Predictive markers for humoral influenza vaccine response in patients with common variable immunodeficiency (CVID)

BACKGROUND: A subgroup of patients with common variable immunodeficiencies (CVID) responds to vaccination. The aim of the study was to try to identify predictive markers for those who developed a humoral immune response after influenza vaccination. METHODS: 48 patients with CVID (29 females, 19 males, mean age 59.4 years) were vaccinated with the A(H1N1) influenza vaccine Pandemrix® and boosted after one month. Blood samples were collected prior to each vaccination and two months later. Patients with a 4-fold titer increase of the hemagglutinin inhibition test (≥ 1:40) were considered responders and compared to non-responders for clinical, immunological and genetic markers. RESULTS: Eight (16.7%) patients responded to the vaccination. A significantly higher proportion of the responders, who showed a Euroclass SmB-Trnorm21norm profile (p=0.03) with a post-germinal center B cell pattern (p=0.04) in blood, suffered from enteropathies (p=0.04) as compared to non-responders. Bronchiectasis on the other hand, was exclusively found among non-responders (n=7), as was autoimmune cytopenia (n=5). Non-responders with a Euroclass SmB-21lowTrnorm profile (p=0.02), had a significantly higher prevalence of progressive antibody deficiency (p=0.048) and, at diagnosis, a higher mean serum IgM level (p=0.03), a lower mean serum IgG1 level (p=0.007), an expansion of absolute counts of cytotoxic CD8+ T-cells (p=0.033) and an increased proportion of memory CD8+ T-cells (p=0.044) in blood. CVID associated HLA markers were not detected in non-responders (p=0.03). CONCLUSION: About one-fifth of the CVID patients achieved protective antibody levels after A(H1N1) vaccination and selected clinical and immunological markers were identified that may predict a positive outcome of influenza vaccination

Stakeholders' perspective on health equity and its indicators in Iran: A qualitative study

Background: To reduce the health inequity, it is necessary to measure and monitor these inequalities. In this regard, in Iran a plan was developed and accordingly 52 indicators to measure equity in health were developed and announced by the Ministry of Health in collaboration with other sectors. This study aims to obtain a deeper understanding of the development of health equity indicators and identify their implementation challenges and proposed solutions from the perspective of policy makers and executives responsible for the indicators development and implementation. Methods: In this qualitative study, data were gathered using semi-structured interviews with 15 Stakeholders involved in the development and implementation of these health equity indicators (at national and provincial levels), and the review and analysis of relevant documents including meeting minutes, working plans and working progress reports. Data were analyzed using a framework analysis approach. Results: Four main themes were identified, including the concept of equity in health and its importance, the use of health equity indicators and process of indicators development, challenges of development and implementation of the indicators and laying the groundwork for the establishment of indicators. The findings showed that policy makers' viewpoint on concepts and indicators is different from those of executives and their perceptions have little in common. The establishment of indicators requires accurate stakeholders' understanding and accurate insight into the issue of equity in health, political will, financing, training and empowerment of organization's employees, legal requirements, and finally a clear action plan. Conclusion: The development of the indicators requires a shared understanding among policy makers and executives. As the attention has been focused recently on the issue, in addition to knowledge improvement, proper solutions with an intersect oral collaboration approach in order to tackle challenges should be considered

Beating ratio 0.5 for weighted oblivious matching problems

ESA 2016 is organized in collaboration with the European Association for Theoretical Computer Science (EATCS) and is a part of ALGO 2016We prove the first non-trivial performance ratios strictly above 0.5 for weighted versions of the oblivious matching problem. Even for the unweighted version, since Aronson, Dyer, Frieze, and Suen first proved a non-trivial ratio above 0.5 in the mid-1990s, during the next twenty years several attempts have been made to improve this ratio, until Chan, Chen, Wu and Zhao successfully achieved a significant ratio of 0.523 very recently (SODA 2014). To the best of our knowledge, our work is the first in the literature that considers the node-weighted and edge-weighted versions of the problem in arbitrary graphs (as opposed to bipartite graphs). (1) For arbitrary node weights, we prove that a weighted version of the Ranking algorithm has ratio strictly above 0.5. We have discovered a new structural property of the ranking algorithm: if a node has two unmatched neighbors at the end of algorithm, then it will still be matched even when its rank is demoted to the bottom. This property allows us to form LP constraints for both the node-weighted and the unweighted oblivious matching problems. As a result, we prove that the ratio for the node-weighted case is at least 0.501512. Interestingly via the structural property, we can also improve slightly the ratio for the unweighted case to 0.526823 (from the previous best 0.523166 in SODA 2014). (2) For a bounded number of distinct edge weights, we show that ratio strictly above 0.5 can be achieved by partitioning edges carefully according to the weights, and running the (unweighted) Ranking algorithm on each part. Our analysis is based on a new primal-dual framework known as matching coverage, in which dual feasibility is bypassed. Instead, only dual constraints corresponding to edges in an optimal matching are satisfied. Using this framework we also design and analyze an algorithm for the edge-weighted online bipartite matching problem with free disposal. We prove that for the case of bounded online degrees, the ratio is strictly above 0.5.published_or_final_versio

Assessors' attitudes toward and experiences of national quality standards: A qualitative study in Iran

To establish a national accreditation system for medical laboratories, Iran has set national standards based on the international standard ISO 15189. Central to the accreditation process are the technical assessors. Their attitude in this regard and their experiences should be identified. This study aims to explore assessors' attitudes toward national laboratory accreditation and their experiences of assessment process in order to identify current gaps and suggest required interventions to solve them. A qualitative study using an open-ended questionnaire was employed. A total of 150 assessors working in the General Directorate of Laboratory Affairs participated in the study. While almost all Iranian laboratory accreditation assessors were generally supportive about the necessity of laboratory accreditation and cited benefits of this process, they pointed to improvement areas including developing assessor selection and appraisal criteria, continuous training, taking into consideration the heterogeneity of laboratories throughout the country, participation of professional associations and adopting measures to increase laboratories' involvement. © 2014 Springer-Verlag Berlin Heidelberg

Coined quantum walks on percolation graphs

Quantum walks, both discrete (coined) and continuous time, form the basis of several quantum algorithms and have been used to model processes such as transport in spin chains and quantum chemistry. The enhanced spreading and mixing properties of quantum walks compared with their classical counterparts have been well-studied on regular structures and also shown to be sensitive to defects and imperfections in the lattice. As a simple example of a disordered system, we consider percolation lattices, in which edges or sites are randomly missing, interrupting the progress of the quantum walk. We use numerical simulation to study the properties of coined quantum walks on these percolation lattices in one and two dimensions. In one dimension (the line) we introduce a simple notion of quantum tunneling and determine how this affects the properties of the quantum walk as it spreads. On two-dimensional percolation lattices, we show how the spreading rate varies from linear in the number of steps down to zero, as the percolation probability decreases to the critical point. This provides an example of fractional scaling in quantum walk dynamics.Comment: 25 pages, 14 figures; v2 expanded and improved presentation after referee comments, added extra figur

Substitutional doping of Cu in diamond: Mott physics with pp orbitals

Discovery of superconductivity in the impurity band formed by heavy doping of boron into diamond (C:B) as well as doping of boron into silicon (Si:B) has provided a rout for the possibility of new families of superconducting materials. Motivated by the special role played by copper atoms in high temperature superconducting materials where essentially Cu $d$ orbitals are responsible for a variety of correlation induced phases, in this paper we investigate the effect of substitutional doping of Cu into diamond. Our extensive first principle calculations averaged over various geometries based on density functional theory, indicates the formation of a mid-gap band, which mainly arises from the $t_{2g}$ and $4p$ states of Cu. For impurity concentrations of more than $\sim 1$2p$bands of neighboring carbon atoms can be ignored. Based on our detailed analysis, we suggest a two band model for the mid-gap states consisting of a quarter-filled hole like$t_{2g}$band, and a half-filled band of$4p$states. Increasing the concentration of the Cu impurity beyond$\sim 5%, completely closes the spectral gap of the host diamond.Comment: 5 figure

Developing a comprehensive evidence-based service package for toddlers with autism in a low resource setting: Early detection, early intervention, and care coordination

Objective: The number of children with autism, who have many unmet needs, is increasing dramatically. However, the existing evidence shows that early identification and intervention are effective in reducing the later costs and burdens of autism spectrum disorder (ASD). Thus, the present study aimed to develop evidence-based services for children with autism in Iran to reduce its impacts on the affected children and their families and to decrease its burden on the society. Method: A 3-step study was conducted based on a modification of the Replicating Effective Programs (REP) framework (step 1: need assessment and situation analysis; step 2: identifying current evidence-based services; step 3: designing the first draft of the package and its core elements). Each step was conducted by a specific methodology. Results: By considering the obtained data, it was found that a package of services with 4 core components to respond to the perceived needs in Iran was needed: (1) early detection of at-risk children; (2) care coordination and facilitation of access to current services; (3) implementation of an evidence-based early intervention program; and (4) training interventionists using an effective educational framework based on evidence-based material. Conclusion: REP framework was used in the present study, which has been shown to be effective in adapting and implementing health care services. By considering the preconditions of REP, a comprehensive package of services, with 4 components was designed for toddlers with autism in Iran. The next step will be to study this package using a multicenter hybrid effectiveness-implementation randomized control trial. © 2019 Tehran University of Medical Sciences. All rights reserved

Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents

Current status of health and social services for children with autism in Iran: Parents� perspectives

Objective: The present study is a part of a larger study that aimed at developing a comprehensive model of service delivery for individuals with autism in Iran based on the local needs and characteristics. In this study, the status of the services provided to those with autism in Iran was investigated based on the perspectives of parents of children with autism. Method: A semi-structured interview was used to qualitatively investigate the status of the services with regards to autism in Iran based on the perspectives of parents of children with autism. Results: This study revealed several barriers, including shortness of eligible professionals, difficulty in access to care for families, high costs, and lack of formal and informal supports, in providing services to those with autism in Iran. Early detection and diagnosis are of prime importance. We also need to train our specialists to diagnose autism based on the standard protocols and tests. Conclusion: In sum, we need a comprehensive program that involves different sectors in charge of health and education in Iran. © 2019 Tehran University of Medical Sciences. All rights reserved

CVID-Associated B Cell Activating Factor Receptor Variants Change Receptor Oligomerization, Ligand Binding, and Signaling Responses.

Binding of the B cell activating factor (BAFF) to its receptor (BAFFR) activates in mature B cells many essential pro-survival functions. Null mutations in the BAFFR gene result in complete BAFFR deficiency and cause a block in B cell development at the transition from immature to mature B cells leading therefore to B lymphopenia and hypogammaglobulinemia. In addition to complete BAFFR deficiency, single nucleotide variants encoding BAFFR missense mutations were found in patients suffering from common variable immunodeficiency (CVID), autoimmunity, or B cell lymphomas. As it remained unclear to which extent such variants disturb the activity of BAFFR, we performed genetic association studies and developed a cellular system that allows the unbiased analysis of BAFFR variants regarding oligomerization, signaling, and ectodomain shedding. In addition to genetic association studies, the BAFFR variants P21R, A52T, G64V, DUP92-95, P146S, and H159Y were expressed by lentiviral gene transfer in DG-75 Burkitt's lymphoma cells and analyzed for their impacts on BAFFR function. Binding of BAFF to BAFFR was affected by P21R and A52T. Spontaneous oligomerization of BAFFR was disturbed by P21R, A52T, G64V, and P146S. BAFF-dependent activation of NF-κB2 was reduced by P21R and P146S, while interactions between BAFFR and the B cell antigen receptor component CD79B and AKT phosphorylation were impaired by P21R, A52T, G64V, and DUP92-95. P21R, G64V, and DUP92-95 interfered with phosphorylation of ERK1/2, while BAFF-induced shedding of the BAFFR ectodomain was only impaired by P21R. Although all variants change BAFFR function and have the potential to contribute as modifiers to the development of primary antibody deficiencies, autoimmunity, and lymphoma, P21R is the only variant that was found to correlate positively with CVID