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Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

BackgroundThere is wide acknowledgement in the literature that social connection is protective against loneliness and depression. More robust research, however, is needed to evaluate interventions that promote social connection. This protocol paper outlines the evaluation of a community-wide social connection program, Connect Local, in metropolitan Melbourne, Australia to support people 65 years and older to increase access to local community services/activities; and to ascertain impact on social connection, loneliness, depressive symptoms, physical and mental wellbeing, and use of health services.MethodsA Type 1 Hybrid design, including program effectiveness, cost-effectiveness, and implementation evaluation of the Connect Local program, will be undertaken. Eighty-eight participants aged ≥65 years with one or more chronic health condition, who are also either experiencing or at risk of loneliness, social isolation and depressive symptoms will be invited to participate in the evaluation. Outcomes, measured at baseline, 3, 6 and 12 months, include loneliness, social isolation, depressive symptoms, social anxiety, goal attainment, wellbeing, quality of life and health care utilisation. A gender and age matched comparator group of 88 individuals will be recruited from outside the intervention local government area. Impact of the intervention on community service providers in the target region will be evaluated using mixed methods, where triangulation will be used to combine the qualitative and quantitative data using a deductive-simultaneous design. Changes in wellbeing and quality of life of community volunteers will also be measured. All groups will be interviewed to ascertain their experience and perceptions of the program. The economic evaluation will use a Social Return on Investment (SROI) approach, to include outcomes at the individual, community, and system levels. Implementation outcomes will consider Reach, Adoption, Feasibility, Acceptability, Appropriateness, Fidelity, and Sustainability of the intervention.DiscussionThis study will provide a better understanding of the impacts of a community-wide social connection approach in older adults, the community and broader system.Clinical trial registrationhttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385192; Identifier ACTRN12623000968673.

Summary: Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

Pedotransfer functions are used to relate gridded databases of soil texture information to the soil hydraulic and thermal parameters of land surface models. The parameters within these pedotransfer functions are uncertain and calibrated through analyses of point soil samples. How these calibrations relate to the soil parameters at the spatial scale of modern land surface models is unclear because gridded databases of soil texture represent an area average. We present a novel approach for calibrating such pedotransfer functions to improve land surface model soil moisture prediction by using observations from the Soil Moisture Active Passive (SMAP) satellite mission within a data assimilation framework. Unlike traditional calibration procedures, data assimilation always takes into account the relative uncertainties given to both model and observed estimates to find a maximum likelihood estimate. After performing the calibration procedure, we find improved estimates of soil moisture and heat flux for the Joint UK Land Environment Simulator (JULES) land surface model (run at a 1 km resolution) when compared to estimates from a cosmic-ray soil moisture monitoring network (COSMOS-UK) and three flux tower sites. The spatial resolution of the COSMOS probes is much more representative of the 1 km model grid than traditional point-based soil moisture sensors. For 11 cosmic-ray neutron soil moisture probes located across the modelled domain, we find an average 22 % reduction in root mean squared error, a 16 % reduction in unbiased root mean squared error and a 16 % increase in correlation after using data assimilation techniques to retrieve new pedotransfer function parameters.

Anthropogenic changes in land use and land cover (LULC) during the pre-industrial Holocene could have affected regional and global climate. Existing scenarios of LULC changes during the Holocene are based on relatively simple assumptions and highly uncertain estimates of population changes through time. Archaeological and palaeoenvironmental reconstructions have the potential to refine these assumptions and estimates. The Past Global Changes (PAGES) LandCover6k initiative is working towards improved reconstructions of LULC globally. In this paper, we document the types of archaeological data that are being collated and how they will be used to improve LULC reconstructions. Given the large methodological uncertainties involved, both in reconstructing LULC from the archaeological data and in implementing these reconstructions into global scenarios of LULC, we propose a protocol to evaluate the revised scenarios using independent pollen-based reconstructions of land cover and climate. Further evaluation of the revised scenarios involves carbon cycle model simulations to determine whether the LULC reconstructions are consistent with constraints provided by ice core records of CO2 evolution and modern-day LULC. Finally, the protocol outlines how the improved LULC reconstructions will be used in palaeoclimate simulations in the Palaeoclimate Modelling Intercomparison Project to quantify the magnitude of anthropogenic impacts on climate through time and ultimately to improve the realism of Holocene climate simulations.

This article presents an analysis of qualitative data collected from general and special education teachers (n = 36) participating in a four-module professional development training focused on preventing bullying among students with disabilities. Analysis was driven by Braun and Clarke (Qualitative Research in Psychology 3:77-101, 2006) six step process for thematic analysis. We report on four major themes: (1) the effect of teachers' identities, including race, gender, age, and cultural and social backgrounds; (2) teacher perspectives of the role of parents in bullying prevention; (3) teacher views concerning bullying between students and best practices for responding to reports of bullying in schools; (4) the influence of sociocultural factors on bullying in classrooms. Taken together, these themes suggest that teachers reflect on their role as the "kind of teacher" that prevents bullying, which has implications for the students within their classroom. Results inform best practices for the design and delivery of instructional programs and workshops that consider teacher identity and create environments that better support teachers in preventing and responding to bullying in their classrooms.

Background: Locomotor and object control skills are considered essential skills for children to learn due to their potential impact in aiding in future healthenhancing physical activity. Evidence indicates that out-of-school time programs (OST) can provide meaningful movement opportunities for children. It has been found that leaders of OST programs are not equipped with the proper training to improve children's motor skills. The purpose of this study was to gather expert consensus on the essential motor skills that should be practiced and evidence-based activities that should be integrated during OST programming. Methods: A three-round Delphi method was used to establish expert consensus on essential motor skills that children (5-10 years of age) should practice and evidence-based activities that should be integrated during OST programming to enhance child motor skill development. Results: Seven experts completed three rounds, and consensus was established (>70% agreement). Five essential motor skills were identified: overhand throwing, kicking, catching, jumping, and striking. Six evidence-based activities were agreed upon: team sport play, racket sports, swimming, resistance training, jogging/walking, and game-based approaches. Conclusion: Results from this study provide specific motor skills and evidence-based activities that program leaders could integrate during OST programming to enhance child motor skill development.

The Forests gAses aeRosols Clouds Exploratory (FARCE) campaign was conducted in March–April 2015 on the tropical island of La Réunion. For the first time, several scientific teams from different disciplines collaborated to provide reference measurements and characterization of La Réunion vegetation, volatile organic compounds (VOCs), biogenic VOCs (BVOCs), (bio)aerosols and composition of clouds, with a strong focus on the Maïdo mountain slope area. The main observations obtained during this 2-month intensive field campaign are summarized. They include characterizations of forest structure, concentrations of VOCs and precursors emitted by forests, aerosol loading and optical properties in the planetary boundary layer (PBL), formation of new particles by nucleation of gas-phase precursors, ice-nucleating particles concentrations, and biological loading in both cloud-free and cloudy conditions. Simulations and measurements confirm that the Maïdo Observatory lies within the PBL from late morning to late evening and that, when in the PBL, the main primary sources impacting the Maïdo Observatory are of marine origin via the Indian Ocean and of biogenic origin through the dense forest cover. They also show that (i) the marine source prevails less and less while reaching the observatory; (ii) when in the PBL, depending on the localization of a horizontal wind shear, the Maïdo Observatory can be affected by air masses coming directly from the ocean and passing over the Maïdo mountain slope, or coming from inland; (iii) bio-aerosols can be observed in both cloud-free and cloudy conditions at the Maïdo Observatory; (iv) BVOC emissions by the forest covering the Maïdo mountain slope can be transported upslope within clouds and are a potential cause of secondary organic aerosol formation in the aqueous phase at the Maïdo Observatory; and (v) the simulation of dynamics parameters, emitted BVOCs and cloud life cycle in the Meso-NH model are realistic, and more advanced Meso-NH simulations should use an increased horizontal resolution (100 m) to better take into account the orography and improve the simulation of the wind shear front zone within which lies the Maïdo Observatory. Using various observations and simulations, this work draws up an inventory of the in situ studies that could be performed in La Réunion and at the Maïdo Observatory. It also aims to develop scientific collaborations and to support future scientific projects in order to better understand the forest–gas–aerosol–cloud system in an insular tropical environment.

Schools are increasingly hiring full-time, unarmed school security professionals (SSPs), who are different from School Resource Officers (SROs), to help facilitate safe and supportive school climates. However, there is a paucity of literature about how they describe and engage with social emotional learning (SEL), particularly equity-focused or transformative SEL. The current study is a secondary data analysis using qualitative responses to content embedded in two online professional development (PD) modules created for school security: SEL and cultural competence (CC). Forty-eight SSPs completed the SEL module and 18 of these SSPs also completed the CC module. Informed by the Collaborative for Academic, Social, and Emotional Learning's transformative SEL literature, researchers sought to understand how SSPs describe SEL and how they apply transformative SEL in their work. A qualitative transcript analysis was performed, and transformative SEL's five subthemes were identified through this iterative process: working collaboratively, equity and inclusion, cultural humility, ties to identity, and advocacy. Findings demonstrated that SSPs who completed the modules apply transformative SEL principles in various, overlapping ways, illustrating their capacity to support student SEL. However, some SSPs struggled to make ties to their own identity, highlighting the need for widespread training and additional emphasis on self-awareness in transformative SEL PD.

Summary Objectives Body‐weight norms may explain why personal evaluations of weight status are often inaccurate. Here, we tested a ‘norm comparison’ explanation of weight status perceptions, whereby personal evaluations of weight status are biased by perceived body‐weight norms. Methods Study 1 examined whether perceptions of how one's own body weight compares to an average person predict personal evaluations of weight status. Study 2 examined whether manipulating perceptions of how one's own body weight compares to an average person influences whether or not a person identifies their own weight status as being overweight. Results In Study 1, if participants rated their body weight as being similar to the body weight of an average person, they were less likely to identify their weight status as being overweight. In Study 2, participants that were led to believe that their body weight was heavier than the average person were more likely to perceive their own weight status as being overweight. Conclusions Personal perceptions of weight status are likely to be shaped by a ‘norm comparison’ process. As overweight becomes more normal, underestimation of weight status amongst individuals with overweight and obesity will be more common.

This study explored cross-sectional associations between prior weight stigma experiences, physical activity (PA) intentions, behaviors, and the acute effects of a weight stigma exposure on PA intentions and behaviors among undergraduate students. Weight-stigma experiences and behavioral intentions were self-reported. Moderate-to-vigorous PA and total PA were assessed using accelerometry. Participants were randomized into two experimental conditions (a weight stigma or control condition) to assess the acute effects of a weight stigma exposure. Forty-nine students (81.6% female; 59.2% Non-Hispanic White; 19.6 ± 1.1 years of age; body mass index: 23.9 ± 4.0 kg/m[superscript 2]) completed the study. Prior weight stigma experiences were positively associated with PA avoidance ([beta] = 12.1 ± 2.7; p < 0.001) but were not associated with positive PA intentions or behaviors (ps > 0.05). There were no differences in positive PA intentions, PA avoidance, or PA behaviors across conditions (all ps > 0.05). Future studies should examine the long-term effects of weight stigma on PA avoidance and objectively measured PA in young college students.

The purpose of this article is to describe how to teach students to use smartpens to record notes in their classes. Notetaking is a complex cognitive process that requires students to listen, process, organize, and record notes, while dealing with the temporal demands of trying to record notes fast enough to keep up with the teacher. Fortunately for students with disabilities, smartpens can help them compensate for slow writing and processing speed by allowing them to record partial notes and then easily amend them after the lecture.

Background/Objectives: There is a subset of patients with pain who become worse after exercise. To explore this, we examined the responses of people with chronic primary pain to a standardized high intensity exercise protocol used to induce delayed onset muscle soreness (DOMS). Methods: Ten participants with a diagnosis of chronic widespread muscle pain (CWMP) were matched by age and reported gender to ten participants without muscle pain (i.e., no pain (NP)). Participants completed a standardized DOMS protocol. Pain intensity in the arm at rest and with movement was assessed using daily electronic diaries. Peak pain, the timing of peak pain, and the time to recovery were compared between groups. Associations of pain variables with the functional connectivity of the sensorimotor (SMN), cerebellum, frontoparietal control (FPN), and default mode network (DMN) both within network nodes and the rest of the brain was assessed. Results: Significant differences in peak pain, the time to peak pain, and the time to recovery were noted between groups for both pain at rest and pain with movement after controlling for catastrophizing and pain resilience. Connectivity across the SMN, FPN, and DMN was associated with all pain-related variables. Significant group differences were identified between groups. Conclusions: A standardized muscle “injury” protocol resulted in more pain, a longer time to peak pain, and a longer time to resolve pain in the patient group compared to the NP group. These differences were associated with differences in connectivity across brain regions related to sensorimotor integration and appraisal. These findings provide preliminary evidence of the dysregulation of responses to muscle (micro)trauma in people with chronic pain.

This study (a) examined the associations among different performance metrics derived from different strategies (i.e., maximum and average scores) and trials from product-oriented measures of motor skills, and (b) explored how different performance metrics from product-oriented assessments of motor skills change in young children with typical development. Children (N = 279; 156 girls; M[subscript age] = 4.44 years) completed a battery of product-oriented assessments for throwing (in meters per second, five trials); kicking (in meters per second, five trials); jumping (in centimeters, five trials); running (in meters per second, two trials); and hopping (in meters per second, four trials--two preferred foot, two nonpreferred foot). A total of 36 performance metrics were derived--throw (n = 7), kick (n = 7), jump (n = 7), run (n = 4), and hop (n = 11). Intraclass correlations examined reliability among performance metrics for each skill; linear mixed models examined whether variations changed across early childhood. There was excellent reliability among all performance metrics for each skill (all ICC > 0.90). Linear mixed models revealed that children's motor performance improved for two metrics of the throw, five variations of the jump, and three metrics of the hop (all p < 0.05). Researchers should be aware that some performance metrics from product-oriented assessments (e.g., maximum and average of three or five trials) are highly related and change, whereas others do not.

The host specificity of Leptinotarsa undecimlineata Stål, a candidate biocontrol agent for Solanum torvum Sw. (turkey berry) a woody pasture weed in Vanuatu was investigated. In no-choice tests, adult L. undecimlineata beetles fed and oviposited on eggplant (Solanum melongena L.) plants, which also supported development of first instar L. undecimlineata larvae through to adult. A systematic review of field host records indicated that L. undecimlineata has never been reported to attack S. melongena throughout most of its native range in Mexico, the Antilles and Colombia, although minor and infrequent spillover attack has been observed in Central America. Choice oviposition, ‘multiple generation’ (continuation) tests, and the relative performance risk score approach (updated to use Firth’s bias reduced logistic regressions) were used to investigate the potential risk posed to S. melongena should L. undecimlineata be released in Vanuatu. The relative risk score approach was inconclusive, indicating a low but not zero risk of S. melongena being a persistent field host for both choice and no-choice tests. In contrast, the multiple generation tests demonstrated that L. undecimlineata cannot persist on S. melongena. Adult feeding was lower and significantly fewer eggs were laid on S. melongena compared to S. torvum in no-choice adult feeding and oviposition tests. The combination of tests used provided an explanation why only minor and infrequent spillover attack on S. melongena has been reported in parts of the native range of L. undecimlineata. We conclude that L. undecimlineata poses a very low risk to S. melongena should it be introduced into Vanuatu. However, the relative performance risk score approach requires further analyses using larger datasets to investigate the potential for threshold scores to be used to reliably predict risk.

Cortical interneuron (CIN) dysfunction is thought to play a major role in neuropsychiatric conditions like epilepsy, schizophrenia and autism. It is therefore essential to understand how the development, physiology, and functions of CINs influence cortical circuit activity and behavior in model organisms such as mice and primates. While transgenic driver lines are powerful tools for studying CINs in mice, this technology is limited in other species. An alternative approach is to use viral vectors such as AAV, which can be used in multiple species including primates and also have potential for therapeutic use in humans. Thus, we sought to discover gene regulatory enhancer elements (REs) that can be used in viral vectors to drive expression in specific cell types. The present study describes the systematic genome-wide identification of putative REs (pREs) that are preferentially active in immature CINs by histone modification chromatin immunoprecipitation and sequencing (ChIP-seq). We evaluated two novel pREs in AAV vectors, alongside the well-established Dlx I12b enhancer, and found that they drove CIN-specific reporter expression in adult mice. We also showed that the identified Arl4d pRE could drive sufficient expression of channelrhodopsin for optogenetic rescue of behavioral deficits in the Dlx5/6+/- mouse model of fast-spiking CIN dysfunction.

The evolution of organic aerosol (OA) and aerosol size distributions within smoke plumes is uncertain due to the variability in rates of coagulation and OA condensation/evaporation between different smoke plumes and at different locations within a single plume. We use aircraft data from the FIREX-AQ campaign to evaluate differences in evolving aerosol size distributions, OA, and oxygen to carbon ratios (O:C) between and within smoke plumes during the first several hours of aging as a function of smoke concentration. The observations show that the median particle diameter increases faster in smoke of a higher initial OA concentration (>1000 µg m−3), with diameter growth of over 100 nm in 8 h – despite generally having a net decrease in OA enhancement ratios – than smoke of a lower initial OA concentration ( µg m−3), which had net increases in OA. Observations of OA and O:C suggest that evaporation and/or secondary OA formation was greater in less concentrated smoke prior to the first measurement (5–57 min after emission). We simulate the size changes due to coagulation and dilution and adjust for OA condensation/evaporation based on the observed changes in OA. We found that coagulation explains the majority of the diameter growth, with OA evaporation/condensation having a relatively minor impact. We found that mixing between the core and edges of the plume generally occurred on timescales of hours, slow enough to maintain differences in aging between core and edge but too fast to ignore the role of mixing for most of our cases.

Background: The efficacy of psychiatric DBS is thought to be driven by the connectivity of stimulation targets with mood-relevant fronto-temporal networks, which is typically evaluated using diffusion-weighted tractography. Objective: Leverage intracranial electrophysiology recordings to better predict the circuit-wide effects of neuromodulation to white matter targets. We hypothesize strong convergence between tractography-predicted structural connectivity and stimulation-induced electrophysiological responses. Methods: Evoked potentials were elicited by single-pulse stimulation to two common DBS targets for treatment-resistant depression – the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VCVS) – in two patients undergoing DBS with stereo-electroencephalographic (sEEG) monitoring. Evoked potentials were compared with predicted structural connectivity between DBS leads and sEEG contacts using probabilistic, patient-specific diffusion-weighted tractography. Results: Evoked potentials and tractography showed strong convergence in both patients in orbitofrontal, ventromedial prefrontal, and lateral prefrontal cortices for both SCC and VCVS stimulation targets. Low convergence was found in anterior cingulate (ACC), where tractography predicted structural connectivity from SCC targets but produced no evoked potentials during SCC stimulation. Further, tractography predicted no connectivity to ACC from VCVS targets, but VCVS stimulation produced robust evoked potentials. Conclusion: The two connectivity methods showed significant convergence, but important differences emerged with respect to the ability of tractography to predict electrophysiological connectivity between SCC and VCVS to regions of the mood-related network. This multimodal approach raises intriguing implications for the use of tractography in surgical targeting and provides new data to enhance our understanding of the network-wide effects of neuromodulation.

An understanding of how heterozygous loss-of-function mutations in autism spectrum disorder (ASD) risk genes, such as TBR1, contribute to ASD remains elusive. Conditional Tbr1 deletion during late mouse gestation in cortical layer 6 neurons (Tbr1layer6 mutants) provides novel insights into its function, including dendritic patterning, synaptogenesis, and cell-intrinsic physiology. These phenotypes occur in heterozygotes, providing insights into mechanisms that may underlie ASD pathophysiology. Restoring expression of Wnt7b largely rescues the synaptic deficit in Tbr1layer6 mutant neurons. Furthermore, Tbr1layer6 heterozygotes have increased anxiety-like behavior, a phenotype seen ASD. Integrating TBR1 chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) data from layer 6 neurons and activity of TBR1-bound candidate enhancers provides evidence for how TBR1 regulates layer 6 properties. Moreover, several putative TBR1 targets are ASD risk genes, placing TBR1 in a central position both for ASD risk and for regulating transcriptional circuits that control multiple steps in layer 6 development essential for the assembly of neural circuits.

ABSTRACT Lassa virus (LASV) is the causative agent of the deadly Lassa fever (LF). Seven distinct LASV lineages circulate through western Africa, among which lineage I (LI), the first to be identified, is particularly resistant to antibody neutralization. Lineage I LASV evades neutralization by half of known antibodies in the GPC-A antibody competition group and all but one of the antibodies in the GPC-B competition group. Here, we solve two cryo-electron microscopy (cryo-EM) structures of LI GP in complex with a GPC-A and a GPC-B antibody. We used complementary structural and biochemical techniques to identify single-amino-acid substitutions in LI that are responsible for immune evasion by each antibody group. Further, we show that LI infection is more dependent on the endosomal receptor lysosome-associated membrane protein 1 (LAMP1) for viral entry relative to LIV. In the absence of LAMP1, LI requires a more acidic fusion pH to initiate membrane fusion with the host cell relative to LIV. IMPORTANCE No vaccine or therapeutics are approved to prevent LASV infection or treat LF. All vaccine platforms currently under development present only the LIV GP sequence. However, our data suggest that the high genetic diversity of LASV may be problematic for designing both a broadly reactive immunogen and therapeutic. Here, we examine antibodies that are highly potent against LIV yet are ineffective against LI. By pinpointing LI mutations responsible for this decrease in antibody efficacy, we suggest that future vaccine platforms may need to incorporate specific LI-like mutations in order to generate a broadly neutralizing antibody response against all LASV lineages.

Introduction Despite widely available vaccinations, Streptococcus pneumoniae (SPN) remains a major cause of morbidity and mortality worldwide, causing community-acquired pneumonia, meningitis, otitis media, sinusitis and bacteraemia. Here, we summarise an ethically approved protocol for a double-blind, randomised controlled trial investigating the effect of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) on pneumococcal nasopharyngeal colonisation acquisition, density and duration using experimental human pneumococcal challenge (EHPC).Methods and analysis Healthy adult participants aged 18–50 years will be randomised to receive PCV13, PPV23 or placebo and then undergo one or two EHPCs involving intranasal administration of SPN at 1-month post-vaccination with serotype 3 (SPN3) and 6 months with serotype 6B (SPN6B). Participants randomised to PCV13 and placebo will also be randomised to one of two clinically relevant SPN3 strains from distinct lineages within clonal complex 180, clades Ia and II, creating five study groups. Following inoculation, participants will be seen on days 2, 7, 14 and 23. During the follow-up period, we will monitor safety, colonisation status, density and duration, immune responses and antigenuria. The primary outcome of the study is comparing the rate of SPN3 acquisition between the vaccinated (PCV13 or PPV23) and unvaccinated (placebo) groups as defined by classical culture. Density and duration of colonisation, comparison of acquisition rates using molecular methods and evaluation of the above measurements for individual SPN3 clades and SPN6B form the secondary objectives. Furthermore, we will explore the immune responses associated with these vaccines, their effect on colonisation and the relationship between colonisation and urinary pneumococcal antigen detection.Ethics and dissemination The study is approved by the NHS Research and Ethics Committee (Reference: 20/NW/0097) and by the Medicines and Healthcare products Regulatory Agency (Reference: CTA 25753/0001/001–0001). Findings will be published in peer-reviewed journals.Trial registration number ISRCTN15728847, NCT04974294.

Currently, the gold standard for high-resolution mapping of cortical electrophysiological activity is invasive electrocorticography (ECoG), a procedure that carries with it the risk of serious morbidity and mortality. Due to these risks, the use of ECoG is largely limited to pre-surgical mapping in intractable epilepsy. Nevertheless, many seminal studies in neuroscience have utilized ECoG to explore domains such as visual perception, attention, auditory processing, and sensorimotor behavior. Studies such as these, occurring in patients with epilepsy rather than healthy controls, may lack generalizability, and are limited by the placement of the electrode arrays over the presumed seizure focus. This manuscript explores the use of optically pumped magnetometers (OPMs) to create a non-invasive alternative to ECoG, which we refer to as magnetocorticography. Because prior ECoG studies reveal that most cognitive processes are driven by multiple, simultaneous independent neuronal assemblies, we characterize the ability of a theoretical 56-channel dense OPM array to resolve simultaneous independent sources, and compare it to currently available SQUID devices, as well as OPM arrays with inter-sensor spacings more typical of other systems in development. Our evaluation of this theoretical system assesses many potential sources of error, including errors of sensor calibration and position. In addition, we investigate the influence of geometrical and anatomical factors on array performance. Our simulations reveal the potential of high-density, on-scalp OPM MEG devices to localize electrophysiological brain responses at unprecedented resolution for a non-invasive device.

Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites, but can be laborious. Herein, we employed peptide microarrays to map linear peptide epitopes (LPEs) recognized following SARS-CoV-2 infection and vaccination. LPEs detected by nonhuman primate (NHP) and patient IgMs after SARS-CoV-2 infection extensively overlapped, localized to functionally important virus regions, and aligned with reported neutralizing antibody binding sites. Similar LPE overlap occurred after infection and vaccination, with LPE clusters specific to each stimulus, where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein function. Vaccine-specific LPEs tended to map to sites known or likely to be affected by structural changes induced by the proline substitutions in the mRNA vaccine’s S protein. Mapping LPEs to regions of known functional importance in this manner may accelerate vaccine evaluation and discovery of targets for site-specific therapeutic interventions.