Heart rate variability and cortisol responses during attentional and working memory tasks in naval cadets

The aim of the project was to study the relationship between heart rate variability (HRV) and cortisol release during cognitive challenging tasks. Forty-nine male naval cadets from the Royal Norwegian Naval Academy were administered computerised versions of attentional and working memory tests. The results from this study support the hypothesis of a negative correlation between HRV and cortisol secretion during cognitive tasks. Confirmation of the hypothesis with the low HRV group scoring higher on cortisol only during performance of cognitive tasks and recovery was also found. Furthermore, a replication of the previous findings of a negative association between cortisol levels and performance were supported when using uncorrected comparisons. None of the correlations survived Bonferonin corrections. The findings are discussed in relation to factors increasing HRV thus improving tolerance to cognitive stress in onboard environments.publishedVersio

Vagally mediated heart rate variability, stress, and perceived social support: a focus on sex differences

Higher vagally mediated heart rate variability (vmHRV), reflecting vagal activity as indexed by heart function and lower stress vulnerability, is associated with higher perceived social support. Seeking social support is an adaptive stress response, and evolutionary theories suggest that females use this strategy more than males. The current study investigated the hypothesis that higher vmHRV is related to higher perceived social support under conditions of higher, relative to lower, stress, and that this association is most prominent in females. A healthy student sample (n = 143; 82 males, 61 females; mean age 19.9) completed the short version of the Medical outcomes study social support survey (MOS) and the Perceived stress scale (PSS). Activity in the high frequency band of heart rate variability (HF-HRV), deducted from five-minute resting electrocardiogram (ECG) recordings, indexed vmHRV. A moderation analysis was conducted, with PSS and sex as moderators of the association between vmHRV and MOS. Statistical effects were adjusted for age, education, physical activity, body mass index (BMI), alcohol and drug use, ECG-derived respiration (EDR), and mean heart rate. Higher PSS scores moderated the association between vmHRV and MOS in females but not males. Lower PSS scores did not moderate the relation between vmHRV and MOS. This suggests that higher vmHRV is associated with higher perceived social support under conditions of higher stress in females but not males, consistent with evolution of different stress management strategies in the sexes. The results may have implications for individualized intervention strategies for increasing vmHRV and perceived social support.publishedVersio

Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG): a feasibility study for a randomized controlled trial

Background Generalised anxiety disorder (GAD) is a frequent and severe disorder among older adults. For older adults with GAD the effect of the recommended treatment, cognitive behaviour therapy (CBT), is reduced. Physical exercise (PE) may enhance the effect of CBT by improving cognitive function and increasing levels of brain-derived neurotrophic factor (BDNF), a predictor of the effect of CBT in patients with anxiety. The aim of the study was to assess the feasibility of a randomized controlled trial (RCT) investigating treatment effect of the combination of CBT and PE for GAD in a sample of older adults, including procedures for assessment and treatment. Methods Four participants aged 62–70 years (M = 65.5, SD = 3.2) with a primary diagnosis of GAD were included. Participants received 15 weeks of PE in combination with 10 weeks of CBT. Participants completed self-report measures, and clinical, biological, physiological and neuropsychological tests at pre-, interim- and post-treatment. Results Procedures, protocols, and results are presented. One participant dropped out during treatment. For the three participants completing, the total adherence to PE and CBT was 80% and 100%, respectively. An independent assessor concluded that the completers no longer fulfilled the criteria for GAD after treatment. Changes in self-report measures suggest symptom reduction related to anxiety and worry. The sample is considered representative for the target population. Conclusions The results indicate that combining CBT and PE for older adults with GAD is feasible, and that the procedures and tests are suitable and manageable for the current sample.publishedVersio

Anger in brain and body: the neural and physiological perturbation of decision-making by emotion

Emotion and cognition are dynamically coupled to bodily arousal: The induction of anger, even unconsciously, can reprioritise neural and physiological resources toward action states that bias cognitive processes. Here we examine behavioural, neural and bodily effects of covert anger processing and its influence on cognition, indexed by lexical decision-making. While recording beat-to-beat blood pressure, the words ANGER or RELAX were presented subliminally just prior to rapid word/non-word reaction-time judgements of letter-strings. Subliminal ANGER primes delayed the time taken to reach rapid lexical decisions, relative to RELAX primes. However, individuals with high trait anger were speeded up by subliminal anger primes. ANGER primes increased systolic blood pressure and the magnitude of this increase predicted reaction time prolongation. Within the brain, ANGER trials evoked an enhancement of activity within dorsal pons and an attenuation of activity within visual occipitotemporal and attentional parietal cortices. Activity within periaqueductal grey matter, occipital and parietal regions increased linearly with evoked blood pressure changes, indicating neural substrates through which covert anger impairs semantic decisions, putatively through its expression as visceral arousal. The behavioural and physiological impact of anger states compromises the efficiency of cognitive processing through action-ready changes in autonomic response that skew regional neural activity

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Exploratory multivariate analysis of the effect of fatty fish consumption and medicinal use on heart rate and heart rate variability data

The overall aim of the present study was to explore the relationship between medicinal use and fatty fish consumption on heart rate variability (HRV) and heart rate (HR) in a group of forensic inpatients on a variety of medications. A total of 49 forensic inpatients, randomly assigned to a fish group (n = 27) or a control group (n = 22) were included in the present study. Before and by the end of the food intervention period HR and HRV were measured during an experimental test procedure. An additional aim of this paper is to show how multivariate data analysis can highlight differences and similarities between the groups, thus being a valuable addition to traditional statistical hypothesis testing. The results indicate that fish consumption may have a positive effect on both HR and HRV regardless of medication, but that the influence of medication is strong enough to mask the true effect of fish consumption. Without correcting for medication, the fish group and control group become indistinguishable (p = 0.0794, Cohen’s d = 0.60). The effect of medication is demonstrated by establishing a multivariate regression model that estimates HR and HRV in a recovery phase based on HR and HRV data recorded during psychological tests. The model performance is excellent for HR data, but yields poor results for HRV when employed on participants undergoing the more severe medical treatments. This indicates that the HRV behavior of this group is very different from that of the participants on no or lower level of medication. When focusing on the participants on a constant medication regime, a substantial improvement in HRV and HR for the fish group compared to the control group is indicated by a principal component analysis and t-tests (p = 0.00029, Cohen’s d = 2.72). In a group of psychiatric inpatients characterized by severe mental health problems consuming different kinds of medication, the fish diet improved HR and HRV, indices of both emotional regulation and physical health

Vagally mediated heart rate variability, stress, and perceived social support: a focus on sex differences

Higher vagally mediated heart rate variability (vmHRV), reflecting vagal activity as indexed by heart function and lower stress vulnerability, is associated with higher perceived social support. Seeking social support is an adaptive stress response, and evolutionary theories suggest that females use this strategy more than males. The current study investigated the hypothesis that higher vmHRV is related to higher perceived social support under conditions of higher, relative to lower, stress, and that this association is most prominent in females. A healthy student sample (n = 143; 82 males, 61 females; mean age 19.9) completed the short version of the Medical outcomes study social support survey (MOS) and the Perceived stress scale (PSS). Activity in the high frequency band of heart rate variability (HF-HRV), deducted from five-minute resting electrocardiogram (ECG) recordings, indexed vmHRV. A moderation analysis was conducted, with PSS and sex as moderators of the association between vmHRV and MOS. Statistical effects were adjusted for age, education, physical activity, body mass index (BMI), alcohol and drug use, ECG-derived respiration (EDR), and mean heart rate. Higher PSS scores moderated the association between vmHRV and MOS in females but not males. Lower PSS scores did not moderate the relation between vmHRV and MOS. This suggests that higher vmHRV is associated with higher perceived social support under conditions of higher stress in females but not males, consistent with evolution of different stress management strategies in the sexes. The results may have implications for individualized intervention strategies for increasing vmHRV and perceived social support

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe