PRODUCT COMPLEMENTARITY IN PRODUCTION: THE BY-PRODUCT CASE

Production Economics,

The accuracy of Bloemfontein-based Emergency Medical Services providers in recognising sepsis

Background: Sepsis is considered a severe life-threatening medical emergency and globally carries a high mortality. Research suggests early recognition of sepsis can lead to early initiation of treatment and effective communication of this condition to the receiving facility by pre-hospital emergency care (PEC) providers. Depending on system operations, this has been shown to improve patient outcomes. However, sepsis often presents non-specifically, and in the absence of validated pre-hospital sepsis screening tools, less than half of sepsis patients seen by PEC providers are recognised. This study aimed to determine the accuracy with which Bloemfontein-based PEC providers recognise sepsis in a series of patient vignettes. Methods: A series of seven case vignettes were presented to a convenient sample of advanced life support (ALS) and intermediate life support (ILS) PEC providers. The PEC providers were asked to review each vignette and indicate whether the patient described had sepsis or not. The vignettes consisted of a clinical case description with signs and symptoms of patients presenting with or without sepsis, and images were shown where relevant. Elements of the Robson Prehospital Severe Sepsis Screening (RPSS) tool were used to populate the sepsis vignettes. Results: A total of 27 ILS and ALS PEC providers in the Bloemfontein area partook in the research study. Thus, a total of 189 vignettes were evaluated for sepsis. PEC providers, both ILS and ALS, recognised sepsis with a sensitivity of 69.63% and a specificity of 37.04% (PPV 73.44%, NPV 32.79%), indicating an accuracy of 60.32%. Although all participants mentioned some motivations for their answers, none of the participants gave specific cut-off value ranges at which point they would suspect sepsis. Conclusion: This vignette-based study found that PEC providers can recognise sepsis with modest accuracy, echoing previous work on this topic. In addition, the study provides a platform for similar studies, which, in turn, could aid in the development of a validated, pre-hospital sepsis screening tool.&nbsp

Infectious Tolerance: Human CD25+ Regulatory T Cells Convey Suppressor Activity to Conventional CD4+ T Helper Cells

Regulatory CD4+CD25+ T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact–mediated suppression of conventional CD4+ T cells by human CD25+ Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25+ Treg cells. Coactivation of CD25+ Treg cells with Treg cell–depleted CD4+ T cells results in anergized CD4+ T cells that in turn inhibit the activation of conventional, freshly isolated CD4+ T helper (Th) cells. This infectious suppressive activity, transferred from CD25+ Treg cells via cell contact, is cell contact–independent and partially mediated by soluble transforming growth factor (TGF)-β. The induction of suppressive properties in conventional CD4+ Th cells represents a mechanism underlying the phenomenon of infectious tolerance. This explains previously published conflicting data on the role of TGF-β in CD25+ Treg cell–induced immunosuppression

The Monash Simple Climate Model experiments (MSCM-DB v1.0): an interactive database of mean climate, climate change, and scenario simulations

This study introduces the Monash Simple Climate Model (MSCM) experiment database. The simulations are based on the Globally Resolved Energy Balance (GREB) model to study three different aspects of climate model simulations: (1) understanding processes that control the mean climate, (2) the response of the climate to a doubling of the CO2 concentration, and (3) scenarios of external forcing (CO2 concentration and solar radiation). A series of sensitivity experiments in which elements of the climate system are turned off in various combinations are used to address (1) and (2). This database currently provides more than 1300 experiments and has an online web interface for fast analysis and free access to the data. We briefly outline the design of all experiments, give a discussion of some results, put the findings into the context of previously published results from similar experiments, discuss the quality and limitations of the MSCM experiments, and also give an outlook on possible further developments. The GREB model simulation is quite realistic, but the model without flux corrections has a root mean square error in the mean state of the surface temperature of about 10 ∘C, which is larger than those of general circulation models (2 ∘C). It needs to be noted here that the GREB model does not simulate circulation changes or changes in cloud cover (feedbacks). However, the MSCM experiments show good agreement to previously published studies. Although GREB is a very simple model, it delivers good first-order estimates, is very fast, highly accessible, and can be used to quickly try many different sensitivity experiments or scenarios. It builds a basis on which conceptual ideas can be tested to first order and it provides a null hypothesis for understanding complex climate interactions in the context of response to external forcing or interactions in the climate subsystems

NFATc2 and NFATc3 transcription factors play a crucial role in suppression of CD4+ T lymphocytes by CD4+ CD25+ regulatory T cells

The phenotype of NFATc2−/− c3−/− (double knockout [DKO]) mice implies a disturbed regulation of T cell responses, evidenced by massive lymphadenopathy, splenomegaly, and autoaggressive phenomena. The population of CD4+ CD25+ T cells from DKO mice lacks regulatory capacity, except a small subpopulation that highly expresses glucocorticoid-induced tumor necrosis factor receptor family–related gene (GITR) and CD25. However, neither wild-type nor DKO CD4+ CD25+ regulatory T cells (T reg cells) are able to suppress proliferation of DKO CD4+ CD25− T helper cells. Therefore, combined NFATc2/c3 deficiency is compatible with the development of CD4+ CD25+ T reg cells but renders conventional CD4+ T cells unresponsive to suppression, underlining the importance of NFAT proteins for sustaining T cell homeostasis

Mast cell-derived mediators promote murine neutrophil effector functions

Mast cells are able to trigger life-saving immune responses in murine models for acute inflammation. In such settings, several lines of evidence indicate that the rapid and protective recruitment of neutrophils initiated by the release of mast cell-derived pro-inflammatory mediators is a key element of innate immunity. Herein, we investigate the impact of mast cells on critical parameters of neutrophil effector function. In the presence of activated murine bone marrow-derived mast cells, neutrophils freshly isolated from bone marrow rapidly lose expression of CD62L and up-regulate CD11b, the latter being partly driven by mast cell-derived TNF and GM-CSF. Mast cells also strongly enhance neutrophil phagocytosis and generation of reactive oxygen species. All these phenomena partly depend on mast cell-derived TNF and to a greater extend on GM-CSF. Furthermore, spontaneous apoptosis of neutrophils is greatly diminished due to the ability of mast cells to deliver antiapoptotic GM-CSF. Finally, we show in a murine model for acute lung inflammation that neutrophil phagocytosis is impaired in mast cell-deficient Kit W-sh /Kit W-sh mice but can be restored upon mast cell engraftment. Thus, a previously underrated feature of mast cells is their ability to boost neutrophil effector functions in immune response

Mast cells partly contribute to allergic enteritis development: Findings in two different mast cell-deficient mice

Allergic enteritis (AE) is a gastrointestinal form of food allergy. The presence of mast cells and granulocytes has been detected in the inflamed tissues in AE. In this study, we aimed to elucidate the role of mast cells in AE development using two mast cell-deficient mouse strains: KIT(W-sh/W-sh) bearing the W-sash (W(sh)) inversion mutation and Cpa3Cre/+, which lack mast cells due to Cre-mediated mast cell eradication, were used in an AE experimental model. The development of clinical symptoms (e.g. drop in body temperature and weight loss) were abolished in both strains, whereas inflammatory levels of AE (e.g. villous atrophy, edema, and granulocyte accumulation) were reduced mainly in KITW-sh/W-sh mice. FACS analysis of the KITW-sh/W-sh intestinal lamina propria, showed a reduction in the eosinophil (CD45+CD11b+SiglecF+cells) and neutrophil (CD45+CD11b+SiglecF−Ly6G+ cells) accumulation. Cpa3Cre/+ mice showed reduced eosinophil (CD45+CD11b+SiglecF+cells) accumulation, but neutrophil (CD45+CD11b+SiglecF−Ly6G+ cells) accumulation was retained at AE sites. The concentrations of CC chemokine ligand 1 (CCL1), a known CC chemokine receptor 8 ligand leading to eosinophil recruitment, was reduced in intestinal homogenates of both mast cell-deficient mouse strains. These results suggest that mast cells play a role in AE development in part by expressing CCL1 and contributing to eosinophil accumulation at AE. This study offers implications for establishing AE treatments that target infiltrating leucocytes in AE tissues.Fil: Blanco Pérez, Frank. No especifíca;Fil: Gonzalez Menendez, Irene. No especifíca;Fil: Stassen, Michael. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Kato, Yoichiro. Tokyo Women's Medical University; JapónFil: Laiño, Jonathan Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Kirberg, Jörg. No especifíca;Fil: Krause, Maren. No especifíca;Fil: Martella, Manuela. No especifíca;Fil: Shibata, Noriyuki. Tokyo Women's Medical University; JapónFil: Quintanilla-Martinez, Leticia. No especifíca;Fil: Feyerabend, Thorsten B.. No especifíca;Fil: Rodewald, Hans Reimer. No especifíca;Fil: Galli, Stephen J.. University of Stanford; Estados UnidosFil: Vieths, Stefan. No especifíca;Fil: Scheurer, Stephan. No especifíca;Fil: Toda, Masako. No especifíca

International Veterinary Epilepsy Task Force consensus report on epilepsy definition, classification and terminology in companion animals

Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, “a common language”, for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies. In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders

Lament as Transitional Justice

Works of human rights literature help to ground the formal rights system in an informal rights ethos. Writers have developed four major modes of human rights literature: protest, testimony, lament, and laughter. Through interpretations of poetry in Carolyn Forché’s anthology, Against Forgetting, and novels from Rwanda, the United States, and Bosnia, I focus on the mode of lament, the literature of mourning. Lament is a social and ritualized form, the purposes of which are congruent with the aims of transitional justice institutions. Both laments and truth commissions employ grieving narratives to help survivors of human rights trauma bequeath to the ghosts of the past the justice of a monument while renewing the survivors’ capacity for rebuilding civil society in the future. Human rights scholars need a broader, extra-juridical meaning for “transitional justice” if we hope to capture its power