66 research outputs found

    Psychological Stress as a Modulator of Functional Recovery Following Spinal Cord Injury

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    There is strong evidence indicating that the social environment triggers changes to the psychological stress response and glucocorticoid receptor function. Considerable literature links the subsequent changes in stress resiliency to physical health. Here, converging evidence for the modulatory role of chronic psychological stress in the recovery process following spinal cord injury (SCI) is presented. Despite the considerable advances in spinal cord injury research, we are still unable to identify the causes of variability in patients’ recovery following injury. We propose that individuals’ past and present life experiences (in the form of stress exposure) may significantly modulate patients’ outcome post SCI. We propose a theoretical model to explain the negative impact of chronic psychological stress on physical and psychological recovery. The stress experienced in life prior to SCI and also as a result of the traumatic injury, could compromise glucocorticoid receptor sensitivity and function, and contribute to high levels of inflammation and apoptosis post SCI, decreasing the tissue remaining at the injury site and undermining recovery of function. Both stress induced glucocorticoid resistance and stress induced epigenetic changes to the glucocorticoid receptor can modulate the NF-кB regulated inflammatory pathways and the Bcl-2 regulated apoptosis pathways. This model not only contributes to the theoretical understanding of the recovery process following injury, but also provides concrete testable hypotheses for future studies

    Waldo Lake Research in 2004

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    The Willamette National Forest has worked with Portland State University, Center for Lakes and Reservoirs (PSU) and the University of Oregon (UO) to investigate ecosystem changes, provide guidance on long-term monitoring methods, assess monitoring data, develop predictive water quality models, and conduct research that will lead to better protection and understanding of the Waldo Lake ecosystem. This report summarizes the second year of collaborative PSU-UO research at Waldo Lake. Research has focused on understanding physical, chemical and biological characteristics of Waldo Lake across a range of spatial and temporal scales. Research tasks that continued from 2003 into 2004 included temperature monitoring, hydrodynamic and water quality model development, climate and hydrological forcing scenario investigation, bathymetric map refinement, and analysis of phytoplankton and zooplankton community changes. Research tasks initiated in 2004 included evaluation of wavelength-specific light attenuation, diel phytoplankton and zooplankton vertical distribution patterns, phytoplankton photoinhibition and photoprotection, and the role of mixotrophy in the pelagic microbial food web. Preliminary efforts were made to characterize Waldo Lake benthos through assessment of algal species diversity and chemical composition of the benthic community, as very little is currently known about the Waldo Lake benthic ecosystem. In addition, an attempt was made to map benthic substrate types through reinterpretation of data collected during the 2003 bathymetric survey

    The DANTE trial protocol: a randomised phase III trial to evaluate the Duration of ANti-PD-1 monoclonal antibody Treatment in patients with metastatic mElanoma.

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    BACKGROUND: Immunotherapy is revolutionising the treatment of patients diagnosed with melanoma and other cancers. The first immune checkpoint inhibitor, ipilimumab (targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)), showed a survival advantage over standard chemotherapy. Subsequently the anti-programmed cell death protein 1 (PD-1) antibodies, nivolumab and pembrolizumab were shown to be more effective than ipilimumab. Ipilimumab combined with nivolumab gives an incremental gain in overall survival compared with nivolumab alone but increases the risk of severe, potentially life-threatening toxicities. In contrast to ipilimumab monotherapy, anti-PD-1 antibodies are licensed to be continued until disease progression. Follow-up of patients recruited to the first trials evaluating 2 years of pembrolizumab showed that three-quarters of responding patients continue responding after stopping treatment. Suggestive of early response, we hypothesised that continuing anti-PD-1 treatment beyond 1 year in progression-free patients may be unnecessary and so designed the DANTE trial. METHODS: DANTE is a multicentre, randomised, phase III, non-inferiority trial to evaluate the duration of anti-PD-1 therapy in patients with metastatic (unresectable stage III and stage IV) melanoma. It uses a two-stage recruitment strategy, registering patients before they complete 1 year of first-line anti-PD-1 +/- CTLA-4 therapy and randomising eligible patients who have received 12 months of treatment and are progression-free at 1 year. At randomisation, 1208 patients are assigned (1:1) to either 1) continue anti-PD-1 treatment until disease progression/ unacceptable toxicity/ for at least 2 years in the absence of disease progression/ unacceptable toxicity or 2) to stop treatment. Randomisation stratifies for baseline prognostic factors. The primary outcome is progression-free survival at 3, 6, 9 and 12 months and then, 6-monthly for up to 4-years. Secondary outcomes collected at all timepoints include overall survival, response-rate and duration and safety, with quality of life and cost-effectiveness outcomes collected 3-monthly for up to 18-months. Sub-studies include a qualitative analysis of patient acceptance of randomisation and sample collection to inform future translational studies into response/ toxicity biomarkers. DISCUSSION: DANTE is a unique prospective trial investigating the optimal duration of anti-PD-1 therapy in metastatic melanoma patients. Outcomes will inform future use of these high burden drugs. TRIAL REGISTRATION: ISRCTN15837212 , 31 July 2018

    Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

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    Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI

    Metaplasticity and behavior: how training and inflammation affect plastic potential within the spinal cord and recovery after injury

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    Research has shown that spinal circuits have the capacity to adapt in response to training, nociceptive stimulation and peripheral inflammation. These changes in neural function are mediated by physiological and neurochemical systems analogous to those that support plasticity within the hippocampus (e.g., long-term potentiation and the NMDA receptor). As observed in the hippocampus, engaging spinal circuits can have a lasting impact on plastic potential, enabling or inhibiting the capacity to learn. These effects are related to the concept of metaplasticity. Behavioral paradigms are described that induce metaplastic effects within the spinal cord. Uncontrollable/unpredictable stimulation, and peripheral inflammation, induce a form of maladaptive plasticity that inhibits spinal learning. Conversely, exposure to controllable or predictable stimulation engages a form of adaptive plasticity that counters these maladaptive effects and enables learning. Adaptive plasticity is tied to an up-regulation of brain derived neurotrophic factor (BDNF). Maladaptive plasticity is linked to processes that involve kappa opioids, the metabotropic glutamate (mGlu) receptor, glia, and the cytokine tumor necrosis factor (TNF). Uncontrollable nociceptive stimulation also impairs recovery after a spinal contusion injury and fosters the development of pain (allodynia). These adverse effects are related to an up-regulation of TNF and a down-regulation of BDNF and its receptor (TrkB). In the absence of injury, brain systems quell the sensitization of spinal circuits through descending serotonergic fibers and the serotonin 1A (5HT 1A) receptor. This protective effect is blocked by surgical anesthesia. Disconnected from the brain, intracellular Cl- concentrations increase (due to a down-regulation of the cotransporter KCC2), which causes GABA to have an excitatory effect. It is suggested that BDNF has a restorative effect because it up-regulates KCC2 and re-establishes GABA-mediated inhibition

    Marketing as a means to transformative social conflict resolution: lessons from transitioning war economies and the Colombian coffee marketing system

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    Social conflicts are ubiquitous to the human condition and occur throughout markets, marketing processes, and marketing systems.When unchecked or unmitigated, social conflict can have devastating consequences for consumers, marketers, and societies, especially when conflict escalates to war. In this article, the authors offer a systemic analysis of the Colombian war economy, with its conflicted shadow and coping markets, to show how a growing network of fair-trade coffee actors has played a key role in transitioning the country’s war economy into a peace economy. They particularly draw attention to the sources of conflict in this market and highlight four transition mechanisms — i.e., empowerment, communication, community building and regulation — through which marketers can contribute to peacemaking and thus produce mutually beneficial outcomes for consumers and society. The article concludes with a discussion of implications for marketing theory, practice, and public policy

    Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

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    OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

    Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

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    It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

    Leading-limb preferences in marmosets ('Callithrix jacchus'): Walking, leaping and landing

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    The leading-limb preferences of 17 common marmosets ('Callithrix jacchus') when they initiated and terminated locomotion were determined from video recordings of the subjects walking on, leaping off, and landing on a plexiglas platform. In a majority of sequences, 11 of 17 subjects landed with the right hand and foot contacting the plexiglas substrate before the left hand and foot. Of the 17 subjects, 8 initiated leaping with the right side of the body, whereas only 3 subjects significantly preferred to initiate leaping with the left hand and foot. Leading-limb preferences displayed during landing were positively correlated with those displayed for leaping and walking, although only two subjects displayed significant leading-limb preferences when walking. By contrast, hand preferences for initiating and terminating locomotion were not related to hand preferences for food holding; 16 of 17 marmosets displayed strong and significant hand preferences for food holding, even though many did not show leading-limb preferences for walking, leaping, or landing. These data seem to suggest that the right arm is stronger in marmosets. The right arm is used initially to decelerate the body and absorb the impact of contact with the landing substrate. The tendency for the right arm to be stronger is balanced by a tendency for the left leg to be stronger (providing the force needed for leaping)
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