162 research outputs found

    Situational Crisis Communication Theory and the Use of Apologies in Five High-Profile Food-Poisoning Incidents

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    This article examines the role that apologies play in situational crisis communication theory (SCCT) and focuses on a number of recent food-poisoning incidents. The article first establishes the importance of trust to firms with a marketing orientation, and the harm that comes when that trust is lost. This is followed by an overview of apologies versus pseudo-apologies and how both factor into the principles of SCCT. Finally, examples of five high-profile apologies related to food-poisoning incidents are provided and the way that the principles of SCCT were applied in each instance, along with the outcome, is explored

    Novel Biopolymers for the Activation and Expansion of T-cells: Towards 3D Scaffolds for Cell Therapy

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    Chimeric Antigen Receptor (CAR) T-cell therapy is an emerging immunotherapy that exhibits promising results against haematological malignancies. Activation is a crucial step in the manufacturing as it renders T-cells susceptible to transduction, initiates expansion, and the development of effector functions. Ex vivo activation is achieved through stimulation of the T-cell receptor complex and co-stimulation, typically provided by anti-CD3 and anti-CD28 antibodies. Antibody coated magnetic beads are currently the most common activation technology, however, they require an additional process step for removal and release testing for residual beads. Furthermore, the beads are expensive, non-biodegradable, and evidence suggests that they are not optimal for antibody presentation due to aggregation. SpheriTech’s biopolymers are low-cost peptide-based polymers that can be cast into a 3D porous structure to which anti-CD3 and anti-CD28 can be bound. The porous structure allows T-cells to be passed through, eliminating the need for a removal step and increasing the surface area for antibody presentation. This thesis aimed to establish SpheriTech’s biopolymer as an alternative manufacturing option. Fundamental characterisation and initial proof-of-concept studies of two iterations of SpheriTech’s biopolymers are presented; termed polymer A and B. Characterisation included structural characterisation, antibody distribution, and biocompatibility. The first polymer was found to possess a macro-porous structure with a median pore diameter of 7.8 ± 0.2 μm, when produced at densities of 0.04 to 0.07 g/cm3; and polymer B was found to possess a super-macro-porous structure with a median pore diameter of 134 μm. aCD3 and aCD28 were successfully attached to both polymers and confirmed with fluorescence imaging. T-cell cultures stimulated with aCD3/aCD38 polymer A displayed a 19 % population expression of activation marker, CD69, 24 hours post-stimulation. Though polymer A demonstrated the potential for T-cell activation; it was limited by a low cell recovery of T-cells (51 %) from the structure. Polymer B was subsequently investigated and exhibited an improved cell recovery of 97 %. Activation and expansion of primary human T-cells were demonstrated with polymer B in both a non-porous and a porous 3D scaffold format. T-cell cultures stimulated with non-porous aCD3/aCD28 polymer B resulted in a 27 and 44 % expression of activation markers CD25 and CD69, respectively, 3 days post-stimulation. Stimulation resulted in an 8.3-fold expansion with > 90 % viability over 14 days, which was comparable to Dynabeads. Expanded T-cell populations were found to be skewed towards CD8+ T-cells (CD4:CD8 ratio of 0.72), and exhibited a 3.6 % decrease in the expression of exhaustion marker, PD-1, than when activated with Dynabeads. The dominant sub-populations of CD4+ and CD8+ T-cells were found to be TEM (40 %) and TCM (38 %), respectively. T-cell cultures expanded with a porous aCD3/aCD28 polymer B scaffold resulted in an 11-fold expansion with a viability of 88 % after 14 days. Expanded T-cell populations had a CD4:CD8 ratio of 1.2 and consisted predominantly of clinically relevant TCM (50 - 84 %) within both CD8+ and CD4+ populations. Stimulation of T-cells with the polymer scaffold was found to induce IFNγ secretion, indicating the expansion of T-cells with an advantageous cytotoxic function. Hence, this thesis has demonstrated the proof-of-concept of a novel T-cell activation and expansion technology using SpheriTech’s biopolymer matrices

    Use of computed tomography imaging during long-term follow-up of nine feline tuberculosis cases

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    Case series summary: Feline tuberculosis is an increasingly recognised potential zoonosis of cats. Treatment is challenging and prognosis can vary greatly between cases. Pulmonary infection requires extended courses of antibiotics, but methodologies for sensitively monitoring response to treatment are currently lacking. In this case series, we retrospectively examined the serial computed tomography (CT) findings in nine cats that had been diagnosed with tuberculosis. Changes in pathology (where applicable to tuberculosis) were correlated with the clinical presentation of each of the cats, the treatment protocol, and previous and contemporary diagnostic investigations. This study found that changes in CT findings during the medium- to long-term management of feline tuberculosis were highly variable between cats. The majority of cats had reduced pathology at re-examination during anti-tuberculous therapy, but pathology only resolved in a minority of cases. In some cases recurrence of pathology detected by CT imaging preceded clinical deterioration, allowing for rapid therapeutic intervention. Relevance and novel information: When considered in combination with clinical findings, CT studies can aid in decision making regarding tapering of antibiotic protocols, or reintroduction of therapy in cases of recurrence or reinfection. This series also highlights that, in some cases, persistent abnormalities can be detected by CT, so complete resolution of CT pathology should not always be a goal in the management of feline tuberculosis

    Supernova Kicks and Misaligned Microquasars

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    The low-mass X-ray binary microquasar GRO J1655-40 is observed to have a misalignment between the jets and the binary orbital plane. Since the current black hole spin axis is likely to be parallel to the jets, this implies a misalignment between the spin axis of the black hole and the binary orbital plane. It is likely the black holes formed with an asymmetric supernova which caused the orbital axis to misalign with the spin of the stars. We ask whether the null hypothesis that the supernova explosion did not affect the spin axis of the black hole can be ruled out by what can be deduced about the properties of the explosion from the known system parameters. We find that this null hypothesis cannot be disproved but we find that the most likely requirements to form the system include a small natal black hole kick (of a few tens of km/s) and a relatively wide pre-supernova binary. In such cases the observed close binary system could have formed by tidal circularisation without a common envelope phase.Comment: Accepted for publication in MNRA

    Praksisutvikling 2010: Samarbeid mellom høgskole og praksisfelt for utvikling av praksisstudier i sykepleierutdanning

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    Rapporten gir ei framstilling av praksisutviklingsprosjekt ved Høgskolen Stord/Haugesund, Avdeling helsefag i 2009-2010. Prosjekta er gjennomførte i samarbeid mellom høgskolen og praksisfeltet, og har som mål å styrke praksislæringa for studentar ved sjukepleiarutdanninga. Felles for prosjekta er at dei tar utgangspunkt i konkrete praksissituasjonar, og siktar mot å utvikle og betre kvaliteten i læresituasjonen. I denne prosjektporteføljen finn vi prosjekt retta mot kompetanseutvikling for kontaktsjukepleiarar, tilrettelegging av praksisplassar innan palliativ omsorg, strukturering av innkomstsamtalar ved innlegging i sjukehus og studentdeltaking i undersøking av ernæringsforhold blant eldre ved ein sjukeheim. Prosjekta har blitt utførte av prosjektgrupper sett saman av lærarar ved høgskolen og sjukepleiarar med studentansvar ved dei ulike praksisstadene knytt til høgskolen. Prosjekta blei gjennomførte i seks kommunar, ved sjukehus og sjukeheimar. Prosjektgruppene har hatt trefire fellesmøte pr. semester, med erfaringsutveksling og kollektiv, gjensidig rettleiing undervegs i prosessen. Dette fellesskapet har skapt møteplassar mellom høgskole og praksisfelt i ein likeverdig atmosfære og har hatt som funksjon både å auke kvaliteten i praksisstudiane og å bygge bru mellom teori og praksis i sjukepleiarutdanninga

    6-benzothiazolyl ureas, thioureas and guanidines are potent inhibitors of ABAD/17β-HSD10 and potential drugs for Alzheimer's disease treatment : design, synthesis and in vitro evaluation

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    Background : The mitochondrial enzyme amyloid beta-binding alcohol dehydrogenase (ABAD) also known as 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) has been connected with the pathogenesis of Alzheimer’s disease (AD). ABAD/ 17β-HSD10 is a binding site for the amyloid-beta peptide (Aβ) inside the mitochondrial matrix where it exacerbates Aβ toxicity. Interaction between these two proteins triggers a series of events leading to mitochondrial dysfunction as seen in AD. Methods : As ABAD’s enzymatic activity is required for mediating Aβ toxicity, its inhibition presents a promising strategy for AD treatment. In this study, a series of new benzothiazolylurea analogues have been prepared and evaluated in vitro for their potency to inhibit ABAD/ 17β-HSD10 enzymatic activity. The most potent compounds have also been tested for their cytotoxic properties and their ability to permeate through blood-brain barrier has been predicted. To explain the structure-activity relationship QSAR and pharmacophore studies have been performed. Results and Conclusions : Compound 12 was identified being the most promising hit compound with good inhibitory activity (IC50 = 3.06 ± 0.40µM) and acceptable cytotoxicity profile comparable to the parent compound of frentizole. The satisfactory physical-chemical properties suggesting its capability to permeate through BBB make compound 12 a novel lead structure for further development and biological assessment.PostprintPeer reviewe

    Functional electrical stimulation for foot drop in multiple sclerosis: a systematic review and meta-analysis of the effect on gait speed

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    Objective: To review the efficacy of functional electrical stimulation (FES) used for foot drop in people with multiple sclerosis (pwMS) on gait speed in short and long walking performance tests. Data sources: Five databases (Cochrane Library, CINAHL, Embase, MEDLINE, Pubmed) and reference lists were searched. Study selection: Studies of both observational and experimental design where gait speed data in pwMS could be extracted were included. Data extraction: Data were independently extracted and recorded. Methodological quality was assessed using the Effective Public Health Practice Project (EPHPP) tool. Data synthesis: Nineteen studies (described in 20 articles) recruiting 490 pwMS were identified and rated moderate or weak, with none gaining a strong rating. All studies rated weak for blinding. Initial and ongoing orthotic and therapeutic effects were assessed with regards to the impact of FES on gait speed in short and long walking tests. Meta-analyses of the short walk tests revealed a significant initial orthotic effect (t = 2.14, p = 0.016) with a mean increase in gait speed of 0.05 meters per second (m/s) and ongoing orthotic effect (t = 2.81, p = 0.003) with a mean increase of 0.08m/s. There were no initial or ongoing effect on gait speed in long walk tests and no therapeutic effect on gait speed in either short or long walk tests. Conclusions: FES used for foot drop has a positive initial and ongoing effect on gait speed in short walking tests. Further fully-powered randomized controlled trials comparing FES with alternative treatments are required

    Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs

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    The extracellular lysophospholipase D autotaxin (ATX) and its product, lysophosphatidic acid, have diverse functions in development and cancer, but little is known about their functions in the immune system. Here we found that ATX had high expression in the high endothelial venules of lymphoid organs and was secreted. Chemokine-activated lymphocytes expressed receptors with enhanced affinity for ATX, which provides a mechanism for targeting the secreted ATX to lymphocytes undergoing recruitment. Lysophosphatidic acid induced chemokinesis in T cells. Intravenous injection of enzymatically inactive ATX attenuated the homing of T cells to lymphoid tissues, probably through competition with endogenous ATX and exertion of a dominant negative effect. Our results support the idea of a new and general step in the homing cascade in which the ectoenzyme ATX facilitates the entry of lymphocytes into lymphoid organs
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