Birds as bioindicators of plastic pollution in terrestrial and freshwater environments: A 30-year review.

Plastic pollution is a global concern that has grown ever more acute in recent years. Most research has focused on the impact of plastic pollution in marine environments. However, plastic is increasingly being detected in terrestrial and freshwater environments with key inland sources including landfills, where it is accessible to a wide range of organisms. Birds are effective bioindicators of pollutants for many reasons, including their high mobility and high intra- and interspecific variation in trophic levels. Freshwater and terrestrial bird species are under-represented in plastic pollution research compared to marine species. We reviewed 106 studies (spanning from 1994 onwards) that have detected plastics in bird species dwelling in freshwater and/or terrestrial habitats, identifying knowledge gaps. Seventy-two studies focused solely on macroplastics (fragments >5 mm), compared to 22 microplastic (fragments <5 mm) studies. A further 12 studies identified plastics as both microplastics and macroplastics. No study investigated nanoplastic (particles <100 nm) exposure. Research to date has geographical and species' biases while ignoring nanoplastic sequestration in free-living freshwater, terrestrial and marine bird species. Building on the baseline search presented here, we urge researchers to develop and validate standardised field sampling techniques and laboratory analytical protocols such as Raman spectroscopy to allow for the quantification and identification of micro- and nanoplastics in terrestrial and freshwater environments and the species therein. Future studies should consistently report the internalised and background concentrations, types, sizes and forms of plastics. This will enable a better understanding of the sources of plastic pollution and their routes of exposure to birds of terrestrial and freshwater environments, providing a more comprehensive insight into the potential impacts on birds.

Race, rituximab, and relapse in TTP.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.

Parental stress, food parenting practices and child snack intake during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruptions to the lives of families. This study aimed to investigate the impact of pandemic-associated stress on food parenting practices including interactions surrounding snacks, and child diet. METHODS: Parents (N = 318) of 2-12-year old children completed a cross-sectional online survey assessing current COVID-19-specific stress, pre-COVID-19 stress, financial stress (e.g. food insecurity), food parenting practices, and child snack intake frequency. Structural Equation Modeling was used to model simultaneous paths of relationships and test direct and indirect effects. RESULTS: Stress, including financial hardship, was higher compared with before the crisis. The majority of children had regular mealtimes and irregular snack times. Higher COVID-19-specific stress was associated with more non-nutritive use of food and snacks (e.g. emotional and instrumental feeding), but also more structure and positive interactions (e.g. eating with or engaging with child around mealtimes). Higher COVID-19-specific stress was also associated with greater child intake frequency of sweet and savory snacks, with some evidence for mediation by snack parenting practices. CONCLUSION: Our findings indicate that stress associated with the COVID-19 pandemic may be linked to child snack intake with potential impacts on child obesity risk, and suggest several modifiable points of intervention within the family context.

Preparations for a European R&D roadmap for an inertial fusion demo reactor.

A European consortium of 15 laboratories across nine nations have worked together under the EUROFusion Enabling Research grants for the past decade with three principle objectives. These are: (a) investigating obstacles to ignition on megaJoule-class laser facilities; (b) investigating novel alternative approaches to ignition, including basic studies for fast ignition (both electron and ion-driven), auxiliary heating, shock ignition, etc.; and (c) developing technologies that will be required in the future for a fusion reactor. A brief overview of these activities, presented here, along with new calculations relates the concept of auxiliary heating of inertial fusion targets, and provides possible future directions of research and development for the updated European Roadmap that is due at the end of 2020. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.

Network topology and stability of homologous multiblock copolymer physical gels.

The mechanical properties of physical gels generated by selectively swelling a homologous series of linear multiblock copolymers are investigated by quasistatic uniaxial tensile tests. We use the slip-tube network model to extract the contributions arising from network crosslinks and chain entanglements. The composition dependence of these contributions is established and considered in terms of simulations that identify the probabilities associated with chain conformations. Dynamic rheology provides additional insight into the characteristics and thermal stability of the molecular networks.

Phylogenetic and functional analysis of ADAMTS13 identifies highly conserved domains essential for allosteric regulation.

The metalloprotease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats member 13) prevents microvascular thrombosis by cleaving von Willebrand factor (VWF) within platelet-rich thrombi, and cleavage depends on allosteric activation of ADAMTS13 by the substrate VWF. Human ADAMTS13 has a short propeptide, metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C), and spacer (S) domains (proximal domains), followed by 7 T and 2 CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains (distal domains). Distal domains inhibit the catalytic proximal domains; binding of distal T8-CUB domains to the VWF D4 domain relieves autoinhibition and promotes cleavage of the nearby VWF A2 domain. However, the role of specific ADAMTS13 distal domains in this allosteric mechanism is not established. Assays of plasma ADAMTS13 from 20 placental mammals, birds, and amphibians show that allosteric regulation is broadly conserved, and phylogenetic analysis of 264 vertebrates shows the long propeptide, T3, T4, T6, and T6a domains have been deleted several times in placental mammals, birds, and fish. Notably, pigeon ADAMTS13 has only 3 distal T domains but was activated normally by human VWF D4 and cleaved VWF multimers, preferentially under fluid shear stress. Human ADAMTS13 constructed to resemble pigeon ADAMTS13 retained normal allosteric regulation and shear-dependent cleavage of VWF. Thus, the T3-T6 domains of human ADAMTS13 are dispensable. Conversely, deletion of T7 or T8 abolished allosteric activation. For most species, some sequence changes in the VWF substrate can markedly increase the rate of cleavage, suggesting that ADAMTS13 and VWF have not evolved to be optimal enzyme-substrate pairs. These properties may reflect evolutionary pressure to balance the risk for VWF-dependent bleeding and thrombosis.

Exploring the "minimal" structure of a functional ADAMTS13 by mutagenesis and small-angle X-ray scattering.

Human ADAMTS13 is a multidomain protein with metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C), and spacer (S) domains, followed by 7 additional T domains and 2 CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains. ADAMTS13 inhibits the growth of von Willebrand factor (VWF)-platelet aggregates by cleaving the cryptic Tyr1605-Met1606 bond in the VWF A2 domain. ADAMTS13 is regulated by substrate-induced allosteric activation; without shear stress, the distal T8-CUB domains markedly inhibit VWF cleavage, and binding of VWF domain D4 or selected monoclonal antibodies (MAbs) to distal ADAMTS13 domains relieves this autoinhibition. By small angle X-ray scattering (SAXS), ADAMTS13 adopts a hairpin-like conformation with distal T7-CUB domains close to the proximal MDTCS domains and a hinge point between T4 and T5. The hairpin projects like a handle away from the core MDTCS and T7-CUB complex and contains distal T domains that are dispensable for allosteric regulation. Truncated constructs that lack the T8-CUB domains are not autoinhibited and cannot be activated by VWF D4 but retain the hairpin fold. Allosteric activation by VWF D4 requires T7, T8, and the 58-amino acid residue linker between T8 and CUB1. Deletion of T3 to T6 produced the smallest construct (delT3-6) examined that could be activated by MAbs and VWF D4. Columba livia (pigeon) ADAMTS13 (pADAMTS13) resembles human delT3-6, retains normal activation by VWF D4, and has a SAXS envelope consistent with amputation of the hairpin containing the dispensable T domains of human ADAMTS13. Our findings suggest that human delT3-6 and pADAMTS13 approach a "minimal" structure for allosterically regulated ADAMTS13.

Biosecurity system reforms and the development of a risk-based surveillance and pathway analysis system for ornamental fish imported into Australia.

The ornamental fish trade in Australia has an estimated value of AUD$350 million and involves importation of up to 20 million fish from 26 approved countries each year. Critical reviews indicated that the biosecurity system did not fully manage the risks associated with fish that were sub-clinically infected with diseases such as megalocytiviruses, or the threats posed by emerging diseases. Subsequent reforms have placed a greater emphasis on managing biosecurity risks off-shore at the source, coupled with an on-arrival surveillance system to assess compliance with biosecurity regulation. This presentation at the first global Conference in Aquatic Animal Epidemiology in Oslo, Norway in September 2016, describes the Department of Agriculture Water Resources' current initiatives to address increased risks in real-time while facilitating safe trade. The department is developing an innovative real-time, responsive risk-based surveillance capability to detect systemic failures on the part of the animal health authorities. The program involves a risk-based sampling algorithm on ornamental fish imported into Australia and testing for megalocytiviruses, spring viraemia of carp virus and Aeromonas salmonicida. We present the system and the results from several trials. The information generated by the verification surveillance system will be quantitative and semi-quantitative in nature and will form the basis of the department's response to detect systematic non-compliances by overseas authorities. Evidence collected through the ongoing analysis of surveillance data will become the basis of real-time feedback to overseas authorities for remedial action at source. Delays in resolving non-compliance issues could result in the suspension of off-shore equivalent measures from particular sources.

Single-shot frequency-resolved optical gating for retrieving the pulse shape of high energy picosecond pulses.

Accurate characterization of laser pulses used in experiments is a crucial step to the analysis of their results. In this paper, a novel single-shot frequency-resolved optical gating (FROG) device is described, one that incorporates a dispersive element which allows it to fully characterize pulses up to 25 ps in duration with a 65 fs per pixel temporal resolution. A newly developed phase retrieval routine based on memetic algorithms is implemented and shown to circumvent the stagnation problem that often occurs with traditional FROG analysis programs when they encounter a local minimum.

Communication: Molecular-level description of constrained chain topologies in multiblock copolymer gel networks.

Network characteristics in physical gels composed of solvated block copolymers varying in molecular design are examined here by dynamic rheology and computer simulations. In two triblock copolymer series, one with chain length (N) varied at constant copolymer composition (f) and the other with f varied at constant N, we discern the dependence of equilibrium network metrics on both N and f. Increasing the block number in a linear multiblock series at constant N and f escalates conformational complexity, which dominates network connectivity classified according to a midblock conformation index.

Channel optimization of high-intensity laser beams in millimeter-scale plasmas.

Channeling experiments were performed at the OMEGA EP facility using relativistic intensity (>10^{18}W/cm^{2}) kilojoule laser pulses through large density scale length (∼390-570 µm) laser-produced plasmas, demonstrating the effects of the pulse's focal location and intensity as well as the plasma's temperature on the resulting channel formation. The results show deeper channeling when focused into hot plasmas and at lower densities, as expected. However, contrary to previous large-scale particle-in-cell studies, the results also indicate deeper penetration by short (10 ps), intense pulses compared to their longer-duration equivalents. This new observation has many implications for future laser-plasma research in the relativistic regime.

Anaesthesia: what a surgeon needs to know.

Surgeons and anaesthetists work closely together, sometimes in challenging circumstances. To help surgeons cooperate with anaesthetists to deliver high quality care for patients, a working knowledge of modern anaesthetic practice is useful. The specialty of anaesthetics is developing rapidly, and periodic updating of this knowledge is likely to be required. This article provides an update of anaesthetic practice for surgeons, covering the varied roles of anaesthetists, preoperative assessment, management on the day of surgery (induction, maintenance and reversal of anaesthetic), general anaesthesia, the role of regional blocks and sedation. It also discusses safety issues, the management of frail patients and future challenges.

Pathophysiology of thrombotic thrombocytopenic purpura.

The discovery of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) revolutionized our approach to thrombotic thrombocytopenic purpura (TTP). Inherited or acquired ADAMTS13 deficiency allows the unrestrained growth of microthrombi that are composed of von Willebrand factor and platelets, which account for the thrombocytopenia, hemolytic anemia, schistocytes, and tissue injury that characterize TTP. Most patients with acquired TTP respond to a combination of plasma exchange and rituximab, but some die or acquire irreversible neurological deficits before they can respond, and relapses can occur unpredictably. However, knowledge of the pathophysiology of TTP has inspired new ways to prevent early deaths by targeting autoantibody production, replenishing ADAMTS13, and blocking microvascular thrombosis despite persistent ADAMTS13 deficiency. In addition, monitoring ADAMTS13 has the potential to identify patients who are at risk of relapse in time for preventive therapy.

Dense plasma heating by crossing relativistic electron beams.

Here we investigate, using relativistic fluid theory and Vlasov-Maxwell simulations, the local heating of a dense plasma by two crossing electron beams. Heating occurs as an instability of the electron beams drives Langmuir waves, which couple nonlinearly into damped ion-acoustic waves. Simulations show a factor 2.8 increase in electron kinetic energy with a coupling efficiency of 18%. Our results support applications to the production of warm dense matter and as a driver for inertial fusion plasmas.

Warfarin traps human vitamin K epoxide reductase in an intermediate state during electron transfer.

Although warfarin is the most widely used anticoagulant worldwide, the mechanism by which warfarin inhibits its target, human vitamin K epoxide reductase (hVKOR), remains unclear. Here we show that warfarin blocks a dynamic electron-transfer process in hVKOR. A major fraction of cellular hVKOR is in an intermediate redox state containing a Cys51-Cys132 disulfide, a characteristic accommodated by a four-transmembrane-helix structure of hVKOR. Warfarin selectively inhibits this major cellular form of hVKOR, whereas disruption of the Cys51-Cys132 disulfide impairs warfarin binding and causes warfarin resistance. Relying on binding interactions identified by cysteine alkylation footprinting and mass spectrometry coupled with mutagenesis analysis, we conducted structure simulations, which revealed a closed warfarin-binding pocket stabilized by the Cys51-Cys132 linkage. Understanding the selective warfarin inhibition of a specific redox state of hVKOR should enable the rational design of drugs that exploit the redox chemistry and associated conformational changes in hVKOR.

Identification and characterization of the elusive mutation causing the historical von Willebrand Disease type IIC Miami.

UNLABELLED: Essentials Von Willebrand disease IIC Miami features high von Willebrand factor (VWF) with reduced function. We aimed to identify and characterize the elusive underlying mutation in the original family. An inframe duplication of VWF exons 9-10 was identified and characterized. The mutation causes a defect in VWF multimerization and decreased VWF clearance from the circulation. SUMMARY: Background A variant of von Willebrand disease (VWD) type 2A, phenotype IIC (VWD2AIIC), is characterized by recessive inheritance, low von Willebrand factor antigen (VWF:Ag), lack of VWF high-molecular-weight multimers, absence of VWF proteolytic fragments and mutations in the VWF propeptide. A family with dominantly inherited VWD2AIIC but markedly elevated VWF:Ag of > 2 U L(-1) was described as VWD type IIC Miami (VWD2AIIC-Miami) in 1993; however, the molecular defect remained elusive. Objectives To identify the molecular mechanism underlying the phenotype of the original VWD2AIIC-Miami. Patients and Methods We studied the original family with VWD2AIIC-Miami phenotypically and by genotyping. The identified mutation was recombinantly expressed and characterized by standard techniques, confocal imaging and in a mouse model, respectively. Results By Multiplex ligation-dependent probe amplification we identified an in-frame duplication of VWF exons 9-10 (c.998_1156dup; p.Glu333_385dup) in all patients. Recombinant mutant (rm)VWF only presented as a dimer. Co-expressed with wild-type VWF, the multimer pattern was indistinguishable from patients' plasma VWF. Immunofluorescence studies indicated retention of rmVWF in unusually large intracellular granules in the endoplasmic reticulum. ADAMTS-13 proteolysis of rmVWF under denaturing conditions was normal; however, an aberrant proteolytic fragment was apparent. A decreased ratio of VWF propeptide to VWF:Ag and a 1-desamino-8-d-arginine vasopressin (DDAVP) test in one patient indicated delayed VWF clearance, which was supported by clearance data after infusion of rmVWF into VWF(-/-) mice. Conclusion The unique phenotype of VWD2 type IIC-Miami results from dominant impairment of multimer assembly, an aberrant structure of mutant mature VWF and reduced clearance in vivo.

The functions of the A1A2A3 domains in von Willebrand factor include multimerin 1 binding.

Multimerin 1 (MMRN1) is a massive, homopolymeric protein that is stored in platelets and endothelial cells for activation-induced release. In vitro, MMRN1 binds to the outer surfaces of activated platelets and endothelial cells, the extracellular matrix (including collagen) and von Willebrand factor (VWF) to support platelet adhesive functions. VWF associates with MMRN1 at high shear, not static conditions, suggesting that shear exposes cryptic sites within VWF that support MMRN1 binding. Modified ELISA and surface plasmon resonance were used to study the structural features of VWF that support MMRN1 binding, and determine the affinities for VWF-MMRN1 binding. High shear microfluidic platelet adhesion assays determined the functional consequences for VWF-MMRN1 binding. VWF binding to MMRN1 was enhanced by shear exposure and ristocetin, and required VWF A1A2A3 region, specifically the A1 and A3 domains. VWF A1A2A3 bound to MMRN1 with a physiologically relevant binding affinity (KD: 2.0 ± 0.4 nM), whereas the individual VWF A1 (KD: 39.3 ± 7.7 nM) and A3 domains (KD: 229 ± 114 nM) bound to MMRN1 with lower affinities. VWF A1A2A3 was also sufficient to support the adhesion of resting platelets to MMRN1 at high shear, by a mechanism dependent on VWF-GPIbα binding. Our study provides new information on the molecular basis of MMRN1 binding to VWF, and its role in supporting platelet adhesion at high shear. We propose that at sites of vessel injury, MMRN1 that is released following activation of platelets and endothelial cells, binds to VWF A1A2A3 region to support platelet adhesion at arterial shear rates.

What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura.

Severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency causes thrombotic thrombocytopenic purpura (TTP), which is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and the absence of oliguric or anuric renal failure. However, some patients with this constellation of findings do not have ADAMTS13 deficiency, and some patients with ADAMTS13 deficiency have renal failure or relatively normal blood counts. Consequently, many investigators and clinicians have incorporated severe ADAMTS13 deficiency into the case definition of TTP. This change has facilitated the timely initiation of treatment for patients with atypical clinical features who otherwise would not be recognized as having TTP. Conversely, excluding severe ADAMTS13 deficiency focuses attention on the diagnosis and treatment of other causes of thrombotic microangiopathy that require different treatment. The rapid return of ADAMTS13 data is important to make the best use of this information.