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Background Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium–long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. Method The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14–35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. Discussion The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. Trial registration ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019.

Background/Objective\ud Healthcare workers play a critical role in the health of a nation, yet rates of healthcare worker stress are disproportionately high. We evaluated whether mindfulness-based cognitive therapy for life (MBCT-L), could reduce stress in healthcare workers and target a range of secondary outcomes. Method: This is the first parallel randomised controlled trial of MBCT-L. Participants were NHS workers, who were randomly assigned (1:1) to receive either MBCT-L or wait-list. The primary outcome was self-reported stress at post-intervention. Secondary variables were well-being, depression, anxiety, and work-related outcomes. Mixed regressions were used. Mindfulness and self/other-compassion were explored as potential mechanisms of effects on stress and wellbeing. Results: We assigned 234 participants to MBCT-L (n = 115) or to wait-list (n = 119). 168 (72%) participants completed the primary outcome and of those who started the MBCT-L 73.40% (n = 69) attended the majority of the sessions. MBCT-L ameliorated stress compared with controls (B = 2.60, 95% CI = 1.63‒3.56; d = -0.72; p < .0001). Effects were also found for well-being, depression and anxiety, but not for work-related outcomes. Mindfulness and self-compassion mediated effects on stress and wellbeing. Conclusions: MBCT-L could be an effective and acceptable part of a wider healthcare workers well-being and mental health strategy.

We extend the domain of liability of foreignness (LOF) research to capital markets and evaluate whether firms incur LOF when attempting to raise debt capital abroad. We rely upon multiple conceptualizations of institutional distance to capture the extent to which distance may contribute to LOF in capital markets. Based on a sample of 361 firms from 45 countries over a 24 year time period, we find that institutional distances lead to increased cost of debt. More importantly, we find that frequency of foreign bond issuance helps to mitigate the LOF. We conclude with a discussion of our results and their implications for future research on understanding how firms address LOF when sourcing debt abroad.

Background:Cognitive behavioral therapy (CBT) is an efficacious intervention for generalized anxiety disorder (GAD). Digital CBT may provide a scalable means of delivering CBT at a population level. We investigated the efficacy of a novel digital CBT program in those with GAD for outcomes of anxiety, worry, depressive symptoms, sleep difficulty, wellbeing, and participant‐specific quality of life. Methods:This online, two‐arm parallel‐group superiority randomized controlled trial compared digital CBT with waitlist control in 256 participants with moderate‐to‐severe symptoms of GAD. Digital CBT (Daylight), was delivered using participants’ own smartphones. Online assessments took place at baseline (Week 0; immediately preceding randomization), mid‐intervention (Week 3; from randomization), post‐intervention (Week 6; primary endpoint), and follow‐up (Week 10). Results:Overall, 256 participants were randomized and intention‐to‐treat analysis foundDaylightreduced symptoms of anxiety compared with waitlist control at post‐intervention, reflecting a large effect size (adjusted difference [95% CI]: 3.22 [2.14, 4.31],d = 1.08). Significant improvements were found for measures of worry; depressive symptoms, sleep difficulty, wellbeing, and participant‐specific quality of life. Conclusion:Digital CBT (Daylight) appears to be safe and efficacious for symptoms of anxiety, worry, and further measures of mental health compared with waitlist control in individuals with GAD.

Building on previous research, this study compared the effects of two brief, online mindfulness-based interventions (MBIs; with and without formal meditation practice) and a no intervention control group in a non-clinical sample. One hundred and fifty-five university staff and students were randomly allocated to a 2-week, self-guided, online MBI with or without mindfulness meditation practice, or a wait list control. Measures of mindfulness, perceived stress, perseverative thinking and anxiety/depression symptoms within were administered before and after the intervention period. Intention to treat analysis identified significant differences between groups on change over time for all measured outcomes. Participation in the MBIs was associated with significant improvements in all measured domains (all ps

Previous research examining the effects of mindfulness-based interventions (MBIs) and their mechanisms of change has been hampered by failure to control for non-specific factors, such as social support and interaction with group members, facilitator contact and expectation of benefit, meaning that it remained possible that benefits of MBIs could have been attributable, perhaps entirely, to non-specific elements. This experimental study examined the effects of a 2-week online mindfulness-based self-help (MBSH) intervention compared to a well-matched classical music control condition and a waitlist control condition on perceived stress. This study also tested mindfulness, self-compassion and worry as mechanisms of the effects of MBSH versus both control conditions on stress. University students and staff (N = 214) were randomised to MBSH, classical music, or waitlist conditions and completed self-report measures pre-, mid- and post-intervention. Post-intervention, MBSH was found to significantly reduce stress compared to both control conditions. Bootstrapping-based mediation analyses used standardised residualised change scores for all variables, with mediators computed as change from baseline to mid-intervention, and the outcome computed as change from baseline to post-intervention. Changes in mindfulness, self-compassion and worry were found to significantly mediate the effects of MBSH versus both control conditions on changes in stress. Findings suggest that cultivating mindfulness specifically confers benefits to stress and that these benefits may occur through improving theorised mechanisms.

In support of the construct validity of mindfulness questionnaires, meta-analytic reviews have reported that scores increase in mindfulness-based interventions (MBIs). However, several studies have also found increased mindfulness scores in interventions with no explicit mindfulness training, raising a question about differential sensitivity to change with treatment. We conducted a systematic review and meta-analysis of 37 randomized controlled trials in which mindfulness questionnaires were administered before and after an evidence-based MBI and a nonmindfulness-based active control condition. The central question was whether increases in mindfulness scores would be greater in the MBI than in the comparison group. On average, participants in MBIs showed significantly greater pre–post changes in mindfulness scores than were seen in active control conditions with no explicit mindfulness elements, with a small overall effect size. This effect was moderated by which mindfulness questionnaire was used, by the type of active control condition, and by whether the MBI and control were matched for amount of session time. When mindfulness facet scores were analyzed separately, MBIs showed significantly greater pre–post increases than active controls in observing, nonjudging, and nonreactivity but not in describing or acting with awareness. Although findings provide partial support for the differential sensitivity of mindfulness questionnaires to change with treatment, the nonsignificant difference in pre–post change when the MBI and control were matched for session time highlights the need to clarify how mindfulness skills are acquired in MBIs and in other interventions and whether revisions to mindfulness questionnaires would increase their specificity to changes in mindfulness skills., Public Significance Statement This review found that scores on mindfulness questionnaires increase more in mindfulness-based interventions than in interventions with no explicit mindfulness training, but not under all conditions. When the two treatments had equal session time, increases in mindfulness scores were similar. Nonmindfulness-based interventions may implicitly cultivate mindfulness skills, or the questionnaires may need revisions to increase their specificity to changes in mindfulness skills.

Compassion has received increasing societal and scientific interest in recent years. The science of compassion requires a tool that can offer valid and reliable measurement of the construct to allow examination of its causes, correlates, and consequences. The current studies developed and examined the psychometric properties of new self-report measures of compassion for others and for the self, the 20-item Sussex-Oxford Compassion for Others Scale (SOCS-O) and 20-item Sussex-Oxford Compassion for the Self Scale (SOCS-S). These were based on the theoretically and empirically supported definition of compassion as comprising five dimensions: (a) recognizing suffering, (b) understanding the universality of suffering, (c) feeling for the person suffering, (d) tolerating uncomfortable feelings, and (e) motivation to act/acting to alleviate suffering. Findings support the five-factor structure for both the SOCS-O and SOCS-S. Scores on both scales showed adequate internal consistency, interpretability, floor/ceiling effects, and convergent and discriminant validity.

Background: Tumour necrosis factor-αlpha inhibitors (TNFαi) are the main biologics (b-MARDs) used to treat active rheumatoid arthritis (RA) in patients that have failed disease modifying treatment (DMARD). However, 10% of patients with rheumatoid arthritis, TNFα inhibitors do not work at all. Patients are continued on this treatment for several months risking side-effects in the hope that the treatment will work. Another 40% of patients respond partially to this treatment and have to also be treated with other drugs such as methotrexate and prednisone in addition to treatment with TNFαi. Biomarkers offer an opportunity to identify before starting or soon after starting treatment with TNFαi which patients will be responders and whether prednisone and other drugs can be reduced and optimise the risk-benefit of treatment. Objectives: We undertook a series of experiments with the following objectives: determine whether cytokine biomarkers will predict which patients with rheumatoid arthritis are: (a) sustained DMARD early treatment responders (b) sustained TNFαi early treatment responders, (c) TNFαi early treatment failures. Methods: We used the Millipore’s MILLIPLEX MAP Human Th17 Magnetic Bead kit for the simultaneous quantification of the following cytokines: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL- 12p70, IL-13, IL-15, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27, IL-28A, IL-31, IL-33, GMCSF, IFNγ, MIP-3α, TNFα and TNFβ. γ, MIP-3α, TNFα and TNFβ. We evaluated 14 patients with RA starting on a DMARD and 26 patients with RA starting on a TNFαi after failing DMARDs. These cytokines were assayed monthly 2 or 3 months prior to starting a TNFαi to evaluate month-to-month cytokine variability and every month up to 5 months after initiation of treatment. RA disease activity was measured using the RA Disease Activity Score (DASCRP28) which includes joint counts, CRP and a patient-reported outcome of health status. All samples were blocked with Heteroblock to reduce rheumatoid factor and other heterophilic antibodies. Rheumatoid factor was measured before and after blocking. The same negative and positive controls were included across all plate runs. All assays were done in singlet to accommodate longitudinal samples. Mixing studies were undertaken to evaluate whether cytokine results could be analysed using quantitative statistics. Results: We had 67 serum samples in the DMARD treated group and 202 serum samples in the TNFαi treated group because of the longitudinal study design. Using mixed effects linear regression to account for longitudinal data in a model that included all 25 cytokines, treatment-time and treatment type (DMARD or TNFαi+/-DMARD), we found that in patients on DMARDs, IL-6, IL-1β, IL-28A, and TNFβ were associated with treatment response. However, in TNFαi treated patients, TNF-a, GM-CSF and IL-6 were associated with treatment response. Only p values Conclusion: In this study of treatment response comparing DMARDs and TNFαi in a longitudinal cohort of 26 patients with a total of 202 samples measuring TNFα and GM-CSF may predict early TNFαi responders. Disclosure of Interests: Marissa Lassere Grant/research support from: I have received research support with educational grant funding from Sanofi-Aventis, Pfizer, MSD, Abbvie, Sue Baker: None declared, Jenny Gu: None declared DOI: 10.1136/annrheumdis-2019-eular.6445

Genome-level data can provide researchers with unprecedented precision to examine the causes and genetic consequences of population declines, which can inform conservation management. Here, we present a high-quality, long-read, de novo genome assembly for one of the world’s most endangered bird species, the ʻAlalā (Corvus hawaiiensis, Hawaiian crow). As the only remaining native crow species in Hawaiʻi, the ʻAlalā survived solely in a captive-breeding program from 2002 until 2016, at which point a long-term reintroduction program was initiated. The high-quality genome assembly was generated to lay the foundation for both comparative genomics studies and the development of population-level genomic tools that will aid conservation and recovery efforts. We illustrate how the quality of this assembly places it amongst the very best avian genomes assembled to date, comparable to intensively studied model systems. We describe the genome architecture in terms of repetitive elements and runs of homozygosity, and we show that compared with more outbred species, the ʻAlalā genome is substantially more homozygous. We also provide annotations for a subset of immunity genes that are likely to be important in conservation management, and we discuss how this genome is currently being used as a roadmap for downstream conservation applications.

Background Healthcare workers experience higher levels of work-related stress and higher rates of sickness absence than workers in other sectors. Psychological approaches have potential in providing healthcare workers with the knowledge and skills to recognise stress and to manage stress effectively. The strongest evidence for effectiveness in reducing stress in the workplace is for stress-management courses based on cognitive behavioural therapy (CBT) principles and mindfulness-based interventions (MBIs). However, research examining effects of these interventions on sickness absence (an objective indicator of stress) and compassion for others (an indicator of patient care) is limited, as is research on brief CBT stress-management courses (which may be more widely accessible) and on MBIs adapted for workplace settings. Methods/design This protocol is for two randomised controlled trials with participant preference between the two trials and 1:1 allocation to intervention or wait-list within the preferred choice. The first trial is examining a one-day CBT stress-management workshop and the second trial an 8-session Mindfulness-Based Cognitive Therapy for Life (MBCT-L) course, with both trials comparing intervention to wait-list. The primary outcome for both trials is stress post-intervention with secondary outcomes being sickness absence, compassion for others, depression symptoms, anxiety symptoms, wellbeing, work-related burnout, self-compassion, presenteeism, and mindfulness (MBCT-L only). Both trials aim to recruit 234 staff working in the National Health Service in the UK. Discussion This trial will examine whether a one-day CBT stress-management workshop and an 8-session MBCT-L course are effective at reducing healthcare staff stress and other mental health outcomes compared to wait-list, and, whether these interventions are effective at reducing sickness absence and presenteeism and at enhancing wellbeing, self-compassion, mindfulness and compassion for others. Findings will help inform approaches offered to reduce healthcare staff stress and other key variables. A note of caution is that individual-level approaches should only be part of the solution to reducing healthcare staff stress within a broader focus on organisational-level interventions and support. Trial registration ISRCTN Registry, ISRCTN11723441. Registered on 16 June 2017. Protocol Version 1: 24 April 2017. Trial Sponsor: Sussex Partnership NHS Foundation Trust (ResearchGovernance@sussexpartnership.nhs.uk). Electronic supplementary material The online version of this article (10.1186/s13063-018-2547-1) contains supplementary material, which is available to authorized users.

In this paper, we show that the price of a premium bond and the price of a discount bond will both move toward face value at an increasing rate as the bonds approach maturity. We present a mathematical proof to show that the decline in premium and discount decline over time, to be referred to as time decay, accelerates as time passes by. We also provide numerical examples and graphical representations to illustrate the time passage effect on bond prices and discuss the implications of the findings to bond investor and asset managers in light of the quantitative easing policies taken by central banks after the 2008 financial crisis.

Research into the effectiveness and mechanisms of mindfulness-based interventions (MBIs) requires reliable and valid measures of mindfulness. The 39-item Five Facet Mindfulness Questionnaire (FFMQ-39) is a measure of mindfulness commonly used to assess change before and after MBIs. However, the stability and invariance of the FFMQ factor structure have not yet been tested before and after an MBI; pre to post comparisons may not be valid if the structure changes over this period. Our primary aim was to examine the factor structure of the FFMQ-39 before and after mindfulness-based cognitive therapy (MBCT) in adults with recurrent depression in remission using confirmatory factor analysis (CFA). Additionally, we examined whether the factor structure of the 15-item version (FFMQ-15) was consistent with that of the FFMQ-39, and whether it was stable over MBCT. Our secondary aim was to assess the general psychometric properties of both versions. CFAs showed that pre-MBCT, a 4-factor hierarchical model (excluding the “observing” facet) best fit the FFMQ-39 and FFMQ-15 data, whereas post-MBCT, a 5-factor hierarchical model best fit the data for both versions. Configural invariance across the time points was not supported for both versions. Internal consistency and sensitivity to change were adequate for both versions. Both FFMQ versions did not differ significantly from each other in terms of convergent validity. Researchers should consider excluding the Observing subscale from comparisons of total scale/subscale scores before and after mindfulness interventions. Current findings support the use of the FFMQ-15 as an alternative measure in research where briefer forms are needed. (PsycINFO Database Record (c) 2016 APA, all rights reserved)

Compassion has long been regarded as a core part of our humanity by contemplative traditions, and in recent years, it has received growing research interest. Following a recent review of existing conceptualisations, compassion has been defined as consisting of the following five elements: 1) recognising suffering, 2) understanding the universality of suffering in human experience, 3) feeling moved by the person suffering and emotionally connecting with their distress, 4) tolerating uncomfortable feelings aroused (e.g., fear, distress) so that we remain open to and accepting of the person suffering, and 5) acting or being motivated to act to alleviate suffering. As a prerequisite to developing a high quality compassion measure and furthering research in this field, the current study empirically investigated the factor structure of the five-element definition using a combination of existing and newly generated self-report items. This study consisted of three stages: a systematic consultation with experts to review items from existing self-report measures of compassion and generate additional items (Stage 1), exploratory factor analysis of items gathered from Stage 1 to identify the underlying structure of compassion (Stage 2), and confirmatory factor analysis to validate the identified factor structure (Stage 3). Findings showed preliminary empirical support for a five-factor structure of compassion consistent with the five-element definition. However, findings indicated that the 'tolerating' factor may be problematic and not a core aspect of compassion. This possibility requires further empirical testing. Limitations with items from included measures lead us to recommend against using these items collectively to assess compassion. Instead, we call for the development of a new self-report measure of compassion, using the five-element definition to guide item generation. We recommend including newly generated 'tolerating' items in the initial item pool, to determine whether or not factor-level issues are resolved once item-level issues are addressed.

It is now well-known that proteins exist at equilibrium as ensembles of conformational states rather than as unique static structures. Here we review from an ensemble perspective important biological effects of such spontaneous fluctuations on protein allostery, function, and evolution. However, rather than present a thorough literature review on each subject, we focus instead on connecting these phenomena through the ensemble-based experimental, theoretical, and computational investigations from our laboratory over the past decade. Special emphasis is given to insights that run counter to some of the prevailing ideas that have emerged over the past 40 years of structural biology research. For instance, when proteins are viewed as conformational ensembles rather than as single structures, the commonly held notion of an allosteric pathway as an obligate series of individual structural distortions loses its meaning. Instead, allostery can result from energetic linkage between distal sites as one Boltzmann distribution of states transitions to another. Additionally, the emerging principles from this ensemble view of proteins have proven surprisingly useful in describing the role of intrinsic disorder in inter-domain communication, functional adaptation mediated by mutational control of fluctuations, and evolutionary conservation of the energetics of protein stability.

Bcl-2 proteins represent a rheostat that controls cellular viability. Obatoclax, a BH3-mimetic, has been designed to specifically target and counteract anti-apoptotic Bcl-2 proteins. We evaluated the biological effects of obatoclax on the anti-tumour activity of rituximab and chemotherapy agents. Obatoclax induced cell death of rituximab/chemotherapy-sensitive (RSCL), -resistant cell lines (RRCL) and primary tumour-cells derived from patients with B-cell lymphomas (N=39). Obatoclax also enhanced the activity of rituximab and had synergistic activity when combined with chemotherapy agents. The ability of Obatoclax to induce PARP cleavage varied between patient samples and was not observed in some RRCL. Inhibition of caspase activity did not affect obatoclax activity, suggesting the existence of caspase-independent death pathways. Autophagy was detected by LC3 conversion and/or electron microscopy in RRCL and in patient-derived tumour cells. Moreover, obatoclax activity was inhibited by Beclin-1 knockdown. In summary, obatoclax is an active Bcl-2 inhibitor that potentiates the activity of chemotherapy agents and, to a lesser degree, rituximab. Defining the molecular events triggered by obatoclax is necessary to further its clinical development and identify potential biomarkers that are predictive of response.

Pim-2 kinase is one of the three highly conserved Pim family members which are known to be involved in cell survival and cell proliferation. Here we demonstrate that like Pim-1, Pim-2 also phosphorylates the cell cycle inhibitor p21Cip1/WAF1 (p21) on Thr145 in vitro and in vivo. Overexpression of Pim-2 in HCT116 cells leads to the increased stability of p21 and results in enhanced levels of both exogenous and endogenous p21 proteins. Knockdown of Pim-2 expression via siRNA results in reduced level of endogenous p21, indicating that like Pim-1, Pim-2 is another legitimate p21 kinase. However, Pim-2 has no influence on the nuclear localization of p21 in HCT116 cells. In addition, Pim-2 is able to arrest the cell cycle at G1/S phase and inhibit cell proliferation through phosphorylation of p21 in HCT116 cells. These data suggest that Pim-2 phosphorylation of p21 enhances p21's stability and inhibits cell proliferation in HCT116 cells.

Thermal adaptation of individual proteins is often achieved through modulating protein stability, with proteins that are adapted to extreme cold environments having increased conformational flexibility when brought to mesophilic conditions. Conversely, proteins adapted to higher temperatures appear less dynamic and are found to be much more stable against thermal denaturation than their mesophilic counterparts. According to the current paradigm, the adaptation of an organism for survival at higher or lower temperatures is facilitated by the adaptation of the component proteins. We note, however, that these observations have been carried out on relatively few proteins. The extent to which the conformational stabilities of all members of the proteome have been modulated for thermal adaptation remains unclear, with no direct experimental strategies to address this issue. Adapted extremophilies are likely to use a multitude of molecular and biophysical strategies for survival and, therefore, evolution of specific biophysical properties of proteins for optimal function may not be necessary for all proteins in the proteome. Using a sequence-based predictor of protein stability, eScape, an in silico examination of several extremophilic proteomes shows a correlation between the collective stability of the proteins and the thermal range of survival for the organism as expected. Unexpectedly, however, the analysis shows that protein thermostability is modified to different extents across the proteome and depends on the functional role for which the protein is involved. Identification of these differences provides unique opportunities to study interdependence within the proteome as well as the role that the proteome plays in the process of evolutionary thermal adaptation.

Populations distributed across a broad thermal cline are instrumental in addressing adaptation to increasing temperatures under global warming. Using a space-for-time substitution design, we tested for parallel adaptation to warm temperatures along two independent thermal clines in Zostera marina, the most widely distributed seagrass in the temperate Northern Hemisphere. A North-South pair of populations was sampled along the European and North American coasts and exposed to a simulated heatwave in a common-garden mesocosm. Transcriptomic responses under control, heat stress and recovery were recorded in 99 RNAseq libraries with similar to 13 000 uniquely annotated, expressed genes. We corrected for phylogenetic differentiation among populations to discriminate neutral from adaptive differentiation. The two southern populations recovered faster from heat stress and showed parallel transcriptomic differentiation, as compared with northern populations. Among 2389 differentially expressed genes, 21 exceeded neutral expectations and were likely involved in parallel adaptation to warm temperatures. However, the strongest differentiation following phylogenetic correction was between the three Atlantic populations and the Mediterranean population with 128 of 4711 differentially expressed genes exceeding neutral expectations. Although adaptation to warm temperatures is expected to reduce sensitivity to heatwaves, the continued resistance of seagrass to further anthropogenic stresses may be impaired by heat-induced downregulation of genes related to photosynthesis, pathogen defence and stress tolerance.

Experimental behavioral assays and animal models are essential to elucidate the mechanisms that underlie behavioral phenotypes associated with disorders such as Autism Spectrum Disorders and Fragil...

In contrast to other viral infections such as CMV, circulating frequencies of HIV-1-specific CD4+ T cells in peripheral blood are quantitatively diminished in the majority of HIV-1-infected individuals. One mechanism for this quantitative defect is preferential infection of HIV-1-specific CD4+ T cells, although

Individual differences in adult human brain structure have been found to reveal a great deal of information about variability in behaviours, cognitive abilities and mental and physical health. Driven by such evidence, what contributes to individual variation in brain structure has gained accelerated attention as a research question. Findings thus far appear to support the notion that an individual’s brain architecture is determined largely by genetic and environmental influences. This review aims to evaluate the empirical literature on whether and how genes and the environment contribute to individual differences in brain structure. It first considers how genetic and environmental effects may separately contribute to brain morphology, by examining evidence from twin, genome-wide association, cross-sectional and longitudinal studies. Next, evidence for the influence of the complex interplay between genetic and environmental factors, characterised as gene-environment interactions and correlations, is reviewed. In evaluating the extant literature, this review will conclude that both genetic and environmental factors play critical roles in contributing to individual variability in brain structure.

For seagrasses, seasonal and daily variations in light and temperature represent the mains factors driving their distribution along the bathymetric cline. Changes in these environmental factors, due to climatic and anthropogenic effects, can compromise their survival. In a framework of conservation and restoration, it becomes crucial to improve our knowledge about the physiological plasticity of seagrass species along environmental gradients. Here, we aimed to identify differences in transcriptomic and proteomic profiles, involved in the acclimation along the depth gradient in the seagrass Posidonia oceanica, and to improve the available molecular resources in this species, which is an important requisite for the application of eco-genomic approaches. To do that, from plant growing in the shallow (-5m) and a deep (-25m) portions of a single meadow, (i) we generated two reciprocal EST (Expressed Sequences Tags) libraries using a Suppressive Subtractive Hybridization (SSH) approach, to obtain depth/specific transcriptional profiles, and (ii) we identified proteins differentially expressed, using the highly innovative USIS mass spectrometry methodology, coupled with 1D-SDS electrophoresis and labeling free approach. Mass spectra were searched in the open source Global Proteome Machine (GPM) engine against plant databases and with the X!Tandem algorithm against a local database. Transcriptional analysis showed both quantitative and qualitative differences between depths. EST libraries had only the 3% of transcripts in common. A total of 315 peptides belonging to 64 proteins were identified by mass spectrometry. ATP synthase subunits were among the most abundant proteins in both conditions. Both approaches identified genes and proteins in pathways related to energy metabolism, transport and genetic information processing, that appear o be the most involved in depth acclimation in P. oceanica. Their putative rules in acclimation to depth were discussed.

Objective. Vascular mild cognitive impairment (VaMCI) is differentiated from mild cognitive impairment (MCI) by the presence of vascular events such as stroke or small vessel disease. Typically, MCI and VaMCI patients present with subjective complaints regarding cognition; however, little is known about the specific nature of these complaints. We aimed to create a profile of subjective cognitive complaints in MCI and VaMCI patients with similar levels of objective cognitive performance.Methods.Twenty MCI and twenty VaMCI patients were recruited from a Memory Disorders Clinic in Toronto. Subjective cognitive complaints were assessed and categorized using the Neuropsychological Impairment Scale.Results.MCI and VaMCI patients achieved similar scores on measures of objective cognitive function (). However, the VaMCI group had more subjective complaints than the MCI group (), particularly in the critical items, cognitive efficiency, memory, and verbal learning domains of the Neuropsychological Impairment Scale.Conclusions. Our findings support the idea that VaMCI and MCI differ in their clinical profiles, independent of neuroimaging. VaMCI patients have significantly more subjective cognitive complaints and may be exhibiting particular deficits in memory, verbal learning, and cognitive efficiency. Our findings promote the need for further research into VaMCI-specific cognitive deficits.