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Michael Weekes

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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.

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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Kelly McNamara A

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Abstract Background Unintended pregnancy (UIP) and substance use disorder (SUD) share underlying root causes with similar potential impacts for women and their offspring in pregnancy, birth and beyond. Furthermore, use of alcohol and other drugs (AOD) increases the risk of UIP. Objectives To assess the available evidence on impact of UIP on health, social and economic outcomes, in women who use AOD. Search Strategy The review was conducted using the Joanna Briggs Institute Methodology for Scoping Reviews and PRISMA reporting guidelines. The search was conducted across multiple electronic databases, including Scopus and Medline, and limited to studies published between January 2000 to June 2023. Selection Criteria Studies reporting on interactions between AOD use and UIP, and subsequent pregnancy, birth, infant, childhood, social or economic outcomes. All patterns and types of AOD use, except isolated use of tobacco, were included. Studies were available in English and conducted in high income countries. Data Collection and Analysis Selected articles were reviewed, and data collected by 2 independent reviewers using a standardised data extraction sheet. Findings were summarised and reported descriptively. Main Results A total of 2383 titles and abstracts were screened, 97 full texts were reviewed, and three studies were selected for inclusion in the scoping review. There was heterogeneity in types and patterns of AOD use, differences in study design and tools to assess pregnancy intention, and each focused on disparate outcomes. No study assessed or reported on birth outcomes. Conclusion There is a paucity of data examining the intersection between AOD use and UIP and further research is needed. Funding The University of Sydney Albert S. McKern Scholarship; Australian National Health and Medical research Council fellowship (APP1197940) and Financial Markets Foundation for Children.

Huanyu Li

and 3 more

Background: Animal models play a crucial role in medicine and biology, but they can’t fully replace human models for studying human biology, disease mechanisms, and drug efficacy. Human organoids offer an opportunity to investigate human diseases and complement animal models. However, research on human organoids lacks comprehensive characterizations. Objective: Identify and describe publications exploring and applying organoids. Methods: Thorough analysis of articles from the past two decades retrieved from Web of Science core collection database. Examined publication year, authors, institutions, countries, references, and keywords. Reviewed top 100 highly cited articles using CiteSpace. Results: Found 6817 original articles on organoids, with a remarkable surge over the past decade (nearly 70-fold increase since 2009). Collaboration among the United States, China, Germany, Netherlands, England, and Japan was prominent. Key figures advancing this field include Clevers Hans, Van Der Laan, Jason R. Spence, and Sato Toshiro. Top articles covered basic research (39%), stem cell development, interactions; biobanking (9%) for organoid cultivation; precision medicine (15%) in cell therapy, drug development; disease modeling (37%) involving pathogen analysis, genetic variant screening. Challenges: high costs, technological barriers, lack of standardized protocols, precise immune system establishment, limited quality clinical trials. Overcoming these requires collaborative efforts, evaluation guidelines. Conclusions: Organoid research focuses on basic research, disease modeling, precision medicine, and biobanking. Prioritizing cost reduction, technology sharing, international standards, and high-quality clinical trials is crucial.

Alvaro Sanchez

and 3 more

This paper explores the relationship between the reliance on different information sources and infodemic exposure in the early phases of the pandemic. The aim is to identify the sources that create less infodemic. We analyze high-quality secondary data from two studies using a 10-country sample: the US, UK, Canada, Brazil, France, Germany, Italy, Japan, South Africa, and South Korea. Study 1 analyzes infodemic exposure through an analysis of 3,723,920 COVID-19 tweets. Likewise, study 2 analyzes reliance on COVID-19 information sources by surveying 10,000 respondents. This research provides perspectives and implications for the infodemic debunking to the government departments, public health organizations, and media industries by analyzing the correlations between these two studies. We found that people who rely on national government information sources about COVID-19 tend to be less exposed to the infodemic. Findings also suggest a correlation between the countries with higher COVID-19 confirmed cases and people’s reliance on the national government information sources. We found that people from countries with more unverified bots tweeting about COVID-19 tend to rely less on family and friends and social media as sources. Evidence also suggests that the most trusted spokespeople are scientists and health professionals rather than politicians. Finally, we observed 70% of the sample´s countries slightly reduced their risk of exposure to the infodemic within 12 months of the pandemic’s start.

Wanyu Liu

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Teerath Kumar

and 3 more

Abhishek Dutta

and 2 more

Moment-based determination of a probability density function (PDF) is widely used in chemical and process engineering applications as they provide an efficient approach to analyze and solve complex systems. In this study, three different approaches are implemented for estimating probability distributions from their moments. These procedures are based on the reconstruction of a distribution knowing only a limited number of moments using Chebyshev polynomials, Hermite polynomials and Lagrange polynomials. To show the applicability of these approaches, various test cases with reduced set of moments are solved with a set of standard distribution families (Normal, Weibull, Log Normal and Bimodal) and with complex distributions (Smoluchowski coagulation equation and population balance equation). The results are compared with their analytical solutions using both small and big variance distributions. The Kolmogorov-Smirnov (K-S) matrix and the RMSE values of the interpolation procedure using Lagrange polynomials predict a better estimation for all the test cases compared to the other approaches including the standard monomial approach (with higher number of moments) implemented in this study. The K-S test values decreased by 19% compared to the standard monomial procedure and 11% compared to both Chebyshev and Hermite polynomial approaches. Similarly, the RMSE values improved by 85% compared to the standard monomial procedure and 62% compared to both Chebyshev and Hermite polynomial approaches. This indicates that the procedure using Lagrange polynomials is a more reliable reconstruction procedure that calculates the approximate distribution using lesser number of moments N which is desirable.

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Abstract: This study delves into an often overlooked facet of animal relationships, shedding light on the intricacies that render these bonds distinct. The research centers on the mechanisms through which animals cultivate friendships, the benefits they derive from such connections, and the myriad manifestations of these relationships across three distinct regions in Bangladesh. Notably, this investigation extends beyond intraspecies interactions to encompass interspecies bonds, including those between humans and feline and ovine companions, the companionship shared between a young feline and a human, human-canine affiliations, and the human-goat relationships. By examining these varied connections, this research seeks to unveil the profound emotional ties that transcend species boundaries and underscore the transformative influence they exert on the well-being of animals.Keywords: Ethology, Zoology, Animal Behavior, Behavioral Diversity, Domestic AnimalsIntroduction: Animals are fascinating creatures that never cease to amaze us with their unique abilities and behaviors. One aspect of their lives that has been gaining attention in recent years is their ability to form deep and lasting friendships with members of their own species and even with members of other species. From unlikely pairings, such as a cat and a man, to more common partnerships, like a dog and a human, these bonds can be heartwarming and fascinating to observe. On the basis of three different regions of Bangladesh, I attempted to investigate some of the most fascinating instances of animal friendship, exploring the scientific underpinnings of these bonds and the priceless lessons they can impart about the relationships we develop with others. In the vast and diverse animal kingdom, friendships transcend species boundaries, defying conventional expectations and captivating the hearts of enthusiasts. It can be a source of protection, with individuals banding together to avoid potential threats. It can also serve as a means of survival, with different species depending on each other for food, shelter, or mutual defense. Perhaps the most significant aspect of animal friendship is the emotional bond that can develop between individuals, transcending the boundaries of instinct and biological necessity. Dolphins are known for forming complex social networks, with individuals often developing strong bonds that can endure throughout their lifetime. Elephants display remarkable empathy and solidarity, offering comfort and support to their fellow herd members in times of distress. Even seemingly solitary big cats have been observed to form social bonds, displaying moments of affection and dependence on one another. While friendships in some animals may have clear evolutionary advantages, others seem to defy any logical explanation. Consider the well-known story of Owen and Mazie, a young hippopotamus and an older turtle who became inseparable friends after meeting in a Kenyan wildlife sanctuary (Hatkoff 2006). Despite their stark differences in size, species, and behavior, their friendship blossomed, captivating the world and reminding us of the unexpected connections that arise in nature. In light of the fact that there had not been any research on this subject from a Bangladeshi perspective, I thought about conducting a study and gathering information to share with everyone, whether they love animals or not.

Gizem Koken

and 8 more

Background: Food-induced immediate response of the esophagus (FIRE) is a new phenomenon that has been described in eosinophilic esophagitis (EoE) patients. It is suspected when unpleasant symptoms occur suddenly on contact of the triggering food with the esophageal surface and recur with repeated exposures. It can often be mistaken for pollen-food allergy syndrome (PFAS) and solid food dysphagia. Data on FIRE is limited to one survey study and case reports, and there are no screening studies conducted on either adults or children with EoE. In this study, we aimed to screen children aged ≥7 years old with EoE for FIRE. Methods: Demographic data were collected from medical records. A questionnaire about FIRE was applied to all participants. Skin prick tests (SPTs) were done on suspected patients to identify the triggering foods. FIRE is defined as suitable clinical symptoms with suspected food allergen exposure. Results: Seventy-eight patients (74.4% male, median age: 13.5 years) were included. Unpleasant and recurrent symptoms distinct from dysphagia with specific foods were reported in %16.7 of the patients, all of whom had concomitant allergic rhinitis (AR). The symptoms described by almost all patients were oropharyngeal itching and tingling (PFAS: 15.3%) excluding only one patient reporting retrosternal narrowing and pressure after specific food consumption (FIRE: 1.2%). Conclusions: Although definitive conclusions regarding the true prevalence of FIRE cannot be made, it does not seem to be common as PFAS. However, it deserves questioning particularly in the presence of concurrent AR and/or PFAS in children with EoE.

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