2,939 research outputs found
Bungeâs Mathematical Structuralism Is Not a Fiction
In this paper, I explore Bungeâs fictionism in philosophy of mathematics. After an overview of Bungeâs views, in particular his mathematical structuralism, I argue that the comparison between mathematical objects and fictions ultimately fails. I then sketch a different ontology for mathematics, based on Thomassonâs metaphysical work. I conclude that mathematics deserves its own ontology, and that, in the end, much work remains to be done to clarify the various forms of dependence that are involved in mathematical knowledge, in particular its dependence on mental/brain states and material objects
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A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.
BackgroundNovel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use.MethodsOur mixed methods approach comprised literature review, clinician consultation (n =â3), and qualitative and quantitative analysis of two stages of patient interview data (n =â14, n =â18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30.ResultsUnique symptom (n =â54) and impact (n =â72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n =â13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n =â7 symptom; n =â3 impact) were selected for the MDS/AML/CMML context.ConclusionSupplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning
CT findings and patterns of e-cigarette or vaping product use-associated lung injury: A multicenter cohort of 160 cases
BACKGROUND: e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown.
RESEARCH QUESTION: What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior?
STUDY DESIGN AND METHODS: CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was defined as diffuse CNs with little or no GGO, whereas a mixed OP pattern was a combination of the two. Other patterns included diffuse alveolar damage (DAD), acute eosinophilic-like pneumonia, and pulmonary hemorrhage. Cases were classified as atypical if they did not fit into a pattern. Imaging findings, pattern frequencies, and injury severity were correlated with substance vaped (marijuana derives [tetrahydrocannabinol] [THC] only, nicotine derivates only, and both), vaping frequency, regional geography, and state recreational THC legality. One-way analysis of variance, Ï
RESULTS: A total of 160 patients (79.4% men) with a mean age of 28.2 years (range, 15-68 years) with EVALI underwent CT scan. Seventy-seven (48.1%), 15 (9.4%), and 68 (42.5%) patients admitted to vaping THC, nicotine, or both, respectively. Common findings included diffuse or lower lobe GGO with subpleural (78.1%), lobular (59.4%), or peribronchovascular (PBV) sparing (40%). Septal thickening (50.6%), lymphadenopathy (63.1%), and CNs (36.3%) were common. PBV sparing was associated with younger age (P = .02). Of 160 subjects, 156 (97.5%) had one of six defined patterns. Parenchymal, airway-centered, and mixed OP patterns were seen in 89 (55.6%), 14 (8.8%), and 32 (20%) patients, respectively. Acute eosinophilic-like pneumonia (six of 160, 3.8%), DAD (nine of 160, 5.6%), pulmonary hemorrhage (six of 160, 3.8%), and atypical (four of 160, 2.5%) patterns were less common. Increased vaping frequency was associated with more severe injury (P = .008). Multivariable analysis showed a negative association between vaping for \u3e 6 months and DAD pattern (P = .03). Two subjects (1.25%) with DAD pattern died. There was no relation between pattern and injury severity, geographic location, and state legality of recreational use of THC.
INTERPRETATION: EVALI typically causes an OP pattern but exists on a spectrum of acute lung injury. Vaping habits do not correlate with CT patterns except for negative correlation between vaping \u3e 6 months and DAD pattern. PBV sparing, not previously described in acute lung injury, is a common finding
Genetic Susceptibility Determines ÎČ-Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird 76)
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The Current Density Distribution in a Segmented-in-Series SOFC,â
A common tubular solid oxide fuel cell (SOFC) design consists of segmented-in-serie
Reasons, Coherence, and Group Rationality
Philosophy and Phenomenological Research, EarlyView
Phenomenological modelling of damage in polymer blends
To describe the constitutive behaviour of a certain class of polymer blends an elastoperfectly-viscoplastic and creep damageable material characterization is proposed. For a composite of 80 % Polystyrene and 20 % Ethylene Propylene Diene Monomer rubber (PSIEPDM) the specific parameters are determined from tensile tests in a particular range of strain velocities. To investigate the applicability of the model, the results of a finite element analysis for a laterally loaded thin plate (plane stress) with a circular hole are compared to measurements. Numerically calculated values are in reasonable agreement with reality; discrepancies can be ascribed to noise in experimental data. The finite element approach is evaluated with respect to the occurrence of mesh-dependence. Mesh-refinement shows convergence of solutions, attributable to the stabilizing influence of the viscous contribution in the constitutive equations
Dipeptidyl-peptidase-4 inhibitors and pancreatic cancer: a cohort study
AimsâDipeptidyl-peptidase-4 inhibitors (DPP-4i) have been implicated with an increased pancreatic cancer risk. We therefore compared pancreatic cancer incidence and diagnostic work-up among initiators of DPP-4i versus sulfonylureas (SU) and thiazolidinediones (TZD). MethodsâMedicare claims data were examined in a new-user active-comparator cohort study. Patients >65 years with no prescriptions for DPP-4i, SU or TZD at baseline were included if they had at least two claims for the same drug within 180 days. Using an as-treated approach and propensity score-adjusted Cox models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer. Diagnostic work-up was compared using risk ratios (RR). RESULTSâIn the DPP-4i vs SU comparison, there were 18,179 DPP4i initiators of which 26 developed pancreatic cancer (follow-up time interquartile range 5â18 months). In the DPP-4i vs TZD comparison there were 29,366 DPP-4i initiators and 52 developed pancreatic cancer. The hazard of pancreatic cancer with DPP-4i was lower relative to SU (HR=0.6, CI 0.4â0.9) and similar to TZD (HR=1.0, CI 0.7â1.4). Excluding first 6 months of follow-up to reduce the potential for reverse causality did not alter results. Probability of diagnostic work-up post-initiation among DPP-4i initiators (79.3%) was similar to TZD (74.1%) (RR=1.06, CI 1.05â1.07) and SU (74.6%) (RR=1.06, CI1.05â1.07). The probability of diagnostic workup pre-index was ~80% for all cohorts. ConclusionâThough limited by sample size and the observed duration of treatment in the US, our well-controlled population based study suggests no increased short-term pancreatic cancer risk with DPP-4i relative to SU or TZD
A KRAB/KAP1-miRNA Cascade Regulates Erythropoiesis Through Stage-Specific Control of Mitophagy
During hematopoiesis, lineage- and stage-specific transcription factors work in concert with chromatin modifiers to direct the differentiation of all blood cells. We explored the role of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor KAP1 in this process. In mice, hematopoietic-restricted deletion of Kap1 resulted in severe hypoproliferative anemia. Kap1-deleted erythroblasts failed to induce mitophagy-associated genes and retained mitochondria. This was due to persistent expression of microRNAs (miRNAs) targeting mitophagy transcripts, itself secondary to a lack of repression by stage-specific KRAB-ZFPs. The KRAB/KAP1-miRNA regulatory cascade is evolutionarily conserved, as it also controls mitophagy during human erythropoiesis. Thus, a multilayered transcription regulatory system is present, in which protein- and RNA-based repressors are superimposed in combinatorial fashion to govern the timely triggering of an important differentiation event
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