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Michael Weekes

and 11 more

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: 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.

Guangming Wang

and 4 more

Tam Hunt

and 1 more

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.

Susanne Schilling*^

and 9 more

Jessica mead

and 6 more

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.  

Mark Ferris

and 14 more

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.

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Kyousuke Kamada 11Department of Neurosurgery, Asahikawa Medical University, Asahikawa, Japankyousuke.kamada@yahoo.comAbstract: The feasibility and safety of brain-computer interface (BCI) systems for patients with acute/subacute stroke have not been established. The aim of this study was to firstly demonstrate the feasibility and safety of a bedside BCI system for inpatients with acute/subacute stroke in a small cohort of inpatients. Four inpatients with early-phase hemiplegic stroke (7–24 days from stroke onset) participated in this study. The portable BCI system showed real-time feedback of sensorimotor rhythms extracted from scalp electroencephalograms (EEGs). Patients attempted to extend the wrist on their affected side, and neuromuscular electrical stimulation was applied only when the system detected significant movement intention-related changes in EEG. Between 120 and 200 training trials per patient were successfully and safely conducted at the bedside over 2–4 days. Our results clearly indicate that the proposed bedside BCI system is feasible and safe. Larger clinical studies are needed to determine the clinical efficacy of the system and its effect size in the population of patients with acute/subacute post-stroke hemiplegia..Keywords : rain-computer interface; electroencephalogram; neuromuscular electrical stimulation; sensorimotor rhythms; stroke1. INTRODUCTIONBrain-computer interface (BCI) technology has already been used successfully to control an external device with the user’s brain activity, and it is expected to be used on patients with strokes, spinal cord injuries, and neuromuscular intractable diseases, to assist their motor functions. In addition, the BCIs are investigated on healthy subjects with regard to human augmentation. Recently, several research groups have shown that BCI can also be used as a tool for promoting neural plasticity, leading to functional recovery from hemiplegia/ hemiparesis after stroke (Shindo et al., 2011; Ushiba & Soekadar, 2016). The clinical application of such rehabilitative BCI-based neurofeedback in patients with stroke is a fastgrowing area of research, and its effectiveness in patients with chronic stroke who have hemiplegia/hemiparesis has recently been confirmed (Broetz et al., 2010; Mukaino et al., 2014).In the acute/subacute phase, the risk of stroke recurrence is higher than that in chronic stroke (Burn et al., 1994; Moroney et al., 1998), and the spontaneous reorganization of the nervous system is unstable. In most cases, patients with acute/subacute stroke cannot perform sitting exercises or transfer to/from a wheelchair because they cannot control their bodies. For all of these reasons, it is difficult for inpatients with acute/subacute stroke to train on a BCI system at regular intervals in a rehabilitation laboratory or a rehabilitation room.Meanwhile, animal studies show critical neural recovery during early rehabilitative training, although the effect decrease with time (Biernaskie et al., 2004; Yang et al., 2003). Furthermore, most evidence suggests that early rehabilitation leads to better outcomes in humans than in animals (Horn et al., 2005; Maulden et al., 2005; Murphy & Corbett, 2009). Therefore, it is clinically important to establish an earlier (bedside) rehabilitative intervention protocol. The current study thus aimed to demonstrate the safety and feasibility of a bedside BCI system for inpatients with acute/subacute stroke. A number of compact and portable embedded BCI systems that have been developed by industry and academia are now available for neurorehabilitation, some of which can potentially be used for bedside treatment in acute stroke. However, from the viewpoint of a clinical-phase approach for the development of rehabilitation evidence (Whyte et al., 2009), the lack of phase 1 or 2 clinical trials has hindered progress in BCI intervention. To test the safety and feasibility of BCI interventions, here, we conducted a case-series study without a control group and conducted trials with our custom-designed BCI system in patients with acute/ subacute hemiparetic stroke. We expect our results to encourage larger phase 3 clinical trials in the future.2. METHODSThe potential risks of acute/subacute-phase interventions include (1) stroke recurrence caused by a rise in the blood pressure due to excessive engagement during training, (2) epileptic seizures, (3) headaches and other adverse nervous system effects, and (4) insufficient acceptance and commitment to the BCI training. To minimize these risks, we carefully selected participants and developed an appropriate intervention design.We used the following criteria for patient selection: (1) ability to understand and follow our instructions and expressed commitment to the training; (2) sufficient cognitive functioning (Mini-Mental State Examination score >27 points); (3) no bilateral motor deficits; (4) no history of epilepsy or medication for epilepsy; (5) no visual deficits; and (6) first-ever stroke.We recruited four inpatients (one female and three males; aged 67.4 ± 14.7 years) who fulfilled these criteria in the early phase (less than 1 month since stroke onset) at Asahikawa Medical University Hospital. The average time from stroke onset to the first intervention was 9.5 days (range 7–13 days) (Table 1). The experiment was repeated two to four times on separate days. All patients were right-handed and received conventional rehabilitation (physical, occupational, and speech-language therapy) for 1.5 hours/day on average.The study was conducted in accordance with the Declaration of Helsinki, and all patients gave written informed consent for participation and publication of their individual data, which was approved by the local ethics committee of Asahikawa Medical University (Number: 15119–2). The trial was retrospectively registered with the UMIN Clinical Trials Registry, number UMIN000023167, on July 14, 2016. Each experiment was completed within one hour, including the EEG setup and disassembly. The patients’ blood pressure was continuously monitored. If a patient felt fatigued or abnormal blood pressure was observed during the training, all experimental procedures were immediately halted.
Mainak Saha1,21Department of Metallurgical and Materials Engineering, National Institute of Technology, Durgapur-713209, India2Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai-600036, IndiaAbstract - While descending through different layers of atmosphere with tremendously high velocities, hypersonic re-entry nosecones fabricated using ultra-high temperature ceramic matrix composites (UHTCMCs) are subjected to repeated thermal shocks. This necessitates extensive investigations on the cyclic oxidation behaviour of UHTCMCs at temperatures ranging from 1100°C to 1300°C (service temperature of the nosecones). To this end, the present work is aimed at investigating the cyclic oxidation behaviour of ZrB2 -20 vol.%MoSi2 (ZM20) UHTCMC (a very widely investigated ZM CMC) by carrying out cycles for 6h, at 1cycle/h and estimating oxidation kinetic law. This has been followed by extensive characterisation using X-Ray Diffraction (XRD) to indicate the phases formed during oxidation and Scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), in order to determine the chemical composition of the oxides formed between 1100°C and 1300°C.Keywords- Borides; ceramic composites; cyclic oxidation; kinetics; oxide layerAmong UHTCs, ZrB2-based ceramics have been reported to be potential candidates for the manufacture of reusable Thermal Protection Systems (TPS) in Hypersonic re-entry nosecones, due to very high thermal conductivity and relatively low density [1,2]. However, the low fracture toughness and poor thermal shock resistance of these ceramics pose major obstacles to their use in extreme environment [3]. Moreover, the poor oxidation resistance of ZrB2 at temperatures above 1200°C, due to formation of B2O3, and a non-protective porous scale of ZrO2 [4], poses restrictions to its use at elevated temperatures, especially above 1200°C. Thus, it becomes extremely important to find materials, which may highly enhance the oxidation resistance of ZrB2 [5-8]. A significant amount of work has already been done in that direction [8-12]. Besides, a significant amount of research has been done on reinforcing diborides like ZrB2, HfB2 and TiB2 with SiC, MoSi2, or ZrSi2 for enhanced oxidation resistance beyond 800°C [3- 23]. However, a limited amount of study has been made on cyclic oxidation of ZM20 at temperatures exceeding 1100°C, which is not at all unlikely, in the context of Hypersonic nosecones, during a high velocity descent through different layers of atmosphere. Thus, the scope of the present study is to investigate the cyclic oxidation behaviour of ZM20 between 1100 and 1300 °C.The important conclusions drawn from the results and discussions of this study have been elucidated. Cyclic oxidation behaviour of ZrB2-20 vol.% MoSi2 composite have been studied at 1100 °C, 1200 °C, 1250 °C and 1300 °C for 6hrs. Monitoring weight change and examining oxide scales draw following conclusions:(i) Weight gain for both the composites increased with increasing temperature and time. (ii) Weight gain occurred due to formation of ZrO2 and SiO2, at elevated temperatures. (iii) The main oxidation products were ZrO2, MoO3 and SiO2. (iv) At 1200 °C and above, the presence of SiC particles markedly improves the resistance to oxidation of the composite due to the formation of borosilicate glass.(v) Due to formation of oxide layer on the surface, the hardness of the samples i.e. its mechanical properties decreased from center to surface.(vi) The cyclic oxidation of the samples follow linear oxidation kinetics from 1100 to 1250 ºC while at 1300 ºC it follows parabolic oxidation kinetics due to the protective action of SiO2 above 1250 ºC.The results of the present study and their analyses lead to the following directions for future work: (i) The oxidation kinetics of the samples beyond 1300 ºC can be studied. (ii) Residual strain calculations can be carried out. (iii) Mathematical modelling study of the oxidation kinetics can be carried out. (iv) TEM study of the samples can be carried out for more precarious measurements. (v) Carrying out diffusion studies on oxide layer.AcknowledgementThe authors are grateful to the Department of Metallurgical and Materials Engineering, NIT Durgapur and Central Research Facility(CRF), IIT Kharagpur, for their support to carry out the work and hereby declare no conflict of interest.

Syed Raza

and 3 more

Objectives: Prostate cancer is one of the most common cancers worldwide in men, with a huge geographical variation both in incidence and mortality. Whereas, the incidence is higher in developed countries, mortality is higher in developing countries. The reasons for high mortality in these countries include variation in practice leading to early diagnosis. Artificial Intelligence (AI) and Machine learning (ML) are increasingly being used to improve the diagnostic accuracy of prostate cancer. We interrogated the published literature to review the usage of AI and ML in the diagnosis of prostate cancer. Methods: Research databases such as SCOPUS, Web of Science (WoS), and Google Scholar were searched to identify articles related to AI/ML in the diagnosis and management of prostate cancer. Key-words included (“prostate” AND “cancer”), (“machine” AND (“learn” OR “learning”)) OR (“artificial” AND (“intelligence” OR “intelligent”)). Results Using a screening criterion, 293 reviewed research papers were identified. The two most consistent themes were predictive modeling and application of AI/ ML tools for cancer grading and radiomics. AI and ML enhance the diagnostic accuracy by reducing the inter-individual variation in Gleason’s scoring, and complimenting the interpretation of multiparametric magnetic resonance imaging (mpMRI). A few publications reported the use of AI/ML tools by combining histopathology and MRI signals. Conclusions: AI and ML can improve the diagnostic accuracy of prostate cancer. Literature is beginning to emerge suggesting to use a combination of demographic features, clinical data, serological markers, pathological grading and radiological factors, and genomic data, to propose accurate non-invasive diagnosis of clinically significant prostate cancer.

Wojciech Feleszko

and 23 more

Multisystem inflammatory syndrome in children (MIS-C) is a rare, but severe complication of coronavirus disease 2019 (COVID-19). It develops approximately four weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and involves hyperinflammation with multisystem injury, commonly progressing to shock. The exact pathomechanism of MIS-C is not known, but immunological dysregulation leading to cytokine storm plays a central role. In response to the emergence of MIS-C, the European Academy of Allergy and Clinical Immunology (EAACI) established a task force (TF) within the Immunology Section in May 2021. With the use of an online Delphi process, TF formulated clinical statements regarding immunological background of MIS-C, diagnosis, treatment, follow-up, and the role of COVID-19 vaccinations. MIS-C case definition is broad, and diagnosis is made based on clinical presentation. The immunological mechanism leading to MIS-C is unclear and depends on activating multiple pathways leading to hyperinflammation. Current management of MIS-C relies on supportive care in combination with immunosuppressive and/or immunomodulatory agents. The most frequently used agents are systemic steroids and intravenous immunoglobulin. Despite good overall short-term outcome, MIS-C patients should be followed-up at regular intervals after discharge, focusing on cardiac disease, organ damage, and inflammatory activity. COVID-19 vaccination is a safe and effective measure to prevent MIS-C. In anticipation of further research, we propose a convenient and clinically practical algorithm for managing MIS-C developed by the Immunology Section of the EAACI.

Jordan Cuff

and 5 more

1. Generalist invertebrate predators are sensitive to weather conditions, but the relationship between their trophic interactions and weather is poorly understood. This study investigates how weather affects the identity and frequency of spider trophic interactions as mediated by prey community structure, web characteristics and density-independent prey choice. 2. Spiders and their locally available prey were collected from barley fields in Wales, UK from April to September 2017-2018. The gut contents of 300 spiders were screened using DNA metabarcoding, analysed via multivariate models, and compared against prey availability using null models. 3. Spiders' trophic interactions changed over time and with weather conditions, primarily related to concomitant changes in their prey communities. Spiders did, however, appear to mitigate the effects of structural changes in prey communities through changing prey preferences according to prevailing weather conditions, possibly facilitated by adaptive web construction. 4. Using these findings, we demonstrate that prey choice data collected under different weather conditions can be used to refine inter-annual predictions of spider trophic interactions, although prey abundance was secondary to diversity in driving the diet of these spiders. By improving our understanding of the interaction between trophic interactions and weather, we can better predict how ecological networks are likely to change in response to variation in weather conditions and, more urgently, global climate change.

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