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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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Most recent documents

Sergio Schenkman

and 4 more

Trypanosoma cruzi, a flagellated protozoan, is the causative agent of Chagas disease. The parasite has developed various mechanisms to get through its intricate life cycle and adapt to different evolutionary phases. T. cruzi proliferates in the insect vector’s digestive tract as an epimastigote form, encountering fluctuating nutrient availability and oxidative stress caused by the digestion of red blood cells from the mammalian host blood meal. To unravel how the parasite’s metabolism adapts to these changing conditions, we conducted an analysis of the chemical species present in epimastigote forms. This involved comparing cultured parasites with those subjected to nutritional deficiency or oxidative stress using untargeted metabolomics. We looked at twenty-one samples: seven biological copies of parasites that were actively growing, seven samples that were put in a medium without nutrients for three hours, and seven samples that were treated with glucose oxidase for thirty minutes to make H 2O 2 continuously. Importantly, in all conditions, parasite viability was maintained when the samples were collected. Upon nutrient removal, we observed a substantial decrease in amino acids and carbohydrate metabolites, accompanied by the accumulation of fatty acids and steroids, with the predominance of inositol and sphingolipid metabolism, along with a simultaneous decrease in the levels of H 2O 2. In the presence of H 2O 2, a significant rise in components of the pentose pathway and specific amino acids such as methionine and serine occurred, along with pathways related to an increase in antioxidant species metabolism such as ribulose 5-phosphate and glyceric acid. Conversely, fatty acid and steroid levels decrease. We found no common increase in metabolites or lipids. In contrast, eight species (succinic acid, glutamic acid, valine, 2-hydroxyisocaproic acid, alanine, indolelactic acid, proline, and lanosterol) were consumed under both stresses. These findings underscore the rapid and distinct enrichment responses in amino acids, lipids, and carbohydrates required to cope with each different environmental condition. This information not only enhances our understanding of T. cruzi’s metabolic flexibility but also opens avenues for studying cellular metabolism changes in diverse environments used by the parasite.

Yunbin Gao

and 6 more

Objective: It is already established that thoracic radiation therapy (TRT) enhances the outcomes of patients with extensive-stage small cell lung cancer (ES-SCLC) after chemotherapy response. This investigation aimed to elucidate TRT’s impact on ES-SCLC patients during immunotherapy. Methods: This retrospective research was authorized by our institute IRB and included histopathology-confirmed ES-SCLC cases that underwent chemoimmunotherapy with or without TRT as primary treatment at our hospital between October 2018 to March 2022. With the help of propensity score matching, the selection bias was minimized. The research endpoints were progression-free survival (PFS) and overall survival (OS), which were determined via Kaplan-Meier, from first-line treatment initiation time. Survivals in different cohorts were compared with the help of a Log-rank test. Furthermore, Cox proportional hazards regression was applied to examine factors linked with survival. With the help of subgroup analyses, the influencing factors on TRT were assessed. Results: This investigation analyzed 172 patients who were followed up for a median of 20.1 months. The median PFS and OS for patients receiving TRT were 11.3 and 24.4 months, respectively, while for those without TRT, the values were 15.9 and 6.6 months (p < 0.001 and p = 0.006, respectively). According to the multivariate Cox regression assessment, thoracic radiotherapy was an independent favourable factor for both OS and PFS. Per the subgroup analysis, patients in all subgroups may have OS beneficial after TRT. Conclusions: Thoracic radiation therapy may improve PFS and OS in ES-SCLC cases undergoing chemoimmunotherapy as the primary treatment. Further investigation by randomized controlled studies is needed for confirmation.

Haerin Cho

and 4 more

Background: Several cases of renal complications including acute kidney injury (AKI) after influenza vaccination have been reported, but the association remains unproven. We evaluated the association between influenza vaccination and AKI occurrence among the Korean elderly in the 2018–2019 and 2019–2020 seasons. Methods: We used a large database that combined vaccination registration data from the Korea Disease Control and Prevention Agency and the claims data from the National Health Insurance Service. The study subjects were patients hospitalized with AKI for the first time following vaccination among those who received one influenza vaccine in the 2018–2019 or 2019–2020 season. Only those who were 65 or older at the date of vaccination were included in our study. We performed a self-controlled case series study in which the risk period was designated as 1 to 28 days after vaccination, and the observation period as each influenza season. We conducted sensitivity analyses with varied risk periods and observation periods. Results: A total of 16,713 and 16,272 AKI events were identified during each influenza season. The adjusted incidence rate ratio (aIRR) for AKI was 0.83 (95% confidence interval [CI]= 0.79–0.87) in the 2018–2019 season. The IRR of the 2019–2020 influenza vaccination was similar to the 2018–2019 season (aIRR=0.86; 95% CI=0.82–0.90). Sensitivity analyses showed similar results. Conclusions: We suggest that influenza vaccination is associated with a lower risk of AKI in the elderly over 65.

Ulrich Schall

and 4 more

Introduction: Online self-assessment tools are becoming more and more common and they serve as a screening tool for specific conditions or assess mental health more broadly. Methods: This study presents preliminary data from an online self-assessment tool for young people within the intended age range of 12 to 30 years. It covers key symptoms of mood and psychotic disorders, as well as risk factors, such as eating issues, substance use, suicidality, and deliberate self-harming behaviours. Participants self-assessed their level of functioning, access to ongoing interventions, and satisfaction with the help received. Based on the severity of mental health problems and the level of risk, different recommendation options of how to seek help were provided with the option to download their assessment as a PDF. Results: Out of a total of 303, 114 participants within the intended age range (65.8% female) gave permission to analyse their data. A high-risk profile was defined by anxiety symptoms, panic attacks, suicidal ideation, and urges to self-harm. Individuals with this profile were more likely to report psychosis or depression symptoms and recreational substance use associated with lower self-assessed day-to-day functioning. Ongoing treatment and the satisfaction with it were not determined by the severity of symptoms. Conclusions: These preliminary results suggest that the online self-assessment tool effectively reaches the intended young audience, particularly those who experience some degree of mental health problems. The tool may act as a motivational step to seeking professional help.

Swayam Mittal 1

and 9 more

In the field of wind turbines, there is growing attention towards. monitoring key components that are susceptible to high failure rates, such as gearbox, shafts, bearings, rotor blades, generators, etc. The usage of vibration sensors on turbine components aid in diagnosing and preventing breakdowns, ensuring reliable and efficient operation. A thorough understanding of degradation minimizes opportunity costs, optimizes maintenance expenses, and enables accurate prediction, planning, and effective mitigation of failures. In this study, two wind turbines from the same wind farm were considered for a detailed investigation of their vibration signature during normal operation. The vibrations were measured using identical sensors placed in the same locations (in both turbines) over an extended period, capturing a wide range of operating conditions. A multitude of methods including time domain analysis, frequency domain analysis, order analysis, envelope analysis were utilized to investigate and obtain a comprehensive understanding of the vibration dataset. These analyses helped identify the presence and extent of faults and abnormalities in the turbines. Moreover, the fault frequencies’ peaks derived from envelope analysis were cross-validated with analytically obtained fault frequencies. This research involves creating a distinctive degradation index, allowing the examination of degradation based on vibration behaviour over time. This effort facilitated the exploration of real-time changes in the degradation index, aiding in the ongoing assessment of wind turbine conditions. The analysis reveals multiple fault frequencies and greater degradation in the second turbine when compared to the first. Another key emphasis in this study involved the utilization of diverse autoregressive models, incorporating additional features to forecast the degradation index for the upcoming 15-day window. The resulting forecasts provide a clear tracking of degradation, offering advance notice for operators to implement timely predictive maintenance measures.

Marek Jastrzebski

and 10 more

Introduction. Precise electrocardiographic localization of accessory pathways (AP) can be challenging. Seminal AP localization studies were limited by complexity of algorithms and sample size.We aimed to create a non-algorithmic method for AP localization based on color-coded maps of AP distribution generated by a web-based application. Methods. APs were categorized into 19 regions/types based on invasive electrophysiologic mapping. Preexcited QRS complexes were categorized into 6 types based on polarity and notch/slur. For each QRS type in each lead the distribution of APs was visualized on a gradient map. The principle of common set was used to combine the single lead maps to create the distribution map for AP with any combination of QRS types in several leads. For the validation phase, a separate cohort of APs was obtained. Results. A total of 804 patients with overt APs were studied. The application used the exploratory dataset of 552 consecutive APs and the corresponding QRS complexes to generate AP localization maps for any possible combination of QRS types in 12 leads. Optimized approach (on average 3 steps) for evaluation of preexcited ECG was developed. The area of maximum probability of AP localization was pinpointed by providing the QRS type for the subsequent leads. The exploratory dataset was validated with the separate cohort of APs (n = 260); p = 0.23 for difference in AP distribution. Conclusions. In the largest dataset of APs to-date, a novel probabilistic and semi-automatic approach to electrocardiographic localization of APs was highly predictive for anatomic localization.

Cyril Chatain

and 5 more

Recent studies suggest that, compared to healthy individuals, people with chronic obstructive pulmonary disease (pwCOPD) present a reduced capacity to perform cognitive-motor dual-task (CMDT). However, these studies were focused on short-duration CMDT offering limited insight to prolonged CMDT inducing fatigue, which can be encountered in daily life. The present study aimed to explore the effect of adding a cognitive task during repeated muscle contractions on muscle endurance, neuromuscular fatigability and cognitive control in pwCOPD compared to healthy participants. Thirteen pwCOPD and thirteen age- and sex-matched healthy participants performed submaximal isometric contractions of the knee extensors until exhaustion in two experimental sessions: (1) without cognitive task and (2) with a concurrent working memory task (i.e., 1-back task). Neuromuscular fatigability (as well as central and peripheral components measured by peripheral magnetic stimulation), cognitive performance and perceived muscle fatigue were assessed throughout the fatiguing tasks. Independently to the experimental condition, pwCOPD exhibited lower muscle endurance compared to healthy participants (p=0.039), mainly explained by earlier peripheral fatigue and faster attainment of higher perceived muscle fatigue (p<0.05). However, neither effect of cognitive task (p=0.223) nor interaction effect (group × condition ; p=0.136) was revealed for muscle endurance. Interestingly, cognitive control was significantly reduced only in pwCOPD at the end of CMDT (p<0.015), suggesting greater difficulty for patients with dual-tasking under fatigue. These findings provide novel insights into how and why fatigue develops in COPD in dual-task context, offering a rationale for including such tasks in rehabilitation programs.

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Karma Norbu

and 3 more

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%.

Selahattin Semiz

and 2 more

Monoclonal antibodies (MAbs) are powerful therapeutic tools in modern medicine and represent a rapidly expanding multi-billion USD market. While bioprocesses are generally well understood and optimized for MAbs, online quality control remains challenging. Notably, N-glycosylation is a critical quality attribute of MAbs as it affects binding to Fcγ receptors (FcγR), impacting the efficacy and safety of MAbs. Traditional N-glycosylation characterization methods are ill-suited for online monitoring of a bioreactor; in contrast, surface plasmon resonance (SPR) represents a promising avenue, as SPR biosensors can record MAb-FcγR interactions in real-time and without labelling. In this study, we produced five lots of differentially glycosylated Trastuzumab (TZM) and finely characterized their glycosylation profile by HILIC-UPLC chromatography. We then compared the interaction kinetics of these MAb lots with four FcγRs including FcγRIIA and FcγRIIB at 5 oC and 25 oC. When interacting with FcγRIIA/B at low temperature, the differentially glycosylated MAb lots exhibited distinct kinetic behaviours, contrary to room-temperature experiments. Galactosylated TZM (1) and core fucosylated TZM (2) could be discriminated and even quantified using an analytical technique based on the area under the curve (AUC) of the signal recorded during the dissociation phase of a SPR sensorgram describing the interaction with FcγRIIA (1) or FcγRII2B (2). Because of the rapidity of the proposed method (less than 5 minutes per measurement) and the small sample concentration it requires (as low as 30 nM, exact concentration not required), it could be a valuable process analytical technology for MAb glycosylation monitoring.

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