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Background: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.

Until recently, applications of neural networks in machine learning have almost exclusively relied on real-valued networks. It was recently observed, however, that complex-valued neural networks (CVNNs) exhibit superior performance in applications in which the input is naturally complex-valued, such as MRI fingerprinting. While the mathematical theory of real-valued networks has, by now, reached some level of maturity, this is far from true for complex-valued networks. In this paper, we analyze the expressivity of complex-valued networks by providing explicit quantitative error bounds for approximating $C^n$ functions on compact subsets of $\mathbb{C}^d$ by complex-valued neural networks that employ the modReLU activation function, given by $\sigma(z) = \mathrm{ReLU}(|z| - 1) \, \mathrm{sgn} (z)$, which is one of the most popular complex activation functions used in practice. We show that the derived approximation rates are optimal (up to log factors) in the class of modReLU networks with weights of moderate growth.

Background Our objective was to describe the clinical course, risk factors and outcomes of patients infected with COVID-19 around the globe comparing cancer to non-cancer patients. Methods We conducted a retrospective cohort study of COVID-19 confirmed cases through an international multicenter collaboration including 17 centers around the world including the United States of America, Brazil, Europe, Far East, Middle East and Australia from January to date. We evaluated the patients’ clinical characteristics, clinical course of the disease, hospitalization and outcome. Death was considered to be COVID-associated if it occurred within 30 days from the time of diagnosis. Results Preliminary data on 571 patients included 186 cancer patients and 385 non-cancer patients. Cancer patients were more likely to have COPD and received steroids but were less likely to have COVID-related symptoms compared to non-cancer patients (84% vs 97%, p< 0.0001). The rate of pneumonia with hypoxia, non-invasive ventilation and mechanical ventilation were similar in both groups. Despite the fact that hospital admissions were significantly higher in non-cancer patients (70% vs 56%, p< 0.001), promising antiviral and immune-related therapy including remdesivir, convalescent plasma and immunomodulators were more commonly used in cancer patients compared to non-cancer patients (P=0.04). Cancer patients had a higher COVID-associated mortality rate compared to non-cancer patients (20% vs 11%, p=0.006). Conclusion Despite the fact that cancer patients received more frequent antiviral and immune-related therapy, the mortality rate among cancer patients was significantly higher than non-cancer patients. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix (Consultant, Research Grant or Support)Clinigen (Consultant)Merck (Consultant, Research Grant or Support)Novartis (Research Grant or Support)Oxford Immunotec (Consultant, Research Grant or Support)Shire/Takeda (Research

Baseline chest computed tomography (BCT) in high‐risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web‐based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow‐up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases (n = 69; 49%), hematology (n = 68; 48%), and others (n = 41; 29%). BCT was performed in 57% (n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X‐ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non‐European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%; IQR 5–15%) and non‐BCT centers (7%; IQR 5–10%) (p = 0.69). Follow‐up computed tomography (CT) for IPA was performed in 98% (n = 90) of centers. In high‐risk hematology patients, baseline CT is becoming a standard‐of‐care. Chest X‐ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome.

Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the “One World One Guideline” initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.

A new Moho depth map has been assembled for Western and Central Europe and the Western Mediterranean area that is exclusively based on published regional Moho depth maps. Tectonic overlays summarize Caledonian and Variscan tectonic units, Permo-Carboniferous fault systems and magmatic provinces, Mesozoic and Cenozoic rift-wrench systems, areas of intraplate compression, the outlines of Alpine orogens and the distribution of oceanic crust. Based on a comparison of these overlays with the Moho depth map we assess processes that controlled the evolution of the crust in the various parts of Europe through time. The present-day crustal configuration of Western and Central Europe results from polyphase Late Palaeozoic to recent lithospheric deformation that overprinted the margin of the Proterozoic East European Craton and particularly the Caledonian and Variscan crustal domains. Following consolidation of the Caledonides, their crustal roots were destroyed in conjunction with Devonian wrench tectonics and back-arc rifting. During the Permo-Carboniferous tectonomagmatic cycle, wrench faulting disrupted the crust of the Variscan Orogen and its foreland and the lithosphere of these regions was thermally destabilized. Late Permian and Mesozoic re-equilibration of the lithosphere-asthenosphere system was interrupted by the development of the Arctic-North Atlantic, Tethyan and associated rift systems. During the Alpine orogenic cycle, intraplate compressional stresses controlled basin inversion-related crustal thickening and lithospheric folding, as well as the evolution of the Rhine-Rhone rift system. Variably deep crustal roots characterize the Alpine orogenic chains. Neogene back-arc extension disrupted the eastern Pyrenees, Betic-Balearic, Apennine and Dinarides orogens.

A new Moho depth map has been assembled for Western and Central Europe and the Western Mediterranean area that is exclusively based on published regional Moho depth maps. Tectonic overlays summarize Caledonian and Variscan tectonic units, Permo-Carboniferous fault systems and magmatic provinces, Mesozoic and Cenozoic rift-wrench systems, areas of intraplate compression, the outlines of Alpine orogens and the distribution of oceanic crust. Based on a comparison of these overlays with the Moho depth map we assess processes that controlled the evolution of the crust in the various parts of Europe through time. The present-day crustal configuration of Western and Central Europe results from polyphase Late Palaeozoic to recent lithospheric deformation that overprinted the margin of the Proterozoic East European Craton and particularly the Caledonian and Variscan crustal domains. Following consolidation of the Caledonides, their crustal roots were destroyed in conjunction with Devonian wrench tectonics and back-arc rifting. During the Permo-Carboniferous tectonomagmatic cycle, wrench faulting disrupted the crust of the Variscan Orogen and its foreland and the lithosphere of these regions was thermally destabilized. Late Permian and Mesozoic re-equilibration of the lithosphere-asthenosphere system was interrupted by the development of the Arctic-North Atlantic, Tethyan and associated rift systems. During the Alpine orogenic cycle, intraplate compressional stresses controlled basin inversion-related crustal thickening and lithospheric folding, as well as the evolution of the Rhine-Rhone rift system. Variably deep crustal roots characterize the Alpine orogenic chains. Neogene back-arc extension disrupted the eastern Pyrenees, Betic-Balearic, Apennine and Dinarides orogens.

A new Moho depth map has been assembled for Western and Central Europe and the Western Mediterranean area that is exclusively based on published regional Moho depth maps. Tectonic overlays summarize Caledonian and Variscan tectonic units, Permo-Carboniferous fault systems and magmatic provinces, Mesozoic and Cenozoic rift-wrench systems, areas of intraplate compression, the outlines of Alpine orogens and the distribution of oceanic crust. Based on a comparison of these overlays with the Moho depth map we assess processes that controlled the evolution of the crust in the various parts of Europe through time. The present-day crustal configuration of Western and Central Europe results from polyphase Late Palaeozoic to recent lithospheric deformation that overprinted the margin of the Proterozoic East European Craton and particularly the Caledonian and Variscan crustal domains. Following consolidation of the Caledonides, their crustal roots were destroyed in conjunction with Devonian wrench tectonics and back-arc rifting. During the Permo-Carboniferous tectonomagmatic cycle, wrench faulting disrupted the crust of the Variscan Orogen and its foreland and the lithosphere of these regions was thermally destabilized. Late Permian and Mesozoic re-equilibration of the lithosphere-asthenosphere system was interrupted by the development of the Arctic-North Atlantic, Tethyan and associated rift systems. During the Alpine orogenic cycle, intraplate compressional stresses controlled basin inversion-related crustal thickening and lithospheric folding, as well as the evolution of the Rhine-Rhone rift system. Variably deep crustal roots characterize the Alpine orogenic chains. Neogene back-arc extension disrupted the eastern Pyrenees, Betic-Balearic, Apennine and Dinarides orogens.

A new Moho depth map has been assembled for Western and Central Europe and the Western Mediterranean area that is exclusively based on published regional Moho depth maps. Tectonic overlays summarize Caledonian and Variscan tectonic units, Permo-Carboniferous fault systems and magmatic provinces, Mesozoic and Cenozoic rift-wrench systems, areas of intraplate compression, the outlines of Alpine orogens and the distribution of oceanic crust. Based on a comparison of these overlays with the Moho depth map we assess processes that controlled the evolution of the crust in the various parts of Europe through time. The present-day crustal configuration of Western and Central Europe results from polyphase Late Palaeozoic to recent lithospheric deformation that overprinted the margin of the Proterozoic East European Craton and particularly the Caledonian and Variscan crustal domains. Following consolidation of the Caledonides, their crustal roots were destroyed in conjunction with Devonian wrench tectonics and back-arc rifting. During the Permo-Carboniferous tectonomagmatic cycle, wrench faulting disrupted the crust of the Variscan Orogen and its foreland and the lithosphere of these regions was thermally destabilized. Late Permian and Mesozoic re-equilibration of the lithosphere-asthenosphere system was interrupted by the development of the Arctic-North Atlantic, Tethyan and associated rift systems. During the Alpine orogenic cycle, intraplate compressional stresses controlled basin inversion-related crustal thickening and lithospheric folding, as well as the evolution of the Rhine-Rhone rift system. Variably deep crustal roots characterize the Alpine orogenic chains. Neogene back-arc extension disrupted the eastern Pyrenees, Betic-Balearic, Apennine and Dinarides orogens.

The simplest scenario for the three known light neutrinos that fits the solar and atmospheric neutrino deficit and a mixed dark matter (MDM) picture of the universe requires them to be highly degenerate with $m_{\nu} \sim$ 1 - 2 eV. We propose an SO(10) grand unified model with an S$_{4}$-horizontal symmetry that leads naturally to such a scenario. An explicit numerical analysis of the quark and lepton sector of the model shows that it can lead to desired mass differences to fit all data only for the small angle non-adiabatic MSW solution to the solar neutrino puzzle., Comment: UMD-PP-94-95; (Latex file; 1 figure available on request)

We present our best estimates of the uncertainties due to heavy particle threshold corrections on the unification scale $M_U$, intermediate scale $M_I$ and coupling constant Alpha_U in the minimal non-supersymmetric SO(10) models. Using these , we update the predictions for proton life-time in these models., Comment: UMD-PP-94-117 ( 20 pages;latex; no figures )

We present our best estimates of the uncertainties due to heavy particle threshold corrections on the unification scale $M_U$, intermediate scale $M_I$ and coupling constant Alpha_U in the minimal non-supersymmetric SO(10) models. Using these , we update the predictions for proton life-time in these models., Comment: UMD-PP-94-117 ( 20 pages;latex; no figures )

The simplest scenario for the three known light neutrinos that fits the solar and atmospheric neutrino deficit and a mixed dark matter (MDM) picture of the universe requires them to be highly degenerate with $m_{\nu} \sim$ 1 - 2 eV. We propose an SO(10) grand unified model with an S$_{4}$-horizontal symmetry that leads naturally to such a scenario. An explicit numerical analysis of the quark and lepton sector of the model shows that it can lead to desired mass differences to fit all data only for the small angle non-adiabatic MSW solution to the solar neutrino puzzle., Comment: UMD-PP-94-95; (Latex file; 1 figure available on request)