Vaccines for COVID-19

Since the emergence of COVID-19, caused by the SARS-CoV-2 virus, at the end of 2019 there has been an explosion of vaccine development. By the 1st September 2020, a staggering number of vaccines (over 200) had started pre-clinical development of which 39 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socialising. Importantly, to effectively control the COVID-19 pandemic, production needs to be scaled up from a small number of pre-clinical doses to enough filled vials to immunise the world's population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS-CoV-2 and the potential for vaccine-induced immunopathology. It describes the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising pre-clinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began, we are at a point where pre-clinical and early clinical data is being generated for the vaccines, an overview of this important area will help our understanding of the next phases

Higgs boson enhancement effects on squark-pair production at the LHC

We study the Higgs boson effects on third-generation squark-pair production in proton-proton collision at the CERN Large Hadron Collider (LHC), including \Stop \Stop^*, \Stop\Sbot^*, and \Sbot \Sbot^*. We found that substantial enhancement can be obtained through s-channel exchanges of Higgs bosons at large $\tan\beta$, at which the enhancement mainly comes from $b\bar b$, $b\bar c$, and $c\bar b$ initial states. We compute the complete set of electroweak (EW) contributions to all production channels. This completes previous computations in the literature. We found that the EW contributions can be significant and can reach up to 25% in more general scenarios and at the resonance of the heavy Higgs boson. The size of Higgs enhancement is comparable or even higher than the PDF uncertainties and so must be included in any reliable analysis. A full analytical computation of all the EW contributions is presented.Comment: 23 pages, 7 figures, 1 tabl

Arduous implementation: Does the Normalisation Process Model explain why it's so difficult to embed decision support technologies for patients in routine clinical practice

Background: decision support technologies (DSTs, also known as decision aids) help patients and professionals take part in collaborative decision-making processes. Trials have shown favorable impacts on patient knowledge, satisfaction, decisional conflict and confidence. However, they have not become routinely embedded in health care settings. Few studies have approached this issue using a theoretical framework. We explained problems of implementing DSTs using the Normalization Process Model, a conceptual model that focuses attention on how complex interventions become routinely embedded in practice.Methods: the Normalization Process Model was used as the basis of conceptual analysis of the outcomes of previous primary research and reviews. Using a virtual working environment we applied the model and its main concepts to examine: the 'workability' of DSTs in professional-patient interactions; how DSTs affect knowledge relations between their users; how DSTs impact on users' skills and performance; and the impact of DSTs on the allocation of organizational resources.Results: conceptual analysis using the Normalization Process Model provided insight on implementation problems for DSTs in routine settings. Current research focuses mainly on the interactional workability of these technologies, but factors related to divisions of labor and health care, and the organizational contexts in which DSTs are used, are poorly described and understood.Conclusion: the model successfully provided a framework for helping to identify factors that promote and inhibit the implementation of DSTs in healthcare and gave us insights into factors influencing the introduction of new technologies into contexts where negotiations are characterized by asymmetries of power and knowledge. Future research and development on the deployment of DSTs needs to take a more holistic approach and give emphasis to the structural conditions and social norms in which these technologies are enacte

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations

Confucius computer: a philosophical digital agent for intergenerational philosophical play

Confucianism is commonly defined as “... a system of philosophical, ethical and political thought based on the teachings of Confucius,” which originated through the teachings of Confucius during the sixth-century BCE. It is a way of life or a philosophy of human nature that considers human relationships as the foundation of the society. Confucius teachings had highly influenced the development of several cultures in Asia, making Confucianism an intangible cultural heritage. In this paper, we are re-acquainting users with an intangible heritage that is part of their everyday, by developing a system that permits experiencing Confucius teachings virtually and interactively. The system can measure philosophical intent of the human and generate meaningful philosophical answers. It is also aimed for intergenerational sharing of Confucius heritage through a simple interactive process with the virtual sage making the experience enjoyable and entertaining. Previous research in natural language processing (NLP) mainly focused on the understanding and delivering of human natural language accurately. In this research, we explored how to apply NLP to model the knowledge and teachings of Confucius, through the natural conversation between human and computer. This virtual Confucius, a chat agent that generates outputs based on Confucius teachings, using a series of algorithms and techniques to improve the matching accuracy between user input and computer output, introduces a novel way of interacting with intangible cultures. Our user evaluation results revealed that there is a positive correlation between relevance and enjoyment, finding their experiences interacting with virtual Confucius very encouraging. Adults who participated in experiencing the virtual Confucius together with their children believed that this system has the potential to improve intergenerational interactions through shared play

Counting and effective rigidity in algebra and geometry

The purpose of this article is to produce effective versions of some rigidity results in algebra and geometry. On the geometric side, we focus on the spectrum of primitive geodesic lengths (resp., complex lengths) for arithmetic hyperbolic 2-manifolds (resp., 3-manifolds). By work of Reid, this spectrum determines the commensurability class of the 2-manifold (resp., 3-manifold). We establish effective versions of these rigidity results by ensuring that, for two incommensurable arithmetic manifolds of bounded volume, the length sets (resp., the complex length sets) must disagree for a length that can be explicitly bounded as a function of volume. We also prove an effective version of a similar rigidity result established by the second author with Reid on a surface analog of the length spectrum for hyperbolic 3-manifolds. These effective results have corresponding algebraic analogs involving maximal subfields and quaternion subalgebras of quaternion algebras. To prove these effective rigidity results, we establish results on the asymptotic behavior of certain algebraic and geometric counting functions which are of independent interest.Comment: v.2, 39 pages. To appear in Invent. Mat

Flavor Physics in an SO(10) Grand Unified Model

In supersymmetric grand-unified models, the lepton mixing matrix can possibly affect flavor-changing transitions in the quark sector. We present a detailed analysis of a model proposed by Chang, Masiero and Murayama, in which the near-maximal atmospheric neutrino mixing angle governs large new b -> s transitions. Relating the supersymmetric low-energy parameters to seven new parameters of this SO(10) GUT model, we perform a correlated study of several flavor-changing neutral current (FCNC) processes. We find the current bound on B(tau -> mu gamma) more constraining than B(B -> X_s gamma). The LEP limit on the lightest Higgs boson mass implies an important lower bound on tan beta, which in turn limits the size of the new FCNC transitions. Remarkably, the combined analysis does not rule out large effects in B_s-B_s-bar mixing and we can easily accomodate the large CP phase in the B_s-B_s-bar system which has recently been inferred from a global analysis of CDF and DO data. The model predicts a particle spectrum which is different from the popular Constrained Minimal Supersymmetric Standard Model (CMSSM). B(tau -> mu gamma) enforces heavy masses, typically above 1 TeV, for the sfermions of the degenerate first two generations. However, the ratio of the third-generation and first-generation sfermion masses is smaller than in the CMSSM and a (dominantly right-handed) stop with mass below 500 GeV is possible.Comment: 44 pages, 5 figures. Footnote and references added, minor changes, Fig. 2 corrected; journal versio

Amygdala Engagement in Response to Subthreshold Presentations of Anxious Face Stimuli in Adults with Autism Spectrum Disorders: Preliminary Insights

Current theoretical models of autism spectrum disorders (ASD) have proposed that impairments in the processing of social/emotional information may be linked to amygdala dysfunction. However, the extent to which amygdala functions are compromised in ASD has become a topic of debate in recent years. In a jittered functional magnetic resonance imaging study, sub-threshold presentations of anxious faces permitted an examination of amygdala recruitment in 12 high functioning adult males with ASD and 12 matched controls. We found heightened neural activation of the amygdala in both high functioning adults with ASD and matched controls. Neither the intensity nor the time-course of amygdala activation differed between the groups. However, the adults with ASD showed significantly lower levels of fusiform activation during the trials compared to controls. Our findings suggest that in ASD, the transmission of socially salient information along sub-cortical pathways is intact: and yet the signaling of this information to structures downstream may be impoverished, and the pathways that facilitate subsequent processing deficient

An Alternative Yukawa Unified SUSY Scenario

Supersymmetric SO(10) Grand Unified Theories with Yukawa unification represent an appealing possibility for physics beyond the Standard Model. However Yukawa unification is made difficult by large threshold corrections to the bottom mass. Generally one is led to consider models where the sfermion masses are large in order to suppress these corrections. Here we present another possibility, in which the top and bottom GUT scale Yukawa couplings are equal to a component of the charged lepton Yukawa matrix at the GUT scale in a basis where this matrix is not diagonal. Physically, this weak eigenstate Yukawa unification scenario corresponds to the case where the charged leptons that are in the 16 of SO(10) containing the top and bottom quarks mix with their counterparts in another SO(10) multiplet. Diagonalizing the resulting Yukawa matrix introduces mixings in the neutrino sector. Specifically we find that for a large region of parameter space with relatively light sparticles, and which has not been ruled out by current LHC or other data, the mixing induced in the neutrino sector is such that $sin^2 2\Theta_{23} \approx 1$, in agreement with data. The phenomenological implications are analyzed in some detail.Comment: 32 pages, 22 Figure