My Paradigm Can Beat Your Paradigm: Some Reflections on Knowledge Conflicts

Disagreements about knowledge generation and application in social work are examined from a paradigmatic level to try to account for the moral indignation often accompanying the disagreements. The positivist paradigm with its pervasive influence on social science inquiry has been challenged in recent times by a more relativistic, interactive, consciousness based paradigm. The problem of standardizing Intersubjectivity , and the process of Inversion of Mastery , are used to examine the paradigm differences. The positivist\u27s accusation that the newer paradigm advocate is irresponsible , and the rejoinder that positivism contributes to a damaging hoax on humankind are the crux of the moral heat of the conflict

Aspirin-Trigge red-Resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury

Acute Lung Injury (ALI) is a severe illness with excess mortality and no specific therapy. Protective actions were recently uncovered for docosahexaenoic acid -derived mediators, including D-series resolvins. Here, we used a murine self-limited model of hydrochloric acid-induced ALI to determine the effects of aspirin-triggered resolvin D1 (AT-RvD1) on mucosal injury. RvD1 and its receptor ALX/FPR2 were identified in murine lung after ALI. AT-RvD1 (~0.5 – 5 μg/kg) decreased peak inflammation, including bronchoalveolar lavage fluid (BALF) neutrophils by ~75%. Animals treated with AT-RvD1 had improved epithelial and endothelial barrier integrity and decreased airway resistance concomitant with increased BALF epinephrine levels. AT-RvD1 inhibited neutrophil-platelet heterotypic interactions by down-regulating both P-selectin and its ligand CD24. AT-RvD1 also significantly decreased levels of BALF pro-inflammatory cytokines, including IL-1β, IL-6, KC and TNF-α, and decreased NF-κB phosphorylated p65 nuclear translocation. Together, these findings indicate that AT-RvD1 displays potent mucosal protection and promotes catabasis after ALI

Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which - once applied to human neutrophils - attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor-deficient mice termed ALX/fpr2/3-/- . These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA

Acute effects of mango leaf extract on cognitive function in healthy adults: a randomised, double-blind, placebo-controlled crossover study

IntroductionExtracts made from the leaves of the edible mango plant (Mangifera indica L., Anacardiaceae) have a long history of medicinal usage, most likely due to the presence of high levels of mangiferin, a polyphenol compound. Previous research has demonstrated that mango leaf extract (MLE) can beneficially modulate cognitive function in both animals and humans. This study aimed to assess the effects of an acute dose of 300 mg MLE (standardised to contain ≥60% mangiferin) on cognitive performance and mood in healthy adults.MethodsIn this double-blind, placebo-controlled, crossover study, 114 healthy men and women (18–43 years) received either MLE or a matched placebo at each testing visit (separated by at least 7 days). Cognitive performance (including the cognitive demand battery) and mood were measured at 30, 180, and 300 min post-dose.ResultsThe results showed that, compared to placebo, the group taking MLE displayed a significant increase in serial 3 s and serial 7 s subtraction errors overall. There were no other significant effects on cognitive performance.DiscussionThe results of the current study suggest that the consumption of 300 mg MLE in the absence of an observed multitasking psychological stressor does not improve cognitive performance or mood at up to 300 min post-dose. Due to the very limited nature of the effects and since they were observed among many analyses, these findings should be treated with caution.Clinical trial registration: http://ClinicalTrials.gov, identifier [NCT05182450]

Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors

The molecular mechanisms leading to aryl hydrocarbon receptor interacting protein (AIP) mutation-induced aggressive, young-onset growth hormone-secreting pituitary tumors are not fully understood. In this study, we have identified that AIP-mutation-positive tumors are infiltrated by a large number of macrophages compared to sporadic tumors. Tissue from pituitary-specific Aip-knockout (AipFlox/Flox;Hesx1Cre/+) mice recapitulated this phenotype. Our human pituitary tumor transcriptome data revealed the "epithelial-to-mesenchymal transition (EMT) pathway" as one of the most significantly altered pathways in AIPpos tumors. Our in vitro data suggest that bone marrow-derived macrophage-conditioned media induces more prominent EMT-like phenotype and enhanced migratory and invasive properties in Aip-knockdown somatomammotroph cells compared to non-targeting controls. We identified that tumor-derived cytokine CCL5 is upregulated in AIP-mutation-positive human adenomas. Aip-knockdown GH3 cell-conditioned media increases macrophage migration, which is inhibited by the CCL5/CCR5 antagonist maraviroc. Our results suggest that a crosstalk between the tumor and its microenvironment plays a key role in the invasive nature of AIP-mutation-positive tumors and the CCL5/CCR5 pathway is a novel potential therapeutic target

Vibrotactile pedals : provision of haptic feedback to support economical driving

The use of haptic feedback is currently an underused modality in the driving environment, especially with respect to vehicle manufacturers. This exploratory study evaluates the effects of a vibrotactile (or haptic) accelerator pedal on car driving performance and perceived workload using a driving simulator. A stimulus was triggered when the driver exceeded a 50% throttle threshold, past which is deemed excessive for economical driving. Results showed significant decreases in mean acceleration values, and maximum and excess throttle use when the haptic pedal was active as compared to a baseline condition. As well as the positive changes to driver behaviour, subjective workload decreased when driving with the haptic pedal as compared to when drivers were simply asked to drive economically. The literature suggests that the haptic processing channel offers a largely untapped resource in the driving environment, and could provide information without overloading the other attentional resource pools used in driving

Evaluating the utility of knowledge-based planning for clinical trials using the TROG 08.03 post prostatectomy radiation therapy planning data

Background and purpose: Poor quality radiotherapy can detrimentally affect outcomes in clinical trials. Our purpose was to explore the potential of knowledge-based planning (KBP) for quality assurance (QA) in clinical trials. Materials and methods: Using 30 in-house post-prostatectomy radiation treatment (PPRT) plans, an iterative KBP model was created according to the multicentre clinical trial protocol, delivering 64 Gy in 32 fractions. KBP was used to replan 137 plans. The KB (knowledge based) plans were evaluated for their ability to fulfil the trial constraints and were compared against their corresponding original treatment plans (OTP). A second analysis between only the 72 inversely planned OTPs (IP-OTPs) and their corresponding KB plans was performed. Results: All dose constraints were met in 100% of KB plans versus 69% of OTPs. KB plans demonstrated significantly less variation in PTV coverage (Mean dose range: KB plans 64.1 Gy-65.1 Gy vs OTP 63.1 Gy-67.3 Gy, p \u3c 0.01). KBP resulted in significantly lower doses to OARs. Rectal V60Gy and V40Gy were 17.7% vs 27.7% (p \u3c 0.01) and 40.5% vs 53.9% (p \u3c 0.01) for KB plans and OTP respectively. Left femoral head (FH) V45Gy and V35Gy were 0.4% vs 7.4% (p \u3c 0.01) and 7.9% vs 34.9% (p \u3c 0.01) respectively. In the second analysis plan improvements were maintained. Conclusions: KBP created high quality PPRT plans using the data from a multicentre clinical trial in a single optimisation. It is a powerful tool for utilisation in clinical trials for patient specific QA, to reduce dose to surrounding OARs and variations in plan quality which could impact on clinical trial outcomes

Asymmetric mid-plane gas in ALMA images of HD 100546

In this paper we present new ALMA observations towards the proto-planet hosting transitional disc of Herbig Ae/Be star HD 100546. This includes resolved 1.3 mm continuum, $^{13}$CO and the first detection of C$^{18}$O in this disc, which displays azimuthal asymmetry in regions spatially coincident with structures previously identified in HST images related to spiral arms. The lower limit on the mass of the dust disc is calculated to be 9.6x10$^{-4}$M$_\odot$. A firm lower-limit on the total gas mass calculated from optically thin, mid-plane tracing C$^{18}$O (2-1) emission is 0.018M$_\odot$ assuming ISM abundances. These mass estimates provide an estimate of gas-to-dust ratio in the disc of 19, the ratio will increase if C$^{18}$O is relatively under-abundant in the disc compared to CO and H2. Through deprojection and azimuthal averaging of the image plane we detect 1.3 mm continuum emission out to 290+/-10 au,$^{13}$CO to 390+/-10 au and C$^{18}$O to 300+/-10au. We measure a radially increasing millimetre spectral index between wavelengths of 867$\mu$m and 1.3 mm, which shows that grain sizes increase towards the star, with solid particles growing to cm scales in the inner disc

Planet formation in intermediate-separation binary systems

ABSTRACT We report the first characterization of the individual discs in the intermediate-separation binary systems KK Oph and HD 144668 at millimetre wavelengths. In both systems, the circumprimary and the circumsecondary discs are detected in the millimetre continuum emission, but not in 13CO nor C18O lines. Even though the disc structure is only marginally resolved, we find indications of large-scale asymmetries in the outer regions of the primary discs, most likely due to perturbation by the companion. The derived dust masses are firmly above debris disc level for all stars. The primaries have about three times more dust in their discs than the secondaries. In the case of HD 144668, the opacity spectral index of the primary and secondary differ by a large margin of 0.69, which may be a consequence of the secondary disc being more compact. Upper limits on the gas masses imply less than 0.1 Mjup in any of these discs, meaning that giant planets can no longer form in them. Considering that there have been no massive gas discs identified to date in intermediate-separation binaries (i.e. binaries at a few hundred au separation), this opens space for speculation whether their binarity causes the removal of gas, with tidal interaction truncating the discs and hence shortening the accretion time-scale. More systematic studies in this respect are sorely needed.</jats:p