| 1. |
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| 2. |
- Kocarnik, J. M., et al.
(författare)
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Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019 A Systematic Analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Jama Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445. ; 8:3, s. 420-488
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3%(95% UI, 20.3%-32.3%) increase in new cases, a 20.9%(95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4%(1.1%-1.8%) in the low SDI quintile to 5.7%(4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and YDALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.
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| 6. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 7. |
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| 8. |
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| 9. |
- Tavakol, M, et al.
(författare)
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Diversity of malignancies in patients with different types of inborn errors of immunity
- 2022
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Ingår i: Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. - : Springer Science and Business Media LLC. - 1710-1484. ; 18:1, s. 106-
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Tidskriftsartikel (refereegranskat)abstract
- Genetic defects in the development, maturation, and/or function of the immune cells can lead to Inborn errors of immunity (IEI) which may predispose patients to malignancies. The overall risk for cancer in children with IEI ranges from 4 to 25% and the type of malignancy is highly dependent on the specific mutant gene underlying IEI. We investigated 3056 IEI patients registered in the Iranian national registry between the years 1999 and 2020 in this retrospective cohort study. The frequency of malignancy and its association with the type of IEI in these patients were evaluated. A total of 82 IEI patients with malignancy were enrolled in this study. Among them, predominantly lymphoma was the most common type of malignancy (67.1%), followed by leukemia (11%), and cancers of the head and neck (7.3%). Among identified lymphoma cancers, non-Hodgkin’s lymphomas were the most frequent type (43.9%) followed by different subtypes of Hodgkin’s lymphoma (23.2%). Solid tumors (18.3%) appeared to be very heterogeneous by type and localization. The correlation between the type of malignancy and survival status and the association between the type of malignancy and IEI entities were unremarkable. The awareness of the association between the presence of IEI and cancer highlights the importance of a synergistic effort by oncologists and immunologists in the early diagnosis of malignancy and personalized therapeutic strategies in IEI patients.
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| 10. |
- Asgardoon, MH, et al.
(författare)
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Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity
- 2020
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 181:9, s. 706-714
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. <b><i>Methods:</i></b> Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children’s Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. <b><i>Results:</i></b> In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was <i>LRBA</i>, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (<i>n</i> = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (<i>n</i> = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. <b><i>Conclusion:</i></b> In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.
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| 11. |
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| 13. |
- Ebrahimi-Fakhari, Darius, et al.
(författare)
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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
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Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
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Tidskriftsartikel (refereegranskat)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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| 14. |
- Rosenhahn, Erik, et al.
(författare)
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Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications
- 2022
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 109:8, s. 1421-1435
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Tidskriftsartikel (refereegranskat)abstract
- PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy, and progressive microcephaly. Further common clinical findings included muscular hyper- and hypotonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, ventriculomegaly, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM domain region that is essential for protein-protein interaction. For further insight into the effects of PPFIBP1 loss of function, we performed automated behavioral phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model, which revealed defects in spontaneous and light-induced behavior and confirmed resistance to the acetylcholinesterase inhibitor aldicarb, suggesting a defect in the neuronal presynaptic zone. In conclusion, we establish bi-allelic loss-of-function variants in PPFIBP1 as a cause of an autosomal recessive severe neurodevelopmental disorder with early-onset epilepsy, microcephaly, and periventricular calcifications.
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| 15. |
- Ahmadi, K., et al.
(författare)
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Inducing Dzyaloshinskii-Moriya interaction in symmetrical multilayers using post annealing
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The interfacial Dzyaloshinskii-Moriya Interaction (iDMI) is an antisymmetric exchange interaction that is induced by the broken inversion symmetry at the interface of, e.g., a ferromagnet/heavy metal. Thus, the presence of iDMI is not expected in symmetrical multilayer stacks of such structures. Here, we use thermal annealing to induce the iDMI in a [Py/Pt](x10) symmetrical multilayer stack. Brillouin light scattering spectroscopy is used to directly evidence the iDMI induction in the annealed sample. Structural characterizations highlight the modified crystallinity as well as a higher surface roughness of the sample after annealing. First principles electronic structure calculations demonstrate a monotonic increase of the iDMI with the interfacial disorder due to the interdiffusion of atoms, depicting the possible origin of the induced iDMI. The presented method can be used to tune the iDMI strength in symmetric multilayers, which are the integral part of racetrack memories, magnonic devices as well as spin-orbitronic elements.
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| 16. |
- Ebrahimi, M., et al.
(författare)
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A Systematic Approach to Automotive Security
- 2023
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Ingår i: Lecture Notes in Computer Science, vol 14000. - Cham : Springer Science and Business Media Deutschland GmbH. - 9783031274800 ; , s. 598-609
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Konferensbidrag (refereegranskat)abstract
- We propose a holistic methodology for designing automotive systems that consider security a central concern at every design stage. During the concept design, we model the system architecture and define the security attributes of its components. We perform threat analysis on the system model to identify structural security issues. From that analysis, we derive attack trees that define recipes describing steps to successfully attack the system’s assets and propose threat prevention measures. The attack tree allows us to derive a verification and validation (V &V) plan, which prioritizes the testing effort. In particular, we advocate using learning for testing approaches for the black-box components. It consists of inferring a finite state model of the black-box component from its execution traces. This model can then be used to generate new relevant tests, model check it against requirements, and compare two different implementations of the same protocol. We illustrate the methodology with an automotive infotainment system example. Using the advocated approach, we could also document unexpected and potentially critical behavior in our example systems.
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| 17. |
- Needham, E. J., et al.
(författare)
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Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:11, s. 4097-4107
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible. Needham et al. reveal elevations in blood biomarkers of brain injury in patients hospitalised with COVID-19. The changes, which were severity-dependent, were associated with dysregulated immune responses including increases in pro-inflammatory cytokines and autoantibodies. Ongoing active brain injury could still be seen months after infection.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 23. |
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| 24. |
- Ebrahimi, E., et al.
(författare)
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Model Checking of Hyperledger Fabric Smart Contracts
- 2023
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Ingår i: IEEE Int. Conf. Emerging Technol. Factory Autom., ETFA. - : Institute of Electrical and Electronics Engineers Inc.. - 9798350339918
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Konferensbidrag (refereegranskat)abstract
- Conducting interactions between shared-purpose organizations that are not entirely trustworthy of each other without centralized oversight is an idea that emerged with the advent of private blockchains such as Hyperledger Fabric and its smart contracts. It is critical to check contracts to ensure their proper functionality, as organizations may collaborate with competitors. Due to the new architecture of Hyperledger Fabric, tools in this area are limited. To formally verify the source code of contracts, we mapped Fabric contract concepts into the Rebeca modeling language. Rebeca is an actor-based language that enables the modeling of concurrent and distributed systems and is supported by a model checking tool, Afra. We have identified vulnerabilities such as deadlock and starvation by examining the desired properties. Using the model checking approach, we could debug the code and hence benefit from speeding up the transactions, creating fewer extra blocks, requiring less storage space to store the ledger, and avoiding wasting computing resources.
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| 25. |
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| 26. |
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| 27. |
- Hosseini, Maryam S., et al.
(författare)
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Application Characterization for Near Memory Processing
- 2021
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Ingår i: 2021 29th Euromicro international conference on parallel, distributed and network-based processing (PDP 2021). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 148-152
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Konferensbidrag (refereegranskat)abstract
- Data movement between memory subsystem and processor unit is a crippling performance and energy bottleneck for data-intensive applications. Near Memory Processing (NMP) is a promising solution to alleviate the data movement bottleneck. The introduction of 3D-stacked memories and more importantly hybrid memory systems enable the long-wished NMP capability. This work explores the feasibility and efficacy of having NMP on the hybrid memory system for a given set of applications. In this paper, we first redefine a set of NMP-centric performance metrics in order to analyze the efficacy of a given processing unit. Leveraging the proposed metrics, we characterize various sets of applications to assess the suitability of a processing unit in terms of performance. Specifically, in this work we motivate the efficiency of NMP subsystems to process memory-intensive applications when 3D-NVM technologies are employed.
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| 28. |
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| 29. |
- Lalegani, Z., et al.
(författare)
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Modeling, design, and synthesis of gram-scale monodispersed silver nanoparticles using microwave-assisted polyol process for metamaterial applications
- 2020
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Ingår i: Optical materials (Amsterdam). - : Elsevier BV. - 0925-3467 .- 1873-1252. ; 108
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Tidskriftsartikel (refereegranskat)abstract
- High-yield monodispersed silver (Ag) nanospheres were modeled, designed, and synthesized by microwaveassisted (MW-assisted) polyol method from AgNO3, polyvinyl pyrrolidone (PVP), and ethylene glycol (EG), as precursors, at 145 degrees C within a short reaction time of 2 min, and the results were compared to those of conventional polyol method. Maintaining the PVP:AgNO3 molar ratio, the effect of increasing the amounts of AgNO3 and PVP at a constant amount of EG (40 mL) on the final product was evaluated. The synthesized nanoparticles (NPs) were characterized by SEM, UV-Vis spectroscopy, FTIR and DLS analysis. The results showed that with increasing the amount of AgNO3 to 0.5 and 1 g, monodispersed Ag nanoparticles (Ag NPs) with particle sizes of 54 and 61 nm were formed, as per the plasmon absorption peaks at 436 and 442 nm, respectively. Moreover, using 40 mL of the EG solution, we could obtain a high yield of the NPs (similar to 90%). The sub-gram yield was excellently high, offering great opportunities for commercializing the procedure. Also, the proposed study paves a new way for Ag NPs realization for different practical applications ranging from MW to optics.
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| 30. |
- Lalegani, Z., et al.
(författare)
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Targeted dielectric coating of silver nanoparticles with silica to manipulate optical properties for metasurface applications
- 2022
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Ingår i: Materials Chemistry and Physics. - : Elsevier BV. - 0254-0584 .- 1879-3312. ; 287, s. 126250-
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Tidskriftsartikel (refereegranskat)abstract
- An epsilon-negative metamaterial (ENM) containing core@shell nanoparticles (NPs) was designed, where silver (Ag) NPs served as core and silica (SiO2) was used as spacer shell. AgNPs were synthesized in large scale, using microwave-assisted polyol method, in three average particle sizes, as 30, 54, and 61 nm, with a narrow particle size distribution. Optical absorption of Ag NPs was investigated using UV-Vis spectroscopy. Their optical behavior was also theoretically predicted for different thicknesses of the SiO2 shell immersed in media of different refractive indices using the Clausius Mossotti equation. Based on the results, optimal outputs were obtained with a SiO2 shell of 10 nm in thickness encompassing 54 nm Ag NPs based on the analytical model and numerical simulations here developed for core-shell structures. Then 10 nm SiO2 shell was grown on 54 nm Ag NPs by sol-gel synthesis. The NPs were then characterized by UV-Vis, TEM, SEM, EDX, DLS, and zeta potential analyses. The synthesized core-shell NPs can be used to establish epsilon-negative properties in polymer layers within visible range of wavelengths.
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| 31. |
- Nakhaei, Niknaz, et al.
(författare)
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A solution technique to cascading link failure prediction
- 2022
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Ingår i: Knowledge-Based Systems. - : Elsevier BV. - 0950-7051 .- 1872-7409. ; 258
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Tidskriftsartikel (refereegranskat)abstract
- The study of complex networks is a new powerful tool that can provide a profitable skeleton to better elucidate technology-related phenomena and interactions between components of real-world networks However, it is not easy to predict the communal behavior of such systems from their elements and on the other hand, the failure of one or few elements can trigger the failure of other elements throughout the network, resulting in network breakdown and catastrophic events at large scales. Therefore, developing predictive mathematical techniques to examine complex networks is one of the biggest challenges of the present time. Knowing that link failure prediction is less studied in the OR literature, the present study articulates a method to predict link failures in complex networks, which is primarily based on Bayesian Belief Networks (BBN) and TOPSIS. The method aims to predict failures based on the affective factors of failures in networks. To this end, effective factors of failures are first detected, and then the graph of the relationship of factors along with their weight is determined. After all, the method provides the prediction for future damaged components. The functionality of the method is validated by an extensive computational analysis employing simulation in scale-free, random, and actual international aviation networks and its performance is compared with other benchmark algorithms. The results and sensitivity analysis experiments arrive at prominent managerial insights and efficacious implications and show that our method can generate high-quality solutions in many networks.
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| 32. |
- Rabiee, Navid, et al.
(författare)
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Green Biomaterials : fundamental principles
- 2023
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Ingår i: Green Biomaterials. - : Taylor & Francis. - 2993-4168. ; 1:1, s. 1-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 33. |
- S.Hosseini, M., et al.
(författare)
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Near Volatile and Non-Volatile Memory Processing in 3D Systems
- 2022
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Ingår i: IEEE Transactions on Emerging Topics in Computing. - : Institute of Electrical and Electronics Engineers (IEEE). - 2168-6750. ; 10:3, s. 1657-1664
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Tidskriftsartikel (refereegranskat)abstract
- The cost of transferring data between the off-chip memory system and compute unit is the fundamental energy and performance bottleneck in modern computing systems. Furthermore, with the advent of emerging data-intensive applications and technology scaling, this bottleneck has continuously increased. To overcome these difficulties, Near Memory Processing (NMP) based on 3D die stacking becomes a potential technology to transform the computation-centric system towards memory-centric system. In this work, we explore the feasibility and efficacy of a NMP architecture based on an emerging Non-Volatile Memory technology (NVM) for data-intensive applications and compare it with the conventional 3D-stacked NMP architecture based on DRAM. We demonstrate the effectiveness of our approach with experimental results.
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| 34. |
- Sharifinejad, N, et al.
(författare)
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Autoimmunity in monogenic combined immune deficiencies with associated or syndromic features
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1023127-
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Tidskriftsartikel (refereegranskat)abstract
- Combined immune deficiencies (CIDs) with associated or syndromic features are a highly heterogeneous subgroup of inherited immune disorders. These patients represent specific clinical complications with an increased risk of autoimmune conditions.MethodsWe analyzed data of monogenic patients with syndromic CIDs adopted from the Iranian inborn errors of immunity registry up to January 2022. A comprehensive comparison in terms of demographic, clinical, and immunological features was performed between patients with and without autoimmunity and also among four mutation groups with the most registered cases including ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations.ResultsA total of 137 patients with monogenic syndromic CIDs were included. Most commonly mutated genes were the ATM [80 (58.4%)] and STAT3 (AD-LOF) [19 (13.9%)], followed by DNMT3B [11 (8%)], and WAS [11 (8%)]. More than 18% of all patients with syndromic CIDs, including most DNMT3B/ZBTB24 mutations patients, were clinically diagnosed with antibody deficiencies before genetic evaluation. Patients with ATM and WAS mutations had the latest age of onset and the lowest age of diagnosis, respectively. Autoimmune disorders were diagnosed in 24 patients at a median age of 3.5 (2.6-6.0) years, 70.6% of which were diagnosed prior to the diagnosis of immunodeficiency. Lymphoproliferation, particularly hepatosplenomegaly, was significantly higher in patients with autoimmunity (p=0.004). Syndromic CID patients with autoimmunity had significantly lower IgG levels. Hematologic autoimmunity mainly immune thrombocytopenic purpura was the most frequent autoimmunity among major groups of ATM, STAT3 (AD-LOF), DNMT3B/ZBTB24, and WAS mutations, however ATM-mutated patients present more diversified involved organs including rheumatologic, gastrointestinal and dermatologic autoimmunity.ConclusionAbout 18% of patients with monogenic syndromic CIDs developed autoimmunity, mainly in the form of hematological immune diseases. Autoimmunity could be an early-onset involvement with a potential diagnostic impact on suspicious cases of syndromic CIDs.
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| 35. |
- Soler, J. M., et al.
(författare)
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Predictive Modeling of a Simple Field Matrix Diffusion Experiment Addressing Radionuclide Transport in Fractured Rock. Is It So Straightforward?
- 2022
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Ingår i: Nuclear Technology. - : Informa UK Limited. - 0029-5450 .- 1943-7471. ; 208:6, s. 1059-1073
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Tidskriftsartikel (refereegranskat)abstract
- The SKB GroundWater Flow and Transport of Solutes Task Force is an international forum in the area of conceptual and numerical modeling of groundwater flow and solute transport in fractured rocks relevant for the deep geological disposal of radioactive waste. Two in situ matrix diffusion experiments in crystalline rock (gneiss) were performed at POSIVA’s ONKALO underground facility in Finland. Synthetic groundwater containing several conservative and sorbing radiotracers was injected at one end of a borehole interval and flowed along a thin annulus toward the opposite end. Several teams performed predictive modeling of the tracer breakthrough curves using “conventional” modeling approaches (constant diffusion and sorption in the rock, no or minimum rock heterogeneity). Supporting information, derived from small-scale laboratory experiments, was provided. The teams were free to implement different concepts, use different codes, and apply the transport and retention parameters that they considered to be most suited (i.e., not a benchmark exercise). The main goal was the comparison of the different sets of results and the analysis of the possible differences for this relatively simple experimental setup with a well-defined geometry. Even though the experiment was designed to study matrix diffusion, the calculated peaks of the breakthrough curves were very sensitive to the assumed magnitude of dispersion in the borehole annulus. However, given the very different timescales for advection and matrix diffusion, the tails of the curves provided information concerning diffusion and retention in the rock matrix regardless of the magnitude of dispersion. In addition, although the task was designed to be a blind modeling exercise, the model results have also been compared to the measured experimental breakthroughs. Experimental results tend to show relatively small activities, wide breakthroughs, and early first arrivals, which are somewhat similar to model results using large dispersivity values.
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