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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.

Objective: Acute bronchiolitis, primarily caused by Respiratory syncytial virus (RSV), is the most common cause of hospitalization in young children. Despite international guidelines supporting clinical diagnosis, laboratory evaluations are often conducted with limited validity. We aim to evaluate the association between C-reactive protein (CRP) levels at admission and disease severity in children hospitalized due to RSV bronchiolitis. Study design: This single center retrospective cohort study included children (0-24 months old) who were hospitalized due to RSV bronchiolitis (January 2018 – March 2022) with CRP levels taken upon admission. Clinical data and severity parameters were extracted using MD-clone platform and the clinical research unit at SUMC. Results: 1,874 children (mean age of 6.7 months, 59% males) with a median CRP level of 1.92mg/dL were included. Children with elevated CRP (>1.92mg/dL) were significantly older (5.1 vs. 3.8 months, p<0.001), had higher rates of pneumonia (9.4% vs. 4.3%, p<0.001 ), urinary tract infection (UTI), (2.2% vs. 0.2%, p<0.001), acute otitis media (AOM), (1.7% vs 0.2%, p<0.001), admissions to pediatric intensive care unit (PICU) (7.4% vs 3.7%, p<0.001), antibiotic treatment (49.8% vs 37.2%, p<0.001) and longer hospitalizations (3.83 vs 3.31 days, p=0.001). Multivariable analysis predicted increased risk for UTI, PICU admission, pneumonia, and longer hospitalization (relative risk of 11.6, 2.25, 1.98, 1.44, respectively, p<0.001)). CRP thresholds of 3.51, 1.9, and 2.81 mg/dL for PICU admission, UTI, and pneumonia, were calculated using Youden’s index with AUC of 0.72, 0.62, and 0.61, respectively. Conclusions: Elevated CRP levels at admission are associated with increased disease severity and higher complication rates in children hospitalized with RSV bronchiolitis.

In this paper, we consider a third order singular differential operator L w + μ w = - w ′′′ + q ( x ) w + μ w in space L 2 ( R ) originally defined on the set C 0 ∞ ( R ) , where C 0 ∞ ( R ) is the set of infinitely differentiable compactly supported functions, μ≥0. Regarding the coefficient q ( x ) , we assume that it is a continuous function in R ( - ∞ , ∞ ) and can be a growing function at infinity. The operator L allows closure in the space L 2 ( R ) and the closure also be denoted by L. In the paper, under certain restrictions on q ( x ) , in addition to the above condition, the existence of the resolvent of the operator L and the existence of the estimate ‖ - w ′′′ ‖ L 2 ( R ) + ‖ q ( x ) w ‖ L 2 ( R ) ≤ c ( ‖ L w ‖ L 2 ( R ) + ‖ w ‖ L 2 ( R ) ) (0.1) have been proved, where c>0 is a constant. Example. Let q ( x ) = e 100 | x | , then the estimate (0.1) holds. The compactness of the resolvent is proved and two-sided estimates for singular numbers ( s-numbers) are obtained. Here we note that the estimates of singular numbers ( s-numbers) show the rate of approximation of the resolvent of the operator L by linear finite-dimensional operators. In the present paper, apparently for the first time, the nuclearity of the resolvent of the third-order differential operator and completeness of its root vectors are proved in the case of an unbounded domain with a greatly growing coefficient q ( x ) at infinity.

Background: Pre-eclampsia is a hypertensive disorder of pregnancy which, left untreated, can cause significant foeto-maternal morbidity. Accordingly, the National Institution for Health and Care Excellence (NICE) recommends that high-risk women be prescribed daily prophylaxis with 75-150mg aspirin from twelve weeks’ gestation until delivery. NICE stratifies risk using eleven maternal risk factors; however, no secondary research has been published evaluating the diagnostic accuracy of this algorithm. Objectives: Quantify the sensitivity and specificity of the NICE risk‑stratification algorithm in predicting pre‑eclampsia in pregnant women ≥16 years. Search Strategy: PubMed, Cochrane Library and SCOPUS. PROSPERO Registration: CRD42023437261. Selection Criteria: Papers with a CBEM Level of Evidence ≤4, published 2010‑2023. Data Collection and Analysis: 20 eligible studies consisting of 892,061 pregnancies were analysed. Logit-transformed sensitivities and specificities were modelled as bivariate distributions with random effects. Main Results: Maximum likelihood estimates for the NICE algorithm’s sensitivity and specificity were 44.7% (95% CI 32.3 – 57.8) and 88.0% (95% CI 87.4-88.7), respectively. There was significant heterogeneity between the studies in this analysis (χ 2(17) = 85.05 (p<.0001), I 2=99.8%) and, consequently, a low degree of certainty in these estimates. Conclusions: The NICE risk‑stratification algorithm performs remarkably poorly when used to predict pre‑eclampsia in any of three gestational categories. Clinicians should advise women that around 1 in 5 high-risk patients and 1 in 25 low-risk patients go on to develop pre‑eclampsia. However, future studies will likely alter these values and the confidence therein. Funding: None Key Words: Pre-eclampsia, High-risk Pregnancy, Sensitivity and Specificity, Predictive Value of Tests, Clinical Decision Rules.

Recently, cognitive-based sentiment analysis has drawn a lot of attention because it focuses on automatically identifying user behaviours like personality characteristics from online social media text. In order to demonstrate the effectiveness of the suggested model for eight key personality traits (Introversion-Extroversion, Intuition-Sensing, Thinking-Feeling, and Judging-Perceiving), we present a hybrid Deep Learning-based model made up of Convolutional Neural Networks with Long Short-Term Memory. On the basis of audio and video recordings of human faces, we provide a model for the identification of personality traits. A web-based platform is created to gather the dataset, allowing users to record voice and video using a microphone and webcam, respectively. The dataset contains videos and audio clips of people of various ages and genders. Applying the proposed CNN+LSTM model on the considered dataset we could achieve an accuracy of 87.07%.

Voice Liveness Detection (VLD) has become one of the hot research topics in the Internet of Things era. Conventional VLD methods are centralized solutions that are trained on abundant data collected from local clients and stored on the server, however, they have the risk of causing data islands and privacy leakage. To address this problem, we propose a novel word-level VLD framework based on asynchronous federated learning (FL) with pop noise, named FL-VLD. Structurally, FL-VLD takes the preprocessed voice for local model training and constructs a global model by only transmitting the learned weights after differential privacy with FL’s central server in an asynchronous manner. In addition, the local network of the framework incorporates the residual network and the spatial grouping enhancement module to optimize the complexity and accuracy of the global model. With the advantage of FL’s distributed structure, FL-VLD solves the data island problem in VLD scenario without threatening users’ privacy. Experimental results on the popular POCO dataset show that our proposal is clearly superior to the traditional centralized methods as well as overperforming other federated schemes in terms of fairness, stability, accuracy, and lightweightness. Further, for attacks involving far-field replay, synthesis, and conversion, FL-VLD has high generalisation capabilities. Finally, the ablation study attests to its efficacy.

We discuss the links between political governance systems and ecological research, education and environmental policy, focusing on the ongoing radical changes to the judicial systems in Israel. This judicial revision has already restricted academic freedom and environmental laws, and has impacted regulatory actions. We are concerned about future defunding of ecological research and nature conservation programs, reduced cross-border ecological collaboration, restrictions of academic teaching of ecology and evolution, a brain drain of ecologists, weakening enforcement of environmental laws, and increased power to polluting corporates. Israel's unique biodiversity, already threatened by its rapidly growing population and high development pressures, make these concerns all the more pressing. We believe that weakening judicial oversight of government actions in other countries is generating similar threats at a global scale.

Spontaneous Spinal Cord Herniation with Post-operative paraplegia- A case report with 10-year follow-upAbstract:Background: Spinal cord herniation is an uncommon diagnosis in the field of spine surgery. The usual presentation of spontaneous spinal cord herniation is in the form of progressive Brown-Sequard syndrome. We describe a case of a 37-year-old male with progressive back pain and sensory deficits due to spinal cord herniation and a post-operative complication associated with reduction of the hernia.Case description: A 37-year-old male presented with insidious onset upper back pain and altered sensations of pain and temperature over the right half of the body below the nipple 2 months before the examination. The patient did not have motor weakness of lower limbs, abnormal/ involuntary movements, or loss of control over the bowel and bladder. MRI of the thoracic spine showed an anterolateral defect(left) at the level of the T2-T3 vertebra. A posterior approach was chosen and the cord with roots was reduced into the dura. The defect was covered by a dural graft (Lyodura) and the wound was closed with a drain insitu. On the 3rd post-operative day, patient developed paraplegia. Patient was treated by exploration and decompression of the hematoma that compressed spinal cord. The deficits were completely recovered at one-month follow-up.Conclusion: Patients with spinal cord herniation and neurologic deficits when treated timely with reduction of the hernia, have good outcomes. The drain should be removed only when the treating team is satisfied regarding the lack of ongoing hemorrhage. The recovery was maintained till the last follow-up at 10 years.Key words: spontaneous spinal cord herniation, spinal cord defect, paraplegia, Brown-Sequard syndrome

Bacillus subtilis is a plant growth promoting bacterium that acts as a microbial fertilizer and biocontrol agent, providing benefits such as boosting crop productivity and improving nutrient content. It is able to produce secondary metabolites and endospores simultaneously, enhancing its ability to survive in unfavorable conditions and eliminate competing microorganisms. Optimizing cultivation methods for the production of B. subtilis MSCL 897 spores on an industrial scale requires a suitable medium, typically made from food industry by-products, and maintaining optimal temperature and pH levels to achieve high vegetative cell and spore densities with maximum productivity and yield. In this study, we demonstrate successful pilot-scale (100 L bioreactor) production of a biocontrol agent B. subtilis with good spore yields (1.5 x 10 9 spores/mL) and a high degree of sporulation (>80%) using a low-cost cultivation media, which showed excellent antifungal activity (1.6-2.3 cm) against several phytopathogenic fungi. An improved methodology for inoculum preparation was investigated to ensure an optimal seed culture state prior to inoculation, promoting process batch-to-batch repeatability. Increasing the molasses concentration in the medium and operating the process in fed-batch mode with additional molasses feed, did not improve the overall spore yield, hence, process operation in batch mode with 10 g/L molasses is preferred. Results also showed that the product quality was not significantly impacted for up to 12 months of storage at room temperature.

Objective: To assess the association between chronotype and depressive symptoms in an infertile population undergoing assisted reproductive technology. Design: Cross-sectional study. Setting: The First Affiliated Hospital of Anhui Medical University Reproductive Medicine Center in Hefei, China. Population: 1022 infertile patients who sought assisted reproductive technology at the Center between August and October 2022, were assessed for inclusion in this study. Methods: On the day of ovulation injection, we collected socio-demographics by inviting infertile patients to complete questionnaires and assessed the subjects’ chronotypes through the Morning and Evening Questionnaire-5 Items (MEQ-5). Main Outcome Measures: Depressive symptoms, assessed with validated Patient Health Questionnaire-9 (PHQ-9) and expressed as PHQ-9 scores. Results: Overall, 9%, 68%, and 22% of participants were categorized as evening, neutral, and morning chronotypes, respectively. There were significant differences between chronotype on levels of depressive symptoms, subjects with morning chronotype (odds ratios = 0.32, 95% confidence intervals: 0.18-0.57) and neutral chronotype (odds ratios = 0.47, 95% confidence intervals: 0.28-0.77) had lower odds of depressive status, compared to those with evening chronotype, but no partner effect of chronotype was found ( p >0.05, respectively). Conclusions: Our findings suggest that morning and neutral chronotypes may be significantly associated with a lower likelihood of depressive symptoms. In addition, the effect of earlier chronotypes in men on depressive symptoms in women warrants relevant clinical attention when considering treatment.

Small, fragmented or isolated populations are at risk of population decline due to fitness costs associated with inbreeding and genetic drift. The King Island scrubtit Acanthornis magna greeniana is a critically endangered endemic subspecies of the nominate Tasmanian scrubtit A. m. magna, with an estimated population of <100 individuals persisting in three patches of swamp forest. The Tasmanian scrubtit is widespread in wet forests on mainland Tasmania. We sequenced the scrubtit genome using PacBio HiFi and undertook a population genomics study of the King Island and Tasmanian scrubtit using a double-digest restriction site-associated DNA (ddRAD) dataset of 5,239 SNP loci. The genome was 1.48 Gb long, comprising 1,518 contigs with an N50 of 7.715 Mb. King Island scrubtits formed one of four overall genetic clusters, but separated into three distinct subpopulations when analysed separately. Pairwise FST values were greater among the King Island scrubtit subpopulations than among most Tasmanian scrubtit subpopulations. Genetic diversity was lower and inbreeding coefficients were higher in the King Island scrubtit than all except one of the Tasmanian scrubtit subpopulations. We observed crown baldness in 8/15 King Island scrubtits, but 0/55 Tasmanian scrubtits. Six loci were significantly associated with baldness, including one within the DOCK11 gene which is linked to early feather development. Contemporary gene flow between King Island scrubtit subpopulations is unlikely, with further field monitoring required to quantify the fitness consequences of its small effective size, low genetic diversity and high inbreeding. Evidence-based conservation actions can then be implemented before the taxon goes extinct.

Zoo populations of threatened species are a valuable resource for the restoration of wild populations. However, their small effective population size poses a risk to long-term viability, especially in species with high genetic load. Recent bioinformatic developments can identify harmful genetic variants in genome data. Here, we advance this approach, analysing the genetic load in the threatened pink pigeon (Nesoenas mayeri). We lift-over the mutation-impact scores that had been calculated for the chicken (Gallus gallus) to estimate the genetic load in six pink pigeons. Additionally, we perform in-silico crossings to predict the genetic load and realised load of potential offspring. We thus identify the optimal mate pairs that are theoretically expected to reproduce offspring with the least inbreeding depression. We use computer simulations to show how genomics-informed conservation can reduce the genetic load and maintain genome-wide diversity, arguing this will become instrumental in maintaining the long-term viability of zoo populations.

Aims. The exposure-response relationship of bevacizumab may be confounded by various factors, i.e. baseline characteristics, time-dependent target engagement and recursive relationships between exposure and response. This work aimed at investigating the exposure-response relationships of bevacizumab in mCRC patients while mitigating potential sources of bias. Methods. Bevacizumab pharmacokinetics was described using target-mediated drug disposition (TMDD) modeling. The relationships between target kinetics, and progression-free (PFS) and overall (OS) survivals were assessed using joint pharmacokinetic and parametric hazard function models. Both potential biases due to prognostic-driven and response-driven of the concentration-effect relationship were mitigated. These models were used to evaluate the effect of increased antigen target levels and clearance, as well as intensified dosing regimen, on survival. Results. Estimated target-mediated pharmacokinetic parameters in 130 assessed patients were: baseline target levels (R0=8.4 nM), steady-state dissociation constant (KSS=10 nM) and antibody-target complexes elimination constant (kint=0.52 day-1). Distribution of R0 was significantly associated with an increased baseline CEA and circulating VEGF levels, and the presence of extra-hepatic metastases. Unbound target levels (R) significantly influenced both progression and death hazard functions. Increased R0 or CL values led to decreased bevacizumab unbound concentrations, increased R levels, and shortened PFS and OS, whereas increasing bevacizumab dose led to decreased R and longer survival. Conclusion. This study is the first to show the relationship between bevacizumab concentrations, target involvement and clinical efficacy by mitigating potential sources of bias. Most of target amount may be tumoral in mCRC. A more in-depth description of this relationship should be made in future studies.