Chickens, more than humans, focus the diversity of their immunoglobulin genes on the complementarity-determining region but utilise amino acids, indicative of a more cross-reactive antibody repertoire.

The mechanisms of B-cell diversification differ greatly between aves and mammals, but both produce B cells and antibodies capable of supporting an effective immune response. To see how differences in the generation of diversity might affect overall repertoire diversity, we have compared the diversity characteristics of immunoglobulin genes from domestic chickens to those from humans. Both use V(D)J gene rearrangement and somatic hypermutation, but only chickens use somatic gene conversion. A range of diversity analysis tools were used to investigate multiple aspects of amino acid diversity at both the germline and repertoire levels. The effect of differing amino acid usages on antibody characteristics was assessed. At both the germline and repertoire levels, chickens exhibited lower amino acid diversity in comparison to the human immunoglobulin genes, especially outside of the complementarity-determining region (CDR). Chickens were also found to possess much larger and more hydrophilic CDR3s with a higher predicted protein binding potential, suggesting that the antigen-binding site in chicken antibodies is more flexible and more polyreactive than that seen in human antibodies.

Among-species variation in hormone concentrations is associated with urban tolerance in birds.

As cities expand across the globe, understanding factors that underlie variation in urban tolerance is vital for predicting changes in patterns of biodiversity. Endocrine traits, like circulating hormone concentrations and regulation of endocrine responses, might contribute to variation in species' ability to cope with urban challenges. For example, variation in glucocorticoid and androgen concentrations has been linked to life-history and behavioural traits that are associated with urban tolerance. However, we lack an understanding of the degree to which evolved differences in endocrine traits predict variation in urban tolerance across species. We analysed 1391 estimates of circulating baseline corticosterone, stress-induced corticosterone, and testosterone concentrations paired with citizen-science-derived urban occurrence scores in a broad comparative analysis of endocrine phenotypes across 71 bird species that differ in their occurrence in urban habitats. Our results reveal context-dependent links between baseline corticosterone and urban tolerance, as well as testosterone and urban tolerance. Stress-induced corticosterone was not related to urban tolerance. These findings suggest that some endocrine phenotypes contribute to a species' tolerance of urban habitats, but also indicate that other aspects of the endocrine phenotype, such as the ability to appropriately attenuate responses to urban challenges, might be important for success in cities.

Metabolomics Markers of COVID-19 Are Dependent on Collection Wave.

The effect of COVID-19 infection on the human metabolome has been widely reported, but to date all such studies have focused on a single wave of infection. COVID-19 has generated numerous waves of disease with different clinical presentations, and therefore it is pertinent to explore whether metabolic disturbance changes accordingly, to gain a better understanding of its impact on host metabolism and enable better treatments. This work used a targeted metabolomics platform (Biocrates Life Sciences) to analyze the serum of 164 hospitalized patients, 123 with confirmed positive COVID-19 RT-PCR tests and 41 providing negative tests, across two waves of infection. Seven COVID-19-positive patients also provided longitudinal samples 2-7 months after infection. Changes to metabolites and lipids between positive and negative patients were found to be dependent on collection wave. A machine learning model identified six metabolites that were robust in diagnosing positive patients across both waves of infection: TG (22:1_32:5), TG (18:0_36:3), glutamic acid (Glu), glycolithocholic acid (GLCA), aspartic acid (Asp) and methionine sulfoxide (Met-SO), with an accuracy of 91%. Although some metabolites (TG (18:0_36:3) and Asp) returned to normal after infection, glutamic acid was still dysregulated in the longitudinal samples. This work demonstrates, for the first time, that metabolic dysregulation has partially changed over the course of the pandemic, reflecting changes in variants, clinical presentation and treatment regimes. It also shows that some metabolic changes are robust across waves, and these can differentiate COVID-19-positive individuals from controls in a hospital setting. This research also supports the hypothesis that some metabolic pathways are disrupted several months after COVID-19 infection.

Pandemic, Epidemic, Endemic: B Cell Repertoire Analysis Reveals Unique Anti-Viral Responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus.

Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both Zaire Ebolavirus (EBOV) and COVID-19 patient cohorts. We also show unique characteristics absent in Respiratory Syncytial Virus or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risk off-target effects.

Age-Related Changes in B Cells Relevant to Vaccine Responses.

Older people have reduced immune responses to infection and vaccination. B cell activation is key for the efficacy of the vaccine response, but there are several age-related changes in B cells which may contribute to the loss of vaccine efficacy. Different subpopulations of B cells have different functions and phenotypes. These populations can change as we age; older people have been shown to have fewer "IgM memory" cells, regulatory B cells and plasma cells and more IgD-CD27- "double-negative" and "age-related B cells." While the overall quantity of antibody in the blood does not change, the quality of the B cell response changes; producing less specific antibodies upon challenge and more autoreactive antibodies. This could be due to changes in selection pressures, as has been demonstrated by repertoire sequencing of different subsets of B cells at different ages. Other changes in antibody repertoire are seen, including greater levels of IgG2 in older people and altered IgG1 IGHV gene usage. Since B cells rely on their environment for efficient responses, some of these changes may be due to age-related changes in accessory cells/signals. Other changes appear to be intrinsic to older/aged B cells themselves, such as their tendency to produce greater levels of inflammatory cytokines.

Describing Return to Work after Stroke: A Feasibility Trial of 12-month Outcomes.

OBJECTIVE: Stroke is the greatest cause of disability in adults. A quarter of strokes affect people of working age, yet under half return to work after stroke. There has been little investigation into what constitutes "return to work" following stroke. The aim of this study is to describe the work metrics of stroke survivor participants in a feasibility randomized controlled trial of an early stroke-specific vocational rehabilitation intervention. METHODS: Retrospective analysis of trial data. Metrics on work status, working hours, workplace accommodations and costs were extracted from trial outcomes gathered by postal questionnaire at 3, 6, and 12 months' post-randomization for 46 stroke participants in a feasibility randomized controlled trial. Participants were randomized to receive vocational rehabilitation (intervention) or usual care (control). RESULTS: Two-thirds (n = 29; 63%) of participants returned to work at some point in the 12 months following stroke. Participants took a mean of 90 days to return to work. Most returned to the same role with an existing employer. Only one-third of participants who were employed full-time at stroke onset were working full-time at 12 months post-stroke. Most participants experienced a reduction in pre-stroke earnings. Workplace accommodations were more common among intervention group participants. More intervention participants than control participants reported satisfaction with work at both 6 and 12 months post-randomization.  Conclusion: This study illustrates the heterogeneous nature of return to work and the dramatic impact of stroke on work status, working hours and income. Longitudinal research should explore the socioeconomic legacy of stroke and include clear definitions of work and accurate measures of working hours and income from all sources.

Immunoglobulin gene analysis as a tool for investigating human immune responses.

The human immunoglobulin repertoire is a hugely diverse set of sequences that are formed by processes of gene rearrangement, heavy and light chain gene assortment, class switching and somatic hypermutation. Early B cell development produces diverse IgM and IgD B cell receptors on the B cell surface, resulting in a repertoire that can bind many foreign antigens but which has had self-reactive B cells removed. Later antigen-dependent development processes adjust the antigen affinity of the receptor by somatic hypermutation. The effector mechanism of the antibody is also adjusted, by switching the class of the antibody from IgM to one of seven other classes depending on the required function. There are many instances in human biology where positive and negative selection forces can act to shape the immunoglobulin repertoire and therefore repertoire analysis can provide useful information on infection control, vaccination efficacy, autoimmune diseases, and cancer. It can also be used to identify antigen-specific sequences that may be of use in therapeutics. The juxtaposition of lymphocyte development and numerical evaluation of immune repertoires has resulted in the growth of a new sub-speciality in immunology where immunologists and computer scientists/physicists collaborate to assess immune repertoires and develop models of immune action.

Descriptions of memory rehabilitation group interventions for neurological conditions: a systematic review.

OBJECTIVE: To establish what aspects of group-based cognitive rehabilitation for memory problems are reported, and to develop a checklist for authors, which may to improve reporting of these interventions in future studies. DATA SOURCES: A systematic search was conducted on Web of Knowledge, CINAHL, MEDLINE, AMED, EMBASE and PsycINFO electronic databases (last search: 01/05/2015). REVIEW METHODS: Articles were included if the sample were adults with a neurological disorder, the intervention was group-based cognitive rehabilitation for memory problems, and if the study was a randomised controlled trial. Articles were independently screened for inclusion and data extracted by two researchers, with the third researcher arbitrating any disputes. RESULTS: Fourteen studies were included in this review. The reporting of certain aspects of an intervention was found to be poor, particularly in relation to: duration of the programme (6 of 14 studies did not report), the development of the intervention (7 of 14 studies did not discuss), and the content and structure of intervention (7 of the 14 studies did not provide details). CONCLUSION: This review found that the overall reporting of memory rehabilitation content and format is poor. Refinement and adaption of pre-existing checklists to capture aspects of cognitive rehabilitation programmes may help authors when reporting complex interventions. A draft checklist is provided that could be refined and validated in further research.

A meta-synthesis of qualitative research on perceptions of people with long-term neurological conditions about group-based memory rehabilitation.

The effectiveness of memory rehabilitation based on randomised controlled trials and meta-analyses has been inconclusive, but patient reports based on qualitative studies have been largely positive. We conducted a meta-synthesis of qualitative studies of group-based memory rehabilitation programmes for people with neurological conditions. Based on systematic searches of electronic databases and reference lists, five papers (87 participants) were selected. Quality appraisal of papers was conducted by two independent reviewers using the Critical Appraisal Skills Programme tool. Data synthesis was guided by the meta-ethnography approach. Five higher order themes were elicited. These suggested that memory rehabilitation was associated with insight and acceptance of participants' neurological condition and resultant cognitive deficits. The therapeutic effects of the groups, with social support and leisure activities, helped with participants' confidence. There were improvements in memory related to better self-awareness and learning to use new skills and strategies to compensate for memory deficits. These improvements also related to other psychological effects, in terms of positively affected mood, confidence and fatigue. Ultimately, these changes had a positive impact on daily life, with changes seen in the personal, inter-personal and professional spheres. Therefore, this synthesis of qualitative studies suggests that memory rehabilitation offers positive outcomes for people with long-term neurological conditions.

The impact of submaximal exercise during heat and/or hypoxia on the cardiovascular and monocyte HSP72 responses to subsequent (post 24 h) exercise in hypoxia.

BACKGROUND: The aims of this study were to describe the cellular stress response to prolonged endurance exercise in acute heat, hypoxia and the combination of heat and hypoxia and to determine whether prior acute exposure to these stressors improved cellular tolerance to a subsequent exercise bout in hypoxia 24 h later. METHODS: Twelve males (age 22 ± 4 years, height 1.77 ± 0.05 m, mass 79 ± 12.9 kg, VO2 max 3.57 ± 0.7 L · min(-1)) completed four trials (30-min rest, 90-min cycling at 50% normoxic VO2 max) in normothermic normoxia (NORM; 18°C, FIO2 = 0.21), heat (HEAT; 40°C, 20% RH), hypoxia (HYP; FIO2 = 0.14) or a combination of heat and hypoxia (COM; 40°C, 20% RH, FIO2 = 0.14) separated by at least 7 days. Twenty-four hours after each trial, participants completed a hypoxic stress test (HST; 15-min rest, 60-min cycling at 50% normoxic VO2 max, FIO2 = 0.14). Monocyte heat shock protein 72 (mHSP72) was assessed immediately before and after each exercise bout. RESULTS: mHSP72 increased post exercise in NORM (107% ± 5.5%, p > 0.05), HYP (126% ± 16%, p < 0.01), HEAT (153% ± 14%, p < 0.01) and COM (161% ± 32%, p < 0.01). mHSP72 had returned to near-resting values 24 h after NORM (97% ± 8.6%) but was elevated after HEAT (130% ± 19%), HYP (118% ± 17%) and COM (131% ± 19%) (p < 0.05). mHSP72 increased from baseline after HSTNORM (118% ± 12%, p < 0.05), but did not increase further in HSTHEAT, HSTHYP and HSTCOM. CONCLUSIONS: The prior induction of mHSP72 as a result of COM, HEAT and HYP attenuated further mHSP72 induction after HST and was indicative of conferred cellular tolerance.

Individual differences in gambling proneness among rats and common marmosets: an automated choice task.

Interest is rising for animal modeling of pathological gambling. Using the operant probabilistic-delivery task (PDT), gambling proneness can be evaluated in laboratory animals. Drawing a comparison with rats, this study evaluated the common marmoset (Callithrix jacchus) using a PDT. By nose- or hand-poking, subjects learnt to prefer a large (LLL, 5-6 pellets) over a small (SS, 1-2 pellets) reward and, subsequently, the probability of occurrence of large-reward delivery was decreased progressively to very low levels (from 100% to 17% and 14%). As probability decreased, subjects showed a great versus little shift in preference from LLL to SS reinforcer. Hence, two distinct subpopulations ("non-gambler" versus "gambler") were differentiated within each species. A proof of the model validity comes from marmosets' reaction to reward-delivery omission. Namely, depending on individual temperament ("gambler" versus "non-gambler"), they showed either persistence (i.e., inadequate pokes towards LLL) or restlessness (i.e., inadequate pokes towards SS), respectively. In conclusion, the marmoset could be a suitable model for preclinical gambling studies. Implementation of the PDT to species other than rats may be relevant for determining its external validity/generalizability and improving its face/construct validity.

Developing stroke-specific vocational rehabilitation: a soft systems analysis of current service provision.

PURPOSE: This study aimed to clarify the existing service provision of stroke-specific vocational rehabilitation (VR) in one English county, in order to facilitate future service development. METHOD: Using soft systems methodology, services in Health, Social Care, Department of Work and Pensions, the voluntary and private sectors, which were identified as supporting return to work after stroke, were mapped using a mixed-methodology approach. RESULTS: A lack of a sanctioned VR pathway meant access to support relied on brokered provision and tacit knowledge. The timing of an intervention was complex and there was a substantial degree of unmet need for mild stroke patients. VR was seen as "non-essential" due to competing commissioning priorities. Service providers from all sectors lacked training and cross-sector partnerships were tenuous and provider roles unclear. CONCLUSIONS: Stroke-specific VR should be delivered by an integrated, cross-sector multi-disciplinary team and integrated commissioning between health and other sectors is necessary. Although early intervention is important, support later on in the recovery process is also necessary. Service providers need adequate training to meet the needs of stroke survivors wishing to return to work and better awareness of best practice guidelines. Business cases which demonstrate the efficacy and cost-effectiveness of VR are vital. Implications for Rehabilitation The timeliness of a vocational rehabilitation (VR) intervention is complex; services need to be responsive to the changing needs of the stroke survivor throughout their recovery process and have better mechanisms to ensure re-entry into the stroke pathway is possible. Return to work is a recognised health outcome; health services need to develop better mechanisms for interagency/cross sector working and liaison with employers and not assume that VR is beyond their remit. Therapists and non-health service providers should receive sufficient training to meet the needs of stroke survivors wishing to return to work. Rehabilitation teams must decide how to implement national guidance within existing resources and what training is needed to deploy SSVR. The lack of a sanctioned pathway results in disorganised and patchy provision of VR for stroke survivors; mild stroke patients can fall through the net and receive little or no support. The journey back to work commences at the point of stroke. Mechanisms for identifying acute stroke survivors who were working at onset and for assessing the impact of the stroke on their work need to be put in place. The entire MDT has a role to play. In the absence of a VR specialist, even patients without obvious disability should be referred for ongoing rehabilitation with detailed work assessment and signposted to employment specialists e.g. disability employment advisors EARLY after stroke. Health-based VR interventions can influence work return and job retention. However, therapists must routinely measure work outcomes to inform their business case and be encouraged to demonstrate these outcomes to local commissioners. Commissioners should consider emerging evidence of early VR interventions on reduced length of stay, health and social care resource use and the wider health benefits of maintaining employment.

Mindfulness-based cognitive therapy for individuals whose lives have been affected by cancer: a randomized controlled trial.

OBJECTIVE: This study evaluated the effectiveness of mindfulness-based cognitive therapy (MBCT) for individuals with a diagnosis of cancer. METHOD: Participants (N = 115) diagnosed with cancer, across site and stage, were randomly allocated to either the treatment or the wait-list condition. Treatment was conducted at 1 site, by a single therapist, and involved participation in 8 weekly 2-hr sessions that focused on mindfulness. Participants meditated for up to 1 hr daily and attended an additional full-day session during the course. Participants were assessed before treatment and 10 weeks later; this second assessment occurred immediately after completion of the program for the treatment condition. The treatment condition was also assessed at 3 months postintervention. All postinitial assessments were completed by assessors who were blind to treatment allocation. RESULTS: There were large and significant improvements in mindfulness (effect size [ES] = 0.55), depression (ES = 0.83), anxiety (ES = 0.59), and distress (ES = 0.53) as well as a trend for quality of life (ES = 0.30) for MBCT participants compared to those who had not received the training. The wait-list group was assessed before and after receiving the intervention and demonstrated similar change. CONCLUSIONS: These improvements represent clinically meaningful change and provide evidence for the provision of MBCT within oncology settings.

The relationship between acute stress disorder and posttraumatic stress disorder in injured children.

This study indexed the relationship between acute stress disorder (ASD) and subsequent posttraumatic stress disorder (PTSD) in injured children. Consecutive children between 7-13 years admitted to a hospital after traumatic injury (n = 76) were assessed for ASD. Children were followed up 6-months posttrauma (n = 62), and administered the PTSD Reaction Index. Acute stress disorder was diagnosed in 10% of patients, and 13% satisfied criteria for PTSD. At 6-months posttrauma, PTSD was diagnosed in 25% of patients who were diagnosed with ASD. Acute stress reactions that did not include dissociation provided better prediction of PTSD than full ASD criteria. These findings suggest that the current ASD diagnosis is not optimal in identifying younger children who are high risk for PTSD development.

The role of panic attacks in acute stress disorder in children.

This study examined the role of peritraumatic panic symptoms during trauma in childhood acute stress. Children (N = 60) who had suffered traumatic injury were administered the Child Acute Stress Reaction Questionnaire, the Child Depression Inventory, and the Physical Reactions Scale to index panic attacks that occurred during the trauma. Panic attacks were experienced during their trauma by 100% of participants with acute stress reactions and 24% of participants without stress reactions. Panic attacks during trauma accounted for 28% of the variance of acute stress reactions, with an additional variance accounted for by age, time since the accident, and dysphoria. These findings are discussed in terms of fear conditioning models of posttraumatic stress.

A prospective study of appraisals in childhood posttraumatic stress disorder.

This study investigated the predictors of posttraumatic stress disorder (PTSD) in children following a diagnosis of traumatic injury. Children (N=76) aged between 7 and 13 who were admitted to hospital following injury were assessed within a month of trauma for acute stress disorder (ASD), negative appraisals, as well as parental stress reactions. Children (N=62) were re-assessed 6-months later for PTSD and negative appraisals. The majority of the variance of chronic posttraumatic stress was accounted for by negative appraisals about future harm. This study supports cognitive models of PTSD, and suggests that younger children who exaggerate their vulnerability after trauma exposure are high risk for PTSD after trauma.

The role of maladaptive appraisals in child acute stress reactions.

OBJECTIVE: To test the prediction of cognitive models of trauma that negative, catastrophic appraisals central to the development of psychopathological stress reactions. DESIGN: A cross-sectional, concurrent design was used. METHODS: Sixty-six children (aged 7-13 years), who were hospitalized after traumatic injury were assessed within 4 weeks of their trauma for acute stress disorder, depression, and administered the Child Post-traumatic Cognitions Inventory (cPTCI). Parental acute stress was also assessed. RESULTS: Children's negative appraisals of their ongoing vulnerability accounted for 44% of the variance of acute stress reactions in children. Injury severity, depression, age, and parental acute stress levels did not account for significant additional variance. CONCLUSIONS: The findings provide support for cognitive models of trauma adaptation and highlight the importance of assessing children's appraisals of their traumatic experience in order to develop effective interventions.

Heart rate as a predictor of posttraumatic stress disorder in children.

OBJECTIVE: This study indexed the relationship between resting heart rates (HRs) after injury and subsequent posttraumatic stress disorder (PTSD) in children. METHOD: Children aged between 7 and 12 years who were hospitalized after traumatic injury (n=76) had their resting HR assessed after injury and were assessed for PTSD 6 months after injury (n=62). RESULTS: Full/subsyndromal PTSD was diagnosed in 27% of children. Children with full/subsyndromal PTSD had higher HRs after trauma than those without PTSD. Children with an elevated HR were more likely to develop PTSD after controlling for age, sex and injury severity (adjusted odds ratio=5.89). CONCLUSIONS: These findings accord with the proposal that fear conditioning shortly after trauma contributes to PTSD in children.