A meta‐analysis of coping strategies and psychological distress in rheumatoid arthritis

Purpose: Theory and research indicate that coping plays a central role in the experience of psychological distress in people with rheumatoid arthritis (RA). This study meta‐analysed the associations of adaptive and maladaptive coping strategies with psychological distress in people with RA to quantify and better understand the proposed differential relationships, as well as the factors that might influence these links. Methods: Searches of four databases identified eligible studies according to a pre‐registered protocol. Two random effects meta‐analyses examined the direction and magnitude of the links between adaptive coping (problem‐focused and emotional approach coping) and maladaptive coping (emotional avoidance and pre‐occupation coping) and psychological distress (stress, anxiety, and depression). Study quality was evaluated using a bespoke tool. Moderator analyses for sample characteristics and distress type were conducted. Results: Searches identified 16 eligible studies with 46 effects. Meta‐analysis of maladaptive coping and distress yielded a significant, medium sized association, k = 12, r = .347, 95% CIs [.23, .46]. Moderator analyses were significant only for type of distress, with effects for depression being larger than that for combined distress. Effects did not vary as a function of age, participant sex, or disease duration. Meta‐analysis for adaptive coping was not significant, k = 10, r = −.155, 95% CIs [−.31, .01]. Conclusions: Findings from this first meta‐analysis of coping and distress in RA indicate that maladaptive but not adaptive coping is associated with greater distress. Further research is needed to grow the evidence base to verify the current findings especially with respect to adaptive coping

The experiences of peer relationships amongst autistic adolescents:A systematic review of the qualitative evidence

Background Peer relationships can be especially difficult for autistic adolescents, given their marked social communication difficulties. The purpose of this systematic review is to synthesise reported qualitative findings on how autistic adolescents experience peer relationships, including the rewards and challenges, from their perspective. The review includes the perspectives of others (e.g. parents, support workers), from included papers where these were reported in addition to the adolescent viewpoint. Method PRISMA guidelines and the Joanna Briggs Institute meta-aggregative approach to qualitative synthesis informed this review process. Articles included were published in the last ten years, specific to autistic adolescents between the ages of 10 and 19. Of the 75 articles meeting eligibility for full-text review, ten matched the final inclusion criteria. Results Findings relating to four main themes emerged from the qualitative synthesis: understanding friendship, having and wanting friends, challenges of peer relationships and overcoming challenges. Fourteen sub-topics are described in detail, for example, that autistic adolescents do have and want friends, though this is often not easily achieved, leading to feelings of loneliness. Findings also revealed experiences of peer rejection and victimisation, and specific factors that might make building positive peer relationships difficult, such as group settings. Conclusions Autistic adolescents face a number of difficulties with understanding social rules and conventions, which seem to make peer relationships difficult. However, due to many autistic adolescents having a desire for friendship, some have developed ways of overcoming these challenges. This review highlights that additional support is needed to support the development of autistic adolescents’ social skills and awareness; further research is needed to establish how this could be done most effectively

Judgement bias: A cognitive measure of affective state in sheep

Sheep welfare is predominately measured by identifying behavioural and physiological changes. While informative, they can often be difficult to interpret, identifying the arousal of a sheep in a particular situation but not the valence (positivity or negativity) of the affective state being experienced. Judgement bias has been proposed as a cognitive measure of affective state valence in animals. The aim of this thesis was to adapt a method of assessing judgement bias for use in sheep to identify cognitive changes influenced by affective states. In all studies, sheep were trained to a go/no-go operant task where they learnt to approach (go response) a bucket when placed in one corner of the testing facility to receive a positive reinforcer (feed reward), and not approach it when in the alternate corner (no-go response) to avoid a negative reinforcer (exposure to a dog or fan forced blower). Judgement bias testing involved exposing the sheep to ambiguous bucket locations between the two learnt ones. The sheep had to judge which way to respond to these ambiguous locations (go/no-go), which would give insight into their affective states. In the first study a restraint and isolation stressor (RIS) for 6 h/day on 3 consecutive days generated a significantly more positive judgement in sheep compared to controls. Two further studies, using a chronic, intermittent treatment and a pharmacological treatment using a serotonin antagonist respectively, generated more pessimistic-like judgement biases in the sheep compared to that of the controls. These studies suggest that judgement bias can identify affective state changes in sheep and that the response differs depending on the nature of the stress. Furthermore, the unexpected result generated from the RIS treatment suggests that judgement bias can be used to measure differently valenced affective states in sheep. Another study conducted into the method itself showed that the sheep learn not to approach the unreinforced ambiguous locations when repeatedly exposed to them and this affects their judgement of the bucket locations. This means that there are a limited number of times that the sheep can be exposed to the testing situations. Despite this and other methodological concerns discussed, these results strongly suggest that judgement bias can be used as a measure of affective state in sheep. The use of this method could help to improve the welfare assessment of sheep in the future, especially if used in conjunction with other measures of affective state

Temperament, age and weather predict social interaction in the sheep flock

The aim of the current study was to investigate the social relationships between individual sheep, and factors that influence this, through the novel application of the statistical multiple membership multiple classification (MMMC) model. In study one 49 ewes (ranging between 1 and 8 years old) were fitted with data loggers, which recorded when pairs of sheep were within 4 m or less of each other, within a social group, for a total of 6 days. In study two proximity data were collected from 45 ewes over 17 days, as were measures of ewe temperament, weight and weather. In study 1 age difference significantly influenced daily contact time, with sheep of the same age spending an average of 20 min 43 s together per day, whereas pairs with the greatest difference in age spent 16 min 33 s together. Maximum daily temperature also significantly affected contact time, being longer on hotter days (34 min 40 s hottest day vs. 18 min 17 s coolest day), as did precipitation (29 min 33 s wettest day vs. 10 min 32 s no rain). Vocalisation in isolation, as a measure of temperament, also affected contacts, with sheep with the same frequency of vocalisations spending more time together (27 min 16 s) than those with the greatest difference in vocalisations (19 min 36 s). Sheep behaviour in the isolation box test (IBT) was also correlated over time, but vocalisations and movement were not correlated. Influences of age, temperature and rain on social contact are all well-established and so indicate that MMMC modelling is a useful way to analyse social structures of the flock. While it has been demonstrated that personality factors affect social relationships in non-human animals, the finding that vocalisation in isolation influences pair social contact in sheep is a novel one

Combined point of care nucleic acid and antibody testing for SARS-CoV-2 following emergence of D614G Spike Variant

Rapid COVID-19 diagnosis in hospital is essential, though complicated by 30-50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant now dominates the pandemic and it is unclear how serological tests designed to detect anti-Spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95CI 57.8-92.9%) by rapid NAAT alone. Combined point of care antibody test and rapid NAAT is not impacted by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era