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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: 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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Most recent documents

Bernard Gerstman

and 3 more

Multi-antimicrobial extrusion (MATE) transporter membrane proteins provide drug and toxin resistivity by expelling compounds from cells. MATE proteins can be pictured as V-shaped. To regulate its functioning, the protein structure can switch between outward-facing (OF) and inward-facing (IF). Pyrococcus furiosus MATE (PfMATE) is the only member of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) superfamily that has available both the IF and OF crystal structures. With the availability of the both the IF and OF structures, we are able to perform computational investigations to determine how protonation of specific amino acids causes a cascade of changes in the protein conformation that allow PfMATE to change its state from OF to IF in order to regulate its antiporter function. Using a variety of computational techniques, we investigated four different systems of IF and OF PfMATE along with the native archaeal lipid bilayer, without or with protonation at the experimentally determined locations within the protein. We performed molecular dynamics (MD) simulations to investigate the flexibility of the four different PfMATE structures, and also performed targeted molecular dynamics (TMD) simulations during which we observe occluded conformations. Our analysis of hydrogen bond changes, potential of mean force, dynamic network analysis, and transfer entropy analysis provides information on how protonation can induce cascading structural changes responsible for the transition between the IF and OF configurations.

Dea Gogishvili

and 5 more

Glial fibrillary acidic protein (GFAP) is a promising biomarker for brain and spinal cord disorders. Recent studies have highlighted the differences in the reliability of GFAP measurements in different biological matrices. The reason for these discrepancies is poorly understood as our knowledge of the protein’s 3-dimensional conformation, proteoforms, and aggregation remains limited. Here, we investigate the structural properties of GFAP under different conditions. For this, we characterised recombinant GFAP proteins from various suppliers and applied hydrogen-deuterium exchange mass spectrometry (HDX-MS) to provide a snapshot of the conformational dynamics of GFAP in artificial CSF compared to the phosphate buffer. Our findings indicate that recombinant GFAP exists in various conformational species. Furthermore, we show that GFAP dimers remained intact under denaturing conditions. HDX-MS experiments show an overall decrease in H-bonding and an increase in solvent accessibility of GFAP in aCSF compared to the phosphate buffer, with clear indications of mixed EX2 and EX1 kinetics. To understand possible structural interface regions and the evolutionary conservation profiles, we combined HDX-MS results with the predicted GFAP-dimer structure by AlphaFold-Multimer. We found that deprotected regions with high structural flexibility in artificial CSF overlap with predicted conserved dimeric interface regions. Our results suggest that GFAP exists in several conformational forms. Structural property predictions combined with the HDX data show an overall deprotection and signatures of aggregation in aCSF. We anticipate that the outcomes of this research will contribute to a deeper understanding of the structural flexibility of GFAP and ultimately shed light on its behaviour in different biological matrices.

Hamed Khalili

and 2 more

Even when the SARS-CoV-2 pandemic recedes, evidence-based researches regarding the effectiveness of pharmaceutical and non-pharmaceutical government interventions (NPIs) remain important. In this study, SARS-CoV-2 data of 30 European countries from early 2020 up to mid 2022 are analyzed using Bayesian machine learning. Four data sources containing each country’s daily NPIs (consisting of 66 government measures, virus variant distributions of 31 virus types, the vaccinated population percentages by the first five doses as well as the reported daily infections in each country) are brought together to undertake a comprehensive assessment of the impact of SARS-CoV-2 influential factors on the spread of the virus. First, a Bayesian deep learning model is constructed with a set of input factors to predict the growth rate of the virus one month ahead of the time from each day. Based on this, the importance and the marginal effect of each relevant influencing input factor on the predicted outcome of the neural network model is computed by applying the relevant algorithms. Subsequently, in order to examine the performed deep learning analysis, a Bayesian statistical inference analysis is performed within each country’s data. For each influencing input factor, the distribution of pandemic growth rates, in the days where the selected explanatory factor has been active, is compared with the distribution of the pandemic growth rates, in the days where the selected explanatory variable has not been active. The results of the statistical inference confirm the predictions of the deep learning model to a significant extent. Similar conclusions from the SARS-CoV-2 experiences of the thirty studied European countries have been drawn.

Yuki Akiyama

and 1 more

TITLE PAGEArticle TypeClinical pictureTitlePenile Injury Caused by Neodymium MagnetsAuthorsYuki Akiyama1, Ryo Ichibayashi2Affiliations1. Department of Orthopaedic Surgery, Toho University Medical Center, Sakura Hospital, Chiba, Japan2. Division of Emergency Medicine Department of Internal Medicine, Toho University Medical Center, Sakura Hospital, Chiba, JapanCorresponding AuthorRyo Ichibayashi, MD, PhDORCID iD of Emergency Medicine Department of Internal MedicineToho University Medical Center, Sakura Hospital564-1 ShimosizuSakura-shi, Chiba 285-8741, JapanPhone: +81-43-462-8811Fax: +81-43-462-8835e-mail: titleDamage caused by neodymium magnetsKeywordsNeodymium magnet, Penile foreign body, Emergency, TreatmentConflict of interestThe authors have no conflict of interest to disclose.Financial supportThe author(s) received no financial support for this article’s research, authorship, and publication.Patient consentWritten informed consent was obtained from the patient to publish this report by the journal’s patient consent policy.Author contributionYA wrote and drafted the manuscript. RI helped draft the manuscript. All authors read and approved the final manuscript.Data availability statementThe data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical considerations.AcknowledgmentsNone.Key clinical messageMultiple neodymium magnets can pinch tissue and cause barotrauma. Be careful if the tissue of the penis or foreskin is pinched, as this may cause foreskin necrosis or damage to the urethra.Clinical picture11-year-old boy. He has no history of developmental disabilities or mental illness. The boy played with a neodymium magnet attached to his penis in the bathroom out of curiosity. However, the neodymium magnet remained attached to his penis and could not be removed, and he was transported to our hospital by ambulance with the chief complaint of penile pain. Emergency crews tried to remove it, but it was impossible because it was painful, and there were concerns that it might damage the foreskin. Two hours had passed since he was transferred to our hospital because he was refused admission by multiple medical institutions. At the time of his visit, his penis had two circular neodymium magnets, each approximately 1 cm in diameter, placed against the foreskin of his penis (Figure 1A). Although it was difficult to remove it by pulling it in the opposite direction, it was possible to remove it by shifting the ground surface. After the foreskin was released, there was a crushed wound, so ointment was applied(Figure 1B). After confirming that there was no problem with the color tone of his glasses, he returned home. The next day, he returned to the outpatient clinic and confirmed that the color of his glans was standard and that he could urinate. Neodymium magnets were developed in Japan in 1982 and have become famous worldwide due to their effectiveness. It is said to be the strongest magnet currently in use. Neodymium magnets are used in various fields and children’s toys [1]. For this reason, accidents such as accidental ingestion by children and insertion into the urinary tract or anus due to sexual preference are problems in the medical field. Accidents caused by multiple neodymium magnets, especially when accidentally swallowed or inserted with a foreign object, are dangerous because they adhere to each other and pinch tissue, resulting in pressure necrosis [2]. This case also had a crush injury to the foreskin. A month later, the scar remained on my foreskin. Barotrauma caused by neodymium magnets often involves damage to thin tissues, including the intestinal tract and mucous membranes. The structures of the corpus cavernosum and the corpus cavernosum of the urethra, which form the penis, are spongy and soft tissues. This tissue becomes rigid as it fills with blood. For this reason, if not only the foreskin but also the corpus cavernosum of the penis is pinched, there is a possibility that blood flow to the corpus cavernosum and damage to the urethra may occur. After removing the neodymium magnet, it is necessary to observe the color of the glans and foreskin and the state of urination.References1. Taylor MA, Spanos SP, Fenton SJ, Russell KW. Ball Magnets Clicked Together on the Epiglottis. Cureus . 2020. 12(5): e8181. doi: 10.7759/cureus.81812. Yuksel C, Ankarali S, Aslan Yuksel N. The use of neodymium magnets in healthcare and their effects on health. North Clin Istanb . 2018; 5(3): 268-273. doi:10.14744/nci.2017.00483Figure 1A Neodymium magnet that pinches the foreskin of the penisB  Foreskin with a crush injury
Downstaging case of hepatocellular carcinoma“Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy”ABSTRACTIntroduction: Transarterial chemoembolization (TACE) is the most used treatment option for patients with intermediate-stage hepatocellular carcinoma (HCC) who are not candidates for a curative approach. Through it, it is possible both to carry out palliative treatment and to reduce the size of the tumor so that the patient is eligible for a curative treatment such as a liver transplant. This modality of offering TACE to reduce the tumor stage and allow curative treatment is called “Downstaging”. Patients with HCC greater than 7 cm generally do not respond very well to chemoembolization to reduce tumor size, and generally this “downstaging” is not performed.Objective: To disseminate information in the medical community about a case of a patient with a hepatocellular carcinoma larger than 7 cm, who underwent chemoembolization to reduce staging and who met eligibility criteria for liver transplantation.Methods: Data were collected from notes in the medical records, after signing the informed consent form by the patient and approval by the Research Ethics Committee.Results: This study presents a case report of a 55-year-old man with chronic liver disease and a history of infection by the hepatitis C virus and the human immunodeficiency virus, who evolved with non-invasive hepatocellular carcinoma in segment VI/VII of the liver out of Milan criteria for curative therapeutic proposal. The patient underwent two sessions of TACE, which were effective in reducing the size of the tumor, making him eligible for curative treatment – liver transplantation.Conclusion: The case in question stands out for being a condition of atypical evolution, where often, due to the size of the tumor, the response to chemoembolization is not so significant. The case report is justified in order to provide information and enable downstaging attempts to be made in patients with similar profiles.Keywords: Hepatocellular carcinoma. Transarterial chemoembolization. TACE. Hepatitis C

L. Schummers

and 11 more

Objective: To determine the characteristics, determinants, and persistent use for prescription opioid episodes initiated postpartum in British Columbia (BC), Canada. Design: Population-based cohort, 2008-2015. Setting: Linked administrative databases including outpatient and inpatient visits and outpatient prescription dispensations for all individuals in BC tested for hepatitis C or HIV. Population: Opioid-naïve individuals aged 13-49 with a delivery hospitalization record. Methods: We used modified Poisson regression to estimate risk ratios (RR) for pre-pregnancy characteristics and adjusted RR (aRR) for delivery characteristics adjusted for potential confounders. Main Outcome Measures: All and persistent (≥90 days) prescription opioid episodes initiated postpartum. Results: Among 292,684 eligible deliveries, 8.8% (95% CI: 8.7% to 8.9%) initiated a postpartum prescription opioid episode and 0.4% (0.4%- 0.5%) had a persistent episode. Persistent prescription opioid episodes were more frequent among cesarean vs. vaginal deliveries (1.0% vs. 0.2%, aRR 5.1 [4.6-5.8]). Opioid episodes varied regionally and declined from 12.8% in 2008 to 7% in 2012-2015. Persistent prescription opioid episodes were associated with pre-pregnancy: mental illness history (RR 2.4 [1.9-3.1]), psychotropic medication use (RRs 3.6-4.9), chronic pain (RR 2.7 [1.8-3.9]) and alcohol misuse (4.6 [2.2-9.7]), and delivery complications: intensive care unit admission (aRR 5.4 [3.3-8.9]), postpartum hospital readmission (aRR 3.9 [3.2-4.8]), and vaginal deliveries with hysterectomy (aRR 23.7 [6.1-91.8]) or tubal ligation/salpingectomy (aRR 14.6 [5.4-39.4]). Conclusions: Persistent prescription opioid episodes were initiated following 0.4% of deliveries. Postpartum pain management strategies should consider the strong associations between pre-pregnancy and delivery characteristics and persistent prescription opioid episodes initiated postpartum.

Luis Montalvo

and 3 more

Climate variability influences genetic and phenotypic diversity within species, impacting biodiversity’s evolution. Gene flow and selection maintain changes in genetic and phenotypic variants along an environmental gradient. We investigated a hybrid zone in western Ecuador, involving two wren species (Aves: Troglodytidae), Campylorhynchus zonatus and C. fasciatus, and their admixed populations. We addressed two primary questions: (1) What is the relative contribution of Isolation by Distance (IBD) and Isolation by Environment (IBE) to genetic differentiation in these species along the western Ecuadorian environmental gradient? (2) Is there evidence of genetic admixture and introgression between these taxa in western Ecuador? We analyzed 4,409 SNPs from 112 blood samples sequenced using ddRadSeq. Clusters ranged from K=2-4, aligning with geographic origins, known phylogenetics, and physical or ecological constraints. IBD was evident across all models, while IBE was less pronounced but still significant for annual mean precipitation and precipitation seasonality. Genetic admixture between C. f. pallescens and C. zonatus gradually changed along the environmental gradient. Genetic differentiation in the two C. f. pallescens populations could be attributed to an unreported potential physical barrier in central western Ecuador. The proximity of the Andes to the coastline restricted lowland habitats, limiting dispersal and gene flow, especially among dry-habitat specialists. Taxonomic changes are not proposed, but the admixture in C. f. pallescens suggests it may be a hybrid between C. z. brevirostris and C. fasciatus, with varying degrees of admixture in western Ecuador and northwestern Peru. This study enhances our understanding of avian population genomics in tropical regions.

Gagandeep Brar

and 5 more

Social bees have been extensively studied for their gut microbial functions, but the significance of the gut microbiota in solitary bees remain less explored. Solitary bee, Megachile rotundata F. females provision their offspring with pollen from various plant species, harboring a diverse microbial community that colonizes larvae guts. The Apilactobacillus is the most abundant microbe, but evidence concerning the effects of Apilactobacillus and other provision microbes on growth and survival are lacking. We hypothesized that the presence of the gut microbiome, and Apilactobacullus in particular, would enhance larval and prepupal development, weight, and survival. We reared larvae on pollen provisions with naturally collected microbial communities (Natural pollen) or devoid of microbial communities (Sterile pollen). We also assessed the impact of introducing Apilactobacillus micheneri by adding it to both types of pollen provisions. Feeding larvae with sterile pollen + A. micheneri led to the highest mortality rate, followed by natural pollen + A. micheneri, sterile pollen. Larval development was significantly delayed in groups fed sterile pollen and sterile pollen + A. micheneri compared to the control. Interestingly, larval and prepupal weights did not significantly differ across treatments compared to natural pollen-fed larvae. 16S rRNA gene sequencing found a dominance of endosymbiont Sodalis when A. micheneri was introduced to natural pollen. The presence of Sodalis with abundant A. micheneri suggests potential crosstalk between both, shaping bee nutrition and health. Hence, this study highlights that the reliance on non-host specific environmental bacteria may not impact fitness of M. rotundata. Keywords: Megachile rotundata, Apilactobacillus micheneri, Sodalis, solitary bee, bee health and nutrition, bee microbiome, growth, survival
Title: Determinants of school absences due to respiratory tract infections among children during COVID-19 pandemic: a cross-sectional study of the Sentinel Schools Network.Antoni Soriano-Arandes1,●,○, Andreu Colom-Cadena2,3,●, Anna Bordas2,3, Fabiana Ganem2,3,4, Lucia Alonso3,5, Marcos Montoro2,3, Mireia Gascon6,7,8, Maria Subirana6,7,8, Ariadna Mas9, Jordi Sunyer6,7,8, Pere Soler-Palacin1, Jordi Casabona2,3,4,8 ; on behalf of Sentinel School Network of Catalonia*Paediatric Infectious Diseases and Immunodeficiencies Unit. Children’s Hospital. Vall d’Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.Centre d’Estudis Epidemiològics sobre les ITS i Sida de Catalunya (CEEISCAT). Badalona, Spain.Institut d’Investigació Germans Trias i Pujol (IGTP), Badalona, Spain.Departament de Pediatria, d’Obstetrícia i Ginecologia i de Medicina Preventiva i de Salut Publica, Universitat Autònoma de Barcelona, Bellaterra, Spain.Fundació Lluita contra les infeccions, Badalona, Spain.ISGlobal, Barcelona. Spain.Universitat Pompeu Fabra (UPF), Barcelona, SpainCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) Instituto de Salud Carlos III, Madrid, Spain.Direcció Assistencial d’Atenció Primària i Comunitària, Institut Català de la Salut, Barcelona, Catalonia, Spain● Contributed equally to this work with: Antoni Soriano-Arandes, Andreu Colom-Cadena○ Corresponding author: Antoni Soriano-Arandes, ORCID: 0000-0001-9613-7228Keywords: COVID-19, respiratory infections, ventilation, school, CO2, Indoor air qualityTo the editor:Different public health measures were implemented during the COVID-19 pandemic to maintain the schools open1,2. Regarding COVID-19 vaccination, at the beginning of this study, more than 92% and 40% of population older than 12 years and children aged 5-11 years in Spain was fully vaccinated against COVID-19, respectively3.Ventilation was proposed as one of the main strategies to reduce aerosol transmission for SARS-CoV-2 during the pandemic. A study from Germany assessed the efficiency of air purifiers in reducing aerosols in high-school classrooms4. However, no clinical endpoints were investigated and, therefore, a very low certainty of evidence was graded by a Cochrane review5. In an Italian study, the authors concluded that ventilation reduced the likelihood of SARS-CoV-2 infection in classrooms by 80%6. Moreover, a survey study from the US reported that elementary schools with face masks and ventilation strategies in place had lower SARS-CoV-2 incidence rates7. In a Lancet Task Force Commission review8, the authors concluded that improving building ventilation systems may carry benefits beyond protection from COVID-19. However, there is scarce evidence that demonstrate the association of epidemiological and environmental risk factors, including CO2 concentrations, with the incidence of respiratory tract infections (RTI) in children who are attending schools.The present study is part of COVID-19 Sentinel Schools Network of Catalonia (CSSNC), a project including 23 schools and 5687 students, teachers and other school staff with the aim to monitor SARS-CoV-2 and other respiratory viruses, their determinants and preventive measures in Catalonia9. The objectives of this study are to assess the potential association of demographic and epidemiological factors, including the indoor environmental conditions (CO2levels) in the classrooms, with students’ school absence due to RTI.We conducted a cross-sectional study in two different periods, the first from April 19 to June 21, 2022, and the second from November 8 to December 21, 2022. The main outcome of the study was the absence of the child from attending the school in person due to RTI or other non-respiratory medical causes. The study population was composed of 253 students (4-11 years) belonging to 20 classrooms, 11 in spring 2022 and 9 in autumn 2022, attending 4 and 16 classrooms of preschool (4 to 5 years-old) and primary school (6 to 11 years-old) stages, respectively. A written informed consent was previously obtained from parents or guardians of children.Absences from school attendance were notified by the tutor/teacher to the study researchers. We proceed to collect epidemiological and clinical/diagnostic data within the first 48 hours through a case report form deposited on the digital platform REDCap©. All the absences (cases) were followed-up through telephone calls made by health professionals until their return to the school. RTI was registered according to the symptoms described during the telephonic interview and confirmed through the computerised health record programme of the Health Ministry (eCAP).Sensors to monitor the CO2 concentrations (DIOXCARE DX700 PDF, Smartcare Services, Spain) were installed in classrooms, recording data every 10 minutes. For the analysis we only used the measurements taken during the time in which the students were in the classroom. We obtained a median [IQR] of CO2 levels which was used to conduct our analyses. All the participating schools received an operational protocol to install the sensor correctly and download data weekly.We calculated the RTI incidence per week and for the total study period. We performed a descriptive analysis of all survey variables, stratifying them by respiratory-related absence or absence due to other causes. Additionally, we ran a univariate logistic model to study the association between the type of absence and each described variable to obtain the corresponding odds ratios, 95% confidence intervals and p-values.Furthermore, we conducted a Latent Class Analysis (LCA) to explore potential groups of students with similar symptomatology. We started exploring the optimal number of latent classes, trying two to five classes, and we selected the best model using the entropy criterion, which indicates the accuracy of the latent classes, combined with other goodness of fit criteria such as BIC, cAIC and likelihood ratio. All these measures suggested that the optimal number of classes was two. However, we also examined the rest of number of classes to see if their classification had more clinical significance. All statistical analyses were performed in R (version 4.2.2).We registered one-hundred and five school absences during the study, 43 in the first study period (spring 2022), and 62 in the last one (autumn 2022) (Figure 1S ). Among these, we could obtain data related to the diagnosis in 98 (93%) cases, the rest of them were lost during the follow-up of the absence. Seventy-one absences were respiratory-related and 27 were due to other causes, mainly with gastrointestinal symptoms (66.7%). Among the absences due to RTI, the most were upper RTI (56/71, 78.9%), and only six (8.5%) were confirmed infections, 2 caused by influenza virus and 4 due to SARS-CoV-2 infection. These results represent a RTI incidence of 15.9 and 33.1 cases per 100 population in the first and second study period, respectively. The maximum weekly RTI incidence was of 10.2 cases per 100 population in December 12-18, 2022.The clinical, epidemiological and environmental characteristics of study sample are summarized in table 1 , categorized by type of absence (respiratory versus non-respiratory). We found a statistically significant association with absences due to RTI when someone else at home had respiratory symptoms (OR=9.12, CI 95%=2.54-33.39). We found a positive association between higher median levels of CO2at class and respiratory-related absences (OR=1.2, CI 95%=0.98-1.46). Moreover, there were more respiratory absences in autumn (OR=2.4, CI 95%=0.97-5.94). However, these last two associations did not reach statistical significance at a level of 0.05; although their p-values were lower than 0.1.No other epidemiological risk factors were associated with RTI incidence, such as household floor level, number of people living at home, living with smokers, having any comorbidity or being vaccinated against COVID-19.Finally, in Figure 1 , we present the symptomatology of absences belonging to each of the two latent classes. We can see that in the first cluster, the most frequent symptoms were cough, nasal congestion and fever, whereas in the second one, fever, gastrointestinal symptoms, and fatigue predominated.Our findings confirm that the RTI incidence during the study period was very high in children attending in the CNSSC schools, and the main medical cause of school absence. Although differences on school absence due to RTI were observed between spring and autumn, they were not statistically significant and in any case they may be due to the respiratory viruses’ seasonal pattern. In fact, the most important and significantly associated risk factor for RTI was the presence of someone else at home with respiratory symptoms, suggesting that households could be the main setting for initiating of the transmission of RTI.We observed a slightly association between RTI and median of CO2 levels in classrooms (p=0.07), which is an indicator of the degree of ventilation. However, we cannot exclude other potential factors such as rainfall, ambient temperature, or air pollutants (e.g. PM2.5, NO2, etc.) influencing on this outcome, as suggested by other authors10. To our knowledge, previous studies assessed the CO2concentration as a proxy of ventilation to evaluate the risk transmission of SARS-CoV-2 in schools11,12, but they did not analyse the association between CO2 median values and RTI incidence.Finally, we studied the symptomatology associated with the school absences through a LCA. The best approach to differentiate RTI from other causes was using two latent classes, and the most frequent symptoms were cough, nasal congestion and fever.The major strength of this study is our extensive data collection on clinical, epidemiological and environmental factors related to the school and also to the households of the participants. However, there were limitations such as possible incomplete reporting of RTI or insufficient sample size to determine small effect sizes. CO2 concentration was only measured in a selection of classrooms per school, so it may not be representative for the entire study period and school.In conclusion, RTI incidence was very high during the study period being the most important and significantly associated factor with RTI to have anyone else at home with respiratory symptoms. This suggests that households and not schools could be the key epidemiological factor for initiating the transmission of RTI to the children. Improving household preventive measures could reduce childhood RTI. In the LCA, the most frequent symptoms associated with RTI were cough, nasal congestion and fever. Although we found a slightly association between RTI and reduced ventilation we cannot exclude other potential factors influencing on this outcome. The study has been crucial to assess the feasibility and potential utility of collecting both school absence and morbidity data for further developing a systematic monitoring system.

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

Gizem Koken

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

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