Discover and publish cutting edge, open research.

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.

Scene flow tracks the three-dimensional (3D) motion of each point in adjacent point clouds. It provides fundamental 3D motion perception for autonomous driving and server robot. Although the Red Green Blue Depth (RGBD) camera or Light Detection and Ranging (LiDAR) capture discrete 3D points in space, the objects and motions usually are continuous in the macro world. That is, the objects keep themselves consistent as they flow from the current frame to the next frame. Based on this insight, the Generative Adversarial Networks (GAN) is utilized to self-learn 3D scene flow with no need for ground truth. The fake point cloud of the second frame is synthesized from the predicted scene flow and the point cloud of the first frame. The adversarial training of the generator and discriminator is realized through synthesizing indistinguishable fake point cloud and discriminating the real point cloud and the synthesized fake point cloud. The experiments on Karlsruhe Institute of Technology and Toyota Technological Institute (KITTI) scene flow dataset show that our method realizes promising results without ground truth. Just as human, the proposed method can identify the similar local structures of two adjacent frames even without knowing the ground truth scene flow. Then, the local correspondence can be correctly estimated, and further the scene flow is correctly estimated.   Corresponding author(s) Email: wanghesheng@sjtu.edu.cn

Leukocyte differential test is a widely performed clinical procedure for screening infectious diseases. Existing hematology analyzers require labor-intensive work and a panel of expensive reagents. Here we report an artificial-intelligence enabled reagent-free imaging hematology analyzer (AIRFIHA) modality that can accurately classify subpopulations of leukocytes with minimal sample preparation. AIRFIHA is realized through training a two-step residual neural network using label-free images of isolated leukocytes acquired from a custom-built quantitative phase microscope. By leveraging the rich information contained in quantitative phase images, we not only achieved high accuracy in differentiating B and T lymphocytes, but also classified CD4 and CD8 cells, therefore outperforming the classification accuracy of most current hematology analyzers. We validated the performance of AIRFIHA in a randomly selected test set and cross-validated it across all blood donors. Owing to its easy operation, low cost, and accurate discerning capability of complex leukocyte subpopulations, we envision AIRFIHA is clinically translatable and can also be deployed in resource-limited settings, e.g., during pandemic situations for the rapid screening of infectious diseases.  Corresponding author(s) Email:    rjzhou@cuhk.edu.hk,  rishikesh.pandey@uconn.edu

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.

Cannabis sativa is an extraordinarily versatile species. Hemp and its cousin marijuana, both C. sativa, have been used for millennia as a source of fibre, oil and for medicinal, spiritual and recreational purposes. Because the consumption of Cannabis can have psychoactive effects, the plant has been widely banned throughout the last century. In the past decade, evidence of its medicinal properties did lead to the relaxation of legislation in many countries around the world. Consequently, the genetics and development of Cannabis as well as Cannabis-derived products are the subject of renewed attention.Here, we review the biology of C. sativa, including recent insights from taxonomy, morphology and genomics, with an emphasis on the genetics of cannabinoid synthesis. Because the female Cannabis flower is of special interest as the site of cannabinoid synthesis, we explore flower development, flowering time well as the species’ unique sex determination system in detail. Furthermore, we outline the tremendous medicinal, engineering, and environmental opportunities that Cannabis bears. Together, the picture emerges that our understanding of Cannabis biology currently progresses at an unusual speed. A future challenge will be to preserve the multi-purpose nature of Cannabis, and to harness its medicinal properties and sustainability advantages simultaneously.

Quantum chemistry must evolve if it wants to fully leverage the benefits of the internet age, where the world wide web offers a vast tapestry of tools that enable users to communicate and interact with complex data at the speed and convenience of a button press. The Open Chemistry project has developed an open source framework that offers an end-to-end solution for producing, sharing, and visualizing quantum chemical data interactively on the web using an array of modern tools and approaches. These tools build on some of the best open source community projects such as Jupyter for interactive online notebooks, coupled with 3D accelerated visualization, state-of-the-art computational chemistry codes including NWChem and Psi4 and emerging machine learning and data mining tools such as ChemML and ANI. They offer flexible formats to import and export data, along with approaches to compare computational and experimental data.

This paper responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on masks for the lay public in the Covid-19 pandemic. I address their charges that my co-authors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms. But before that, I remind Martin et al that the evidence on mask wearing goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly-framed objections. I challenge my critics’ apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and engage, scientifically and morally, with the dreadful tragedy that is unfolding across the world.

This Supporting information includes interactive plots, videos, and data captured while performing evaluation and validation experiments for our paper. 

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.  

Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield across global regions is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control and pollination services in adjacent crops using a global dataset of 529 sites. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimize floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.

Researchers' ability to accurately screen fossil and subfossil specimens for preservation of DNA and protein sequences remains limited. Thermal exposure and geologic age are usable proxies for sequence preservation on a broad scale but are of nominal use for specimens of similar depositional environments. Cell and tissue biomolecular histology is thus proposed as a novel proxy for determining sequence preservation potential of ancient specimens with improved accuracy. Biomolecular histology as a proxy is hypothesized to elucidate why fossils/subfossils of some depositional environments preserve sequences while others do not and to facilitate selection of ancient specimens for use in molecular studies.

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.

Microorganisms are implicated in the irreversible degradation that usually occurs during the distribution and storage of food items. This action proceeds as biological and/or chemical reactions in foods, handling wares, and food processing facilities, and are also dependent on other several environmental factors. This review discusses the main mechanisms involved in the loss of food quality for most important food items, including the growth and associated metabolism of microorganisms resulting in the possible changes, formation of toxic compounds with adverse biological effects, and the subsequent counteractive effects of antibacterial elements used in food handling (with emphasis on copper). Meanwhile, as food spoilage poses a huge economic burden worldwide, evidence shows that the knowledge of spoilage mechanisms and food interactions with microorganisms is still limited, and in effect, perspectives and outlooks are presented as guides for the future design of wares for food handling applications.

1. While territoriality is one of the key mechanisms influencing carnivore space use, most studies quantify resource selection and movement in the absence of conspecific influence or territorial structure without inference on resource selection processes. 2. Our analysis incorporated intra-specific competition in a resource selection framework, via territorial data of conspecifics, to investigate mechanisms of territoriality and to better understand the role of neighboring packs on African wild dog habitat selection. We fit integrated step selection functions to 3-hour GPS data from 12 collared wild dog packs in the Okavango Delta, and estimated selection coefficients using a conditional Poisson likelihood with random effects. 3. Packs selected for the outline of their neighbors’ 30-day boundary (defined as their 90% kernel density estimate), and for the outline of their own 90-day core (defined as their 50% kernel density estimate). Neighbors’ 30-day boundary had a greater influence on resource selection than any habitat feature. Habitat selection differed when they were within versus beyond their neighbors’ 30-day boundary. 4. Pack size, pack age, pup presence, and seasonality all mediated how packs responded to neighbors, and seasonal dynamics altered the strength of residency. While newly-formed packs and packs with pups avoided their neighbors’ boundary, older packs and those without pups selected for it. Packs also selected for the boundary of larger neighboring packs more strongly than that of smaller ones. 5. Social structure within packs has implications for how they interact with conspecifics, and therefore how they are distributed across the landscape. Future research should continue to investigate how territorial processes are mediated by social dynamics and, in turn, how territorial structure mediates resource selection and movement. These results could inform the development of a human-wildlife conflict (HWC) mitigation tool by co-opting the mechanisms of conspecific interactions to manage space use of endangered carnivores.

Goals This multicenter, retrospective research aims to compare effectiveness and tolerability of paclitaxel-based chemotherapy combined with immune checkpoint inhibitors (ICIs) versus chemotherapy alone as a first-line treatment of HER2-negative AGC in a real-world setting. Background Platinum-based chemotherapy combined with ICIs is now becoming the standard first-line therapy of HER2-negative AGC. In China, paclitaxel has shown good efficacy and tolerability in AGC as an alternative for first-line therapy. Combining ICIs with paclitaxel-based chemotherapy may lead to improved tumor immune microenvironment, but evidence in paclitaxel combing with ICIs as first-line regimen is lacking. Methods 86 patients with HER2-negative AGC were enrolled from 2017 to 2022. Among them, 57 patients received paclitaxel-based chemotherapy plus ICIs, and 29 patients received paclitaxel-based chemotherapy alone. We compared the efficacy and incidence of adverse events between the two therapy options. Results Significant improvements in median PFS (8.77 versus 7.47 months; P=0.048) and median OS (15.70 versus 14.33 months; P=0.048) were observed in the ICIs combined with paclitaxel-based chemotherapy group. Meanwhile, the ICIs plus chemotherapy group demonstrated significantly improved ORR (50.9% vs. 27.6%; P=0.039) and DCR (98.3% vs. 82.8%; P=0.015), and the side effects were tolerable. Conclusion In summary, for HER2-negative AGC, ICIs plus paclitaxel-based chemotherapy is effective with mild toxicities, which should be considered as an alternative first-line therapy regimen.

The means of tunnel mathematics (the theory of functions of spatial complex variable) allow to find an analytical solution for problem of supersonic flow around a cone in the area of boundary layer and beyond. The peculiar feature of Navier-Stokes equations is that they allow to determine analytical velocity fields of fluids only for small number of simple problems. Of course, the problem of supersonic motion of fluid around a cone is not included in this number. Tunnel mathematics is a method for finding analytical vector velocity fields for steady flows of fluids with axial symmetry. The Navier-Stokes equations themselves are then used to determine pressure and temperature distributions. The main theorem of tunnel mathematics allows to find these distributions for planes z = const (it is similar to the constructing of slices of brain at MRI procedure). Further, collecting these “slices”, we can obtain full space distributions of pressure and temperature around a supersonic cone. At this stage of investigations, the conclusions obtained by means tunnel mathematics make it possible to qualitatively judge the thickness of boundary layer on the cone surface, the shape of the shock wave and weather the shock wave intersects the boundary layer or not. First of all, we focused on ensuring that resulting solutions corresponded to the physical pattern of phenomena. No doubt, solutions obtained by means tunnel mathematics must be confirmed experimentally.

Transistor operation beyond cutoff frequency as THz signal rectifiers has attracted increasing attention, lately. As a result, further development of different models has been carried out of the rectification and detection of this THz signal within different transistor structures. The common theory for THz detection by FETs is based on the well-known plasma wave model. However, recently reported THz rectification in HBT devices challenged this plasma wave model, as it may not apply to the THz detection and rectification within HBTs. We propose a simple nonlinear analytical model for describing the induced THz rectified signals in HBTs. This nonlinear analytical model is not only applicable to HBTs but also to FETs. Our proposed model is primarily based on the Taylor series expansion of the device's multivariable, nonlinear static I-V characteristics function. We validate our proposed analytical model by performing TCAD simulations for a typical SiGe HBT structure for both unbiased and biased collector operation modes. The results of the simulations demonstrate good agreement with the suggested nonlinear analytical model. Furthermore, we present a parametric study to investigate the contribution of effective device parameters such as base length, base width, base doping, emitter doping, and collector doping on the behavior of the HBT as a THz rectifier. The findings of this study shed light on the effects of these parameters and their role in shaping the performance of the HBT as a THz rectifier.

Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for pediatric patients with relapsed or refractory B cell acute lymphoblastic leukemia (R/R B ALL). Cytokine release syndrome (CRS) is a common toxicity after CAR T cell therapy and fever is often the first symptom. Differentiating CRS from infection after CAR T cell therapy can be challenging. Plasma microbial cell free DNA (mcfDNA) is a novel diagnostic tool which allows for qualitative and quantitative assessment of over 1,000 organisms. This pilot study sought to characterize mcfDNA results in pediatric patients with R/R B ALL in the first two months after CAR T cell therapy.

This paper tackles worldwide road-safety and traffic-management issues by implementing vehicle speed detection and license plate identification technologies. A holistic method to improve road-safety and traffic control addresses limited training data issues. The study stresses the necessity for an efficient and reliable vehicle recognition, license plate identification, and character segmentation system for precise speed detection. A three-class Vehicle Detection model and customized models for Numberplate detection, Character-segmentation, and Character-Detection are presented to suit this need. Creating complete training and testing datasets requires thorough data preparation, hand clipping, and labeling. Data augmentation separates validation and testing subsets while expanding the dataset. A robust and automatic system for real-time vehicle speed detection and license plate identification is the major contribution of this research. The suggested system uses advanced deep learning to monitor and regulate traffic efficiently, reducing manual intervention and improving road-safety. Experimental findings reveal that the Vehicle Detection model can recognize automobiles and the specialized models can detect license plates, segment characters, and detect characters. The output of one model feeds into the input of another on a distributed system, thus these four models can operate simultaneously. These results demonstrate the system's ability to improve road-safety and urban traffic management.

Long-term survival after reduced-dose radiotherapy in pediatric nasopharyngeal carcinomaWen Shen Looi, MBBS, FRCR, FAMS1, Ah Moy Tan, MBBS2, Shui Yen Soh, MBBS2, Yoke Lim Soong, MBBS1, Ru Xin Wong, MBBS11Division of Radiation OncologyNational Cancer Centre Singapore2Haematology/Oncology ServiceKK Women’s and Children’s Hospital

IntroductionInternational continence society defined mixed urinary incontinence (MUI) as “complaint of involuntary loss of urine associated with urgency and also with effort or physical exertion or on sneezing or coughing”., which include both urgency urinary incontinence (UUI) and stress urinary incontinence (SUI) complaints. Urinary incontinence affects social behaviors, financial burden such as using class of drugs, rehabilitation floor muscles, and psychological suffering such as dissatisfaction in sexual activity. Diagnosis of urinary incontinence is based on history, physical examinations and supplemental evaluations like dye test, cystoscopy, urodynamic study, urine analysis, urine culture, and imaging technics. (1)At the first, conservative treatments are performed for patient such as biofeedback, pelvic floor muscle exercise, electrical stimulation and drug treatment. In the second step of treatment, surgery is considered. The surgery is usually used to address the failure of normal anatomic support of the bladder neck and proximal urethra, and intrinsic sphincter deficiency, meanwhile its implementation should be approached with caution for carefully. In some cases, surgery intervention also failed and other novel interventions should be considered. (2)Platelet rich fibrin glue, stem cells, butolonium toxins and TVT separately applied for treatment of patients, but this is the first time that these mixed modalities were used for the treatment of mixed urinary incontinence which did not respond to pharmaceutical and surgical treatment.

Hepatocellular carcinoma (HCC) represents a significant global cause of cancer-related mortality. Hepatitis B virus (HBV)infection is a major etiologic factor leading to HCC. While noteworthy progress has been made in managing HBV replication, achieving a cure for HBV-related HCC (HBV-HCC) remains challenging, and the overall survival outcome for HCC remains suboptimal. HBV persistence is attributed to a myriad of mechanisms, encompassing both innate and adaptive immune responses. Regulatory T cells(Tregs) are pivotal in upholding immune tolerance and modulating excessive immune activation. During HBV infection, Tregs mediate specific T cell suppression, thereby contributing to both persistent infection and the mitigation of liver inflammatory responses. Studies have demonstrated an augmented expression of circulating and intrahepatic Tregs in HBV-HCC, which correlates with impaired CD8 + T cells function. Consequently, Tregs play a dual role in the context of HBV infection and the progression of HBV-HCC. In this comprehensive review, we discuss pertinent studies concerning Tregs in HBV infection, HBV-related cirrhosis and HCC. Furthermore, we provide valuable treatment strategies pertinent to liver cancer management.

Objective: Diagnosis of Aortic arch (AoA) anatomy is critical for planning cardiac surgery/intervention and in diagnosing associated congenital heart defects. AoA sidedness is traditionally diagnosed with echocardiography as being contralateral to the direction of the first brachiocephalic artery in suprasternal view, but this method can be challenged by numerous anatomic variants and clinical conditions. The objective of this study was to assess feasibility of trachea visualization with echocardiography in pediatric patients, and using this landmark to identify AoA sidedness and potential for double aortic arch (DAA). Methods: A prospective study was performed on patients <18 years old who were undergoing Chest CT/MRI to serve as gold standard for confirming AoA anatomy. A right-to-left echocardiographic sagittal sweep was performed from the suprasternal notch and used to categorize 1) Left AoA = right SVC-trachea-AoA, 2) Right AoA= SVC-AoA-trachea, 3) DAA = SVC-AoA-trachea-AoA. The proportion of successful sweeps and diagnostic accuracy were calculated. Results: 100 consecutive patients were scanned (44% female; median age of 8.8 yr, range 2d–17.9 yr; median BSA 1.14 m 2, range 0.2–2.7; right AOA in 4%). Diagnosis of AoA sidedness was possible in 97% (95% CI: 94–100%, p < 0.01) and correct in 100% when the trachea was seen. Conclusion: Tracheal imaging with echo is reliable, easy, and reproducible method in patients of various sizes and levels of acuity to define AoA sidedness.

Micro-Doppler (mD) characteristics of the cone space targets (CSTs) have attracted great attention due to the potential for discrimination between targets and decoys. However, current investigations mainly focus on CSTs with perfectly smooth surfaces. This Letter reveals that mD characteristics of CSTs are associated with surface roughness, and the generated data set used for CST recognition should contain rough target samples. Finally, simulation results via the electromagnetic computation verify the correctness of the analysis.