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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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The Impact of NDIS pricing on Ballarat Disability Providers - AliceJane WebbWe need to firstly understand the policy making environment in order to influence the NDIS/NDA funding knowing who has the power to make decisions and changes is key, develop a well-defined understanding of the issues in order to create a clear unified solution and then advocate and lobby for new NDIS prices and a new Multi Enterprise Agreement. Gaining the attention of policymakers is complex, being able to simplicity present the problem and solution can ease any confusion around the issues raised (Cullerton et al., 2016).We need a proficient and successful NDIS market for disability support services that include:Quality frameworks for servicesFinancially viable for all three stakeholder groupsTraining and development for service provider employeesFair and effective enterprise agreement for service provider employeesTransparent pricing and calculationsEducation/advocacy for clients with a disabilityOur advocacy project will try to achieve these six key areas through a communication strategy that involves social media, talking with politicians, writing journal articles, talking at conferences and supporting other service providers and advocacy groups to join in.Look at his through the stages of the critical reflection model- deconstruct, confront, theorise, and think otherwise (Ramachandran, 2017), each stage of the model has an intention.The four stages look at a critical evaluation of the issue and advocacy strategy. The first two stages look at the meanings and discourses in applying the solution (Henderson & Noble, 2015). The final two staged assist in reconstructing through thinking about other evidence and possibilities on similar and differing topics (Thomas, 1999).The four stages assist in critically rethinking and reflecting academically whilst working through the possible issues and concerns with the implementation (Gur-Ze’ev, Masschelein & Blake, 2001).To deconstruct the issues and practices including problems of practice within this stage we try to understand the various perspectives that exist (Bartesaghi et al., 2018). This requires pulling apart analysis of what has or might happen in practice, especially practice that is taken for granted or have become normalised. Prior to the National Disability Insurance Scheme (NDIS), the disability sector had a different structure with three main groups of stakeholders, the customer who pays the bills (government agencies such as the Department of Health and Human Services), consumers who require the services, people with a disability (PWD) and the service providers who design and provide services for the consumers. The NDIS saw changes in many areas, mainly in the government role from the customer who paid the bills for the consumers, to the regulator and policy maker causing several perspective changes (DSS, 2012 & NDIA, 2019). The following table outlines the stakeholders as they are presently and their relevant perspectives and goals.The government perspective of the NDIS is focused on the best possible services for PWD with the least expense and maintaining that Australia wide (DHHS, 2016, & NDIA, 2018). The client perspectives include a service that supports their individual needs, quality of life improvement and freedom to choose and make informed decisions (NDIA, 2019 & DHHS, 2016). Service providers want to look after their employees through training, development, ethical and safe working conditions, to stay financially viable and provide the best possible cost-effective services to PWD (Foster, 2019 & Hubbard, 2019 & Jaworski et al., 2018). With three differing perspectives and goals it is difficult to come together and design the best and most sustainable disability sector.The confronting stage looks at the three perspectives (Government, Provider and Client) and confronts the assumptions underlining practice including an examination of the historical, social and cultural contexts involved (Loja et al., 2013).

Yilang Xu

and 5 more

Antarctic coastal polynyas are hotspots of biological production with intensive springtime phytoplankton blooms that strongly depend on meltwater-induced restratification in the upper part of the water column. However, the fundamental physics that determine spatial inhomogeneity of the spring restratification remain unclear. Here, we investigate how different meltwaters affecting springtime restratification and thus phytoplankton bloom in Antarctic coastal polynyas. A high-resolution coupled ice-shelf/sea-ice/ocean model is used to simulate an idealized coastal polynya similar to the Terra Nova Bay Polynya. To evaluate the contribution of various meltwater sources, we conduct sensitivity simulations that alter physical factors such as alongshore winds, ice shelf basal melt rates, and surface freshwater runoff. Our findings indicate that sea ice meltwater from offshore is the primary buoyancy source of polynya near-surface restratification, particularly in the outer-polynya region where chlorophyll concentration tends to be high. Downwelling-favorable alongshore winds can direct offshore sea ice away and prevent sea ice meltwater from entering the polynya region. Although the ice shelf basal meltwater can ascend to the polynya surface, much of it is mixed vertically over the water column and confined horizontally to a narrow coastal region, and thus does not contribute significantly to the polynya near-surface restratification. Surface runoff from ice shelf surface melt could contribute greatly to the polynya near-surface restratification. Nearby ice tongues and headlands strongly influence the restratification process through modifying polynya circulation and meltwater transport pathways. Results of this study can help explain observed spatiotemporal variability in restratification and associated biological productivity in Antarctic coastal polynyas.

Yan Barabinot

and 2 more

Zijuan Hu

and 7 more

As a particularly common minerals in granites, the presence of feldspar and altered feldspar-chlorite gouges at hydrothermal conditions have important implications in fault strength and reactivation. We present laboratory observations of frictional strength and stability of feldspar (K-feldspar and albite) and altered feldspar-chlorite gouges under conditions representative of deep geothermal reservoirs to evaluate the impact on fault stability. Velocity‐ stepping experiments are performed at a confining stress of 95 MPa, pore pressures of 35-90 MPa and temperatures of 120-400°C representative of in situ conditions for such reservoirs. Our experiment results show that the feldspar gouge is frictionally strong (μ~0.71) at all experimental temperatures (~120-400℃) but transits from velocity-strengthening to velocity-weakening at T>120°C. Increasing the pore pressure increases the friction coefficient (~0.70-0.87) and the gouge remains velocity weakening, but this weakening decreases as pore pressures increase. The presence of alteration-sourced chlorite leads to a transition from velocity weakening to velocity strengthening in the mixed gouge at experimental temperatures and pore pressures. As a ubiquitous mineral in reservoir rocks, feldspar is shown to potentially contribute to unstable sliding over ranges in temperature and pressure typical in deep hydrothermal reservoirs. These findings emphasize that feldspar minerals may increase the potential for injection-induced seismicity on pre-existing faults if devoid of chlorite alteration.

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The profound association between music and human emotion has transcended epochs, underscoring the capacity of musical compositions to elicit a spectrum of feelings, from exuberance to introspection. In the contemporary landscape, the intersection of music and technological advancements has engendered a paradigmatic shift in the creation and interpretation of musical compositions. Central to this transformation is the integration of artificial intelligence (AI) into the realm of music composition, a domain historically governed by human creativity. This research endeavors to navigate this juncture, unraveling the prospect of imbuing AI-generated music with heightened emotional resonance, thereby amplifying the scope of artistic expression. At the crux of this exploration lies the innovative utilization of Generative Adversarial Networks (GANs) to infuse the synthesized musical compositions with an intricate tapestry of human-like emotions. This paper sets out to elucidate the multifaceted dimensions of this venture by charting a trajectory that traverses the historical lineage of emotional undertones in music, culminating in a contemporary synergy between AI capabilities and human sentiment. Our approach is encapsulated within the nexus of technology and creativity, where GANs are envisaged as a conduit to facilitate the infusion of emotions into AI-generated musical compositions. In subsequent sections, we delve into an immersive analysis of the seminal role that music has played in articulating emotions throughout history. Moreover, we embark on a comprehensive exploration of the confluence of AI advancements and the nuanced realm of emotional resonance, delineating the profound possibilities that emerge from this amalgamation. Crucially, the research postulates a novel framework that leverages GANs to imbue AI-generated harmonies with a poignant emotional depth, elucidating the pivotal role of technology in elevating the emotive tenor of musical compositions. The subsequent chapters unravel the intricate methodology underpinning this research, encapsulating data collection processes, GAN architecture elucidation, techniques for embedding emotional facets, and the meticulous training process. Furthermore, a meticulous analysis of the emotional impact of AI-generated music on human perception is presented, both quantitatively and qualitatively, shedding light on the efficacy of the GAN-powered approach. Conclusively, the research extends its purview to expound upon the ethical considerations embedded within this paradigmatic juncture, while also envisioning potential trajectories for the practical application and validation of the proposed GAN-powered methodology. As the curtains are drawn on this introductory exposition, the subsequent sections promise a symphony of insights, culminating in a harmonious synthesis of AI ingenuity and human emotional resonance within the tapestry of musical composition.

Xiangkun He

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Ensuring safety and achieving human-level driving performance remain challenges for autonomous vehicles, especially in safety-critical situations. As a key component of artificial intelligence, reinforcement learning is promising and has shown great potential in many complex tasks; however, its lack of safety guarantees limits its real-world applicability. Hence, further advancing reinforcement learning, especially from the safety perspective, is of great importance for autonomous driving. As revealed by cognitive neuroscientists, the amygdala of the brain can elicit defensive responses against threats or hazards, which is crucial for survival in and adaptation to risky environments. Drawing inspiration from this scientific discovery, we present a fear-neuro-inspired reinforcement learning framework to realize safe autonomous driving through modeling the amygdala functionality. This new technique facilitates an agent to learn defensive behaviors and achieve safe decision making with fewer safety violations. Through experimental tests, we show that the proposed approach enables the autonomous driving agent to attain state-of-the-art performance compared to the baseline agents and perform comparably to 30 certified human drivers, across various safety-critical scenarios. The results demonstrate the feasibility and effectiveness of our framework while also shedding light on the crucial role of simulating the amygdala function in the application of reinforcement learning to safety-critical autonomous driving domains.

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