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Michael Weekes

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Nick K. Jones1,2*, Lucy Rivett1,2*, Chris Workman3, Mark Ferris3, Ashley Shaw1, Cambridge COVID-19 Collaboration1,4, Paul J. Lehner1,4, Rob Howes5, Giles Wright3, Nicholas J. Matheson1,4,6¶, Michael P. Weekes1,7¶1 Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK2 Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, UK3 Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, UK4 Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK5 Cambridge COVID-19 Testing Centre and AstraZeneca, Anne Mclaren Building, Cambridge, UK6 NHS Blood and Transplant, Cambridge, UK7 Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK*Joint first authorship¶Joint last authorshipCorrespondence: [email protected] UK has initiated mass COVID-19 immunisation, with healthcare workers (HCWs) given early priority because of the potential for workplace exposure and risk of onward transmission to patients. The UK’s Joint Committee on Vaccination and Immunisation has recommended maximising the number of people vaccinated with first doses at the expense of early booster vaccinations, based on single dose efficacy against symptomatic COVID-19 disease.1-3At the time of writing, three COVID-19 vaccines have been granted emergency use authorisation in the UK, including the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is whether this vaccine prevents or promotes asymptomatic SARS-CoV-2 infection, rather than symptomatic COVID-19 disease, because sub-clinical infection following vaccination could continue to drive transmission. This is especially important because many UK HCWs have received this vaccine, and nosocomial COVID-19 infection has been a persistent problem.Through the implementation of a 24 h-turnaround PCR-based comprehensive HCW screening programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT), we previously demonstrated the frequent presence of pauci- and asymptomatic infection amongst HCWs during the UK’s first wave of the COVID-19 pandemic.4 Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and cycle threshold (Ct) values in the asymptomatic arm of our programme, which now offers weekly screening to all staff.Vaccination of HCWs at CUHNFT began on 8th December 2020, with mass vaccination from 8th January 2021. Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence of COVID-19 amongst HCWs remained approximately constant; and (b) we screened comparable numbers of vaccinated and unvaccinated HCWs. Over this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed from individuals reporting well to work. We stratified HCWs <12 days or > 12 days post-vaccination because this was the point at which protection against symptomatic infection began to appear in phase III clinical trial.226/3,252 (0·80%) tests from unvaccinated HCWs were positive (Ct<36), compared to 13/3,535 (0·37%) from HCWs <12 days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact test, Figure). This suggests a four-fold decrease in the risk of asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days post-vaccination, compared to unvaccinated HCWs, with an intermediate effect amongst HCWs <12 days post-vaccination.A marked reduction in infections was also seen when analyses were repeated with: (a) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%) unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold reduction, p=0·00001); (b) inclusion of PCR tests which were positive at the limit of detection (Ct>36, 42/3,268 (1·29%) vs 15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of the period of analysis to include six weeks from December 28th to February 7th 2021 (113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction, p=1x10-9). In addition, the median Ct value of positive tests showed a non-significant trend towards increase between unvaccinated HCWs and HCWs > 12 days post-vaccination (23·3 to 30·3, Figure), suggesting that samples from vaccinated individuals had lower viral loads.We therefore provide real-world evidence for a high level of protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time of predominant transmission of the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a population with a relatively low frequency of prior infection (7.2% antibody positive).5This work was funded by a Wellcome Senior Clinical Research Fellowship to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), and an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also received from Addenbrooke’s Charitable Trust and the Cambridge Biomedical Research Centre. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing and the Cambridge COVID-19 Testing Centre.

Guangming Wang

and 4 more

Tam Hunt

and 1 more

Tam Hunt [1], Jonathan SchoolerUniversity of California Santa Barbara Synchronization, harmonization, vibrations, or simply resonance in its most general sense seems to have an integral relationship with consciousness itself. One of the possible “neural correlates of consciousness” in mammalian brains is a combination of gamma, beta and theta synchrony. More broadly, we see similar kinds of resonance patterns in living and non-living structures of many types. What clues can resonance provide about the nature of consciousness more generally? This paper provides an overview of resonating structures in the fields of neuroscience, biology and physics and attempts to coalesce these data into a solution to what we see as the “easy part” of the Hard Problem, which is generally known as the “combination problem” or the “binding problem.” The combination problem asks: how do micro-conscious entities combine into a higher-level macro-consciousness? The proposed solution in the context of mammalian consciousness suggests that a shared resonance is what allows different parts of the brain to achieve a phase transition in the speed and bandwidth of information flows between the constituent parts. This phase transition allows for richer varieties of consciousness to arise, with the character and content of that consciousness in each moment determined by the particular set of constituent neurons. We also offer more general insights into the ontology of consciousness and suggest that consciousness manifests as a relatively smooth continuum of increasing richness in all physical processes, distinguishing our view from emergentist materialism. We refer to this approach as a (general) resonance theory of consciousness and offer some responses to Chalmers’ questions about the different kinds of “combination problem.”  At the heart of the universe is a steady, insistent beat: the sound of cycles in sync…. [T]hese feats of synchrony occur spontaneously, almost as if nature has an eerie yearning for order. Steven Strogatz, Sync: How Order Emerges From Chaos in the Universe, Nature and Daily Life (2003) If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.Nikola Tesla (1942) I.               Introduction Is there an “easy part” and a “hard part” to the Hard Problem of consciousness? In this paper, we suggest that there is. The harder part is arriving at a philosophical position with respect to the relationship of matter and mind. This paper is about the “easy part” of the Hard Problem but we address the “hard part” briefly in this introduction.  We have both arrived, after much deliberation, at the position of panpsychism or panexperientialism (all matter has at least some associated mind/experience and vice versa). This is the view that all things and processes have both mental and physical aspects. Matter and mind are two sides of the same coin.  Panpsychism is one of many possible approaches that addresses the “hard part” of the Hard Problem. We adopt this position for all the reasons various authors have listed (Chalmers 1996, Griffin 1997, Hunt 2011, Goff 2017). This first step is particularly powerful if we adopt the Whiteheadian version of panpsychism (Whitehead 1929).  Reaching a position on this fundamental question of how mind relates to matter must be based on a “weight of plausibility” approach, rather than on definitive evidence, because establishing definitive evidence with respect to the presence of mind/experience is difficult. We must generally rely on examining various “behavioral correlates of consciousness” in judging whether entities other than ourselves are conscious – even with respect to other humans—since the only consciousness we can know with certainty is our own. Positing that matter and mind are two sides of the same coin explains the problem of consciousness insofar as it avoids the problems of emergence because under this approach consciousness doesn’t emerge. Consciousness is, rather, always present, at some level, even in the simplest of processes, but it “complexifies” as matter complexifies, and vice versa. Consciousness starts very simple and becomes more complex and rich under the right conditions, which in our proposed framework rely on resonance mechanisms. Matter and mind are two sides of the coin. Neither is primary; they are coequal.  We acknowledge the challenges of adopting this perspective, but encourage readers to consider the many compelling reasons to consider it that are reviewed elsewhere (Chalmers 1996, Griffin 1998, Hunt 2011, Goff 2017, Schooler, Schooler, & Hunt, 2011; Schooler, 2015).  Taking a position on the overarching ontology is the first step in addressing the Hard Problem. But this leads to the related questions: at what level of organization does consciousness reside in any particular process? Is a rock conscious? A chair? An ant? A bacterium? Or are only the smaller constituents, such as atoms or molecules, of these entities conscious? And if there is some degree of consciousness even in atoms and molecules, as panpsychism suggests (albeit of a very rudimentary nature, an important point to remember), how do these micro-conscious entities combine into the higher-level and obvious consciousness we witness in entities like humans and other mammals?  This set of questions is known as the “combination problem,” another now-classic problem in the philosophy of mind, and is what we describe here as the “easy part” of the Hard Problem. Our characterization of this part of the problem as “easy”[2] is, of course, more than a little tongue in cheek. The authors have discussed frequently with each other what part of the Hard Problem should be labeled the easier part and which the harder part. Regardless of the labels we choose, however, this paper focuses on our suggested solution to the combination problem.  Various solutions to the combination problem have been proposed but none have gained widespread acceptance. This paper further elaborates a proposed solution to the combination problem that we first described in Hunt 2011 and Schooler, Hunt, and Schooler 2011. The proposed solution rests on the idea of resonance, a shared vibratory frequency, which can also be called synchrony or field coherence. We will generally use resonance and “sync,” short for synchrony, interchangeably in this paper. We describe the approach as a general resonance theory of consciousness or just “general resonance theory” (GRT). GRT is a field theory of consciousness wherein the various specific fields associated with matter and energy are the seat of conscious awareness.  A summary of our approach appears in Appendix 1.  All things in our universe are constantly in motion, in process. Even objects that appear to be stationary are in fact vibrating, oscillating, resonating, at specific frequencies. So all things are actually processes. Resonance is a specific type of motion, characterized by synchronized oscillation between two states.  An interesting phenomenon occurs when different vibrating processes come into proximity: they will often start vibrating together at the same frequency. They “sync up,” sometimes in ways that can seem mysterious, and allow for richer and faster information and energy flows (Figure 1 offers a schematic). Examining this phenomenon leads to potentially deep insights about the nature of consciousness in both the human/mammalian context but also at a deeper ontological level.

Susanne Schilling*^

and 9 more

Jessica mead

and 6 more

The construct of wellbeing has been criticised as a neoliberal construction of western individualism that ignores wider systemic issues including increasing burden of chronic disease, widening inequality, concerns over environmental degradation and anthropogenic climate change. While these criticisms overlook recent developments, there remains a need for biopsychosocial models that extend theoretical grounding beyond individual wellbeing, incorporating overlapping contextual issues relating to community and environment. Our first GENIAL model \cite{Kemp_2017} provided a more expansive view of pathways to longevity in the context of individual health and wellbeing, emphasising bidirectional links to positive social ties and the impact of sociocultural factors. In this paper, we build on these ideas and propose GENIAL 2.0, focusing on intersecting individual-community-environmental contributions to health and wellbeing, and laying an evidence-based, theoretical framework on which future research and innovative therapeutic innovations could be based. We suggest that our transdisciplinary model of wellbeing - focusing on individual, community and environmental contributions to personal wellbeing - will help to move the research field forward. In reconceptualising wellbeing, GENIAL 2.0 bridges the gap between psychological science and population health health systems, and presents opportunities for enhancing the health and wellbeing of people living with chronic conditions. Implications for future generations including the very survival of our species are discussed.  

Mark Ferris

and 14 more

IntroductionConsistent with World Health Organization (WHO) advice [1], UK Infection Protection Control guidance recommends that healthcare workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) should use fluid resistant surgical masks type IIR (FRSMs) as respiratory protective equipment (RPE), unless aerosol generating procedures (AGPs) are being undertaken or are likely, when a filtering face piece 3 (FFP3) respirator should be used [2]. In a recent update, an FFP3 respirator is recommended if “an unacceptable risk of transmission remains following rigorous application of the hierarchy of control” [3]. Conversely, guidance from the Centers for Disease Control and Prevention (CDC) recommends that HCWs caring for patients with COVID-19 should use an N95 or higher level respirator [4]. WHO guidance suggests that a respirator, such as FFP3, may be used for HCWs in the absence of AGPs if availability or cost is not an issue [1].A recent systematic review undertaken for PHE concluded that: “patients with SARS-CoV-2 infection who are breathing, talking or coughing generate both respiratory droplets and aerosols, but FRSM (and where required, eye protection) are considered to provide adequate staff protection” [5]. Nevertheless, FFP3 respirators are more effective in preventing aerosol transmission than FRSMs, and observational data suggests that they may improve protection for HCWs [6]. It has therefore been suggested that respirators should be considered as a means of affording the best available protection [7], and some organisations have decided to provide FFP3 (or equivalent) respirators to HCWs caring for COVID-19 patients, despite a lack of mandate from local or national guidelines [8].Data from the HCW testing programme at Cambridge University Hospitals NHS Foundation Trust (CUHNFT) during the first wave of the UK severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic indicated a higher incidence of infection amongst HCWs caring for patients with COVID-19, compared with those who did not [9]. Subsequent studies have confirmed this observation [10, 11]. This disparity persisted at CUHNFT in December 2020, despite control measures consistent with PHE guidance and audits indicating good compliance. The CUHNFT infection control committee therefore implemented a change of RPE for staff on “red” (COVID-19) wards from FRSMs to FFP3 respirators. In this study, we analyse the incidence of SARS-CoV-2 infection in HCWs before and after this transition.

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Tommy Patton

and 9 more

Numerous challenges hinder the development of neuroprotective treatments for Parkinson’s disease, with a regularly identified issue being the lack of clinically relevant animal models. Viral vector overexpression of α-synuclein is widely considered the most relevant model, however this has been limited by high variability and inconsistency. One potential method of optimisation is pairing it with a secondary insult such as FN075, a synthetic molecule demonstrated to accelerate α-synucleinopathy. Thus, the aim of this study was to investigate if sequential infusion of AAV-α-synuclein and FN075 into the rat brain can replicate α-synucleinopathy, nigrostriatal pathology and motor dysfunction associated with Parkinson’s disease. Rats received a unilateral injection of AAV-α-synuclein (or AAV-GFP) into two sites in the substantia nigra, followed 4 weeks later by unilateral injection of FN075 (or vehicle) into the striatum. Animals underwent behavioural testing every 4 weeks until sacrifice at 20 weeks, followed by immunohistochemistry assessment post-mortem. As anticipated, AAV-α-synuclein led to extensive overexpression of human α-synuclein throughout the nigrostriatal pathway, as well as elevated levels of pathological and aggregated forms of the protein. However, the sequential administration of FN075 into the striatum did not exacerbate any of the α-synuclein pathology. Furthermore, despite the extensive α-synuclein pathology, neither administration of AAV-α-synuclein nor FN075, alone or in combination, was sufficient to induce dopaminergic degeneration or motor deficits. In conclusion, this approach did not replicate the key characteristics of Parkinson’s disease, and further studies are required to create more representational models for testing of novel compounds and treatments for Parkinson’s disease.

Eric Owusu Mensah

and 1 more

Alison Talbot

and 4 more

Background: Obesity has been associated with human obstructive sleep apnoea and canine brachycephalic obstructive airway syndrome. To the authors’ knowledge the effect of body condition score (BCS) on structures of the oropharynx , nasopharynx and upper airway of the horse has not been investigated. Objectives: To investigate the effect of BCS on tongue area and height, soft palate angle and basihyoid depth in the horse. Study Design: Retrospective, analytical, cross-sectional. Methods: Computed tomographic (CT) images of the head of 44 horses were assessed. DICOM viewing software was used to measure head length, basihyoid-skin depth, soft palate angle (SPA), midline tongue area and dorsoventral height (DVH) of the tongue in two locations. BCS were assigned at the time of CT examinations. Results: Increased BCS led to an increased mean SPA (mean difference=2.56 ˚ ; P=0.019) and increased median basihyoid depth (mean difference=0.246cm; P=0.006). Following adjustments made for the effect of head length on tongue measures, significant correlation was identified between SPA and tongue area (Spearman’s r=0.544; P=0.007); SPA and DVH of the tongue at the level of the hard palate (Spearman’s r=0.562; P=0.004) and SPA and DVH of the tongue at the lingual process of the basihyoid bone (Spearman’s r=0.690; P<0.001). No significant correlation was identified between variables with sex or age of horses. Conclusions: Increased BCS increases SPA and basihyoid bone depth. Increases in tongue size measurements increase SPA. Results from this study warrant further investigation into the clinical significance of the effects of BCS on the upper airways of the horse.

Zijian Ding

and 5 more

Plant-microbial interactions (PMI) play a crucial role in plant growth, fitness and productivity, primarily through the mutualism and antagonism interactions between plants and soil microorganisms. The colonization of arbuscular mycorrhizal (AM) fungi and pathogen are often used to speculate on the effects of microorganisms on plant growth, i.e. plant-microbial interactions (PMI). However, empirical studies demonstrate the relationship between AM fungi or pathogen and PMI effects remains limited, especially under different biotic and abiotic conditions. Here, we evaluated the colonization rates of AM fungi and pathogen across 13 grassland species under individual or communal conditions, in both overgrazed and restored soil. Furthermore, we investigated the relationship between AM fungi or pathogen and PMI. Our results showed that forbs exhibited significantly higher rates of AM fungal colonization compared to graminoids in community condition and overgrazed soil while graminoid roots showed higher pathogen infestation compared to forbs in individual condition and overgrazed soil. Generally, there was a positive correlation between PMI and AM fungal colonization but a negative correlation between PMI and pathogen disease. The PMI of graminoids exhibited a negative correlation with pathogen disease in individual condition and overgrazed soil, but showed no correlation with AM fungal colonization. On the other hand, the PMI of forbs showed a positive correlation with AM colonization in both restored and overgrazed soil, as well as in both individual and community experiments. However, there was no correlation between PMI of forbs and pathogen disease. The PMI of graminoids and forbs in grassland ecosystems can be driven by distinct soil microorganisms. These insights enable us to better understand how soil mutualists and pathogen mediate PMI effects on plant growth, with implications for grassland management and restoration.

Wei Guo

and 6 more

The importance of fine-root diameter for ecosystem functioning is increasingly recognized; yet, much remains to be learned about the variation in fine-root diameter at large scale. We conducted an analysis of fine-root diameter for 1,163 plant species to detect root diameter patterns in relation to resource availability (e.g. carbon, nitrogen and water), stress intensity (e.g. plant/soil biodiversity, soil bulk density) and temperature. First- to fourth-order root diameter showed non-linear relationships with latitude and/or mean annual temperature (except for first-order root diameter). The diameter of five root orders decreased with increasing mean annual precipitation, but increased with net primary production (NPP), which was the strongest determinant of fine-root diameter. Increasing soil biodiversity was associated with decreasing root diameter of fourth- to fifth-order roots while increased plant biodiversity was associated with decreasing diameter of first- to third-order roots. Total soil nitrogen had a positive effect on first-order root diameter, but a negative effect on fourth- and fifth-order root diameter. The patterns reversed for total soil phosphorus. First- to third-order and fifth-order root diameters increased with increasing soil bulk density. Second- to fourth-order root diameter increased with soil pH. Overall, the variables related to climate, biology and soil explained 44% to 63% of the total variance in the diameter of the different root orders. The unique patterns of plasticity observed in fine-root diameter across root orders in response to varying environmental conditions contributes to a diversification of strategies for nutrient/water acquisition and transport under climate change.

Malou Storm

and 9 more

Gut bacterial communities provide flexibility to hosts during dietary changes. Despite the increasing number of studies exploring the associations between broader dietary guilds of mammalian hosts and their gut bacteria, it is generally unclear how diversity and variability in consumed diets link to gut bacteria in wild non-primate mammals. Here we contribute to filling this gap by exploring consumed diets and gut bacterial community compositions with metabarcoding of faecal samples for two African mammals, Civettictis civetta and Genetta spp., from the family Viverridae. For each individual sample, we characterised bacterial communities and identified dietary taxa by sequencing vertebrate, invertebrate, and plant markers. This led us to establish diet compositions that diverged from what has previously been found from visual identification methods. Specifically, while the two genera have been categorised into the same dietary guild, we detected more animal dietary items than plant items in C. Civetta, while in Genetta spp. we observed an opposite pattern. We further found that individuals with similar diets have similar gut bacterial communities in both species. This association tended to be driven by specific associations of dietary items to specific gut bacterial taxa, rather than entire communities, implying diet-driven selection for specific gut microbes in individual wild hosts. Our findings underline the importance of molecular tools for improving characterisations of wild mammalian diets and highlight the opportunities for simultaneously disentangling links between diets and gut symbionts. Such insights can inform robustness and flexibility in host-microbe symbioses to dietary change associated with seasonal and habitat change.

KALLIOPI KERAMIDA

and 1 more

Discrimination of myocardial function changes: evolution of chronic kidney disease or hemodialysis effect?Kalliopi Keramida, MD, MSc, PHD, FESC, FHFA, FICOS,1Konstantinos Papadopoulos, MD, PhD, FESC, FEACVI21 Cardiology Department, General Anti-Cancer, Oncological Hospital Agios Savvas, Athens, Greece2Echocardiography department, Interbalkan Medical Center, Thessaloniki, GreeceCorresponding author: Kalliopi Keramida, General Anti-Cancer Oncological Hospital, Agios Savvas Athens, GreeceAleksandras Avenue 171, 11522, Athens, Greece,[email protected] on “Effect of hemodialysis on left atrial function in patients with end-stage renal failure evaluated by two-dimensional speckle-tracking imaging”Chronic kidney disease, often advancing to end-stage renal disease (ESRD), poses a significant challenge to public health, as costly treatments like dialysis or kidney transplantation become essential for survival. Globally, the number of individuals with ESRD that need renal replacement therapy is estimated to range between 4.902 and 9.701 million with a trend to double by 2030 (1). Cardiovascular (CV) disease is a prevalent complication and the leading cause of mortality among individuals with ESRD undergoing hemodialysis (HD). Heart failure (HF), sudden cardiac death, ischemic cardiomyopathy and stroke are the main causes of CV mortality (2). Echocardiography is the main imaging modality used for the long-term surveillance of ESRD patients.Myocardial remodeling and dysfunction, are prevalent in different stages of chronic kidney disease (CKD), leading to uremic cardiomyopathy and HF with either preserved (3) or reduced ejection fraction later in the course of the disease (4). However, myocardial remodeling, including left ventricular (LV) hypertrophy, dilatation, fibrosis, and dysfunction are not confined to the LV only. The left atrium (LA) is also affected by this remodeling process. LA dilatation and dysfunction have been studied in several trials, revealing their prognostic value in patients with CKD (5, 6). Miao Y et colleagues (7) used two-dimensional speckle tracking imaging to assess concurrently LA and LV function changes induced by HD in ESRD patients. The authors demonstrated LV and LA remodeling in ESRD patients compared to controls (increased LV wall thickness, LV volumes and LA volume), with higher rates of diastolic dysfunction and elevated filling pressures measured by E/E’ ratio, but LV systolic performance, assessed by LV ejection fraction (LVEF) and LV Global Longitudinal Strain (LVGLS) similar to controls. Further assessment of LA function indices [reservoir (LASr), conduit (LAScd) and contractile (LASct) strain], demonstrated significantly baseline reduced LA strain values, compared to controls, and further reduction of LASr and LAScd after HD. LASct remained stable without further deterioration after HD (7).This elegant study included a control group to compare the left heart strain values between patients with ESRD and healthy subjects and delineated the undeniable remodeling of both left heart chambers (7). Although the baseline echocardiographic parameters used for LV systolic function assessment (LVEF, LVGLS) did not differ between controls and ESRD patients in this study, previously published trials have shown that ESRD patients have impaired LVGLS (8) and myocardial work indices (9, 10). Furthermore, there is consensus in literature, that these patients have diastolic dysfunction expressed by increased LA volume and E/e’, findings relevant to the LV remodeling with wall thickening and increased filling pressures. A more sensitive marker of diastolic dysfunction in HF, irrespective of LVEF, is the LA strain (11) that has already proven its prognostic role in ESRD patients (6). However, clinicians and researchers need to be careful, as the three different LA strain parameters, reflect different properties of LA and LV and are related to volume status. More specifically, LASr expresses LA pressure and/or LA stiffness. LAScd reflects LV relaxation and/or LV pressure in early diastole, while LASct is indicative of LV compliance, LV end-diastolic pressure and/or LA contractility (5). LA strain is load-dependent and previous research has demonstrated that it is more accurate in depressed EF rather than in normal and if we are about to be specific for increased LV filling pressures, we need to use the LASr<18% as a cut-off value (12).The changes induced by HD in strain-related parameters of LV and LA, are explained by their pre- and after-load dependency. LVGLS was decreased after HD due to decrease of preload and afterload (decreased systolic blood pressure), decrease of LV end-diastolic volume and myocardial stunning and troponin release (13). The inclusion of myocardial work (MW) analysis in the echocardiographic assessment of these patients, can help in the clarification of the cause of LVGLS change after HD (9). Myocardial work includes the afterload of the patient by measuring the blood pressure with a simple brachial cuff and it is less-load dependent than GLS. A meta-analysis for LV strain evaluation showed reduction of LV GLS when afterload is increased, which may lead to false conclusions about the LV performance (14). In HD patients, reduction of both LVGLS and MW would suggest true deterioration of systolic performance, while reduction of GLS with increase of MW would detect blood pressure changes and not LV systolic impairment.LASr and LAScd components are decreased immediately after HD, confirming their load dependency, while LASct remains unchanged, being independent of volume status and preload (7). LASct mainly reflects LA systolic function and LV compliance (7), related to the disease progression. The effects of blood pressure changes induced by HD, are not included in the assessment of LA function. A less-load dependent marker of LA function, maybe similar to LV MW (namely “LA Myocardial Work”), taking into account volume and pressure changes, would be more sensitive in detecting acute LA cardiomyopathy and diastolic dysfunction in ESRD patients after HD. Research should be done in that way, including large series of healthy subjects first and patients as well with different stages of diastolic and systolic dysfunction. If such marker is developed, this will detect definitely atrial myopathy in different populations with applicability in CKD patients. The current application of MW is validated for LV function and with afterload involvement only (15). No preload data or increased LV diastolic pressures are included into the equation. This method looks promising for accurate evaluation of the true LV work, but more research should be done in different populations.In concluding, LV GLS and LA strain are sensitive markers that can detect subclinical LV dysfunction and atrial myopathy but with the restrictions of load and pressure dependency. Myocardial Work may further help discriminate the true impairment of the LV function in ESRD patients and can be included into the echocardiographic follow-up protocol of these patients (Figure). A new marker of LA function, independent from volume changes and LV filling pressures should be developed in order to detect subtle changes of LA function and possibly guide the treatment in this high-risk population.

Vyctoria Pereira

and 11 more

Influenza circulation was significantly affected in 2020–21 by the COVID-19 pandemic. During this time, few influenza cases were recorded. However, in the summer of 2021–22, an increase in atypical influenza cases was observed, leading to the resurgence of influenza in the southernmost state of Brazil, Rio Grande do Sul (RS). The present study aimed to identify FLUAV, FLUBV, and SARS-CoV-2 circulation and characterize influenza genomes in suspected COVID-19 patients using high-throughput sequencing technology. Respiratory samples (n = 694) from patients in RS were selected between July 2021 and August 2022. The samples were typed reverse transcriptase real-time PCR (RT-qPCR) and showed 32.13% (223/694) of the samples to be positive for SARS-CoV-2, 7.06% for FLUAV (49/694). FLUBV was not detected. RT-qPCR data also showed 0.57% of the cases had FLUAV and SARS-CoV-2 co-infections. Whole genome sequencing of the FLUAV positive specimens produced 15 complete genomes of H3N2 subtype with phylogenetic placement in the 3C.2a1b.2a.2a.3 subclade. Mutation analysis showed 73 amino acid substitutions in addition to several nonsynonymous mutations. The detected percentage of FLUAV (7.06%) is relatively similar to the total number of flu cases requiring hospitalization in RS state (8.9%), including those admitted to intensive care units for severe complications. This study provides insights into influenza virus circulation in the south of Brazil during the Omicron wave of the COVID-19 pandemic and reinforces the importance of H3N2 as a major driver of severe respiratory disease in the region along with the SARS-CoV-2 Omicron wave at the beginning of 2022.

Sharon Downie

and 5 more

Abstract Background: Health workforce supply is critical to ensuring the delivery of essential healthcare, and may be enhanced via mechanisms which alter the scopes of practice of health professions. The aim of this paper is to study the collective perspectives of allied health decision-makers on factors which influence their development and implementation of advanced and extended scope of practice initiatives, and the timing/catalyst and application of their decision-making. Methods: A grounded-theory, qualitative study of the experiences of allied health directors and senior managers across two Australian jurisdictions. Results: Twenty allied health decision-makers met study eligibility criteria. Data coding of interview transcripts identified 14 factors specific to scope of practice change, spanning rational (n=8) and non-rational (n=6) decision-making approaches. Leadership, Governance, Organisational need, Resourcing, Knowledge & Skills – clinical, Supporting resources, Knowledge & skills – change and Sustainability were identified as being rational and enabling in and of themselves, with Leadership seen as being most influential. Comparatively, the non-rational factors of Socio-economic & political environment, Perceived patient need, Organisational environment, Change culture & appetite, Perceived professional territorialism and Actual professional territorialism were more varied, and primarily influenced the timing/catalyst and application of decision-making. Conclusion : Allied health decision-makers hold a complex, systems-level understanding of scope of practice change. Whilst rational decision criteria were predominant and seen to enable scope change, non-rational influences reflected greater variation in decision timing/catalyst and application, thus emphasising the human dimensions of decision-making. Further research is required to better understand how decision-makers integrate and weight decision-making factors to inform the development of structured decision tools.

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Karma Norbu

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Introduction: Scrub typhus is a neglected life threatening acute febrile illness caused by bacteria Orientia tsutsugamushi and it is a vector-borne zoonotic disease. In 2009, scrub typhus outbreak at Gedu has awakened Bhutan on the awareness and testing of the disease.Information and data of the study highlights the need for in depth surveillance, awareness among prescribers and initiate preventive measures in the country. Methods: We used retrospective descriptive study through review of laboratory registers across three health centres in Zhemgang district, south central Bhutan. The laboratories registers have been transcribed into CSV file using Microsoft excel. Variables of interest were collected from the registers and then analysed using open statistical software R, (R Core Team (2020). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.) And use of mStats package, (MyoMinnOo (2020). mStats: Epidemiological DataAnalysis. R package version 3.4.0.) Results: Of the total 922 tests prescribed for suspected scrub typhus in the three health centers in Zhemgang, only 8.2 % (n=76) were tested positive. Of these, Panbang Hospital had highest reported positive for scrub typhus with 56.6 %( n=43) followed by Yebilaptsa Hospital 35.5 %( n=27) and Zhemgang Hospital with 7.9 %( n=6). The female gender is comparably more affected as opposed to male with 57.9% (n=44) of the positive cases being female. The prevalence of scrub typhus seems to be affected by the seasonal variation as the months of Spring, Summer and Autumn together accounts for 98.7%(n=75) of total positive cases. The year 2019 noted significant scrub typhus cases accounting to 89.5 %(n=68) of the total positive cases over the two years. Conclusions:The overall tests tested positive of the scrub typhus infection within two years was 8.2%.

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