Showing papers by "Trinity College, Dublin published in 2020"

A minimal common outcome measure set for COVID-19 clinical research

Abstract: Summary Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.

WFH Guidelines for the Management of Hemophilia, 3rd edition

Abstract: Alok Srivastava 1 | Elena Santagostino 2 | Alison Dougall 3 | Steve Kitchen 4 | Megan Sutherland 5 | Steven W. Pipe 6 | Manuel Carcao 7 | Johnny Mahlangu 8 | Margaret V. Ragni 9 | Jerzy Windyga 10 | Adolfo Llinás 11 | Nicholas J. Goddard 12 | Richa Mohan 13 | Pradeep M. Poonnoose 14 | Brian M. Feldman 15 | Sandra Zelman Lewis 16 | H. Marijke van den Berg 17 | Glenn F. Pierce 18 | on behalf of the WFH Guidelines for the Management of Hemophilia panelists and co-authors*

Mental health in the COVID-19 pandemic.

Abstract: During any outbreak of an infectious disease, the population’s psychological reactions play a critical role in shaping both spread of the disease and the occurrence of emotional distress and social disorder during and after the outbreak. Despite this fact, sufficient resources are typically not provided to manage or attenuate pandemics’ effects on mental health and wellbeing. While this might be understandable in the acute phase of an outbreak, when health systems prioritize testing, reducing transmission and critical patient care, psychological and psychiatric needs should not be overlooked during any phase of pandemic management. There are many reasons for this. It is known that psychological factors play an important role in adherence to public health measures (such as vaccination) and in how people cope with the threat of infection and consequent losses. These are clearly crucial issues to consider in the management of any infectious disease, including Covid-19. Psychological reactions to pandemics include maladaptive behaviours, emotional distress and defensive responses. People who are prone to psychological problems are especially vulnerable. All of these features are in clear evidence during the current Covid-19 pandemic. One study of 1210 respondents from 194 cities in China in January and February 2020 found that 54% of respondents rated the psychological impact of the Covid-19 outbreak as moderate or severe; 29% reported moderate to severe anxiety symptoms; and 17% reported moderate to severe depressive symptoms. Notwithstanding possible response bias, these are very high proportions—and it is likely that some people are at even greater risk. During the 2009 H1N1 influenza outbreak (‘swine flu’), a study of mental health patients found that children and patients with neurotic and somatoform disorders were significantly over-represented among those expressing moderate or severe concerns. Against this background, and as the Covid-19 pandemic continues to spread around the world, we hypothesize a number of psychological impacts that merit consideration now rather than later. In the first instance, it should be recognized that, even in the normal course of events, people with established mental illness have a lower life expectancy and poorer physical health outcomes than the general population. As a result, people with pre-existing mental health and substance use disorders will be at increased risk of infection with Covid-19, increased risk of having problems accessing testing and treatment and increased risk of negative physical and psychological effects stemming from the pandemic. Second, we anticipate a considerable increase in anxiety and depressive symptoms among people who do not have preexisting mental health conditions, with some experiencing post-traumatic stress disorder in due course. There is already evidence that this possibility has been under-recognized in China during the current pandemic. Third, it can be anticipated that health and social care professionals will be at particular risk of psychological symptoms, especially if they work in public health, primary care, emergency services, emergency departments and intensive or critical care. The World Health Organization has formally recognized this risk to healthcare workers, so more needs to be done to manage anxiety and stress in this group and, in the longer term, help prevent burnout, depression and post-traumatic stress disorder. There are several steps that can and should be taken now to minimize the psychological and psychiatric effects of the Covid19 pandemic. First, while it might be ostensibly attractive to re-deploy mental health professionals to work in other areas of healthcare, this should be avoided. Such a move would almost certainly worsen outcomes overall and place people with mental illness at disproportionate risk of deteriorations in physical and

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

Abstract: The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.

Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel

Abstract: Abstract

FLAG Review 2019

Abstract: We review lattice results related to pion, kaon, D-meson, B-meson, and nucleon physics with the aim of making them easily accessible to the nuclear and particle physics communities. More specifically, we report on the determination of the light-quark masses, the form factor $f_+(0)$ arising in the semileptonic $K \rightarrow \pi $ transition at zero momentum transfer, as well as the decay constant ratio $f_K/f_\pi $ and its consequences for the CKM matrix elements $V_{us}$ and $V_{ud}$. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of $SU(2)_L\times SU(2)_R$ and $SU(3)_L\times SU(3)_R$ Chiral Perturbation Theory. We review the determination of the $B_K$ parameter of neutral kaon mixing as well as the additional four B parameters that arise in theories of physics beyond the Standard Model. For the heavy-quark sector, we provide results for $m_c$ and $m_b$ as well as those for D- and B-meson decay constants, form factors, and mixing parameters. These are the heavy-quark quantities most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. We review the status of lattice determinations of the strong coupling constant $\alpha _s$. Finally, in this review we have added a new section reviewing results for nucleon matrix elements of the axial, scalar and tensor bilinears, both isovector and flavor diagonal.

Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection.

Abstract: Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (67/128; 52.3%) at median of 10 weeks after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.

Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

Abstract: Summary Background Isocitrate dehydrogenase 1 (IDH1) mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma, a relatively uncommon cancer with a poor clinical outcome. The aim of this international phase 3 study was to assess the efficacy and safety of ivosidenib (AG-120)—a small-molecule targeted inhibitor of mutated IDH1—in patients with previously treated IDH1-mutant cholangiocarcinoma. Methods This multicentre, randomised, double-blind, placebo-controlled, phase 3 study included patients from 49 hospitals in six countries aged at least 18 years with histologically confirmed, advanced, IDH1-mutant cholangiocarcinoma who had progressed on previous therapy, and had up to two previous treatment regimens for advanced disease, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned (2:1) with a block size of 6 and stratified by number of previous systemic treatment regimens for advanced disease to oral ivosidenib 500 mg or matched placebo once daily in continuous 28-day cycles, by means of an interactive web-based response system. Placebo to ivosidenib crossover was permitted on radiological progression per investigator assessment. The primary endpoint was progression-free survival by independent central review. The intention-to-treat population was used for the primary efficacy analyses. Safety was assessed in all patients who had received at least one dose of ivosidenib or placebo. Enrolment is complete; this study is registered with ClinicalTrials.gov , NCT02989857 . Findings Between Feb 20, 2017, and Jan 31, 2019, 230 patients were assessed for eligibility, and as of the Jan 31, 2019 data cutoff date, 185 patients were randomly assigned to ivosidenib (n=124) or placebo (n=61). Median follow-up for progression-free survival was 6·9 months (IQR 2·8–10·9). Progression-free survival was significantly improved with ivosidenib compared with placebo (median 2·7 months [95% CI 1·6–4·2] vs 1·4 months [1·4–1·6]; hazard ratio 0·37; 95% CI 0·25–0·54; one-sided p Interpretation Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma. Funding Agios Pharmaceuticals.

The genetic architecture of the human cerebral cortex

Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Changes in Physical Activity and Sedentary Behavior in Response to COVID-19 and Their Associations with Mental Health in 3052 US Adults.

Abstract: The COVID-19 pandemic altered many facets of life. We aimed to evaluate the impact of COVID-19-related public health guidelines on physical activity (PA), sedentary behavior, mental health, and their interrelations. Cross-sectional data were collected from 3052 US adults 3–8 April 2020 (from all 50 states). Participants self-reported pre- and post-COVID-19 levels of moderate and vigorous PA, sitting, and screen time. Currently-followed public health guidelines, stress, loneliness, positive mental health (PMH), social connectedness, and depressive and anxiety symptoms were self-reported. Participants were grouped by meeting US PA guidelines, reporting ≥8 h/day of sitting, or ≥8 h/day of screen time, pre- and post-COVID-19. Overall, 62% of participants were female, with age ranging from 18–24 (16.6% of sample) to 75+ (9.3%). Self-reported PA was lower post-COVID among participants reporting being previously active (mean change: −32.3% [95% CI: −36.3%, −28.1%]) but largely unchanged among previously inactive participants (+2.3% [−3.5%, +8.1%]). No longer meeting PA guidelines and increased screen time were associated with worse depression, loneliness, stress, and PMH (p < 0.001). Self-isolation/quarantine was associated with higher depressive and anxiety symptoms compared to social distancing (p < 0.001). Maintaining and enhancing physical activity participation and limiting screen time increases during abrupt societal changes may mitigate the mental health consequences.

A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum.

Abstract: Extracellular vesicles (EVs) are nano-sized vesicles containing nucleic acid and protein cargo that are released from a multitude of cell types and have gained significant interest as potential diagnostic biomarkers. Human serum is a rich source of readily accessible EVs; however, the separation of EVs from serum proteins and non-EV lipid particles represents a considerable challenge. In this study, we compared the most commonly used isolation techniques, either alone or in combination, for the isolation of EVs from 200 µl of human serum and their separation from non-EV protein and lipid particles present in serum. The size and yield of particles isolated by each method was determined by nanoparticle tracking analysis, with the variation in particle size distribution being used to determine the relative impact of lipoproteins and protein aggregates on the isolated EV population. Purification of EVs from soluble protein was determined by calculating the ratio of EV particle count to protein concentration. Finally, lipoprotein particles co-isolated with EVs was determined by Western blot analysis of lipoprotein markers APOB and APOE. Overall, this study reveals that the choice of EV isolation procedure significantly impacts EV yield from human serum, together with the presence of lipoprotein and protein contaminants.

BCG-induced trained immunity: can it offer protection against COVID-19?

Abstract: Bacillus Calmette–Guerin (BCG) vaccination has been reported to decrease susceptibility to respiratory tract infections, an effect proposed to be mediated by the general long-term boosting of innate immune mechanisms, also termed trained immunity. Here, we discuss the non-specific beneficial effects of BCG against viral infections and whether this vaccine may afford protection to COVID-19. Could the BCG vaccine be used to bridge the gap until a specific COVID-19 vaccine is developed? Luke O’Neill and Mihai Netea discuss the science behind this approach.

Anxiety and depression in the Republic of Ireland during the COVID-19 pandemic

Abstract: BACKGROUND: The COVID-19 pandemic in Ireland resulted in a nationwide quarantine on March 27th , 2020 This study represents the first assessment of rates of anxiety and depression in the general population of Ireland during the pandemic AIMS: Our first aim was to estimate the probable prevalence rates of generalized anxiety disorder (GAD) and depression, and to identify sociodemographic risk factors associated with screening positive for GAD or depression Our second aim was to determine if COVID-19 related anxiety was highest amongst those in society at greatest risk of morality from COVID-19 METHOD: Self-report data was collected from a nationally representative Irish sample (N = 1,041) online between March 31st and April 5th ;the first week of the nationwide quarantine measures Recognised cut-off scores on the GAD-7 and PHQ-9 were used to estimate rates of GAD and depression Correlates of screening positive for GAD or depression were assessed using logistic regression analysis RESULTS: GAD (20 0%), depression (22 8%), and GAD or depression (27 7%) were common Screening positive for GAD or depression was associated with younger age, female sex, loss of income due to COVID-19, COVID-19 infection, and higher perceived risk of COVID-19 infection Citizens aged 65 and older had significantly higher levels of COVID-19 related anxiety than adults aged 18-34 CONCLUSIONS: Initial results from this multi-wave study monitoring changes in population anxiety and depression throughout the pandemic indicate that GAD and depression were common experiences in the population during the initial phase of the COVID-19 pandemic

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

COVID19 coagulopathy in Caucasian patients.

Abstract: Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung-centric coagulopathy may play an important role. Elevated D-dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3-4-fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African-Americans. In this study, we investigated COVID19 coagulopathy in Caucasian patients. Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity. Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC). In rare COVID19 cases where DIC does develop, it tends to be restricted to late-stage disease. Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary-specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC. Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.

Production and processing of graphene and related materials

Abstract: © 2020 The Author(s). We present an overview of the main techniques for production and processing of graphene and related materials (GRMs), as well as the key characterization procedures. We adopt a 'hands-on' approach, providing practical details and procedures as derived from literature as well as from the authors' experience, in order to enable the reader to reproduce the results. Section I is devoted to 'bottom up' approaches, whereby individual constituents are pieced together into more complex structures. We consider graphene nanoribbons (GNRs) produced either by solution processing or by on-surface synthesis in ultra high vacuum (UHV), as well carbon nanomembranes (CNM). Production of a variety of GNRs with tailored band gaps and edge shapes is now possible. CNMs can be tuned in terms of porosity, crystallinity and electronic behaviour. Section II covers 'top down' techniques. These rely on breaking down of a layered precursor, in the graphene case usually natural crystals like graphite or artificially synthesized materials, such as highly oriented pyrolythic graphite, monolayers or few layers (FL) flakes. The main focus of this section is on various exfoliation techniques in a liquid media, either intercalation or liquid phase exfoliation (LPE). The choice of precursor, exfoliation method, medium as well as the control of parameters such as time or temperature are crucial. A definite choice of parameters and conditions yields a particular material with specific properties that makes it more suitable for a targeted application. We cover protocols for the graphitic precursors to graphene oxide (GO). This is an important material for a range of applications in biomedicine, energy storage, nanocomposites, etc. Hummers' and modified Hummers' methods are used to make GO that subsequently can be reduced to obtain reduced graphene oxide (RGO) with a variety of strategies. GO flakes are also employed to prepare three-dimensional (3d) low density structures, such as sponges, foams, hydro- or aerogels. The assembly of flakes into 3d structures can provide improved mechanical properties. Aerogels with a highly open structure, with interconnected hierarchical pores, can enhance the accessibility to the whole surface area, as relevant for a number of applications, such as energy storage. The main recipes to yield graphite intercalation compounds (GICs) are also discussed. GICs are suitable precursors for covalent functionalization of graphene, but can also be used for the synthesis of uncharged graphene in solution. Degradation of the molecules intercalated in GICs can be triggered by high temperature treatment or microwave irradiation, creating a gas pressure surge in graphite and exfoliation. Electrochemical exfoliation by applying a voltage in an electrolyte to a graphite electrode can be tuned by varying precursors, electrolytes and potential. Graphite electrodes can be either negatively or positively intercalated to obtain GICs that are subsequently exfoliated. We also discuss the materials that can be amenable to exfoliation, by employing a theoretical data-mining approach. The exfoliation of LMs usually results in a heterogeneous dispersion of flakes with different lateral size and thickness. This is a critical bottleneck for applications, and hinders the full exploitation of GRMs produced by solution processing. The establishment of procedures to control the morphological properties of exfoliated GRMs, which also need to be industrially scalable, is one of the key needs. Section III deals with the processing of flakes. (Ultra)centrifugation techniques have thus far been the most investigated to sort GRMs following ultrasonication, shear mixing, ball milling, microfluidization, and wet-jet milling. It allows sorting by size and thickness. Inks formulated from GRM dispersions can be printed using a number of processes, from inkjet to screen printing. Each technique has specific rheological requirements, as well as geometrical constraints. The solvent choice is critical, not only for the GRM stability, but also in terms of optimizing printing on different substrates, such as glass, Si, plastic, paper, etc, all with different surface energies. Chemical modifications of such substrates is also a key step. Sections IV-VII are devoted to the growth of GRMs on various substrates and their processing after growth to place them on the surface of choice for specific applications. The substrate for graphene growth is a key determinant of the nature and quality of the resultant film. The lattice mismatch between graphene and substrate influences the resulting crystallinity. Growth on insulators, such as SiO2, typically results in films with small crystallites, whereas growth on the close-packed surfaces of metals yields highly crystalline films. Section IV outlines the growth of graphene on SiC substrates. This satisfies the requirements for electronic applications, with well-defined graphene-substrate interface, low trapped impurities and no need for transfer. It also allows graphene structures and devices to be measured directly on the growth substrate. The flatness of the substrate results in graphene with minimal strain and ripples on large areas, allowing spectroscopies and surface science to be performed. We also discuss the surface engineering by intercalation of the resulting graphene, its integration with Si-wafers and the production of nanostructures with the desired shape, with no need for patterning. Section V deals with chemical vapour deposition (CVD) onto various transition metals and on insulators. Growth on Ni results in graphitized polycrystalline films. While the thickness of these films can be optimized by controlling the deposition parameters, such as the type of hydrocarbon precursor and temperature, it is difficult to attain single layer graphene (SLG) across large areas, owing to the simultaneous nucleation/growth and solution/precipitation mechanisms. The differing characteristics of polycrystalline Ni films facilitate the growth of graphitic layers at different rates, resulting in regions with differing numbers of graphitic layers. High-quality films can be grown on Cu. Cu is available in a variety of shapes and forms, such as foils, bulks, foams, thin films on other materials and powders, making it attractive for industrial production of large area graphene films. The push to use CVD graphene in applications has also triggered a research line for the direct growth on insulators. The quality of the resulting films is lower than possible to date on metals, but enough, in terms of transmittance and resistivity, for many applications as described in section V. Transfer technologies are the focus of section VI. CVD synthesis of graphene on metals and bottom up molecular approaches require SLG to be transferred to the final target substrates. To have technological impact, the advances in production of high-quality large-area CVD graphene must be commensurate with those on transfer and placement on the final substrates. This is a prerequisite for most applications, such as touch panels, anticorrosion coatings, transparent electrodes and gas sensors etc. New strategies have improved the transferred graphene quality, making CVD graphene a feasible option for CMOS foundries. Methods based on complete etching of the metal substrate in suitable etchants, typically iron chloride, ammonium persulfate, or hydrogen chloride although reliable, are time- and resourceconsuming, with damage to graphene and production of metal and etchant residues. Electrochemical delamination in a low-concentration aqueous solution is an alternative. In this case metallic substrates can be reused. Dry transfer is less detrimental for the SLG quality, enabling a deterministic transfer. There is a large range of layered materials (LMs) beyond graphite. Only few of them have been already exfoliated and fully characterized. Section VII deals with the growth of some of these materials. Amongst them, h-BN, transition metal tri- and di-chalcogenides are of paramount importance. The growth of h-BN is at present considered essential for the development of graphene in (opto) electronic applications, as h-BN is ideal as capping layer or substrate. The interesting optical and electronic properties of TMDs also require the development of scalable methods for their production. Large scale growth using chemical/physical vapour deposition or thermal assisted conversion has been thus far limited to a small set, such as h-BN or some TMDs. Heterostructures could also be directly grown.

Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection

Abstract: Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. However, it is unknown if COVID-19 results in persistent fatigue in those recovered from acute infection. We examined the prevalence of fatigue in individuals recovered from the acute phase of COVID-19 illness using the Chalder Fatigue Score (CFQ-11). We further examined potential predictors of fatigue following COVID-19 infection, evaluating indicators of COVID-19 severity, markers of peripheral immune activation and circulating pro-inflammatory cytokines. Of 128 participants (49.5 ± 15 years; 54% female), more than half reported persistent fatigue (52.3%; 45/128) at 10 weeks (median) after initial COVID-19 symptoms. There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (leukocyte, neutrophil or lymphocyte counts, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention.

Inhibiting extracellular vesicles formation and release: a review of EV inhibitors.

Abstract: It is now becoming well established that vesicles are released from a broad range of cell types and are involved in cell-to-cell communication, both in physiological and pathological conditions. Once outside the cell, these vesicles are termed extracellular vesicles (EVs). The cellular origin (cell type), subcellular origin (through the endosomal pathway or pinched from the cell membrane) and content (what proteins, glycoproteins, lipids, nucleic acids, metabolites) are transported by the EVs, and their size, all seem to be contributing factors to their overall heterogeneity. Efforts are being invested into attempting to block the release of subpopulations of EVs or, indeed, all EVs. Some such studies are focussed on investigating EV inhibitors as research tools; others are interested in the longerterm potential of using such inhibitors in pathological conditions such as cancer. This review, intended to be of relevance to both researchers already well established in the EV field and newcomers to this field, provides an outline of the compounds that have been most extensively studied for this purpose, their proposed mechanisms of actions and the findings of these studies.

An overview of the qualitative descriptive design within nursing research

Abstract: BackgroundQualitative descriptive designs are common in nursing and healthcare research due to their inherent simplicity, flexibility and utility in diverse healthcare contexts. However, the applic...

Strength, Weakness, Opportunity, Threat (SWOT) Analysis of the Adaptations to Anatomical Education in the United Kingdom and Republic of Ireland in Response to the Covid-19 Pandemic.

Abstract: The Covid-19 pandemic has driven the fastest changes to higher education across the globe, necessitated by social distancing measures preventing face-to-face teaching. This has led to an almost immediate switch to distance learning by higher education institutions. Anatomy faces some unique challenges. Intrinsically, anatomy is a three-dimensional subject that requires a sound understanding of the relationships between structures, often achieved by the study of human cadaveric material, models, and virtual resources. This study sought to identify the approaches taken in the United Kingdom and Republic of Ireland to deliver anatomical education through online means. Data were collected from 14 different universities in the United Kingdom and Republic of Ireland and compared adopting a thematic analysis approach. Once themes were generated, they were collectively brought together using a strength, weakness, opportunity, threat (SWOT) analysis. Key themes included the opportunity to develop new online resources and the chance to engage in new academic collaborations. Academics frequently mentioned the challenge that time constrains could place on the quality and effectiveness of these resources; especially as in many cases the aim of these resources was to compensate for a lack of exposure to cadaveric exposure. Comparisons of the actions taken by multiple higher education institutions reveal the ways that academics have tried to balance this demand. Discussions will facilitate decisions being made by higher education institutions regarding adapting the curriculum and assessment methods in anatomy.

Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion.

Abstract: PURPOSE: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU) Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies METHODS: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus RESULTS: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung CONCLUSION: A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA

Global distribution of carbonate rocks and karst water resources

Abstract: Karst regions offer a variety of natural resources such as freshwater and biodiversity, and many cultural resources. The World Karst Aquifer Map (WOKAM) is the first detailed and complete global geodatabase concerning the distribution of karstifiable rocks (carbonates and evaporites) representing potential karst aquifers. This study presents a statistical evaluation of WOKAM, focusing entirely on karst in carbonate rocks and addressing four main aspects: (1) global occurrence and geographic distribution of karst; (2) karst in various topographic settings and coastal areas; (3) karst in different climatic zones; and (4) populations living on karst. According to the analysis, 15.2% of the global ice-free continental surface is characterized by the presence of karstifiable carbonate rock. The largest percentage is in Europe (21.8%); the largest absolute area occurs in Asia (8.35 million km2). Globally, 31.1% of all surface exposures of carbonate rocks occur in plains, 28.1% in hills and 40.8% in mountains, and 151,400 km or 15.7% of marine coastlines are characterized by carbonate rocks. About 34.2% of all carbonate rocks occur in arid climates, followed by 28.2% in cold and 15.9% in temperate climates, whereas only 13.1 and 8.6% occur in tropical and polar climates, respectively. Globally, 1.18 billion people (16.5% of the global population) live on karst. The highest absolute number occurs in Asia (661.7 million), whereas the highest percentages are in Europe (25.3%) and North America (23.5%). These results demonstrate the global importance of karst and serve as a basis for further research and international water management strategies.

Targeting immunometabolism as an anti-inflammatory strategy

Abstract: The growing field of immunometabolism has taught us how metabolic cellular reactions and processes not only provide a means to generate ATP and biosynthetic precursors, but are also a way of controlling immunity and inflammation. Metabolic reprogramming of immune cells is essential for both inflammatory as well as anti-inflammatory responses. Four anti-inflammatory therapies, DMF, Metformin, Methotrexate and Rapamycin all work by affecting metabolism and/or regulating or mimicking endogenous metabolites with anti-inflammatory effects. Evidence is emerging for the targeting of specific metabolic events as a strategy to limit inflammation in different contexts. Here we discuss these recent developments and speculate on the prospect of targeting immunometabolism in the effort to develop novel anti-inflammatory therapeutics. As accumulating evidence for roles of an intricate and elaborate network of metabolic processes, including lipid, amino acid and nucleotide metabolism provides key focal points for developing new therapies, we here turn our attention to glycolysis and the TCA cycle to provide examples of how metabolic intermediates and enzymes can provide potential novel therapeutic targets.

Bio-based and biodegradable polymers - State-of-the-art, challenges and emerging trends

Abstract: Frontiers of bio-based and biodegradable polymers are constantly expanding in a view to achieve sustainability. Hence, designing sustainable bioplastics made of either bio-based or biodegradable polymers opens up opportunities to overcome resource depletion and plastic pollution. This review presents a broad perspective on state-of-the-art technologies in bioplastics manufacturing along with the challenges underlying their production, application and post-consumer waste management. Recent scientific advances are catalysing the sustainable design of bioplastics to overcome the present challenges of plastic waste and emerging end-of-life options are contributing to circular economy. As research insights into developing sustainable bioplastics are rapidly evolving, their production and waste management approaches are not limited to those discussed in this review.