This paper proposes a general class of regression models for continuous proportions when the data contain zeros or ones. The proposed class of models assumes that the response variable has a mixed ...continuous–discrete distribution with probability mass at zero or one. The beta distribution is used to describe the continuous component of the model, since its density has a wide range of different shapes depending on the values of the two parameters that index the distribution. We use a suitable parameterization of the beta law in terms of its mean and a precision parameter. The parameters of the mixture distribution are modeled as functions of regression parameters. We provide inference, diagnostic, and model selection tools for this class of models. A practical application that employs real data is presented.
Abstract (C–X–C motif) ligand (CXCL)10 (CXCL10) belongs to the ELR− CXC subfamily chemokine. CXCL10 exerts its function through binding to chemokine (C–X–C motif) receptor 3 (CXCR3), a seven ...trans-membrane receptor coupled to G proteins. CXCL10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, autoimmune thyroiditis, Graves' disease and ophthalmopathy), or systemic (such as rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, mixed cryoglobulinemia, Sjögren syndrome, or systemic sclerosis). The secretion of CXCL10 by cluster of differentiation (CD)4 +, CD8 +, natural killer (NK) and NK-T cells is dependent on interferon (IFN)-γ, which is itself mediated by the interleukin-12 cytokine family. Under the influence of IFN-γ, CXCL10 is secreted by several cell types including endothelial cells, fibroblasts, keratinocytes, thyrocytes, preadipocytes, etc. Determination of high level of CXCL10 in peripheral fluids is therefore a marker of host immune response, especially T helper (Th)1 orientated T-cells. In tissues, recruited Th1 lymphocytes may be responsible for enhanced IFN-γ and tumor necrosis factor-α production, which in turn stimulates CXCL10 secretion from a variety of cells, therefore creating an amplification feedback loop, and perpetuating the autoimmune process. Further studies are needed to investigate interactions between chemokines and cytokines in the pathogenesis of autoimmune diseases and to evaluate whether CXCL10 is a novel therapeutic target in various autoimmune diseases.
Inflated beta distributions Ospina, Raydonal; Ferrari, Silvia L. P.
Statistical papers (Berlin, Germany),
2010/1, Letnik:
51, Številka:
1
Journal Article
Recenzirano
This paper considers the issue of modeling fractional data observed on 0,1), (0,1 or 0,1. Mixed continuous-discrete distributions are proposed. The beta distribution is used to describe the ...continuous component of the model since its density can have quite different shapes depending on the values of the two parameters that index the distribution. Properties of the proposed distributions are examined. Also, estimation based on maximum likelihood and conditional moments is discussed. Finally, practical applications that employ real data are presented.
•We define the one-parameter discrete Bell distribution, which has a simple form for its probability mass function.•It is shown to be a particular solution of a multiple Poisson process.•It is useful ...for modeling count data with greater variability than the Poisson distribution allows.•We introduce a Bell regression model with statistical inference procedures, diagnostic tools, and computer implementation.•An application to real data suggests that the new model is useful in practice.
In this paper we define and study the one-parameter discrete Bell distribution, which has a very simple form for its probability mass function. In particular, we show that this discrete distribution is a particular solution of a multiple Poisson process. By considering the distribution studied in this article, we introduce a new regression model where the response variable is a count. Further, residuals are also proposed for the new count regression model. An empirical application is considered to show the usefulness of the Bell regression model in practice.
L’articolo intende partire dal concetto di automatismo insito nel luogo comune, inteso nella sua accezione più ampia, per enucleare alcuni punti fondamentali della riflessione di Jean Paulhan, ...direttore della NRF negli anni centrali del Novecento, anche alla luce del contributo di Henri Meschonnic in relazione al proverbio in quanto atto linguistico caratterizzato da ri-enunciabilità. Le considerazioni sul ritmo che ne conseguono, già sfruttate dalle sperimentazioni linguistiche di Paulhan e da dadaisti e surrealisti, vanno nella direzione di riscoprire il côté intersoggettivo che, quale fonte nascosta alla base del luogo comune, permette anche di mettere in discussione e rivitalizzare i cliché stessi. Rielaborazione che funziona da specola nei confronti dei pregiudizi e degli automatismi nascosti nel linguaggio. Verranno così evidenziati i punti di contatto tra la fonte nascosta che sostanzia il luogo comune, il défigement operato da Robert Desnos e le tele di Edward Hopper.
Th1 Chemokines in Autoimmune Endocrine Disorders Fallahi, Poupak; Ferrari, Silvia Martina; Ragusa, Francesca ...
The journal of clinical endocrinology and metabolism,
04/2020, Letnik:
105, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract
Context
The CXC chemokine receptor CXCR3 and its chemokines CXCL10, CXCL9, and CXCL11 are implicated in the pathogenesis of autoimmune diseases. Here, we review these chemokines in ...autoimmune thyroiditis (AT), Graves disease (GD), thyroid eye disease (TED), type 1 diabetes (T1D), and Addison’s disease (AAD).
Evidence Acquisition
A PubMed review of the literature was conducted, searching for the above-mentioned chemokines in combination with AT, GD, TED, T1D, and AAD.
Evidence Synthesis
Thyroid follicular cells in AT and GD, retroorbital cells in TED (fibroblasts, preadipocytes, myoblasts), β cells and islets in T1D, and adrenal cells in AAD respond to interferon-γ (IFN-γ) stimulation producing large amounts of these chemokines. Furthermore, lymphocytes and peripheral blood mononuclear cells (PBMC) are in part responsible for the secreted Th1 chemokines. In AT, GD, TED, T1D, and AAD, the circulating levels of these chemokines have been shown to be high. Furthermore, these chemokines have been associated with the early phases of the autoimmune response in all the above-mentioned disorders. High levels of these chemokines have been associated also with the “active phase” of the disease in GD, and also in TED. Other studies have shown an association with the severity of hypothyroidism in AD, of hyperthyroidism in GD, with severity of TED, or with fulminant T1D.
Conclusion
The reviewed data have shown the importance of the Th1 immune response in different endocrine autoimmune diseases, and many studies have suggested that CXCR3 and its chemokines might be considered as potential targets of new drugs for the treatment of these disorders.
Immune checkpoint inhibitors are drugs that inhibit the “checkpoint molecules”. Different types of cancer immune checkpoint inhibitors have been approved recently: CTLA-4 monoclonal antibodies (as ...ipilimumab); anti-PD-1 monoclonal antibodies (as pembrolizumab and nivolumab); and anti-PD-L1 monoclonal antibodies (as atezolizumab, avelumab, and durmalumab). The increased immune response induced by these agents leads to immune-related adverse events (irAEs), that can vary from mild to fatal, according to the organ system and severity. Immune-related endocrine toxicities are thyroid dysfunctions, hypophysitis, adrenal insufficiency, and type 1 diabetes mellitus, and are usually irreversible in 50%. In particular, hypophysitis is the most frequent anti-CTLA-4-antibodies-related irAE, while thyroid abnormalities (as hypothyroidism, thyrotoxicosis, painless thyroiditis, or even “thyroid storm”) are more frequently associated with anti-PD-1-antibodies. The combination of anti-CTLA-4-antibodies, with anti-PD-1-antibodies, is associated with about 30% of irAEs. Clinical signs and symptoms vary according to the influenced target organ. Endocrinopathies can often be managed by the treating oncologist. However in more severe cases (i.e. in the presence of insulin-dependent diabetes, adrenal insufficiency, or disorders of gonadal hormones, or severe hyperthyroidism, or hypothyroidism, or long-lasting management of hypophysitis) an endocrinological evaluation, and a prompt therapy, are needed.
Biological aging is a process associated with a gradual decline in tissues' homeostasis based on the progressive inability of the cells to self-renew. Cellular senescence is one of the hallmarks of ...the aging process, characterized by an irreversible cell cycle arrest due to reactive oxygen species (ROS) production, telomeres shortening, chronic inflammatory activation, and chromatin modifications. In this review, we will describe the effects of senescence on tissue structure, extracellular matrix (ECM) organization, and nucleus architecture, and see how these changes affect (are affected by) mechano-transduction. In our view, this is essential for a deeper understanding of the progressive pathological evolution of the cardiovascular system and its relationship with the detrimental effects of risk factors, known to act at an epigenetic level.
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