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  • 1
    In: Genome Medicine, Springer Science and Business Media LLC, Vol. 15, No. 1 ( 2023-04-05)
    Abstract: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7 , with an OR of 27.68 (95%CI 1.5–528.7, P  = 1.1 × 10 −4 ) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P  = 2.1 × 10 −4 ). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P  = 3.4 × 10 −3 ), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P  = 7.7 × 10 −8 ). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P  = 1.68 × 10 −5 ). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
    Type of Medium: Online Resource
    ISSN: 1756-994X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2484394-5
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  • 2
    Online Resource
    Online Resource
    Optica Publishing Group ; 2018
    In:  Optics Letters Vol. 43, No. 22 ( 2018-11-15), p. 5500-
    In: Optics Letters, Optica Publishing Group, Vol. 43, No. 22 ( 2018-11-15), p. 5500-
    Type of Medium: Online Resource
    ISSN: 0146-9592 , 1539-4794
    Language: English
    Publisher: Optica Publishing Group
    Publication Date: 2018
    detail.hit.zdb_id: 243290-0
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  • 3
    In: ECS Transactions, The Electrochemical Society, Vol. 108, No. 2 ( 2022-05-20), p. 19-30
    Abstract: This paper presents the characterization of alumina passivation layers using second harmonic generation (SHG). Based on nonlinear optics, the technique has the advantage of being rapid and non-destructive, especially for thin oxide layers. For the materials under study, the SHG is sensitive to the electronic and structural properties of the interface, particularly to the interfacial electric field (E dc ), and thus allowing to characterize fixed oxide charges (Q ox ) in the oxide and interface traps density (D it ). Time-dependent SHG (TD-SHG) is firstly used here to probe samples with various D it and a total oxide charges (Q tot ), previously extracted using corona oxide characterization of semiconductor (COCOS). The measurement conditions are adjusted to focus on the impact of the fixed charges on the SHG signal. A more detailed analysis of the SHG versus input polarization is conducted in both experiments and simulations and it shows coherent evolution tendencies with the oxide charge.
    Type of Medium: Online Resource
    ISSN: 1938-5862 , 1938-6737
    Language: Unknown
    Publisher: The Electrochemical Society
    Publication Date: 2022
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  • 4
    In: ECS Meeting Abstracts, The Electrochemical Society, Vol. MA2020-01, No. 15 ( 2020-05-01), p. 1050-1050
    Abstract: The quality of interfaces between dielectrics and semiconductors has a tremendous impact on the performances of semiconductor devices. High-k dielectrics are omnipresent in the gate stack of advanced MOSFETs. They are also used as passivation layers for silicon in fields such as solar cells [ 1 ] or image sensors [ 2 ]. When referring to passivation, two mechanisms can be identified: chemical passivation (quantified by the interface state density, D it ) and electric-field passivation (quantified by fixed oxide charge density, Q ox ). An ideal characterization method for passivated silicon should give access to both chemical and field-effect relevant quantities (ideally being able to distinguish them) in a non-destructive way. Among the commonly used techniques, we can cite electrical methods based on current or capacitance monitoring of simple test devices [ 3 ], Corona characterization of semiconductors [ 4 ], carrier lifetime extraction [ 5 ] conducted through photoconductance or photoluminescence decay measurements, etc. The choice among these several options is based on criteria such as sensitivity, non-destructiveness, possibility of direct on-wafer probing without any additional device fabrication steps, ability to discriminate D it and Q ox , capability to provide a high spatial resolution. A recent technique which could meet all these criteria is the second harmonic generation (SHG) [ 6 ], provided that an appropriate calibration method is developed for D it and Q ox extraction. The SHG is a non-linear optics phenomenon: when a high intensity laser beam of wavelength λ reaches a sample, a second harmonic wave at λ/2 is generated by the sample. For centrosymmetric materials (such as silicon, SiO 2 , Al 2 O 3 , etc.) the SHG signal contains two parts: one related to the symmetry breaking inherently present at interfaces between two different materials, and another one produced by any “static” electric field in the sample [ 7 ]. Such field is present at the vicinity of dielectric-to-semiconductor interfaces due to charge trapping by various mechanisms. In other words, the magnitude of the generated SHG signal contains information on both D it and Q ox This technique has already been used for dielectric characterization with various modalities (SHG versus power, time, wavelength ...) [ 8 ], [ 9 ], [ 10 ]. The SHG proved very promising (sensitive, non-destructive, applied directly on-wafer, etc.); however its extensive use still needs a more general calibration methodology. Such a methodology requires not only SHG measurements, but also real Q ox /D it values extracted by classical electrical methods on the same samples and modeling to understand/anticipate the expected effect of these parameters on the SHG signal. In this paper, we’ll discuss all these issues based on a review of our recent advances on how to exploit SHG for dielectrics on semiconductor characterization. Acknowledgements This work was supported by Region Rhône Alpes (ARC6 program), the French National Research Agency within the framework of the OXYGENE project (ANR-17-CE05-0034) and French National Plan Nano2022, within the IPCEI Nanoelectronics for Europe program. [1] A. G. Aberle, "Surface passivation of crystalline silicon solar cells: a review," Progress in Photovoltaics: Research and Applications, vol. 8, pp. 473-487, 2000. [2] J. L. Regolini, D. Benoit, and P. Morin, "Passivation issues in active pixel CMOS image sensors," Microelectronics Reliability, vol. 47, pp. 739-742, 2007. [3] D. K. Schroder, Semiconductor Material and Device Chracterization , 3rd Edition ed. New Jersey: John Wiley & sons, 2006. [4] M. Wilson, J. Lagowski, L. Jastrzebski, A. Savtchouk, and V. Faifer, "COCOS (corona oxide characterization of semiconductor) non-contact metrology for gate dielectrics," AIP Conference Proceedings, vol. 550, pp. 220-225, 2001. [5] D. K. Schroder, "Carrier lifetimes in silicon," Electron Devices, IEEE Transactions on, vol. 44, pp. 160-170, 1997. [6] G. Lupke, "Characterization of semiconductor interfaces by second-harmonic generation," Surface Science Reports, vol. 35, pp. 75-161, 1999. [7] J. E. Sipe, D. J. Moss, and H. M. van Driel, "Phenomenological theory of optical second- and third-harmonic generation from cubic centrosymmetric crystals," Physical Review B, vol. 35, pp. 1129-1141, 1987. [8] J. Price, M. Lei, P. S. Lysaght, G. Bersuker, and M. C. Downer, "Charge trapping defects in Si/SiO2/Hf(1−x)SixO2 film stacks characterized by spectroscopic second-harmonic generation," Journal of Vacuum Science & Technology B, vol. 29, p. 04D101, 2011. [9] N. M. Terlinden, G. Dingemans, V. Vandalon, R. H. E. C. Bosch, and W. M. M. Kessels, "Influence of the SiO2 interlayer thickness on the density and polarity of charges in Si/SiO2/Al2O3 stacks as studied by optical second-harmonic generation," Journal of Applied Physics, vol. 115, p. 033708, 2014. [10] H. Park, J. Qi, Y. Xu, K. Varga, S. M. Weiss, B. R. Rogers , et al. , "Boron induced charge traps near the interface of Si/SiO2 probed by second harmonic generation," Physica Status Solidi (b), vol. 247, pp. 1997-2001, 2010.
    Type of Medium: Online Resource
    ISSN: 2151-2043
    Language: Unknown
    Publisher: The Electrochemical Society
    Publication Date: 2020
    detail.hit.zdb_id: 2438749-6
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  • 5
    In: The Lancet Respiratory Medicine, Elsevier BV, Vol. 9, No. 3 ( 2021-03), p. 295-304
    Type of Medium: Online Resource
    ISSN: 2213-2600
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 6
    Online Resource
    Online Resource
    SPIE-Intl Soc Optical Eng ; 2003
    In:  Optical Engineering Vol. 42, No. 10 ( 2003-10-01), p. 2800-
    In: Optical Engineering, SPIE-Intl Soc Optical Eng, Vol. 42, No. 10 ( 2003-10-01), p. 2800-
    Type of Medium: Online Resource
    ISSN: 0091-3286
    Language: English
    Publisher: SPIE-Intl Soc Optical Eng
    Publication Date: 2003
    detail.hit.zdb_id: 2010512-5
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  • 7
    In: Seminars in Arthritis and Rheumatism, Elsevier BV, Vol. 50, No. 5 ( 2020-10), p. 879-884
    Type of Medium: Online Resource
    ISSN: 0049-0172
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2048942-0
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  • 8
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2809-2809
    Abstract: Abstract 2809 Background: TP53 gene mutations, frequent in AML and MDS with complex karyotype, have recently been found in about 20% of lower risk MDS with del 5q, where they possibly conferred resistance to lenalidomide (LEN), and a higher risk of AML progression (Jadersten, JCO, 2011). We assessed the incidence and prognostic value of TP53 mutations in 79 lower risk MDS with del 5q, treated or not with LEN, and analysed in early disease phase or after progression to higher risk MDS or AML. Methods: IPSS low and int 1 (Lower) risk MDS with del 5q were analysed at diagnosis or onset of LEN (“early phase”) and/or after progression to IPSS high or int 2 (higher) risk MDS or AML. LEN was administered at 5 or 10 mg/d during 16 weeks, and continued in erythroid responders until relapse or disease progression. TP53 mutations were detected by the functional FASAY technique, assessing the transcriptional activity of p53 by co-transfecting an open gap repair plasmid with the product of amplification of TP53 from patients in yeasts whose growth is dependent on p53 functionality. The detection limit of this technique is around 10–15% (Flaman, PNAS 1995). Mutations found by FASAY were confirmed by direct sequencing, using Sanger method and /or (more recently) high sensitivity (1%) Next Generation Sequencing (NGS) by pyrosequencing (GS Junior System-Roche, with the IRON II plate design). Results: 79 lower risk MDS with del 5q from 6 French centers of the GFM were analyzed, including 62 at diagnosis or onset of LEN (“early phase”), and 17 after progression to higher risk MDS or AML (5 of the latter were also retrospectively analysed on early phase samples). Overall, 28 (35%) of the 79 patients had TP53 mutation, including 16 (26%) of the 62 pts analyzed at early phase and 12 (70%) of the 17 evaluated after higher risk MDS or AML progression (p= 0.001). The 62 early phase pts had marrow blasts 〈 5% and 5–9% in 91 and 9% of the cases, isolated del 5q, del 5q+1 and del5q+ 〉 1 (complex karyotype) in 84, 14 and 2% of the cases, and IPSS low and int 1 in 80 and 20% of the cases, respectively. No significant difference was found between mutated and non mutated cases for baseline characteristics including gender, age, WHO classification, cytogenetic complexity and IPSS. In the 5 pts analysed after progression where early phase samples were available, who all had received LEN, 4 had TP53 mutation at progression. In all of them, TP53 mutation was already detectable during early phase. However, the percentage of mutated colonies found by FASAY increased with progression, from 18 to 75%, 26 to 55%, 12 to 87% and 13 to 23%, respectively, showing an increase of the size of the mutated clone at progression. Among the 43 pts analyzed in early phase who received LEN (we excluded the 5 pts analysed after progression where early phase samples were available, to avoid bias), 36 (84 %) had isolated del 5q, 6 (14%) del 5q+1, and 1 (2%) had complex karyotype. IPSS was low in 73% and int-1 in 27%. 12/43 (28%) had TP53 mutation. 63% of the 43 pts achieved erythroid response, and 9 (47%) of the 19 pts evaluable at erythroid response achieved cytogenetic response. Erythroid response was seen in 45% mutated vs 71% non mutated cases (p= 0.258). Cytogenetic response was seen in 1/8(12%) mutated vs 8/11 (73%) non mutated cases (p=0.020). In those 43 pts who received LEN, the cumulative incidence (CI) of AML evolution, with death as a competitive event, did not significantly differ between patients with or without TP53 mutation (3 year CI of 35% vs 30%, p=0.33). Finally, in those pts, TP53 mutational status had no significant impact on OS (median 49 months in mutated pts vs not reached in non mutated pts, p=0.48, figure 1). Conclusion: We confirm the presence of TP53 mutations in about 25 % of lower risk MDS with del 5q analysed in early disease phase. TP53 mutations, in those patients, were not correlated with other baseline parameters. When treated with LEN, mutated cases had similar hematological response, lower cytogenetic response but no significant difference in progression to higher risk MDS or AML and survival compared to non mutated cases. The high incidence of TP 53 mutations at progression to higher risk MDS/AML (70%), and the increase in the TP53 mutated clone size observed during progression in pts with a baseline mutation support the pathophysiological importance of TP53 mutations in disease progression in lower risk MDS with del 5q. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Cardiovascular Diabetology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2022-10-19)
    Abstract: It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75] , I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I 2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup.
    Type of Medium: Online Resource
    ISSN: 1475-2840
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2093769-6
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  • 10
    In: Diabetes Care, American Diabetes Association, Vol. 43, No. 11 ( 2020-11-01), p. e174-e177
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
    detail.hit.zdb_id: 1490520-6
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