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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.

Scene flow tracks the three-dimensional (3D) motion of each point in adjacent point clouds. It provides fundamental 3D motion perception for autonomous driving and server robot. Although the Red Green Blue Depth (RGBD) camera or Light Detection and Ranging (LiDAR) capture discrete 3D points in space, the objects and motions usually are continuous in the macro world. That is, the objects keep themselves consistent as they flow from the current frame to the next frame. Based on this insight, the Generative Adversarial Networks (GAN) is utilized to self-learn 3D scene flow with no need for ground truth. The fake point cloud of the second frame is synthesized from the predicted scene flow and the point cloud of the first frame. The adversarial training of the generator and discriminator is realized through synthesizing indistinguishable fake point cloud and discriminating the real point cloud and the synthesized fake point cloud. The experiments on Karlsruhe Institute of Technology and Toyota Technological Institute (KITTI) scene flow dataset show that our method realizes promising results without ground truth. Just as human, the proposed method can identify the similar local structures of two adjacent frames even without knowing the ground truth scene flow. Then, the local correspondence can be correctly estimated, and further the scene flow is correctly estimated.   Corresponding author(s) Email: wanghesheng@sjtu.edu.cn

Leukocyte differential test is a widely performed clinical procedure for screening infectious diseases. Existing hematology analyzers require labor-intensive work and a panel of expensive reagents. Here we report an artificial-intelligence enabled reagent-free imaging hematology analyzer (AIRFIHA) modality that can accurately classify subpopulations of leukocytes with minimal sample preparation. AIRFIHA is realized through training a two-step residual neural network using label-free images of isolated leukocytes acquired from a custom-built quantitative phase microscope. By leveraging the rich information contained in quantitative phase images, we not only achieved high accuracy in differentiating B and T lymphocytes, but also classified CD4 and CD8 cells, therefore outperforming the classification accuracy of most current hematology analyzers. We validated the performance of AIRFIHA in a randomly selected test set and cross-validated it across all blood donors. Owing to its easy operation, low cost, and accurate discerning capability of complex leukocyte subpopulations, we envision AIRFIHA is clinically translatable and can also be deployed in resource-limited settings, e.g., during pandemic situations for the rapid screening of infectious diseases.  Corresponding author(s) Email:    rjzhou@cuhk.edu.hk,  rishikesh.pandey@uconn.edu

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.

Cannabis sativa is an extraordinarily versatile species. Hemp and its cousin marijuana, both C. sativa, have been used for millennia as a source of fibre, oil and for medicinal, spiritual and recreational purposes. Because the consumption of Cannabis can have psychoactive effects, the plant has been widely banned throughout the last century. In the past decade, evidence of its medicinal properties did lead to the relaxation of legislation in many countries around the world. Consequently, the genetics and development of Cannabis as well as Cannabis-derived products are the subject of renewed attention.Here, we review the biology of C. sativa, including recent insights from taxonomy, morphology and genomics, with an emphasis on the genetics of cannabinoid synthesis. Because the female Cannabis flower is of special interest as the site of cannabinoid synthesis, we explore flower development, flowering time well as the species’ unique sex determination system in detail. Furthermore, we outline the tremendous medicinal, engineering, and environmental opportunities that Cannabis bears. Together, the picture emerges that our understanding of Cannabis biology currently progresses at an unusual speed. A future challenge will be to preserve the multi-purpose nature of Cannabis, and to harness its medicinal properties and sustainability advantages simultaneously.

Quantum chemistry must evolve if it wants to fully leverage the benefits of the internet age, where the world wide web offers a vast tapestry of tools that enable users to communicate and interact with complex data at the speed and convenience of a button press. The Open Chemistry project has developed an open source framework that offers an end-to-end solution for producing, sharing, and visualizing quantum chemical data interactively on the web using an array of modern tools and approaches. These tools build on some of the best open source community projects such as Jupyter for interactive online notebooks, coupled with 3D accelerated visualization, state-of-the-art computational chemistry codes including NWChem and Psi4 and emerging machine learning and data mining tools such as ChemML and ANI. They offer flexible formats to import and export data, along with approaches to compare computational and experimental data.

This paper responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on masks for the lay public in the Covid-19 pandemic. I address their charges that my co-authors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms. But before that, I remind Martin et al that the evidence on mask wearing goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly-framed objections. I challenge my critics’ apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and engage, scientifically and morally, with the dreadful tragedy that is unfolding across the world.

This Supporting information includes interactive plots, videos, and data captured while performing evaluation and validation experiments for our paper. 

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.  

Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield across global regions is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control and pollination services in adjacent crops using a global dataset of 529 sites. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimize floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.

Researchers' ability to accurately screen fossil and subfossil specimens for preservation of DNA and protein sequences remains limited. Thermal exposure and geologic age are usable proxies for sequence preservation on a broad scale but are of nominal use for specimens of similar depositional environments. Cell and tissue biomolecular histology is thus proposed as a novel proxy for determining sequence preservation potential of ancient specimens with improved accuracy. Biomolecular histology as a proxy is hypothesized to elucidate why fossils/subfossils of some depositional environments preserve sequences while others do not and to facilitate selection of ancient specimens for use in molecular studies.

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.

Atrial fibrillation is significantly associated with morbidity and mortality and erodes the quality and quantity of life. It is standard of care to treat patients with AF and an increased risk of stroke with oral anticoagulation therapy, but the more daunting question many clinicians face is whether to pursue a “rate-only” or “rhythm” control strategy. Historical studies over the years have sought to answer this question but have found no significant difference in major clinical outcomes between the two strategies. There are opportunities based on new data to improve the natural history of the disease. The EAST AFnet trial for the first time revealed a significant morbidity and mortality advantage to rhythm control therapy when performed early in the disease process of AF and in the setting of comprehensive medical management that was maintained. The CABANA trial clearly demonstrated that catheter ablation was a more effective long-term treatment of AF in general and significantly lowers risk of AF progression compared to medical therapy. Like multiple prior trials of rhythm management strategies, when rhythm control was effective in these trials, independent of therapy assignment, there was a significantly lower risk of adverse outcomes and death. These contemporary data provide optimism that the pervasive mortality risk in patients with AF observed over the past 50 years may be improved by the timing, use, and efficacy of use of therapeutic interventions.

Previous research has examined the impact of family and school separately on adolescents' psychological well-being. This study focuses on the integrated role of family and school to observe their effects on children's psychological well-being. Using a random sample of 1180 Chinese children from Grades 4 to 9, this study explores the psychological well-being of rural Chinese children within this joint family-school framework. The PROCESS macro is used to conduct the moderation analysis. Results of this study show that attachment security is significantly and directly related and indirectly associated with adolescents' psychological well-being through the intermediary mechanism of self-efficacy. Moreover, peer isolation moderates the relationship between psychological well-being with attachment security and its association with self-efficacy. This study contributes to confirming self-efficacy and peer isolation's mediating and moderating role and highlights the family-school as two synergistic links that influence adolescents' psychological well-being.

The loss of coastal wetlands represents a grave threat to waterbirds, prompting the use of artificial wetlands, such as aquaculture ponds, as a means of conservation. Aquaculture ponds are common in coastal areas and provide production value and ecological function as waterbird habitats. However, certain piscivorous birds may cause economic losses to the aquaculture industry. Different types of ponds provide habitat for various bird assemblages, and waterbirds exhibit nocturnal feeding behavior and utilize habitats distinct from those used during the day. Most waterbird surveys were conducted during the daytime, limiting our understanding of their nocturnal habitat utilization. This study conducted diurnal and nocturnal surveys on shorebirds, waterfowl, and Black-crowned Night Heron (Nycticorax nycticorax) ten times in three aquaculture ponds situated in the Cigu District of Tainan, namely fish/shrimp, hard clam, and abandoned ponds between October 2021 and November 2022. The results showed no significant difference in shorebird density between day and night. However, shorebird density in fish/shrimp ponds was significantly higher than in abandoned ponds. Conversely, waterfowl density exhibits a significant increase in abandoned ponds compared to the other two pond types, irrespective of diurnal or nocturnal conditions. Furthermore, waterfowl density in abandoned ponds was significantly higher during daylight compared to the nocturnal period. In the daytime, the density of night herons was significantly higher in abandoned ponds than in the other two ponds. Nevertheless, during nighttime, fish/shrimp ponds exhibit the highest density of night herons, significantly surpassing that found in hard clam ponds. Notably, water coverage also influences the density of both shorebirds and waterfowl. The foraging frequency of waterfowl and night herons was greater during nocturnal hours, while shorebirds did not exhibit significant variations between day and night. Consequently, this study underscores the significance of considering both diurnal and nocturnal habitats in formulating strategies for waterbird conservation.

Amelia Yin,1,2 Wenyan Fu,1,2 Anthony Elengickal,2 Joonhee Kim2, Yang Liu,1,2, Anne Bigot,3 Kamal Mamchaoui,3 Jarrod A. Call,4 and Hang Yin1,2,#1 Center for Molecular Medicine, The University of Georgia, Athens, GA 30602, USA2 Department of Biochemistry and Molecular Biology, The University of Georgia, Athens, GA 30602, USA3 Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, F-75013 Paris, France4 Department of Physiology and Pharmacology, The University of Georgia, Athens, GA 30602, USA# Correspondence: hyin@uga.edu

Waterborne transmission of the bacterium L. pneumophila has emerged as a major cause of severe nosocomial infections of major public health impact. The major route of transmission involves the uptake of aerosolized bacteria, often from the contaminated hot water systems of large buildings. Public health regulations aimed at controlling the mesophilic pathogen are generally concerned with acute pasteurization and maintaining high temperatures at the heating systems and throughout the plumbing of hot water systems, but L. pneumophila is often able to survive these treatments due to both bacterium-intrinsic and environmental factors. Previous work has established an experimental evolution system to model the observations of increased heat resistance in repeatedly but unsuccessfully pasteurized L. pneumophila populations. Here, we show rapid fixation of novel alleles in lineages selected for resistance to heat shock and shifts in mutational profile related to increases in the temperature of selection. Gene-level and nucleotide-level parallelisms between independently-evolving lineages show the centrality of the DnaJ/DnaK chaperone system in the heat resistance of L. pneumophila. Inference of epistatic interactions through reverse genetics shows an unexpected interaction between DnaJ/DnaK and the polyhydroxybutyrate-accumulation energy storage mechanism used by the species to survive long-term starvation in low-nutrient environments.

Background: Colic is the commonest emergency in first opinion equine practice. Early referral is important for horses requiring surgery. Fast localised abdominal ultrasonography of horses (FLASH) is frequently used as a diagnostic tool in the investigation of colic at referral hospitals, but its use in first opinion practice has not been evaluated. Objective: To assess the value of FLASH scanning in the primary assessment of horses with colic in the field, using a portable wireless ultrasound system. Study design: Prospective study (2018-2021). Methods: Any horse examined for colic as an emergency in a first opinion ambulatory practice was eligible for inclusion in the study. A FLASH examination was performed using a wireless handheld ultrasound scanner, with the images displayed on a smartphone or tablet. The findings on FLASH scans and outcome of the case (recovered, referred for surgery or euthanised without referral) were recorded. Results: 135 equids with acute colic were evaluated. Of the 135 horses, 49 (36%) had an abnormal finding on FLASH scanning, including distended loops of small intestine (n=34), thickened small intestinal walls (n=23) and/or distension of the stomach (n=7). Reduced small intestinal motility was recorded in 52 animals (38%). Follow-up information was available in all animals: 50 (37%) were euthanised due to clinical deterioration and the owners’ decision not to undertake surgery; 85/135 (63%) survived, including 5/85 (6%) that underwent surgery and 80/85 (94%) that resolved with medical management. Main limitations: Small number of cases. Lack of results of post-mortem examination of horses that were euthanised. Potential selection bias. Conclusion: The FLASH technique can be valuable in the primary assessment of horses with colic in first opinion ambulatory practice. Further evaluation with more cases is required.

Predators can affect ecosystems through non-consumptive effects on their prey, which can lead to cascading effects on the vegetation. In mammalian communities, such cascading effects on whole ecosystems have mainly been demonstrated in protected areas, but the extent to which such effects may occur in more human-dominated landscapes remains disputable. With the recolonisation of wolves (Canis lupus) in Europe, understanding the potential for such cascading processes becomes crucial for understanding the ecological consequences of wolf recovery and making appropriate management recommendations. Here, we investigate the evidence for non-consumptive effects of wolves on their wild ungulate prey and cascading effects on the vegetation in European landscapes. We reviewed empirical studies reporting wild ungulate responses to wolves involving spatio-temporal behaviour at large and fine spatial scales, activity patterns, vigilance, grouping, physiological effects, and effects on the vegetation. We reveal that non-consumptive effects of wolves in Europe have been studied in few regions and with focus on regions with low human impact and are highly context-dependent and might often be overruled by human-related factors. Further, we highlight the need for a description of human influence in NCE studies. We discuss challenges in NCE research and the potential for advances in future research on NCE of wolves in a human dominated landscape. Further, we emphasise the need for wildlife management to restore ecosystem complexity and processes, to allow non-consumptive predator effects to occur.

Since wolf-year 2014-2015, wolves have been recolonizing the Netherlands, even though the small size of the country and the high densities of humans and livestock. In this article, the main policies on wolves and methods of monitoring wolves in the Netherlands are explained. Field monitoring is mostly done by a coordinated network of volunteers and use of genetics in both monitoring and livestock depredation events. The strategy of collecting and validation of the data is in line with the German standards, including a close collaboration between the genetic laboratories in the CEwolf consortium. In nine years of wolf monitoring, 15.347 reports of possible sightings of wolves and their tracks have been documented and validated. Of these, 3666 reports (24%) classified as direct proof of wolf (C1) and 651 reports (4%) classified as indirect proof of wolf (C2). Most abundant proof of wolves are sightings verified by imagery (N=2652), scats (N=942) and livestock depredation events (N=648). Up to April 2023, 90 wolf individuals were genetically identified in the Netherlands. These originated from Germany (36%), Belgium (13%) and the French Italian-Alps (3%) or were born in the Netherlands (27%). The first wolf territory was established in July 2018 and the population has increased since, with four wolf packs, five wolf pairs and one solitary territorial wolf in the Netherlands at the end of wolf year 2022/2023. Most of the 648 livestock depredation events involved sheep (94%). In only nine events, it was confirmed that the wolf deterrent fencing was correctly placed. The perception on wolves to the Netherlands seem to be ambiguous, even though the authorities aim for coexistence between humans, livestock and wolves. An increase in international cooperation regarding expertise with human-wildlife conflict and coexistence is recommended.

A reexamination of clinical principles of long-term opioid therapy (LTOT) for chronic pain is long overdue amid the ongoing opioid crisis. Most patients on LTOT report ineffectiveness (poor pain control, function, and health), but still find deprescribing challenging. Although prescribed as analgesics, opioids more likely provide pain relief primarily through reward system actions (enhanced relief and motivation) and placebo effect and less through anti-nociceptive effects. The unavoidable physiologic LTOT dependence can automatically lead to a paradoxical worsening of pain, disability, and medical instability (maladaptive opioid dependence) without addiction due to allostatic opponent neuroadaptations involving reward/anti-reward and nociceptive/anti-nociceptive systems. This opioid induced chronic pain syndrome (OICP) can persist/progress whether LTOT dose is maintained at the same level, increased, decreased, or discontinued. Current conceptualization of LTOT as a straightforward long-term analgesic therapy appears incongruous in view of the complex mechanisms of opioid action, LTOT dependence and OICP. LTOT can be more appropriately conceptualized as therapeutic induction and maintenance of an adaptive LTOT dependence for functional improvement irrespective of analgesic benefits. Adaptive LTOT dependence should be ideally used for a limited time to achieve maximum functional recovery and deprescribed while maintaining functional gains. Patients on LTOT should be regularly reevaluated to identify if maladaptive LTOT dependence with OICP has diminished any functional gains or lead to ineffectiveness. Ineffective LTOT (with maladaptive LTOT dependence) should be modified to make it safer and more effective. An adequately functional life without opioids is the ideal healthy long-term goal for both LTOT initiation and LTOT modification.

Pain and opioid use disorder (OUD) are inextricably linked, as the former can be a risk factor for the development of the latter, and over a third of persons with OUD suffer concomitant chronic pain. Assessing pain among people with OUD is challenging, be-cause ongoing opioid use brings changes in pain responses and most pain assess-ment tools have not been validated for this population. In this narrative review, we dis-cuss the fundamentals of pain assessment for populations with OUD. First, we de-scribe biological, psychological, and social aspects of the pain experience among people with OUD, as well as how opioid-related phenomena and healthcare dispari-ties in this population may contribute to the pain experience. Second, we review meth-ods to assess pain including: (1) traditional self-reported methods, such visual analog scales, and structured questionnaires; (2) behavioral observations and physiological indicators; (3) and laboratory-based approaches, such as functional brain imaging, electroencephalography, and quantitative sensory testing. These methods are consid-ered from a perspective that encompasses both pain and OUD. Finally, we discuss strategies for improving pain assessment in persons with OUD and implications for future research, including educational strategies for multidisciplinary teams. Substan-tial gaps persist in our knowledge, particularly regarding the applicability of current pain assessment methods to persons with OUD, as well as the generalizability of the existing results from adjacent populations. As research linking pain and OUD evolves, considering the needs of diverse populations with complex psychosocial back-grounds, we will be better equipped to reduce these gaps.

The incidence of drug administration errors in hospitals in India is not known. We aimed to extract and investigate India-specific incidents of intrathecal tranexamic acid (TXA) administration during spinal anaesthesia. Our secondary aim was to identify any publications related to national drug error and reporting systems for hospitals in India. We analysed eleven published reports of tranexamic acid administration intrathecally in place of heavy bupivacaine. The primary cause was the availability of look-like TXA and local anaesthetic (heavy 0.5% bupivacaine) ampoules in operating rooms. We found three manufacturers designed, manufactured and supplied identical TXA and heavy bupivacaine ampules. In addition, different manufacturers had similar products available in operating rooms. We searched PubMed and Google Scholar for any publication on India’s national medication error reporting system for hospitals. There was no publication on the national medication safety system involving hospitals. It demonstrates there needs to be a federal structure to report and monitor medication administration and other types of errors in hospitals in India. We highlight potential difficulties and barriers in creating a national system to notify, monitor and prevent medication errors in hospitals in India.

Offspring phenotype in most organisms is significantly mediated by genetically-based traits inherited from both parents. For instance, in many well-studied organisms, such as mammals, traits like body size and morphology are heritable and are passed on from one generation to the next. In invertebrates, such as arthropods, the situation is more complex, because traits like growth rate and body size are often more strongly correlated with biotic and abiotic parameters like food quality and availability and temperature. Thus, growth and body size are less based on heritability from parents (‘nature’) and more influenced by short-term environmental factors (‘nurture’). Here, we evaluate maternal and host size-related effects on the development of an asexually reproducing (= female only) parasitoid, Gelis agilis on pre-pupae in cocoons of its host, the primary parasitoid, Cotesia glomerata. Female G. agilis from two adult size classes, ‘small’ (mean 0.7 mg) or ‘large’ (mean 1.2 mg) were allowed to parasitize cocoons of differing size along a continuum from ~1.2 mg to ~4.0 mg and the body size and development time of their offspring was measured. In both body size classes of G. agilis mothers, offspring adult body size correlated strongly with host cocoon size, whereas there was no maternal effect on offspring size. Our results reveal that host quality completely overrides any effects of maternal size on the development of G. agilis. Given that parasitoids are under strong selection for optimal exploitation, allocation and utilization of limited resources contained in individual hosts, we argue that host quality is far more of a constraint on parasitoid development and fitness than traits inherited from one or both parents when producing sexually.