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Currier J.M.,Memphis Veterans Administration Medical Center | Holland J.M.,University of Nevada, Las Vegas | Chisty K.,University of Tennessee Health Science Center | Allen D.,University of Tennessee Health Science Center
Journal of Traumatic Stress | Year: 2011

Crises in personal meaning may be a critical aspect of psychological maladjustment following combat. Using the newly developed Integration of Stressful Life Events Scale (ISLES), this study examined the role of meaning made of a salient stressor following a combat deployment in Iraq or Afghanistan. In a sample of 169 returning service members, findings supported the distinctiveness of meaning made of a stressor (as assessed by the ISLES), factor analytically and as a correlate of several relevant clinical outcomes. In particular, when the model contained potential confounds and psychiatric symptoms, meaning made in the months and years following combat was uniquely associated with the severity of posttraumatic stress symptoms, β = -.39, and referrals for mental health care, β = -.69, in the sample. The present findings highlight the importance of the subjective meaning made of traumatic life events and also suggest that posttraumatic stress and other psychiatric symptomatology may not account for the full clinical picture among many service men and women. © 2011 International Society for Traumatic Stress Studies. Source


Strom T.S.,Memphis Veterans Administration Medical Center | Strom T.S.,University of Tennessee Health Science Center
PLoS ONE | Year: 2013

Unlike anemias, most thrombocytopenias cannot be separated into those due to impaired production and those due to accelerated consumption. While rapid clearance of labeled platelets from the bloodstream can be followed in thrombocytopenic individuals, no model exists for quantitatively inferring from autologous or allogeneic platelet consumption data what changes in random consumption, lifespan dependent consumption, and platelet production rate may have caused the thrombocytopenia. Here we describe a numerical analysis model which resolves these issues. The model applies three parameter values (a random consumption rate constant, a lognormally-distributed platelet lifespan, and the standard deviation of the latter) to a matrix comprising a series of platelet cohorts which are sequentially produced and fractionally consumed in a series of time intervals. The cohort platelet counts achieved after equilibration of production and consumption both enumerate the population age distribution and sum to the population platelet count. Continued platelet consumption after production is halted then serves to model in vivo platelet consumption data, with consumption rate in the first such interval defining the equilibrium platelet production rate. We use a least squares fitting procedure to find parameter values which best fit observed platelet consumption data obtained in WT and thrombocytopenic WASP(-) mice. Equilibrium platelet age distributions are then 'grafted' into the matrix to allow modeling of the consumption of WT platelets in WASP(-) recipients, and vice versa. The optimal parameter values obtained indicate that random WT platelet consumption accounts for a larger fraction of platelet turnover than was previously suspected. Platelet WASP deficiency accelerates random consumption, and a trans effect of recipient WASP deficiency contributes to this. Application of the model to clinical data will allow distinctions to be made between thrombocytopenias due primarily to impaired platelet production and those due to acceleration of random or lifespan-dependent platelet consumption. Source


Strom T.S.,University of Tennessee Health Science Center | Strom T.S.,Memphis Veterans Administration Medical Center | Anur P.,Oregon Health And Science University | Prislovsky A.,Memphis Veterans Administration Medical Center
PLoS ONE | Year: 2011

The study of ex vivo phagocytosis via flow cytometry requires that one distinguish experimentally between uptake and adsorption of fluorescently labeled targets by phagocytes. Removal of the latter quantity from the analysis is the most common means of analyzing such data. Because the probability of phagocytosis is a function of the probability of adsorption, and because partially quenched fluorescence after uptake often overlaps with that of negative controls, this approach is suboptimal at best. Here, we describe a numerical analysis model which overcomes these limitations. We posit that the random adsorption of targets to macrophages, and subsequent phagocytosis, is a function of three parameters: the ratio of targets to macrophages (m), the mean fluorescence intensity imparted to the phagocyte by the internalized target (alpha), and the probability of phagocytosis per adsorbed target (p). The potential values of these parameters define a parameter space and their values at any point in parameter space can be used to predict the fraction of adsorption(+) and [adsorption(-), phagocytosis(+)] cells that might be observed experimentally. By systematically evaluating the points in parameter space for the latter two values and comparing them to experimental data, the model arrives at sets of parameter values that optimally predict such data. Using activated THP-1 cells as macrophages and platelets as targets, we validate the model by demonstrating that it can distinguish between the effects of experimental changes in m, alpha, and p. Finally, we use the model to demonstrate that platelets from a congenitally thrombocytopenic WAS patient show an increased probability of ex vivo phagocytosis. This finding correlates with other evidence that rapid in vivo platelet consumption contributes significantly to the thrombocytopenia of WAS. Our numerical analysis method represents a useful and innovative approach to multivariate analysis. Source


Prislovsky A.,Memphis Veterans Administration Medical Center | Strom T.S.,Memphis Veterans Administration Medical Center | Strom T.S.,University of Tennessee Health Science Center
Experimental Hematology | Year: 2013

Thrombocytopenia caused by rapid platelet consumption contributes to the severe thrombocytopenia of Wiskott-Aldrich syndrome (WAS) and to the milder thrombocytopenia seen in murine WAS. We show that rapid clearance of 111In-labeled murine WASP(-) platelets correlates with enhanced splenic uptake. Using platelets labeled with a pH-sensitive fluorescent marker (pHrodo), we quantify normal platelet uptake by red pulp macrophages (RPMs), and demonstrate its enhancement after invivo opsonization of platelets. The spleens of WASP(-) mice contain an increased number of RPM, and rapid clearance of WASP(-) platelets in WASP(-) mice in turn generates an increased number of pHrodo(+) splenic RPMs. To separately assess the platelet intrinsic and recipient-dependent functions involved in the clearance and splenic phagocyte uptake of WASP(-) platelets, we performed "crossed" pHrodo(+) platelet injection studies (wild type [WT] to WASP(-), WASP(-) to WT). We show that an extrinsic effect of recipient WASP deficiency on the clearance of WASP(-) platelets correlates with increased platelet uptake by RPMs. An intrinsic effect of platelet WASP deficiency on platelet clearance does not, however, correlate with increased total uptake by WT or WASP(-) RPMs. In contrast to other published findings, we find no evidence of a baseline or antibody-induced increase in phosphatidyl serine exposure on WASP(-) platelets. Our findings suggest that an increased number of RPMs in WASP(-) mice contributes significantly to the increased platelet consumption rate in WASP(-) mice. This might explain the consistent efficacy of splenectomy in murine and clinical WAS. © 2013. Source

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