The Keen model is designed to represent an economy as a dynamic system governed by the interactions between private debt, wage share, and employment rate. When certain conditions are met, the model ...can lead to a debt spiral, which accurately mimics the impact of a financial crisis on an economy. This manuscript presents a recipe for breaking this spiral by expressing Keen's model as an affine nonlinear system that can be modified through policy interventions. We begin by considering critical initial conditions that resemble a financial crisis to achieve this goal. We then locate a desired point within the system's vector field that leads to a desirable equilibrium and design a path towards it. This path is later followed using one-step-ahead optimal control. We illustrate our approach by presenting simulated control scenarios.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Review of the growing evidence indicating the importance of Btk in innate immune responses aside from its role in humoral immunity.
Btk is the protein affected in XLA, a disease identified as a B ...cell differentiation defect. Btk is crucial for B cell differentiation and activation, but its role in other cells is not fully understood. This review focuses on the function of Btk in monocytes, neutrophils, and platelets and the receptors and signaling cascades in such cells with which Btk is associated.
Background Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first ...year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. Objective Our objective was to assess the effect of mycobacterial disease in patients with CGD. Methods We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. Results Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae , or Mycobacterium ulcerans . Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. Conclusion Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.
ABSTRACT
IL‐12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and ...salmonella. IL‐12Rβ1 is a receptor chain of both the IL‐12 and the IL‐23 receptor and deficiency of IL‐12Rβ1 thus abolishes both IL‐12 and IL‐23 signaling. IL‐12Rβ1 deficiency is caused by bi‐allelic mutations in the IL12RB1 gene. Mutations resulting in premature stop codons, such as nonsense, frame shift, and splice site mutations, represent the majority of IL‐12Rβ1 deficiency causing mutations (66%; 46/70). Also every other morbid mutation completely inactivates the IL‐12Rβ1 protein. In addition to disease‐causing mutations, rare and common variations with unknown functional effect have been reported in IL12RB1. All these variants have been deposited in the online IL12RB1 variation database (www.LOVD.nl/IL12RB1). In this article, we review the function of IL‐12Rβ1 and molecular genetics of human IL12RB1.
IL‐12Rβ1 deficiency is an autosomal recessive disorder that predisposes to severe infections with otherwise poorly pathogenic mycobacteria and salmonella. Seventy unique IL12RB1 mutations in 198 individuals are known that almost invariably result in the same cellular phenotype: absence of IL‐12Rβ1 expression on the cell surface (in all but one) and absence of IL‐12 and IL‐23 responses (in all). No genotype–phenotype relationship exists. This manuscript reviews the function of IL‐12Rβ1 and molecular genetics of IL12RB1, and introduces the IL12RB1 mutation database.
Purpose
Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria ...and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019.
Methods
Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds.
Results
Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (
n
= 6), DHR (
n
= 27), and NBT plus DHR (
n
= 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0–186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to
CYBB
(
n
= 64),
NCF1
(
n
= 7),
NCF2
(
n
= 7), and
CYBA
(
n
= 5) mutations.
Conclusions
The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of
CYBA
and
NCF2
mutations were identified, expanding the spectrum of known causal mutations.
Purpose
Patients with primary immunodeficiency diseases (PIDD) may present with recurrent infections affecting different organs, organ-specific inflammation/autoimmunity, and also increased cancer ...risk, particularly hematopoietic malignancies. The diversity of PIDD and the wide age range over which these clinical occurrences become apparent often make the identification of patients difficult for physicians other than immunologists. The aim of this report is to develop a tool for educative programs targeted to specialists and applied by clinical immunologists.
Methods
Considering the data from national surveys and clinical reports of experiences with specific PIDD patients, an evidence-based list of symptoms, signs, and corresponding laboratory tests were elaborated to help physicians other than immunologists look for PIDD.
Results
Tables including main clinical manifestations, restricted immunological evaluation, and possible related diagnosis were organized for general practitioners and 5 specialties. Tables include information on specific warning signs of PIDD for pulmonologists, gastroenterologists, dermatologists, hematologists, and infectious disease specialists.
Conclusions
This report provides clinical immunologists with an instrument they can use to introduce specialists in other areas of medicine to the warning signs of PIDD and increase early diagnosis. Educational programs should be developed attending the needs of each specialty.
Durante la pandemia por el virus SARS-CoV-2, que inició en 2019, se ha observado que la mayoría de individuos afectados tiene un cuadro clínico leve o es completamente asintomática. Sin embargo, ...alrededor de 15% de los afectados tendrán una enfermedad grave y potencialmente fatal asociada con un síndrome de hiperinflamación, parecido al síndrome de activación macrofágica. Se ha documentado que las personas con cuadros clínicos leves tienen una respuesta inmune innata eficiente y una respuesta adaptativa, que elimina a las células infectadas por virus, dejando memoria inmunológica. Los cuadros graves se originan en individuos con estados proinflamatorios que tienen una respuesta inmunitaria innata tardía, un fenómeno de hiperinflamación y “tormenta de citocinas”, inducido por el sistema inmune innato, que se asocia con defectos en la inmunidad adaptativa.
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