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A phase 2 randomized, double-blind, placebo-controlled trial of MHAA4549A, a monoclonal antibody, plus oseltamivir in patients hospitalized with severe influenza a virus infection

For patients hospitalized with severe influenza A virus infection, morbidity and mortality remain high. MHAA4549A, a human monoclonal antibody targeting the influenza A virus hemagglutinin stalk, has demonstrated pharmacological activity in animal studies and in a human influenza A challenge study. We evaluated the safety and efficacy of MHAA4549A plus oseltamivir against influenza A virus infecti

Genetically programmed changes in transcription of the novel progranulin regulator

Abstract: Progranulin is a glycoprotein marking chronic inflammation in obesity and type 2 diabetes. Previous studies suggested PSRC1 (proline and serine rich coiled-coil 1) to be a target of genetic variants associated with serum progranulin levels. We aimed to identify potentially functional variants and characterize their role in regulation of PSRC1. Phylogenetic module complexity analysis (PMC

A treatment planning and delivery comparison of volumetric modulated arc therapy with or without flattening filter for gliomas, brain metastases, prostate, head/neck and early stage lung cancer

Background. Flattening filter-free (FFF) beams are an emerging technology that has not yet been widely implemented as standard practice in radiotherapy centers. To facilitate the clinical implementation of FFF, we attempted to elucidate the difference in plan quality and treatment delivery time compared to flattening filter beams (i.e. standard, STD) for several patient groups. We hypothesize that

Von Willebrand factor mediates pneumococcal aggregation and adhesion in blood flow

Streptococcus pneumoniae is a major cause of community acquired pneumonia and septicaemia in humans. These diseases are frequently associated with thromboembolic cardiovascular complications. Pneumococci induce the exocytosis of endothelial Weibel-Palade Bodies and thereby actively stimulate the release of von Willebrand factor (VWF), which is an essential glycoprotein of the vascular hemostasis.

The regional European atmospheric transport inversion comparison, EUROCOM : First results on European-wide terrestrial carbon fluxes for the period 2006-2015

Atmospheric inversions have been used for the past two decades to derive large-scale constraints on the sources and sinks of CO2 into the atmosphere. The development of dense in situ surface observation networks, such as ICOS in Europe, enables in theory inversions at a resolution close to the country scale in Europe. This has led to the development of many regional inversion systems capable of as

HIMMELI v1.0 : HelsinkI Model of MEthane buiLd-up and emIssion for peatlands

Wetlands are one of the most significant natural sources of methane (CH4) to the atmosphere. They emit CH4 because decomposition of soil organic matter in waterlogged anoxic conditions produces CH4, in addition to carbon dioxide (CO2). Production of CH4 and how much of it escapes to the atmosphere depend on a multitude of environmental drivers. Models simulating the processes leading to CH4 emissi

Towards physiologically meaningful water-use efficiency estimates from eddy covariance data

Intrinsic water-use efficiency (iWUE) characterizes the physiological control on the simultaneous exchange of water and carbon dioxide in terrestrial ecosystems. Knowledge of iWUE is commonly gained from leaf-level gas exchange measurements, which are inevitably restricted in their spatial and temporal coverage. Flux measurements based on the eddy covariance (EC) technique can overcome these limit

Characterization of a membrane binding loop leads to engineering botulinum neurotoxin B with improved therapeutic efficacy

Botulinum neurotoxins (BoNTs) are a family of bacterial toxins with seven major serotypes (BoNT/A-G). The ability of these toxins to target and bind to motor nerve terminals is a key factor determining their potency and efficacy. Among these toxins, BoNT/B is one of the two types approved for medical and cosmetic uses. Besides binding to well-established receptors, an extended loop in the C-termin

Problems in variation interpretation guidelines and in their implementation in computational tools

Background: ACMG/AMP and AMP/ASCO/CAP have released guidelines for variation interpretation, and ESHG for diagnostic sequencing. These guidelines contain recommendations including the use of computational prediction methods. The guidelines per se and the way they are implemented cause some problems. Methods: Logical reasoning based on domain knowledge. Results: According to the guidelines, several

Early intervention with compression garments prevents progression in mild breast cancer-related arm lymphedema : a randomized controlled trial

Background: Early diagnosis and compression treatment are important to prevent progression in breast cancer-related arm lymphedema (BCRAL). However, some mild BCRAL can be reversible, and therefore, compression treatment may not be needed. The aim of this study was to investigate the proportion of women with mild BCRAL showing progression/no progression of lymphedema after treatment with or withou

The ikaite to calcite transformation : Implications for palaeoclimate studies

Marine sedimentary ikaite is the parent mineral to glendonite, stellate pseudomorphs found throughout the geological record which are most usually composed of calcite. Ikaite is known to be metastable at earth surface temperatures and pressures, readily breaking down to more stable carbonate polymorphs when exposed to warm (ambient) conditions. Yet the process of transformation of ikaite to calcit

Weak population genetic structure in Eurasian spruce bark beetle over large regional scales in Sweden

The Eurasian spruce bark beetle, Ips typographus, is a major pest, capable of killing spruce forests during large population outbreaks. Recorded dispersal distances of individual beetles are typically within hundreds of meters or a few kilometers. However, the connectivity between populations at larger distances and longer time spans and how this is affected by the habitat is less studied, despite

Statin use and patterns of breast cancer recurrence in the Malmö Diet and Cancer Study

Background: Accumulating evidence suggests that statins have a beneficial effect on breast cancer prognosis. Previous studies have reported a positive association between statin use and breast cancer survival; however, the relationship between statin use and patterns of breast cancer recurrence remains unclear. Patients and methods: We identified all Malmö Diet and Cancer Study (MDCS) participants

FAIRVASC: A semantic web approach to rare disease registry integration

Rare disease data is often fragmented within multiple heterogeneous siloed regional disease registries, each containing a small number of cases. These data are particularly sensitive, as low subject counts make the identification of patients more likely, meaning registries are not inclined to share subject level data outside their registries. At the same time access to multiple rare disease datase

The role of hyperthermic intraperitoneal intraoperative chemotherapy in ovarian cancer

Epithelial ovarian cancer (EOC) is the fourth most common gynecologic cancer in Europe and is the leading cause of death among women with gynecologic malignancies. This is due to the fact that the majority of the patients are diagnosed with advanced stage disease. In these stages, extensive intraperitoneal metastases are often present, making therapy more difficult. The current standard treatment

Phobos base : Concept of operations and architecture for a permanent human presence on the Martian moon Phobos

This paper is based on the work done for the 2017 AIAA Student Design Competition-Human Spaceflight: Phobos Base. One of humanity's major challenges when travelling to Mars is represented by the existence of an atmosphere around the red planet. In fact, even though the Martian atmospheric density is only about 1% of that of Earth, the entry, descent and landing (EDL) procedure for large payloads i

Spatial heterogeneity of soil carbon exchanges and their drivers in a boreal forest

Boreal forests have a large impact on the global greenhouse gas balance and their soils constitute an important carbon (C) reservoir. Mature boreal forests are typically a net CO2 sink, but there are also examples of boreal forests that are persistent CO2 sources. The reasons remain often unknown, presumably due to a lack of understanding of how biotic and abiotic drivers interact to determine the

The Environmental Gaze : Visual perspectives on monitoring landscapes of ecological devastation

The increasing application of monitoring technologies and the specific perspectives afforded through them are transforming our understanding of and relationship to our environment. Through systems of mass data accrual, the physical processes and elemental attributes of regional and planetary landscapes are transformed into media, such as digital multilayered maps, graphs, thermal imaging, models,