Neuro-fuzzy knowledge processing in intelligent learning environments for improved student diagnosis

In this paper, a neural network implementation for a fuzzy logic-based model of the diagnostic process is proposed as a means to achieve accurate student diagnosis and updates of the student model in Intelligent Learning Environments. The neuro-fuzzy synergy allows the diagnostic model to some extent "imitate" teachers in diagnosing students' characteristics, and equips the intelligent learning environment with reasoning capabilities that can be further used to drive pedagogical decisions depending on the student learning style. The neuro-fuzzy implementation helps to encode both structured and non-structured teachers' knowledge: when teachers' reasoning is available and well defined, it can be encoded in the form of fuzzy rules; when teachers' reasoning is not well defined but is available through practical examples illustrating their experience, then the networks can be trained to represent this experience. The proposed approach has been tested in diagnosing aspects of student's learning style in a discovery-learning environment that aims to help students to construct the concepts of vectors in physics and mathematics. The diagnosis outcomes of the model have been compared against the recommendations of a group of five experienced teachers, and the results produced by two alternative soft computing methods. The results of our pilot study show that the neuro-fuzzy model successfully manages the inherent uncertainty of the diagnostic process; especially for marginal cases, i.e. where it is very difficult, even for human tutors, to diagnose and accurately evaluate students by directly synthesizing subjective and, some times, conflicting judgments

Foliar calcium effects on quality and primary and secondary metabolites of white-fleshed ‘Lemonato’ peaches

‘Lemonato’ is a Greek peach melting-flesh white-flesh cultivar with high nutritional value highly appreciated by the consumers. This study aimed to evaluate the effect of pre-harvest foliar calcium application on fruit quality, primary metabolite profile, antioxidant activity, total phenolic content, and phenolic profile of the ‘Lemonato’ peach, clone ‘Stamatis’. The experiment was conducted for two years, 2019 and 2020, in two commercial orchards at Kato Lehonia and Agios Vlasios regions, central Greece, where the ‘Lemonato’ clone ‘Stamatis’ is traditionally cultivated. The treatments were organic calcium (Ca), calcium–silicate in nanoparticles (Ca–Si), and calcium chloride (CaCl2). Foliar application of the different Ca formulations, commonly used as a horticultural practice, were not effective at improving the fruit quality characteristics in this clone, which is characterized by fruit softening during ripening. The study revealed the sugars and organic acid composition and phenolic profile of the ‘Lemonato’ peach, clone ‘Stamatis’. Peach fruit quality, primary metabolites, and phenolic compounds of the two orchards showed a different response to organic Ca and Ca–Si, indicating that genetic or environmental factors may also be involved. A higher concentration of organic Ca and CaCl2 increased the peach fruit phenolic compounds content and the total antioxidant activity, improving the fruit nutritional qualit

British Society for Immunology & United Kingdom Primary Immunodeficiency Network (UKPIN) consensus guideline for the management of immunoglobulin replacement therapy

Currently there is no guideline to support the use of immunoglobulin replacement therapy (IgRT) in primary and secondary immunodeficiency disorders in UK. The UK Primary Immunodeficiency Network (UK-PIN) and the British Society of Immunology (BSI) joined forces to address this need. Given the paucity of evidence a modified Delphi approach was employed covering statements for the initiation, monitoring, discontinuation of IgRT as well as home therapy programme. A group of 6 consultant immunologists and 3 nurse specialists created the statements, reviewed responses and feedback and agreed on final recommendations. This guideline includes 22 statements for initiation, 22 statements for monitoring, 11 statement for home therapy and 19 statements for discontinuation of IgRT. Further areas of research are proposed to improve future delivery of care

A robust model for read count data in exome sequencing experiments and implications for copy number variant calling

Exome sequencing has proven to be an effective tool to discover the genetic basis of Mendelian disorders. It is well established that copy number variants (CNVs) contribute to the etiology of these disorders. However, calling CNVs from exome sequence data is challenging. A typical read depth strategy consists of using another sample (or a combination of samples) as a reference to control for the variability at the capture and sequencing steps. However, technical variability between samples complicates the analysis and can create spurious CNV calls

Serum and Tissue Biomarkers Associated With Composite of Relevant Endpoints for Sj\uf6gren Syndrome (CRESS) and Sj\uf6gren Tool for Assessing Response (STAR) to B Cell–Targeted Therapy in the Trial of Anti–B Cell Therapy in Patients With Primary Sj\uf6gren Syndrome (TRACTISS)

\ua9 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.Objective: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sj\uf6gren Syndrome (cCRESS) and candidate Sj\uf6gren Tool for Assessing Response (STAR) composite endpoints. Methods: Longitudinal analysis of peripheral blood and SG biopsies was performed pre- and post-treatment from the Trial of Anti–B Cell Therapy in Patients With Primary Sj\uf6gren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing. Results: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class-switched memory B cells within the SG. Furthermore, rituximab significantly down-regulated genes involved in immune-cell recruitment, lymphoid organization alongside antigen presentation, and T cell co-stimulatory pathways. In the peripheral compartment, rituximab down-regulated immunoglobulins and auto-antibodies together with pro-inflammatory cytokines and chemokines. Interestingly, patients classified as responders according to STAR displayed significantly higher baseline levels of C-X-C motif chemokine ligand-13 (CXCL13), interleukin (IL)-22, IL-17A, IL-17F, and tumor necrosis factor-α (TNF-α), whereas a longitudinal analysis of serum T cell–related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS-responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fcγ-receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration. Conclusion: Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification. (Figure presented.)

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients

Inhibitor of DNA Binding 3 Limits Development of Murine Slam-Associated Adaptor Protein-Dependent “Innate” γδ T cells

Id3 is a dominant antagonist of E protein transcription factor activity that is induced by signals emanating from the alphabeta and gammadelta T cell receptor (TCR). Mice lacking Id3 were previously shown to have subtle defects in positive and negative selection of TCRalphabeta+ T lymphocytes. More recently, Id3(-/-) mice on a C57BL/6 background were shown to have a dramatic expansion of gammadelta T cells.Here we report that mice lacking Id3 have reduced thymocyte numbers but increased production of gammadelta T cells that express a Vgamma1.1+Vdelta6.3+ receptor with restricted junctional diversity. These Vgamma1.1+Vdelta6.3+ T cells have multiple characteristics associated with "innate" lymphocytes such as natural killer T (NKT) cells including an activated phenotype, expression of the transcription factor PLZF, and rapid production of IFNg and interleukin-4. Moreover, like other "innate" lymphocyte populations, development of Id3(-/-) Vgamma1.1+Vdelta6.3+ T cells requires the signaling adapter protein SAP.Our data provide novel insight into the requirements for development of Vgamma1.1+Vdelta6.3+ T cells and indicate a role for Id3 in repressing the response of "innate" gammadelta T cells to SAP-mediated expansion or survival

Organic residues in archaeology - the highs and lows of recent research

YesThe analysis of organic residues from archaeological materials has become increasingly important to our understanding of ancient diet, trade and technology. Residues from diverse contexts have been retrieved and analysed from the remains of food, medicine and cosmetics to hafting material on stone arrowheads, pitch and tar from shipwrecks, and ancient manure from soils. Research has brought many advances in our understanding of archaeological, organic residues over the past two decades. Some have enabled very specific and detailed interpretations of materials preserved in the archaeological record. However there are still areas where we know very little, like the mechanisms at work during the formation and preservation of residues, and areas where each advance produces more questions rather than answers, as in the identification of degraded fats. This chapter will discuss some of the significant achievements in the field over the past decade and the ongoing challenges for research in this area.Full text was made available in the Repository on 15th Oct 2015, at the end of the publisher's embargo period

HAE international home therapy consensus document

Hereditary angioedema (C1 inhibitor deficiency, HAE) is associated with intermittent swellings which are disabling and may be fatal. Effective treatments are available and these are most useful when given early in the course of the swelling. The requirement to attend a medical facility for parenteral treatment results in delays. Home therapy offers the possibility of earlier treatment and better symptom control, enabling patients to live more healthy, productive lives. This paper examines the evidence for patient-controlled home treatment of acute attacks ('self or assisted administration') and suggests a framework for patients and physicians interested in participating in home or self-administration programmes. It represents the opinion of the authors who have a wide range of expert experience in the management of HAE