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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

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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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Inez L. Vanwersch

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Objective To develop an evidence-based and simple screening tool to estimate calcium intake in pregnant women, suitable for use in daily clinical practice. Design Cross-sectional analysis within a cohort study Population and setting We extracted all data from the Rotterdam Periconceptional cohort (PREDICT study) conducted at the Erasmus MC, University Medical Centre in Rotterdam, the Netherlands, between November 2014 and December 2020. Methods Data was extracted from food frequency questionnaires. The estimated average requirement of 750 m/day was defined as the lower limit for an adequate calcium intake. We created a prediction model, using multivariable binary logistic regression with backward stepwise selection. We developed a simple screening tool based on the prediction model. Main outcome measures Probability of adequate calcium intake Results 694 participants are included, of which 201 (29%) had an adequate calcium intake. Total daily or weekly intakes of cheese, milk, and yogurt or curd were selected as predictors for the prediction model. The model had excellent discrimination (AUC 0.858), a good fit (Brier score 0.136, HL statistic p=0.499) and satisfactory calibration. The test accuracy measures were: sensitivity 80.9%, specificity 77.1%, PPV 89.7%, NPV 62.2%. A color coded digital screening tool was developed for use in clinical practice. Conclusions This evidence-based and simple screening tool is a reliable and efficient instrument to predict inadequate calcium intakes in pregnancy, which can easily be incorporated in daily clinical practice and existing pregnancy coaching platforms.
The reliability of Electroencephalography (EEG) measurements on normal human neurophysiology can be used to determine whether changes in brain electrical activity in subjects with neurological diseases have potential in the diagnosis or follow-up of the patients, being more crucial in neurodegenerative diseases where reliable measures across time might be needed. The objective of this study is to report the reliability of relative band powers extracted from a two-year four-session resting-EEG longitudinal study conditioned by an automated pipeline that leverages state of the art EEG signal-processing approaches involving ICA, wavelet-ICA, and normalization by a recording-specific constant. The Intraclass Correlation Coefficient (ICC) was used as a measure of reliability. Similarly, to assess the association between age and relative performance. The results of the ICC for EEG data acquisition and preprocessing process showed high significant reliability, where an average ICC of 0.91 ± 0.04 was obtained for neural related Independent Components (ICs) and 0.92 ± 0.03 for ROIs (p-value < 5% for all data). This study shows that after performing four EEG recording sessions for 43-subject, the recorded measurements were replicable, and the correlation of relative power with the age of healthy subjects is consistent with the literature. These results suggest that relative power measured from EEGs preprocessed with the automated pipeline is a replicable metric across sessions, and, consequently, is useful for the study of relative power changes caused by the progression of neurodegenerative pathologies such as Alzheimer’s disease.

Mugenzi Leon

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Deciphering the evolutionary forces controlling insecticide resistance in malaria vectors remains a prerequisite to designing molecular tools to detect and assess resistance impact on control tools. Here, we demonstrate that a 4.3kb transposon-containing structural variation drives pyrethroid resistance in central/eastern African populations of the malaria vector Anopheles funestus. In this study, we analysed Pooled template sequencing data and direct sequencing to identify an insertion of 4.3kb containing putative transposons in the intergenic region of two P450s CYP6P5-CYP6P9b in mosquitoes of the malaria vector Anopheles funestus from Uganda. We then designed a PCR assay to track its spread temporally and regionally and decipher its role in insecticide resistance. The insertion originates in or near Uganda in East Africa, where it is fixed and has spread to high frequencies in the Central African nation of Cameroon but is still at low frequency in West Africa and absent in Southern Africa. A strong association was established between this SV and pyrethroid resistance in field populations (SV+ vs SV-; OR=29, P< 0.0001) and is reducing pyrethroid-only nets’ efficacy. Genetic crosses and qRT-PCR revealed that this SV enhances the overexpression of CYP6P9a/b but not CYP6P5. A marked and rapid selection was observed with the 4.3kb-SV frequency increasing from 3% in 2014 to 98 % in 2021 in Cameroon. Our findings highlight the underexplored role and rapid spread of SVs in the evolution of insecticide resistance and provide additional tools for molecular surveillance of insecticide resistance.

Sandra Vardeh

and 5 more

The Australian range of little penguins, Eudyptula minor, extends around southern Australia, with range-edge sites near the large cities of Perth (west) and Sydney (east). Both range-edges are closer to the equator than the range-core, being likely to experience similar heating with climate change. As a result, movement to one range-edge is not an option for little penguins, unlike in many other species. Therefore, adaptation at the range edge might be very important for little penguins. Capacity for future adaptation depends upon the variability each site holds, and the amount of exchange between sites. In peripheral sites, incoming dispersal might either forestall demographic collapse and replenish genetic variation (good), or overcome local adaptation and increase disease transmission (bad). We aimed to establish the genetic variability in each site, and the exchange (dispersal) of individuals between sites. Genetic markers included biparentally-inherited microsatellites, and maternally-inherited mitochondrial DNA sequence. For microsatellites, no site appeared to have critically low variation, including the peripheral sites, however there was a significant but slight trend of increased variation from east to west. In contrast, mitochondrial DNA showed a pattern of significantly reduced variation at the two range-edges, possibly indicating differential dispersal patterns in males and females. There appear to be two main genetically distinct groups, in the west and the east, but analysis of lifetime dispersal patterns across the Australian range also suggests complex dispersal, sometimes with high dispersal or similarity between locations that are not adjacent. Our work suggests that despite some differentiation, little penguin sites are interdependent due to complex dispersal patterns, and all have valuable genetic variation. In particular, the peripheral sites are not depauperate of variation, and are moderately connected to the remainder of the distribution, so possibly may be able to adapt in response to climate warming.
Changes in telomere length are increasingly used to indicate species’ response to environmental stress across diverse taxa. Despite this broad use, few studies have explored telomere length in plants. However, rapid advances in sequencing approaches and bioinformatic tools now allow estimation of telomere length using whole genome sequencing (WGS) data. Thus, evaluation of new approaches for measuring telomere length in plants are needed. Traditionally, telomere length has been quantified using quantitative polymerase chain reaction (qPCR). While WGS has been extensively used in humans, no study to date has compared the effectiveness of WGS in estimating telomere length in plants relative to traditional qPCR approaches. In this study, we use one hundred Populus clones re-sequenced using short-read Illumina sequencing to quantify telomere length using three different bioinformatic approaches, Computel, K-seek, and TRIP, in addition to qPCR. Overall, telomere length estimates varied across different bioinformatic approaches, but were highly correlated across methods for individual genotypes. A positive correlation was observed between WGS estimates and qPCR, however, Computel estimates exhibited the greatest correlation. Computel incorporates genome coverage into telomere length calculations, suggesting that genome coverage is likely important to telomere length quantification when using WGS data. Overall, telomere estimates from WGS provided greater precision and accuracy of telomere length estimates relative to qPCR. The findings suggest WGS is a promising approach for assessing telomere length, and as the field of telomere ecology evolves may provide added value to assaying response to biotic and abiotic environments for plants needed to accelerate plant breeding and conservation management.

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Mulugeta Tuji Dugda

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Large earthquakes, especially those occurring in a city or population centers, create devastation and havoc, and often times kindle several deaths and injuries, and significant infrastructure damage that lead to several billions of dollars in losses. Marine earthquakes are the leading cause of large tsunamis which cause deaths, destruction, displacement of population, and a possible nuclear meltdown. Thus, prediction of earthquake or its aftershocks or earthquake early warning system has a great potential to mitigate the loss of life as well as different kinds of damage. Earthquake prediction would mean forecasting the occurrence of an earthquake by providing both its magnitude estimate and accurate location. Earthquake prediction has been an important area of seismology research for quite a while, and it looks like it will continue to be an important area of research. Recently, with the implementation of deep learning in seismology, scientists have been able to detect, predict, and model seismic waves and earthquake aftershocks. Earthquake aftershocks are generally triggered by changes in stress formed by large earthquakes that happen within, or surrounding a given fault network system. The main goal of this study is to investigate the improvement of aftershock pattern predictions with the implementation of tuning and optimizing of deep learning parameters. To achieve these goals, we have developed an algorithm that can help first gather mainshock-aftershock sequence data. Some of the criteria used in identifying earthquakes that initiate an aftershock is to look at earthquakes that happen within a certain radius, the values we attempted are within about 0.5 degrees range, and within a certain period, from few seconds to several weeks of the occurrence of the main shock. For the sequence identification, we have been using seismic data from the United States Geological Survey (USGS)-National Earthquake Information Center (NEIC). We are also looking at different open-source data gathered by researchers for a similar study. The deep neural networks we are implementing make use of Keras python Toolkit, and Theano and Tensorflow libraries, with a plan to use PyTorch python library instead of Theano library in the future because of some maintenance issues. To this point our attempts have shown a good progress.

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