Investigating the physiological ecology of mesopelagic zooplankton in the Scotia Sea (Southern Ocean) using lipid and stable isotope signatures

The mesopelagic zooplankton community plays an important role in the cycling and sequestration of carbon via the biological pump. However, little is known about the physiology and ecology of key taxa found within this region, hindering our understanding of their influence on the pathways of energy and organic matter cycling. We sampled the eight most abundant zooplankton (Calanoides acutus, Rhincalanus gigas, Paraeuchaeta spp., Chaetognatha, Euphausia triacantha, Thysanoessa spp., Themisto gaudichaudii and Salpa thompsoni) from within the mesopelagic zone in the Scotia Sea during a sinking diatom bloom and investigated their physiological ecology using lipid biomarkers and stable isotopic signatures of nitrogen. Data suggest that the large calanoid copepods, C. acutus and R. gigas, were in, or emerging from, a period of metabolic inactivity during the study period (November 15th – December 15th 2017). Abundant, but decreasing lipid reserves in the predominantly herbivorous calanoid copepods, suggest these animals may have been metabolising previously stored lipids at the time of sampling, rather than deriving energy solely from the diatom bloom. This highlights the importance of understanding the timing of diapause of overwintering species as their feeding is likely to have an impact on the turnover of particulate organic matter (POM) in the upper mesopelagic. The δ15N signatures of POM became enriched with increasing depth, whereas all species of zooplankton except T. gaudichaudii did not. This suggests that animals were feeding on fresher, surface-derived POM, rather than reworked particles at depth, likely influencing the quantity and quality of organic matter leaving the upper mesopelagic. Our study highlights the complexity of mesopelagic food webs and suggests that the application of broad trophic functional types may lead to an incorrect understanding of ecosystem dynamics

Relationships between Reading Ability and Child Mental Health: Moderating Effects of Self-Esteem

Objective: Children with reading difficulties are at elevated risk for externalising (e.g., conduct disorder) and internalising (e.g., anxiety and depression) mental health problems. Reading ability is also negatively associated with self-esteem, a consistent predictor of child and adolescent mental health more broadly. This study examined whether self-esteem moderated and/or mediated relationships between reading ability and mental health. Method: One hundred and seventeen children (7-12 years) completed standardised reading assessments (Castles and Coltheart Test 2; CC2) and self-report measures of mental health (Strengths and Difficulties Questionnaire; SDQ) and self-esteem (Coopersmith Self-esteem Inventory). Non-verbal intelligence (IQ) was measured using the block design and matrix reasoning subscales of the Wechsler Abbreviated Scale of Intelligence, and was controlled for in all multivariate analyses. Results: Reading ability was negatively associated with internalising symptoms. This relationship was not moderated by self-esteem. Poor readers also reported more total difficulties and externalising symptoms, but only at low levels of self-esteem. There was no evidence that self-esteem mediated relationships between reading ability and mental health. Conclusions: Poor reading was associated with internalising symptoms. Self-esteem moderated the impact of reading ability on total difficulties and externalising symptoms, with high self-esteem buffering against negative impacts of poor reading. However, the reliability of the self-esteem scale used in the study was poor and findings need replication using a reliable and valid self-esteem measure, as well as other measures of child mental health. If replicated, future research should examine whether interventions aiming to improve self-esteem can reduce the risk of externalising problems in children with reading difficulties

STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological NKG2Dhi CD8+T cell dysregulation and accumulation

The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co -exist-ing autoimmunity. To investigate whether these mutations are the cause or consequence of CD8+ T cell clonal expansions and autoimmunity, we analyzed patients and mice with germline STAT3 GOF mutations. STAT3 GOF mutations drove the accumulation of effector CD8+ T cell clones highly expressing NKG2D, the receptor for stress-induced MHC-class-I-related molecules. This subset also expressed genes for granzymes, perforin, interferon-y, and Ccl5/Rantes and required NKG2D and the IL-15/IL-2 receptor IL2RB for maximal accumula-tion. Leukocyte-restricted STAT3 GOF was sufficient and CD8+ T cells were essential for lethal pathology in mice. These results demonstrate that STAT3 GOF mutations cause effector CD8+ T cell oligoclonal accumu-lation and that these rogue cells contribute to autoimmune pathology, supporting the hypothesis that somatic mutations in leukemia/lymphoma driver genes contribute to autoimmune disease.Peer reviewe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Validation of the Emotiv EPOC EEG system for research quality auditory event-related potentials in children

Background. Previous work has demonstrated that a commercial gaming electroencephalography (EEG) system, Emotiv EPOC, can be adjusted to provide valid auditory event-related potentials (ERPs) in adults that are comparable to ERPs recorded by a research-grade EEG system, Neuroscan. The aim of the current study was to determine if the same was true for children.Method. An adapted Emotiv EPOC system and Neuroscan system were used to make simultaneous EEG recordings in nineteen 6- to 12-year-old children under “passive” and “active” listening conditions. In the passive condition, children were instructed to watch a silent DVD and ignore 566 standard (1,000 Hz) and 100 deviant (1,200 Hz) tones. In the active condition, they listened to the same stimuli, and were asked to count the number of ‘high’ (i.e., deviant) tones.Results. Intraclass correlations (ICCs) indicated that the ERP morphology recorded with the two systems was very similar for the P1, N1, P2, N2, and P3 ERP peaks (r = .82 to .95) in both passive and active conditions, and less so, though still strong, for mismatch negativity ERP component (MMN; r = .67 to .74). There were few differences between peak amplitude and latency estimates for the two systems.Conclusions. An adapted EPOC EEG system can be used to index children’s late auditory ERP peaks (i.e., P1, N1, P2, N2, P3) and their MMN ERP component

Acoustic backscatter data from two visits to site P3 (P3A and P3B) during COMICS cruise DY086 in November to December, 2017

Acoustic backscatter data was collected at five frequencies (18, 38, 70, 120 and 200 kHz) across two visits to site P3, South Georgia, aboard the RRS Discovery during DY086. Acoustic backscatter was measured with the Simrad EK60. The data consistently shows no evidence of synchronised diel vertical migration