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Nick K. Jones1,2*, Lucy Rivett1,2*, Chris Workman3, Mark Ferris3, Ashley Shaw1, Cambridge COVID-19 Collaboration1,4, Paul J. Lehner1,4, Rob Howes5, Giles Wright3, Nicholas J. Matheson1,4,6¶, Michael P. Weekes1,7¶1 Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK2 Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK3 Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, UK4 Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK5 Cambridge COVID-19 Testing Centre and AstraZeneca, Anne Mclaren Building, Cambridge, UK6 NHS Blood and Transplant, Cambridge, UK7 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK*Joint first authorship¶Joint last authorshipCorrespondence: mpw1001@cam.ac.ukThe UK has initiated mass COVID-19 immunisation, with healthcare workers (HCWs) given early priority because of the potential for workplace exposure and risk of onward transmission to patients. The UK’s Joint Committee on Vaccination and Immunisation has recommended maximising the number of people vaccinated with first doses at the expense of early booster vaccinations, based on single dose efficacy against symptomatic COVID-19 disease.1-3At the time of writing, three COVID-19 vaccines have been granted emergency use authorisation in the UK, including the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is whether this vaccine prevents or promotes asymptomatic SARS-CoV-2 infection, rather than symptomatic COVID-19 disease, because sub-clinical infection following vaccination could continue to drive transmission. This is especially important because many UK HCWs have received this vaccine, and nosocomial COVID-19 infection has been a persistent problem.Through the implementation of a 24 h-turnaround PCR-based comprehensive HCW screening programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT), we previously demonstrated the frequent presence of pauci- and asymptomatic infection amongst HCWs during the UK’s first wave of the COVID-19 pandemic.4 Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and cycle threshold (Ct) values in the asymptomatic arm of our programme, which now offers weekly screening to all staff.Vaccination of HCWs at CUHNFT began on 8th December 2020, with mass vaccination from 8th January 2021. Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence of COVID-19 amongst HCWs remained approximately constant; and (b) we screened comparable numbers of vaccinated and unvaccinated HCWs. Over this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed from individuals reporting well to work. We stratified HCWs <12 days or > 12 days post-vaccination because this was the point at which protection against symptomatic infection began to appear in phase III clinical trial.226/3,252 (0·80%) tests from unvaccinated HCWs were positive (Ct<36), compared to 13/3,535 (0·37%) from HCWs <12 days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact test, Figure). This suggests a four-fold decrease in the risk of asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days post-vaccination, compared to unvaccinated HCWs, with an intermediate effect amongst HCWs <12 days post-vaccination.A marked reduction in infections was also seen when analyses were repeated with: (a) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%) unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold reduction, p=0·00001); (b) inclusion of PCR tests which were positive at the limit of detection (Ct>36, 42/3,268 (1·29%) vs 15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of the period of analysis to include six weeks from December 28th to February 7th 2021 (113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction, p=1x10-9). In addition, the median Ct value of positive tests showed a non-significant trend towards increase between unvaccinated HCWs and HCWs > 12 days post-vaccination (23·3 to 30·3, Figure), suggesting that samples from vaccinated individuals had lower viral loads.We therefore provide real-world evidence for a high level of protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time of predominant transmission of the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a population with a relatively low frequency of prior infection (7.2% antibody positive).5This work was funded by a Wellcome Senior Clinical Research Fellowship to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), and an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also received from Addenbrooke’s Charitable Trust and the Cambridge Biomedical Research Centre. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing and the Cambridge COVID-19 Testing Centre.

Scene flow tracks the three-dimensional (3D) motion of each point in adjacent point clouds. It provides fundamental 3D motion perception for autonomous driving and server robot. Although the Red Green Blue Depth (RGBD) camera or Light Detection and Ranging (LiDAR) capture discrete 3D points in space, the objects and motions usually are continuous in the macro world. That is, the objects keep themselves consistent as they flow from the current frame to the next frame. Based on this insight, the Generative Adversarial Networks (GAN) is utilized to self-learn 3D scene flow with no need for ground truth. The fake point cloud of the second frame is synthesized from the predicted scene flow and the point cloud of the first frame. The adversarial training of the generator and discriminator is realized through synthesizing indistinguishable fake point cloud and discriminating the real point cloud and the synthesized fake point cloud. The experiments on Karlsruhe Institute of Technology and Toyota Technological Institute (KITTI) scene flow dataset show that our method realizes promising results without ground truth. Just as human, the proposed method can identify the similar local structures of two adjacent frames even without knowing the ground truth scene flow. Then, the local correspondence can be correctly estimated, and further the scene flow is correctly estimated.   Corresponding author(s) Email: wanghesheng@sjtu.edu.cn

Leukocyte differential test is a widely performed clinical procedure for screening infectious diseases. Existing hematology analyzers require labor-intensive work and a panel of expensive reagents. Here we report an artificial-intelligence enabled reagent-free imaging hematology analyzer (AIRFIHA) modality that can accurately classify subpopulations of leukocytes with minimal sample preparation. AIRFIHA is realized through training a two-step residual neural network using label-free images of isolated leukocytes acquired from a custom-built quantitative phase microscope. By leveraging the rich information contained in quantitative phase images, we not only achieved high accuracy in differentiating B and T lymphocytes, but also classified CD4 and CD8 cells, therefore outperforming the classification accuracy of most current hematology analyzers. We validated the performance of AIRFIHA in a randomly selected test set and cross-validated it across all blood donors. Owing to its easy operation, low cost, and accurate discerning capability of complex leukocyte subpopulations, we envision AIRFIHA is clinically translatable and can also be deployed in resource-limited settings, e.g., during pandemic situations for the rapid screening of infectious diseases.  Corresponding author(s) Email:    rjzhou@cuhk.edu.hk,  rishikesh.pandey@uconn.edu

Tam Hunt [1], Jonathan SchoolerUniversity of California Santa Barbara Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a combination of gamma, beta and theta synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and attempts to coalesce these data into a solution to what we see as the “easy part” of the Hard Problem, which is generally known as the “combination problem” or the “binding problem.” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a relatively smooth continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach as a (general) resonance theory of consciousness and offer some responses to Chalmers’ questions about the different kinds of “combination problem.”  At the heart of the universe is a steady, insistent beat: the sound of cycles in sync…. [T]hese feats of synchrony occur spontaneously, almost as if nature has an eerie yearning for order. Steven Strogatz, Sync: How Order Emerges From Chaos in the Universe, Nature and Daily Life (2003) If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.Nikola Tesla (1942) I.               Introduction Is there an “easy part” and a “hard part” to the Hard Problem of consciousness? In this paper, we suggest that there is. The harder part is arriving at a philosophical position with respect to the relationship of matter and mind. This paper is about the “easy part” of the Hard Problem but we address the “hard part” briefly in this introduction.  We have both arrived, after much deliberation, at the position of panpsychism or panexperientialism (all matter has at least some associated mind/experience and vice versa). This is the view that all things and processes have both mental and physical aspects. Matter and mind are two sides of the same coin.  Panpsychism is one of many possible approaches that addresses the “hard part” of the Hard Problem. We adopt this position for all the reasons various authors have listed (Chalmers 1996, Griffin 1997, Hunt 2011, Goff 2017). This first step is particularly powerful if we adopt the Whiteheadian version of panpsychism (Whitehead 1929).  Reaching a position on this fundamental question of how mind relates to matter must be based on a “weight of plausibility” approach, rather than on definitive evidence, because establishing definitive evidence with respect to the presence of mind/experience is difficult. We must generally rely on examining various “behavioral correlates of consciousness” in judging whether entities other than ourselves are conscious – even with respect to other humans—since the only consciousness we can know with certainty is our own. Positing that matter and mind are two sides of the same coin explains the problem of consciousness insofar as it avoids the problems of emergence because under this approach consciousness doesn’t emerge. Consciousness is, rather, always present, at some level, even in the simplest of processes, but it “complexifies” as matter complexifies, and vice versa. Consciousness starts very simple and becomes more complex and rich under the right conditions, which in our proposed framework rely on resonance mechanisms. Matter and mind are two sides of the coin. Neither is primary; they are coequal.  We acknowledge the challenges of adopting this perspective, but encourage readers to consider the many compelling reasons to consider it that are reviewed elsewhere (Chalmers 1996, Griffin 1998, Hunt 2011, Goff 2017, Schooler, Schooler, & Hunt, 2011; Schooler, 2015).  Taking a position on the overarching ontology is the first step in addressing the Hard Problem. But this leads to the related questions: at what level of organization does consciousness reside in any particular process? Is a rock conscious? A chair? An ant? A bacterium? Or are only the smaller constituents, such as atoms or molecules, of these entities conscious? And if there is some degree of consciousness even in atoms and molecules, as panpsychism suggests (albeit of a very rudimentary nature, an important point to remember), how do these micro-conscious entities combine into the higher-level and obvious consciousness we witness in entities like humans and other mammals?  This set of questions is known as the “combination problem,” another now-classic problem in the philosophy of mind, and is what we describe here as the “easy part” of the Hard Problem. Our characterization of this part of the problem as “easy”[2] is, of course, more than a little tongue in cheek. The authors have discussed frequently with each other what part of the Hard Problem should be labeled the easier part and which the harder part. Regardless of the labels we choose, however, this paper focuses on our suggested solution to the combination problem.  Various solutions to the combination problem have been proposed but none have gained widespread acceptance. This paper further elaborates a proposed solution to the combination problem that we first described in Hunt 2011 and Schooler, Hunt, and Schooler 2011. The proposed solution rests on the idea of resonance, a shared vibratory frequency, which can also be called synchrony or field coherence. We will generally use resonance and “sync,” short for synchrony, interchangeably in this paper. We describe the approach as a general resonance theory of consciousness or just “general resonance theory” (GRT). GRT is a field theory of consciousness wherein the various specific fields associated with matter and energy are the seat of conscious awareness.  A summary of our approach appears in Appendix 1.  All things in our universe are constantly in motion, in process. Even objects that appear to be stationary are in fact vibrating, oscillating, resonating, at specific frequencies. So all things are actually processes. Resonance is a specific type of motion, characterized by synchronized oscillation between two states.  An interesting phenomenon occurs when different vibrating processes come into proximity: they will often start vibrating together at the same frequency. They “sync up,” sometimes in ways that can seem mysterious, and allow for richer and faster information and energy flows (Figure 1 offers a schematic). Examining this phenomenon leads to potentially deep insights about the nature of consciousness in both the human/mammalian context but also at a deeper ontological level.

Cannabis sativa is an extraordinarily versatile species. Hemp and its cousin marijuana, both C. sativa, have been used for millennia as a source of fibre, oil and for medicinal, spiritual and recreational purposes. Because the consumption of Cannabis can have psychoactive effects, the plant has been widely banned throughout the last century. In the past decade, evidence of its medicinal properties did lead to the relaxation of legislation in many countries around the world. Consequently, the genetics and development of Cannabis as well as Cannabis-derived products are the subject of renewed attention.Here, we review the biology of C. sativa, including recent insights from taxonomy, morphology and genomics, with an emphasis on the genetics of cannabinoid synthesis. Because the female Cannabis flower is of special interest as the site of cannabinoid synthesis, we explore flower development, flowering time well as the species’ unique sex determination system in detail. Furthermore, we outline the tremendous medicinal, engineering, and environmental opportunities that Cannabis bears. Together, the picture emerges that our understanding of Cannabis biology currently progresses at an unusual speed. A future challenge will be to preserve the multi-purpose nature of Cannabis, and to harness its medicinal properties and sustainability advantages simultaneously.

Quantum chemistry must evolve if it wants to fully leverage the benefits of the internet age, where the world wide web offers a vast tapestry of tools that enable users to communicate and interact with complex data at the speed and convenience of a button press. The Open Chemistry project has developed an open source framework that offers an end-to-end solution for producing, sharing, and visualizing quantum chemical data interactively on the web using an array of modern tools and approaches. These tools build on some of the best open source community projects such as Jupyter for interactive online notebooks, coupled with 3D accelerated visualization, state-of-the-art computational chemistry codes including NWChem and Psi4 and emerging machine learning and data mining tools such as ChemML and ANI. They offer flexible formats to import and export data, along with approaches to compare computational and experimental data.

This paper responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on masks for the lay public in the Covid-19 pandemic. I address their charges that my co-authors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms. But before that, I remind Martin et al that the evidence on mask wearing goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly-framed objections. I challenge my critics’ apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and engage, scientifically and morally, with the dreadful tragedy that is unfolding across the world.

This Supporting information includes interactive plots, videos, and data captured while performing evaluation and validation experiments for our paper. 

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues including increasing burden of chronic disease, widening inequality, concerns over environmental degradation and anthropogenic climate change. While these criticisms overlook recent developments, there remains a need for biopsychosocial models that extend theoretical grounding beyond individual wellbeing, incorporating overlapping contextual issues relating to community and environment. Our first GENIAL model \cite{Kemp_2017} provided a more expansive view of pathways to longevity in the context of individual health and wellbeing, emphasising bidirectional links to positive social ties and the impact of sociocultural factors. In this paper, we build on these ideas and propose GENIAL 2.0, focusing on intersecting individual-community-environmental contributions to health and wellbeing, and laying an evidence-based, theoretical framework on which future research and innovative therapeutic innovations could be based. We suggest that our transdisciplinary model of wellbeing - focusing on individual, community and environmental contributions to personal wellbeing - will help to move the research field forward. In reconceptualising wellbeing, GENIAL 2.0 bridges the gap between psychological science and population health health systems, and presents opportunities for enhancing the health and wellbeing of people living with chronic conditions. Implications for future generations including the very survival of our species are discussed.  

Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield across global regions is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control and pollination services in adjacent crops using a global dataset of 529 sites. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimize floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.

Researchers' ability to accurately screen fossil and subfossil specimens for preservation of DNA and protein sequences remains limited. Thermal exposure and geologic age are usable proxies for sequence preservation on a broad scale but are of nominal use for specimens of similar depositional environments. Cell and tissue biomolecular histology is thus proposed as a novel proxy for determining sequence preservation potential of ancient specimens with improved accuracy. Biomolecular histology as a proxy is hypothesized to elucidate why fossils/subfossils of some depositional environments preserve sequences while others do not and to facilitate selection of ancient specimens for use in molecular studies.

IntroductionConsistent with World Health Organization (WHO) advice [1], UK Infection Protection Control guidance recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In a recent update, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

Background: Colostrum contains substances such as hormones, enzymes, polyamides, nucleic acid derivatives and amino acid derivatives. Their range also includes immunomodulating substances, proline-rich polypeptides (PRP), immunoglobulins as well as bacteriostatic compounds. Based on its biological properties as well as the influence of Toll-like receptors on immune response traits of farm animals and humans, we hypothesised that gene expression for Toll-like receptors in foals is dependent on the quality of colostrum. Objectives: The aim of the study was to evaluate the impact of the quality of colostrum on the level of expression of selected Toll-like receptor genes (TLR3, TLR4, and TLR7). Study design: The experiments were conducted on 25 foals Polis Pony breed. Blood samples were collected up to 30 days of age according to the following scheme: before first suckling, at the 1st, 3rd, 5th, 10th, 20th, and 30th, day of age. Colostrum was obtained before the first suckling, 24 hr and 3 days after the delivery. Methods: Gene expression analyses were performed on Illumina Eco using a commercial kit TaqMan®MGB probes. The quality of colostrum was assessed using an optical refractometer. Total immunoglobulin level was calculated from the spectrophotometric method. Immunoglobulin G level were measured using ELISA assay Microplate Reader using 96-well plates coated with monoclonal antibodies against equine IgG. Results: The quality of colostrum significantly correlated with TLR4 and TLR7 expression. Foals that ingested colostrum with low immunoglobulin content displayed higher level of TLR4 gene expression, while in case of TLR7 the opposite trend was shown. Main limitations: It is likely that fat and the proportion of individual fatty acids in colostrum affect the action of membrane Toll-like receptors Conclusions: The expression of genes for TLR3 and TLR4 in peripheral blood is dependent on immunoglobulin concentration in mammary gland secretion suckled by foals.

The current research was designed to assess degree of sediment contamination by heavy metal in the Thamirabarani River by using pollution indicators and multivariate statistical methods. Between September 2020 and August 2021, seasonal basis sediment samples are collected from five distinct locations and subjected to standardised analysis. These statistical techniques, including Two-way ANOVA, Pearson Correlation Index, PCA and CA., were demonstrated the research. The quality of sediment needs to be better understanding about the statistical methods. Three factors that account for 95.4% of the data’s total variation were found using PCA.The sediment’s heavy metal contamination were distributed in the following sequence Fe > Mn > Cu > Zn > Al > Cd > Ni. The contamination was evaluated pollution indicators method such EF, CF, Igeo and PLI. Estimated EF values show that there is a noticeable enrichment of pollutants in copper (Cu). Therefore, river water can be used for irrigation securely, but it need to go through a lot of processing is necessary before for home uses in order to avoid negative public health effects.

Traditional molecular biology tools have elucidated the identities and functions of RNA molecules, which are essential to the understanding of gene transcription and protein translation. Deepening this research field would further require the direct visualization of RNA dynamics such as the DNA-RNA interactions and RNA-protein interactions. Towards this goal, the rise of RNA imaging tools over the past 15 years has reformed how we looked at these processes. In this emerging topic, we first highlighted recent advances on three main RNA imaging tools based on the species of interacting molecules: RNA-RNA pairing, RNA-protein binding, and small molecule-RNA complex. We introduced the advantages of these tools from a technical viewpoint, including binding affinity, fluorescent turn-on ratio, stability, and impacts on targeted RNA. Next, we discussed new rising opportunities and future directions, echoing the state-of-the-art imaging tools in the fields of fluorescent proteins and small fluorescent molecules. Together, we believe this emerging field will bring new insights on how we study RNA biology in living systems.

This paper presents a framework combining Monte Carlo Simulation (MCS) and the Newmark sliding block model with Representative slip surfaces (RSS) (model II) and Multiple response surfaces method (MRSM) to conduct seismic reliability analysis and risk assessment of soil slopes. An empirical threshold is introduced to define the limit state function to identify the failure samples in MCS and the sliding area and Newmark sliding displacement are multiplied to quantify the failure consequence. The proposed methodology is illustrated through a soil slope with multiple layers. The calculation results demonstrate that traditional Newmark sliding block model (model I) tend to underestimate the variations of yield acceleration. Both the failure probability and landslide risk exhibit decreasing trends with the increase of threshold. Significant discrepancy in failure probability and landslide risk between two models is found even for a small threshold. It is therefore, the proposed methodology is highly recommended in seismic reliability analysis and risk assessment. The contributions of RSSs to the failure probability and landslide risk are insensitive to the variation of displacement thresholds.

Background and Purpose: 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the oxoreduction of cortisone to cortisol, thereby amplifying levels of active glucocorticoids. It is considered a pharmaceutical target in metabolic disease and cognitive impairments. 11β-HSD1 also converts some 7oxo-steroids to their 7β-hydroxy forms. A recent study in mice described the ratio of tauroursodeoxycholic acid (TUDCA)/tauro-7oxolithocholic acid (T7oxoLCA) as a biomarker for decreased 11β-HSD1 oxoreductase activity. The present study aimed to evaluate the equivalent bile acid ratio glycoursodeoxycholic acid (GUDCA)/glyco-7oxolithocholic acid (G7oxoLCA) as a biomarker for pharmacological 11β-HSD1 inhibition in humans and compare it with the currently applied urinary (5α-tetrahydrocortisol+tetrahydrocortisol)/tetrahydrocortisone ((5αTHF+THF)/THE) ratio. Experimental Approach: Bile acid profiles were analyzed by ultra-HPLC tandem-MS in blood samples from two independent, double-blind placebo-controlled clinical studies on the orally administered selective 11β-HSD1 inhibitor AZD4017. The blood GUDCA/G7oxoLCA ratio was compared with the urinary tetrahydro-glucocorticoid ratio for the ability to detect 11β-HSD1 inhibition. Key Results: No significant alterations were observed in the bile acid profiles following 11β-HSD1 inhibition by AZD4017, except for an increase of the secondary bile acid G7oxoLCA. The enzyme product/substrate ratio GUDCA/G7oxoLCA was found to be more reliable to detect 11β-HSD1 inhibition than the absolute G7oxoLCA concentration in both cohorts. Comparison of the blood GUDCA/G7oxoLCA ratio with the urinary (5αTHF+THF)/THE ratio revealed that both ratios successfully detect 11β-HSD1 inhibition. Conclusion and Implications: 11β-HSD1 inhibition does not cause major alterations in bile acid homeostasis. The GUDCA/G7oxoLCA ratio represents the first blood biomarker of pharmacological 11β-HSD1 inhibition and may replace or complement the urinary (5αTHF+THF)/THE ratio biomarker.

This paper provides new information on molecular properties of the humin fraction (HM) isolated from the mollic horizons of Phaeozem and Chernozem soils developed from different parent materials in the temperate climatic zone of Poland. In our work we did not extract this fraction by dissolution but isolated it by exhaustive extraction of humic and fulvic acids with NaOH and then removing the mineral fraction with HF/HCl treatment. Obtained HM reflects the properties of this fraction that naturally occurres in the soil environment. The assessment of the structural properties of the HM was carried out using the spectroscopic methods ( 13C CP MAS NMR, FTIR, EPR), HPLC, SEM-EDX, and elemental composition analyses. The 13C CP MAS NMR spectra of the HM showed the advantage of aromatic structures over other organic components. The FTIR spectra confirmed that the content of aromatic structures dominated over the aliphatic ones, ranging from 7.05 to 10.32%. The EPR study indicated evidence of an unpaired electron situated on the condensed aromatic moieties. The HPLC investigation revealed the dominance of hydrophobic fractions, ranging from 77.41 to 80.83%. The ash content, ranging from 22.89 to 54.50%, as well as SEM-EDS study indicate that the isolated HM is not a pure organic fraction but constituted strongly bound organo-mineral compounds, resistant to further treatment with an alkali and HF/HCl mixture. This fraction represents the most resistant pool of the SOM that plays a crucial role in soil carbon sequestration and due to high functional group content contributes to the maintenance of soil and its ecosystem services.

A broadband heterogeneous circularly polarized (CP) dipole antenna with a backed cavity is presented in this letter. The proposed antenna consists of a pair of rotational symmetric short-circuited heterogeneous branches and a Γ-shaped feed structure. Each branch is designed to be axe-shaped so that the antenna can achieve a broad 3dB axial ratio (AR) bandwidth. The coupled feeding method assures the antenna is wideband, and the shorting-to-the-ground technique miniaturizes the lateral dimensions of the antenna. The profile of the proposed antenna is around 0.16λL (λL denotes the wavelength of the lower bound frequency). The introduction of a back cavity effectively enhances the boresight gain and improves the isolation level if the antenna is used to form an array. Finally, the design is prototyped, and the measurement results agree well with the simulation. The fractal -10 dB S11 bandwidth and 3dB AR bandwidths are 54.3% (2.74-4.78 GHz) and 45.9% (3.15-5.03 GHz), respectively. The antenna’s efficiency exceeds 91.5% over the target frequency band.

Covid-19 causedhospitalizations, severe disease and deaths in any age, including in the youngest children. The aim of this multicenter national study is to characterize the clinical and the prognostic role of lung ultrasound (LUS) in children with Covid-19. We enrolled children between 1 month and 18 years of age diagnosed with SARS-CoV2 infection and whounderwenta lung ultrasound within 6 hours from firstmedical evaluation. A total of 213 children were enrolled, 51.6%were male, median age was2 years and 5 months (IQR 4mm- 11 yearsand4 months).One hundred and fortyeight (69.4%) children were admitted in hospital, 9 (6.1%) in pediatric intensive care unit.We found an inverse correlation between the LUS score and the oxygen saturationatthe clinical evaluation (r = −0.16; p = 0.019). Moreover, LUS scores were significantly higher in patients requiring oxygen supplementation (8 (IQR 3 - 19) vs 2 (IQR 0 - 4); p= 0.001). Among LUS pathological findings, irregular pleural line, sub-pleural consolidations and pleural effusions were significantly more frequentin patients whoneeded oxygen supplementation (p = 0.007; p = 0.006 andp = 0.001, respectively). This multicentric study confirmed that LUS is able to detect Covid-19 low respiratory tract involvement, which is characterized by pleural line irregularities, vertical artifacts and subpleural consolidations. Notably, children with higher LUS score have an higher risk of hospitalization or need for oxygen supplementation, supporting LUS as a valid and safe point-of-care first level tool for the clinical evaluation of children with Covid-19.

Introduced alien species have direct and indirect effects on native communities, leading to lower taxonomic diversity and negative impacts on ecosystem functioning. Moreover, other aspects of diversity could be negatively affected, through alteration of functional and phylogenetic diversity of a community. This is particularly evident in habitats where human disturbance may favour alien species, posing an additional stressor on native communities. Following the community resistance hypothesis (higher diversity, higher resistance to invasion), we hypothesized: i) higher taxonomic, functional and phylogenetic diversity (TD, FD and PD respectively) in non-invaded bird communities (i.e. no alien bird species); and, ii) lower alien species impact on all diversity metrics in less human-disturbed areas. We surveyed bird communities in a modified Mediterranean landscape subject to varying levels of human disturbance. We tested whether TD, FD and PD indices were significantly different between non-invaded and invaded bird communities, and assessed the effect of landscape composition and configuration on these indices. We found that non-invaded communities retained higher TD and FD than invaded communities. Alien birds occupied novel parts of the functional space in invaded communities, but that they did not fully compensate for the taxonomic and functional diversity loss caused by the absence of native species. These results were consistent across different habitats, suggesting weak environmental filtering of communities. Generally, both communities were negatively affected by more human-disturbed areas (e.g. agriculture and urban areas) and enhanced by forest areas and by landscape heterogeneity. Our results suggest that the occurrence of alien birds negatively affects TD and FD (but not PD) of bird community assemblages, but that this impact is stronger in human-modified landscapes. Therefore, since the conservation of biodiversity in anthropogenic habitats is a worldwide challenge, researchers should prioritize efforts to assess the effects of alien species on communities inhabiting those habitats.

Understanding how geographic range limits are shaped is a central and challenging question in ecology that has become particularly critical in the context of global environmental changes. A central hypothesis in several theories for range limitations is that the density, fitness and performance of individuals decrease towards the edge of the range as organisms become maladapted when approaching the limit of their environmental tolerance (‘Abundant-centre Hypothesis’). Energy is a critical resource, especially in winter when environmental conditions deteriorate, and this hypothesis predicts that high energy expenditure (low performance) at the range limit would lead to rapidly dwindling body mass and reduced fitness. We investigated this hypothesis in an Arctic breeding seabird wintering in the North-Atlantic, the black-legged kittiwake (Rissa tridactyla). From 2008 to 2019, we tracked 118 adult kittiwakes (n= 178 tracks) with geolocation devices and saltwater immersion sensors to estimate the time-activity budget and energy expenditure of individuals during winter, and estimated their reproductive success after their return to the colony during summer. Density was indeed higher towards the center of the range. However, contrary to the predictions, the energy expenditure of individuals was higher at the centre of the range and decreased towards the edge. In contrast, there were no spatial differences in the reproductive success of individuals wintering at the centre versus at the edge of their range. We conclude that performance and fitness did not increase towards the centre of the range, implying that although resource acquisition was likely higher at the abundant centre, energy expenditure was also higher, so that individual fitness was constant across the range.

This study demonstrates the sustainable synthesis of multifunctional CIS@MIL-101(Cr) composites for water treatment applications. The composites were prepared via hybridization of CuInS2 with MIL-101(Cr) resulting in the formation of CIS nanoplates incorporated into MIL-101(Cr). The composites exhibited high visible light photocatalytic activity due to their low band gap energy and were tested for tetracycline photodegradation achieving a degradation efficiency of 98.8%. The material showed high stability after four cycles, and the effects of reactive species on photodegradation were investigated. The kinetics and mechanism of the photocatalytic process were studied, and HPLC-MS analysis was conducted to identify intermediate products. These results demonstrate the potential of using waste PET to create new semiconductors for water pollution control, promoting a circular material pathway.

Background: Adolescents with cancer routinely report feelings of isolation and exclusion, including from medical decision-making. To address this problem and support adolescents, we designed and implemented into clinical practice the novel, virtual, weekly Teens4Teens peer support group and patient education program. Objective: We examined the views of participating adolescents, program guest speakers, and program moderators as they pertained to the need for the program and its feasibility, acceptability, and perceived impact. Methods: We recruited all available adolescents, moderators, and guest speakers who participated in Teens4Teens to take part in audio-recorded, semi-structured interviews. Interviews were transcribed, coded, and analyzed using thematic analysis. Results: We conducted 21 interviews across participant groups. We identified four broad themes: pathways into the Teen4Teens program, Teens4Teens implementation capacity, perspectives of the positive impact of Teens4Teens and suggestions to improve Teens4Teens. These themes described a perceived need for adolescent-centered psychosocial programing in pediatric cancer care, provided lessons on how best to build and apply such a program in practice, and highlighted the value of the program for both adolescents and clinicians’ acceptability, feasibility, and perceived utility. Conclusion: Adolescents, guest speakers, and moderators valued Teens4Teens and made suggestions to retain or improve capacity to routinely implement the program. Adolescent-tailored psychosocial programming such as Teens4Teens is positioned to be integrated into clinical care with relative ease and may serve to improve the cancer care experience of adolescents and their families.