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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: mpw1001@cam.ac.ukThe 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

Tra Van Dong

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With many practical applications print human life today such as manufacturing surveillance cameras, analyzing and processing customer behavior, …, the problem of face detection and head pose estimation on digital images is being noticed by many researchers. A large number of proposed deep learning models have state-of-the-art accuracies such as YOLO, SSD, and MTCNN, solving the problem of face detection or HopeNet, FSA-Net, and RankPmodelsodel used for head pose estimation problems. According to big many state-of-the-art methods, the process of this task consists of 2 parts face detection to head pose estimation. These two steps are completely independent and do not share information with each other. This makes the model clear print setup but does not leverage most of the featured resources extracted in each model. In this thesis, we proposed the PoseMultitask model with the motivation to leverage the features extracted from the face detection model, sharing them with the head pose estimation branch to improve accuracy. Also, with the variety of data, the Euler angle domain representing the face is large, our model can predict results in the 360° Euler angle domain. Applying the multi-tasking learning method, the PoseMultitask model can simultaneously predict the position and direction of the human head. To increase the ability to predict the head direction of the model, we change the representation of the human face from the rom Euler angle to vectors from the Rotation matrix.

Eriks Elksnis

and 4 more

RECALCITRANT MULTIDRUG-RESISTANT PSEUDOMONAS KERATITIS WITH SUBSEQUENT TRIPLE PROCEDUREAuthors: Ēriks Elksnis1,2,4, Eva Elksne1,3, Olita Lūse1,2, Juris Vanags1,4, Guna Laganovska1,4Affiliations:Riga Stradins University, Riga, LatviaLatvian American Eye CenterChildren’s Clinical University Hospital, Riga, LatviaPauls Stradins Clinical University HospitalCorrespondence to: Ēriks Elksnis. ORCID 0000-0002-7899-8224Riga Stradins University, Dzirciema street 16, Riga, Latvia. LV1007.Data availability statement : We hereby transfer, assign, or otherwise convey all copyright ownership, including any and all rights incidental thereto, exclusively to the journal, in the event that such work is published by the journalConflict of interest disclosure : Authors declare no potential conflicts of interest.Ethics approval statement : All procedures performed involving this case were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Consent statement: Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy.KEY CLINICAL MESSAGERecalcitrant Pseudomona aeruginosa keratitis is a challenging case in ophthalmology and can lead to irreversible blindness if not treated properly and in time.KEYWORDS: Pseudomona aeruginosa, recalcitrant keratitis, penetrating keratoplasty.INTRODUCTIONCorneal opacity is the 5th leading cause of blindness and visual impairment, affecting approximately 6 million people worldwide; additionally, it is responsible for 1.5–2.0 million new cases of monocular blindness per year. Among all etiologies (such as infection, trauma, and inflammation), infectious keratitis (IK) is the main cause of corneal blindness, with an estimated incidence ranging from 2.5–799 per 100,000 population years (Ting et al. 2021).Pseudomonas aeruginosa (P. aeruginosa ) is a gram-negative aerobic pathogen that can cause a wide range of infections and is one of the main causative pathogens of bacterial keratitis, especially in contact lens-associated keratitis, potentially leading to sight-threatening complications if not appropriately treated (Hilliam, Kaye & Winstanley 2020).A particular characteristic of multidrug resistant Pseudomonas keratitis is its rapid progression, in which corneal destruction can be completed within 24–48 hours in some of the more virulent bacterial strains (Reynolds & Kollef 2021). Therefore, P. aeruginosa -caused keratitis is often associated with a high-cost long treatment period and poor visual outcomes (Hilliam, Kaye & Winstanley 2020).CASE PRESENTATIONA 60-year-old female presented to a tertiary medical center in May 2021 with progressive vision loss, purulent discharge, photophobia, foreign body sensation, and pain in the left eye (LE).Three weeks prior, the patient developed a foreign body sensation in her LE due to contact lenses remaining unremoved for one night. She had visited her local ophthalmologist and been prescribed topical tobramycin/dexamethasone 3 mg/mL four times daily, cyclopentolate 10 mg/mL twice daily, and dexpenthenolum once daily before bedtime. There was clinical improvement during the first 5 days of therapy; however, severe clinical worsening followed. The patient returned to the outpatient department 8 days after the first consultation, and treatment was changed to topical chloramphenicol/dexamethasone 1 mg/2 mg/mL six times daily, cyclopentolate 10 mg/mL twice daily and oral doxycycline 100 mg twice daily. Despite treatment, the symptoms worsened in the following week.On the presenting day at the tertiary medical center, the best corrected visual acuity (BCVA) was 20/25 in the right eye (RE) and hand-motion (HM) vision in the LE. The RE was unremarkable on initial examination, whereas slit-lamp examination of the LE revealed a massive amount of purulent discharge in the conjunctival fornixes and intense mixed conjunctival injection. A large epithelial defect in the cornea was present, associated with a ring-like stromal infiltrate 3.1 mm in height, which was “soupy” in appearance owing to stromal necrosis. A hypopyon 3.2 mm in height was observed (Figure 1A). Both the lids were swollen and erythematous. As the posterior segment could not be visualized, B-scan ultrasonography of the LE was performed and confirmed a flat retina with no vitritis.Corneal scrapings and cultures were obtained from LE. Cultures were acquired using a sterile cotton-tipped swab and placed in transport medium. The scrapings were placed on a glass slide and, together with the culture, forwarded to a microbiology laboratory.Topical chloramphenicol/dexamethasone was discontinued, and levofloxacin 5 mg/mL eyedrops were initially administered every hour. Additionally, cyclopentolate 10 mg/mL was administered twice daily to control pain and prevent synechia, artificial tear drops were administered to aid wound healing, and oral doxycycline 100 mg twice daily was administered to prevent keratolysis.After 12 hours, the condition worsened; discharge remained in the same amount, however, the hypopyon increased to 5.4 mm in height, with an infiltration spread 360 °around the limbus and significant corneal edema (Figure 1B).Levofloxacin was switched to moxifloxacin 5 mg/mL eye drops every hour. As a result, the amount of purulent discharge reduced, yet the central corneal infiltrate and ulcer remained unchanged, with remarkable stromal necrosis and corneal thinning in the nasal limbs (Figure 1C).On the fourth day from admission, multidrug resistantP.aeruginosa  was isolated from the culture. (Table 1). Based on these results, and after consultation with an infectologist, moxifloxacin was changed to fortified piperacillin 1.5 mg/mL/tazobactam 12 mg/mL eye drops every hour.

Paolo Biella

and 5 more

Cold-adapted species endangered by global change are crucial cases for understanding range dynamics and its interface with conservation. In view of climate change and their sensitivity, Alpine insects should modify their distribution by reducing ranges, while being unable of sufficient displacements and mostly moving uphill. To test these hypotheses, we targeted four threatened, high-altitude bumblebees differing in subgenera and elevation ranges, and covering the main central and south European mountains. We performed species distribution models including climate and habitat, and we described elevation uphill and the year of change with broken-line regressions. Results indicate that climate change will cause severe future range contractions across large areas, more in the Apennines (80% - 85% ca) than the Alps and Pyrenees (24 - 56% ca), with mostly concentric retreats as future extents will nearly entirely be included in the present ones. Remarkably, since the ‘80s elevation uplift has started by about 325 - 535 m, a period coinciding with the beginning of the main warming, and will continue. The size and distribution of climate refugia will challenge conservation: they will be small and context specific (2-60% of current areas), but while in the Apennines and Pyrenees they will be nearly entirely within Protected Areas, only a third will be so for the Alps. Such impressive distribution changes demonstrates that cold-adapted bumblebees can accurately track climate change and be precise sentinels of it, and these results link with the investigated species being specialists with specific habitat requirements of temperature and glacier presence. Overall, the distribution of cold specialist bumblebees driven by climate change demonstrates that conservation should act upon the dynamic realities of species ranges because their range reduction, the impossibility of finding new areas and the movement uphill emerge as consistent patterns.
The effect of climate change on the ecological niche of species represents one of the main threats in maintaining processes and functions in mountain ecosystems. However, these links have rarely been assessed due to the lack of application of ecological niche models at the species assemblage level. Therefore, in this study we integrated species ecological niche modeling techniques to predict assemblage changes in tropical montane systems. We estimate species richness and functional diversity for 2040 and 2060, based on the modeled niche of 39 native tree-shrub-herbaceous species of the montane of Mexico, using a model selection protocol for Maxent and Minimal Volume Ellipsoid (MVE) models in which we selected models based on the statistical significance of the partial ROC test, low omission rates, values of the area under the curve, and the Akaike Information Criterion. We project functional diversity, considering nine functional traits related to primary productivity, rate of decomposition, and natural regeneration. Our results show a high loss rate of species richness and functional diversity at low elevations (1500-2800 m a.s.l.). At high altitudes (2800-3500 m a.s.l.), we find a greater richness of species, without increases in functional diversity. We find that tree species are more likely to maintain their current geographic distribution ranges, while herbaceous species show a large loss of species richness at low and mid-elevations. Therefore, we provide evidence that the effects of climate change will promote imbalances in species assemblage and probably cause a loss of processes and functions, such as soil decomposition and soil organic matter, mainly in low-elevation areas.

Xugang Wang

and 2 more

To save the communication bandwidth and the missile-borne computing resources, a distributed cooperative guidance law based on the event-triggered mechanism is proposed, which enables the missiles with large differences in spatial location and velocity to achieve simultaneous attacks with only a few dozen information exchanges. The guidance process is divided into two stages. The first stage is the cooperative guidance stage, where missiles achieve consensus of the time-to-go estimates through information exchange. In this stage, each missile is designed with an event-triggered function based on its own state error, and the missile only updates and transmits its information in the communication network when the error meets the set threshold, effectively reducing the occupancy rate of missile-borne resources during the cooperation process. The second stage is the independent guidance stage, where missiles can hit the target simultaneously while keeping the communication network silent. This is achieved by ensuring that the time-to-go estimates of missiles can represent the real time-to-go after achieving consensus. By the design of the two-stage guidance law and the replacement of the event-triggered function, the cooperative guidance system can be ensured to remain stable in scenarios where the leader missile is present and destroyed, and exclude Zeno behavior. The stability of the cooperative guidance law is rigorously proved by algebraic graph theory, matrix theory, and the Lyapunov method. Finally, The numerical simulation results demonstrate the validity of the algorithm and the correctness of the stability analysis.

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Gizem Koken

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Background: Food-induced immediate response of the esophagus (FIRE) is a new phenomenon that has been described in eosinophilic esophagitis (EoE) patients. It is suspected when unpleasant symptoms occur suddenly on contact of the triggering food with the esophageal surface and recur with repeated exposures. It can often be mistaken for pollen-food allergy syndrome (PFAS) and solid food dysphagia. Data on FIRE is limited to one survey study and case reports, and there are no screening studies conducted on either adults or children with EoE. In this study, we aimed to screen children aged ≥7 years old with EoE for FIRE. Methods: Demographic data were collected from medical records. A questionnaire about FIRE was applied to all participants. Skin prick tests (SPTs) were done on suspected patients to identify the triggering foods. FIRE is defined as suitable clinical symptoms with suspected food allergen exposure. Results: Seventy-eight patients (74.4% male, median age: 13.5 years) were included. Unpleasant and recurrent symptoms distinct from dysphagia with specific foods were reported in %16.7 of the patients, all of whom had concomitant allergic rhinitis (AR). The symptoms described by almost all patients were oropharyngeal itching and tingling (PFAS: 15.3%) excluding only one patient reporting retrosternal narrowing and pressure after specific food consumption (FIRE: 1.2%). Conclusions: Although definitive conclusions regarding the true prevalence of FIRE cannot be made, it does not seem to be common as PFAS. However, it deserves questioning particularly in the presence of concurrent AR and/or PFAS in children with EoE.

Shen Shen

and 3 more

Optimizing the spatial configuration of diverse best management practices (BMPs) can provide valuable decision-making support for comprehensive watershed management. Most existing methods focus on selecting BMP types and locations but neglect their implementation time or order in management scenarios, which are often investment-restricted. This study proposes a new simulation-optimization framework for determining the implementation plan of BMPs by using the net present value to calculate the economic costs of BMP scenarios and the time-varying effectiveness of BMPs to evaluate the environmental effectiveness of BMP scenarios. The proposed framework was implemented based on a Spatially Explicit Integrated Modeling System and demonstrated in an agricultural watershed case study. This case study optimized the implementation time of four erosion control BMPs in a specific spatial configuration scenario under a 5-year stepwise investment process. The proposed method could effectively provide more feasible BMP scenarios with a lower overall investment burden with only a slight loss of environmental effectiveness. Time-varying BMP effectiveness data should be gathered and incorporated into watershed modeling and scenario optimization to better depict the environmental improvement effects of BMPs over time. The proposed framework was sufficiently flexible to be applied to other technical implementations and extensible to more actual application cases with sufficient BMP data. Overall, this study demonstrated the basic idea of extending the spatial optimization of BMPs to a spatiotemporal level by considering stepwise investment, emphasizing the value of integrating physical geographic processes and anthropogenic influences.

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