Discourses on Fantasy: A Narrative Allegory

This project, though officially designated by the English Department as a creative thesis, is really a hybrid work that combines creative writing with literary criticism. The work is structured as a dream vision, a literary genre popular in the Middle Ages in which a narrator receives some form of instruction or wisdom through an allegorical dream. Examples include The Pearl, The Romance of the Rose, and Chaucer\u27s House of Fame. In this thesis, the allegorical space of the dream vision provides a platform for a series of essays structured as dialogues. These dialogues explore the aesthetics and politics of modern fantasy and supernatural literature, focusing particularly on the opposition of this literature, which often draws on ancient and medieval source material, to modern capitalist society. The discourses themselves are not strictly critical, but incorporate subjectivity, metaphor, and symbolism in their investigation of cultural texts

Patterns and determinants of response to novel therapies in juvenile and adult-onset polyarthritis

Biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Amongst these, polyarticular Juvenile-Idiopathic Arthritis (pJIA) and Rheumatoid Arthritis (RA) display similarities in terms of disease pathophysiology and response pattern to b/tsDMARDs. Indeed, therapeutic efficacy of novel targeted drugs is variable among individual patients, in both RA and pJIA. Mechanisms and determinants of this heterogeneous response are diverse and complex, such that development of true “precision”-medicine strategies has proven highly challenging. In this review, we will discuss pathophysiological, patient-specific, drug-specific and environmental factors contributing to individual therapeutic response in polyarticular JIA in comparison to what is known in RA. Although some biomarkers have been identified that stratify for the likelihood of either therapeutic response or non-response, few have proved useful in clinical practice so far, likely due to the complexity of treatment-response mechanisms. Consequently, we propose a pragmatic, patient-centered and clinically-based approach, i.e. personalized instead of biomarker-based precision medicine in JIA

Left ventricular diverticulum: incidental finding on dual source cardiac ct

The purpose of this retrospective study is to describe the prevalence, size and location of left ventricular (LV) diverticulum- diverticuli on cardiac dual source CT. Dual source computed tomography cardiac angiography (DS CTCA) was performed in 482 patients. Where literature states their rare occurrence, this retrospective study demonstrates the fairly common finding of incidental LV diverticulum on DS CTCA examinations. LV diverticuli were found incidentally in 20 out of 482 patients (4.1%), a substantially higher incidence than previously reported. Although diverticuli were most common along the inferoseptal wall (45%) they also occurred in all parts of the left ventricular wall. Multiple diverticuli were found in 30% of patients. Dimensions of the LV diverticuli varied enormously. LV diverticuli are reported to be frequently associated with other congenital anomalies. Complications ranging from sudden death and heart failure to embolic events have been described in literature. No relevant associated anomaly or complication was present in the studied 20 patients. Our data support the hypothesis that LV diverticuli, incidentally found in adulthood, follow a benign course and can be managed conservatively. More knowledge is however required to understand history and prognosis about this condition

Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling

This article presents a mechanism of action hypothesis to explain the rapid antidepressant effects of esmethadone (REL-1017) and other uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists and presents a corresponding mechanism of disease hypothesis for major depressive disorder (MDD). Esmethadone and other uncompetitive NMDAR antagonists may restore physiological neural plasticity in animal models of depressive-like behavior and in patients with MDD via preferential tonic block of pathologically hyperactive GluN2D subtypes. Tonic Ca2+ currents via GluN2D subtypes regulate the homeostatic availability of synaptic proteins. MDD and depressive behaviors may be determined by reduced homeostatic availability of synaptic proteins, due to upregulated tonic Ca2+ currents through GluN2D subtypes. The preferential activity of low-potency NMDAR antagonists for GluN2D subtypes may explain their rapid antidepressant effects in the absence of dissociative side effects

Cama de frango como substrato para a produção de biogás após diferentes períodos de estocagem.

RESUMO: Na avicultura a cama de frango é produzida sazonalmente, em função do modo de produção. Para obter energia do biogás por meio da biodigestão da cama de frango, de forma contínua, o armazenamento do resíduo pode ser uma solução. Ensaios de Potencial Bioquímico de Metano (BMP) foram utilizados neste trabalho para estimar a capacidade de produção de biogás e metano da cama de frango removida após o sexto lote de reutilização e a diferentes tempos de armazenamento após a coleta, assim, verificar a viabilidade de utilização da cama de frango como um substrato em unidade produtora de biogás. A produção de biogás e metano, nas amostras em diferentes períodos de armazenamento, foi comparada: antes de armazenar 245 LN biogas.kgSV adic-1 e 159 LN CH4.kgSV adic-11, seis meses com 252 LN biogas.kgSV adic-1 e 160 LN CH4.kgSV adic-1 e um ano 209 LN biogas.kgSV adic-1 e 117 LNCH4.kgSV adic-1, demonstrando que o período de armazenamento é caracterizado por uma relativa perda do conteúdo de matéria orgânica após um ano, contudo, não há diferença significativa entre a produção de biogás e metano após seis meses armazenada e antes de armazenar. Verificou-se a viabilidade da estocagem de cama de frango do sexto lote de reutilização, no período de seis meses, sem perda significativa de matéria orgânica para a conversão em biogás e metano. ABSTRACT: In poultry litter is produced seasonally due to production mode. To get energy from biogas through the bio digestion of poultry litter, continuously, the storage of the residue can be a solution. Biochemical Methane Potential (BMP) assays were used in this study to estimate the production of biogas and methane poultry litter removed after the sixth lot of reuse and in different storage times after collect, so check the feasibility of use poultry litter as a feedstock in biogas producer unit. The production of biogas and methane in the samples in different periods of storage was compared: before storage 245 LN biogas.kgVS add-1 E 159 LN C H4 kg SV add-1, six months with 252 LN biogas.kgVS add-1 e 160 LN C H4 kg SV add-1 and a year 209 LN biogas.kgVS add-1 and one year 117 LN C H4 kg SV add-1, demonstrating that the storage period is characterized by a relative loss of content of organic matter after a year, however there's no significant difference between the production of biogas and methane in six months storaged and before storage . It was verified the viability of storage of poultry litter of the sixth lot of reuse, in the six-month period, without significant loss of organic matter for conversion to biogas and methane

Hereditary C1q Deficiency is Associated with Type 1 Interferon-Pathway Activation and a High Risk of Central Nervous System Inflammation

\ua9 The Author(s) 2024.Hereditary C1q deficiency (C1QDef) is a rare monogenic disorder leading to defective complement pathway activation and systemic lupus erythematosus (SLE)-like manifestations. The link between impairment of the complement cascade and autoimmunity remains incompletely understood. Here, we assessed type 1 interferon pathway activation in patients with C1QDef. Twelve patients with genetically confirmed C1QDef were recruited through an international collaboration. Clinical, biological and radiological data were collected retrospectively. The expression of a standardized panel of interferon stimulated genes (ISGs) in peripheral blood was measured, and the level of interferon alpha (IFNα) protein in cerebrospinal fluid (CSF) determined using SIMOA technology. Central nervous system (encompassing basal ganglia calcification, encephalitis, vasculitis, chronic pachymeningitis), mucocutaneous and renal involvement were present, respectively, in 10, 11 and 2 of 12 patients, and severe infections recorded in 2/12 patients. Elevated ISG expression was observed in all patients tested (n = 10/10), and serum and CSF IFNα elevated in 2/2 patients. Three patients were treated with Janus-kinase inhibitors (JAKi), with variable outcome; one displaying an apparently favourable response in respect of cutaneous and neurological features, and two others experiencing persistent disease despite JAKi therapy. To our knowledge, we report the largest original series of genetically confirmed C1QDef yet described. Additionally, we present a review of all previously described genetically confirmed cases of C1QDef. Overall, individuals with C1QDef demonstrate many characteristics of recognized monogenic interferonopathies: particularly, cutaneous involvement (malar rash, acral vasculitic/papular rash, chilblains), SLE-like disease, basal ganglia calcification, increased expression of ISGs in peripheral blood, and elevated levels of CSF IFNα

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

Purpose: Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases. Methods: We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations. Results: We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy. Conclusions: Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia