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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

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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

Hang Liang

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Wave-induced fatigue damage is inevitable for the deepwater steel catenary riser (SCR). To accurately evaluate the fatigue performance of the full-scale SCR using small-size specimens, five kinds of fatigue testing strategies were explored, considering the effect of welding residual stress. Further, the corresponding fatigue tests were conducted regarding the welded joint specimens with the same weld profile, and the relevant differences in fatigue testing results were comprehensively analyzed. Through comparison with the full-scale resonant bending fatigue testing results, the most equivalent strategy using small-scale specimens was confirmed. The relevant results indicated that compared with the fatigue lives of full-scale pipeline joint specimens, the fatigue testing lives under the constant applied maximum stress of the yield strength for base material or the constant applied mean stress of the peak value of transverse welding residual stress strategy are relatively lower. The fatigue life values obtained from the high-stress ratio testing strategy are higher, especially in the low-stress range region. Comparatively, the fatigue lives obtained under the 80 mm wide specimen without the cutting process strategy were higher in the high-stress range region. The variable applied mean stress strategy using the 25 mm wide welded joint specimen was most suitable for equivalence with full-scale fatigue testing results, and the difference in the fatigue life testing results was only 9.7%. The difference between the applied mean stress and the actual transverse welding residual stress under various fatigue testing strategies is the key to affecting the equivalence of fatigue testing results.

Fani Pantouli

and 11 more

Background and Purpose Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behaviours. Multiple studies have highlighted the potential of oxytocin (OT) to ameliorate behavioural abnormalities in animal models and subjects with ASD. Clinical trials, however, yielded disappointing results. Our study aimed at challenging hypotheses accounting for such negative results by assessing the behavioural effects of different regimens of OT administration in the Oprm1 null mouse model of ASD. Experimental Approach We assessed the effects of intranasal OT injected once at different doses and time points following administration, or chronically, on ASD-related behaviours in Oprm1+/+ and Oprm1-/- mice. We then tested whether pairing intranasal OT injection with social experience would influence its outcome on ASD-like core symptoms, and measured gene expression in several regions of the reward/social circuit. Key Results Acute intranasal OT improved social behaviour in Oprm1-/- mice at a moderate dose (0.3 IU) shortly after administration (5 min). Effects on non-social behaviours were limited. Chronic OT at this dose maintained beneficial effects in Oprm1 null mice but was deleterious in wild-type mice. Finally, improvements in the social behaviour of Oprm1-/- mice were greater and longer lasting when OT was administered in a social context, while the expression of OT and vasopressin receptor genes, as well as marker genes of striatal projection neurons, was suppressed. Conclusions and implications Our results highlight the importance of considering dosage and social context when evaluating the effects of OT treatment in ASD.

Lotfollah Davoodi

and 8 more

IntroductionVulvovaginitis is inflammation of the vulvovaginal mucous membranes (1) that responsible of some of pediatric gynecology consultations (2). Prepubertal girls commonly experience a gynecologic issue, which is often characterized by symptoms such as vulvovaginal itching, discharge, irritation, burning or skin changes. The development of these symptoms is primarily influenced by anatomic, physiological, and behavioral factors specific to this age group (3). Streptococcuspyogenes , Haemophilus influenzae andEnterobius vermicularis emerge as the predominant pathogens, while fungal and viral infections exhibit lower occurrence rates (4). The presence of genital discomfort or a burning sensation during urination is often observed in cases of vulvovaginitis. This condition, which is more prevalent in prepubescent girls, can caused by a deficiency of estrogen and poor local hygiene leading to infection of the vaginal mucosa. Despite the lack of precise data on its prevalence, these predisposing factors are known to contribute to the development of vulvovaginitis (3).In addition, favor factors of development of this disease include local alkaline pH, thin labia minora and reauctioned estrogen stimulus during the prepubertal period results in thinning of the vulvovaginal epithelium. Among prepubertal girls, the most common clinical presentation is nonspecific vulvovaginitis caused by endogenous vaginal flora (5). One of the most agents of vulvovaginitis is a parasite calledEnterobius vermicularis (E. vermicularis ) (4). This worm exhibits the most extensive geographical distribution among helminths (6). Its induced infection is a global phenomenon and is recognized as the most prevalent form of helminth infection (7). This condition is prevalent across all age groups and socioeconomic backgrounds, although it is particularly widespread among children between the ages of five and fourteen (8, 9). It is important to note that parasitic infections even in children may lead to malnutrition and decreased learning abilities (10). Embryonated eggs can be detected on various surfaces such as fingernails, clothing, house dust and other objects. Once these eggs are ingested, they undergo hatching within the stomach, giving rise to larvae.These larvae then make their way to the cecum, where they undergo further development and eventually reach adulthood as pinworms, measuring approximately 1 cm in length. The gravid adult female worms exhibit a nocturnal migration to the perianal region, where they lay a substantial number of eggs, up to 11,000 in total. These eggs become infective within a relatively short period of time, approximately six hours after being deposited. The lifespan of E.vermicularis typically ranges from 11 to 35 days (8). Transmission of the infection takes place via direct transmission from an infected individual through the oral-anal route, or through the dispersal of airborne eggs from contaminated clothing or bed linen. Upon ingestion, the eggs hatch and release larvae within the intestine (11).Adult worms in girls may also infiltrate the vagina to release eggs and consequently leading to the development of vulvovaginitis. In 1980, Vaughan reported one of the first enterobiasis in direct observation of vaginal region (9, 12). Moreover, these worms possess the ability to invade the endometrial cavity, thereby inducing endometritis and salpingitis in affected patients (9). For diagnosis collection of eggs from infected area (anus or vagina) can be achieved through the use of the cellophane swab or scotch tape swab method. stool examination not be a reliable means of detecting eggs (13). Cases have been documented wherein this worm have traversed the entire of the reproductive system and penetrated the peritoneal cavity by means of the fallopian tubes (9). In this paper we presented a 4 years Iranian girl that suffered of vulvovaginitis caused by E. vermicularis . her family infected by this parasitic helminth too.

Julien Dreyfus

and 1 more

Advancing Transcatheter Valve Replacement for Severe Aortic Regurgitation: Innovations in Devices and Multi-Modality ImagingJulien Dreyfus, MD, PhD1; David Messika-Zeitoun, MD, PhD21: Cardiology Department, Centre Cardiologique du Nord, 32-36 rue des moulins gémeaux, 93200 Saint-Denis, France2: Division of Cardiology, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, CanadaWord Count : 912 wordsAddress for correspondence :Julien Dreyfus, Department of Cardiology, Centre Cardiologique du Nord, Saint-Denis, France. Tel: +33149334803, Fax: +33149334143, E-mail: [email protected] patients with severe symptomatic aortic regurgitation (AR) who are deemed at high surgical risk, off-label use of transcatheter aortic valve replacement (TAVR) is increasingly performed. However, the rate of complications is high in this subset, including migration, paravalvular regurgitation, pacemaker implantation, stroke, bleeding, vascular complication, acute renal failure, surgical conversion and mortality.(1)In this issue of Echocardiography , Hu et al (ref) present their findings on 70 patients (56% of males, mean age=74±8 years) with severe symptomatic AR (all in NYHA functional class III or IV) on native or bioprosthetic valves who underwent a TAVR using the Vita-Flow valves (Microport), a novel self-expanding valve (Figure). The population was divided into two groups: group A consisted of 40 patients with aortic root dilatation or valve prolapse and no valvular calcifications, while group B comprised 30 patients with aortic valve degeneration and/or mild senile calcifications (Agatston score ranging from 0 to 100). All interventions were performed under general anesthesia, with procedural guidance provided by both fluoroscopy and real-time three-dimensional echocardiography. A comprehensive pre-procedural assessment of the anatomy was conducted using both transesophageal echocardiography (TEE) and computed tomography (MSCT) and dedicated software. The study focuses on the utility of echocardiography in the pre-procedural screening, intra-procedural monitoring, and 30-day post-procedural follow-up, while also identifying potential predictors for post-procedural complications.The main results from the study can be summarized as follow:Multimodality imaging analysis demonstrated significant concordance between TEE and MSCT especially in the assessment of the annulus and aorta dimensions, as well as left and right coronary artery height, enabling accurate device sizing.The procedural success rate was high (96%) and there were no deaths at 30 days.Multiple underlying mechanisms of AR were successfully treated.Mild peri-valvular leakage was observed in 16% of cases but no moderate or greater peri-valvular leakage was reported.Incidence of significant complications was low, with 3% experiencing iliac artery dissection, 4% encountering stroke, and 3% developing acute renal insufficiency within 30 days post-procedure. No migration was reported.A noteworthy 22% of patients required new pacemaker implantation due to complete atrioventricular block, with a median implantation time of 6 days with right bundle branch block as the only independent predictor.Procedural success correlated with a positive left ventricular and atrial remodeling at 30 days (reductions in left atrial and left ventricular diameters, and improvement of the left ventricular ejection fraction).The main limitations of this study include its retrospective single-center design, small sample size (although relatively large for a single center), mix of TAVR on native valves and valve-in-valve procedures, and a short follow-up period.A significant proportion of patients with surgical indications for severe AR are not referred, often due to high surgical risk or comorbidities(2,3). Transcatheter treatment of AR is currently on the rise but is much more challenging than for aortic stenosis, notably due to the absence of calcifications.TAVR is currently mostly performed using prostheses developed for aortic stenosis. A recent multicenter registry (PANTHEON) including 201 patients treated with commercially available devices (self-expandable and balloon expendable valves developed for AS) showed that with improvements in TAVR devices, in experienced centers and in selected patients, satisfactory outcomes can be achieved in a majority of patients, but that complications rates remained high (12% of embolization or migration at 1 month and 10% of moderate or greater residual leakage), regardless of prosthesis type. Critically, these complications were associated with high mortality or hospitalization for heart failure rates at 1 year (approximately 25%). Rates of permanent pacemaker implantation were also high (approximately 22%), often associated with device oversizing.(1)Several devices designed for the management of AR are currently available or under evaluation. Presently, the JenaValve Trilogy system (JenaValve Technology) is the only dedicated device to have received Conformité Européenne (CE) mark approval for the transcatheter treatment of patients with AR. A recent multicenter registry, comprising 58 consecutive patients from 6 centers across Germany, demonstrated excellent outcomes with a 98% implantation success rate, the absence of moderate or severe paravalvular regurgitation, a 30-day mortality rate of 1.7%, and a 19.6% rate of new permanent pacemaker implantation.(4) The Jena-Valve ALIGN-AR Pivotal Trial (NCT04415047) included 177 patients with 91% of procedures performed under general anesthesia. The trial yielded a procedural success rate of 95%, with 3% of patients necessitating subsequent surgery. Only 0.6% experienced moderate or severe paravalvular regurgitation, and 30-day mortality rate was 2.2%. Additionally, 24% of patients received new pacemaker implantation, a rate that tended to decrease with experience, particularly with refined strategies for device sizing and positioning.The J-Valve (JC Medical), specifically designed for the treatment of patients with AR, is another alternative. A recent study including 27 patients for compassionate use found a procedural success rate of 81% overall and 100% in the last 15 cases, with no patient having residual AR of moderate or greater degree at 30 days and a 13% rate of new pacemaker implantation.(5)In conclusion, there is a genuine enthusiasm for transcatheter AR management, driven by both industry innovation and clinical demand. Dedicated devices seem to perform better than devices commercially used for aortic stenosis, but pacemaker implantation rate remains high. Multimodal imaging plays a pivotal role in patient and device selection, procedural guidance, and follow-up. Although echocardiography seems accurate, as for aortic stenosis, MSCT will remain the method of choice for pre-intervention procedural planning. As the landscape rapidly evolves, refining patient selection, procedural techniques, and postprocedural care will be paramount to ensuring optimal outcomes in this challenging patient population.

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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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