Macro- and micro-geographic variation of short-beaked common dolphin’s whistles in the Mediterranean Sea and Atlantic Ocean

Author Posting. © The Author(s), 20113. This is the author's version of the work. It is posted here by permission of Taylor & Francis for personal use, not for redistribution. The definitive version was published in Ethology Ecology & Evolution 26 (2014): 392-404, doi:10.1080/03949370.2013.851122.Genetic studies have shown that there are small but significant differences between the short-beaked common dolphin populations in the Atlantic Ocean and those in the Mediterranean Sea. The short-beaked common dolphin is a highly vocal species with a wide sound production repertoire including whistles. Whistles are continuous, narrowband, frequency-modulated signals that can show geographic variation in dolphin species. This study tests whether the differences, highlighted by genetic studies, are recognisable in the acoustic features of short-beaked common dolphin’s whistles in the two adjacent areas of the Atlantic Ocean and the Mediterranean Sea. From a selected sample of good quality whistles (514 recorded in the Atlantic and 193 in the Mediterranean) 10 parameters of duration, frequency and frequency modulation were measured. Comparing data among basins, differences were found for duration and all frequency parameters except for minimum frequency. Modulation parameters showed the highest coefficient of variation. Through discriminant analysis we correctly assigned 75.7% of sounds to their basins. Furthermore, micro-geographic analysis revealed similarity between the sounds recorded around the Azores and the Canary archipelagos and between the Bay of Biscay and the Mediterranean Sea. Results are in agreement with the hypothesis proposed by previous genetic studies that two distinct populations are present, still supposing a gene flow between the basins. This study is the first to compare shortbeaked common dolphin’s whistles of the Atlantic Ocean and the Mediterranean areas.Data collection and processing in the Azores was conducted under projects POCTI/BSE/38991/01, PTDC/MAR/74071/2006 and M2.1.2/F/012/2011, supported by FCT (Fundação para a Ciência e a Tecnologia) and DRCTC/SRCTE (Secretaria Regional de Ciência, Tecnologia e Equipamentos), FEDER funds, the Competitiveness Factors Operational (COMPETE), QREN European Social Fund and Proconvergencia Açores Program. We acknowledge funds provided by FCT to LARSyS Associated Laboratory & IMAR-University of the Azores/ the Thematic Area E of the Strategic Project (OE & Compete) and by the DRCTC – Government of the Azores pluriannual funding. M.A. Silva was supported by an FCT postdoctoral grant (SFRH/ BPD/29841/2006). I. Cascão and R. Prieto were supported by FCT doctoral grants (SFRH/BD/ 41192/2007 and SFRH/BD/32520/2006, respectively) and R. Prieto by a research grant from the Azores Regional Fund for Science and Technology (M3.1.5/F/115/2012). Data collection by SECAC (Society for the Study of Cetaceans in the Canary Archipelago) was funded by the U.E. LIFE programme – project LIFE INDEMARES (LIFE 07/NAT/E/000732)- and the Fundación Biodiversidad, under the Spanish Ministry of Environment, Rural and Marine Affairs (project ZEC-TURSIOPS).2014-11-0

Dolphin whistles can be useful tools in identifying units of conservation

Data collection and processing in the Azores was funded by Fundação para a Ciência e a Tecnologia (FCT) and Fundo Regional da Ciência e Tecnologia (FRCT), through research projects TRACE-PTDC/MAR/74071/2006 and MAPCET-M2.1.2/F/012/2011 (FEDER, the Competitiveness Factors Operational (COMPETE), QREN European Social Fund, and Pro convergencia Açores/EU Program). We also thank FCT for supporting MARE (UID/MAR/04292/2019) and OKEANOS (UIB/05634/2020), as well as for the research grants awarded to PR (SFRH/BPD/108007/2015) and CI (Project Awareness - PTDC/BIA-BMA/30514/2017). SMA is supported through project SUMMER (H2020-EU.3.2.3.1, GA 817806). Data collection by SECAC was funded by the EU LIFE programme—project LIFE INDEMARES (LIFE 07/NAT/E/000732)— and the Fundación Biodiversidad under the Spanish Ministry of Environment, Rural and Marine Affairs (project ZEC-TURSIOPS). EP was supported by a LLP/Erasmus grant 2010–2011 for collecting data in the Canary Islands.Background: Prioritizing groupings of organisms or ‘units’ below the species level is a critical issue for conservation purposes. Several techniques encompassing different time-frames, from genetics to ecological markers, have been considered to evaluate existing biological diversity at a sufficient temporal resolution to define conservation units. Given that acoustic signals are expressions of phenotypic diversity, their analysis may provide crucial information on current differentiation patterns within species. Here, we tested whether differences previously delineated within dolphin species based on i) geographic isolation, ii) genetics regardless isolation, and iii) habitat, regardless isolation and genetics, can be detected through acoustic monitoring. Recordings collected from 104 acoustic encounters of Stenella coeruleoalba, Delphinus delphis and Tursiops truncatus in the Azores, Canary Islands, the Alboran Sea and the Western Mediterranean basin between 1996 and 2012 were analyzed. The acoustic structure of communication signals was evaluated by analyzing parameters of whistles in relation to the known genetic and habitat-driven population structure. Results: Recordings from the Atlantic and Mediterranean were accurately assigned to their respective basins of origin through Discriminant Function Analysis, with a minimum 83.8% and a maximum 93.8% classification rate. A parallel pattern between divergence in acoustic features and in the genetic and ecological traits within the basins was highlighted through Random Forest analysis. Although it is not yet possible to establish a causal link between each driver and acoustic differences between basins, we showed that signal variation reflects fine-scale diversity and may be used as a proxy for recognizing discrete units. Conclusion: We recommend that acoustic analysis be included in assessments of delphinid population structure, together with genetics and ecological tracer analysis. This cost-efficient non-invasive method can be applied to uncover distinctiveness and local adaptation in other wide-ranging marine species.Publisher PDFPeer reviewe

Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: a multicenter, retrospective analysis

Background: Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell lung cancer (NSCLC) has improved the survival of patients. However, a substantial percentage of patients do not respond to this treatment. We examined the use of DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in patients recruited with current stage IV NSCLC. Methods: In this multicentre study, we recruited adult patients from 15 hospitals in France, Spain, and Italy who had histologically proven stage IV NSCLC and had been exposed to PD-1 blockade during the course of the disease. The study structure comprised a discovery cohort to assess the correlation between epigenetic features and clinical benefit with PD-1 blockade and two validation cohorts to assess the validity of our assumptions. We first established an epigenomic profile based on a microarray DNA methylation signature (EPIMMUNE) in a discovery set of tumour samples from patients treated with nivolumab or pembrolizumab. The EPIMMUNE signature was validated in an independent set of patients. A derived DNA methylation marker was validated by a single-methylation assay in a validation cohort of patients. The main study outcomes were progression-free survival and overall survival. We used the Kaplan-Meier method to estimate progression-free and overall survival, and calculated the differences between the groups with the log-rank test. We constructed a multivariate Cox model to identify the variables independently associated with progression-free and overall survival. Findings: Between June 23, 2014, and May 18, 2017, we obtained samples from 142 patients: 34 in the discovery cohort, 47 in the EPIMMUNE validation cohort, and 61 in the derived methylation marker cohort (the T-cell differentiation factor forkhead box P1 [FOXP1]). The EPIMMUNE signature in patients with stage IV NSCLC treated with anti-PD-1 agents was associated with improved progression-free survival (hazard ratio [HR] 0·010, 95% CI 3·29 × 10 −4–0·0282; p=0·0067) and overall survival (0·080, 0·017–0·373; p=0·0012). The EPIMMUNE-positive signature was not associated with PD-L1 expression, the presence of CD8+ cells, or mutational load. EPIMMUNE-negative tumours were enriched in tumour-associated macrophages and neutrophils, cancer-associated fibroblasts, and senescent endothelial cells. The EPIMMUNE-positive signature was associated with improved progression-free survival in the EPIMMUNE validation cohort (0·330, 0·149–0·727; p=0·0064). The unmethylated status of FOXP1 was associated with improved progression-free survival (0·415, 0·209–0·802; p=0·0063) and overall survival (0·409, 0·220–0·780; p=0·0094) in the FOXP1 validation cohort. The EPIMMUNE signature and unmethylated FOXP1 were not associated with clinical benefit in lung tumours that did not receive immunotherapy. Interpretation: Our study shows that the epigenetic milieu of NSCLC tumours indicates which patients are most likely to benefit from nivolumab or pembrolizumab treatments. The methylation status of FOXP1 could be associated with validated predictive biomarkers such as PD-L1 staining and mutational load to better select patients who will experience clinical benefit with PD-1 blockade, and its predictive value should be evaluated in prospective studies

Cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in progressive neurodegenerative conditions: a scoping review

BACKGROUND: Despite their potentially significant impact, cognitive disability may be overlooked in a number of progressive neurodegenerative conditions, as other difficulties dominate the clinical picture. OBJECTIVE: We examined the extent, nature and range of the research evidence relating to cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in Parkinsonian disorders, multiple sclerosis (MS), frontotemporal dementias (FTD), motor neuron disease and Huntington’s disease. METHODS: Scoping review based on searches of MEDLINE and CINAHL up to 15 March 2016. RESULTS: We included 140 eligible papers. Over half of the studies, and almost all the randomised controlled trials, related to MS, while a number of single case studies described interventions for people with FTD. CR interventions addressed functional ability, communication and interaction, behaviour or memory. The majority of psychotherapy interventions involved cognitive behavioural therapy for depression or anxiety. Self-management interventions were mainly available for people with MS. There were few reports of interventions specific to caregivers. Numerous methodological challenges were identified. CONCLUSIONS: The limited range of studies for all conditions except MS suggests a need firstly to synthesise systematically the available evidence across conditions and secondly to develop well-designed studies to provide evidence about the effectiveness of CR and other psychological interventions

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction