171 research outputs found

    Probability and Nonlocality in Many Minds Interpretations of Quantum Mechanics

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    We argue that a certain type of many minds (and many worlds) interpretations of quantum mechanics due to Lockwood (and Deutsch) do not provide a coherent interpretation of the quantum mechanical probabilistic algorithm. By contrast, in Albert and Loewer's version of the many minds interpretation there is a coherent interpretation of the quantum mechanical probabilities. We consider Albert and Loewer's probability interpretation in the context of Bell-type and GHZ-type states and argue that it exhibits a certain form of nonlocality which is, however, much weaker than Bell's nonlocality.Comment: 22 pages, last section rewritten, to appear in British Journal for the Philosophy of Scienc

    Bone marrow precursors of nonobese diabetic mice develop into defective macrophage-like dendritic cells in vitro

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    The NOD mouse spontaneously develops autoimmune diabetes. Dendritic cells (DC) play a crucial role in the autoimmune response. Previous studies have reported a defective DC generation in vitro from the NOD mouse bone marrow (BM), but a deviated development of myeloid precursors into non-DC in response to GM-CSF was not considered. In this study, we demonstrate several abnormalities during myeloid differentiation of NOD BM precursors using GM-CSF in vitro. 1) We found reduced proliferation and increased cell death in NOD cultures, which explain the previously reported low yield of DC progeny in NOD. Cell yield in NOR cultures was normal. 2) In a detailed analysis GM-CSF-stimulated cultures, we observed in both NOD and NOR mice an increased frequency of macrophages, identified as CD11c(+)/MHCII(-) cells with typical macrophage morphology, phenotype, and acid phosphatase activity. This points to a preferential maturation of BM precursors into macrophages in mice with the NOD background. 3) The few CD11c(+)/MHCII(high) cells that we obtained from NOD and NOR cultures, which resembled prototypic mature DC, appeared to be defective in stimulating allogeneic T cells. These DC had also strong acid phosphatase activity and elevated expression of monocyte/macrophage markers. In conclusion, in this study we describe a deviated development of myeloid BM precursors of NOD and NOR mice into macrophages and macrophage-like DC in vitro. Potentially, these anomalies contribute to the dysfunctional regulation of tolerance in NOD mice yet are insufficient to induce autoimmune diabetes because they occurred partly in NOR mice

    Explaining the unobserved: why quantum mechanics is not only about information

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    A remarkable theorem by Clifton, Bub and Halvorson (2003)(CBH) characterizes quantum theory in terms of information--theoretic principles. According to Bub (2004, 2005) the philosophical significance of the theorem is that quantum theory should be regarded as a ``principle'' theory about (quantum) information rather than a ``constructive'' theory about the dynamics of quantum systems. Here we criticize Bub's principle approach arguing that if the mathematical formalism of quantum mechanics remains intact then there is no escape route from solving the measurement problem by constructive theories. We further propose a (Wigner--type) thought experiment that we argue demonstrates that quantum mechanics on the information--theoretic approach is incomplete.Comment: 34 Page

    Aberrant levels of hematopoietic/neuronal growth and differentiation factors in euthyroid women at risk for autoimmune thyroid disease

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    Background Subjects at risk for major mood disorders have a higher risk to develop autoimmune thyroid disease (AITD) and vice-versa, implying a shared pathogenesis. In mood disorder patients, an abnormal profile of hematopoietic/neuronal growth factors is observed, suggesting that growth/differentiation abnormalities of these cell lineages may predispose to mood disorders. The first objective of our study was to investigate whether an aberrant profile of these hematopoietic/neuronal growth factors is also detectable in subjects at risk for AITD. A second objective was to study the inter relationship of these factors with previously determined and published growth factors/cytokines in the same subjects. Methods We studied 64 TPO-Ab-negative females with at least 1 first-or second-degree relative with AITD, 32 of whom did and 32 who did not seroconvert to TPO-Ab positivity in 5-year follow-up. Subjects were compared with 32 healthy controls (HCs). We measured serum levels of brain-derived neurotrophic factor (BDNF), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF) and IL-7 at baseline. Results BDNF was significantly lower (8.2 vs 18.9 ng/ml, P<0.001), while EGF (506.9 vs 307.6 pg/ml, P = 0.003) and IGFBP-2 (388.3 vs 188.5 ng/ml, P = 0.028) were significantly higher in relatives than in HCs. Relatives who seroconverted in the next 5 years had significantly higher levels of SCF than non-seroconverters (26.5 vs 16.7 pg/ml, P = 0.017). In a cluster analysis with the previously published growth factors/cytokines SCF clustered together with IL-1ÎČ, IL-6 and CCL-3, of which high levels also prec

    Aspirin: A review of its neurobiological properties and therapeutic potential for mental illness

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    There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor-α and interleukin (IL)--6, but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders

    An Alternative Interpretation of Statistical Mechanics

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    In this paper I propose an interpretation of classical statistical mechanics that centers on taking seriously the idea that probability measures represent complete states of statistical mechanical systems. I show how this leads naturally to the idea that the stochasticity of statistical mechanics is associated directly with the observables of the theory rather than with the microstates (as traditional accounts would have it). The usual assumption that microstates are representationally significant in the theory is therefore dispensable, a consequence which suggests interesting possibilities for developing non-equilibrium statistical mechanics and investigating inter-theoretic answers to the foundational questions of statistical mechanics

    MxA as a clinically applicable biomarker for identifying systemic interferon type I in primary Sjögren's syndrome

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    Objective: To establish an easy and practical assay for identifying systemic interferon (IFN) type I bioactivity in patients with primary Sjögren's syndrome (pSS). The IFN type I signature is present in over half of the pSS patients and identifies a subgroup with a higher disease activity. This signature is currently assessed via laborious expression profiles of multiple IFN type I-inducible genes. Methods: In a cohort of 35 pSS patients, myxovirus-resistance protein A (MxA) was assessed as a potential biomarker for ty

    Hospital Admissions Due to Ischemic Heart Diseases and Prescriptions of Cardiovascular Diseases Medications in England and Wales in the Past Two Decades

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    Objectives: The aim of this study was to explore the trend of ischemic heart disease (IHD) admission and the prescriptions of IHD medications in England and Wales. Methods: A secular trends study was conducted during the period of 1999 to 2019. We extracted hospital admission data for patients from all age groups from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Prescriptions of IHD medications were extracted from the Prescription Cost Analysis database from 2004 to 2019. The chi-squared test was used to assess the difference between the admission rates and the difference between IHD medication prescription rates. The trends in IHD-related hospital admission and IHD-related medication prescription were assessed using a Poisson model. The correlation between hospital admissions for IHD and its IHD medication-related prescriptions was assessed using the Pearson correlation coefficient. Results: Our study detected a significant increase in the rate of cardiovascular disease (CVD) medication prescriptions in England and Wales, representing a rise in the CVD medications prescription rate of 41.8% (from 539,334.95 (95% CI = 539,286.30–539,383.59) in 2004 to 764,584.55 (95% CI = 764,545.55–764,623.56) in 2019 prescriptions per 100,000 persons), with a mean increase of 2.8% per year during the past 15 years. This increase was connected with a reduction in the IHD hospital admission rate by 15.4% (from 838.50 (95% CI = 836.05–840.94) in 2004 to 709.78 (95% CI = 707.65–711.92) in 2019 per 100,000 persons, trend test, p < 0.01), with a mean decrease of 1.02% per year during the past 15 years and by 5% (from 747.43 (95% CI = 745.09–749.77) in 1999 to 709.78 (95% CI = 707.65–711.92) in 2019 per 100,000 persons, trend test, p < 0.01) with a mean decrease of 0.25% per year during the past two decades in England and Wales. Conclusion: The rate of hospitalisation due to IHD has decreased in England and Wales during the past two decades. Hospitalisation due to IHD was strongly and negatively correlated with the increase in the rates of dispensing of IHD-related medications. Other factors contributing to this decline could be the increase in controlling IHD risk factors during the past few years. Future studies exploring other risk factors that are associated with IHD hospitalisation are warranted

    Feasibility and acceptability of Problem Management Plus (PM+) among Syrian refugees and asylum seekers in Switzerland: a mixed-method pilot randomized controlled trial

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    Background: Syrian refugees in Switzerland face several barriers in accessing mental health care. Cost-effective psychological interventions are urgently needed to meet the mental health needs of refugees. Problem Management Plus (PM+) is an evidence-based, psychological intervention delivered by trained non-specialist ‘helpers’. Objective: To assess the feasibility and acceptability of PM+ among Syrian refugees in Switzerland. Methods: We conducted a single-blind pilot randomized controlled trial (RCT) with Syrian refugees impaired by psychological distress (K10 > 15 and WHODAS 2.0 > 16). Participants were randomized to PM+ or Enhanced Treatment As Usual (ETAU). Participants were assessed at baseline, and 1 week and 3 months after the intervention, and completed measures indexing mental health problems and health care usage. Semi-structured interviews were conducted with different stakeholders. Results: N = 59 individuals were randomized into PM+ (n = 31) or ETAU (n = 28). N = 18 stakeholders were interviewed about facilitators and barriers for the implementation of PM+. Retention rates in the trial (67.8%) and mean intervention attendance (M = 3.94 sessions, SD = 1.97) were high. No severe events related to the study were reported. These findings indicate that the trial procedures and PM+ were feasible, acceptable and safe. Conclusions: The findings support the conduct of a definitive RCT and show that PM+ might have the potential to be scaled-up in Switzerland. The importance, as well as the challenges, of implementing and scaling-up PM+ in high-income countries, such as Switzerland, are discussed

    An activated set point of T-cell and monocyte inflammatory networks in recent-onset schizophrenia patients involves both pro- and anti-inflammatory forces

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    We recently described a pro-inflammatory gene expression signature in the monocytes of 60% of patients with recent-onset schizophrenia (SCZ). Here we investigated whether the T-cell system is also in a pro-inflammatory state. A detailed fluorescence-activated cell sorting (FACS) analysis, e. g. of CD3(+) CD25(+) T cells, IFN-gamma(+), IL-4(+), IL-17A(+) (CD4(+)) lymphocytes and CD4(+) CD25(high)FoxP3(+) regulatory T cells, was performed on peripheral blood of 26 patients with recent-onset SCZ (in 19 of whom the inflammatory gene expression signature of the monocyte had been determined) and in age-/gender-matched healthy controls. Various relevant T-cell cytokines, e.g. sCD25, IFN-gamma, IL-17A and IL-4, were measured in serum by a multiplex assay. We detected : (a) not only higher percentages of pro-inflammatory-prone monocytes, activated CD3(+) CD25(+) T cells and pro-inflammatory Th17 cells in patients, but also higher percentages of anti-inflammatory CD4(+) CD25(high)FoxP3(+) regulatory T cells and IL-4(+) lymphocytes; (b) that this activated T-cell set point was reflected in significantly raised serum levels of sCD25; (c) that the up-regulation of IL-4(+)-containing lymphocytes was predominantly found in patients characterized by a monocyte pro-inflammatory set point; and (d) that regulatory T-cell and Th17-cell numbers were higher in patients irrespective of the pro-inflammatory state of the monocytes. Our data do not support the concept that the T-cell system is in a simple pro-inflammatory state in recent-onset SCZ, but do show that the monocyte and T-cell networks are activated and involve both pro-and anti-inflammatory forces. This suggests control within an activated inflammatory system
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