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: [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.

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: [email protected]

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:    [email protected],  [email protected]

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.

Background: International oral health policy directions led by the World Health Organization call for the inclusion of oral health within universal health coverage. The aim of this study is to perform a budget impact analysis of a policy option for a more cost-efficient oral health workforce skill-mix (dentists and oral health therapists) to provide public oral healthcare in Victoria, Australia. Methods: Two hypothetical standard care pathways were developed. A dynamic population Markov model was generated in TreeAge software, with a time horizon of six years. Two scenarios were modelled to determine: 1) base-case scenario: the threshold the dentist workforce could reduce per year, while achieving the same service delivery outputs, and 2) alternative scenario: the potential cost-savings for utilising an optimally cost-efficient oral health workforce skill-mix. Results: The threshold analysis showed a minimum reduction of 13% of the dentist workforce being replaced with oral health therapists can occur without having any impact on the same service delivery outputs. Under the alternative scenario, the potential cost-savings would be AUD$1,425,037 (SD 58,954). Conclusions: Governments and policy-decision makers should consider strategies in training, attracting, and retaining oral health therapists to achieve an optimally cost-efficient oral health workforce skill-mix when delivering public oral healthcare.

A document by Yanjun Feng. Click on the document to view its contents.

This letter introduces an innovative approach for minimizing energy consumption in multi-UAV (Unmanned Aerial Vehicles) networks using Deep Reinforcement Learning (DRL), with a focus on optimizing the Age of Information (AoI) in disaster environments. We propose a hierarchical UAV deployment strategy that facilitates cooperative trajectory planning, ensuring timely data collection and transmission while minimizing energy consumption. By formulating the inter-UAV network path planning problem as a Markov Decision Process (MDP), we apply a Deep Q-Network (DQN) strategy to enable real-time decision-making that accounts for dynamic environmental changes, obstacles, and UAV battery constraints. Our extensive simulation results, conducted in both rural and urban scenarios, demonstrate the effectiveness of employing a memory access approach within the DQN framework, significantly reducing energy consumption up to 33.25\% in rural settings and 74.20\% in urban environments compared to non-memory approaches. By integrating AoI considerations with energy-efficient UAV control, this work offers a robust solution for maintaining fresh data in critical applications, such as disaster response, where ground-based communication infrastructures are compromised. The use of replay memory approach, particularly the online history approach, proves crucial in adapting to changing conditions and optimizing UAV operations for both data freshness and energy consumption.

A document by Sevil Gaffarzadeh rad . Click on the document to view its contents.

Background: Near-misses are errors that have the potential to cause an adverse event but fail to do so because of chance or because they are intercepted. By 2021, Sri Lanka had only established systems for maternal and blood transfusion services. Methods: A new, holistic near-miss reporting system was developed and piloted at a large tertiary hospital in 2022 to guide subsequent nationwide implementation. During the pre-interventional phase, national-level consultative meetings (n=20), key informant interviews (n=10) and focus groups (n=22) were convened with purposively selected representatives of professional colleges, academia, medical administrators, and senior staff of the participating hospital to identify existing methods of reporting near-misses. A near-miss reporting format and guidelines were designed with input from national-level consultative meetings. Training on the new system for medical and nursing officers, periodic reminders to staff, and dissemination of preventive measures for patient safety incidents were implemented as interventions. A pre-post evaluation was conducted to identify the effect of the new system, and stakeholders’ views on potential for nationwide implementation. Results: Eight near-misses were reported three months following implementation, compared to none prior to implementation. Study participants expressed satisfaction with the new system’s user-friendliness, clarity, non-punitiveness, voluntary nature, and confidentiality protection. The system was perceived to be suitable for national implementation following refinements. Conclusions: This evidence-based near-miss reporting system, combined with the complementary activities implemented in the pilot setting, should now be introduced into additional hospitals before national implementation to further enhance its design, support from stakeholders, and quality and safety impact.

Kwestia pokojowego rozstrzygania sporów między państwami ma kluczowe znaczenie w prawie międzynarodowym i porządku międzynarodowym. Jak słusznie zauważa Wojciech Stankiewicz, chęć zachowania pokoju zmusza do działań, których istotą jest ograniczenie lub rozwiązanie sporów i uniemożliwienie przekształcenia się ich w konflikt zbrojny. W podpisanej dnia 26 czerwca 1945 r. w San Francisco Karcie Narodów Zjednoczonych. znajduje się rozdział VI "Pokojowe załatwianie sporów" (Chapter on Pacific Settlement of Disputes). Zgodnie z treścią zawartego w rozdziale VI art. 33 ust. 1: "Strony w sporze, którego dalsze trwanie może narazić na niebezpieczeństwo utrzymanie międzynarodowego pokoju i bezpieczeństwa, powinny przede wszystkim dążyć do jego rozstrzygnięcia w drodze rokowań, badań, pośrednictwa, koncyliacji, arbitrażu, postępowania sądowego, odwołania się do organów lub porozumień regionalnych, albo innymi sposobami pokojowymi stosownie do swego wyboru". Art. 33 ust. 1 Karty Narodów Zjednoczonych nie wspomina na temat procedury "dobrych usług", jednak mowa jest w nim o "innych pokojowych sposobach" rozstrzygania sporów. Katalog środków regulowania sporów, który został zawarty w art. 33 Karty Narodów Zjednoczonych, jest jednak otwarty. Celem niniejszego artykułu jest przedstawienie instytucji dobrych usług oraz wskazanie przykładów zastosowania dobrych usług przez państwa w polityce zagranicznej. Poruszona kwestia będzie wymagała analizy normatywnej kluczowych przepisów prawa międzynarodowego, zawartych w dwóch konwencji haskich z 1899 r. i 1907 r., które dotyczą pokojowego załatwiania sporów międzynarodowych. W opracowaniu posłużono się głównie metodami: prawnohistoryczną i formalno-dogmatyczną. (...)

A document by Oliva Henintsoa RAKOTONIRAINY. Click on the document to view its contents.

Aim: The anti-TNF antibody Infliximab (IFX) has therapeutic efficacy in rheumatoid arthritis (RA). However, some patients do not respond. We aimed to identify factors associated with IFX exposure, of clinical response, and of the response at immunologic level. Methods: We performed a prospective observational study of repeated measures in patients with RA treated with IFX from July 2014 to August 2020 at Bellvitge University Hospital. For IFX exposure, we measured IFX trough concentrations (Cmin), and antibodies towards IFX (ATI). For the clinical response we evaluated the Disease Activity Score-28 for Rheumatoid Arthritis using erythrocyte sedimentation rate (ESR) (DAS28-ESR) and C-reactive protein (CRP) (DAS28-CRP). For the immunologic response, we determined total serum concentration of TNF, and IL-6. Finally, we performed a mixed-effects analysis to determine factors associated with IFX Cmin, clinical response and IL-6 and TNF concentrations. Results: We collected a total of 120 samples cor-responding to 22 patients. IFX Cmin were associated with ATI presence and serum IL-6. DAS28-ESR was associated with sex, ESR, CRP, and serum IL-6 influenced DAS28-ESR. Finally, IL-6 concentration was associated with ESR and CRP, and TNF concentration with CRP, IFX Cmin, and IL-6 concentration. Conclusions: IFX Cmin was highly associated with the presence of ATI. IFX Cmin significantly contributed to TNF serum concentrations in patients with undetectable ATI and IL-6 concentration, which in turn was associated with serum TNF and DAS28-ESR score. Additional population pharmacockinetic analysis with rich sampling are warranted to confirm our results.

Background: COVID-19 has imposed significant burden on healthcare systems worldwide. The need for simple, rapid, and affordable diagnostic tests to support the existing costly and demanding polymerase chain reaction (PCR) assay is very necessary. Methods: This study evaluated the performance characteristics of three (3) COVID-19 rapid antigen test kits: DG Rapid, SD Rapid and SS Rapid. They were compared with the gold standard real-time reverse transcriptase- PCR (rRT-PCR) for the detection of SARS-CoV-2 nucleocapsid antigen in 75 archived samples. Results: Of the 75 samples tested, 38 (50.7%) were positive and 37 (49.3%) were negative for SARS-CoV-2 RNA by rRT-PCR assay. No false positive was recorded. The DG Rapid kit detected 30 (78.9%) true positives and 8 (21.1%) false negatives. SD Rapid kit detected 28 (73.7%) true positives and 10 (26.3%) false negatives, while the SS Rapid kit detected 19 (50.0%) true positives and 19 (50.0%) false negatives. Specificity of each test kit was 100% (CI 95%), but the sensitivity of the DG Rapid, SD Rapid, and SS Rapid kits was 79%, 74%, and 50% (CI 95%), respectively. Higher sensitivities among samples with Ct values <29.99 were recorded for each kit. Also, the DG Rapid kit demonstrated 79% excellent agreement with rRT-PCR, while the SD Rapid and SS Rapid kits demonstrated good agreement with rRT-PCR with 73% and 50% Cohen’s kappa values, respectively. Conclusion: The study suggests that DG Rapid and SD Rapid kits are reliable alternatives to rRT-PCR for the detection of SARS-CoV-2 infection, especially in resource-limited settings like Ghana.

A document by Miles Weinberger. Click on the document to view its contents.

Video human action recognition is an important academic issue, and due to the challenges involved in the problem, such as complex scenes, large changes in spatial scale, and irregular deformation of the identified targets, the algorithm generally has some shortcomings such as large parameter quantities and high computational costs. This paper proposes a new computing framework based on lightweight deep learning models, using time-domain Fourier transform to generate motion salience maps to highlight human motion areas in feature extraction in which video intrasegment and inter-segment Feature differences at different time scales are used to obtain action information at different time granularity, to conduct more accurate action model of the human action with varying spatio-temporal scales. Additionally, an action excitation method based on the deformable convolution is proposed to solve problems of irregular deformation, spatial multi-scale changes, and the loss of underlying information as the network depth increases. Data experiments are proposed to verify the effectiveness of the proposed algorithm in terms of computational efficiency and accuracy.

Peach Leaf Curl Disease, caused by the fungus Taphrina deformans, is characterized by reddish hypertrophic and hyperplasic leaf areas. To comprehend the biochemical imbalances caused by the disease an integrated approach including metabolomics, lipidomics, proteomics and complementary biochemical techniques was undertaken. Symptomatic and asymptomatic areas were dissected from leaves with increasing extension of the disease. A differential metabolic behaviour was identified in symptomatic areas with respect to either asymptomatic areas or healthy leaves. Symptomatic areas showed an altered chloroplastic functioning and composition which includes decrease in the photosynthetic machinery, alteration in plastidic lipids, and decreased starch, carotenoid and chlorophyll biosynthesis. In symptomatic areas, decreases in chloroplast redox-homeostasis proteins and in triacylglycerols double bond index were observed. Proteomic data revealed an up-regulation of phenylpropanoid and mevalonate pathways and down-regulation of the plastidic methylerythritol phosphate route. Amino acid pools were affected, with up-regulation of proteins involved in asparagine synthesis. Curled areas exhibited a metabolic shift towards functioning as a sink tissue importing sugars and producing energy through fermentation and respiration and reductive power via the pentose phosphate route. As the disease progresses, reduced asymptomatic areas and healthy leaves diminishes photosynthates production thereby limiting fruit production and ultimately tree survival.