Characterization of the complications associated with plasma exchange for thrombotic thrombocytopaenic purpura and related thrombotic microangiopathic anaemias: a single institution experience.

Plasma exchange (PEX) is a life-saving therapeutic procedure in patients with thrombotic thrombocytopaenic purpura (TTP) and other thrombotic microangiopathic anaemias (TMAs). However, it may be associated with significant complications, exacerbating the morbidity and mortality in this patient group

Cryptic Seed Heteromorphism in Packera tomentosa (Asteraceae) : Differences in Seed Mass Characteristics and Germination

Germination requirements of seeds can dictate when and where plant offspring establish. Microsites available for germination vary spatially and temporally in factors such as temperature and moisture; thus, the production of seeds with identical requirements may limit germination. When seed mass influences germination and offspring establishment, the production of seeds with a range of sizes encourages differential behavior in progeny. Seed heteromorphism, the production of two or more seed types with different forms and/or behaviors by the same plant, may be "cryptic" when seed types have different behaviors but similar morphologies. Although rarely documented, cryptic seed heteromorphism may be widespread among plant taxa. The production by a plant of seeds with variable mass or heteromorphism may increase the number of microsites favorable for germination. I investigated seed mass variation and seed heteromorphism in Packera tomentosa (Michx.) C. Jeffrey (woolly ragwort, Asteraceae), a clonal plant found in disturbed habitats in the coastal plain of the southeastern U.S. Like most members of the Asteraceae, P. tomentosa displays flowering heads that contain disc and ray florets, which produce central and peripheral seeds, respectively. Seeds were collected from 50 purported clones of P. tomentosa at East Carolina University's West Research Campus (WRC), Pitt County, North Carolina. Seed mass was compared among- and within-genetic individuals as well as between floret types of a flowering head. Amplified fragment length polymorphism (AFLP) profiles confirmed that all 50 clones were unique genetic individuals or "genets", verifying that seedling recruitment does occur in this population of P. tomentosa. I compared total mass and allocation to the embryo and pericarp between central and peripheral seeds. An initial study investigated germinability and speed of germination for both seed types in controlled conditions. I then tested the germination response of central and peripheral seeds to frequent, intermediate, and infrequent watering intervals. A final study determined whether germination speed or success of central and peripheral seeds was influenced by aging and/or cold stratification. Overall, seed mass of Packera tomentosa was highly variable among- and within-plants. Larger seeds exhibited faster, higher germination. Central and peripheral seeds did not have different morphologies, but differed in mass characteristics and germination. Central seeds were 11% heavier with 80% larger embryos than were peripheral seeds, whereas peripheral seeds allocated 17% more of total mass to the fruit coat than did central seeds. Differences in total mass between seed types appear to be driven by embryo size. Central seeds germinated at a higher proportion than did peripheral seeds (74.5 vs. 36.0%, respectively) and germinated faster than peripheral seeds (32.8 vs. 36.2 d, respectively). Differences in germination may be due to pericarp thickness or embryo size. Central seeds exhibited greater germination success in frequent and infrequent watering intervals, but not in the intermediate watering interval. Both seeds types showed lowest germination in response to infrequent watering, suggesting germination success decreases in drought conditions. Germination speed increased in central seeds following aging; thus, central seeds after-ripen. In contrast, peripheral seeds germinated faster after cold stratification, suggesting they delay germination and are stimulated by cooler temperatures. Cryptic seed heteromorphism occurs in Packera tomentosa, supporting the suggestion that this trait may be more common than is documented, particularly in the Asteraceae. In P. tomentosa, variation in germination behavior resulting from seed mass variation and seed heteromorphism may spread the risks associated with germination among many offspring phenotypes, potentially functioning as bet-hedging strategies and providing success in the unpredictable environments this species inhabits.M.S

Using a Contextual Effects Measurement Approach to Understand the Influence of Community on Individual Behavior

A social organization perspective identifies processes operating in the community that may influence an individual’s behavior. To understand such processes, researchers can apply a contextual effects measurement approach, which is used to assess the influence of group-level effects on lower level outcomes. However, few community studies employ this approach. The purpose of this article is to present and evaluate the merits of the contextual effects measurement approach

An analysis of the structure of Saturn's magnetic field using charged particle absorption signatures

A new technique is derived for determining the structure of Saturn's magnetic field. This technique uses the observed positions of charged particle absorption signatures due to the satellites and rings of Saturn to determine the parameters of an axially symmetric, spherical harmonic model of the magnetic field using the method of least squares. Absorption signatures observed along the Pioneer 11, Voyager 1, and Voyager 2 spacecraft trajectories are used to derive values for the orientation of the magnetic symmetry axis relative to Saturn's axis of rotation, the axial displacement of the center of the magnetic dipole from the center of Saturn, and the magnitude of the external field component. Comparing these results with the magnetic field model parameters deduced from analyses of magnetometer data leads us to prefer models that incorporate a northward offset of the dipole center by about 0.05 R_s

Plasma exchange for COVID-19 thrombo-inflammatory disease.

Severe COVID-19 disease is a hyperinflammatory, pro-thrombotic state. We undertook plasma exchange (PEX) to determine its effects on organ function and thrombo-inflammatory markers. Seven critically ill adults with severe COVID-19 respiratory failure (PaO2:FiO2 ratio 800 IU/L and D-dimer >1000 μg/L (or doubling from baseline) received PEX, daily, for a minimum of 5 days. No other immunomodulatory medications were initiated during this period. Seven patients matched for age and baseline biochemistry were a comparator group. Coagulation screening revealed no evidence of coagulopathy. However, von Willebrand Factor (VWF) activity, antigen and VWF antigen: ADAMTS13 ratio, Factor VIII and D-dimers were all elevated. Following 5 days of PEX, plasma levels of all the above, and ferritin levels, were significantly reduced (P < .05) while lymphocyte counts normalized (P < .05). The PaO2:FiO2 ratio increased from a median interquartile range (IQR) of 11.6 (10.8-19.7) kPa to 18.1 (16.0-25.9) kPa (P < .05). Similar improvements were not observed in controls. Acute kidney injury (AKI) occurred among five patients in the control arm but not in patients receiving PEX. PEX improved oxygenation, decreased the incidence of AKI, normalized lymphocyte counts and reduced circulating thrombo-inflammatory markers including D-Dimer and VWF Ag:ADAMTS13 ratio

Pharmacology beyond the patient – The environmental risks of human drugs

The presence of pharmaceuticals in the environment is a growing global concern and although environmental risk assessment is required for approval of new drugs in Europe and the USA, the adequacy of the current triggers and the effects-based assessments has been questioned. Objective: To provide a comprehensive analysis of all regulatory compliant aquatic ecotoxicity data and evaluate the current triggers and effects-based environmental assessments to facilitate the development of more efficient approaches for pharmaceuticals toxicity testing. Methods: Publicly-available regulatory compliant ecotoxicity data for drugs targeting human proteins was compiled together with pharmacological information including drug targets, Cmax and lipophilicity. Possible links between these factors and the ecotoxicity data for effects on, growth, mortality and/or reproduction, were evaluated. The environmental risks were then assessed based on a combined analysis of drug toxicity and predicted environmental concentrations based on European patient consumption data. Results: For most (88%) of the of 975 approved small molecule drugs targeting human proteins a complete set of regulatory compliant ecotoxicity data in the public domain was lacking, highlighting the need for both intelligent approaches to prioritize legacy human drugs for a tailored environmental risk assessment and a transparent database that captures environmental data. We show that presence/absence of drug-target orthologues are predictive of susceptible species for the more potent drugs. Drugs that target the endocrine system represent the highest potency and greatest risk. However, for most drugs (>80%) with a full set of ecotoxicity data, risk quotients assuming worst-case exposure assessments were below one in all European countries indicating low environmental risks for the endpoints assessed. Conclusion: We believe that the presented analysis can guide improvements to current testing procedures, and provide valuable approaches for prioritising legacy drugs (i.e. those registered before 2006) for further ecotoxicity testing. For drugs where effects of possible concern (e.g. behaviour) are not captured in regulatory tests, additional mechanistic testing may be required to provide the highest confidence for avoiding environmental impacts.AstraZeneca Global SHE Research Programm

Cyber Insurance: recent advances, good practices & challenges

The aim of this ENISA report is to raise awareness for the most impact to market advances, by shortly identifying the most significant cyber insurance developments for the past four years – during 2012 to 2016 – and to capture the good practices and challenges during the early stages of the cyber insurance lifecycle, i.e. before an actual policy is signed, laying the ground for future work in the area

Comparison of two‐dimensional and three‐dimensional simulations of dense nonaqueous phase liquids (DNAPLs): Migration and entrapment in a nonuniform permeability field

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95015/1/wrcr10030.pd

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013 . Scientific opinion on Dietary Reference Values for fluoride

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for fluoride, which are provided as Adequate Intake (AI) from all sources, including non-dietary sources. Fluoride is not an essential nutrient. Therefore, no Average Requirement for the performance of essential physiological functions can be defined. Nevertheless, the Panel considered that the setting of an AI is appropriate because of the beneficial effects of dietary fluoride on prevention of dental caries. The AI is based on epidemiological studies (performed before the 1970s) showing an inverse relationship between the fluoride concentration of water and caries prevalence. As the basis for defining the AI, estimates of mean fluoride intakes of children via diet and drinking water with fluoride concentrations at which the caries preventive effect approached its maximum whilst the risk of dental fluorosis approached its minimum were chosen. Except for one confirmatory longitudinal study in US children, more recent studies were not taken into account as they did not provide information on total dietary fluoride intake, were potentially confounded by the use of fluoride-containing dental hygiene products, and did not permit a conclusion to be drawn on a dose-response relationship between fluoride intake and caries risk. The AI of fluoride from all sources (including non-dietary sources) is 0.05 mg/kg body weight per day for both children and adults, including pregnant and lactating women. For pregnant and lactating women, the AI is based on the body weight before pregnancy and lactation. Reliable and representative data on the total fluoride intake of the European population are not available