Influenza A virus causes maternal and fetal pathology via innate and adaptive vascular inflammation in mice

Influenza A virus (IAV) infection during pregnancy causes severe maternal and perinatal complications, despite a lack of vertical transmission of IAV across the placenta. Here, we demonstrate a significant alteration in the maternal vascular landscape that underpins the maternal and downstream fetal pathology to IAV infection in mice. In IAV infection of nonpregnant mice, the local lung inflammatory response was contained to the lungs and was self-resolving, whereas in pregnant mice, virus dissemination to major maternal blood vessels, including the aorta, resulted in a peripheral "vascular storm," with elevated proinflammatory and antiviral mediators and the influx of Ly6Clow and Ly6Chigh monocytes, plus neutrophils and T cells. This vascular storm was associated with elevated levels of the adhesion molecules ICAM and VCAM and the pattern-recognition receptors TLR7 and TLR9 in the vascular wall, resulting in profound vascular dysfunction. The sequalae of this IAV-driven vascular storm included placental growth retardation and intrauterine growth restriction, evidence of placental and fetal brain hypoxia, and increased circulating cell free fetal DNA and soluble Flt1. In contrast, IAV infection in nonpregnant mice caused no obvious alterations in endothelial function or vascular inflammation. Therefore, IAV infection during pregnancy drives a significant systemic vascular alteration in pregnant dams, which likely suppresses critical blood flow to the placenta and fetus. This study in mice provides a fundamental mechanistic insight and a paradigm into how an immune response to a respiratory virus, such as IAV, is likely to specifically drive maternal and fetal pathologies during pregnancy.Stella Liong, Osezua Oseghale, Eunice E. To, Kurt Brassington, Jonathan R. Erlich, Raymond Luong ... et al

Formulas for the Rayleigh wave speed in orthotropic elastic solids

Formulas for the speed of Rayleigh waves in orthotropic compressible elastic materials are obtained in explicit form by using the theory of cubic equations. Different formulas are obtained by using different forms of the (cubic) secular equation. Each formula is expressed as a continuous function of three dimensionless material parameters, which are the ratios of certain elastic constants. It is interesting to note that one of the formulas includes as a special case the formula obtained recently by Malischewsky for isotropic materials

On formulas for the Rayleigh wave speed

A formula for the speed of Rayleigh waves in isotropic materials is obtained by using the theory of cubic equations. It is expressed as a continuous function of a certain material parameter. The formula obtained by Malischewsky [Wave Motion 31 (2000) 93] is explained on the same basis and its connection with our formula is identified

On Rayleigh waves in incompressible orthotropic elastic solids

In this paper the secular equation for the Rayleigh wave speed in an incompressible orthotropic elastic solid is obtained in a form that does not admit spurious solutions. It is then shown that inequalities on the material constants that ensure positive definiteness of the strain–energy function guarantee existence and uniqueness of the Rayleigh wave speed. Finally, an explicit formula for the Rayleigh wave speed is obtaine

Geometrie in 7

Copy held by FIZ Karlsruhe / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Challenges facing radiation oncologists in the management of older cancer patients: Consensus of the international geriatric radiotherapy group

The management of older cancer patients remains difficult because of data paucity. Radiation oncologists need to identify potential issues which could affect treatment of those patients. A workshop was organized in Barcelona among international radiation oncologists with special interest in the management of older cancer patients on April 22, 2018. The following consensus was reached: 1. Older cancer patients often faced unconscious discriminating bias from cancer specialists and institutions because of their chronological age. 2. Advances in radiotherapy techniques have allowed patients with multiple co-morbidities precluding surgery or systemic therapy to achieve potential cure in early disease stages. 3. The lack of biomarkers for frailty remains an impediment to future research. 4. Access to healthcare insurance and daily transportation remains an issue in many countries; 5. Hypofractionation, brachytherapy, or stereotactic techniques may be ideally suited for older cancer patients to minimize transportation issues and to improve tolerance to radiotherapy. 6. Patients with locally advanced disease who are mentally and physically fit should receive combined therapy for potential cure. 7. The role of systemic therapy alone or combined with radiotherapy for frail patients needs to be defined in future clinical trials because of targeted agents or immunotherapy may be less toxic compared to conventional chemotherapy