Constraints on Crustal Stress from Coseismic Slip Models and Focal Mechanisms.

Constraining crustal stress that leads to earthquakes is an active area of research with profound implications on understanding the forces that deform the surface of the earth and generate slip on faults. Surface deformation related to strain accumulation on faults prior to, during and following earthquakes are recorded geodetically (InSAR and GPS). These data are used to infer fault geometries and models of coseismic slip of an earthquake. Seismic energy radiated during earthquakes are used to produce focal mechanisms, which are geometric representations of faults, and provide insight on stress changes due to earthquakes. However, earthquakes are the response to stress accumulation on faults, but direct measurements of accumulated stress are difficult. In this dissertation, I develop, test, and apply a Bayesian Monte Carlo (BMC) estimation technique to infer crustal stress from both focal mechanisms and coseismic slip models, the latter of which has never been done prior to the work I present here. I apply the BMC method to investigate stresses leading to the 2008 Wenchuan, China, earthquake, and to the 1999 İzmit and Düzce, Turkey, earthquakes. I use various coseismic slip models from all three events, aftershock focal mechanisms of the Wenchuan earthquake, and seismicity recorded in the Sea of Marmara, adjacent to the İzmit earthquake. I find that a homogeneous stress is statistically consistent with slip during the Wenchuan earthquake, and that heterogeneous stresses along the trace of the mainshock, previously argued for based on aftershock focal mechanisms, may simply reflect ambiguities in the interpretation of stress from focal mechanisms. Coseismic slip models from the İzmit and Düzce earthquakes are also consistent with a homogeneous stress along all fault segments that slipped in those earthquakes, particularly if the coefficient of fault friction is about 0.2 or less. In the Sea of Marmara, inferred stresses from focal mechanisms indicate that stress differs from the eastern to the western segments of the Main Marmara fault. Additionally, results indicate a potential stress rotation along the western segment between about 1999 and 2003, towards a transform stress regime similar to the stress leading to the İzmit and Düzce earthquakes.PHDGeologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111551/1/lmedina_1.pd

Malformación venosa del útero

Venous malformations are benign vascular lesions that rarely appear in the uterus. They are made up of abnormal veins, of different sizes and proportions, with spongiform configuration and random disposition. In the literature, some cases have been previously reported, using the term "cavernous hemangioma", but according to recent changes in terminology, approved by the International Society for the Study of Vascular Abnormalities (ISSVA), the use of this term is discouraged, and the diagnosis of Venous malformation is suggested, if the histopathological findings are met. We present the case of a 44-year-old woman, with abnormal vaginal bleeding and a clinical diagnosis of myomatosis and myoma aborted by the internal cervical orifice, in whom the histopathological study revealed the presence of a venous malformation that compromised the myometrium and endometrium, with subsequent formation of a polyp.Las malformaciones venosas son lesiones vasculares benignas infrecuentes que se presentan en el útero. Están conformadas por venas anormales, de diferentes tamaños y proporciones, con configuración espongiforme y disposición al azar. En la literatura, han sido previamente reportados algunos casos, usando el término “hemangioma cavernoso”, pero según los cambios recientes en la terminología, aprobados por Sociedad Internacional para el Estudio de las Anormalidades Vasculares (ISSVA), se desaconseja el uso de este término y se sugiere el de “Malformación venosa”, si se cumplen los hallazgos histopatológicos al momento de hacer el diagnóstico. Presentamos el caso de una mujer de 44 años, con cuadro de hemorragia vaginal anormal y diagnóstico clínico de miomatosis y mioma abortado por el orificio cervical interno, el estudio histopatológico reveló la presencia de una malformación venosa que comprometía el miometrio y endometrio, con formación subsecuente de un pólipo. &nbsp

Malformación venosa del útero

Venous malformations are benign vascular lesions that rarely appear in the uterus. They are made up of abnormal veins, of different sizes and proportions, with spongiform configuration and random disposition. In the literature, some cases have been previously reported, using the term "cavernous hemangioma", but according to recent changes in terminology, approved by the International Society for the Study of Vascular Abnormalities (ISSVA), the use of this term is discouraged, and the diagnosis of Venous malformation is suggested, if the histopathological findings are met. We present the case of a 44-year-old woman, with abnormal vaginal bleeding and a clinical diagnosis of myomatosis and myoma aborted by the internal cervical orifice, in whom the histopathological study revealed the presence of a venous malformation that compromised the myometrium and endometrium, with subsequent formation of a polyp.Las malformaciones venosas son lesiones vasculares benignas infrecuentes que se presentan en el útero. Están conformadas por venas anormales, de diferentes tamaños y proporciones, con configuración espongiforme y disposición al azar. En la literatura, han sido previamente reportados algunos casos, usando el término “hemangioma cavernoso”, pero según los cambios recientes en la terminología, aprobados por Sociedad Internacional para el Estudio de las Anormalidades Vasculares (ISSVA), se desaconseja el uso de este término y se sugiere el de “Malformación venosa”, si se cumplen los hallazgos histopatológicos al momento de hacer el diagnóstico. Presentamos el caso de una mujer de 44 años, con cuadro de hemorragia vaginal anormal y diagnóstico clínico de miomatosis y mioma abortado por el orificio cervical interno, el estudio histopatológico reveló la presencia de una malformación venosa que comprometía el miometrio y endometrio, con formación subsecuente de un pólipo. &nbsp

Gargantuan hail in Argentina

On 8 February 2018, a supercell storm produced gargantuan (>15 cm or >6 in. in maximum dimension) hail as it moved over the heavily populated city of Villa Carlos Paz in Córdoba Province, Argentina. Observations of gargantuan hail are quite rare, but the large population density here yielded numerous witnesses and social media pictures and videos from this event that document multiple large hailstones. The storm was also sampled by the newly installed operational polarimetric C-band radar in Córdoba. During the RELAMPAGO campaign, the authors interviewed local residents about their accounts of the storm and uncovered additional social media video and photographs revealing extremely large hail at multiple locations in town. This article documents the case, including the meteorological conditions supporting the storm (with the aid of a high-resolution WRF simulation), the storm's observed radar signatures, and three noteworthy hailstones observed by residents. These hailstones include a freezer-preserved 4.48-in. (11.38 cm) maximum dimension stone that was scanned with a 3D infrared laser scanner, a 7.1-in. (18 cm) maximum dimension stone, and a hailstone photogrammetrically estimated to be between 7.4 and 9.3 in. (18.8-23.7 cm) in maximum dimension, which is close to or exceeds the world record for maximum dimension. Such a well-observed case is an important step forward in understanding environments and storms that produce gargantuan hail, and ultimately how to anticipate and detect such extreme events.Fil: Kumjian, Matthew R.. State University of Pennsylvania; Estados UnidosFil: Gutierrez, Rachel. State University of Pennsylvania; Estados UnidosFil: Soderholm, Joshua S.. Universitat Bonn; AlemaniaFil: Nesbitt, Stephen William. University of Illinois at Urbana; Estados UnidosFil: Maldonado, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Luna, Lorena Medina. National Center for Atmospheric Research; Estados UnidosFil: Marquis, James. Pacific Northwest National Laboratory; Estados UnidosFil: Bowley, Kevin A.. State University of Pennsylvania; Estados UnidosFil: Alvarez Imaz, María de Los Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Salio, Paola Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentin

Gargantuan Hail Documenting an Extreme Forecasting Challenge

I n the scientific literature, some studies have identified “giant” hail as those stones with maximum dimensions exceeding 10 cm or 4 in. We propose a new size class for hailstones with maximum dimensions exceeding 15 cm or 6 in. (referred to here as “gargantuan hail”) to represent the upper extreme of hail sizes. As these are rare cases, only a few studies have specifically documented giant and gargantuan hail events, and most are individual case studies. One study of giant and gargantuan hailstones from the Aurora, Nebraska, storm of 2003 showed that every stone evaluated exhibited an outer (i.e., final) growth layer indicating wet growth, and in some cases this layer was of quite substantial thickness. Another study used social media reports to identify giant hail that ultimately became certified state records. It suggested that the occurrence of giant or gargantuan hail is significantly underreported. None of the aforementioned studies focused on observedtorm properties or environments. In con- trast, a 2013 study documented the synoptic and mesoscale environment of the super- cell that produced the Vivian, South Dakota, hailstone (which registers as the world re- cord for maximum dimension of 20 cm or 8 in.). Analysis indicated that the environment was indeed supportive of severe convective storms, but not indicative of such large hail as was observedFil: Kumjian, Matthew R.. State University of Pennsylvania; Estados UnidosFil: Gutierrez, Rachel. State University of Pennsylvania; Estados UnidosFil: Soderholm, Joshua S.. State University of Pennsylvania; Estados UnidosFil: Nesbitt, Stephen William. University of Illinois at Urbana; Estados UnidosFil: Maldonado, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Medina Luna, Lorena. National Center for Atmospheric Research; Estados UnidosFil: Marquis, James. Pacific Northwest National Laboratory; Estados UnidosFil: Bowley, Kevin A.. State University of Pennsylvania; Estados UnidosFil: Alvarez Imaz, María de Los Milagros. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Salio, Paola Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentin

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk