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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

Addison A. Cuneo

and 2 more

Opportunities for Trauma-Informed Medical Care in Cystic FibrosisTo the Editor:People living with Cystic Fibrosis (PwCF) face a lifetime of potentially traumatic medical experiences. These experiences can range from invasive medical treatments (e.g. venipuncture, nasogastric tube placement) to daily illness-related events (e.g. illness related bullying). These experiences place PwCF at high risk for a type of posttraumatic stress called Medical Traumatic Stress (MTS)[1]. With the growing recognition of the high prevalence and impact of MTS, we anticipate that cystic fibrosis care teams may soon be tasked with integrating trauma-informed medical care into their clinical practices. CF care teams are well poised to prevent and screen for MTS because they 1) create the environment for many illness-related experiences; 2) have established workflows for mental health screening; and, in many cases, 3) have trusting relationships with PwCF and their families. Here, we seek to highlight the opportunities for implementing trauma-informed medical care within the cystic fibrosis-specific context.MTS is defined as the psychological and physiological responses of children and their families to pain, injury, serious illness, medical procedures, and invasive or frightening treatment experiences[2]. MTS is common in PwCF – 55% of these youth report experiencing potentially traumatic medical experiences and 30% report MTS symptoms[1]. MTS symptoms have the potential to impact medical care, health outcomes and quality of life[3].While highly effective modulator therapies may decrease the frequency and severity of medical care, PwCF have identified these therapies as an additional source of potentially traumatic experiences[4]. New potentially traumatic medical experiences in modulator-eligible PwCF can include lost sense of purpose as their identity shifts from a “sick” person to a “well” person; survivor guilt from benefiting from therapies not available to others; and financial distress as they face planning for a longer than anticipated life expectancy [4]. The challenge of navigating the healthcare system, such as advocating with care teams and insurance companies, has been identified as potentially traumatic by PwCF, particularly those who are modulator-ineligible[4].A trauma-informed approach to medical care may be helpful for cystic fibrosis care teams to mitigate MTS. The Pediatric Psychosocial Preventive Health Model (PPPHM) provides a framework for tiered implementation of trauma-informed medical care[5]. It includes recommendations for universal practices gauged towards all children and families, targeted approaches for those at high risk of developing MTS, and treatment for those with severe, escalating, or persistent MTS symptoms (Figure 1).Universal MTS interventions for PwCF include prevention and screening. Preventive interventions can include MTS awareness education for all PwCF, family members of PwCF and cystic fibrosis care team members. This education can highlight approaches to modifying potentially traumatic medical experiences and identifying MTS symptoms that indicate the need for further support. Universal systems interventions may also include the implementation of workflows to minimize the traumatic potential of healthcare experiences (e.g. workflows to minimize needle distress with comfort positioning, numbing cream, and distraction as part of standard care. Care teams can also integrate shared decision-making processes to optimize patient perception of control and implement systems that facilitate communication between cystic fibrosis care team and PwCF.While annual mental health screening for depression and anxiety is the current recommendation for all PwCF, healthcare providers should consider integrating routine MTS screening into their practice. Screening workflows can include screening for patient risk factors and MTS symptoms, as well as family member symptoms of MTS. Currently, there are no screening tools designed to specifically capture the cystic fibrosis experience of MTS; however, acute stress screeners such as the Acute Stress Checklist for Children can aid in the identification of MTS, thereby guiding providers on who to refer for further mental health assessments or support. One common concern regarding screening for MTS is managing the burden of time as well as supporting those PwCF who screen at-risk. Thus, in planning for MTS screening, teams ought to consider the time required for screening, appropriate training for those performing the screening, and the development of a clear workflow for management and referrals. While these barriers require a thoughtful approach to processes and care, the benefits outweigh the consequences of not screening. MTS is present for many regardless of if screening occurs and screening allows the medical team to optimize overall healthcare.The second tier of the PPPHM recommends targeted approaches to MTS for those with risk factors or early symptoms. Possible MTS risk factors in PwCF include parent posttraumatic stress disorder, high daily medication burden, and emergency room and intensive care [1]. Interventions for PwCF who have MTS risk factors or early symptoms may include increasing support during potentially traumatic medical experiences (e.g. having a child life expert prepare a patient before a procedure); altering the medical care plan when possible (e.g. minimizing daily medication burden); educating family members on what to say to PwCF before, during, and after potentially traumatic medical experiences; and integrating patient-specific resilience factors into individualized coping and support plans. In some cases, brief therapeutic psychological interventions may help address specific symptoms (e.g., targeted CBT needle phobia interventions, behavioral sleep interventions, brief psychoeducation interventions).The third tier of the PPPHM recommends treatment for MTS symptoms that impact medical care or impair daily functions. PwCF with significant MTS symptoms should be referred to a mental health provider with expertise in the treatment of trauma symptoms. Ideally, the provider should have familiarity with chronic medical conditions, and, ideally, cystic fibrosis specifically. While we do not yet have evidence-based MTS-specific interventions for PwCF, approaches may include cognitive behavioral techniques such as restructuring of hospital-related thoughts, behavioral activation, or trauma-focused cognitive behavioral therapy. Mental health providers could also collaborate with families and cystic fibrosis care teams to develop an individualized plan for minimizing re-traumatization and reducing the impact of MTS on medical care and quality of life.In summary, given the substantial impact that MTS can have on PwCF, cystic fibrosis care teams should consider integrating trauma-informed approaches into the medical care of PwCF to optimize overall health (including mental health). Comprehensive approaches to MTS mitigation in PwCF include 1) universal awareness, prevention, and screening, 2) targeted interventions for those at high risk, and 3) individualized MTS treatment administered by mental health professionals. To optimize cystic fibrosis care with attention to MTS, future research should prioritize more definitive identification of MTS risk factors, the development of validated cystic fibrosis-specific MTS screening tools, the creation and dissemination of evidence-based MTS prevention programs, and the development of evidence-based MTS mental health interventions tailored to PwCF.Figure 1: Application of the Pediatric Psychosocial Preventative Health Model to Cystic Fibrosis. Adapted with permission from the Center for Healthcare Delivery Science at Nemours Children’s Health System 2018-2019. All rights reserved[5].

Mohamed Boutjdir

and 2 more

Marco Perrig

and 5 more

Global environmental changes are predicted to lead to warmer average temperatures and more extreme weather events thereby affecting wildlife population dynamics by altering demographic processes. Extreme weather events can reduce food resources and mortality, but the contribution of such events to demographic processes are poorly understood. Estimates of season-specific survival probabilities are crucial for understanding mechanisms underlying annual mortality. However, only few studies have investigated survival at sufficient temporal resolution to assess the contribution of extreme weather events. Here, we analysed biweekly survival probabilities of 307 radio-tracked juvenile little owls (Athene noctua) from fledging to their first breeding attempt in the following spring. Biweekly survival probabilities were lowest during the first weeks after fledging in summer and increased over autumn to winter. The duration of snow cover in winter had a strong negative effect on survival probability, while being well fed during the nestling stage increased survival during the first weeks after fledging and ultimately led to a larger proportion of birds surviving the first year. Overall annual survival probability over the first year varied by 34.3 % between 0.117 (95 % credible interval 0.052 – 0.223) and 0.178 (0.097 – 0.293) depending on the severity of the winter, and up to 0.233 (0.127 – 0.373) for well-fed fledglings. The season with the lowest survival was the post-fledging period (0.508; 0.428 – 0.594) in years with mild winters, and the winter in years with extensive snow cover (0.481; 0.337 – 0.626). We therefore show that extreme weather events reduced the proportion of first-year survivors. Increasingly warmer winters with less snow cover may therefore increase annual survival probability of juvenile little owls in central Europe, but environmental changes reducing food supply during the nestling period can have similarly large effects on annual juvenile survival and therefore the viability of populations.

Angela Bordin

and 4 more

I aimed to better understand the community ecology of sympatric birdlife in subtropical South East Queensland, Australia using patterns of temporal species co-occurrence and principles from network theory. In line with expectation, a hierarchical clustering analysis showed that dates that were successive were joined by the shortest branch lengths because of similar patterns of observed bird species. The only date sampled in the Southern hemisphere Autumn was awarded its own branch in the tree, indicating these observations were relatively distinct. Estimates of total observed bird biomass were substantively higher in the Autumn sample. Ranking each species on its average pairwise correlation to the other 87 species in the set shows that, unsurprisingly, raptors (such as Whistling Kites, Haliastur splenurus) tend to be the most negatively correlated (hypergeometric enrichment statistic P = 0.00029) indicating their presence is inhibitory to other avian species. On the other hand, Silvereyes (Zosterops lateralis) possess the highest number of total connections, the highest radiality (or ‘network influence’) metric within the inferred co-occurrence network and have the second highest average positive correlation to all other bird species in the set (+0.32). Collectively, this means Silvereyes can be seen as an indicators whose presence indicates an enhanced likelihood of observing a diversity of other bird species. Network clustering analysis detects a large module of positively connected bird species within the overall structure (dominated by non-threatening diminutive species as Z. lateralis, Little Friarbirds Philomon citreogularis and Red Backed Fairy Wrens Malurus melanocephalus), whereas all but one of the raptors sit on the periphery. The use of the PCIT network reconstruction algorithm is demonstrated for the first time in community ecology.

Victor Andreev

and 5 more

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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%.

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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