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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: [email protected] 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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Kumuda KB

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This study provides a comprehensive assessment of the current status of the Chitravathi River catchment area in Chikkaballapura District, Karnataka, with the goal of transforming it into a perennial river. The study aims to benchmark the river and its catchment, identify the drivers of degradation, and propose approaches to conserve and enhance the riverine ecosystem. The Chitravathi River, part of the Pennar River basin, traverses a drought-prone region, experiencing significant seasonal variations in flow due to over-extraction of groundwater and changing land use patterns. The catchment area, covering approximately 539 sq. km and comprising 264 villages, is characterized by low drainage density and stream frequency, indicating high retention of rainwater but excessive groundwater extraction exceeding annual recharge rates. The study documents significant land use changes, population growth, and increased economic activity impacting water demand. It highlights issues such as water quality challenges due to fluoride, nitrate, and TDS contamination, and the unsustainable use of groundwater. The report also outlines current government initiatives to augment water availability, such as the Hebbala-Nagavara Valley and Yettinahole projects, and emphasizes the need for ecologically sustainable cropping patterns and terrain-specific recharge structures. The findings underscore the importance of integrated water management strategies and policy interventions to rejuvenate the Chitravathi River and ensure sustainable water resources for the region.

Yang Zhou

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Otolith is one of the most commonly used tools to trace fish life history, as its formation is affected by environmental factors during growth. This study investigates the otolith micro-chemical information of Schizothorax grahami from the upper (U1, U2, U3), middle (M1, M2, M3) and lower (L1, L2, L3) reaches in the source section of Chishui River, China, as well as the metal content of the water corresponding to fish habitats. Seventeen active elements in otolith were detected, and calcium (Ca) content was the highest (175605.4*10-6 g/g). Only strontium (Sr) was regularly distributed in otolith rings by face-scan images with a relatively small coefficient of variation. A paired two t-test showed that the values of Sr: Ca were significant differences among the samples from the three reaches through otolith line scans. In the correlation test after the first-order difference processing, the change frequency of Sr: Ca values in the otolith corresponded better to the line plots and significantly differed among the three reaches, especially the samples from the U3 and L2 sites. Therefore, analyzing Sr in the otolith of S. grahami from three reaches can differentiate fish stocks and reveal their unique life histories. The magnesium (Mg) in the otolith core at the early stage of fish life was significantly higher than that of the non-core area. Likewise, Mg content was higher in the fish spawning ground than in the non-spawning ground. Presumably, Mg content in the otolith was correlated to the water environment of the spawning ground. Meanwhile, the values of Mg: Ca in the otolith core showed significant differences among the samples from U3, L2 and the other sites, indicating that fish in these samples came from different spawning grounds. The characteristics of Mg in the otolith can reflect the life history of S. grahami in the Chishui River and the location of spawning grounds. This study indicates that strontium and magnesium in otolith can be used to trace the life history of S. grahami in the Chishui River and aid fishery management for different fish stocks.

Lillian McGilp

and 7 more

Northern Wild Rice (NWR; Zizania palustris L.) is an aquatic, annual grass with significant ecological, cultural, and economic importance to the Great Lakes region of North America. In this study, we assembled and genotyped a diverse collection of 839 NWR individuals using genotyping-by-sequencing (GBS) and obtained 5,955 single-nucleotide polymorphisms (SNPs). Our collection consisted of samples from 12 wild NWR populations collected across Minnesota and Western Wisconsin, some of which were collected over two time points; a representative collection of cultivated NWR varieties and breeding populations; and a Zizania aquatica outgroup. Using these data, we characterized the genetic diversity, relatedness, and population structure of this broad collection of NWR genotypes. We found that wild populations of NWR clustered primarily by their geographical location, with some clustering patterns likely influenced by historical ecosystem management. Cultivated populations were genetically distinct from wild populations, suggesting limited gene flow between the semi-domesticated crop and its wild counterparts. The first genome-wide scans of putative selection events in cultivated NWR suggest that the crop is undergoing heavy selection pressure for traits conducive to irrigated paddy conditions. Overall, this study presents a large set of SNP markers for use in NWR genetic studies and provides new insights into the gene flow, history, and complexity of wild and cultivated populations of NWR.

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C.T. O’Connor

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Kawakawa ( Macropiper excelsum), is an endemic plant of Aotearoa New Zealand. Kawakawa holds cultural significance to Māori as a rākau rongoā (medicinal plant). Kawakawa is traditionally used internally to relieve gastrointestinal and genitourinary problems as well as topically to treat a range of skin conditions and may have anti-diabetic properties. The kawakawa looper/whangawhanga ( Cleora scriptaria) creates characteristic holes in kawakawa leaves and traditional mātauranga Māori (Māori knowledge) has identified that leaves eaten by the caterpillars have greater healing properties. To substantiate this traditional knowledge, we used Rapid Evaporative Ionisation Mass Spectrometry (REIMS), a metabolomics fingerprinting technique that does not require sample preparation and is suitable for spatial analysis, to measure metabolite differences between leaves exposed to different caterpillars. Three species; brindled bell moth ( Epalxiphora axenana), brown headed leafroller ( Ctenopseustis obliquana), and kawakawa looper ( Cleora scriptaria), were fed on kawakawa leaves. Leaves with and without caterpillar damage were harvested from plants, adhering to Māori principles (tikanga), and stored at -80°C. REIMS with a laser interface was used to generate metabolite fingerprints from caterpillar eaten and non-eaten sections from the same leaf and other non-eaten leaves from the same plant, and differences determined using multivariate modelling. There were substantial differences in the metabolomic fingerprint between eaten and non-eaten leaves of the same kawakawa plants, and of uneaten leaves from plants that had no insect herbivory. We found no difference between artificially hole punched leaves and non-eaten leaves, suggesting that metabolic variation in leaves is due to the interaction between caterpillars and leaves. Further, differences were observed between eaten leaves of the three caterpillar species emphasising the specificity of plant responses to herbivore feeding. Our results support the mātauranga that the caterpillar causes a change in plant chemical composition, potentially increasing the plant’s medicinal value.

Julian Karoliny

and 4 more

In wireless communications, trustworthiness computation has emerged as a crucial aspect of safeguarding modern systems against cybersecurity threats, ensuring reliable data transmission and upholding user trust. However, there is no unified definition of trustworthiness computation in the literature, and it is often presented as a specifically tailored adaptation of attack detection mechanisms. In contrast, this work introduces a general method for trustworthiness computation in wireless networks. It leverages key system characteristics, such as the channel, timing, and packet information to identify measurable Quality of Service (QoS) features with sufficient sensitivity across varying operational conditions.  Building on these features, a novel three-step approach is applied. It employs changepoint detection to identify potential trustworthiness issues, calculates indicators based on the observed features, and finally combines them into a quantitative representation of trustworthiness. This systematic method effectively distinguishes between regular statistical variations in QoS features and actual trustworthiness issues. The applicability of the presented approach is demonstrated using a typical IEEE 802.11 wireless link, where different QoS features and scenarios are defined. These scenarios include network attacks, system malfunctions, and typical operational conditions.  Our trustworthiness computation method correctly alerts the system to all trustworthiness issues that we challenge it with.

Ali Saeibehrouzi

and 3 more

Solute transport in unsaturated porous media is of interest in many engineering and environmental applications. The interplay between small-scale, local forces and the porous microstructure exerts a strong control on the transport of fluids and solutes at the larger, macroscopic scales. Heterogeneity in pore geometry is intrinsic to natural materials across a large range of scales. This multiscale nature, and the intricate links between two-phase flow and solute transport, remain far from well understood, by and large. Here, we use high-resolution direct simulation to quantify solute mixing and dispersion behavior within correlated porous media during drainage under an unfavorable viscosity ratio. Through analysis of flow and transport at multiple realizations, we find that increasing spatial correlations in pore sizes increase the size of the required Representative Elementary Volume (REV). We show that increasing the correlation length enhances solute dispersivity through its impact on the spatial distribution of low-velocity (diffusion-dominated) and high-velocity (advection-dominated) regions. Fluid saturation is shown to directly affect diffusive mass flux among high-and low-velocity zones. Another indirect effect of correlated heterogeneity on solute transport is through its control of the drainage patterns via repeated alteration in the connectivity of flowing pathways. Our findings improve quantitative understanding of solute mixing and dispersion under two-phase conditions, highly relevant to some of our most urgent environmental problems.

Florian Stroebl

and 3 more

Optimal Experimental Design (OED) aims to maximize information about model parameters with minimal experiments. Methodically, OED is based on the principle of maximizing Fisher information. The calculation of an optimized test plan thereby requires a qualified estimate, i.e. a priori information, about the true value of the parameters to be estimated. This paper introduces a novel Multi-Stage Optimal Experimental Design (MS-OED) framework that integrates Latin Hypercube (LH) sampling and OED for scenarios lacking prior system knowledge. The Virtual Experimental Framework (VEF) evaluates multiple experimental setups, assessing their impact on parameter estimation accuracy. Applied to lithium ion (Li-ion) battery calendar aging, our MS-OED framework demonstrates, that reducing the duration of initial LH experiments allows for more effective subsequent OED stages, achieving a 92% reduction in the standard deviation of parameter estimates compared to single-stage design of experiments (DoE). This approach also reduces the experimental duration required to achieve similar confidence levels in parameter estimation to 32% of the time needed by conventional single-stage DoE. Sensitivity analysis further confirms the robustness of the pi-OED approach against uncertainties in initial parameter estimates for the given parametric model. The results highlight the framework's potential to significantly enhance the efficiency and accuracy of experiments, particularly in applications where prior knowledge is limited.

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