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2.
J Microsc ; 294(3): 397-410, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38691400

RESUMO

In the dynamic landscape of scientific research, imaging core facilities are vital hubs propelling collaboration and innovation at the technology development and dissemination frontier. Here, we present a collaborative effort led by Global BioImaging (GBI), introducing international recommendations geared towards elevating the careers of Imaging Scientists in core facilities. Despite the critical role of Imaging Scientists in modern research ecosystems, challenges persist in recognising their value, aligning performance metrics and providing avenues for career progression and job security. The challenges encompass a mismatch between classic academic career paths and service-oriented roles, resulting in a lack of understanding regarding the value and impact of Imaging Scientists and core facilities and how to evaluate them properly. They further include challenges around sustainability, dedicated training opportunities and the recruitment and retention of talent. Structured across these interrelated sections, the recommendations within this publication aim to propose globally applicable solutions to navigate these challenges. These recommendations apply equally to colleagues working in other core facilities and research institutions through which access to technologies is facilitated and supported. This publication emphasises the pivotal role of Imaging Scientists in advancing research programs and presents a blueprint for fostering their career progression within institutions all around the world.


Assuntos
Pesquisadores , Humanos , Mobilidade Ocupacional , Pesquisa Biomédica/métodos , Escolha da Profissão
3.
Chem Soc Rev ; 53(5): 2603-2642, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38305761

RESUMO

Humans and other animals produce a diverse collection of antibodies, many of which bind to carbohydrate chains, referred to as glycans. These anti-glycan antibodies are a critical part of our immune systems' defenses. Whether induced by vaccination or natural exposure to a pathogen, anti-glycan antibodies can provide protection against infections and cancers. Alternatively, when an immune response goes awry, antibodies that recognize self-glycans can mediate autoimmune diseases. In any case, serum anti-glycan antibodies provide a rich source of information about a patient's overall health, vaccination history, and disease status. Glycan microarrays provide a high-throughput platform to rapidly interrogate serum anti-glycan antibodies and identify new biomarkers for a variety of conditions. In addition, glycan microarrays enable detailed analysis of the immune system's response to vaccines and other treatments. Herein we review applications of glycan microarray technology for serum anti-glycan antibody profiling.


Assuntos
Polissacarídeos , Vacinas , Animais , Humanos , Polissacarídeos/metabolismo , Anticorpos , Carboidratos , Análise em Microsséries
4.
ArXiv ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38351940

RESUMO

Together with the molecular knowledge of genes and proteins, biological images promise to significantly enhance the scientific understanding of complex cellular systems and to advance predictive and personalized therapeutic products for human health. For this potential to be realized, quality-assured image data must be shared among labs at a global scale to be compared, pooled, and reanalyzed, thus unleashing untold potential beyond the original purpose for which the data was generated. There are two broad sets of requirements to enable image data sharing in the life sciences. One set of requirements is articulated in the companion White Paper entitled "Enabling Global Image Data Sharing in the Life Sciences," which is published in parallel and addresses the need to build the cyberinfrastructure for sharing the digital array data (arXiv:2401.13023 [q-bio.OT], https://doi.org/10.48550/arXiv.2401.13023). In this White Paper, we detail a broad set of requirements, which involves collecting, managing, presenting, and propagating contextual information essential to assess the quality, understand the content, interpret the scientific implications, and reuse image data in the context of the experimental details. We start by providing an overview of the main lessons learned to date through international community activities, which have recently made considerable progress toward generating community standard practices for imaging Quality Control (QC) and metadata. We then provide a clear set of recommendations for amplifying this work. The driving goal is to address remaining challenges, and democratize access to common practices and tools for a spectrum of biomedical researchers, regardless of their expertise, access to resources, and geographical location.

5.
Clin Cosmet Investig Dermatol ; 16: 3091-3105, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915422

RESUMO

Background: Patient-reported outcome measures (PROMs) are needed to measure outcomes that matter to people with nail conditions, from their perspective. Objective: To design a comprehensive new PROM (NAIL-Q) to measure outcomes important in toenail and fingernail conditions. Methods: A mixed methods iterative approach was used. Phase 1 involved concept elicitation interviews that were audio-recorded, transcribed, and coded line-by-line. Concepts were developed into scales and refined through cognitive debriefing interviews with patients and expert input. Data was then collected from an international sample using a crowdsource platform. Eligible participants were aged ≥18 years with a nail condition for at least 3 months. Rasch Measurement Theory (RMT) analysis was used to examine item and scale performance. Other psychometric tests included test-retest reliability, and convergent and construct validity. Results: Phase 1 interviews involved 23 patients with 10 nail conditions and input from 11 dermatologists. The analysis led to the development of 84 items for field-testing. In Phase 2, 555 participants completed the survey. Toenail conditions (n = 441) were more common than fingernail conditions (n = 186). The RMT analysis reduced the number of items tested to 45 in 7 scales measuring nail appearance, health-related quality of life concerns, and treatment outcomes. All items had ordered thresholds and nonsignificant chi-square p values. Reliability statistics with and without extremes for the Person Separation Index were ≥0.79 and Cronbach's alpha were ≥0.83, and for intraclass correlation coefficients were ≥0.81. Construct validity was further supported in that most participants agreed that the NAIL-Q was easy to understand, asked relevant and important questions in a respectful way, and that it should be used to inform clinical care. Conclusion: The NAIL-Q is a rigorously designed and tested PROM that measures nail appearance, health-related quality of life and treatment outcomes. This PROM can be used in clinical practice to inform patient care and to include the patient perspective in research.

6.
Elife ; 122023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37995198

RESUMO

Antibodies are critical reagents to detect and characterize proteins. It is commonly understood that many commercial antibodies do not recognize their intended targets, but information on the scope of the problem remains largely anecdotal, and as such, feasibility of the goal of at least one potent and specific antibody targeting each protein in a proteome cannot be assessed. Focusing on antibodies for human proteins, we have scaled a standardized characterization approach using parental and knockout cell lines (Laflamme et al., 2019) to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins. Side-by-side comparisons of all antibodies against each target, obtained from multiple commercial partners, have demonstrated that: (i) more than 50% of all antibodies failed in one or more applications, (ii) yet, ~50-75% of the protein set was covered by at least one high-performing antibody, depending on application, suggesting that coverage of human proteins by commercial antibodies is significant; and (iii) recombinant antibodies performed better than monoclonal or polyclonal antibodies. The hundreds of underperforming antibodies identified in this study were found to have been used in a large number of published articles, which should raise alarm. Encouragingly, more than half of the underperforming commercial antibodies were reassessed by the manufacturers, and many had alterations to their recommended usage or were removed from the market. This first study helps demonstrate the scale of the antibody specificity problem but also suggests an efficient strategy toward achieving coverage of the human proteome; mine the existing commercial antibody repertoire, and use the data to focus new renewable antibody generation efforts.


Commercially produced antibodies are essential research tools. Investigators at universities and pharmaceutical companies use them to study human proteins, which carry out all the functions of the cells. Scientists usually buy antibodies from commercial manufacturers who produce more than 6 million antibody products altogether. Yet many commercial antibodies do not work as advertised. They do not recognize their intended protein target or may flag untargeted proteins. Both can skew research results and make it challenging to reproduce scientific studies, which is vital to scientific integrity. Using ineffective commercial antibodies likely wastes $1 billion in research funding each year. Large-scale validation of commercial antibodies by an independent third party could reduce the waste and misinformation associated with using ineffective commercial antibodies. Previous research testing an antibody validation pipeline showed that a commercial antibody widely used in studies to detect a protein involved in amyotrophic lateral sclerosis did not work. Meanwhile, the best-performing commercial antibodies were not used in research. Testing commercial antibodies and making the resulting data available would help scientists identify the best study tools and improve research reliability. Ayoubi et al. collaborated with antibody manufacturers and organizations that produce genetic knock-out cell lines to develop a system validating the effectiveness of commercial antibodies. In the experiments, Ayoubi et al. tested 614 commercial antibodies intended to detect 65 proteins involved in neurologic diseases. An effective antibody was available for about two thirds of the 65 proteins. Yet, hundreds of the antibodies, including many used widely in studies, were ineffective. Manufacturers removed some underperforming antibodies from the market or altered their recommended uses based on these data. Ayoubi et al. shared the resulting data on Zenodo, a publicly available preprint database. The experiments suggest that 20-30% of protein studies use ineffective antibodies, indicating a substantial need for independent assessment of commercial antibodies. Ayoubi et al. demonstrated their side-by-side antibody comparison methods were an effective and efficient way of validating commercial antibodies. Using this approach to test commercial antibodies against all human proteins would cost about $50 million. But it could save much of the $1 billion wasted each year on research involving ineffective antibodies. Independent validation of commercial antibodies could also reduce wasted efforts by scientists using ineffective antibodies and improve the reliability of research results. It would also enable faster, more reliable research that may help scientists understand diseases and develop new therapies to improve patient's lives.


Assuntos
Anticorpos , Proteoma , Humanos , Anticorpos/química
7.
J Cyst Fibros ; 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036321

RESUMO

The concomitant use of elexacaftor/tezacaftor/ivacaftor (ETI) and strong CYP3A inducers including rifampin and rifabutin is not recommended due to the risk of drug-drug interactions (DDI). This presents a significant challenge to the treatment of non-tuberculous mycobacteria precluding the first line treatment. While rifabutin induces CYP3A activity, its effect appears to be moderate compared to rifampin. In this study, we investigated three cases in which concomitant use of rifabutin and CFTR modulators (ETI or ivacaftor monotherapy) was used, and these cases suggest that addition of rifabutin did not compromise the efficacy of ETI or ivacaftor as evidenced by pulmonary function and sweat chloride testing. A full physiologically based pharmacokinetic model predicted lung concentrations of ETI upon rifabutin coadministration to exceed the half-maximal effective concentrations (EC50) determined from chloride transport in phe508del human bronchial epithelial cells. This study provides preliminary evidence in support of the use of rifabutin in patients receiving ETI.

8.
Microsc Microanal ; 29(2): 616-634, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37749742

RESUMO

This article outlines a global study conducted by the Association of Biomedical Resource Facilities (ABRF) Light Microscopy Research Group (LMRG). The results present a novel 3D tissue-like biologically relevant standard sample that is affordable and straightforward to prepare. Detailed sample preparation, instrument-specific image acquisition protocols and image analysis methods are presented and made available to the community. The standard consists of sub-resolution and large well characterized relative intensity fluorescence microspheres embedded in a 120 µm thick 3D gel with a refractive index of 1.365. The standard allows the evaluation of several properties as a function of depth. These include the following: 1) microscope resolution with automated analysis of the point-spread function (PSF), 2) automated signal-to-noise ratio analysis, 3) calibration and correction of fluorescence intensity loss, and 4) quantitative relative intensity. Results demonstrate expected refractive index mismatch dependent losses in intensity and resolution with depth, but the relative intensities of different objects at similar depths are maintained. This is a robust standard showing reproducible results across laboratories, microscope manufacturers and objective lens types (e.g., magnification, immersion medium). Thus, these tools will be valuable for the global community to benchmark fluorescence microscopes and will contribute to improved scientific rigor and reproducibility.


Assuntos
Processamento de Imagem Assistida por Computador , Reprodutibilidade dos Testes , Microscopia de Fluorescência/métodos
9.
bioRxiv ; 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37398479

RESUMO

Antibodies are critical reagents to detect and characterize proteins. It is commonly understood that many commercial antibodies do not recognize their intended targets, but information on the scope of the problem remains largely anecdotal, and as such, feasibility of the goal of at least one potent and specific antibody targeting each protein in a proteome cannot be assessed. Focusing on antibodies for human proteins, we have scaled a standardized characterization approach using parental and knockout cell lines (Laflamme et al., 2019) to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins. Side-by-side comparisons of all antibodies against each target, obtained from multiple commercial partners, demonstrates that: i) more than 50% of all antibodies failed in one or more tests, ii) yet, ~50-75% of the protein set was covered by at least one high-performing antibody, depending on application, suggesting that coverage of human proteins by commercial antibodies is significant; and iii) recombinant antibodies performed better than monoclonal or polyclonal antibodies. The hundreds of underperforming antibodies identified in this study were found to have been used in a large number of published articles, which should raise alarm. Encouragingly, more than half of the underperforming commercial antibodies were reassessed by the manufacturers, and many had alterations to their recommended usage or were removed from the market. This first such study helps demonstrate the scale of the antibody specificity problem but also suggests an efficient strategy toward achieving coverage of the human proteome; mine the existing commercial antibody repertoire, and use the data to focus new renewable antibody generation efforts.

10.
Br J Nurs ; 32(11): 522-525, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37289714

RESUMO

The World Health Organization (2019) has determined that patient safety is a global public health challenge. In UK clinical areas, policies and procedures are in place for the safe prescribing and delivery of blood and blood product transfusions, yet patient safety incidences continue. Undergraduate nurse education and training may provide the underlying knowledge to practitioners, while postgraduate standalone training sessions support skill development. However, over time, without regular experience, competence will diminish. Nursing students may have little exposure to transfusion practice and COVID-19 may have exacerbated this challenge with a reduction in placement availability. The use of simulation to support theory with follow-up and ongoing drop-in training sessions may help to inform practitioners and improve patient safety in the management and delivery of blood and blood product transfusion.


Assuntos
COVID-19 , Bacharelado em Enfermagem , Enfermeiras e Enfermeiros , Humanos , Transfusão de Sangue , Bacharelado em Enfermagem/métodos , Segurança do Paciente , Competência Clínica
11.
J Food Prot ; 86(6): 100074, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37030629

RESUMO

Globalization of the food supply chain has created conditions favorable for emergence and spread of multidrug-resistant (MDR) foodborne pathogens. In November 2021, the UK Health Security Agency detected an outbreak of 17 cases infected with the same strain of MDR extended spectrum beta-lactamase (ESBL)-producing Shigella sonnei. Phylogenetic analysis of whole-genome sequencing data revealed the outbreak was closely related to strains of S. sonnei isolated from travelers returning to the UK from Egypt. None of the outbreak cases reported travel and all 17 cases reported eating food from a restaurant/food outlet in the week prior to symptom onset, of which 11/17 (64.7%) ate at branches of the same national restaurant franchise. All 17 cases were adults and 14/17 (82.4%) were female. Ingredient-level analyses of the meals consumed by the cases identified spring onions as the common ingredient. Food chain investigations revealed that the spring onions served at the implicated restaurants could be traced back to a single Egyptian producer. The foodborne transmission of ESBL-producing bacteria is an emerging global health concern, and concerted action from all stakeholders is required to ensure an effective response to mitigate the risks to public health.


Assuntos
Disenteria Bacilar , Shigella sonnei , Adulto , Humanos , Feminino , Masculino , Cebolas , Disenteria Bacilar/epidemiologia , Disenteria Bacilar/microbiologia , Filogenia , Reino Unido , Surtos de Doenças , beta-Lactamases/genética , Antibacterianos/farmacologia
12.
Br J Nurs ; 32(7): 326-332, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37027412

RESUMO

Evidence suggests that blood transfusion errors tend to occur because of an external stimulus, limiting control for the professional administering it. Whether it be cognitive bias, human traits, organisational or human factors, errors should be prevented because they put the safety of the patient at risk from major morbidity and mortality. The authors explored the literature that looked at the blood transfusion errors that occur, suggesting interventions that may have a positive impact on patient safety. A review of the literature was undertaken using key words and limiters to focus the search. The review found that, when practitioners do not perform skills or interventions regularly, competence diminishes. Training and rolling refresher programmes appeared to improve retention and knowledge, therefore enhancing patient safety. Consequently, the impact of human factors in the healthcare setting requires more comprehensive investigation. Nurses may have the knowledge and understanding regarding blood transfusions; however, the environment in which they work could contribute to the likelihood of errors.


Assuntos
Transfusão de Sangue , Segurança do Paciente , Humanos , Atenção à Saúde
13.
Curr Opin Chem Biol ; 74: 102281, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36905763

RESUMO

Anti-glycan monoclonal antibodies have important applications in human health and basic research. Therapeutic antibodies that recognize cancer- or pathogen-associated glycans have been investigated in numerous clinical trials, resulting in two FDA-approved biopharmaceuticals. Anti-glycan antibodies are also utilized to diagnose, prognosticate, and monitor disease progression, as well as to study the biological roles and expression of glycans. High-quality anti-glycan mAbs are still in limited supply, highlighting the need for new technologies for anti-glycan antibody discovery. This review discusses anti-glycan monoclonal antibodies with applications to basic research, diagnostics, and therapeutics, focusing on recent advances in mAbs targeting cancer- and infectious disease-associated glycans.


Assuntos
Anticorpos Monoclonais , Neoplasias , Humanos , Anticorpos Monoclonais/uso terapêutico , Polissacarídeos/metabolismo
14.
Sci Rep ; 13(1): 4223, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36918704

RESUMO

In mesenchymal cell motility, several migration patterns have been observed, including directional, exploratory and stationary. Two key members of the Rho-family of GTPases, Rac and Rho, along with an adaptor protein called paxillin, have been particularly implicated in the formation of such migration patterns and in regulating adhesion dynamics. Together, they form a key regulatory network that involves the mutual inhibition exerted by Rac and Rho on each other and the promotion of Rac activation by phosphorylated paxillin. Although this interaction is sufficient in generating wave-pinning that underscores cellular polarization comprised of cellular front (high active Rac) and back (high active Rho), it remains unclear how they interact collectively to induce other modes of migration detected in Chinese hamster Ovary (CHO-K1) cells. We previously developed a six-variable (6V) reaction-diffusion model describing the interactions of these three proteins (in their active/phosphorylated and inactive/unphosphorylated forms) along with other auxiliary proteins, to decipher their role in generating wave-pinning. In this study, we explored, through computational modeling and image analysis, how differences in timescales within this molecular network can potentially produce the migration patterns in CHO-K1 cells and how switching between migration modes could occur. To do so, the 6V model was reduced to an excitable 4V spatiotemporal model possessing three different timescales. The model produced not only wave-pinning in the presence of diffusion, but also mixed-mode oscillations (MMOs) and relaxation oscillations (ROs). Implementing the model using the Cellular Potts Model (CPM) produced outcomes in which protrusions in the cell membrane changed Rac-Rho localization, resulting in membrane oscillations and fast directionality variations similar to those observed experimentally in CHO-K1 cells. The latter was assessed by comparing the migration patterns of experimental with CPM cells using four metrics: instantaneous cell speed, exponent of mean-square displacement ([Formula: see text]-value), directionality ratio and protrusion rate. Variations in migration patterns induced by mutating paxillin's serine 273 residue were also captured by the model and detected by a machine classifier, revealing that this mutation alters the dynamics of the system from MMOs to ROs or nonoscillatory behaviour through variation in the scaled concentration of an active form of an adhesion protein called p21-Activated Kinase 1 (PAK). These results thus suggest that MMOs and adhesion dynamics are the key mechanisms regulating CHO-K1 cell motility.


Assuntos
Proteínas rac de Ligação ao GTP , Proteínas rho de Ligação ao GTP , Animais , Cricetinae , Paxilina/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Células CHO , Espécies Reativas de Oxigênio/metabolismo , Cricetulus , Movimento Celular/fisiologia , Proteínas rac de Ligação ao GTP/metabolismo , Polaridade Celular
15.
Vet Rec ; 192(1): e2341, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36352759

RESUMO

BACKGROUND: Toxocarosis is a globally distributed zoonotic disease, but sources of infection are not well documented over large geographical scales. To determine levels of environmental contamination, soil from 142 parks and recreational areas across the UK and Ireland was assessed for the presence of Toxocara. METHODS: Toxocara ova (eggs) were isolated from soil samples by sieving and flotation and then enumerated. Individual eggs were isolated and imaged, and a subset was characterised by species-specific PCR and Sanger sequencing. RESULTS: Characteristic Toxocara-type eggs were found in 86.6% of parks, with an average of 2.1 eggs per 50 g of topsoil. Representative eggs were confirmed as Toxocara canis by Sanger sequencing, with many eggs containing developed larvae, hence being viable and potentially infective. Positive samples were more common, and egg density was higher, in parks with greater perceived levels of dog fouling. LIMITATIONS: Samples were collected at a single timepoint and with limited spatial mapping within parks. Further study is needed to discern spatiotemporal differences within parks and recreational areas. CONCLUSION: Toxocara is widespread in soil in public parks, indicating a need for further efforts to reduce egg shedding from pet dogs. Standardised methods and large-scale surveys are required to evaluate risk factors for egg presence and the impact of interventions.


Assuntos
Doenças do Cão , Toxocaríase , Animais , Cães , Toxocara , Solo , Irlanda/epidemiologia , Toxocaríase/epidemiologia , Reino Unido/epidemiologia , Contagem de Ovos de Parasitas/veterinária , Fezes , Doenças do Cão/epidemiologia
16.
Int J Parasitol ; 52(10): 691-703, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36113619

RESUMO

Gastrointestinal nematode (GIN) parasites in grazing cattle are a major cause of production loss and their control is increasingly difficult due to anthelmintic resistance and climate change. Rotational grazing can support control and decrease reliance on chemical intervention, but is often complex due to the need to track grazing periods and infection levels, and the effect of weather on larval availability. In this paper, a simulation model was developed to predict the availability of infective larvae of the bovine GIN, Ostertagia ostertagi, at the level of individual pastures. The model was applied within a complex rotational grazing system and successfully reproduced observed variation in larval density between fields and over time. Four groups of cattle in their second grazing season (n = 44) were followed throughout the temperate grazing season with regular assessment of GIN faecal egg counts, which were dominated by O. ostertagi, animal weight and recording of field rotations. Each group of cattle was rotationally grazed on six group-specific fields throughout the 2019 grazing season. Maps and calendars were produced to illustrate the change in pasture infectivity (density of L3 on herbage) across the 24 separate grazing fields. Simulations predicted differences in pasture contamination levels in relation to the timing of grazing and the return period. A proportion of L3 was predicted to persist on herbage over winter, declining to similar intensities across fields before the start of the following grazing season, irrespective of contamination levels in the previous year. Model predictions showed good agreement with pasture larval counts. The model also simulated differences in seasonal pasture infectivity under rotational grazing in systems that differed in temperature and rainfall profiles. Further application could support individual farm decisions on evasive grazing and refugia management, and improved regional evaluation of optimal grazing strategies for parasite control. The integration of weather and livestock movement is inherent to the model, and facilitates consideration of climate change adaptation through improved disease control.


Assuntos
Anti-Helmínticos , Doenças dos Bovinos , Helmintos , Enteropatias Parasitárias , Nematoides , Infecções por Nematoides , Bovinos , Animais , Infecções por Nematoides/epidemiologia , Infecções por Nematoides/veterinária , Infecções por Nematoides/tratamento farmacológico , Fazendas , Contagem de Ovos de Parasitas/veterinária , Doenças dos Bovinos/parasitologia , Enteropatias Parasitárias/veterinária , Anti-Helmínticos/uso terapêutico
17.
J Infect ; 85(3): 306-317, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35718205

RESUMO

OBJECTIVES: We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001. METHODS: We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017. RESULTS: Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18-55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively. CONCLUSIONS: VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , COVID-19/terapia , Vacinas contra COVID-19/efeitos adversos , Método Duplo-Cego , Humanos , Imunização Passiva , Imunogenicidade da Vacina , SARS-CoV-2 , Soroterapia para COVID-19
18.
Methods Mol Biol ; 2476: 75-93, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35635698

RESUMO

Longitudinal magnetic tweezers (L-MT) have seen wide-scale adoption as the tool of choice for stretching and twisting a single DNA molecule. They are also used to probe topological changes in DNA as a result of protein binding and enzymatic activity. However, in the longitudinal configuration, the DNA molecule is extended perpendicular to the imaging plane. As a result, it is only possible to infer biological activity from the motion of the tethered paramagnetic microsphere. Described here is a "transverse" magnetic tweezers (T-MT) geometry featuring simultaneous control of DNA extension and spatially coincident video-rate epi-fluorescence imaging. Unlike in L-MT, DNA tethers in T-MT are extended parallel to the imaging plane between two micron-sized spheres, and importantly protein targets on the DNA can be localized using fluorescent nanoparticles. The T-MT can manipulate a long DNA construct at molecular extensions approaching the contour length defined by B-DNA helical geometry, and the measured entropic elasticity agrees with the wormlike chain model (force <35 pN). By incorporating a torsionally constrained DNA tether, the T-MT would allow both the relative extension and twist of the tether to be manipulated, while viewing far-red emitting fluorophore-labeled targets. This T-MT design has the potential to enable the study of DNA binding and remodeling processes under conditions of constant force and defined torsional stress.


Assuntos
DNA , Magnetismo , DNA/química , Fenômenos Magnéticos , Magnetismo/métodos , Microscopia de Fluorescência , Nanotecnologia
19.
Br J Learn Disabil ; 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35602323

RESUMO

Background: During the COVID-19 pandemic, social distancing measures were enforced and the national lockdown underlined our reliance on virtual means as a way to communicate. This new way of interacting highlighted that people with an intellectual disability were a large proportion of a digitally excluded population. Methods: A service evaluation, using a mixed method design in the form of four self-reported outcome measures and qualitative feedback. Findings: Clinical services need to continue when face to face sessions are not possible. Remote groups can be an alternative option not only when self-isolating due to pandemics but when living in remote locations, having physical health problems or excessive expenses and travel costs. Conclusions: Online dramatherapy groups can be a beneficial alternative when face to face groups are not possible or challenging to attend due to access difficulties. Online groups can offer opportunities to meet with peers, build relationships, improve confidence and learn new skills in technology.

20.
Med Sci Educ ; 32(1): 209-219, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35186437

RESUMO

Modern scientific research has demonstrated that race is a social construct rather than a biological construct. Yet, medical education research suggests that medical faculty still sometimes characterize race and racial differences as biological during lectures. To explore this dynamic, we reviewed (1) how race is presented in the preclinical curriculum of an undergraduate medical institution and (2) how preclinical faculty both define race and attribute disparate health outcomes to race. In part 1 of the study, the authors conducted a retrospective summative content analysis of all first-year preclinical lectures during the 2018-2019 academic year. In part 2, the authors administered a survey to preclinical faculty on the understanding of race, and responses were assessed through conventional content analysis. A number of faculty suggested a biological basis for racial differences during lectures, though survey results suggested that the majority characterize race as a social construct. Faculty knowledge of race and racial differences as a social construct was not reflected in the majority of the curricular analysis. Instead, the lectures showed that faculty predominantly discussed race without context (e.g., as a standalone epidemiological statistic or an unexplained factor of risk, diagnosis, prognosis, or treatment), or with a biological context. We conclude that there is a discrepancy between preclinical faculty knowledge of race and the presentation of race and racial differences in lectures. This discrepancy has implications on medical education. We offer possible explanations for this discrepancy as well as resources for preclinical faculty development to bridge this gap.

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