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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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Lily Duggan

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Formal quantitative surveys of wild animal abundance or activity, and assessments of the integrity of the complex natural ecosystems they live in, are typically quite laborious and meaningful analysis of the data obtained may require considerable time and expertise. This study describes the development and evaluation of a practical procedure for semi-quantitative synthesis of consensus subjective impressions accumulated by a small team of investigators who visited 32 different locations distributed in or around a community-based Wildlife Management Area in southern Tanzania. The subjective natural ecosystem integrity index scores obtained represent a holistic indicator of all aspects of land use, wildlife and human activities, which correlated strongly with objective indicators of wild animal community or whole natural ecosystem integrity that were estimated directly from formally collected quantitative survey data by the same investigators at the same locations. Also, comparative regression analysis indicated that the SNEII was a far more sensitive to variations in observed human activities than any of the objective alternatives, correspondingly yielding far more detailed insights into ongoing conservation challenges. This simple procedure for summarizing the overall, multi-faceted subjective impressions of individuals traversing extensive conservation areas may well be applicable through participatory approaches to routine programmatic monitoring by community-based staff with minimal training, and may therefore be more practically useful to devolved conservation areas like WMAs than conventional objective statistical synthetic indices relying on laborious collection and analysis of quantitative survey data.

Ningjing Cui

and 2 more

Language control in bilingual speakers is thought to be implicated in effectively switching between languages, inhibiting the non-intended language, and continuously monitoring what to say and what has been said. It has been a matter of controversy concerning whether language control operates in a comparable manner to cognitive control processes in non-linguistic domains (domain-general) or if it is exclusive to language processing (domain-specific). As midfrontal theta oscillations have been considered as an index of cognitive control, examining whether a midfrontal theta effect is evident in tasks requiring bilingual control could bring new insights to the ongoing debate. To this end, we reanalysed the EEG data from two previous bilingual production studies where Dutch-English bilinguals named pictures based on colour cues. Specifically, we focused on three fundamental control processes in bilingual production: switching between languages, inhibition of the nontarget language, and monitoring of speech errors. Theta power increase was observed in switch trials compared to repeat trials, with a midfrontal scalp distribution. However, this midfrontal theta effect was absent in switch trials following a short sequence of same-language trials compared to a long sequence, suggesting a missing modulation of inhibitory control. Similarly, increased midfrontal theta power was observed when participants failed to switch to the intended language compared to correct responses. Altogether, these findings tentatively support the involvement of domain-general cognitive control mechanisms in bilingual switching.

Gopal V

and 17 more

Background Viral interference is the concept that different viruses have an effect on the incidence of other viruses– either positive or negative. While this has been demonstrated in vitro and in animal models, it is not well described in large observational studies. Methods We analysed all patients tested for positive respiratory viruses between January 2016– December 2019 just prior to the pandemic in the National University Hospital laboratory, Singapore. Nasal, throat, and/ or nasopharyngeal swabs were collected by treating clinicians and tested by either multiplex PCR or immunofluorescence. Survival plots were created to study the time for a second viral infection following the initial respiratory viral detection. Results RSV (HR: 0.63, 95%CI: 0.43–0.92; p<0.01) and influenza (HR: 0.41, 95%CI: 0.27-0.61; p<0.001) -positive cases showed a greater delay in subsequent respiratory infections compared to other pathogens, suggesting relative protection, while enterovirus/ rhinovirus (HR: 2.05, 95%CI: 1.52-2.77; p<0.001) and Parainfluenza (HR: 1.76, 95%CI: 1.18-2.63; p<0.001) showed heightened susceptibility. No significant associations were found for Adenovirus, seasonal coronaviruses, and other pathogens. Conclusion We found that it is possible that prior infections with Influenza virus or RSV conferred significant cross-protection against subsequent circulating respiratory viral infections for the next 4 years. Larger studies are needed to explore mechanisms behind this possible broad-spectrum antiviral response in human hosts as this may have implications for vaccination strategies.

Sevilay Yeğinoğlu

and 1 more

Objectives: Xerostomia is defined as the subjective feeling of dry mouth. It is a condition that affects millions of patients worldwide. The aim was to study prevalence and severity of self-reported xerostomia by sociodemographic variables and to evaluate self-reported halitosis, burning mouth, and mouth sores. Methods: A questionnaire regarding sociodemographic data and the 11-item Xerostomia Inventory was delivered to patients, 20-65 years of age applied to the XXXX University Faculty of Dentistry for dental treatment before the COVID-19 pandemic. Statistical analyses were performed to determine the relationships between the presence of xerostomia and other variables such as age, gender, the presence of a systemic disease, medication use, smoking, alcohol consumption, and the use of removable prostheses. Results: A total of 300 patients were included in the study; a prevalence of xerostomia of 54.6% was identified. A significant relationship was found between age and xerostomia ( p = 0.023; p = 0.001). The prevalence of xerostomia decreased as age increased. Xerostomia was more common in female patients ( p = 0.028; p = 0.004). The prevalence of xerostomia was found to be high, not only in the elderly, but also in younger adults. Conclusion: Xerostomia was reported in approximately one in two patients in an adult Turkish population. Factors associated with xerostomia were age, female gender and the number of cigarettes smoked per day. In this study, the high prevalence of xerostomia was due to smoking.

Richard Osei-Yeboah

and 11 more

Background Older adults in nursing and care homes (NCHs) are vulnerable to severe respiratory syncytial virus (RSV) infection, hospitalisation, and death. This study aimed to gather data on RSV disease among older adults in NCHs and identify reported risk factors for RSV hospitalisation and case fatality. Methods The study protocol was registered in PROSPERO (CRD42022371908). We searched MEDLINE, EMBASE and Global Health databases to identify articles published between 2000 and 2023. Observational and experimental studies conducted among older adults in NCHs requiring assistive care and reporting RSV illness were included and relevant data were extracted. Results Of 18,690 studies screened, 32 were selected for full-text review and 20 were included. Overall, the number of NCH residents ranged from 42 to 1,459 with a mean age between 67.6 and 85 years. Attack rates ranged from 6.7 – 47.6% and annual incidence ranged from 0.5 – 14%. Case fatality rates ranged from 7.7 – 23.1%. We found similar annual incidence rates of RSV-positive acute respiratory infection (ARI) of 4,582 (95% CI: 3,259 – 6,264) and 4,785 (95% CI: 2,258 – 10,141) per 100,000 reported in two studies. Annual incidence rate of RSV-positive lower respiratory tract infection was 3,040 (95% CI: 1,986 – 4,454) cases per 100,000 adults. Annual RSV-ARI hospital admission rates were between 600 (95% CI: 190 -10,000) and 1,104 (95% CI: 350 – 1,930) per 100,000 person-years. Among all RSV disease cases, commonly reported chronic medical conditions included chronic obstructive pulmonary disease (COPD), heart failure, ischemic heart disease, coronary artery disease, hypertension, diabetes, kidney dysfunction, cerebrovascular accident, malignancies, dementia, and those with a Charlson comorbidity score > 6.5. Conclusion Data on RSV infection among NCH residents are limited and largely heterogeneous but document a high risk of illness, frequent hospitalisation, and high mortality. Preventive interventions, such as vaccination should be considered for this high-risk population. Nationally representative epidemiologic studies and NCH-based viral pathogen surveillance could more precisely assess the burden on NCH residents.

Lionel Benchimol

and 6 more

Summary: This prospective study investigates the impact of local anesthesia on ciliary function in nasal epithelium. The primary objective was to assess whether lidocaine 2% and naphazoline 0.5% nasal spray alter ciliary beat frequency and pattern in subjects undergoing nasal brushing, aiming to enhance primary ciliary dyskinesia (PCD) diagnosis. Hypothesis: It was hypothesized that local anesthesia administration would not significantly affect ciliary function in nasal epithelium. Study design: A prospective, simple-blind randomized study was conducted between 2020 and 2023. The study employed digital high-speed videomicroscopy to analyze ciliary beat frequency and pattern. Patient/subject selection: A cohort of 38 participants was recruited, consisting of 25 healthy volunteers and 13 referred individuals (including 7 diagnosed with PCD). Selection criteria ensured absence of chronic respiratory diseases, recent respiratory tract infections, or regular use of nasal medications. Methodology: Participants underwent nasal brushing with administration of lidocaine and naphazoline nasal spray in one nostril and saline in the contralateral nostril. Ciliary beat frequency and pattern were measured using digital high-speed videomicroscopy. Results: Nasal spray administration did not significantly alter ciliary beat frequency or pattern compared to saline (p = 0.841 and p = 0.125, respectively). Subgroup analysis revealed consistent results across healthy volunteers, referred patients, and PCD patients. Conclusion: Local anesthesia with lidocaine and naphazoline spray did not affect ciliary function outcomes. These findings support the safe use of these agents in clinical practice for PCD diagnostic procedures. Further research with larger cohorts is warranted for validation.

Erin Voss

and 1 more

Genes involved in reproduction often evolve rapidly due to postcopulatory sexual selection (PCSS) driven by male-male competition and male-female sexual conflict, but the impact of PCSS on gene expression has been under-explored. Further, though multiple tissues contribute to male reproductive success, most studies have focused on the testes. To explore the influence of mating system variation on gene expression in the Peromyscus male reproductive tract, we generated RNAseq libraries and quantified gene expression in the testis, seminal vesicle, epididymis, and liver of wild-caught monogamous P. californicus and polygynandrous P. boylii and P. maniculatus males and tested for positive and relaxed selection on Peromyscus-expressed genes using published rodent genomes. We identified 3,627 mating-system associated differentially expressed genes (MS-DEGs), where expression shifted in the same direction in P. maniculatus and P. boylii relative to P. californicus. Gene expression variation was most strongly associated with mating behavior in the seminal vesicles, where 89% of differentially expressed genes were MS-DEGs, including two key seminal fluid proteins, Svs2 and Pate4. Though but most genes showing evidence of positive selection or differential expression did not overlap, 203 MS-DEGs showed evidence of positive selection. Additionally, fourteen reproductive genes were under tree-wide positive selection but showed evidence of convergent relaxed selection in P. californicus and Microtus ochrogaster, a distantly related monogamous species. Changes in transcript abundance and gene sequence evolution in association with mating behavior suggest that male mice may respond to variation in sexual selection by altering aspects of sperm motility, sperm-egg binding, and copulatory plug formation.

Jie Mi

and 11 more

Objective: The interferon-γ (IFN-γ) release assays still fail to meet the diagnostic needs of etiology negative tuberculosis (TB) patients. The purpose of this paper is to explore the value of the IL-2-enzyme-linked immunospot (ELISPOT) assay in the auxiliary diagnosis of TB. Methods: We recruited 127 TB patients, 49 non-TB patients with other diseases (NTB), and 198 healthy people, whose peripheral blood mononuclear cells were isolated and stimulated by Mtb-specific antigen CFP-10/ESAT-6 fusion protein to study the changes of T cells secreting IFN-γ and Interleukin-2 (IL-2) by ELISPOT method. Results: The combination of IFN-γ and IL-2 had an area under the curve (AUC) of 0.867 (IFN-γ: 0.835, IL-2: 0.866) in the diagnosis of TB and could increase the sensitivity of IFN-γ detection alone from 79.5% to 86.6%. The cut-off value for IL-2 and IFN-γ was 16. IL-2 could increase the positive diagnostic rates of IFN-γ-ELISPOT (-) in the etiologically positive and negative ATB patients by 9.4% and 7.1%. In the ATB group, the positive rates and the numbers of spot-forming cells (SFC) of IFN-γ and IL-2 showed significant differences compared to the normal control subjects and NTB group (P<0.05). And SFCs of IFN-γ-ELISPOT were significantly higher than that of IL-2-ELISPOT in ATB patients. Before the treatment, the SFC values of the etiologically positive TB patients were higher than those of the etiologically negative patients. However, this situation was totally reversed after anti-TB treatment. After effective treatment, the positive rates and SFC values of IFN-γ and IL-2 in TB patients decreased and exhibited a decreasing and increasing trend in etiologically positive and negative TB patients, respectively. Conclusions: The combination of IL-2 and IFN-γ could improve the diagnostic sensitivity of single-factor detection in TB patients and these two cytokines could be used as effective biomarkers for the treatment monitoring in TB patients.

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Mohammad Rowshan

and 4 more

Channel coding plays a pivotal role in ensuring reliable communication over wireless channels. With the growing need for ultra-reliable communication in emerging wireless use cases, the significance of channel coding has amplified. Furthermore, minimizing decoding latency is crucial for critical-mission applications, while optimizing energy efficiency is paramount for mobile and the Internet of Things (IoT) communications. As the fifth generation (5G) of mobile communications is currently in operation and 5G-advanced is on the horizon, the objective of this paper is to assess prominent channel coding schemes in the context of recent advancements and the anticipated requirements for the sixth generation (6G). In this paper, after considering the potential impact of channel coding on key performance indicators (KPIs) of wireless networks, we review the evolution of mobile communication standards and the organizations involved in the standardization, from the first generation (1G) to the current 5G, highlighting the technologies integral to achieving targeted KPIs such as reliability, data rate, latency, energy efficiency, spectral efficiency, connection density, and traffic capacity. Following this, we delve into the anticipated requirements for potential use cases in 6G. The subsequent sections of the paper focus on a comprehensive review of three primary coding schemes utilized in past generations and their recent advancements: lowdensity parity-check (LDPC) codes, turbo codes (including convolutional codes), and polar codes (alongside Reed-Muller codes). Additionally, we examine alternative coding schemes like Fountain codes (also known as rate-less codes), sparse regression codes, among others. Our evaluation includes a comparative analysis of error correction performance and the performance of hardware implementation for these coding schemes, providing insights into their potential and suitability for the upcoming 6G era. Lastly, we will briefly explore considerations such as higher-order modulations and waveform design, examining their contributions to enhancing key performance indicators in conjunction with channel coding schemes.
The involvement of users in the product development process can significantly enhance product quality. The relationship between user experience and knowledge in product design contributes to product efficiency during the development phase. Users often struggle to align their perceptions, leading to extended product usage times and an inability to react to potential performance variations. Product manufacturers also face challenges in identifying suitable features that can positively impact product success and marketability. User experience in product interactions, encompassing both aesthetic and functional aspects, plays a pivotal role in influencing user evaluations and distinguishing characteristics crucial for achieving product success. Determining user knowledge’s influence on product success characteristics can provide valuable insights for the new product development process. This study conducted a survey to gather user experiences and knowledge, aiming to enhance the understanding of how users perceive products. This understanding is crucial for identifying product success characteristics, encompassing aspects such as specifications, sustainability, and recognition, which are instrumental in achieving overall product success. The results of the survey indicate that user knowledge, emotional experiences, and product attribute knowledge can assist product designers and manufacturers in identifying key characteristics for success during the early stages of the new product development process.

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%.

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