200 research outputs found

    M-sequence geomagnetic polarity time scale (MHTC12) that steadies global spreading rates and incorporates astrochronology constraints

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    Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 117 (2012): B06104, doi:10.1029/2012JB009260.Geomagnetic polarity time scales (GPTSs) have been constructed by interpolating between dated marine magnetic anomalies assuming uniformly varying spreading rates. A strategy to obtain an optimal GPTS is to minimize spreading rate fluctuations in many ridge systems; however, this has been possible only for a few spreading centers. We describe here a Monte Carlo sampling method that overcomes this limitation and improves GPTS accuracy by incorporating information on polarity chron durations estimated from astrochronology. The sampling generates a large ensemble of GPTSs that simultaneously agree with radiometric age constraints, minimize the global variation in spreading rates, and fit polarity chron durations estimated by astrochronology. A key feature is the inclusion and propagation of data uncertainties, which weigh how each piece of information affects the resulting time scale. The average of the sampled ensemble gives a reference GPTS, and the variance of the ensemble measures the time scale uncertainty. We apply the method to construct MHTC12, an improved version of the M-sequence GPTS (Late Jurassic-Early Cretaceous, ~160–120 Ma). This GPTS minimizes the variation in spreading rates in a global data set of magnetic lineations from the Western Pacific, North Atlantic, and Indian Ocean NW of Australia, and it also accounts for the duration of five polarity chrons established from astrochronology (CM0r through CM3r). This GPTS can be updated by repeating the Monte Carlo sampling with additional data that may become available in the future.A.M. and J.H. were supported by NSF grant OCE 09–26306, M.T. was supported by a Woods Hole Oceanographic Institution postdoctoral scholarship, and J.E.T.C. was supported by NSF grant OCE 09–60999.2012-12-3

    The absence of donor-derived IL-13 exacerbates the severity of acute graft-versus-host disease following allogeneic bone marrow transplantation

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    Acute graft versus host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT) predominantly involves a Th1-type cytokine response. Interestingly, the Th2-cytokine, Interleukin-13 (IL-13), produced by alloreactive donor T cells in vitro was recently shown to correlate with clinical aGVHD severity. Using an established mouse model, we show that the systemic cytokine milieu following allo-BMT with IL-13−/− donors is characterized by decreases in serum Th2 cytokines and an increase in serum TNFΑ, and ultimately correlates with higher aGVHD mortality compared to allogeneic controls. In vitro studies further demonstrate that both exogenous and T cell-derived IL-13 can regulate TNFΑ production by macrophages following lipopolysaccharide stimulation. Thus, donor-derived IL-13 may have a role in modulating inflammatory cytokine release that is associated with aGVHD. Pediatr Blood Cancer 2008;50:911–914. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58037/1/21228_ftp.pd

    The relationship between back pain and mortality in older adults varies with disability and gender: results from the Cambridge City over-75s Cohort (CC75C) study.

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    BACKGROUND: This study aims to determine whether older adults reporting back pain (BP) are at increased risk of premature mortality, specifically, to examine the association with disabling/non-disabling pain separately. METHODS: Participants aged ≥75 years were recruited to the Cambridge City over-75s Cohort (CC75C) study. Participants answered interviewer-administered questions on BP and were followed up until death. The relationship between BP and mortality was examined using Cox regression, adjusted for potential confounding factors. Separate models were computed for men and women. RESULTS: From 1174 individuals with BP data, the date of death was known for 1158 (99%). A significant association was found between disabling BP and mortality (hazard ratio: 1.4; 95% confidence interval: 1.1-1.8) and this remained, albeit of borderline significance, following adjustment for socio-demographic variables and potential disease markers (1.3; 0.99-1.7). Further, this association was found to vary with sex: women experienced a 40% increase in the risk of mortality associated with disabling BP (1.4; 1.1-1.9), whereas no such increase was observed for men (1.0; 0.5-1.9). Participants with non-disabling BP were not at increased risk of mortality. CONCLUSIONS: This study confirmed previous findings regarding the relationship between pain and excess mortality. Further, we have shown that, among older adults, this association is specific to disabling pain and to women. Clinicians should be aware not only of the short-term implications of disabling BP but also the longer-term effects. Future research should attempt to understand the mechanisms underpinning this relationship to avoid excess mortality and should aim to determine why the relationship differs in men and women

    Healthcare recommendations for Joubert syndrome

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    Joubert syndrome (JS) is a recessive neurodevelopmental disorder defined by a characteristic cerebellar and brainstem malformation recognizable on axial brain magnetic resonance imaging as the "Molar Tooth Sign". Although defined by the neurological features, JS is associated with clinical features affecting many other organ systems, particularly progressive involvement of the retina, kidney, and liver. JS is a rare condition; therefore, many affected individuals may not have easy access to subspecialty providers familiar with JS (e.g., geneticists, neurologists, developmental pediatricians, ophthalmologists, nephrologists, hepatologists, psychiatrists, therapists, and educators). Expert recommendations can enable practitioners of all types to provide quality care to individuals with JS and know when to refer for subspecialty care. This need will only increase as precision treatments targeting specific genetic causes of JS emerge. The goal of these recommendations is to provide a resource for general practitioners, subspecialists, and families to maximize the health of individuals with JS throughout the lifespan

    CXCR2 chemokine receptor antagonism enhances DOP opioid receptor function via allosteric regulation of the CXCR2–DOP receptor heterodimer

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    Opioid agonists have a broad range of effects on cells of the immune system, including modulation of the inflammatory response, and opioid and chemokine receptors are co-expressed by many white cells. Hetero-oligomerization of the human DOP opioid and chemokine CXCR2 receptors could be detected following their co-expression by each of co-immunoprecipitation, three different resonance energy transfer techniques and the construction of pairs of individually inactive but potentially complementary receptor G-protein α subunit fusion proteins. Although DOP receptor agonists and a CXCR2 antagonist had no inherent affinity for the alternative receptor when either receptor was expressed individually, use of cells that expressed a DOP opioid receptor construct constitutively, and in which expression of a CXCR2 receptor construct could be regulated, demonstrated that the CXCR2 antagonist enhanced the function of DOP receptor agonists only in the presence of CXCR2. This effect was observed for both enkephalin- and alkaloid-based opioid agonists, and the effective concentrations of the CXCR2 antagonist reflected CXCR2 receptor occupancy. Entirely equivalent results were obtained in cells in which the native DOP opioid receptor was expressed constitutively and in which expression of the isolated CXCR2 receptor could be induced. These results indicate that a CXCR2 receptor antagonist can enhance the function of agonists at a receptor for which it has no inherent direct affinity by acting as an allosteric regulator of a receptor that is a heterodimer partner for the CXCR2 receptor. These results have novel and important implications for the development and use of small-molecule therapeutics

    Prognostic factors for perceived recovery or functional improvement in non-specific low back pain: secondary analyses of three randomized clinical trials

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    The objective of this study was to report on secondary analyses of a merged trial dataset aimed at exploring the potential importance of patient factors associated with clinically relevant improvements in non-acute, non-specific low back pain (LBP). From 273 predominantly male army workers (mean age 39 ± 10.5 years, range 20–56 years, 4 women) with LBP who were recruited in three randomized clinical trials, baseline individual patient factors, pain-related factors, work-related psychosocial factors, and psychological factors were evaluated as potential prognostic variables in a short-term (post-treatment) and a long-term logistic regression model (6 months after treatment). We found one dominant prognostic factor for improvement directly after treatment as well as 6 months later: baseline functional disability, expressed in Roland–Morris Disability Questionnaire scores. Baseline fear of movement, expressed in Tampa Scale for Kinesiophobia scores, had also significant prognostic value for long-term improvement. Less strongly associated with the outcome, but also included in our final models, were supervisor social support and duration of complaints (short-term model), and co-worker social support and pain radiation (long-term model). Information about initial levels of functional disability and fear-avoidance behaviour can be of value in the treatment of patient populations with characteristics comparable to the current army study population (e.g., predominantly male, physically active, working, moderate but chronic back problems). Individuals at risk for poor long-term LBP recovery, i.e., individuals with high initial level of disability and prominent fear-avoidance behaviour, can be distinguished that may need additional cognitive-behavioural treatment

    A bio-psycho-social exercise program (RÜCKGEWINN) for chronic low back pain in rehabilitation aftercare - Study protocol for a randomised controlled trial

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    <p>Abstract</p> <p>Background</p> <p>There is strong, internationally confirmed evidence for the short-term effectiveness of multimodal interdisciplinary specific treatment programs for chronic back pain. However, the verification of long-term sustainability of achieved effects is missing so far. For long-term improvement of pain and functional ability high intervention intensity or high volume seems to be necessary (> 100 therapy hours). Especially in chronic back pain rehabilitation, purposefully refined aftercare treatments offer the possibility to intensify positive effects or to increase their sustainability. However, quality assured goal-conscious specific aftercare programs for the rehabilitation of chronic back pain are absent.</p> <p>Methods/Design</p> <p>This study aims to examine the efficacy of a specially developed bio-psycho-social chronic back pain specific aftercare intervention (RÜCKGEWINN) in comparison to the current usual aftercare (IRENA) and a control group that is given an educational booklet addressing pain-conditioned functional ability and back pain episodes. Overall rehabilitation effects as well as predictors for compliance to the aftercare programs are analysed. Therefore, a multicenter prospective 3-armed randomised controlled trial is conducted. 456 participants will be consecutively enrolled in inpatient and outpatient rehabilitation and assigned to either one of the three study arms. Outcomes are measured before and after rehabilitation. Aftercare programs are assessed at ten month follow up after dismissal form rehabilitation.</p> <p>Discussion</p> <p>Special methodological and logistic challenges are to be mastered in this trial, which accrue from the interconnection of aftercare interventions to their residential district and the fact that the proportion of patients who take part in aftercare programs is low. The usability of the aftercare program is based on the transference into the routine care and is also reinforced by developed manuals with structured contents, media and material for organisation assistance as well as training manuals for therapists in the aftercare.</p> <p>Trial Registration</p> <p>Trial Registration number: NCT01070849</p
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