32 research outputs found

    On the occurrence of egg masses of the diamondshaped squid Thysanoteuthis rhombus Troschel, 1857 in the subtropical eastern Atlantic (Canary Islands). A potential commercial species?

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    8 páginas, 2 figuras, 1 tablaData on opportunistic sightings of diamond-shaped squid Thysanoteuthis rhombus egg masses in the Canary Islands (Atlantic Ocean) are presented. A total of 16 egg masses of this species were recorded and photographed from 2000 to 2010 around the western islands of the archipelago (El Hierro, Tenerife and La Gomera). These data reveal the existence of an important spawning area for diamond-shaped squid around the Canary Islands, in subtropical east Atlantic waters. We provide preliminary data for the potential development of an artisanal fishery focused on this species, and a discussion on its potential impacts on the marine ecosystem.This work has been supported by the project “Cetáceos, Oceanografía y Biodiversidad de las Aguas Profundas de La Palma y El Hierro” funded by the Ministry of Sciences and Innovation of the Spanish Government, grant number CETOBAPH-CGL2009-1311218.Peer reviewe

    Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

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    BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

    Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

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    Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

    All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ɓ2010

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    Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

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    Forouzanfar MH, Afshin A, Alexander LT, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. LANCET. 2016;388(10053):1659-1724.Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57.8% (95% CI 56.6-58.8) of global deaths and 41.2% (39.8-42.8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211.8 million [192.7 million to 231.1 million] global DALYs), smoking (148.6 million [134.2 million to 163.1 million]), high fasting plasma glucose (143.1 million [125.1 million to 163.5 million]), high BMI (120.1 million [83.8 million to 158.4 million]), childhood undernutrition (113.3 million [103.9 million to 123.4 million]), ambient particulate matter (103.1 million [90.8 million to 115.1 million]), high total cholesterol (88.7 million [74.6 million to 105.7 million]), household air pollution (85.6 million [66.7 million to 106.1 million]), alcohol use (85.0 million [77.2 million to 93.0 million]), and diets high in sodium (83.0 million [49.3 million to 127.5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Copyright (C) The Author(s). Published by Elsevier Ltd

    Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

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    Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≀ 18 years: 69, 48, 23; 85%), older adults (≄ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    Meiofaunal diversity from Los Abrigos del PorĂ­s and Los Cristianos beaches (Tenerife, Canary Islands)

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    Este trabajo sintetiza la tesis doctoral que con el tĂ­tulo 'Biodiversidad meiofaunal de las playas de Los Abrigos del PorĂ­s y de Los Cristianos en la isla de Tenerife. Estructura y dinĂĄmica de sus comunidades' y bajo la direcciĂłn de Jorge NĂșñez y MarĂ­a del Carmen Brito fue defendida en el Departamento de BiologĂ­a Animal de la Universidad de La Laguna en diciembre de 2004.Se analizan las variaciones estacionales de la estructura meiofaunal de dos playas de la isla de Tenerife (Los Abrigos del PorĂ­s y Los Cristianos), desde mayo de 2000 hasta abril de 2001. En cada una de las localidades, se seleccionaron dos puntos de muestreo, uno en el intermareal inferior y otro en el submareal somero (3 m de profundidad). El intermareal de Los Abrigos del PorĂ­s estuvo caracterizado por la presencia de arenas medias, y la estructura meiofaunal estuvo dominada por los copĂ©podos harpacticoides. Las especies mĂĄs abundantes fueron el copĂ©podo Ectinosomatidae sp. 1 y el poliqueto Microphthalmus pseudoaberrans. El submareal de Los Abrigos del PorĂ­s se caracterizĂł por una alternancia de arenas finas y medias, siendo los nematodos el grupo taxonĂłmico mĂĄs abundante. Las especies mĂĄs abundantes fueron los nematodos Siphonolaimus sp1 y Siphonolaimus sp2. El intermareal de Los Cristianos se caracterizĂł por una dominancia de arenas finas, siendo los nematodos el grupo taxonĂłmico mĂĄs abundante. En la segunda quincena de noviembre se produjo un cambio drĂĄstico en la estructura meiofaunal debido al aporte terrĂ­geno procedente de un barranco adyacente. Las especies mĂĄs abundantes fueron Odontophora sp. 3 y Theristus sp. El submareal de Los Cristianos se caracterizĂł por la presencia de arenas finas, siendo dominantes los nematodos en la estructura meiofaunal. Las especies mĂĄs abundantes fueron los nematodos Daptonema hirsutum, Pomponema sedecima y Oncholaimellus calvadosicus. Se realiza una correlaciĂłn entre los factores abiĂłticos analizados (granulometrĂ­a, materia orgĂĄnica, nitrĂłgeno y carbonatos) y las especies meiofaunales mĂĄs abundantes en cada una de las estaciones de muestreo.Community structure and seasonal variations. Two localities, Los Abrigos del PorĂ­s and Los Cristianos, of the south coast of Tenerife were sampled from May 2000 and April 2001 in order to describe seasonal variations of the meiofaunal community. In each locality, two stations were selected, one in the lower intertidal and one in the shallow subtidal (3 m deep). The intertidal of Los Abrigos del PorĂ­s was characterized by medium sands that were dominated by harpacticoid copepods, being the most abundant species the copepod Ectinosomatidae sp1 and the polychaete Microphthalmus pseudoaberrans. The subtidal of Los Abrigos del PorĂ­s was characterized by fine and medium sands, and nematodes dominated the meiofauna structure, being Siphonolaimus sp1 and Siphonolaimus sp2 the most dominant species. The intertidal of Los Cristianos was characterized by fine sands, being the nematodes the dominant taxonomic group. In the first fortnight of November a run-off from an adjacent ravine triggered an abrupt change in the meiofaunal structure of the sediments. The most abundant species were the nematodes Odontophora sp. 3 and Theristus sp. The subtidal of Los Cristianos was characterized by fine sands, being dominated by nematodes. The most dominant species were Daptonema hirsutum, Pomponema sedecima and Oncholaimellus calvadosicus. A correlation between abiotic factors (granulometry, organic matter, carbonates and nitrogen) and the most abundant species of the four stations is provided

    Revised species records reveal the Canary Islands as a cephalopod biodiversity hotspot

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    13 pages, 3 figures, 2 tableCephalopods are a diverse group of species, with a high ecological and economic relevance. Despite this, its species diversity has been studied in few places at regional scale. We herein aim to update the current state of knowledge and diversity of cephalopods fauna of the Canary Islands. We carried out a systematic review of the available literature regarding cephalopod species in the area spanned from 1834 to 2019. More specifically, we reviewed (a) records of historic and recent research cruises; (b) records of species from scientific literature and technical reports; and (c) stomach contents analysis of top predators. A total of 48 documents, including scientific literature, technical reports, and species referenced in museums collections of cephalopods caught around the Canary Islands were identified. The current species richness in different habitats from coastal to deep-sea zones was determined according to records and previous information on the ecology of each species. These records revealed that this small archipelago holds 85 confirmed species belonging to 31 families, representing ca. 10% of the overall known cephalopod diversity. The cephalopod community was dominated by oceanic cephalopods, followed by shelf-slope and coastal cephalopods species with 65, 11, and 9 species, respectively. 47% of the species showed a wide geographic distribution (33 cosmopolitan and 7 presents in more than one ocean), whereas 19 are only encountered in the Atlantic Ocean and Mediterranean Sea and 26 are exclusively Atlantic. This species richness is comparable to other cephalopod biodiversity hotspots, such as the Indian Ocean Ridge or the Caribbean. The Canarian cephalopod diversity likely to be underestimated, since scarce information exists on species inhabiting the deeper water layers around the Canary Islands. This work represents the first baseline of cephalopod biodiversity around the Canary Islands; hence, it constitutes a first step to develop future research on this taxonomic groupThis work has been partially funded by the Spanish Ministry of Sciences and Innovation via the National Plan Research Projects (DeepCet CTM2017-88686-P)Peer reviewe

    New Data on the Systematics of Comb-fin Squids Chtenopteryx spp. (Cephalopoda: Chtenopterygidae) from the Canary Islands

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    11 pages, 5 figures, 11 tablesThe systematics of the comb-fin squid species is problematic and poorly resolved. In total, 53 specimens of comb-fin squids (Chtenopteryx spp.) were caught at depths ranging from 30 to 800 m off the Canary Islands (NE Atlantic Ocean). Mantle lengths of the individuals ranged from 18 to 43 mm and the sample included immature, mature male and mature female specimens. Two species of comb-fin squids, Chtenopteryx canariensis and C. sicula, were identified by combining traditional morphological characters with a molecular analysis of a fragment of the cytochrome c oxidase subunit I (COI) gene. Intra- and interspecific genetic distances and maximum likelihood tree analyses based on COI sequences available from GenBank suggest the existence of at least four species, two from the Pacific and two from the Atlantic Ocean. Our data expand the current geographic range of C. canariensis from the NE to NW Atlantic. In the GenBank database, several sequences of comb-fin squid in different species-specific clades have been attributed only to C. sicula, indicating the possible existence of cryptic species and the need to re-analyse these data.Peer reviewe
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