes the results of Das and Lin [7] to more general correlated error structures

Robustness in laying hens

NARCIS (Netherlands)

Star, L.

2008-01-01

The aim of the project ‘The genetics of robustness in laying hens’ was to investigate nature and regulation of robustness in laying hens under sub-optimal conditions and the possibility to increase robustness by using animal breeding without loss of production. At the start of the project, a robust

Comparing alertness and injury severity following motor vehicular ...

African Journals Online (AJOL)

Background: From casual observation of injury patterns in Motor Vehicular Accidents (MVAs), it was sometimes observed that if the victim had been more alert and reacts protectively, injury severity might be reduced. Protective response is often expected to minimize the severity of injuries. Objective: To determine the ...

Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response

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Nikolay V. Ogryzko

2014-02-01

Full Text Available Interleukin-1 (IL-1, the ‘gatekeeper’ of inflammation, is the apical cytokine in a signalling cascade that drives the early response to injury or infection. Expression, processing and secretion of IL-1 are tightly controlled, and dysregulated IL-1 signalling has been implicated in a number of pathologies ranging from atherosclerosis to complications of infection. Our understanding of these processes comes from in vitro monocytic cell culture models as lines or primary isolates, in which a range and spectra of IL-1 secretion mechanisms have been described. We therefore investigated whether zebrafish embryos provide a suitable in vivo model for studying IL-1-mediated inflammation. Structurally, zebrafish IL-1β shares a β-sheet-rich trefoil structure with its human counterpart. Functionally, leukocyte expression of IL-1β was detectable only following injury, which activated leukocytes throughout zebrafish embryos. Migration of macrophages and neutrophils was attenuated by inhibitors of either caspase-1 or P2X7, which similarly inhibited the activation of NF-κB at the site of injury. Zebrafish offer a new and versatile model to study the IL-1β pathway in inflammatory disease and should offer unique insights into IL-1 biology in vivo.

Dendrite Injury Triggers DLK-Independent Regeneration

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Michelle C. Stone

2014-01-01

Full Text Available Axon injury triggers regeneration through activation of a conserved kinase cascade, which includes the dual leucine zipper kinase (DLK. Although dendrites are damaged during stroke, traumatic brain injury, and seizure, it is not known whether mature neurons monitor dendrite injury and initiate regeneration. We probed the response to dendrite damage using model Drosophila neurons. Two larval neuron types regrew dendrites in distinct ways after all dendrites were removed. Dendrite regeneration was also triggered by injury in adults. Next, we tested whether dendrite injury was initiated with the same machinery as axon injury. Surprisingly, DLK, JNK, and fos were dispensable for dendrite regeneration. Moreover, this MAP kinase pathway was not activated by injury to dendrites. Thus, neurons respond to dendrite damage and initiate regeneration without using the conserved DLK cascade that triggers axon regeneration.

Molecular and cellular responses to renal injury : a (phospho)-proteomic approach

NARCIS (Netherlands)

Graauw, Marjo de

2007-01-01

Our kidneys play a major role in regulating the body’s internal environment, via transportation of water, salt, potassium and waste products. As a result of this transport function, cells within the kidney are relatively sensitive to injury. This injury can occur when the kidneys are exposed to

The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease

Science.gov (United States)

Kokiko-Cochran, Olga N.; Godbout, Jonathan P.

2018-01-01

The post-injury inflammatory response is a key mediator in long-term recovery from traumatic brain injury (TBI). Moreover, the immune response to TBI, mediated by microglia and macrophages, is influenced by existing brain pathology and by secondary immune challenges. For example, recent evidence shows that the presence of beta-amyloid and phosphorylated tau protein, two hallmark features of AD that increase during normal aging, substantially alter the macrophage response to TBI. Additional data demonstrate that post-injury microglia are “primed” and become hyper-reactive following a subsequent acute immune challenge thereby worsening recovery. These alterations may increase the incidence of neuropsychiatric complications after TBI and may also increase the frequency of neurodegenerative pathology. Therefore, the purpose of this review is to summarize experimental studies examining the relationship between TBI and development of AD-like pathology with an emphasis on the acute and chronic microglial and macrophage response following injury. Furthermore, studies will be highlighted that examine the degree to which beta-amyloid and tau accumulation as well as pre- and post-injury immune stressors influence outcome after TBI. Collectively, the studies described in this review suggest that the brain’s immune response to injury is a key mediator in recovery, and if compromised by previous, coincident, or subsequent immune stressors, post-injury pathology and behavioral recovery will be altered. PMID:29686672

Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis by possible reduction of NLRP3 activation and up-regulation of NET expression.

Science.gov (United States)

Li, Yong; Pan, Yiyuan; Gao, Lin; Lu, Guotao; Zhang, Jingzhu; Xie, Xiaochun; Tong, Zhihui; Li, Baiqiang; Li, Gang; Li, Weiqin

2018-01-22

Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms. Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20 μg/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1β, and interleukin (IL)-1β in pancreatic tissue was detected by Western blot and real-time PCR. Dexmedetomidine at 20 μg/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20 μg/kg significantly down-regulated the expression of NLRP3, pro-IL-1β, and IL-1β in pancreatic tissue, but up-regulated the expression of NET in both mouse models. Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2.

Science.gov (United States)

Khan, Mohammad Farhan; Spurgeon, Sarah; von der Haar, Tobias

2018-05-14

Phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is one of the best studied and most widely used means for regulating protein synthesis activity in eukaryotic cells. This pathway regulates protein synthesis in response to stresses, viral infections, and nutrient depletion, among others. We present analyses of an ordinary differential equation-based model of this pathway, which aim to identify its principal robustness-conferring features. Our analyses indicate that robustness is a distributed property, rather than arising from the properties of any one individual pathway species. However, robustness-conferring properties are unevenly distributed between the different species, and we identify a guanine nucleotide dissociation inhibitor (GDI) complex as a species that likely contributes strongly to the robustness of the pathway. Our analyses make further predictions on the dynamic response to different types of kinases that impinge on eIF2. Copyright © 2018 Elsevier Ltd. All rights reserved.

Trampoline injuries in children.

Science.gov (United States)

McDermott, C; Quinlan, J F; Kelly, I P

2006-06-01

We reviewed the records of children referred to our hospital between April and September 2005 who had been injured whilst trampolining. Of 88 such children there were 33 boys and 55 girls with a mean age of 8 years 6 months (2 years 4 months to 15 years 9 months). Most of the injuries (53; 60%) occurred when bouncing and 34 (39%) were secondary to falls from the trampoline. The cause of injury was unknown in one child. The injured child was supervised in only 35 cases (40%). In 31 (35%) cases, the injury was related to the presence of others on the trampoline. A total of 36 (40%) children required surgery. Fractures of the upper limbs occurred in 62 cases (70%). Injuries related to the recreational use of trampolines are a significant cause of childhood injury. Our results suggest strongly that there is a need for clear guidelines on safe and responsible use of domestic trampolines.

Injuries in synchronized skating.

Science.gov (United States)

Dubravcic-Simunjak, S; Kuipers, H; Moran, J; Simunjak, B; Pecina, M

2006-06-01

Synchronized skating is a relatively new competitive sport and data about injuries in this discipline are lacking. Therefore the purpose of this study was to investigate the frequency and pattern of acute and overuse injuries in synchronized skaters. Before and during the World Synchronized Skating Championship 2004, a questionnaire inquiring about the frequency of injuries in this skating discipline was given to 23 participating teams. A total of 514 women and 14 men senior skaters completed the questionnaires (100 % response). Two hundred and eighteen (42.4 %) female and 6 (42.9 %) male skaters had suffered from acute injuries during their synchronized skating career. As some skaters had suffered from more than one injury, the total number of acute injuries in females was 398 and in males 14. In female skaters 19.8 % of acute injuries were head injuries, 7.1 % trunk, 33.2 % upper, and 39.9 % lower extremity injuries. In male skaters 14.3 % were head injuries, 28.6 % upper, and 57.1 % lower extremity injuries, with no report of trunk injuries. Sixty-nine female and 2 male skaters had low back problems and 112 female and 2 male skaters had one or more overuse syndromes during their skating career. Of 155 overuse injuries in female skaters, 102 (65.8 %) occurred during their figure skating career, while 53 injuries (34.2 %) only occurred when they skated in synchronized skating teams. In male skaters, out of 5 overuse injuries, 4 (80 %) occurred in their figure skating career, while 1 (20 %) occurred during their synchronized skating career. Out of the total of 412 injuries, 338 (82 %) occurred during on-ice practice, while 74 (18 %) happened during off-ice training. Ninety-one (26.9 %) acute injures occurred while practicing individual elements, and 247 (73.1 %) on-ice injuries occurred while practicing different team elements. We conclude that injuries in synchronized skating should be of medical concern due to an increasing number of acute injuries, especially

Vascular Response to Intra-arterial Injury in the Thrombospondin-1 Null Mouse

OpenAIRE

Budhani, Faisal; Leonard, Katherine A.; Bergdahl, Andreas; Gao, Jimin; Lawler, Jack; Davis, Elaine C.

2007-01-01

Thrombospondin-1 (TSP-1) is a multifunctional, extracellular matrix protein that has been implicated in the regulation of smooth muscle cell proliferation, migration and differentiation during vascular development and injury. Vascular injury in wildtype and TSP-1 null mice was carried out by insertion of a straight spring guidewire into the femoral artery via a muscular arterial branch. Blood flow was restored after the muscular branch was ligated. The injury completely denuded the endotheliu...

Stimulus fear relevance and the speed, magnitude, and robustness of vicariously learned fear.

Science.gov (United States)

Dunne, Güler; Reynolds, Gemma; Askew, Chris

2017-08-01

Superior learning for fear-relevant stimuli is typically indicated in the laboratory by faster acquisition of fear responses, greater learned fear, and enhanced resistance to extinction. Three experiments investigated the speed, magnitude, and robustness of UK children's (6-10 years; N = 290; 122 boys, 168 girls) vicariously learned fear responses for three types of stimuli. In two experiments, children were presented with pictures of novel animals (Australian marsupials) and flowers (fear-irrelevant stimuli) alone (control) or together with faces expressing fear or happiness. To determine learning speed the number of stimulus-face pairings seen by children was varied (1, 10, or 30 trials). Robustness of learning was examined via repeated extinction procedures over 3 weeks. A third experiment compared the magnitude and robustness of vicarious fear learning for snakes and marsupials. Significant increases in fear responses were found for snakes, marsupials and flowers. There was no indication that vicarious learning for marsupials was faster than for flowers. Moreover, vicariously learned fear was neither greater nor more robust for snakes compared to marsupials, or for marsupials compared to flowers. These findings suggest that for this age group stimulus fear relevance may have little influence on vicarious fear learning. Copyright © 2017 Elsevier Ltd. All rights reserved.

A population of Pax7-expressing muscle progenitor cells show differential responses to muscle injury dependent on developmental stage and injury extent

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Stefanie eKnappe

2015-08-01

Full Text Available Muscle regeneration in vertebrates occurs by the activation of quiescent progenitor cells that express pax7 and replace and repair damaged fibers. We have developed a mechanical injury paradigm in zebrafish to determine whether developmental stage and injury size affect the regeneration dynamics of damaged muscle. We found that both small, focal injuries and large injuries affecting the entire myotome lead to the expression of myf5 and myogenin. Their expression was prolonged in older larvae, indicating a slower process of regeneration. We characterized the endogenous behavior of a population of muscle-resident Pax7-expressing cells using a pax7a:eGFP transgenic line and found that GFP+ cell migration in the myotome dramatically declined between 5 and 7 days post fertilization (dpf. Following a small injury, we observed that GFP+ cells responded by extending processes, before migrating to the injured fibers. Furthermore, these cells responded more rapidly to injury in 4dpf larvae compared to 7dpf. Interestingly, we did not see GFP+ fibers after repair of small injuries, indicating that pax7a-expressing cells did not contribute to fiber formation in this injury context. On the contrary, numerous GFP+ fibers could be observed after a large single myotome injury. Both injury models were accompanied by an increased number of proliferating GFP+ cells, which was more pronounced in larvae injured at 4dpf than 7dpf, This indicates intriguing developmental differences, even at these relatively early ages. Our data also suggests an interesting disparity in the role that pax7a-expressing muscle progenitor cells play during muscle regeneration, which may reflect the extent of muscle damage.

Central canal ependymal cells proliferate extensively in response to traumatic spinal cord injury but not demyelinating lesions.

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Steve Lacroix

Full Text Available The adult mammalian spinal cord has limited regenerative capacity in settings such as spinal cord injury (SCI and multiple sclerosis (MS. Recent studies have revealed that ependymal cells lining the central canal possess latent neural stem cell potential, undergoing proliferation and multi-lineage differentiation following experimental SCI. To determine whether reactive ependymal cells are a realistic endogenous cell population to target in order to promote spinal cord repair, we assessed the spatiotemporal dynamics of ependymal cell proliferation for up to 35 days in three models of spinal pathologies: contusion SCI using the Infinite Horizon impactor, focal demyelination by intraspinal injection of lysophosphatidylcholine (LPC, and autoimmune-mediated multi-focal demyelination using the active experimental autoimmune encephalomyelitis (EAE model of MS. Contusion SCI at the T9-10 thoracic level stimulated a robust, long-lasting and long-distance wave of ependymal proliferation that peaked at 3 days in the lesion segment, 14 days in the rostral segment, and was still detectable at the cervical level, where it peaked at 21 days. This proliferative wave was suppressed distal to the contusion. Unlike SCI, neither chemical- nor autoimmune-mediated demyelination triggered ependymal cell proliferation at any time point, despite the occurrence of demyelination (LPC and EAE, remyelination (LPC and significant locomotor defects (EAE. Thus, traumatic SCI induces widespread and enduring activation of reactive ependymal cells, identifying them as a robust cell population to target for therapeutic manipulation after contusion; conversely, neither demyelination, remyelination nor autoimmunity appears sufficient to trigger proliferation of quiescent ependymal cells in models of MS-like demyelinating diseases.

Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.

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Heewon Park

Full Text Available The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc. and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.

Neuroinflammatory responses to traumatic brain injury: etiology, clinical consequences, and therapeutic opportunities

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Lozano D

2015-01-01

Full Text Available Diego Lozano,* Gabriel S Gonzales-Portillo,* Sandra Acosta, Ike de la Pena, Naoki Tajiri, Yuji Kaneko, Cesar V Borlongan Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA *These authors contributed equally to this work Abstract: Traumatic brain injury (TBI is a serious public health problem accounting for 1.4 million emergency room visits by US citizens each year. Although TBI has been traditionally considered an acute injury, chronic symptoms reminiscent of neurodegenerative disorders have now been recognized. These progressive neurodegenerative-like symptoms manifest as impaired motor and cognitive skills, as well as stress, anxiety, and mood affective behavioral alterations. TBI, characterized by external bumps or blows to the head exceeding the brain’s protective capacity, causes physical damage to the central nervous system with accompanying neurological dysfunctions. The primary impact results in direct neural cell loss predominantly exhibiting necrotic death, which is then followed by a wave of secondary injury cascades including excitotoxicity, oxidative stress, mitochondrial dysfunction, blood–brain barrier disruption, and inflammation. All these processes exacerbate the damage, worsen the clinical outcomes, and persist as an evolving pathological hallmark of what we now describe as chronic TBI. Neuroinflammation in the acute stage of TBI mobilizes immune cells, astrocytes, cytokines, and chemokines toward the site of injury to mount an antiinflammatory response against brain damage; however, in the chronic stage, excess activation of these inflammatory elements contributes to an “inflamed” brain microenvironment that principally contributes to secondary cell death in TBI. Modulating these inflammatory cells by changing their phenotype from proinflammatory to antiinflammatory would likely promote therapeutic effects on TBI. Because neuroinflammation occurs at

Association of brain injury and neonatal cytokine response during therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy.

Science.gov (United States)

Orrock, Janet E; Panchapakesan, Karuna; Vezina, Gilbert; Chang, Taeun; Harris, Kari; Wang, Yunfei; Knoblach, Susan; Massaro, An N

2016-05-01

Cytokines have been proposed as mediators of neonatal brain injury via neuroinflammatory pathways triggered by hypoxia-ischemia. Limited data are available on cytokine profiles in larger cohorts of newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Serum cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-α, and interferon-γ were measured in newborns with HIE at 24 and 72 h of TH. Differences between infants with favorable (survivors with mild/no magnetic resonance imaging (MRI) injury) vs. adverse outcome (death or moderate/severe MRI injury) were compared using mixed models to adjust for covariates. Data from 36 term newborns with HIE (favorable outcome: n = 20, adverse outcome: n = 16) were evaluated. Cytokines IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were elevated in the adverse relative to favorable outcome group at 24 h. IL-6 remained significantly elevated in the adverse outcome group at 72 h. IL-6 and IL-10 remained significantly associated with outcome group after controlling for covariates. Inflammatory cytokines are elevated in HIE newborns with brain injury by MRI. In particular, IL-6 and IL-10 were associated with adverse outcomes after controlling for baseline characteristics and severity of presentation. These data suggest that cytokine response may identify infants in need of additional neuroprotective interventions.

Hypertonic saline solution reduces the oxidative stress responses in traumatic brain injury patients

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Mojtaba Mojtahedzadeh

2014-01-01

Full Text Available Background: Oxidative stress processes play an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI. Hypertonic saline (HTS has advantages as being preferred osmotic agent, but few studies investigated oxidant and antioxidant effects of HTS in TBI. This study was designed to compare two different regimens of HTS 5% with mannitol on TBI-induced oxidative stress. Materials and Methods: Thirty-three adult patients with TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 h as bolus, 500 cc of HTS 5%as infusion for 24 h or 1 g/kg mannitol of 20% as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 h based on patient′s response for 3 days. Serum total antioxidant power (TAP, reactive oxygen species (ROS and nitric oxide (NO were measured at baseline and daily for 3 days. Results: Initial serum ROS and NO levels in patients were higher than control(6.86± [3.2] vs. 1.57± [0.5] picoM, P = 0.001, 14.6± [1.6] vs. 7.8± [3.9] mM, P = 0.001, respectively. Levels of ROS have decreased for all patients, but reduction was significantly after HTS infusion and mannitol (3. 08 [±3.1] to 1.07 [±1.6], P = 0.001, 5.6 [±3.4] to 2.5 [±1.8], P = 0.003 respectively. During study, NO levels significantly decreased in HTS infusion but significantly increased in mannitol. TAP Levels had decreased in all patients during study especially in mannitol (P = 0.004. Conclusion: Hypertonic saline 5% has significant effects on the oxidant responses compared to mannitol following TBI that makes HTS as a perfect therapeutic intervention for reducing unfavorable outcomes in TBI patients.

Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with systemic inflammatory response

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Hasegawa Naoki

2009-09-01

Full Text Available Abstract Bacterial genome is characterized by frequent unmethylated cytosine-phosphate-guanine (CpG motifs. Deleterious effects can occur when synthetic oligodeoxynucleotides (ODN with unmethylated CpG dinucleotides (CpG-ODN are administered in a systemic fashion. We aimed to evaluate the effect of intratracheal CpG-ODN on lung inflammation and systemic inflammatory response. C57BL/6J mice received intratracheal administration of CpG-ODN (0.01, 0.1, 1.0, 10, or 100 μM or control ODN without CpG motif. Bronchoalveolar lavage (BAL fluid was obtained 3 or 6 h or 1, 2, 7, or 14 days after the instillation and subjected to a differential cell count and cytokine measurement. Lung permeability was evaluated as the BAL fluid-to-plasma ratio of the concentration of human serum albumin that was injected 1 h before euthanasia. Nuclear factor (NF-κB DNA binding activity was also evaluated in lung homogenates. Intratracheal administration of 10 μM or higher concentration of CpG-ODN induced significant inflammatory cell accumulation into the airspace. The peak accumulation of neutrophils and lymphocytes occurred 1 and 2 days after the CpG-ODN administration, respectively. Lung permeability was increased 1 day after the 10 μM CpG-ODN challenge. CpG-ODN also induced nuclear translocation of NF-κB and upregulation of various inflammatory cytokines in BAL fluid and plasma. Histopathology of the lungs and liver revealed acute lung injury and liver damage with necrosis, respectively. Control ODN without CpG motif did not induce any inflammatory change. Since intratracheal CpG-ODN induced acute lung injury as well as systemic inflammatory response, therapeutic strategies to neutralize bacterial DNA that is released after administration of bactericidal agents should be considered.

Characterizing and predicting the robustness of power-law networks

International Nuclear Information System (INIS)

LaRocca, Sarah; Guikema, Seth D.

2015-01-01

Power-law networks such as the Internet, terrorist cells, species relationships, and cellular metabolic interactions are susceptible to node failures, yet maintaining network connectivity is essential for network functionality. Disconnection of the network leads to fragmentation and, in some cases, collapse of the underlying system. However, the influences of the topology of networks on their ability to withstand node failures are poorly understood. Based on a study of the response of 2000 randomly-generated power-law networks to node failures, we find that networks with higher nodal degree and clustering coefficient, lower betweenness centrality, and lower variability in path length and clustering coefficient maintain their cohesion better during such events. We also find that network robustness, i.e., the ability to withstand node failures, can be accurately predicted a priori for power-law networks across many fields. These results provide a basis for designing new, more robust networks, improving the robustness of existing networks such as the Internet and cellular metabolic pathways, and efficiently degrading networks such as terrorist cells. - Highlights: • Examine relationship between network topology and robustness to failures. • Relationship is statistically significant for scale-free networks. • Use statistical models to estimate robustness to failures for real-world networks

Hamstring Muscle Injuries, a Rehabilitation Protocol Purpose.

Science.gov (United States)

Valle, Xavier; L Tol, Johannes; Hamilton, Bruce; Rodas, Gil; Malliaras, Peter; Malliaropoulos, Nikos; Rizo, Vicenc; Moreno, Marcel; Jardi, Jaume

2015-12-01

Hamstring acute muscle injuries are prevalent in several sports including AFL football (Australian Football League), sprinting and soccer, and are often associated with prolonged time away from sport. In response to this, research into prevention and management of hamstring injury has increased, but epidemiological data shows no decline in injury and re-injury rates, suggesting that rehabilitation programs and return to play (RTP) criteria have to be improved. There continues to be a lack of consensus regarding how to assess performance, recovery and readiness to RTP, following hamstring strain injury. The aim of this paper was to propose rehabilitation protocol for hamstring muscle injuries based on current basic science and research knowledge regarding injury demographics and management options. Criteria-based (subjective and objective) progression through the rehabilitation program will be outlined along with exercises for each phase, from initial injury to RTP.

Surfing-related ocular injuries.

Science.gov (United States)

Kim, J W; McDonald, H R; Rubsamen, P E; Luttrull, J K; Drouilhet, J H; Frambach, D A; Boyer, D S; Lambrou, F H; Hendrick, A; Weiss, J N; Engstrom, R E; Ing, M

1998-01-01

This report evaluates the clinical characteristics of surfing-related ocular trauma to learn the nature of such injuries and propose possible preventive measures. The authors reviewed 11 cases of surfing-related eye injuries caused by direct trauma from the surfboard, studying their mechanism of injury, the associated ocular complications, and the anatomic and visual outcomes of surgical repair. Surfing-related ocular injuries occurred exclusively in young males (mean age, 24.8 years; range, 14-37 years). The mechanism of injury most frequently responsible was impact with the sharp nose of the surfboard following a fall. Serious posterior segment complications were observed in all 11 patients, with nine patients suffering ruptured globes. Despite immediate medical attention, five patients did not recover ambulatory levels of visual acuity (>5/200). Surfing-related ocular trauma presenting to the retinal specialist typically leaves the patient with a permanent visual disability. Important factors contributing to these high-velocity injuries include the sharply pointed nose of the surfboard and the leash keeping the surfer in close proximity to the board following a fall. A simple modification in surfboard design such as blunting the sharp nose of the surfboard, or appropriate protective guards fitted over the surfboard nose, should lessen the severity of such injuries.

Spontaneous Transient Lateral Thoracic Lung Herniation Resulting in Systemic Inflammatory Response Syndrome (SIRS and Subsequent Contralateral Lung Injury

Directory of Open Access Journals (Sweden)

Antony Kaliyadan

2011-01-01

Full Text Available Lung herniation is a relatively rare clinical entity that is most commonly either congenital or acquired traumatically. We describe a case of spontaneous lung herniation secondary to acute cough in an obese male smoker complicated by contralateral acute lung injury and systemic inflammatory response syndrome (SIRS. Mechanisms of lung herniation, classification, diagnosis, and management will be discussed.

Robust control design verification using the modular modeling system

International Nuclear Information System (INIS)

Edwards, R.M.; Ben-Abdennour, A.; Lee, K.Y.

1991-01-01

The Modular Modeling System (B ampersand W MMS) is being used as a design tool to verify robust controller designs for improving power plant performance while also providing fault-accommodating capabilities. These controllers are designed based on optimal control theory and are thus model based controllers which are targeted for implementation in a computer based digital control environment. The MMS is being successfully used to verify that the controllers are tolerant of uncertainties between the plant model employed in the controller and the actual plant; i.e., that they are robust. The two areas in which the MMS is being used for this purpose is in the design of (1) a reactor power controller with improved reactor temperature response, and (2) the design of a multiple input multiple output (MIMO) robust fault-accommodating controller for a deaerator level and pressure control problem

A robust sound perception model suitable for neuromorphic implementation.

Science.gov (United States)

Coath, Martin; Sheik, Sadique; Chicca, Elisabetta; Indiveri, Giacomo; Denham, Susan L; Wennekers, Thomas

2013-01-01

We have recently demonstrated the emergence of dynamic feature sensitivity through exposure to formative stimuli in a real-time neuromorphic system implementing a hybrid analog/digital network of spiking neurons. This network, inspired by models of auditory processing in mammals, includes several mutually connected layers with distance-dependent transmission delays and learning in the form of spike timing dependent plasticity, which effects stimulus-driven changes in the network connectivity. Here we present results that demonstrate that the network is robust to a range of variations in the stimulus pattern, such as are found in naturalistic stimuli and neural responses. This robustness is a property critical to the development of realistic, electronic neuromorphic systems. We analyze the variability of the response of the network to "noisy" stimuli which allows us to characterize the acuity in information-theoretic terms. This provides an objective basis for the quantitative comparison of networks, their connectivity patterns, and learning strategies, which can inform future design decisions. We also show, using stimuli derived from speech samples, that the principles are robust to other challenges, such as variable presentation rate, that would have to be met by systems deployed in the real world. Finally we demonstrate the potential applicability of the approach to real sounds.

A Robust Sound Perception Model Suitable for Neuromorphic Implementation

Directory of Open Access Journals (Sweden)

Martin eCoath

2014-01-01

Full Text Available We have recently demonstrated the emergence of dynamic feature sensitivity through exposure to formative stimuli in a real-time neuromorphic system implementing a hybrid analogue/digital network of spiking neurons. This network, inspired by models of auditory processing in mammals, includes several mutually connected layers with distance-dependent transmission delays and learning in the form of spike timing dependent plasticity, which effects stimulus-driven changes in the network connectivity.Here we present results that demonstrate that the network is robust to a range of variations in the stimulus pattern, such as are found in naturalistic stimuli and neural responses. This robustness is a property critical to the development of realistic, electronic neuromorphic systems.We analyse the variability of the response of the network to `noisy' stimuli which allows us to characterize the acuity in information-theoretic terms. This provides an objective basis for the quantitative comparison of networks, their connectivity patterns, and learning strategies, which can inform future design decisions. We also show, using stimuli derived from speech samples, that the principles are robust to other challenges, such as variable presentation rate, that would have to be met by systems deployed in the real world. Finally we demonstrate the potential applicability of the approach to real sounds.

Behavioral and anatomical characterization of the bilateral sciatic nerve chronic constriction (bCCI) injury: correlation of anatomic changes and responses to cold stimuli

OpenAIRE

Datta, Sukdeb; Chatterjee, Koel; Kline, Robert H; Wiley, Ronald G

2010-01-01

Abstract Background Unilateral constrictive sciatic nerve injury (uCCI) is a common neuropathic pain model. However, the bilateral constrictive injury (bCCI) model is less well studied, and shows unique characteristics. In the present study, we sought to correlate effects of bCCI on nocifensive responses to cold and mechanical stimuli with selected dorsal horn anatomic markers. bCCI or sham ligation of both rat sciatic nerves were followed up to 90 days of behavioural testing. Additional rats...

Illness perceptions and mood states are associated with injury-related outcomes in athletes

NARCIS (Netherlands)

van Wilgen, C. Paul; Kaptein, Ad A.; Brink, Michel S.

2010-01-01

Background. Athletes have to cope adequately with the consequences of their injury in order to return into sports as soon as possible. Besides the physical characteristics of the injury, illness perceptions and emotional responses impact the behavioural responses to the injury. Purpose. To apply

The Relationship of Parental Warm Responsiveness and Negativity to Emerging Behavior Problems Following Traumatic Brain Injury in Young Children

Science.gov (United States)

Wade, Shari L.; Cassedy, Amy; Walz, Nicolay C.; Taylor, H. Gerry; Stancin, Terry; Yeates, Keith Owen

2013-01-01

Parenting behaviors play a critical role in the child's behavioral development, particularly for children with neurological deficits. This study examined the relationship of parental warm responsiveness and negativity to changes in behavior following traumatic brain injury (TBI) in young children relative to an age-matched cohort of children with orthopedic injuries (OI). It was hypothesized that responsive parenting would buffer the adverse effects of TBI on child behavior, whereas parental negativity would exacerbate these effects. Children, ages 3–7 years, hospitalized for TBI (n = 80) or OI (n = 113), were seen acutely and again 6 months later. Parent–child dyads were videotaped during free play. Parents completed behavior ratings (Child Behavior Checklist; T. M. Achenbach & L. A. Rescorla, 2001) at both visits, with baseline ratings reflecting preinjury behavior. Hypotheses were tested using multiple regression, with preinjury behavior ratings, race, income, child IQ, family functioning, and acute parental distress serving as covariates. Parental responsiveness and negativity had stronger associations with emerging externalizing behaviors and attention-deficit/hyperactivity disorder symptoms among children with severe TBI. Findings suggest that parenting quality may facilitate or impede behavioral recovery following early TBI. Interventions that increase positive parenting may partially ameliorate emerging behavior problems. PMID:21244154

Robust Growth Determinants

OpenAIRE

Doppelhofer, Gernot; Weeks, Melvyn

2011-01-01

This paper investigates the robustness of determinants of economic growth in the presence of model uncertainty, parameter heterogeneity and outliers. The robust model averaging approach introduced in the paper uses a flexible and parsi- monious mixture modeling that allows for fat-tailed errors compared to the normal benchmark case. Applying robust model averaging to growth determinants, the paper finds that eight out of eighteen variables found to be significantly related to economic growth ...

Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

Science.gov (United States)

Noguera-Ortega, Estela; Blanco-Cabra, Núria; Rabanal, Rosa Maria; Sánchez-Chardi, Alejandro; Roldán, Mónica; Guallar-Garrido, Sandra; Torrents, Eduard; Luquin, Marina; Julián, Esther

2016-01-01

The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines’ production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae-treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer. PMID:27265565

Revisiting Robustness and Evolvability: Evolution in Weighted Genotype Spaces

Science.gov (United States)

Partha, Raghavendran; Raman, Karthik

2014-01-01

Robustness and evolvability are highly intertwined properties of biological systems. The relationship between these properties determines how biological systems are able to withstand mutations and show variation in response to them. Computational studies have explored the relationship between these two properties using neutral networks of RNA sequences (genotype) and their secondary structures (phenotype) as a model system. However, these studies have assumed every mutation to a sequence to be equally likely; the differences in the likelihood of the occurrence of various mutations, and the consequence of probabilistic nature of the mutations in such a system have previously been ignored. Associating probabilities to mutations essentially results in the weighting of genotype space. We here perform a comparative analysis of weighted and unweighted neutral networks of RNA sequences, and subsequently explore the relationship between robustness and evolvability. We show that assuming an equal likelihood for all mutations (as in an unweighted network), underestimates robustness and overestimates evolvability of a system. In spite of discarding this assumption, we observe that a negative correlation between sequence (genotype) robustness and sequence evolvability persists, and also that structure (phenotype) robustness promotes structure evolvability, as observed in earlier studies using unweighted networks. We also study the effects of base composition bias on robustness and evolvability. Particularly, we explore the association between robustness and evolvability in a sequence space that is AU-rich – sequences with an AU content of 80% or higher, compared to a normal (unbiased) sequence space. We find that evolvability of both sequences and structures in an AU-rich space is lesser compared to the normal space, and robustness higher. We also observe that AU-rich populations evolving on neutral networks of phenotypes, can access less phenotypic variation compared to

The Influence of Injury Definition on Injury Burden in Preprofessional Ballet and Contemporary Dancers.

Science.gov (United States)

Kenny, Sarah J; Palacios-Derflingher, Luz; Whittaker, Jackie L; Emery, Carolyn A

2018-03-01

Study Design Cohort study. Background Multiple operational definitions of injury exist in dance research. The influence that these different injury definitions have on epidemiological estimations of injury burden among dancers warrants investigation. Objective To describe the influence of injury definition on injury prevalence, incidence, and severity in preprofessional ballet and contemporary dancers. Methods Dancers registered in full-time preprofessional ballet (n = 85; 77 female; median age, 15 years; range, 11-19 years) and contemporary (n = 60; 58 female; median age, 19 years; range, 17-30 years) training completed weekly online questionnaires (modified Oslo Sports Trauma Research Centre questionnaire on health problems) using 3 injury definitions: (1) time loss (unable to complete 1 or more classes/rehearsals/performances for 1 or more days beyond onset), (2) medical attention, and (3) any complaint. Physical therapists completed injury report forms to capture dance-related medical attention and time-loss injuries. Percent agreement between injury registration methods was estimated. Injury prevalence (seasonal proportion of dancers injured), incidence rates (count of new injuries per 1000 dance-exposure hours), and severity (total days lost) were examined across each definition, registration method, and dance style. Results Questionnaire response rate was 99%. Agreement between registration methods ranged between 59% (time loss) and 74% (injury location). Depending on definition, registration, and dance style, injury prevalence ranged between 9.4% (95% confidence interval [CI]: 4.1%, 17.7%; time loss) and 82.4% (95% CI: 72.5%, 89.8%; any complaint), incidence rates between 0.1 (95% CI: 0.03, 0.2; time loss) and 4.9 (95% CI: 4.1, 5.8; any complaint) injuries per 1000 dance-hours, and days lost between 111 and 588 days. Conclusion Time-loss and medical-attention injury definitions underestimate the injury burden in preprofessional dancers. Accordingly, injury

Breast Regression Protein-39/Chitinase 3-Like 1 Promotes Renal Fibrosis after Kidney Injury via Activation of Myofibroblasts.

Science.gov (United States)

Montgomery, Tinika A; Xu, Leyuan; Mason, Sherene; Chinnadurai, Amirtha; Lee, Chun Geun; Elias, Jack A; Cantley, Lloyd G

2017-11-01

The normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein-39 (BRP-39), also known as chitinase 3-like 1 (CHI3L1) and encoded by the Chi3l1 gene, is expressed at high levels by macrophages during the early stages of kidney repair and promotes tubular cell survival via IL-13 receptor α 2 (IL13R α 2)-mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI. In wild-type mice, failure to resolve tubular injury after unilateral ischemia-reperfusion injury (U-IRI) led to sustained low-level Chi3l1 mRNA expression by renal cells and promoted macrophage persistence and severe interstitial fibrosis. Analysis of macrophages isolated from wild-type kidneys 14 days after U-IRI revealed high-level expression of the profibrotic BRP-39 receptor Ptgdr2 / Crth2 and expression of the profibrotic markers Lgals3 , Pdgfb , Egf , and Tgfb In comparison, injured kidneys from mice lacking BRP-39 had significantly fewer macrophages, reduced expression of profibrotic growth factors, and decreased accumulation of extracellular matrix. BRP-39 depletion did not affect myofibroblast accumulation but did attenuate myofibroblast expression of Col1a1 , Col3a1 , and Fn1 Together, these results identify BRP-39 as an important activator of macrophage-myofibroblast crosstalk and profibrotic signaling in the setting of maladaptive kidney repair. Copyright © 2017 by the American Society of Nephrology.

Respiratory mechanics in brain injury: A review

OpenAIRE

Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

2016-01-01

Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case ...

Effects of Dexmedetomidine Infusion on Inflammatory Responses and Injury of Lung Tidal Volume Changes during One-Lung Ventilation in Thoracoscopic Surgery: A Randomized Controlled Trial

Directory of Open Access Journals (Sweden)

Chun-Yu Wu

2018-01-01

Full Text Available One-lung ventilation in thoracic surgery provokes profound systemic inflammatory responses and injury related to lung tidal volume changes. We hypothesized that the highly selective a2-adrenergic agonist dexmedetomidine attenuates these injurious responses. Sixty patients were randomly assigned to receive dexmedetomidine or saline during thoracoscopic surgery. There is a trend of less postoperative medical complication including that no patients in the dexmedetomidine group developed postoperative medical complications, whereas four patients in the saline group did (0% versus 13.3%, p=0.1124. Plasma inflammatory and injurious biomarkers between the baseline and after resumption of two-lung ventilation were particularly notable. The plasma high-mobility group box 1 level decreased significantly from 51.7 (58.1 to 33.9 (45.0 ng.ml−1 (p<0.05 in the dexmedetomidine group, which was not observed in the saline group. Plasma monocyte chemoattractant protein 1 [151.8 (115.1 to 235.2 (186.9 pg.ml−1, p<0.05] and neutrophil elastase [350.8 (154.5 to 421.9 (106.1 ng.ml−1, p<0.05] increased significantly only in the saline group. In addition, plasma interleukin-6 was higher in the saline group than in the dexmedetomidine group at postoperative day 1 [118.8 (68.8 versus 78.5 (58.8 pg.ml−1, p=0.0271]. We conclude that dexmedetomidine attenuates one-lung ventilation-associated inflammatory and injurious responses by inhibiting alveolar neutrophil recruitment in thoracoscopic surgery.

Firework-related childhood injuries in Greece: a national problem.

Science.gov (United States)

Vassilia, Konte; Eleni, Petridou; Dimitrios, Trichopoulos

2004-03-01

During a 5-year period, out of 110066 children with injuries recorded in the Greek Emergency Department Injury Surveillance System (EDISS), 91 had firework-related injuries. Descriptive analyses and the Barrell matrix were used to determine risk factors and extrapolated national firework childhood injury figures were calculated. The estimated annual incidence of childhood firework injuries treated in the emergency departments of hospitals countrywide, was 7 per 100000 children years. Seventy percent of injuries concerned older children (10-14 years), mostly boys with self-inflicted injuries, whereas girls suffered injuries as bystanders. A sharp peak in spring was noted, when the Greek Orthodox Easter is celebrated. Illicitly sold fireworks caused most injuries, but in eight instances homemade firecrackers were responsible.

Signal Transduction Pathways Involved in Brain Death-Induced Renal Injury

NARCIS (Netherlands)

Bouma, H. R.; Ploeg, R. J.; Schuurs, T. A.

Kidneys derived from brain death organ donors show an inferior survival when compared to kidneys derived from living donors. Brain death is known to induce organ injury by evoking an inflammatory response in the donor. Neuronal injury triggers an inflammatory response in the brain, leading to

Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus

Directory of Open Access Journals (Sweden)

Chu Ketan

2012-04-01

Full Text Available Abstract Background Neuroinflammation plays an important role in cerebral ischemia/reperfusion (I/R injury. The P2X7 receptor (P2X7R has been reported to be involved in the inflammatory response of many central nervous system diseases. However, the role of P2X7Rs in transient global cerebral I/R injury remains unclear. The purpose of this study is to determine the effects of inhibiting the P2X7R in a rat model of transient global cerebral I/R injury, and then to explore the association between the P2X7R and neuroinflammation after transient global cerebral I/R injury. Methods Immediately after infusion with the P2X7R antagonists Brilliant blue G (BBG, adenosine 5′-triphosphate-2′,3′-dialdehyde (OxATP or A-438079, 20 minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO method in rats. Survival rate was calculated, neuronal death in the hippocampal CA1 region was observed using H & E staining, and DNA cleavage was observed by deoxynucleotidyl transferase-mediated UTP nick end labeling TUNEL. In addition, behavioral deficits were measured using the Morris water maze, and RT-PCR and immunohistochemical staining were performed to measure the expression of IL-1β, TNF-α and IL-6, and to identify activated microglia and astrocytes. Results The P2X7R antagonists protected against transient global cerebral I/R injury in a dosage-dependent manner. A high dosage of BBG (10 μg and A-0438079 (3 μg, and a low dosage of OxATP (1 μg significantly increased survival rates, reduced I/R-induced learning memory deficit, and reduced I/R-induced neuronal death, DNA cleavage, and glial activation and inflammatory cytokine overexpression in the hippocampus. Conclusions Our study indicates that inhibiting P2X7Rs protects against transient global cerebral I/R injury by reducing the I/R-induced inflammatory response, which suggests inhibition of P2X7Rs may be a promising therapeutic strategy for clinical treatment of

Advances in Crash Response

Centers for Disease Control (CDC) Podcasts

2009-06-29

In this podcast, Dr. Richard C. Hunt, Director of CDC's Division of Injury Response, provides an overview on the benefits of using an Advanced Automatic Collision Notification system, or AACN, to help with emergency triage of people injured in vehicle crashes.  Created: 6/29/2009 by National Center for Injury Prevention and Control (NCIPC), Division of Injury Response (DIR).   Date Released: 6/29/2009.

Reliability-Based Robust Design Optimization of Structures Considering Uncertainty in Design Variables

Directory of Open Access Journals (Sweden)

Shujuan Wang

2015-01-01

Full Text Available This paper investigates the structural design optimization to cover both the reliability and robustness under uncertainty in design variables. The main objective is to improve the efficiency of the optimization process. To address this problem, a hybrid reliability-based robust design optimization (RRDO method is proposed. Prior to the design optimization, the Sobol sensitivity analysis is used for selecting key design variables and providing response variance as well, resulting in significantly reduced computational complexity. The single-loop algorithm is employed to guarantee the structural reliability, allowing fast optimization process. In the case of robust design, the weighting factor balances the response performance and variance with respect to the uncertainty in design variables. The main contribution of this paper is that the proposed method applies the RRDO strategy with the usage of global approximation and the Sobol sensitivity analysis, leading to the reduced computational cost. A structural example is given to illustrate the performance of the proposed method.

Brain and Serum Androsterone is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

Directory of Open Access Journals (Sweden)

Richard J Servatius

2016-08-01

Full Text Available Exposure to lateral fluid percussion (LFP injury consistent with mild traumatic brain injury (mTBI persistently attenuates acoustic startle responses (ASRs in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM. ASRs were measured post injury days (PIDs 1, 3, 7, 14, 21 and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34, PID 35 (S35, on both days (2S, or the experimental context (CON. Levels of the neurosteroids pregnenolone (PREG, allopregnanolone (ALLO, and androsterone (ANDRO were determined for the prefrontal cortex, hippocampus and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30 and 60 min post-stressor for determination of corticosterone (CORT levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

Structural robustness with suboptimal responses for linear state space model

Science.gov (United States)

Keel, L. H.; Lim, Kyong B.; Juang, Jer-Nan

1989-01-01

A relationship between the closed-loop eigenvalues and the amount of perturbations in the open-loop matrix is addressed in the context of performance robustness. If the allowable perturbation ranges of elements of the open-loop matrix A and the desired tolerance of the closed-loop eigenvalues are given such that max(j) of the absolute value of Delta-lambda(j) (A+BF) should be less than some prescribed value, what is a state feedback controller F which satisfies the closed-loop eigenvalue perturbation-tolerance requirement for a class of given perturbation in A? The paper gives an algorithm to design such a controller. Numerical examples are included for illustration.

Return to driving after severe traumatic brain injury: increased risk of traffic accidents and personal responsibility.

Science.gov (United States)

Bivona, Umberto; DʼIppolito, Mariagrazia; Giustini, Marco; Vignally, Pascal; Longo, Eloise; Taggi, Franco; Formisano, Rita

2012-01-01

To determine the frequency of road traffic accidents among individuals who start or resume driving after severe traumatic brain injury (TBI) and to investigate their responsibility for these accidents. Observational/retrospective study. Sixty adults with severe TBI and their caregivers. Return to Driving Questionnaire and Glasgow Outcome Scale. Thirty of the 60 participants started to drive or resumed driving after TBI. Nineteen (63%) of them were involved in traffic accidents, with personal responsibility in 26 of 36 after return to driving. Participants caused a significantly higher number of accidents after TBI than before. The ability to drive is frequently compromised after severe TBI. Specific rehabilitation of this complex activity should be a main goal of social reintegration programs in this population.

Robustness of structures

DEFF Research Database (Denmark)

Vrouwenvelder, T.; Sørensen, John Dalsgaard

2009-01-01

After the collapse of the World Trade Centre towers in 2001 and a number of collapses of structural systems in the beginning of the century, robustness of structural systems has gained renewed interest. Despite many significant theoretical, methodical and technological advances, structural...... of robustness for structural design such requirements are not substantiated in more detail, nor have the engineering profession been able to agree on an interpretation of robustness which facilitates for its uantification. A European COST action TU 601 on ‘Robustness of structures' has started in 2007...... by a group of members of the CSS. This paper describes the ongoing work in this action, with emphasis on the development of a theoretical and risk based quantification and optimization procedure on the one side and a practical pre-normative guideline on the other....

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents

DEFF Research Database (Denmark)

Vesikari, Timo; Østergaard, Lars Jørgen; Diez-Domingo, Javier

2015-01-01

BACKGROUND: Neisseria meningitidis serogroup B (MnB) is a leading cause of invasive meningococcal disease in adolescents and young adults. A recombinant factor H binding protein (fHBP) vaccine (Trumenba(®); bivalent rLP2086) was recently approved in the United States in individuals aged 10-25 years....... Immunogenicity and safety of 2- or 3-dose schedules of bivalent rLP2086 were assessed in adolescents. METHODS: Healthy adolescents (11 to ... bactericidal antibody assay using human complement (hSBA). Safety assessments included local and systemic reactions and adverse events. RESULTS: Bivalent rLP2086 was immunogenic when administered as 2 or 3 doses; the most robust hSBA responses occurred with 3 doses. The proportion of subjects with hSBA titers...

Severe ocular injuries in Greek children.

Science.gov (United States)

Mela, Ephigenia K; Georgakopoulos, Constantinos D; Georgalis, Athanasios; Koliopoulos, John X; Gartaganis, Sotirios P

2003-02-01

To determine the epidemiological characteristics of severe eye injuries in childhood, in a mixed urban and rural Greek setting. Retrospective analysis of 95 cases (103 eyes) of eye injuries in children younger than 17 years of age admitted to the Department of Ophthalmology, University Hospital of Patras, Greece, during a five-year period. The data were analyzed with respect to age, sex, type, cause and mode of injury, method of management, duration of hospitalization and final visual deficit. The average age was 9.8 years and males were involved in 80% of the cases. The most common type of eye injury was mechanical closed-globe injury (71.8%). Mechanical open-globe injuries were found in 21.3% of the eyes, while burns comprised 6.7% of the injuries. Most injuries were agent-related, with blows and falls being responsible most often. Multiple operations were part of the treatment in 11.6% of the eyes; 14.5% of the eyes were blinded and 15.5% had significant final visual acuity loss. These hospital-based data suggest that there is a need for health education of both parents and children, since some injuries in children could easily have been prevented.

Prevention of Eye Injuries

OpenAIRE

Pashby, Tom

1981-01-01

In Canada 30,000 people are registered as blind; in one third of these, blindness might have been avoided. Prevention is the key to reducing the number of eye injuries and blind eyes. The role of the family physician in early identification of treatable conditions and in the education of patients is discussed, but responsibility for prevention belongs to all physicians. The success of prevention is seen in the great reduction in eye injuries in industry and sports since eye protectors have be...

Illness representations in patients with hand injury.

LENUS (Irish Health Repository)

Chan, Jeffrey C Y

2009-07-01

Differences in illness perception about hand injury may partly explain the variation in health behaviours such as adherence to post-operative therapy, coping strategy, emotional response and eventual clinical outcome. This study examined the illness perception of patients with hand injuries in the acute trauma setting.

Complement elevation in spinal cord injury.

Science.gov (United States)

Rebhun, J; Botvin, J

1980-05-01

Laboratory studies revealed an elevated complement in 66% of patients with spinal cord injury. It is postulated that the activated complement may be a component of self-feeding immunological mechanism responsible for the failure of regeneration of a mature mammalian spinal cord. There was no evidence that such an injury had any effect on pre-existing atopy.

Dirt bikes injuries in children.

Science.gov (United States)

Abdelgawad, A A; Maxfield, D; Tran, S; Mclean, S; Kanlic, E M

2013-12-01

Dirt bike riding is becoming a more popular recreational activity among children. Injuries associated with this recreational activity did not gain attention in the medical literature. The purpose of this study is to assess orthopedic injuries associated with dirt bike riding. We retrospectively studied injuries occurring in children less than 18 years old, while riding dirt bikes, that required admission to the trauma department in our level one trauma center during the period 2000-2010. There were 24 admissions (23 patients). The mean age was 13. Fourteen patients had brain injuries. Six patients had abdominal injuries. One patient died shortly after arriving to the emergency department. Fourteen patients had face and neck injuries. The average injury severity score was 8.5. Thirteen patients' admissions (54 %) had orthopedic fractures. Five of 13 patients (38 %) suffered more than one fracture. Eight patients needed orthopedic intervention (seven of these were in operating room under general anesthesia and one in the emergency department under conscious sedation). Femur fracture was the most common cause for performing surgery in this group of patients. Riding dirt bikes is not a safe recreational activity. Orthopedic injuries constitute a major component of the injuries affecting children riding dirt bikes. Orthopedic surgeons (being responsible for treating most of these children) have the obligation to warn the community against the possible dangers facing children who ride dirt bikes.

Environmental Noise, Genetic Diversity and the Evolution of Evolvability and Robustness in Model Gene Networks

Science.gov (United States)

Steiner, Christopher F.

2012-01-01

The ability of organisms to adapt and persist in the face of environmental change is accepted as a fundamental feature of natural systems. More contentious is whether the capacity of organisms to adapt (or “evolvability”) can itself evolve and the mechanisms underlying such responses. Using model gene networks, I provide evidence that evolvability emerges more readily when populations experience positively autocorrelated environmental noise (red noise) compared to populations in stable or randomly varying (white noise) environments. Evolvability was correlated with increasing genetic robustness to effects on network viability and decreasing robustness to effects on phenotypic expression; populations whose networks displayed greater viability robustness and lower phenotypic robustness produced more additive genetic variation and adapted more rapidly in novel environments. Patterns of selection for robustness varied antagonistically with epistatic effects of mutations on viability and phenotypic expression, suggesting that trade-offs between these properties may constrain their evolutionary responses. Evolution of evolvability and robustness was stronger in sexual populations compared to asexual populations indicating that enhanced genetic variation under fluctuating selection combined with recombination load is a primary driver of the emergence of evolvability. These results provide insight into the mechanisms potentially underlying rapid adaptation as well as the environmental conditions that drive the evolution of genetic interactions. PMID:23284934

A spatial generalized ordered response model to examine highway crash injury severity.

Science.gov (United States)

Castro, Marisol; Paleti, Rajesh; Bhat, Chandra R

2013-03-01

This paper proposes a flexible econometric structure for injury severity analysis at the level of individual crashes that recognizes the ordinal nature of injury severity categories, allows unobserved heterogeneity in the effects of contributing factors, as well as accommodates spatial dependencies in the injury severity levels experienced in crashes that occur close to one another in space. The modeling framework is applied to analyze the injury severity sustained in crashes occurring on highway road segments in Austin, Texas. The sample is drawn from the Texas Department of Transportation (TxDOT) crash incident files from 2009 and includes a variety of crash characteristics, highway design attributes, driver and vehicle characteristics, and environmental factors. The results from our analysis underscore the value of our proposed model for data fit purposes as well as to accurately estimate variable effects. The most important determinants of injury severity on highways, according to our results, are (1) whether any vehicle occupant is ejected, (2) whether collision type is head-on, (3) whether any vehicle involved in the crash overturned, (4) whether any vehicle occupant is unrestrained by a seat-belt, and (5) whether a commercial truck is involved. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mechanical injury induces brain endothelial-derived microvesicle release: Implications for cerebral vascular injury during traumatic brain injury

Directory of Open Access Journals (Sweden)

Allison M. Andrews

2016-02-01

Full Text Available It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and mechanotransduction. However, our understanding of vascular remodeling following traumatic brain injury (TBI remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs, such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury. Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB, which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24 and 48 hrs. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 hrs post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing

Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury.

Science.gov (United States)

Andrews, Allison M; Lutton, Evan M; Merkel, Steven F; Razmpour, Roshanak; Ramirez, Servio H

2016-01-01

It is well established that the endothelium responds to mechanical forces induced by changes in shear stress and strain. However, our understanding of vascular remodeling following traumatic brain injury (TBI) remains incomplete. Recently published studies have revealed that lung and umbilical endothelial cells produce extracellular microvesicles (eMVs), such as microparticles, in response to changes in mechanical forces (blood flow and mechanical injury). Yet, to date, no studies have shown whether brain endothelial cells produce eMVs following TBI. The brain endothelium is highly specialized and forms the blood-brain barrier (BBB), which regulates diffusion and transport of solutes into the brain. This specialization is largely due to the presence of tight junction proteins (TJPs) between neighboring endothelial cells. Following TBI, a breakdown in tight junction complexes at the BBB leads to increased permeability, which greatly contributes to the secondary phase of injury. We have therefore tested the hypothesis that brain endothelium responds to mechanical injury, by producing eMVs that contain brain endothelial proteins, specifically TJPs. In our study, primary human adult brain microvascular endothelial cells (BMVEC) were subjected to rapid mechanical injury to simulate the abrupt endothelial disruption that can occur in the primary injury phase of TBI. eMVs were isolated from the media following injury at 2, 6, 24, and 48 h. Western blot analysis of eMVs demonstrated a time-dependent increase in TJP occludin, PECAM-1 and ICAM-1 following mechanical injury. In addition, activation of ARF6, a small GTPase linked to extracellular vesicle production, was increased after injury. To confirm these results in vivo, mice were subjected to sham surgery or TBI and blood plasma was collected 24 h post-injury. Isolation and analysis of eMVs from blood plasma using cryo-EM and flow cytometry revealed elevated levels of vesicles containing occludin following brain trauma

Study of cervical cord injury without radiological abnormality using MRI at injury

International Nuclear Information System (INIS)

Park, Jin-Soo; Ei, Terumi; Uchida, Yoko; Kodai, Yujiro; Yasumatsu, Hideo; Yoshino, Kazutaka; Hirakawa, Takashi.

1994-01-01

This study was undertaken, using MRI at the time of injury, to examine cervical cord injury without radiological abnormality. The subjects were 30 patients (24 men and 6 women) seen during the 4-year period 1989-1993, who ranged in age from 31 to 83 years (an average age of 62.8 years). Of these patients, 10 had a slightly irregular alignment of the vertebral body on plain X-rays. These 10 patients were examined using MRI early after sustaining trauma (within 24 hours in 9 and 48 hours in one). As a result, spinal cord was seen as isointensity on T1-weighted images and hyperintensity on T2-weighted images, corresponding to irregular alignment. These findings suggest that reduction of a dislocation may transiently occur due to patient transfer or natural elasticity, as plain X-rays indicated no evidence of bone abnormalities. Thus injuries like dislocations may have occurred at the time of trauma, and structural changes of the vertebral body may be responsible for the occurrence of cervical spinal cord. Spinal cord injuries, even if not evidenced on plain X-rays, should not be categorized as non-osseous injuries. (N.K.)

Robustness of Structures

DEFF Research Database (Denmark)

Sørensen, John Dalsgaard

2008-01-01

This paper describes the background of the robustness requirements implemented in the Danish Code of Practice for Safety of Structures and in the Danish National Annex to the Eurocode 0, see (DS-INF 146, 2003), (DS 409, 2006), (EN 1990 DK NA, 2007) and (Sørensen and Christensen, 2006). More...... frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new structures essential....... According to Danish design rules robustness shall be documented for all structures in high consequence class. The design procedure to document sufficient robustness consists of: 1) Review of loads and possible failure modes / scenarios and determination of acceptable collapse extent; 2) Review...

Apoptosis-induced lymphopenia in sepsis and other severe injuries.

Science.gov (United States)

Girardot, Thibaut; Rimmelé, Thomas; Venet, Fabienne; Monneret, Guillaume

2017-02-01

Sepsis and other acute injuries such as severe trauma, extensive burns, or major surgeries, are usually followed by a period of marked immunosuppression. In particular, while lymphocytes play a pivotal role in immune response, their functions and numbers are profoundly altered after severe injuries. Apoptosis plays a central role in this process by affecting immune response at various levels. Indeed, apoptosis-induced lymphopenia duration and depth have been associated with higher risk of infection and mortality in various clinical settings. Therapies modulating apoptosis represent an interesting approach to restore immune competence after acute injury, although their use in clinical practice still presents several limitations. After briefly describing the apoptosis process in physiology and during severe injuries, we will explore the immunological consequences of injury-induced lymphocyte apoptosis, and describe associations with clinically relevant outcomes in patients. Therapeutic perspectives targeting apoptosis will also be discussed.

A Robust Synchronization to Enhance the Power Quality of Renewable Energy Systems

DEFF Research Database (Denmark)

Hadjidemetriou, Lenos; Kyriakides, Elias; Blaabjerg, Frede

2015-01-01

The increasing penetration of renewable energy sources (RESs) in the power grid requires high-quality power injection under various grid conditions. The synchronization method, usually a phase-locked loop (PLL) algorithm, is directly affecting the response of the grid-side converter of the RES....... This paper proposes a new PLL algorithm that uses an advanced decoupling network implemented in the stationary reference frame with limited requirements for processing time to enable a fast and accurate synchronization even under harmonic distorted voltage and low-voltage grid faults. The robust response...... of the proposed PLL is validated, and the effect of the proposed synchronization on the performance of the grid-connected renewable energy system is investigated. This investigation proves that the robust, accurate, and dynamic response of the new PLL can enhance the quality of the injected power from the RES...

Blast Injuries: What Clinicians Need to Know

Centers for Disease Control (CDC) Podcasts

In this podcast, Dr. Richard C. Hunt, Director of the CDC’s Division of Injury Response, National Center for Injury Prevention and Control provides a brief overview for health care providers on how to respond and care for persons injured by an explosion or blast event.

Physiological and foliar injury responses of Prunus serotina, Fraxinus americana, and Acer rubrum seedlings to varying soil moisture and ozone

International Nuclear Information System (INIS)

Schaub, M.; Skelly, J.M.; Steiner, K.C.; Davis, D.D.; Pennypacker, S.P.; Zhang, J.; Ferdinand, J.A.; Savage, J.E.; Stevenson, R.E.

2003-01-01

High soil water availability favors ozone uptake, increases foliar injury, and exacerbates the negative ozone effect on gas exchange of seedlings of deciduous tree species. - Sixteen black cherry (Prunus serotina, Ehrh.), 10 white ash (Fraxinus americana, L.) and 10 red maple (Acer rubrum, L.) 1-year old seedlings were planted per plot in 1997 on a former nursery bed within 12 open-top chambers and six open plots. Seedlings were exposed to three different ozone scenarios (ambient air: 100% O 3 ; non-filtered air: 98% ambient O 3 ; charcoal-filtered air: 50% ambient O 3 ) within each of two different water regimes (nine plots irrigated, nine plots non-irrigated) during three growing seasons. During the 1998 and 1999 growing season, leaf gas exchange, plant water relations, and foliar injury were measured. Climatic data, ambient- and chamber-ozone-concentrations were monitored. We found that seedlings grown under irrigated conditions had similar (in 1998) but significantly higher gas exchange rates (in 1999) than seedlings grown within non-irrigated plots among similar ozone exposures. Cherry and ash had similar ozone uptake but cherry developed more ozone-induced injury (<34% affected leaf area, LAA) than ash (<5% LAA), while maple rarely showed foliar injury, indicating the species differed in ozone sensitivity. Significantly more severe injury on seedlings grown under irrigated conditions than seedlings grown under non-irrigated conditions demonstrated that soil moisture altered seedling responses to ambient ozone exposures

Robust and distributed hypothesis testing

CERN Document Server

Gül, Gökhan

2017-01-01

This book generalizes and extends the available theory in robust and decentralized hypothesis testing. In particular, it presents a robust test for modeling errors which is independent from the assumptions that a sufficiently large number of samples is available, and that the distance is the KL-divergence. Here, the distance can be chosen from a much general model, which includes the KL-divergence as a very special case. This is then extended by various means. A minimax robust test that is robust against both outliers as well as modeling errors is presented. Minimax robustness properties of the given tests are also explicitly proven for fixed sample size and sequential probability ratio tests. The theory of robust detection is extended to robust estimation and the theory of robust distributed detection is extended to classes of distributions, which are not necessarily stochastically bounded. It is shown that the quantization functions for the decision rules can also be chosen as non-monotone. Finally, the boo...

Injuries in professional Rugby Union.

Science.gov (United States)

Targett, S G

1998-10-01

To document injury rates in professional rugby players in the Rugby Super 12 competition and to act as a pilot study for future studies of rugby injuries. Prospective longitudinal study encompassing the 1997 Super 12 rugby season. A New Zealand Super 12 rugby squad. 25 professional rugby players (replacement players were used for unavailable players, so although 30 different players were used during the season, there were only 25 in the squad at any one time). An "injury" was defined as something that prevented a player from taking part in two training sessions, from playing the next week, or something requiring special medical treatment (suturing or special investigations). An injury was "significant" if it prevented the player from being able to play one week after sustaining it (that is, if it made the player miss the next match). The overall injury rate was 120/1000 player hours. The rate of significant injuries was 45/1000 player hours. Those playing the position of "forward" had a higher overall injury rate than other players, but there was no difference in significant injury rate between the forwards and the backs. Injuries that caused players to miss game time occurred almost exclusively during the pre-season program or in the final third of the season. The majority of injuries were musculo-tendinous sprains or strains. The phase of play responsible for the majority of injuries was the tackle. The most frequently injured body part was the head and face. No catastrophic injuries occurred during the study period. Injury rates increase with increasing grade of rugby, injury rates in the Super 12 competition being higher than in first grade rugby. There is very little quality data on rugby injuries, and the few studies available use different methods of data collection and injury definition. There is a pressing need for the collection of accurate ongoing epidemiological data on injuries in rugby.

Polynomial algebra reveals diverging roles of the unfolded protein response in endothelial cells during ischemia-reperfusion injury.

Science.gov (United States)

Le Pape, Sylvain; Dimitrova, Elena; Hannaert, Patrick; Konovalov, Alexander; Volmer, Romain; Ron, David; Thuillier, Raphaël; Hauet, Thierry

2014-08-25

The unfolded protein response (UPR)--the endoplasmic reticulum stress response--is found in various pathologies including ischemia-reperfusion injury (IRI). However, its role during IRI is still unclear. Here, by combining two different bioinformatical methods--a method based on ordinary differential equations (Time Series Network Inference) and an algebraic method (probabilistic polynomial dynamical systems)--we identified the IRE1α-XBP1 and the ATF6 pathways as the main UPR effectors involved in cell's adaptation to IRI. We validated these findings experimentally by assessing the impact of their knock-out and knock-down on cell survival during IRI. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Robustness Property of Robust-BD Wald-Type Test for Varying-Dimensional General Linear Models

Directory of Open Access Journals (Sweden)

Xiao Guo

2018-03-01

Full Text Available An important issue for robust inference is to examine the stability of the asymptotic level and power of the test statistic in the presence of contaminated data. Most existing results are derived in finite-dimensional settings with some particular choices of loss functions. This paper re-examines this issue by allowing for a diverging number of parameters combined with a broader array of robust error measures, called “robust- BD ”, for the class of “general linear models”. Under regularity conditions, we derive the influence function of the robust- BD parameter estimator and demonstrate that the robust- BD Wald-type test enjoys the robustness of validity and efficiency asymptotically. Specifically, the asymptotic level of the test is stable under a small amount of contamination of the null hypothesis, whereas the asymptotic power is large enough under a contaminated distribution in a neighborhood of the contiguous alternatives, thus lending supports to the utility of the proposed robust- BD Wald-type test.

Injury risk factors among telemark skiers.

Science.gov (United States)

Tuggy, M L; Ong, R

2000-01-01

We performed a population survey of telemark skiers over two ski seasons to determine specific risk factors for injury. The survey inquired about the skier's sex, experience, equipment used, injuries, and number of days skied in each season. The respondents completed the surveys whether or not they were injured while skiing. We received 677 responses from telemark skiing clubs, with 19,962 skier-days of data. The number of self-reported injuries was 178, for an overall self-reported injury rate of 8.9 per 1000 skier-days. Knee injuries (N = 48) were the most common injury (27%), followed by thumb (N = 32, 18%) and shoulder (N = 21, 12%) injuries. Specific risk factors for injury were identified with multivariate regression and survival analysis. The skill level of the skier had a significant injury-sparing effect, as did the use of plastic telemark boots. The protective effect of the plastic boots was likely due to the increased stability they provided compared with traditional leather boots. There were fewer knee injuries with the recently available releasable bindings for telemark skis. Sex and age had no significant impact on injury rates in this study population. As all reported deaths associated with telemark sking were due to environmental hazards, skiers must continue to pay close attention to these hazards in the backcountry.

Effect of systemic inflammatory response in the development of encephalopathy in severe thermal injury

Directory of Open Access Journals (Sweden)

Sorokina O.Y.

2015-11-01

Full Text Available The article discusses the burn encephalopathy as a manifestation of organ dysfunction. Purpose: to determine the impact of the systemic inflammatory response to the development of en­cephalopathy in thermal injury. The study involved 104 patients, who were divided into two groups depending on the severity of the burn injury. The development of SIRS in patients was confirmed by high levels of IL-6 during the whole period of observation. The level of IL-6 did not affect the development, timing and duration of sleep disorders in both groups. The level of LII on the day 1 affects the development of sleep disorders in group 1 (R=0.499, p=0.041. Development of insomnia correlated with the shift of leukocyte formula to the left in group 2 on the day 5 (R=0.349, p=0.020. We found a relationship between the development of delirium, its duration and the level of young forms of neutrophils in patients of 1 (R=0.563, p=0.001 and 2 (R=0.3488, p=0.003 groups. Development of delirium, its timing and duration correlated with the level of IL-6 on day 3 (R=0.812, p=0,049, R=0.5903, p=0.079 and R=0.615, p=0.059, respectively in the group 2. The extent of the inflammatory reaction determined the disorders of thought (R=-0.545, p=0.036, memory (R=-0.547, p=0.023 and the dynamic of the recovery of cognitive functions in patients of group 1. Cognitive deficit correlated with the level of IL-6 (R=0.760, p=0.079 and the level of young forms of neutrophils (R=-0.603, p=0,013 in group 2. Thus, SIRS is a defining moment in the development of nervous system dysfunction in severe thermal injury.

Visitor injuries in Hawai'i.

Science.gov (United States)

Ho, Hao Chih; Speck, Cora S R; Kumasaki, Jennifer

2009-12-01

Over seven million tourists visit the Hawaiian Islands each year. Popular visitor activities such as surfing, scuba diving, ocean kayaking, parasailing, bicycle tours and hiking each have risks of serious injury. This study reviews visitors' activities that led to serious injuries requiring treatment at the state's only trauma center while vacationing in Hawai'i. A retrospective electronic medical record review was conducted of all visitor and resident trauma patients admitted to The Queen's Medical Center (QMC) from January 2002-December 2006. Patient demographics, injury type and severity, mechanism of injury, and discharge status were collected and analyzed. A total of 8244 patients were admitted to QMC for major traumatic injuries over the five year study period. Of these, 466 (5.7%) were visitors. The most common mechanisms of visitor injuries were falls (23.6%), water-related injuries (22.8%), motor vehicle crashes (18.7%), motorcycle, moped, and recreational vehicle crashes (12.2%), assaults (7.3%), and bicycle crashes (4.0%). A disproportionate number of visitors sustained serious injuries while engaging in water-related activities: Visitors account for only 12.6% of the population on any given day, yet comprise 44.2% of the total admissions for Hawai'i's water-related injuries. Head and spine injuries make up over two-thirds (68.2%) of these water-related visitor injuries. As a general category, falls were responsible for the highest number of visitor trauma admissions. Of the recreational activities leading to high numbers of trauma admissions, water-related activities are the leading causes of serious injuries among visitors to Hawai'i. Water-related injury rates are significantly higher for Hawai'i's visitors than residents. Water safety education for visitors should be developed in multiple languages to educate and protect Hawai'i's visitors and visitor industry.

Respiratory, cardiovascular and metabolic responses during different modes of overground bionic ambulation in persons with motor-incomplete spinal cord injury: A case series

Directory of Open Access Journals (Sweden)

Jochen Kressler

2017-09-01

Full Text Available Objective: To investigate the effects of overground bionic ambulation with variable assistance on cardiorespiratory and metabolic responses in persons with motor-incomplete spinal cord injury. Design: Case series. Subjects: Four participants with chronic, motor-incomplete spinal cord injury. Methods: Subjects completed a maximal graded exercise test on an arm-ergometer and 3 6-min bouts of overground bionic ambulation using different modes of assistance, i.e. Maximal, Adaptive, Fixed. Cardiorespiratory (oxygen consumption and metabolic (caloric expenditure and substrate utilization measures were taken using a mobile metabolic cart at each overground bionic ambulation assistance. Results: Cardiorespiratory responses ranged from low (24% VO2peak for the least impaired and fittest individual to supramaximal (124% VO2peak for the participant with the largest impairments and the lowest level of fitness. Different overground bionic ambulation assistive modes elicited small (3–8% VO2peak differences in cardiorespiratory responses for 3 participants. One participant had a large (28% VO2peak difference in cardiorespiratory responses to different modes of overground bionic ambulation. Metabolic responses mostly tracked closely with cardiorespiratory responses. Total energy expenditure ranged from 1.39 to 7.17 kcal/min. Fat oxidation ranged from 0.00 to 0.17 g/min across participants and different overground bionic ambulation modes. Conclusion: Overground bionic ambulation with variable assistance can substantially increase cardiorespiratory and metabolic responses; however, these responses vary widely across participants and overground bionic ambulation modes.

Work-related injuries and illnesses reported by World Trade Center response workers and volunteers.

Science.gov (United States)

Perritt, Kara R; Herbert, Robin; Levin, Stephen M; Moline, Jacqueline

2011-12-01

In 2002, the Mount Sinai Center for Occupational and Environmental Medicine, with support from the National Institute for Occupational Safety and Health (NIOSH), began coordinating the World Trade Center (WTC) Worker and Volunteer Medical Screening Program (MSP) to monitor the health of qualified WTC responders. Enrolled participants were offered a clinical examination; interviewed to collect medical, mental health, and exposure information; and requested to complete a self-administered medical questionnaire. The objective of this study was to better understand work-related injuries and illnesses sustained on-site by WTC responders. A descriptive analysis of select data from the MSP self-administered medical questionnaire was conducted. Data collected July 2002 through April 2004 from MSP participants enrolled at the Mount Sinai clinic were reviewed using univariate statistical techniques. Records from 7,810 participants were analyzed, with most participants associated with either the construction industry (n = 2,623, 34%) or law enforcement (n = 2,036, 26%). Approximately a third of the participants (n = 2,486, 32%) reported at least one injury or illness requiring medical treatment that was sustained during WTC work/volunteer activities. Of the total 4,768 injuries/illnesses reported by these participants, respiratory complaints were most common (n = 1,350, 28%), followed by traumatic injuries excluding eye injuries (n = 961, 20%), eye injuries/ailments (n = 709, 15%), chest pain (n = 375, 8%), headaches (n = 359, 8%), skin conditions (n = 178, 4%), and digestive system conditions (n = 163, 3%). Participants reported that 36% of injuries/illnesses were treated off-site and 29% were treated on-site, with the remaining not specifying treatment location. Off-site treatment was prevalent for respiratory complaints, psychological stress, and chest pain. On-site treatment was predominate for eye injuries/ailments and traumatic injuries excluding eye injuries. Study

Resveratrol Neuroprotection in Stroke and Traumatic CNS injury

Science.gov (United States)

Lopez, Mary; Dempsey, Robert J; Vemuganti, Raghu

2015-01-01

Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection. PMID:26277384

Mannan-binding lectin is involved in the protection against renal ischemia/ reperfusion injury by dietary restriction

NARCIS (Netherlands)

Shushimita; P. van der Pol (Pieter); R.W.F. de Bruin (Ron); J.N.M. IJzermans (Jan); C. van Kooten (Cees); F.J.M.F. Dor (Frank)

2015-01-01

textabstractPreoperative fasting and dietary restriction offer robust protection against renal ischemia/ reperfusion injury (I/RI) in mice.We recently showed that Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on

Mechanism and patterns of cervical spine fractures-dislocations in vertebral artery injury

Directory of Open Access Journals (Sweden)

Pankaj Gupta

2012-01-01

Full Text Available Purpose: To identify the fracture patterns and mechanism of injury, based on subaxial cervical spine injury classification system (SLIC, on non-contrast computed tomography (NCCT of cervical spine predictive of vertebral artery injury (VAI. Patients and Methods: We retrospectively analyzed cervical spine magnetic resonance imaging (MRI of 320 patients who were admitted with cervical spine injury in our level I regional trauma center over a period of two years (April 2010 to April 2012. Diagnosis of VAI was based on hyperintensity replacing the flow void on a T2-weighted axial image. NCCT images of the selected 43 patients with MRI diagnosis of VAI were then assessed for the pattern of injury. The cervical spinal injuries were classified into those involving the C1 and C2 and subaxial spine. For the latter, SLIC was used. Results: A total of 47 VAI were analyzed in 43 patients. Only one patient with VAI on MRI had no detectable abnormality on NCCT. C1 and C2 injuries were found in one and six patients respectively. In subaxial injuries, the most common mechanism of injury was distraction (37.5% with facet dislocation with or without fracture representing the most common pattern of injury (55%. C5 was the single most common affected vertebral level. Extension to foramen transversarium was present in 20 (42.5% cases. Conclusion: CT represents a robust screening tool for patients with VAI. VAI should be suspected in patients with facet dislocation with or without fractures, foramina transversarium fractures and C1-C3 fractures, especially type III odontoid fractures and distraction mechanism of injury.

Platelet-rich plasma (PRP for acute muscle injury: a systematic review.

Directory of Open Access Journals (Sweden)

Mohamad Shariff A Hamid

Full Text Available INTRODUCTION: Acute muscle injury is one of the commonest injuries that often result in loss of training and competition time. The best management for muscle injury has not been identified. Sports medicine practitioners used several approaches in attempt to accelerate time to recovery from muscle injury. More recently growing interest focussed on autologous blood product injection. METHODS: A literature search was conducted systematically using OvidMEDLINE, PubMed, EMBASE, SPORTDiscus and CINAHL databases to retrieve articles published until December 2012. Controlled trials and controlled laboratory studies comparing different strategies to promote early recovery of muscle injury were included. The methodological quality of studies was assessed. RESULTS: There are limited studies on the effects of PRP therapy for muscle injury. Three in vivo laboratory studies and one pilot human study were reviewed. The laboratory studies reported histological evidence on significant acceleration of muscle healing in animals treated with autologous conditioned serum (ACS, platelet-rich plasma (PRP and platelet rich fibrin matrix (PRFM. A pilot human study found athletes treated with repeated ACS injection recovers significantly faster than retrospective controls. CONCLUSION: Several in vivo laboratory studies suggest beneficial effects of ACS, PRP and PRFM in accelerating muscle recovery. Evidence to suggest similar effects on humans is however limited, as valuable information from robust human controlled trials is still not available at this moment. Hence, more studies of satisfactory methodological quality with platelet-rich plasma interventions on muscle injury are justified.

An ex vivo spinal cord injury model to study ependymal cells in adult mouse tissue.

Science.gov (United States)

Fernandez-Zafra, Teresa; Codeluppi, Simone; Uhlén, Per

2017-08-15

Traumatic spinal cord injury is characterized by an initial cell loss that is followed by a concerted cellular response in an attempt to restore the damaged tissue. Nevertheless, little is known about the signaling mechanisms governing the cellular response to injury. Here, we have established an adult ex vivo system that exhibits multiple hallmarks of spinal cord injury and allows the study of complex processes that are difficult to address using animal models. We have characterized the ependymal cell response to injury in this model system and found that ependymal cells can become activated, proliferate, migrate out of the central canal lining and differentiate in a manner resembling the in vivo situation. Moreover, we show that these cells respond to external adenosine triphosphate and exhibit spontaneous Ca 2+ activity, processes that may play a significant role in the regulation of their response to spinal cord injury. This model provides an attractive tool to deepen our understanding of the ependymal cell response after spinal cord injury, which may contribute to the development of new treatment options for spinal cord injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Depletion of GGA1 and GGA3 mediates post-injury elevation of BACE1

Science.gov (United States)

Walker, Kendall R.; Kang, Eugene L.; Whalen, Michael J.; Shen, Yong; Tesco, Giuseppina

2012-01-01

Traumatic brain injury (TBI) is one of the most robust environmental risk factors for Alzheimer’s disease (AD). Compelling evidence is accumulating that a single event of TBI is associated with increased levels of Aβ. However, the underlying molecular mechanisms remain unknown. We report here that the BACE1 interacting protein, GGA3, is depleted while BACE1 levels increase in the acute phase post-injury (48hrs) in a mouse model of TBI. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We next found that head trauma potentiates BACE1 elevation in GGA3 null mice in the acute phase post-TBI and discovered that GGA1, a GGA3 homologue, is a novel caspase-3 substrate depleted at 48 hrs post-TBI. Moreover, GGA1 silencing potentiates BACE1 elevation induced by GGA3 deletion in neurons in vitro indicating that GGA1 and GGA3 synergistically regulate BACE1. Accordingly, we found that levels of both GGA1 and GGA3 are depleted while BACE1 levels are increased in a series of post-mortem AD brains. Finally, we show that GGA3 haploinsufficiency results in sustained elevation of BACE1 and Aβ levels while GGA1 levels are restored in the subacute phase (7 days) post-injury. In conclusion, our data indicate that depletion of GGA1 and GGA3 engender a rapid and robust elevation of BACE1 in the acute phase post-injury. However, the efficient disposal of the acutely accumulated BACE1 solely depends on GGA3 levels in the sub-acute phase of injury. PMID:22836275

Robust control of an industrial boiler system; a comparison between two approaches: Sliding mode control and H∞ technique

International Nuclear Information System (INIS)

Moradi, Hamed; Bakhtiari-Nejad, Firooz; Saffar-Avval, Majid

2009-01-01

To achieve a good performance of the utility boiler, dynamic variables such as drum pressure, steam temperature and water level of drum must be controlled. In this paper, a linear time invariant (LTI) model of a boiler system is considered in which the input variables are feed-water and fuel mass rates. However this dynamic model may associate with uncertainties. With considering the uncertainties of the dynamic model, a sliding mode controller is designed. After representation of the uncertain dynamic system in general control configuration and modelling the parametric uncertainties, nominal performance, robust stability and robust performance are analyzed by the concept of structured singular value μ. Using an algorithm for μ-analysis and applying an inversed-base controller, robust stability and nominal performance are guaranteed but robust performance is not satisfied. Finally, an optimal robust controller is designed based on μ-synthesis with DK-iteration algorithm. Both optimal robust and sliding mode controllers guarantee robust performance of the system against the uncertainties and result in desired time responses of the output variables. By applying H ∞ robust control, system tracks the desire reference inputs in a less time and with smoother time responses. However, less control efforts, feedwater and fuel mass rates, are needed when the sliding mode controller is applied.

Amygdala activation as a marker for selective attention toward neutral faces in a chronic traumatic brain injury population.

Science.gov (United States)

Young, Leanne R; Yu, Weikei; Holloway, Michael; Rodgers, Barry N; Chapman, Sandra B; Krawczyk, Daniel C

2017-09-01

There has been great interest in characterizing the response of the amygdala to emotional faces, especially in the context of social cognition. Although amygdala activation is most often associated with fearful or angry stimuli, there is considerable evidence that the response of the amygdala to neutral faces is both robust and reliable. This characteristic of amygdala function is of particular interest in the context of assessing populations with executive function deficits, such as traumatic brain injuries, which can be evaluated using fMRI attention modulation tasks that evaluate prefrontal control over representations, notably faces. The current study tested the hypothesis that the amygdala may serve as a marker of selective attention to neutral faces. Using fMRI, we gathered data within a chronic traumatic brain injury population. Blood Oxygenation Level Dependent (BOLD) signal change within the left and right amygdalae and fusiform face areas was measured while participants viewed neutral faces and scenes, under conditions requiring participants to (1) categorize pictures of faces and scenes, (2) selectively attend to either faces or scenes, or (3) attend to both faces and scenes. Findings revealed that the amygdala is an effective marker for selective attention to neutral faces and, furthermore, it was more face-specific than the fusiform face area. Copyright © 2017 Elsevier Ltd. All rights reserved.

Robust Adaptive Exponential Synchronization of Stochastic Perturbed Chaotic Delayed Neural Networks with Parametric Uncertainties

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Yang Fang

2014-01-01

Full Text Available This paper investigates the robust adaptive exponential synchronization in mean square of stochastic perturbed chaotic delayed neural networks with nonidentical parametric uncertainties. A robust adaptive feedback controller is proposed based on Gronwally’s inequality, drive-response concept, and adaptive feedback control technique with the update laws of nonidentical parametric uncertainties as well as linear matrix inequality (LMI approach. The sufficient conditions for robust adaptive exponential synchronization in mean square of uncoupled uncertain stochastic chaotic delayed neural networks are derived in terms of linear matrix inequalities (LMIs. The effect of nonidentical uncertain parameter uncertainties is suppressed by the designed robust adaptive feedback controller rapidly. A numerical example is provided to validate the effectiveness of the proposed method.

Guaranteeing robustness of structural condition monitoring to environmental variability

Science.gov (United States)

Van Buren, Kendra; Reilly, Jack; Neal, Kyle; Edwards, Harry; Hemez, François

2017-01-01

Advances in sensor deployment and computational modeling have allowed significant strides to be recently made in the field of Structural Health Monitoring (SHM). One widely used SHM strategy is to perform a vibration analysis where a model of the structure's pristine (undamaged) condition is compared with vibration response data collected from the physical structure. Discrepancies between model predictions and monitoring data can be interpreted as structural damage. Unfortunately, multiple sources of uncertainty must also be considered in the analysis, including environmental variability, unknown model functional forms, and unknown values of model parameters. Not accounting for these sources of uncertainty can lead to false-positives or false-negatives in the structural condition assessment. To manage the uncertainty, we propose a robust SHM methodology that combines three technologies. A time series algorithm is trained using "baseline" data to predict the vibration response, compare predictions to actual measurements collected on a potentially damaged structure, and calculate a user-defined damage indicator. The second technology handles the uncertainty present in the problem. An analysis of robustness is performed to propagate this uncertainty through the time series algorithm and obtain the corresponding bounds of variation of the damage indicator. The uncertainty description and robustness analysis are both inspired by the theory of info-gap decision-making. Lastly, an appropriate "size" of the uncertainty space is determined through physical experiments performed in laboratory conditions. Our hypothesis is that examining how the uncertainty space changes throughout time might lead to superior diagnostics of structural damage as compared to only monitoring the damage indicator. This methodology is applied to a portal frame structure to assess if the strategy holds promise for robust SHM. (Publication approved for unlimited, public release on October-28

Contribution of Histologic Chorioamnionitis and Fetal Inflammatory Response Syndrome to Increased Risk of Brain Injury in Infants With Preterm Premature Rupture of Membranes.

Science.gov (United States)

Lu, Hong-Yan; Zhang, Qiang; Wang, Qiu-Xia; Lu, Jun-Ying

2016-08-01

To determine the association of histologic chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) with brain injuries in infants born to mothers with preterm premature rupture of membranes. A total of 103 singleton infants born to mothers with preterm premature rupture of membranes were enrolled. The placental inflammation was confirmed by HCA, and FIRS was defined in fetuses with preterm labor and an elevation of the fetal plasma interleukin-6 concentration. Examination of brain images was conducted to confirm the existence of brain injuries. Based on placental HCA and umbilical cord blood interleukin-6 level, all patients were divided into three groups: HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+). Among all infants with preterm premature rupture of membranes, 53.40% were exposed to HCA, 20.38% experienced FIRS, and the overall incidence of brain injuries was 38.83%. The incidence of brain injury in HCA(-)FIRS(+), HCA(+)FIRS(-), and HCA(+)FIRS(+) groups were 20.83%, 41.18%, and 76.19%, respectively. HCA at the advanced grades and stages was associated with increased risk of brain injury. Umbilical cord blood levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and granulocyte-colony stimulating factor (G-CSF) in premature infants with brain injuries were significantly higher than in those without brain injuries. Infants diagnosed with both HCA and FIRS showed significantly higher levels of IL-8, TNF-α, and G-CSF than those with HCA alone. Preterm infants exposed to severe chorioamnionitis had an increased risk of brain injury. IL-6, IL-8, TNF-α, and G-CSF in cord blood were associated with brain injuries in preterm infants and may be used as extradiagnostic criteria. Copyright © 2016 Elsevier Inc. All rights reserved.

associated injuries and complications in floating knee management

African Journals Online (AJOL)

Materials and Methods: The investigation lasted ten years from 1st January, 2000 to ... hemarthrosis, 2 paralysis of fibular nerve associated to a displaced fracture of neck of ... Keywords: Associated injuries, complications, Floating knee, Management ... Road traffic accidents were responsible for 51 cases ... cerebral injuries.

Sevoflurane posttreatment prevents oxidative and inflammatory injury in ventilator-induced lung injury.

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Julie Wagner

Full Text Available Mechanical ventilation is a life-saving clinical treatment but it can induce or aggravate lung injury. New therapeutic strategies, aimed at reducing the negative effects of mechanical ventilation such as excessive production of reactive oxygen species, release of pro-inflammatory cytokines, and transmigration as well as activation of neutrophil cells, are needed to improve the clinical outcome of ventilated patients. Though the inhaled anesthetic sevoflurane is known to exert organ-protective effects, little is known about the potential of sevoflurane therapy in ventilator-induced lung injury. This study focused on the effects of delayed sevoflurane application in mechanically ventilated C57BL/6N mice. Lung function, lung injury, oxidative stress, and inflammatory parameters were analyzed and compared between non-ventilated and ventilated groups with or without sevoflurane anesthesia. Mechanical ventilation led to a substantial induction of lung injury, reactive oxygen species production, pro-inflammatory cytokine release, and neutrophil influx. In contrast, sevoflurane posttreatment time dependently reduced histological signs of lung injury. Most interestingly, increased production of reactive oxygen species was clearly inhibited in all sevoflurane posttreatment groups. Likewise, the release of the pro-inflammatory cytokines interleukin-1β and MIP-1β and neutrophil transmigration were completely prevented by sevoflurane independent of the onset of sevoflurane administration. In conclusion, sevoflurane posttreatment time dependently limits lung injury, and oxidative and pro-inflammatory responses are clearly prevented by sevoflurane irrespective of the onset of posttreatment. These findings underline the therapeutic potential of sevoflurane treatment in ventilator-induced lung injury.

Correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury

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Bing-Feng Tian

2018-07-01

Full Text Available Objective: To study the correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury. Methods: A total of 110 patients with traumatic brain injury who were treated in our hospital between January 2015 and December 2016 were collected as the observation group, and 60 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. Serum GFAP, S100B and NSE levels as well as oxidative stress index and insulin resistance index levels of two groups of subjects were detected, and Pearson test was used to further evaluate the correlation of serum GFAP, S100B and NSE contents with oxidative stress response and insulin resistance in patients with traumatic brain injury. Results: Serum GFAP, S100B and NSE contents of observation group were significantly higher than those of normal control group; serum oxidative stress indexes MDA, MPO and LPO contents were higher than those of normal control group while SOD and TAC contents were lower than those of normal control group; serum insulin resistance indexes GLU, INS and HOMA-IR levels were higher than those of control group. Pearson test showed that serum GFAP, S100B and NSE contents in patients with traumatic brain injury were directly correlated with post-traumatic oxidative stress and insulin resistance. Conclusion: The serum GFAP, S100B and NSE contents increase in patients with traumatic brain injury, and the increase is directly correlated with the oxidative stress and insulin resistance.

Chronic Pain Following Spinal Cord Injury: The Role of Immunogenetics and Time of Injury Pain Treatment

Science.gov (United States)

2016-10-01

experience inflammation in response to opioid exposure. Critically , this genetic variability may significantly impact the long-term health and quality of...polymorphic. Hence, an individual may have a genetic predisposition to over respond in a proinflammatory fashion to the spinal cord injury, and/or to...life of the individual. Thus both genetics and drug exposure at the time of injury may be contributing factors individually and/or interactively

Chest injuries associated with earthquakes: an analysis of injuries sustained during the 2008 Wen-Chuan earthquake in China.

Science.gov (United States)

Hu, Jia; Guo, Ying-Qiang; Zhang, Er-Yong; Tan, Jin; Shi, Ying-Kang

2010-08-01

The goal of this study was to analyze the patterns, therapeutic modalities, and short-term outcomes of patients with chest injuries in the aftermath of the Wen-Chuan earthquake, which occurred on May 12, 2008 and registered 8.0 on the Richter scale. Of the 1522 patients who were referred to the West China Hospital of Sichuan University from May 12 to May 27, 169 patients (11.1%) had suffered major chest injuries. The type of injury, the presence of infection, Abbreviated Injury Score (AIS 2005), New Injury Severity Score (NISS), treatment, and short-term outcome were all documented for each case. Isolated chest injuries were diagnosed in 129 patients (76.3%), while multiple injuries with a major chest trauma were diagnosed in 40 patients (23.7%). The mean AIS and the median NISS of the hospitalized patients with chest injuries were 2.5 and 13, respectively. The mortality rate was 3.0% (5 patients). Most of the chest injuries were classified as minor to moderate trauma; however, coexistent multiple injuries and subsequent infection should be carefully considered in medical response strategies. Coordinated efforts among emergency medical support groups and prior training in earthquake preparedness and rescue in earthquake-prone areas are therefore necessary for efficient evacuation and treatment of catastrophic casualties.

Robustness Analyses of Timber Structures

DEFF Research Database (Denmark)

Kirkegaard, Poul Henning; Sørensen, John Dalsgaard; Hald, Frederik

2013-01-01

The robustness of structural systems has obtained a renewed interest arising from a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. In order to minimise the likelihood of such disproportionate structural failures, many mo...... with respect to robustness of timber structures and will discuss the consequences of such robustness issues related to the future development of timber structures.......The robustness of structural systems has obtained a renewed interest arising from a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. In order to minimise the likelihood of such disproportionate structural failures, many...... modern building codes consider the need for the robustness of structures and provide strategies and methods to obtain robustness. Therefore, a structural engineer may take necessary steps to design robust structures that are insensitive to accidental circumstances. The present paper summaries issues...

Individual differences in perception and response to experimental ...

African Journals Online (AJOL)

Background: Pain is a protective sensation that alerts an individual to injury from the environment. Experience of pain is characterised by robust individual differences and complex environmental ... Data were presented as mean ± SD. Differences and statistical significance between the means were determined using t test.

Set-Membership Identification for Robust Control Design

Science.gov (United States)

1993-04-28

Clauifica lion) ( U) Set-Memnbership Identification for Robust Control Design ___________________ 1. PERSONAL A UTHOR(SI Dr. Robert L. Kosul. Final Report...Shalom, E.Tse "Caution, probing, and the value of information in the control of un- certain systems", Annals of Economic and Social Measurement, 5/3, pp...knowing a bound on I the impulse response is quantitative. A similar clasoitication can be made regarding signal charateristics . Knowing that a signal is

QUALITY IMPROVEMENT IN MULTIRESPONSE EXPERIMENTS THROUGH ROBUST DESIGN METHODOLOGY

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M. Shilpa

2012-06-01

Full Text Available Robust design methodology aims at reducing the variability in the product performance in the presence of noise factors. Experiments involving simultaneous optimization of more than one quality characteristic are known as multiresponse experiments which are used in the development and improvement of industrial processes and products. In this paper, robust design methodology is applied to optimize the process parameters during a particular operation of rotary driving shaft manufacturing process. The three important quality characteristics of the shaft considered here are of type Nominal-the-best, Smaller-the-better and Fraction defective. Simultaneous optimization of these responses is carried out by identifying the control parameters and conducting the experimentation using L9 orthogonal array.

Telemark skiing injuries: characteristics and risk factors.

Science.gov (United States)

Federiuk, C S; Mann, N C

1999-01-01

To determine the types of injuries associated with telemark skiing and the effects of ability level, equipment, and terrain. A survey was mailed to a sample of North American telemark skiers. Completed surveys were returned by 548 telemarkers (response rate = 74.5%). The mean age was 42.7 (+/- 9.3) years, and 69% were male. A total of 439 injury events resulted in 494 body injuries, reported by 285 skiers (52%). Lower-extremity injuries (n = 231) were more frequent than upper-extremity injuries (n = 187). Knee injuries were most common with 128 cases, followed by 80 thumb, 66 shoulder, and 44 ankle injuries. Surgery was required in 39 cases. Skiers suffering thumb injuries with sequela lasting greater than 3 months were 10.1 times less likely to have sought medical attention than skiers with other long-term injuries (p boot type and overall knee or ankle injury, but risk of severe ankle injury was increased in leather boots compared to plastic (OR = 8.0, CI = 1.05, 60.59). Release bindings were used by 27.9% of all skiers but were in use in only 18.7% of injury events, suggesting that release plates have a protective effect against injury (OR = 0.59, p knee, thumb, shoulder, and ankle are most frequently injured telemark skiing. Injuries are more likely to occur at lift-served areas than in the backcountry. Thumb injuries are often ignored and may result in long-term sequela. Ankle injuries appear more severe in leather boots. Release bindings appear protective against injury, but they often do not release.

Robust Pitch Estimation Using an Optimal Filter on Frequency Estimates

DEFF Research Database (Denmark)

Karimian-Azari, Sam; Jensen, Jesper Rindom; Christensen, Mads Græsbøll

2014-01-01

of such signals from unconstrained frequency estimates (UFEs). A minimum variance distortionless response (MVDR) method is proposed as an optimal solution to minimize the variance of UFEs considering the constraint of integer harmonics. The MVDR filter is designed based on noise statistics making it robust...

Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

Science.gov (United States)

Lorimore, S A; Wright, E G

2003-01-01

To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The

Robust Optimization of Thermal Aspects of Friction Stir Welding Using Manifold Mapping Techniques

DEFF Research Database (Denmark)

Larsen, Anders Astrup; Lahaye, Domenico; Schmidt, Henrik Nikolaj Blicher

2008-01-01

The aim of this paper is to optimize a friction stir welding process taking robustness into account. The optimization problems are formulated with the goal of obtaining desired mean responses while reducing the variance of the response. We restrict ourselves to a thermal model of the process...

Changes in Oxidative Stress Markers and Biological Markers of Muscle Injury with Aging at Rest and in Response to an Exhaustive Exercise

Science.gov (United States)

Bouzid, Mohamed Amine; Hammouda, Omar; Matran, Regis; Robin, Sophie; Fabre, Claudine

2014-01-01

Purpose The aim of this study was to evaluate whether oxidative stress markers and biomarkers of muscle injury would be affected by aging at rest and in response to an incremental exhaustive exercise. Methods Fifteen young (20.3±2.8 years) and fifteen older adults (65.1±3.5 years) performed an incremental cycle ergometer test to exhaustion. Before and after exercise, oxidative stress [superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), ascorbic acid, α-Tocopherol, malondialdehyde (MDA)] and muscle injury [creatine kinase (CK), lactate deshydrogenase (LDH)] biomarkers were assessed. Results At rest, there was no difference in oxidative stress markers and LDH level between the groups, however CK was significantly higher in the young group than the elderly group (pantioxidant efficiency and an increase in oxidative stress damage. Furthermore, older adults would not more susceptible to exercise-induced muscle injury than young people. PMID:24618679

Initial and sustained brain responses to threat anticipation in blood-injection-injury phobia

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Leonie Brinkmann

2017-01-01

Full Text Available Blood-injection-injury (BII phobia differs from other subtypes of specific phobia in that it is associated with elevated disgust-sensitivity as well as specific autonomic and brain responses during processing of phobia-relevant stimuli. To what extent these features play a role already during threat anticipation is unclear. In the current fMRI experiment, 16 female BII phobics and 16 female healthy controls anticipated the presentation of phobia-specific and neutral pictures. On the behavioral level, anxiety dominated the anticipatory period in BII phobics relative to controls, while both anxiety and disgust were elevated during picture presentation. By applying two different models for the analysis of brain responses to anticipation of phobia-specific versus neutral stimuli, we found initial and sustained increases of activation in anterior cingulate cortex (ACC, insula, lateral and medial prefrontal cortex (PFC, thalamus and visual areas, as well as initial activation in the amygdala for BII phobics as compared to healthy controls. These results suggest that BII phobia is characterized by activation of a typical neural defense network during threat anticipation, with anxiety as the predominant emotion.

Robustness analysis of bogie suspension components Pareto optimised values

Science.gov (United States)

Mousavi Bideleh, Seyed Milad

2017-08-01

Bogie suspension system of high speed trains can significantly affect vehicle performance. Multiobjective optimisation problems are often formulated and solved to find the Pareto optimised values of the suspension components and improve cost efficiency in railway operations from different perspectives. Uncertainties in the design parameters of suspension system can negatively influence the dynamics behaviour of railway vehicles. In this regard, robustness analysis of a bogie dynamics response with respect to uncertainties in the suspension design parameters is considered. A one-car railway vehicle model with 50 degrees of freedom and wear/comfort Pareto optimised values of bogie suspension components is chosen for the analysis. Longitudinal and lateral primary stiffnesses, longitudinal and vertical secondary stiffnesses, as well as yaw damping are considered as five design parameters. The effects of parameter uncertainties on wear, ride comfort, track shift force, stability, and risk of derailment are studied by varying the design parameters around their respective Pareto optimised values according to a lognormal distribution with different coefficient of variations (COVs). The robustness analysis is carried out based on the maximum entropy concept. The multiplicative dimensional reduction method is utilised to simplify the calculation of fractional moments and improve the computational efficiency. The results showed that the dynamics response of the vehicle with wear/comfort Pareto optimised values of bogie suspension is robust against uncertainties in the design parameters and the probability of failure is small for parameter uncertainties with COV up to 0.1.

Robust MR spine detection using hierarchical learning and local articulated model.

Science.gov (United States)

Zhan, Yiqiang; Maneesh, Dewan; Harder, Martin; Zhou, Xiang Sean

2012-01-01

A clinically acceptable auto-spine detection system, i.e., localization and labeling of vertebrae and inter-vertebral discs, is required to have high robustness, in particular to severe diseases (e.g., scoliosis) and imaging artifacts (e.g. metal artifacts in MR). Our method aims to achieve this goal with two novel components. First, instead of treating vertebrae/discs as either repetitive components or completely independent entities, we emulate a radiologist and use a hierarchial strategy to learn detectors dedicated to anchor (distinctive) vertebrae, bundle (non-distinctive) vertebrae and inter-vertebral discs, respectively. At run-time, anchor vertebrae are detected concurrently to provide redundant and distributed appearance cues robust to local imaging artifacts. Bundle vertebrae detectors provide candidates of vertebrae with subtle appearance differences, whose labels are mutually determined by anchor vertebrae to gain additional robustness. Disc locations are derived from a cloud of responses from disc detectors, which is robust to sporadic voxel-level errors. Second, owing to the non-rigidness of spine anatomies, we employ a local articulated model to effectively model the spatial relations across vertebrae and discs. The local articulated model fuses appearance cues from different detectors in a way that is robust to abnormal spine geometry resulting from severe diseases. Our method is validated by 300 MR spine scout scans and exhibits robust performance, especially to cases with severe diseases and imaging artifacts.

LMI–based robust controller design approach in aircraft multidisciplinary design optimization problem

Directory of Open Access Journals (Sweden)

Qinghua Zeng

2015-07-01

Full Text Available This article proposes a linear matrix inequality–based robust controller design approach to implement the synchronous design of aircraft control discipline and other disciplines, in which the variation in design parameters is treated as equivalent perturbations. Considering the complicated mapping relationships between the coefficient arrays of aircraft motion model and the aircraft design parameters, the robust controller designed is directly based on the variation in these coefficient arrays so conservative that the multidisciplinary design optimization problem would be too difficult to solve, or even if there is a solution, the robustness of design result is generally poor. Therefore, this article derives the uncertainty model of disciplinary design parameters based on response surface approximation, converts the design problem of the robust controller into a problem of solving a standard linear matrix inequality, and theoretically gives a less conservative design method of the robust controller which is based on the variation in design parameters. Furthermore, the concurrent subspace approach is applied to the multidisciplinary system with this kind of robust controller in the design loop. A multidisciplinary design optimization of a tailless aircraft as example is shown that control discipline can be synchronous optimal design with other discipline, especially this method will greatly reduce the calculated amount of multidisciplinary design optimization and make multidisciplinary design optimization results more robustness of flight performance.

Psychologic stress related to injury and impact on sport performance.

Science.gov (United States)

Nippert, Angela H; Smith, Aynsley M

2008-05-01

Injury rates are high among children and adolescent athletes. Psychosocial stressors, such as personality, history of stressors, and life event stress can influence injury occurrence. After injury, those same factors plus athletic identity, self-esteem, and significant others-such as parents, coaches, and teammates-can affect injury response, recovery and subsequent sport performance. Goal setting, positive self-talk, attribution theory, and relaxation or mental imagery are psychologic interventions that can help injured athletes cope with psychosocial stressors. Medical professionals should be aware of the potential influence that psychosocial stressors and psychologic interventions can have on injury occurrence, injury recovery, and sport performance.

Employee assistance programs, drug testing, and workplace injury.

Science.gov (United States)

Waehrer, Geetha M; Miller, Ted R; Hendrie, Delia; Galvin, Deborah M

2016-06-01

Little is known about the effects of employee assistance programs (EAPs) on occupational injuries. Multivariate regressions probed a unique data set that linked establishment information about workplace anti-drug programs in 1988 with occupational injury rates for 1405 establishments. EAPs were associated with a significant reduction in both no-lost-work and lost-work injuries, especially in the manufacturing and transportation, communication and public utilities industries (TCPU). Lost-work injuries were more responsive to specific EAP characteristics, with lower rates associated with EAPs staffed by company employees (most likely onsite). Telephone hotline services were associated with reduced rates of lost-work injuries in manufacturing and TCPU. Drug testing was associated with reductions in the rate of minor injuries with no lost work, but had no significant relationship with lost-work injuries. This associational study suggests that EAPs, especially ones that are company-staffed and ones that include telephone hotlines, may prevent workplace injuries. Copyright © 2016. Published by Elsevier Ltd.

Health status, job stress and work-related injury among Los Angeles taxi drivers.

Science.gov (United States)

Wang, Pin-Chieh; Delp, Linda

2014-01-01

Taxi drivers work long hours for low wages and report hypertension, weight gain, and musculoskeletal pain associated with the sedentary nature of their job, stressful working conditions, and poor dietary habits. They also experience a high work-related fatality rate. The objective of this study is to examine the association of taxi drivers' health status and level of job stress with work-related injury and determine if a potential interaction exists. A survey of 309 Los Angeles taxi drivers provides basic data on health status, job stress, and work-related injuries. We further analyzed the data using a Modified Poisson regression approach with a robust error variance to estimate the relative risk (RR) and the 95% confidence intervals (CI) of work-related injuries. Focus group results supplemented and helped interpret the quantitative data. The joint effect of good health and low job stress was associated with a large reduction in the incidence of injuries, consistent with the hypothesis that health status and stress levels modify each other on the risk of work-related injury. These results suggest that the combination of stress reduction and health management programs together with changes in the stressful conditions of the job may provide targeted avenues to prevent injuries.

Spinal Cord Injury Rehabilitation in Nepal

Directory of Open Access Journals (Sweden)

Nabina Shah

2013-06-01

Full Text Available Spinal cord injury is a major trauma, with its short and long term effects and consequences to the patient, his friends and family. Spinal cord injury is addressed in the developed countries with standard trauma care system commencing immediately after injury and continuing to the specialized rehabilitation units. Rehabilitation is important to those with spinal injury for both functional and psychosocial reintegration. It has been an emerging concept in Nepal, which has been evident with the establishment of the various hospitals with rehabilitation units, rehabilitation centres and physical therapy units in different institutions. However, the spinal cord injury rehabilitation setting and scenario is different in Nepal from those in the developed countries since spinal cord injury rehabilitation care has not been adequately incorporated into the health care delivery system nor its importance has been realized within the medical community of Nepal. To name few, lack of human resource for the rehabilitation care, awareness among the medical personnel and general population, adequate scientific research evidence regarding situation of spinal injury and exorbitant health care policy are the important hurdles that has led to the current situation. Hence, it is our responsibility to address these apparent barriers to successful implementation and functioning of rehabilitation so that those with spinal injury would benefit from enhanced quality of life. Keywords: rehabilitation; spinal injury.

Designing a robust high-speed CMOS-MEMS capacitive humidity sensor

International Nuclear Information System (INIS)

Lazarus, N; Fedder, G K

2012-01-01

In our previous work (Lazarus and Fedder 2011 J. Micromech. Microeng. 21 0650281), we demonstrated a CMOS-MEMS capacitive humidity sensor with a 72% improvement in sensitivity over the highest previously integrated on a CMOS die. This paper explores a series of methods for creating a faster and more manufacturable high-sensitivity capacitive humidity sensor. These techniques include adding oxide pillars to hold the plates apart, spin coating polymer to allow sensors to be fabricated more cheaply, adding a polysilicon heater and etching away excess polymer in the release holes. In most cases a tradeoff was found between sensitivity and other factors such as response time or robustness. A robust high-speed sensor was designed with a sensitivity of 0.21% change in capacitance per per cent relative humidity, while dropping the response time constant from 70 to 4s. Although less sensitive than our design, the sensor remains 17% more sensitive than the most sensitive interdigitated designs successfully integrated with CMOS. (paper)

International Conference on Robust Statistics

CERN Document Server

Filzmoser, Peter; Gather, Ursula; Rousseeuw, Peter

2003-01-01

Aspects of Robust Statistics are important in many areas. Based on the International Conference on Robust Statistics 2001 (ICORS 2001) in Vorau, Austria, this volume discusses future directions of the discipline, bringing together leading scientists, experienced researchers and practitioners, as well as younger researchers. The papers cover a multitude of different aspects of Robust Statistics. For instance, the fundamental problem of data summary (weights of evidence) is considered and its robustness properties are studied. Further theoretical subjects include e.g.: robust methods for skewness, time series, longitudinal data, multivariate methods, and tests. Some papers deal with computational aspects and algorithms. Finally, the aspects of application and programming tools complete the volume.

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

Directory of Open Access Journals (Sweden)

Veronica eSebastian

2013-05-01

Full Text Available Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within in a single task. Thus we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM with a sequence of 4 baited and 4 unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test two weeks after training. Multiple training trials not only provide robust training, but also test the subjects’ ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing two weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze.

Science.gov (United States)

Sebastian, Veronica; Diallo, Aissatou; Ling, Douglas S F; Serrano, Peter A

2013-01-01

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

Traumatic Stress, Depression, and Recovery: Child and Parent Responses After Emergency Medical Care for Unintentional Injury.

Science.gov (United States)

Kassam-Adams, Nancy; Bakker, Anne; Marsac, Meghan L; Fein, Joel A; Winston, Flaura Koplin

2015-11-01

To assess psychological symptoms in injured children (aged 8-17 years) and their parents after emergency department (ED) care to examine the relationship between posttraumatic stress and depression symptoms, co-occurrence of symptoms within families, and the relationship of these symptoms to parent-reported overall recovery. Children and parents (n = 263 child-parent dyads) were enrolled during ED treatment for unintentional injury. Approximately 5 months later, children and parents (n = 178 dyads) completed standardized measures of posttraumatic stress and depression symptoms and parents reported on child overall recovery. Follow-up assessments found significant posttraumatic stress symptoms in 15% of children and 5% of parents, significant depression symptoms in 13% of children and 16% of parents, and problematic overall recovery in 17% of children. For both children and parents, posttraumatic stress and depression symptom severity were strongly associated. Child and parent symptoms were only modestly associated with each other, and there were few families in which both child and parent had significant posttraumatic stress or depression. Parent symptoms, but not child symptoms, were inversely associated with children's overall recovery. For about 1 in 6 children and parents, unintentional injury treated in the ED can be associated with negative psychological sequelae and suboptimal recovery. Within families, child and parent responses may differ; their relative association with overall recovery deserves additional research. To promote emotional recovery, ED clinicians should be aware of the potential psychological impact of unintentional injury, provide timely evidence-based anticipatory guidance, and communicate these concerns to primary care clinicians.

Robust Scientists

DEFF Research Database (Denmark)

Gorm Hansen, Birgitte

their core i nterests, 2) developing a selfsupply of industry interests by becoming entrepreneurs and thus creating their own compliant industry partner and 3) balancing resources within a larger collective of researchers, thus countering changes in the influx of funding caused by shifts in political...... knowledge", Danish research policy seems to have helped develop politically and economically "robust scientists". Scientific robustness is acquired by way of three strategies: 1) tasting and discriminating between resources so as to avoid funding that erodes academic profiles and push scientists away from...

Robust high temperature oxygen sensor electrodes

DEFF Research Database (Denmark)

Lund, Anders

Platinum is the most widely used material in high temperature oxygen sensor electrodes. However, platinum is expensive and the platinum electrode may, under certain conditions, suffer from poisoning, which is detrimental for an oxygen sensor. The objective of this thesis is to evaluate electrode...... materials as candidates for robust oxygen sensor electrodes. The present work focuses on characterising the electrochemical properties of a few electrode materials to understand which oxygen electrode processes are limiting for the response time of the sensor electrode. Three types of porous platinum......-Dansensor. The electrochemical properties of the electrodes were characterised by electrochemical impedance spectroscopy (EIS), and the structures were characterised by x-ray diffraction and electron microscopy. At an oxygen partial pressures of 0.2 bar, the response time of the sensor electrode was determined by oxygen...

Survey on the Contemporary Management of Intraoperative Urethral Injuries During Penile Prosthesis Implantation.

Science.gov (United States)

Sexton, Stephanie J; Granieri, Michael A; Lentz, Aaron C

2018-04-01

Intraoperative urethral injury is an uncommon event during the placement of a penile prosthesis, and alternative management strategies have been proposed with continuation of implantation after urethral injury. To evaluate surgeon practices in the management of intraoperative urethral injury. An online survey was sent to the society listservs of the Genitourinary Reconstructive Surgeons (GURS) and the Sexual Medicine Society of North America (SMSNA). Physicians were queried on their fellowship training, experience with penile prosthesis implantation, and management of urethral injuries during prosthesis placement. The response data were analyzed using SAS 9.4 (SAS Institute, Cary, NC, USA). The χ 2 test and Fisher exact test were used to determine associations between variables. Survey responses. 131 survey responses were analyzed. Of the responders, 41.2% were GURS fellowship trained, 19.1% were SMSNA trained, 30.5% were non-fellowship trained, and 9.2% were trained in other fellowships. 25.4% of participants performed more than 50 implantations per year, 37.7% performed 20 to 50 per year, and 36.9% performed fewer than 20 per year. Urethral injury during prosthesis implantation was uncommon, with 26.2% reporting 0 injury, 58.5% reporting 1 to 3 injuries, and 15.4% reporting more than 3 career injuries. Injuries were most commonly encountered during corporal dilation (71.1%) compared with corporal exposure (12.5%) or penile straightening maneuvers (7.0%). There was no statistically significant difference with aborting or continuing implantation among GURS-trained, SMSNA-trained, other fellowship-trained, and non-fellowship-trained surgeons. Of all responders, 55% would abort the procedure after distal urethral injury, whereas 45% would continue the procedure with unilateral or bilateral insertion of cylinders. Patient factors that increased likelihood of terminating the procedure in the case of urethral injury included immunosuppression, spinal cord injury, and

Robust Trust in Expert Testimony

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Christian Dahlman

2015-05-01

Full Text Available The standard of proof in criminal trials should require that the evidence presented by the prosecution is robust. This requirement of robustness says that it must be unlikely that additional information would change the probability that the defendant is guilty. Robustness is difficult for a judge to estimate, as it requires the judge to assess the possible effect of information that the he or she does not have. This article is concerned with expert witnesses and proposes a method for reviewing the robustness of expert testimony. According to the proposed method, the robustness of expert testimony is estimated with regard to competence, motivation, external strength, internal strength and relevance. The danger of trusting non-robust expert testimony is illustrated with an analysis of the Thomas Quick Case, a Swedish legal scandal where a patient at a mental institution was wrongfully convicted for eight murders.

The rodeo athlete: injuries - Part II.

Science.gov (United States)

Meyers, Michael C; Laurent, C Matthew

2010-10-01

A previous instalment to this review focused on the sport science for rodeo, the history behind the sport and what is currently known about the physical and physiological status, coronary risk profile, strength and power levels, event-specific kinesiological and biomechanical aspects, nutritional habits and psychological indices associated with the rodeo athlete. In regards to injury, rodeo is well known for its high-velocity, high-impact atmosphere where athletes compete against the clock and uncooperative livestock. Considered by many to be a dangerous sport with high vulnerability towards trauma and frequent injuries, animal/human contact events comprise ∼80% of reported injuries. Severe trauma includes fractures, dislocations, subluxations, concussions, ligament ruptures, pneumothorax and various neurapraxias. Head and neck trauma account for 10-29% of total trauma and up to 63% of upper body injuries, with concussion incidence rates of 3.4 per 1000 competitive exposures. The incidence of thoracic, back and abdominal injuries comprise 11-84% of trauma, while shoulder injuries, involving anterior/posterior arthralgia, inflammation, instability and increasing weakness, account for 8-15% of upper extremity cases. Lower extremity trauma accounts for 26-34% of cases, with the majority involving the knee. Many believe that the incidence of trauma is underestimated, with studies hampered by numerous limitations such as a lack of injury awareness, missing data, poor injury recall, an array of reporting sources, delays in subject response and treatment, no uniform definition of injury or reporting system and predisposing factors prior to injury. Primary mechanisms of injuries are attributed to physical immaturity, fatigue, age and experience, behaviour, the violent nature of the sport and lack of adequate medical intervention. Although there is limited adherence to organized conditioning programmes, when properly planned, sport-specific conditioning may enhance

Robustness Analysis of Timber Truss Structure

DEFF Research Database (Denmark)

Rajčić, Vlatka; Čizmar, Dean; Kirkegaard, Poul Henning

2010-01-01

The present paper discusses robustness of structures in general and the robustness requirements given in the codes. Robustness of timber structures is also an issues as this is closely related to Working group 3 (Robustness of systems) of the COST E55 project. Finally, an example of a robustness...... evaluation of a widespan timber truss structure is presented. This structure was built few years ago near Zagreb and has a span of 45m. Reliability analysis of the main members and the system is conducted and based on this a robustness analysis is preformed....

Neuronal response of the hippocampal formation to injury: blood flow, glucose metabolism, and protein synthesis

International Nuclear Information System (INIS)

Kameyama, M.; Wasterlain, C.G.; Ackermann, R.F.; Finch, D.; Lear, J.; Kuhl, D.E.

1983-01-01

The reaction of the hippocampal formation to entorhinal lesions was studied from the viewpoints of cerebral blood flow ([ 123 I]isopropyl-iodoamphetamine[IMP])-glucose utilization ([ 14 C]2-deoxyglucose), and protein synthesis ([ 14 C]leucine), using single- and double-label autoradiography. Researchers' studies showed decreased glucose utilization in the inner part, and increased glucose utilization in the outer part of the molecular layer of the dentate gyrus, starting 3 days after the lesion; increased uptake of [ 123 I]IMP around the lesion from 1 to 3 days postlesion; and starting 3 days after the lesion, marked decrease in [ 14 C]leucine incorporation into proteins and cell loss in the dorsal CA1 and dorsal subiculum in about one-half of the rats. These changes were present only in animals with lesions which invaded the ventral hippocampal formation in which axons of CA1 cells travel. By contrast, transsection of the 3rd and 4th cranial nerves resulted, 3 to 9 days after injury, in a striking increase in protein synthesis in the oculomotor and trochlear nuclei. These results raise the possibility that in some neurons the failure of central regeneration may result from the cell's inability to increase its rate of protein synthesis in response to axonal injury

Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission

Science.gov (United States)

2016-12-01

the extent of injury to determine if variable severity of injury might account for these conflicting responses. Our work on this project has...of phrenic motor output post-CSC; we are currently determining if variability in injury severity can account for these conflicting findings. These...Award Number: W81XWH-13-1-0410 TITLE: Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission

Breviscapine ameliorates CCl4‑induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation.

Science.gov (United States)

Liu, Yu; Wen, Pei-Hao; Zhang, Xin-Xue; Dai, Yang; He, Qiang

2018-05-02

Acute liver injury is characterized by fibrosis, inflammation and apoptosis, leading to liver failure, cirrhosis or cancer and affecting the clinical outcome in the long term. However, no effective therapeutic strategy is currently available. Breviscapine, a mixture of flavonoid glycosides, has been reported to have multiple biological functions. The present study aimed to investigate the effects of breviscapine on acute liver injury induced by CCl4 in mice. C57BL/6 mice were subjected to intraperitoneal injection with CCl4 for 8 weeks with or without breviscapine (15 or 30 mg/kg). Mice treated with CCl4 developed acute liver injury, as evidenced by histological analysis, Masson trichrome and Sirius Red staining, accompanied with elevated levels of alanine aminotransferase and aspartate aminotransferase. Furthermore, increases in pro‑inflammatory cytokines, chemokines and apoptotic factors, including caspase‑3 and poly(ADP ribose) polymerase‑2 (PARP‑2), were observed. Breviscapine treatment significantly and dose‑dependently reduced collagen deposition and the fibrotic area. Inflammatory cytokines were downregulated by breviscapine through inactivating Toll‑like receptor 4/nuclear factor-κB signaling pathways. In addition, co‑administration of breviscapine with CCl4 decreased the apoptotic response by enhancing B‑cell lymphoma-2 (Bcl‑2) levels, while reducing Bcl‑2‑associated X protein, apoptotic protease activating factor 1, caspase‑3 and PARP activity. Furthermore, CCl4‑induced oxidative stress was blocked by breviscapine through improving anti‑oxidants and impeding mitogen‑activated protein kinase pathways. The present study highlighted that breviscapine exhibited liver‑protective effects against acute hepatic injury induced by CCl4 via suppressing inflammation and apoptosis.

Human Precision-Cut Liver Slices as an ex Vivo Model to Study Idiosyncratic Drug-Induced Liver Injury

NARCIS (Netherlands)

Hadi, Mackenzie; Westra, Inge M.; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, M.T.; Groothuis, Geny M. M.

Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Because of the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict

Qualitative Robustness in Estimation

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Mohammed Nasser

2012-07-01

Full Text Available Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Times New Roman","serif";} Qualitative robustness, influence function, and breakdown point are three main concepts to judge an estimator from the viewpoint of robust estimation. It is important as well as interesting to study relation among them. This article attempts to present the concept of qualitative robustness as forwarded by first proponents and its later development. It illustrates intricacies of qualitative robustness and its relation with consistency, and also tries to remove commonly believed misunderstandings about relation between influence function and qualitative robustness citing some examples from literature and providing a new counter-example. At the end it places a useful finite and a simulated version of   qualitative robustness index (QRI. In order to assess the performance of the proposed measures, we have compared fifteen estimators of correlation coefficient using simulated as well as real data sets.

Use of Robust z in Detecting Unstable Items in Item Response Theory Models

Science.gov (United States)

Huynh, Huynh; Meyer, Patrick

2010-01-01

The first part of this paper describes the use of the robust z[subscript R] statistic to link test forms using the Rasch (or one-parameter logistic) model. The procedure is then extended to the two-parameter and three-parameter logistic and two-parameter partial credit (2PPC) models. A real set of data was used to illustrate the extension. The…

Robust Temperature Control of a Thermoelectric Cooler via μ -Synthesis

Science.gov (United States)

Kürkçü, Burak; Kasnakoğlu, Coşku

2018-02-01

In this work robust temperature control of a thermoelectric cooler (TEC) via μ -synthesis is studied. An uncertain dynamical model for the TEC that is suitable for robust control methods is derived. The model captures variations in operating point due to current, load and temperature changes. A temperature controller is designed utilizing μ -synthesis, a powerful method guaranteeing robust stability and performance. For comparison two well-known control methods, namely proportional-integral-derivative (PID) and internal model control (IMC), are also realized to benchmark the proposed approach. It is observed that the stability and performance on the nominal model are satisfactory for all cases. On the other hand, under perturbations the responses of PID and IMC deteriorate and even become unstable. In contrast, the μ -synthesis controller succeeds in keeping system stability and achieving good performance under all perturbations within the operating range, while at the same time providing good disturbance rejection.

Robustness in econometrics

CERN Document Server

Sriboonchitta, Songsak; Huynh, Van-Nam

2017-01-01

This book presents recent research on robustness in econometrics. Robust data processing techniques – i.e., techniques that yield results minimally affected by outliers – and their applications to real-life economic and financial situations are the main focus of this book. The book also discusses applications of more traditional statistical techniques to econometric problems. Econometrics is a branch of economics that uses mathematical (especially statistical) methods to analyze economic systems, to forecast economic and financial dynamics, and to develop strategies for achieving desirable economic performance. In day-by-day data, we often encounter outliers that do not reflect the long-term economic trends, e.g., unexpected and abrupt fluctuations. As such, it is important to develop robust data processing techniques that can accommodate these fluctuations.

Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

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Gang Chen

2008-01-01

Full Text Available Although N-acetylcysteine (NAC has been shown to be neuroprotective for traumatic brain injury (TBI, the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB and inflammatory proteins such as interleukin-1β (IL-1β, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and intercellular adhesion molecule-1 (ICAM-1 after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

Burn injury reduces neutrophil directional migration speed in microfluidic devices.

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Kathryn L Butler

2010-07-01

Full Text Available Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72-120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.

Robust Programming by Example

OpenAIRE

Bishop , Matt; Elliott , Chip

2011-01-01

Part 2: WISE 7; International audience; Robust programming lies at the heart of the type of coding called “secure programming”. Yet it is rarely taught in academia. More commonly, the focus is on how to avoid creating well-known vulnerabilities. While important, that misses the point: a well-structured, robust program should anticipate where problems might arise and compensate for them. This paper discusses one view of robust programming and gives an example of how it may be taught.

Evaluation of safety climate and employee injury rates in healthcare.

Science.gov (United States)

Cook, Jacqueline M; Slade, Martin D; Cantley, Linda F; Sakr, Carine J

2016-09-01

Safety climates that support safety-related behaviour are associated with fewer work-related injuries, and prior research in industry suggests that safety knowledge and motivation are strongly related to safety performance behaviours; this relationship is not well studied in healthcare settings. We performed analyses of survey results from a Veterans Health Administration (VHA) Safety Barometer employee perception survey, conducted among VHA employees in 2012. The employee perception survey assessed 6 safety programme categories, including management participation, supervisor participation, employee participation, safety support activities, safety support climate and organisational climate. We examined the relationship between safety climate from the survey results on VHA employee injury and illness rates. Among VHA facilities in the VA New England Healthcare System, work-related injury rate was significantly and inversely related to overall employee perception of safety climate, and all 6 safety programme categories, including employee perception of employee participation, management participation, organisational climate, supervisor participation, safety support activities and safety support climate. Positive employee perceptions of safety climate in VHA facilities are associated with lower work-related injury and illness rates. Employee perception of employee participation, management participation, organisational climate, supervisor participation, safety support activities and safety support climate were all associated with lower work-related injury rates. Future implications include fostering a robust safety climate for patients and healthcare workers to reduce healthcare worker injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Robust Reliability or reliable robustness? - Integrated consideration of robustness and reliability aspects

DEFF Research Database (Denmark)

Kemmler, S.; Eifler, Tobias; Bertsche, B.

2015-01-01

products are and vice versa. For a comprehensive understanding and to use existing synergies between both domains, this paper discusses the basic principles of Reliability- and Robust Design theory. The development of a comprehensive model will enable an integrated consideration of both domains...

Chest Injuries Associated with Head Injury

African Journals Online (AJOL)

Traumatic brain injury (TBI) is a common cause of mortality and severe morbidity. Although there have been significant advances in management, associated severe injuries, in particular chest injuries, remain a major challenge. Extracranial injuries, especially chest injuries increase mortality in patients with TBI in both short.

Role of Extracellular RNA and TLR3‐Trif Signaling in Myocardial Ischemia–Reperfusion Injury

Science.gov (United States)

Chen, Chan; Feng, Yan; Zou, Lin; Wang, Larry; Chen, Howard H.; Cai, Jia‐Yan; Xu, Jun‐Mei; Sosnovik, David E.; Chao, Wei

2014-01-01

Background Toll‐like receptor 3 (TLR3) was originally identified as the receptor for viral RNA and represents a major host antiviral defense mechanism. TLR3 may also recognize extracellular RNA (exRNA) released from injured tissues under certain stress conditions. However, a role for exRNA and TLR3 in the pathogenesis of myocardial ischemic injury has not been tested. This study examined the role of exRNA and TLR3 signaling in myocardial infarction (MI), apoptosis, inflammation, and cardiac dysfunction during ischemia‐reperfusion (I/R) injury. Methods and Results Wild‐type (WT), TLR3−/−, Trif−/−, and interferon (IFN) α/β receptor‐1 deficient (IFNAR1−/−) mice were subjected to 45 minutes of coronary artery occlusion and 24 hours of reperfusion. Compared with WT, TLR3−/− or Trif−/− mice had smaller MI and better preserved cardiac function. Surprisingly, unlike TLR(2/4)‐MyD88 signaling, lack of TLR3‐Trif signaling had no impact on myocardial cytokines or neutrophil recruitment after I/R, but myocardial apoptosis was significantly attenuated in Trif−/− mice. Deletion of the downstream IFNAR1 had no effect on infarct size. Importantly, hypoxia and I/R led to release of RNA including microRNA from injured cardiomyocytes and ischemic heart, respectively. Necrotic cardiomyocytes induced a robust and dose‐dependent cytokine response in cultured cardiomyocytes, which was markedly reduced by RNase but not DNase, and partially blocked in TLR3‐deficient cardiomyocytes. In vivo, RNase administration reduced serum RNA level, attenuated myocardial cytokine production, leukocytes infiltration and apoptosis, and conferred cardiac protection against I/R injury. Conclusion TLR3‐Trif signaling represents an injurious pathway during I/R. Extracellular RNA released during I/R may contribute to myocardial inflammation and infarction. PMID:24390148

Rogue-Elephant-Inflicted Panfacial Injuries: A Rare Case Report

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Santosh Kumar Yadav

2012-01-01

Full Text Available Attacks by elephants, the largest of the “large animals,” produce many fatalities a year. Most attacks are provoked, although rogue elephants are occasionally responsible. Trampling, goring, tossing the individual with the trunk, or crushing with the knees produces the injuries. Injuries from encounters with large animals represent a significant health risk for rural communities. Wild-animal-inflicted maxillofacial injuries are rare, and limited literature is available describing their management. We present a case of severe maxillofacial injuries caused by the attack of a rogue elephant.

Naural Responses to Injury: Prevention, Protection, and Repair. Volume 8. Vision, Laser Eye Injury, and Infectious Diseases

National Research Council Canada - National Science Library

Bazan, Nicolas

1997-01-01

Four specific aims were proposed in the original grant application. Develop a new confocal microscope that can be used in living eyes to understand the earliest stages of trauma, laser injuries, and disease...

Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model: mechanisms underlying orofacial allodynias and headache

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Golam Mustafa

2017-01-01

Full Text Available Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, especially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain. Our results exhibited significant alterations in the excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity. Moreover, we also detected a robust alteration in the expression of serotonin, and inhibitory molecule norepinephrine in the nucleus tractus solitaries, which might indicate the possibility of an alteration in visceral pain, and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury. Collectively, widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.

Downhill ski injuries in children and adolescents.

Science.gov (United States)

Meyers, Michael C; Laurent, C Matthew; Higgins, Robert W; Skelly, William A

2007-01-01

Downhill skiing is considered to be an enjoyable activity for children and adolescents, but it is not without its risks and injuries. Injury rates now range between 3.9 and 9.1 injuries per 1000 skier days, and there has been a well documented increase in the number of trauma cases and fatalities associated with this sport. Head and neck injuries are considered the primary cause of fatal injuries and constitute 11-20% of total injuries among children and adolescents. Cranial trauma is responsible for up to 54% of total hospital injuries and 67% of all fatalities, whereas thoracoabdominal and spine injuries comprise 4-10% of fatalities. Furthermore, there has been an increase in the proportion of upper extremity trauma with acromioclavicular dislocations, and clavicle and humeral fractures accounting for the majority (22-79%) of the injuries. However, the most common and potentially serious injuries in children and adolescents are those to the lower extremity, with knee sprains and anterior cruciate ligament tears accounting for up to 47.7% of total injuries. Knee sprains and grade III ligament trauma associated with lower leg fractures account for 39-77% of ski injuries in this young population. Approximately 15% of downhill skiing injuries among children and adolescents are caused by musculoskeletal immaturity. Other factors include excessive fatigue, age, level of experience, and inappropriate or improperly adjusted equipment. Collisions and falls constitute a significant portion (up to 76%) of trauma, and are commonly associated with excessive speed, adverse slope conditions, overconfidence leading to carelessness, and behavioural patterns within and among gender. The type and severity of injuries are typically functions of biomechanical efficiency, skiing velocity or slope conditions; however, a multiplicative array of intrinsic and extrinsic factors may simultaneously be involved. Despite extensive efforts to provide a comprehensive picture of the aetiology of

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury

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Westerdahl Ann-Charlotte

2010-06-01

Full Text Available Abstract Background Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Results Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. Conclusions This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper

Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.

Science.gov (United States)

Ryge, Jesper; Winther, Ole; Wienecke, Jacob; Sandelin, Albin; Westerdahl, Ann-Charlotte; Hultborn, Hans; Kiehn, Ole

2010-06-09

Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be

The perceived benefits of the Maties Injury Programme among ...

African Journals Online (AJOL)

Conclusions: The theoretical benefits of providing a specialised sports injury assessment as part of the Campus Health Services for athletes at Stellenbosch University have been supported by the encouraging responses of patients. Incorporating sports injury programmes into campus health services at more universities ...

Mitigating the risk of musculoskeletal injury: A systematic review of the most effective injury prevention strategies for military personnel.

Science.gov (United States)

Wardle, Sophie L; Greeves, Julie P

2017-11-01

To update the current injury prevention strategy evidence base for making recommendations to prevent physical training-related musculoskeletal injury. We conducted a systematic review to update the evidence base on injury prevention strategies for military personnel. Literature was systematically searched and extracted from five databases, and reported according to PRISMA guidelines. Sixty one articles meeting the inclusion criteria and published during the period 2008-2015 were selected for systematic review. The retrieved articles were broadly categorised into six injury prevention strategies; (1) conditioning, (2) footwear modifications, (3) bracing, (4) physical activity volume, (5) physical fitness, and (6) leadership/supervision/awareness. The majority of retrieved articles (n=37 (of 61) evaluated or systematically reviewed a conditioning intervention of some nature. However, the most well-supported strategies were related to reducing physical activity volume and improving leadership/supervision/awareness of injuries and injury prevention efforts. Several injury prevention strategies effectively reduce musculoskeletal injury rates in both sexes, and many show promise for utility with military personnel. However, further evaluation, ideally with prospective randomised trials, is required to establish the most effective injury prevention strategies, and to understand any sex-specific differences in the response to these strategies. Copyright © 2017. Published by Elsevier Ltd.

Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS

DEFF Research Database (Denmark)

Babcock, Alicia A; Kuziel, William A; Rivest, Serge

2003-01-01

Innate responses in the CNS are critical to first line defense against infection and injury. Leukocytes migrate to inflammatory sites in response to chemokines. We studied leukocyte migration and glial chemokine expression within the denervated hippocampus in response to axonal injury caused by e...

Clinical Response of 277 Patients with Spinal Cord Injury to Stem Cell Therapy in Iraq

Science.gov (United States)

Hammadi, Abdulmajeed Alwan; Marino, Andolina; Farhan, Saad

2012-01-01

Background and Objectives: Spinal cord injury is a common neurological problem secondary to car accidents, war injuries and other causes, it may lead to varying degrees of neurological disablement, and apart from physiotherapy there is no available treatment to regain neurological function loss. Our aim is to find a new method using autologous hematopoietic stem cells to gain some of the neurologic functions lost after spinal cord injury. Methods and Results: 277 patients suffering from spinal cord injury were submitted to an intrathecally treatment with peripheral stem cells. The cells were harvested from the peripheral blood after a treatment with G-CSF and then concentrated to 4∼ 6 ml. 43% of the patients improved; ASIA score shifted from A to B in 88 and from A to C in 32. The best results were achieved in patients treated within one year from the injury. Conclusions: Since mesenchymal cells increase in the peripheral blood after G-CSF stimulation, a peripheral blood harvest seems easier and cheaper than mesenchymal cell cultivation prior to injection. It seems reasonable treatment for spinal cord injury. PMID:24298358

Human precision-cut liver slices as an ex vivo model to study idiosyncratic drug-induced liver injury

NARCIS (Netherlands)

Hadi, Mackenzie; Westra, Inge; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, Maja; Groothuis, Genoveva

2013-01-01

Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Due to the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict and to

Brain injuries from blast.

Science.gov (United States)

Bass, Cameron R; Panzer, Matthew B; Rafaels, Karen A; Wood, Garrett; Shridharani, Jay; Capehart, Bruce

2012-01-01

Traumatic brain injury (TBI) from blast produces a number of conundrums. This review focuses on five fundamental questions including: (1) What are the physical correlates for blast TBI in humans? (2) Why is there limited evidence of traditional pulmonary injury from blast in current military field epidemiology? (3) What are the primary blast brain injury mechanisms in humans? (4) If TBI can present with clinical symptoms similar to those of Post-Traumatic Stress Disorder (PTSD), how do we clinically differentiate blast TBI from PTSD and other psychiatric conditions? (5) How do we scale experimental animal models to human response? The preponderance of the evidence from a combination of clinical practice and experimental models suggests that blast TBI from direct blast exposure occurs on the modern battlefield. Progress has been made in establishing injury risk functions in terms of blast overpressure time histories, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold. Enhanced thoracic protection from ballistic protective body armor likely plays a role in the occurrence of blast TBI by preventing lung injuries at blast intensities that could cause TBI. Principal areas of uncertainty include the need for a more comprehensive injury assessment for mild blast injuries in humans, an improved understanding of blast TBI pathophysiology of blast TBI in animal models and humans, the relationship between clinical manifestations of PTSD and mild TBI from blunt or blast trauma including possible synergistic effects, and scaling between animals models and human exposure to blasts in wartime and terrorist attacks. Experimental methodologies, including location of the animal model relative to the shock or blast source, should be carefully designed to provide a realistic blast experiment with conditions comparable to blasts on humans. If traditional blast scaling is

Food supply chain network robustness : a literature review and research agenda

NARCIS (Netherlands)

Vlajic, J.V.; Hendrix, E.M.T.; Vorst, van der J.G.A.J.

2008-01-01

Today’s business environment is characterized by challenges of strong global competition where companies tend to achieve leanness and maximum responsiveness. However, lean supply chain networks (SCNs) become more vulnerable to all kind of disruptions. Food SCNs have to become robust, i.e. they

A robust response to combination immune checkpoint inhibitor therapy in HPV-related small cell cancer: a case report.

Science.gov (United States)

Ho, Won Jin; Rooper, Lisa; Sagorsky, Sarah; Kang, Hyunseok

2018-05-09

Human papillomavirus-related small cell carcinoma of the head and neck is an extremely rare, aggressive subtype with poor outcomes. Therapeutic options are limited and are largely adopted from small cell lung cancer treatment paradigms. This report describes a 69-year old male who was diagnosed of HPV-related oropharyngeal cancer with mixed small cell and squamous cell pathology which was clinically aggressive and progressed through multimodal platinum-based therapies. Upon manifestation of worsening metastatic disease, the patient was initiated on a combination of ipilimumab and nivolumab. Within 2 months of starting immunotherapy, a robust partial response was observed. During the treatment course, the patient developed immune-related adverse effects including new diabetes mellitus, colitis, and hypothyroidism. The disease-specific survival was 26 months. Combination immunotherapy may be an attractive option for HPV-related small cell head and neck cancers resistant to other treatment modalities and thus warrants further evaluation.

Robust

DEFF Research Database (Denmark)

2017-01-01

‘Robust – Reflections on Resilient Architecture’, is a scientific publication following the conference of the same name in November of 2017. Researches and PhD-Fellows, associated with the Masters programme: Cultural Heritage, Transformation and Restoration (Transformation), at The Royal Danish...

Review: Deciphering animal robustness. A synthesis to facilitate its use in livestock breeding and management.

Science.gov (United States)

Friggens, N C; Blanc, F; Berry, D P; Puillet, L

2017-12-01

As the environments in which livestock are reared become more variable, animal robustness becomes an increasingly valuable attribute. Consequently, there is increasing focus on managing and breeding for it. However, robustness is a difficult phenotype to properly characterise because it is a complex trait composed of multiple components, including dynamic elements such as the rates of response to, and recovery from, environmental perturbations. In this review, the following definition of robustness is used: the ability, in the face of environmental constraints, to carry on doing the various things that the animal needs to do to favour its future ability to reproduce. The different elements of this definition are discussed to provide a clearer understanding of the components of robustness. The implications for quantifying robustness are that there is no single measure of robustness but rather that it is the combination of multiple and interacting component mechanisms whose relative value is context dependent. This context encompasses both the prevailing environment and the prevailing selection pressure. One key issue for measuring robustness is to be clear on the use to which the robustness measurements will employed. If the purpose is to identify biomarkers that may be useful for molecular phenotyping or genotyping, the measurements should focus on the physiological mechanisms underlying robustness. However, if the purpose of measuring robustness is to quantify the extent to which animals can adapt to limiting conditions then the measurements should focus on the life functions, the trade-offs between them and the animal's capacity to increase resource acquisition. The time-related aspect of robustness also has important implications. Single time-point measurements are of limited value because they do not permit measurement of responses to (and recovery from) environmental perturbations. The exception being single measurements of the accumulated consequence of a

Level of agreement between patient and proxy responses to the EQ-5D health questionnaire 12 months after injury.

Science.gov (United States)

Gabbe, Belinda J; Lyons, Ronan A; Sutherland, Ann M; Hart, Melissa J; Cameron, Peter A

2012-04-01

Health-related quality of life represents a patient's experiences and expectations and should be collected from the patient. In trauma, collection of information from the patient can be challenging, particularly for subgroups where cognitive impairment is prevalent, increasing reliance on proxy reporting. This study assessed the agreement between patient and proxy reporting of health-related quality of life 12 months after injury. The Victorian State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry collect EQ-5D data at 12 months after injury. Cases where data were collected from the patient and proxy were extracted. Agreement between patient and proxy responses was compared using kappa (K) coefficients for the individual EQ-5D items, and Bland-Altman plots and Wilcoxon signed-rank tests for the EQ-5D summary score and visual analog scale (VAS). Agreement between patient and proxy respondents was substantial for the mobility (K = 0.61) and personal care items (K = 0.67) and moderate for the usual activities (K = 0.50), pain/discomfort (K = 0.42), and anxiety/depression items (K = 0.47). The mean difference between proxy and patient-reported scores for the VAS (0.74, 95% confidence interval: -2.73, 4.21) and the EQ-5D summary score (-0.02, 95% confidence interval: -0.07, 0.03) was small, but the limits of agreement were wide (-34.22 to 35.71 for VAS and -0.55 to 0.51 for summary score), suggesting no systematic bias. Although proxy and patient responses for the EQ-5D VAS may differ, the differences show random variability rather than systematic bias. Group comparisons using proxy responses are unlikely to be biased, but proxy responses should be used with caution when assessing individual patient recovery.

Robustness in Railway Operations (RobustRailS)

DEFF Research Database (Denmark)

Jensen, Jens Parbo; Nielsen, Otto Anker

This study considers the problem of enhancing railway timetable robustness without adding slack time, hence increasing the travel time. The approach integrates a transit assignment model to assess how passengers adapt their behaviour whenever operations are changed. First, the approach considers...

Antioxidant Approaches to Management of Ionizing Irradiation Injury

Directory of Open Access Journals (Sweden)

Joel Greenberger

2015-01-01

Full Text Available Ionizing irradiation induces acute and chronic injury to tissues and organs. Applications of antioxidant therapies for the management of ionizing irradiation injury fall into three categories: (1 radiation counter measures against total or partial body irradiation; (2 normal tissue protection against acute organ specific ionizing irradiation injury; and (3 prevention of chronic/late radiation tissue and organ injury. The development of antioxidant therapies to ameliorate ionizing irradiation injury began with initial studies on gene therapy using Manganese Superoxide Dismutase (MnSOD transgene approaches and evolved into applications of small molecule radiation protectors and mitigators. The understanding of the multiple steps in ionizing radiation-induced cellular, tissue, and organ injury, as well as total body effects is required to optimize the use of antioxidant therapies, and to sequence such approaches with targeted therapies for the multiple steps in the irradiation damage response.

Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

Directory of Open Access Journals (Sweden)

Songhui Zhai

2016-09-01

Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission.

Science.gov (United States)

Hennebelle, Marie; Zhang, Zhichao; Metherel, Adam H; Kitson, Alex P; Otoki, Yurika; Richardson, Christine E; Yang, Jun; Lee, Kin Sing Stephen; Hammock, Bruce D; Zhang, Liang; Bazinet, Richard P; Taha, Ameer Y

2017-06-28

Linoleic acid (LA; 18:2 n-6), the most abundant polyunsaturated fatty acid in the US diet, is a precursor to oxidized metabolites that have unknown roles in the brain. Here, we show that oxidized LA-derived metabolites accumulate in several rat brain regions during CO 2 -induced ischemia and that LA-derived 13-hydroxyoctadecadienoic acid, but not LA, increase somatic paired-pulse facilitation in rat hippocampus by 80%, suggesting bioactivity. This study provides new evidence that LA participates in the response to ischemia-induced brain injury through oxidized metabolites that regulate neurotransmission. Targeting this pathway may be therapeutically relevant for ischemia-related conditions such as stroke.

Robust statistical methods with R

CERN Document Server

Jureckova, Jana

2005-01-01

Robust statistical methods were developed to supplement the classical procedures when the data violate classical assumptions. They are ideally suited to applied research across a broad spectrum of study, yet most books on the subject are narrowly focused, overly theoretical, or simply outdated. Robust Statistical Methods with R provides a systematic treatment of robust procedures with an emphasis on practical application.The authors work from underlying mathematical tools to implementation, paying special attention to the computational aspects. They cover the whole range of robust methods, including differentiable statistical functions, distance of measures, influence functions, and asymptotic distributions, in a rigorous yet approachable manner. Highlighting hands-on problem solving, many examples and computational algorithms using the R software supplement the discussion. The book examines the characteristics of robustness, estimators of real parameter, large sample properties, and goodness-of-fit tests. It...

Robust Frequency Invariant Beamforming with Low Sidelobe for Speech Enhancement

Science.gov (United States)

Zhu, Yiting; Pan, Xiang

2018-01-01

Frequency invariant beamformers (FIBs) are widely used in speech enhancement and source localization. There are two traditional optimization methods for FIB design. The first one is convex optimization, which is simple but the frequency invariant characteristic of the beam pattern is poor with respect to frequency band of five octaves. The least squares (LS) approach using spatial response variation (SRV) constraint is another optimization method. Although, it can provide good frequency invariant property, it usually couldn’t be used in speech enhancement for its lack of weight norm constraint which is related to the robustness of a beamformer. In this paper, a robust wideband beamforming method with a constant beamwidth is proposed. The frequency invariant beam pattern is achieved by resolving an optimization problem of the SRV constraint to cover speech frequency band. With the control of sidelobe level, it is available for the frequency invariant beamformer (FIB) to prevent distortion of interference from the undesirable direction. The approach is completed in time-domain by placing tapped delay lines(TDL) and finite impulse response (FIR) filter at the output of each sensor which is more convenient than the Frost processor. By invoking the weight norm constraint, the robustness of the beamformer is further improved against random errors. Experiment results show that the proposed method has a constant beamwidth and almost the same white noise gain as traditional delay-and-sum (DAS) beamformer.

Changes in event-related potential functional networks predict traumatic brain injury in piglets.

Science.gov (United States)

Atlan, Lorre S; Lan, Ingrid S; Smith, Colin; Margulies, Susan S

2018-06-01

Traumatic brain injury is a leading cause of cognitive and behavioral deficits in children in the US each year. None of the current diagnostic tools, such as quantitative cognitive and balance tests, have been validated to identify mild traumatic brain injury in infants, adults and animals. In this preliminary study, we report a novel, quantitative tool that has the potential to quickly and reliably diagnose traumatic brain injury and which can track the state of the brain during recovery across multiple ages and species. Using 32 scalp electrodes, we recorded involuntary auditory event-related potentials from 22 awake four-week-old piglets one day before and one, four, and seven days after two different injury types (diffuse and focal) or sham. From these recordings, we generated event-related potential functional networks and assessed whether the patterns of the observed changes in these networks could distinguish brain-injured piglets from non-injured. Piglet brains exhibited significant changes after injury, as evaluated by five network metrics. The injury prediction algorithm developed from our analysis of the changes in the event-related potentials functional networks ultimately produced a tool with 82% predictive accuracy. This novel approach is the first application of auditory event-related potential functional networks to the prediction of traumatic brain injury. The resulting tool is a robust, objective and predictive method that offers promise for detecting mild traumatic brain injury, in particular because collecting event-related potentials data is noninvasive and inexpensive. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Robust Manufacturing Control

CERN Document Server

2013-01-01

This contributed volume collects research papers, presented at the CIRP Sponsored Conference Robust Manufacturing Control: Innovative and Interdisciplinary Approaches for Global Networks (RoMaC 2012, Jacobs University, Bremen, Germany, June 18th-20th 2012). These research papers present the latest developments and new ideas focusing on robust manufacturing control for global networks. Today, Global Production Networks (i.e. the nexus of interconnected material and information flows through which products and services are manufactured, assembled and distributed) are confronted with and expected to adapt to: sudden and unpredictable large-scale changes of important parameters which are occurring more and more frequently, event propagation in networks with high degree of interconnectivity which leads to unforeseen fluctuations, and non-equilibrium states which increasingly characterize daily business. These multi-scale changes deeply influence logistic target achievement and call for robust planning and control ...

Fatal occupational injuries in Taiwan, 1994-2005.

Science.gov (United States)

Ho, Shu-Chen; Wang, Li-Yu; Ho, Chi-Kung; Yang, Chun-Yuh

2010-04-01

This study examines the trends in rates of fatal occupational injuries in Taiwan by demographic group and occupation for 1994-2005. Data on deaths due to injuries at work from 1994 through 2005 were obtained from the Department of Health which is responsible for the death registration system in Taiwan. Employment data, which were used as the denominators of fatality rates in this study, were retrieved from the Directorate-General of Budget and Accounting Statistics 'Employment and Earnings' database. A Poisson regression model was used to examine the trends in rates of fatal occupational injuries in various occupations while controlling for demographic characteristics. Overall fatal occupational injury rates declined during the study period among all demographic groups and occupations. Adjusted annual changes in rates of fatal injuries ranged from a decrease of 13.6% a year in machine operators/related workers to a decrease of 35.9% in clerks. The annual decrement was faster for males than for females and for older workers compared to young workers. Despite declining rates, the number of fatal occupational injuries in Taiwan remains significant because of the growing work force. Future research should focus on the disparities in fatal injury trends.

Injury Characteristics of Low-Energy Lisfranc Injuries Compared With High-Energy Injuries.

Science.gov (United States)

Renninger, Christopher H; Cochran, Grant; Tompane, Trevor; Bellamy, Joseph; Kuhn, Kevin

2017-09-01

Lisfranc injuries result from high- and low-energy mechanisms though the literature has been more focused on high-energy mechanisms. A comparison of high-energy (HE) and low-energy (LE) injury patterns is lacking. The objective of this study was to report injury patterns in LE Lisfranc joint injuries and compare them to HE injury patterns. Operative Lisfranc injuries were identified over a 5-year period. Patient demographics, mechanism of injury, injury pattern, associated injuries, missed diagnoses, clinical course, and imaging studies were reviewed and compared. HE mechanism was defined as motor vehicle crash, motorcycle crash, direct crush, and fall from greater than 4 feet and LE mechanism as athletic activity, ground level twisting, or fall from less than 4 feet. Thirty-two HE and 48 LE cases were identified with 19.3 months of average follow-up. There were no differences in demographics or missed diagnosis frequency (21% HE vs 18% LE). Time to seek care was not significantly different. HE injuries were more likely to have concomitant nonfoot fractures (37% vs 6%), concomitant foot fractures (78% vs 4%), cuboid fractures (31% vs 6%), metatarsal base fractures (84% vs 29%), displaced intra-articular fractures (59% vs 4%), and involvement of all 5 rays (23% vs 6%). LE injuries were more commonly ligamentous (68% vs 16%), with fewer rays involved (2.7 vs 4.1). LE mechanisms were a more common cause of Lisfranc joint injury in this cohort. These mechanisms generally resulted in an isolated, primarily ligamentous injury sparing the lateral column. Both types had high rates of missed injury that could result in delayed treatment. Differences in injury patterns could help direct future research to optimize treatment algorithms. Level III, comparative series.

Aberrant innate immune activation following tissue injury impairs pancreatic regeneration.

Directory of Open Access Journals (Sweden)

Alexandra E Folias

Full Text Available Normal tissue architecture is disrupted following injury, as resident tissue cells become damaged and immune cells are recruited to the site of injury. While injury and inflammation are critical to tissue remodeling, the inability to resolve this response can lead to the destructive complications of chronic inflammation. In the pancreas, acinar cells of the exocrine compartment respond to injury by transiently adopting characteristics of progenitor cells present during embryonic development. This process of de-differentiation creates a window where a mature and stable cell gains flexibility and is potentially permissive to changes in cellular fate. How de-differentiation can turn an acinar cell into another cell type (such as a pancreatic β-cell, or a cell with cancerous potential (as in cases of deregulated Kras activity is of interest to both the regenerative medicine and cancer communities. While it is known that inflammation and acinar de-differentiation increase following pancreatic injury, it remains unclear which immune cells are involved in this process. We used a combination of genetically modified mice, immunological blockade and cellular characterization to identify the immune cells that impact pancreatic regeneration in an in vivo model of pancreatitis. We identified the innate inflammatory response of macrophages and neutrophils as regulators of pancreatic regeneration. Under normal conditions, mild innate inflammation prompts a transient de-differentiation of acinar cells that readily dissipates to allow normal regeneration. However, non-resolving inflammation developed when elevated pancreatic levels of neutrophils producing interferon-γ increased iNOS levels and the pro-inflammatory response of macrophages. Pancreatic injury improved following in vivo macrophage depletion, iNOS inhibition as well as suppression of iNOS levels in macrophages via interferon-γ blockade, supporting the impairment in regeneration and the

Robustness - theoretical framework

DEFF Research Database (Denmark)

Sørensen, John Dalsgaard; Rizzuto, Enrico; Faber, Michael H.

2010-01-01

More frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure combined with increased requirements to efficiency in design and execution followed by increased risk of human errors has made the need of requirements to robustness of new struct...... of this fact sheet is to describe a theoretical and risk based framework to form the basis for quantification of robustness and for pre-normative guidelines....

Dietary nitrate attenuates renal ischemia-reperfusion injuries by modulation of immune responses and reduction of oxidative stress.

Science.gov (United States)

Yang, Ting; Zhang, Xing-Mei; Tarnawski, Laura; Peleli, Maria; Zhuge, Zhengbing; Terrando, Niccolo; Harris, Robert A; Olofsson, Peder S; Larsson, Erik; Persson, A Erik G; Lundberg, Jon O; Weitzberg, Eddie; Carlstrom, Mattias

2017-10-01

Ischemia-reperfusion (IR) injury involves complex pathological processes in which reduction of nitric oxide (NO) bioavailability is suggested as a key factor. Inorganic nitrate can form NO in vivo via NO synthase-independent pathways and may thus provide beneficial effects during IR. Herein we evaluated the effects of dietary nitrate supplementation in a renal IR model. Male mice (C57BL/6J) were fed nitrate-supplemented chow (1.0mmol/kg/day) or standard chow for two weeks prior to 30min ischemia and during the reperfusion period. Unilateral renal IR caused profound tubular and glomerular damage in the ischemic kidney. Renal function, assessed by plasma creatinine levels, glomerular filtration rate and renal plasma flow, was also impaired after IR. All these pathologies were significantly improved by nitrate. Mechanistically, nitrate treatment reduced renal superoxide generation, pro-inflammatory cytokines (IL-1β, IL-6 and IL-12 p70) and macrophage infiltration in the kidney. Moreover, nitrate reduced mRNA expression of pro-inflammatory cytokines and chemo attractors, while increasing anti-inflammatory cytokines in the injured kidney. In another cohort of mice, two weeks of nitrate supplementation lowered superoxide generation and IL-6 expression in bone marrow-derived macrophages. Our study demonstrates protective effect of dietary nitrate in renal IR injury that may be mediated via modulation of oxidative stress and inflammatory responses. These novel findings suggest that nitrate supplementation deserve further exploration as a potential treatment in patients at high risk of renal IR injury. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A Robust Multivariable Feedforward/Feedback Controller Design for Integrated Power Control of Boiling Water Reactor Power Plants

International Nuclear Information System (INIS)

Shyu, S.-S.; Edwards, Robert M.

2002-01-01

In this paper, a methodology for synthesizing a robust multivariable feedforward/feedback control (FF/FBC) strategy is proposed for an integrated control of turbine power, throttle pressure, and reactor water level in a nuclear power plant. In the proposed method, the FBC is synthesized by the robust control approach. The feedforward control, which is generated via nonlinear programming, is added to the robust FBC system to further improve the control performance. The plant uncertainties, including unmodeled dynamics, linearization, and model reduction, are characterized and estimated. The comparisons of simulation responses based on a nonlinear reactor model demonstrate the achievement of the proposed controller with specified performance and endurance under uncertainty. It is also important to note that all input variables are manipulated in an orchestrated manner in response to a single output's setpoint change

Influence of manual therapy on functional mobility after joint injury in a rat model.

Science.gov (United States)

Ruhlen, Rachel L; Snider, Eric J; Sargentini, Neil J; Worthington, Bart D; Singh, Vineet K; Pazdernik, Vanessa K; Johnson, Jane C; Degenhardt, Brian F

2013-10-01

Animal models can be used to investigate manual therapy mechanisms, but testing manipulation in animal models is problematic because animals cannot directly report their pain. To develop a rat model of inflammatory joint injury to test the efficacy of manual therapy in reducing nociception and restoring function. The authors induced acute inflammatory joint injury in rats by injecting carrageenan into the ankle and then measured voluntary running wheel activity in treated and untreated rats. Treatments included manual therapy applied to the ankle and knee of the injured limb and several analgesic medications (eg, morphine, ketorolac, prednisone). Intra-articular injection of carrageenan to the ankle produced significant swelling (diameter of the ankle increased by 64% after injection; P=.004) and a robust reduction in voluntary running wheel activity (running distance reduced by 91% compared with controls; Pmanual therapy nor analgesic medications increased running wheel activity relative to untreated rats. Voluntary running wheel activity appears to be an appropriate functional measure to evaluate the impact of an acute inflammatory joint injury. However, efforts to treat the injury did not restore running relative to untreated rats.

Robustness Assessment of Spatial Timber Structures

DEFF Research Database (Denmark)

Kirkegaard, Poul Henning

2012-01-01

Robustness of structural systems has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. In order to minimise the likelihood of such disproportionate structural failures many modern buildi...... to robustness of spatial timber structures and will discuss the consequences of such robustness issues related to the future development of timber structures.......Robustness of structural systems has obtained a renewed interest due to a much more frequent use of advanced types of structures with limited redundancy and serious consequences in case of failure. In order to minimise the likelihood of such disproportionate structural failures many modern building...... codes consider the need for robustness of structures and provide strategies and methods to obtain robustness. Therefore a structural engineer may take necessary steps to design robust structures that are insensitive to accidental circumstances. The present paper summaries issues with respect...

Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens.

Science.gov (United States)

Lokhandwala, Shehnaz; Waghela, Suryakant D; Bray, Jocelyn; Martin, Cameron L; Sangewar, Neha; Charendoff, Chloe; Shetti, Rashmi; Ashley, Clay; Chen, Chang-Hsin; Berghman, Luc R; Mwangi, Duncan; Dominowski, Paul J; Foss, Dennis L; Rai, Sharath; Vora, Shaunak; Gabbert, Lindsay; Burrage, Thomas G; Brake, David; Neilan, John; Mwangi, Waithaka

2016-11-01

The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ + ) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Lip and tooth injuries at public swimming pools in Austria.

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Lechner, Katharina; Connert, Thomas; Kühl, Sebastian; Filippi, Andreas

2017-06-01

There is an increased risk of orofacial injuries in swimming pool facilities. Nevertheless, only a few studies have addressed this issue. The aim of this study was to identify the frequency of lip and tooth injuries at public swimming pools in Austria. A further aim was to examine which gender and age groups were affected, where and why these injuries occurred, and whether pool attendants had sufficient knowledge of dental first-aid measures. A total of 764 pool attendants in Austria were contacted by telephone and 689 participated in the study (90.2%). The attendants were interviewed retrospectively about accident occurrences in 2014 by a standardized questionnaire. Responses to the provision of first aid and choice of storage medium for avulsed teeth were subsequently evaluated. The frequency of lip injuries was 19.0%, and tooth injuries were 11.3%. Male bathers (P < .05) and children under 12 years (P < .001) most frequently suffered injuries. The waterslide was the most common accident site. The most common cause of lip injuries was slipping on wet surfaces (39.0%), and for tooth injuries it was collisions with other persons or objects (each 28.1%). The pool attendants' responses were predominantly good or sufficient on first aid, with the exception of what storage medium to choose. Tooth rescue boxes were available in only 8.6% of all pool facilities. Orofacial injuries are a frequently occurring problem in swimming pool facilities. The pool attendants' knowledge on first-aid care of tooth injuries could still be improved. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury.

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MacManes, Matthew David

2017-08-01

Animals living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. These animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert-adapted rodent Peromyscus eremicus survives, reproductively mature adults were subjected to 72 h of water deprivation, during which they lost, on average, 23% of their body weight. The animals reacted via a series of changes in the kidney, which included modulating expression of genes responsible for reducing the rate of transcription and maintaining water and salt balance. Extracellular matrix turnover appeared to be decreased, and apoptosis was limited. In contrast to the canonical human response, serum creatinine and other biomarkers of kidney injury were not elevated, suggesting that changes in gene expression related to acute dehydration may effectively prohibit widespread kidney damage in the cactus mouse. Copyright © 2017 the American Physiological Society.

ORBITAL INJURIES

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Andrej Kansky

2002-12-01

Full Text Available Background. Orbit is involved in 40% of all facial fractures. There is considerable variety in severity, ranging from simple nondisplaced to complex comminuted fractures. Complex comminuted fractures (up to 20% are responsible for the majority of complications and unfavorable results. Orbital fractures are classified as internal orbital fractures, zygomatico-orbital fractures, naso-orbito-ethmoidal fractures and combined fractures. The ophtalmic sequelae of midfacial fractures are usually edema and ecchymosis of the soft tissues, subconjuctival hemorrhage, diplopia, iritis, retinal edema, ptosis, enophthalmos, ocular muscle paresis, mechanical restriction of ocular movement and nasolacrimal disturbances. More severe injuries such as optic nerve trauma and retinal detachments have also been reported. Within the wide range of orbital fractures small group of complex fractures causes most of the sequelae. Therefore identification of severe injuries and adequate treatment is of major importance. The introduction of craniofacial techniques made possible a wide exposure even of large orbital wall defects and their reconstruction by bone grafts. In spite of significant progress, repair of complex orbital wall defects remains a problem even for the experienced surgeons.Results. In 1999 121 facial injuries were treated at our department (Clinical Centre Ljubljana Dept. Of Maxillofacial and Oral Surgery. Orbit was involved in 65% of cases. Isolated inner orbital fractures presented 4% of all fractures. 17 (14% complex cases were treated, 5 of them being NOE, 5 orbital (frame and inner walls, 3 zygomatico-orbital, 2 FNO and 2 maxillo-orbital fractures.Conclusions. Final result of the surgical treatment depends on severity of maxillofacial trauma. Complex comminuted fractures are responsable for most of the unfavorable results and ocular function is often permanently damaged (up to 75% in these fractures.

Nonlinear Dynamics in Gene Regulation Promote Robustness and Evolvability of Gene Expression Levels.

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Steinacher, Arno; Bates, Declan G; Akman, Ozgur E; Soyer, Orkun S

2016-01-01

Cellular phenotypes underpinned by regulatory networks need to respond to evolutionary pressures to allow adaptation, but at the same time be robust to perturbations. This creates a conflict in which mutations affecting regulatory networks must both generate variance but also be tolerated at the phenotype level. Here, we perform mathematical analyses and simulations of regulatory networks to better understand the potential trade-off between robustness and evolvability. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics, through the creation of regions presenting sudden changes in phenotype with small changes in genotype. For genotypes embedding low levels of nonlinearity, robustness and evolvability correlate negatively and almost perfectly. By contrast, genotypes embedding nonlinear dynamics allow expression levels to be robust to small perturbations, while generating high diversity (evolvability) under larger perturbations. Thus, nonlinearity breaks the robustness-evolvability trade-off in gene expression levels by allowing disparate responses to different mutations. Using analytical derivations of robustness and system sensitivity, we show that these findings extend to a large class of gene regulatory network architectures and also hold for experimentally observed parameter regimes. Further, the effect of nonlinearity on the robustness-evolvability trade-off is ensured as long as key parameters of the system display specific relations irrespective of their absolute values. We find that within this parameter regime genotypes display low and noisy expression levels. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics. Our results provide a possible solution to the robustness-evolvability trade-off, suggest an explanation for

Nonlinear Dynamics in Gene Regulation Promote Robustness and Evolvability of Gene Expression Levels.

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Arno Steinacher

Full Text Available Cellular phenotypes underpinned by regulatory networks need to respond to evolutionary pressures to allow adaptation, but at the same time be robust to perturbations. This creates a conflict in which mutations affecting regulatory networks must both generate variance but also be tolerated at the phenotype level. Here, we perform mathematical analyses and simulations of regulatory networks to better understand the potential trade-off between robustness and evolvability. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics, through the creation of regions presenting sudden changes in phenotype with small changes in genotype. For genotypes embedding low levels of nonlinearity, robustness and evolvability correlate negatively and almost perfectly. By contrast, genotypes embedding nonlinear dynamics allow expression levels to be robust to small perturbations, while generating high diversity (evolvability under larger perturbations. Thus, nonlinearity breaks the robustness-evolvability trade-off in gene expression levels by allowing disparate responses to different mutations. Using analytical derivations of robustness and system sensitivity, we show that these findings extend to a large class of gene regulatory network architectures and also hold for experimentally observed parameter regimes. Further, the effect of nonlinearity on the robustness-evolvability trade-off is ensured as long as key parameters of the system display specific relations irrespective of their absolute values. We find that within this parameter regime genotypes display low and noisy expression levels. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics. Our results provide a possible solution to the robustness-evolvability trade-off, suggest

Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium

International Nuclear Information System (INIS)

Beaver, Laura M.; Stemmy, Erik J.; Constant, Stephanie L.; Schwartz, Arnold; Little, Laura G.; Gigley, Jason P.; Chun, Gina; Sugden, Kent D.

2009-01-01

Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0-24 h) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis

A Comparative Theoretical and Computational Study on Robust Counterpart Optimization: I. Robust Linear Optimization and Robust Mixed Integer Linear Optimization

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Li, Zukui; Ding, Ran; Floudas, Christodoulos A.

2011-01-01

Robust counterpart optimization techniques for linear optimization and mixed integer linear optimization problems are studied in this paper. Different uncertainty sets, including those studied in literature (i.e., interval set; combined interval and ellipsoidal set; combined interval and polyhedral set) and new ones (i.e., adjustable box; pure ellipsoidal; pure polyhedral; combined interval, ellipsoidal, and polyhedral set) are studied in this work and their geometric relationship is discussed. For uncertainty in the left hand side, right hand side, and objective function of the optimization problems, robust counterpart optimization formulations induced by those different uncertainty sets are derived. Numerical studies are performed to compare the solutions of the robust counterpart optimization models and applications in refinery production planning and batch process scheduling problem are presented. PMID:21935263

The cost and distribution of firefighter injuries in a large Canadian Fire Department.

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Frost, D M; Beach, T A C; Crosby, I; McGill, S M

2016-11-22

There is limited data available regarding the cost of firefighter injuries. This information is necessary to develop targeted injury prevention strategies. To categorize the cost of injuries filed in 2012 by firefighters from a from a large department by job duty, injury type, body part affected, and the general motion pattern employed at the time of injury. Data were taken from reports filed by CFD personnel and claims filed with the Workers' Compensation Board (WCB) of Alberta between January 1, 2012 and December 31, 2012. Of the 244 injuries reported, 65% were categorized as sprains and strains, the most frequent of which affected the back (32%). The total cost of all claims was $555,955; 77% were sprain/strain-related. Knee and back injuries were most costly ($157,383 and $100,459). Categorized by job duty, most sprains/strains (31%) were sustained while attending to fire station responsibilities, although physical training was associated with the highest costs (34%). Fireground operations were attributed to 18% of sprains/strains and 16% of costs. Lifting injuries were more frequent (23%) and costly (20%) than all injuries. The most common and costly injuries occurred while attending to fire station-related responsibilities and during physical training.

Respiratory mechanics in brain injury: A review.

Science.gov (United States)

Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

2016-02-04

Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.

Role of Non-neuronal Cells in Tauopathies After Brain Injury

Science.gov (United States)

2017-09-01

AWARD NUMBER: W81XWH-15-1-0422 TITLE: Role of Nonneuronal Cells in Tauopathies After Brain Injury PRINCIPAL INVESTIGATOR: Sally A. Frautschy...AND SUBTITLE 5a. CONTRACT NUMBER Role of Non-neuronal Cells in Tauopathies After Brain Injury 5b. GRANT NUMBER W81XWH-15-1-0422 5c. PROGRAM...traumatic brain injury (TBI), specific inflammatory factors (complement proteins) elevated during long asymptomatic prodromal period are responsible

A Robust Response of the Hadley Circulation to Global Warming

Science.gov (United States)

Lau, William K M.; Kim, Kyu-Myong

2014-01-01

Tropical rainfall is expected to increase in a warmer climate. Yet, recent studies have inferred that the Hadley Circulation (HC), which is primarily driven by latent heating from tropical rainfall, is weakened under global warming. Here, we show evidence of a robust intensification of the HC from analyses of 33 CMIP5 model projections under a scenario of 1 per year CO2 emission increase. The intensification is manifested in a deep-tropics squeeze, characterized by a pronounced increase in the zonal mean ascending motion in the mid and upper troposphere, a deepening and narrowing of the convective zone and enhanced rainfall in the deep tropics. These changes occur in conjunction with a rise in the region of maximum outflow of the HC, with accelerated meridional mass outflow in the uppermost branch of the HC away from the equator, coupled to a weakened inflow in the return branches of the HC in the lower troposphere.

An algorithm for robust non-linear analysis of radioimmunoassays and other bioassays

International Nuclear Information System (INIS)

Normolle, D.P.

1993-01-01

The four-parameter logistic function is an appropriate model for many types of bioassays that have continuous response variables, such as radioimmunoassays. By modelling the variance of replicates in an assay, one can modify the usual parameter estimation techniques (for example, Gauss-Newton or Marquardt-Levenberg) to produce parameter estimates for the standard curve that are robust against outlying observations. This article describes the computation of robust (M-) estimates for the parameters of the four-parameter logistic function. It describes techniques for modelling the variance structure of the replicates, modifications to the usual iterative algorithms for parameter estimation in non-linear models, and a formula for inverse confidence intervals. To demonstrate the algorithm, the article presents examples where the robustly estimated four-parameter logistic model is compared with the logit-log and four-parameter logistic models with least-squares estimates. (author)

Training volume and soft tissue injury in professional and non-professional rugby union players: a systematic review.

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Ball, Shane; Halaki, Mark; Orr, Rhonda

2017-07-01

To investigate the relationship between training volume and soft tissue injury incidence, and characterise soft tissue injury in rugby union players. A systematic search of electronic databases was performed. The search strategy combined terms covering: training volume and injury, and rugby union, and players of all levels. Medline, SPORTDiscus, Web of Science, Embase, PubMed. Studies were included if they reported: male rugby union players, a clear definition of a rugby union injury, the amount of training volume undertaken by participants, and epidemiological data for soft-tissue injuries including the number or incidence. 15 studies were eligible for inclusion. Overall match and training injury incidence ranged from 3.3 to 218.0 injuries/1000 player match hours and 0.1-6.1 injuries/1000 player training hours, respectively. Muscle and tendon as well as joint (non-bone) and ligament injuries were the most frequently occurring injuries. The lower limb was the most prevalent injury location. Injury incidence was higher in professional rugby union players than non-professional players. Contact events were responsible for the greatest injury incidence. For non-contact mechanisms, running was responsible for the highest injury incidence. Inconsistent injury definitions hindered reliable comparison of injury data. The lack of reporting training volumes in hours per player per week limited the ability to investigate associations between training volume and injury incidence. A higher level of play may result in higher match injury incidence. Muscle and tendon injuries were the most common type of soft tissue injury, while the lower limb was the most common location of injury in rugby union players, and running was responsible for the highest injury incidence during non-contact events. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Acute Liver Injury Is Independent of B Cells or Immunoglobulin M.

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James A Richards

Full Text Available Acute liver injury is a clinically important pathology and results in the release of Danger Associated Molecular Patterns, which initiate an immune response. Withdrawal of the injurious agent and curtailing any pathogenic secondary immune response may allow spontaneous resolution of injury. The role B cells and Immunoglobulin M (IgM play in acute liver injury is largely unknown and it was proposed that B cells and/or IgM would play a significant role in its pathogenesis.Tissue from 3 models of experimental liver injury (ischemia-reperfusion injury, concanavalin A hepatitis and paracetamol-induced liver injury and patients transplanted following paracetamol overdose were stained for evidence of IgM deposition. Mice deficient in B cells (and IgM were used to dissect out the role B cells and/or IgM played in the development or resolution of injury. Serum transfer into mice lacking IgM was used to establish the role IgM plays in injury.Significant deposition of IgM was seen in the explanted livers of patients transplanted following paracetamol overdose as well as in 3 experimental models of acute liver injury (ischemia-reperfusion injury, concanavalin A hepatitis and paracetamol-induced liver injury. Serum transfer into IgM-deficient mice failed to reconstitute injury (p = 0.66, despite successful engraftment of IgM. Mice deficient in both T and B cells (RAG1-/- mice (p<0.001, but not B cell deficient (μMT mice (p = 0.93, were significantly protected from injury. Further interrogation with T cell deficient (CD3εKO mice confirmed that the T cell component is a key mediator of sterile liver injury. Mice deficient in B cells and IgM mice did not have a significant delay in resolution following acute liver injury.IgM deposition appears to be common feature of both human and murine sterile liver injury. However, neither IgM nor B cells, play a significant role in the development of or resolution from acute liver injury. T cells appear to be key

Robust procedures in chemometrics

DEFF Research Database (Denmark)

Kotwa, Ewelina

properties of the analysed data. The broad theoretical background of robust procedures was given as a very useful supplement to the classical methods, and a new tool, based on robust PCA, aiming at identifying Rayleigh and Raman scatters in excitation-mission (EEM) data was developed. The results show...

Stochastic Mesocortical Dynamics and Robustness of Working Memory during Delay-Period.

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