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Abstract Worldwide, governments are implementing strategies to combat marine litter. However, their effectiveness is largely unknown because we lack tools to systematically monitor marine litter over broad spatio-temporal scales. Metre-sized aggregations of floating debris generated by sea-surface convergence lines have been reported as a reliable target for detection from satellites. Yet, the usefulness of such ephemeral, scattered aggregations as proxy for sustained, large-scale monitoring of marine litter remains an open question for a dedicated Earth-Observation mission. Here, we track this proxy over a series of 300,000 satellite images of the entire Mediterranean Sea. The proxy is mainly related to recent inputs from land-based litter sources. Despite the limitations of in-orbit technology, satellite detections are sufficient to map hot-spots and capture trends, providing an unprecedented source-to-sink view of the marine litter phenomenon. Torrential rains largely control marine litter inputs, while coastal boundary currents and wind-driven surface sweep arise as key drivers for its distribution over the ocean. Satellite-based monitoring proves to be a real game changer for marine litter research and management. Furthermore, the development of an ad-hoc sensor can lower the minimum detectable concentration by one order of magnitude, ensuring operational monitoring, at least for seasonal-to-interannual variability in the mesoscale.

Abstract Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways and neurocognitive performance regulate epigenetic dynamics in these disorders. The current combined and transdiagnostic study investigated whether inflammatory, oxidative stress, adhesion molecule, neurocognitive and functional performance are significant predictors of telomere dynamics in a sample stratified by global DNA methylation levels. Peripheral blood inflammation, oxidative stress and adhesion molecule biomarkers and neurocognitive function were assessed twice over a 1-year period in 80 individuals, including 16 with schizophrenia (SZ), 16 with bipolar disorder (BD), 16 with major depressive disorder (MDD), 15 with T2DM, and 17 healthy controls (HCs). Leukocyte telomere length (LTL) was measured by qRT-PCR using deoxyribonucleic acid (DNA) extracted from peripheral blood samples. A posteriori, individuals were classified based on their global methylation score (GMS) at baseline into two groups: the below-average methylation (BM) and above-average methylation (AM) groups. Hierarchical and k-means clustering methods, mixed one-way analysis of variance and linear regression analyses were performed. Overall, the BM group showed a significantly higher leukocyte telomere length (LTL) than the AM group at both time points (p = 0.02; η2p = 0.06). Moreover, the BM group had significantly lower levels of tumor necrosis factor alpha (TNF-α) (p = 0.03; η2p = 0.06) and C-reactive protein (CRP) (p = 0.03; η2p = 0.06) than the AM group at the 1-year follow-up. Across all participants, the regression models showed that oxidative stress (reactive oxygen species [ROS]) (p = 0.04) and global cognitive score [GCS] (p = 0.02) were significantly negatively associated with LTL, whereas inflammatory (TNF-α) (p = 0.04), adhesion molecule biomarkers (inter cellular adhesion molecule [ICAM]) (p = 0.009), and intelligence quotient [IQ] (p = 0.03) were significantly positively associated with LTL. Moreover, the model predictive power was increased when tested in both groups separately, explaining 15.8% and 28.1% of the LTL variance at the 1-year follow-up for the AM and BM groups, respectively. Heterogeneous DNA methylation in individuals with T2DM and severe mental disorders seems to support the hypothesis that epigenetic dysregulation occurs in a transdiagnostic manner. Our results may help to elucidate the interplay between epigenetics, molecular processes and neurocognitive function in these disorders. DNA methylation and LTL are potential therapeutic targets for transdiagnostic interventions to decrease the risk of comorbidities.

Introduction COVID-19 is associated with higher morbimortality in pregnant people compared with non-pregnant people. At present, the benefits of maternal immunisation are considered to outweigh the risks, and therefore, vaccination is recommended during pregnancy. However, additional information is needed on the safety of the vaccines in this population.Methods and analysis This a retrospective cohort nested case–control study in pregnant people who attended maternity hospitals from eight Latin American and Caribbean countries. A perinatal electronic clinical history database with neonatal and obstetric information will be used. The proportion of pregnant people immunised with COVID-19 vaccines of the following maternal and neonatal events will be described: preterm infant, small for gestational age, low birth weight, stillbirth, neonatal death, congenital malformations, maternal near miss and maternal death. Moreover, the risk of prematurity, small for gestational age and low birth weight associated with exposure to COVID-19 vaccines will be estimated. Each case will be matched with two groups of three randomly selected controls. Controls will be matched by hospital and mother’s age (±3 years) with an additional matching by delivery date and conception time in the first and second control groups, respectively. The estimated required sample size for the main analysis (exposure to any vaccine) concerning ‘non-use’ is at least 1009 cases (3027 controls) to detect an increased probability of vaccine-associated event risk of 30% and at least 650 cases (1950 controls) to detect 30% protection. Sensitivity and secondary analyses considering country, type of vaccine, exposure windows and completeness of immunisation will be reported.Ethics The study protocol was reviewed by the Ethical Review Committee on Research of the Pan American Health Organization. Patient informed consent was waived due to the retrospective design and the utilisation of anonymised data (Ref. No: PAHOERC.0546.01). Results will be disseminated in open access journals.

Abstract Background Myocarditis and pericarditis have been associated most notably with mRNA vaccines, but the association with a recently authorized adjuvated vaccine (NVX-CoV2373) is controversial. Objective The aim was to analyze the cases of myocarditis and pericarditis in association with NVX-CoV2373 reported to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase), applying disproportionality analyses. Patients and methods The main characteristics of the ICSRs reporting myopericarditis with NVX-CoV2373 have been summarized. Reporting odds ratios (RORs) as a measure of disproportionality for reported myopericarditis (November 1967–August 2022) have been calculated for NVX-CoV2373; mRNA and adenoviral vector-based vaccines were also included as a reference. Results In total, 61 ICSRs included NVX-CoV2373. Most of the reports originated in Australia (50; 82.0%); 24 (39.3%) were considered serious. None of them were fatal. The median age of individuals was 35.5 years old, and most were males (38; 62.3%). Chest pain was the most common co-reported event 43 (70.5%). The median induction period was 3 days after immunization. Increased disproportionality for myopericarditis was found for NVX-CoV2373 (ROR 14.47, 95% confidence interval [CI] 11.22–18.67) and mRNA vaccines: BNT162b2 (ROR 17.15, 95% CI 16.88–17.42) and mRNA-1273 (ROR 6.92, 95% CI 6.77–7.08). Higher values were found in males. The adenoviral vector-based vaccine Ad26.COV2.S showed slightly increased disproportionality (ROR 1.83, 95% CI 1.70–1.98), whereas no increased disproportionality was found for ChAdOx1. Conclusions NVX-CoV2373 vaccine showed a similar increased disproportionality as mRNA vaccines. More evidence from controlled studies is necessary; however, a precautionary approach is warranted. Healthcare professionals should be aware of the potential occurrence of myopericarditis with this new vaccine.

Abstract Background Public health initiatives for improving adherence to primaquine based regimens and enhancing effective pharmacovigilance are needed to support the efforts for malaria elimination in real world conditions. Methods A multicomponent patient-oriented strategy using a Smart Safety Surveillance (3S) approach including: (1) educational materials for treatment counselling and identification of warning symptoms of haemolytic anaemia; (2) an mHealth component using Short Message Service (SMS) treatment reminders and (3) development and implementation of follow-up phone surveys three days after treatment completion, using a web-based platform linked to the local information system of malaria. Adherence was measured using the Morisky Medication Adherence Scale. Self-reported events were registered using a structured questionnaire and communicated to the Brazilian Health Regulatory Agency. Results Educational materials were disseminated to 5594 patients, of whom 1512 voluntarily entered the mHealth component through the local information system; 7323 SMS were sent, and 1062 participants completed a follow-up survey after treatment. The mean age of patients was 37.36 years (SD 13.65), 61.24% were male, 98.54% were infected with. Plasmodium vivax and 95.90% received a short regimen of chloroquine plus primaquine (CQ + PQ 7 days), as per malaria case management guidelines in Brazil. From the 1062 surveyed participants 93.31% were considered adherent to the treatment. Most of the patients (95.20%) reported at least one adverse event. Headache, lack of appetite and nausea/vomiting were the most frequently reported adverse events by 77.31%, 70.90% and 56.78% of the patients respectively. A quarter of the patients reported anxiety or depression symptoms; 57 (5.37%) patients reported 5 to 6 warning symptoms of haemolytic anaemia including jaundice and dark urine in 44 (4.14%). Overall, three patients presenting symptoms of haemolytic anaemia attended a hospital and were diagnosed with G6PD deficiency, and one had haemolysis. All of them recovered. Conclusions Under real world conditions, a multicomponent patient-oriented strategy using information and communication technologies allowed health care providers to reinforce treatment adherence and enhance safety surveillance of adverse events associated with regimens using primaquine. Active monitoring through phone surveys also reduced under-reporting of ADRs. This approach is low-cost, scalable and able to support prioritized activities of the national malaria programme.

Resumen: Introducción y objetivos: La ecocardiografía transesofágica (ETE) es una herramienta muy importante en cirugía cardíaca. En este artículo describimos el impacto de los hallazgos intraoperatorios con ETE en la cirugía cardíaca. Método: Estudio prospectivo y descriptivo de pacientes sometidos a cirugía programada con circulación extracorpórea a los que se realiza una ETE intraoperatoria antes y después de la cirugía. Los datos recogidos fueron la confirmación de la indicación quirúrgica, los nuevos hallazgos preoperatorios y postoperatorios, el cambio en la actitud terapéutica y la reentrada en circulación extracorpórea postoperatoria. Resultados: El número de pacientes fue de 488. En 122 de ellos (25%) se encontraron nuevos hallazgos, en 57 (11,68%) se realizó un cambio en la actitud terapéutica, en 31 (6,35%) se encontraron hallazgos postoperatorios y en 13 (2,6%) se volvió a entrar en circulación extracorpórea. Conclusiones: La ETE es una herramienta de calidad y seguridad para el paciente; su uso intraoperatorio debería ser obligatorio en cirugía cardíaca. Abstract: Introduction and objectives: Transoesophageal echocardiography (TOE) is a very important tool in cardiac surgery. A description is presented in this article on the impact of the findings using TOE during cardiac surgery. Method: A prospective and descriptive study was conducted on patients undergoing scheduled surgery with cardiopulmonary bypass (CPB) to which TOE is performed before and after surgery. The data collected were: the confirmation of the surgical indication, the new pre-operative and post-operative findings, the modifications in the planned surgery, and the re-entry into CPB. Results: The study included 488 patients. New findings were found in 122 patients (25%), which a led to a change in the planned surgery in 57 (11.68%). In the 31 patients (6.35%) in whom postoperative problems were found, 13 (2.6%) needed re-entry into CPB. Conclusions: Using TOE during surgery is a safety and quality tool for the patient, and its use should be required in cardiac surgery. Palabras clave: Ecocardiografía transesofágica, Hallazgos intraoperatorios, Hallazgos preoperatorios, Hallazgos postoperatorios, Cirugía cardiaca, Keywords: Transoesophageal echocardiography, Intra-operative findings, Pre-operative findings, Post-operative findings, Cardiac surgery

Resumen: Paciente de 78 años con aneurisma sacular en el arco aórtico, la paciente es tratada con una endoprótesis multicapa moduladora de flujo. A los 3 meses se comprueba la trombosis completa del aneurisma. Abstract: Patient 78 years old, with aortic arch saccular aneurysm, the patient is treated with a multilayer flow modulator stent. Three months after, we observe the complete aneurysm thrombosis. Palabras clave: Aneurisma de arco aórtico, Multicapa moduladora de flujo, Keywords: Aortic arch aneurysm, Multilayer flow modulator

Abstract Background Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are childhood onset neurodevelopmental disorders that may persist into adulthood. ASD and ADHD tend to run in families and may have a significant negative impact on the health and longevity of those with the disorder and their relatives. The aim of this study will be to analyze the risk of mortality among children, adolescents, and adults with ASD or ADHD and their first-degree relatives. Methods/design We will conduct a systematic review and meta-analysis of observational studies. Searches of PubMed/MEDLINE, EMBASE, PsycINFO, SCOPUS, and ISI Web of Science will be used to identify epidemiological studies. Eligible studies will be observational studies reporting study-specific data for all-cause mortality or cause-specific mortality in children, adolescents, or adults with ASD or ADHD and/or their first-degree relatives. Cohort studies and case-control studies will be included. The primary outcome will be all-cause mortality. The secondary outcome will be cause-specific mortality. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study risk of bias/methodological quality will be appraised by two reviewers independently. The methodological quality of epidemiological studies will be appraised using the Newcastle-Ottawa Scale (NOS). Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary studies will be conducted where appropriate. Subgroup analyses for exploring statistical heterogeneity, if feasible, will include gender, age group, ethnicity, comorbidities, classification of cause of death, and relevant study characteristics. Discussion Our study will establish the extent of the epidemiological evidence underlying the risk of mortality among children, adolescents, and adults with ASD or ADHD and their first-degree relatives. We anticipate that our findings will be of interest to patients, their families, caregivers, healthcare professionals, scientists, and policy makers. Implications for future epidemiological research will be discussed. Systematic review registration PROSPERO CRD42017059955 .

Abstract Background Anorexia nervosa is characterized by a severe restriction of caloric intake, low body weight, fear of gaining weight or of becoming fat, and disturbance of body image. Pathogenesis of the disorder may include genetic predisposition, hormonal changes and a combination of environmental, psychosocial, and cultural factors. Cancer is the second leading cause of death worldwide. At present, no systematic reviews and meta-analyses have evaluated the risk of cancer in people with anorexia nervosa. The objective of this study will be to evaluate the association between anorexia nervosa and the risk of developing or dying from cancer. Methods/design This study protocol is part of a systematic collection and assessment of multiple systematic reviews and meta-analyses (umbrella review) evaluating the association of cancer and multiple central nervous system disorders. We designed a specific protocol for a new systematic review and meta-analysis of observational studies of anorexia nervosa with risk of developing or dying from any cancer. Data sources will be PubMed, Embase, Scopus, Web of Science, and manual screening of references. Observational studies (case–control and cohort) in humans that examined the association between anorexia nervosa and risk of developing or dying from cancer will be sought. The primary outcomes will be cancer incidence and cancer mortality in association with anorexia nervosa. Secondary outcomes will be site-specific cancer incidence and mortality, respectively. Screening of abstracts and full texts, and data abstraction will be performed by two team members independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. The quality of studies will be assessed by using the Ottawa-Newcastle scale by two team members independently. Random effects models will be conducted where appropriate. Subgroup and additional analyses will be conducted to explore the potential sources of heterogeneity. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. Discussion Findings from this systematic review will inform an ongoing umbrella review on cancer and central nervous system disorders. Our systematic review and meta-analysis of observational studies will establish the extent of the epidemiological evidence underlying the association between anorexia nervosa and cancer. Systematic review registration PROSPERO CRD42017067462.

Abstract Background The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer. Methods/design We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer’s disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down’s syndrome, epilepsy, Huntington’s disease, multiple sclerosis, Parkinson’s disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. Discussion Our study will establish the extent of the epidemiological evidence underlying the associations between central nervous system disorders and cancer and will provide a rigorous and updated synthesis of a range of important site-specific cancer outcomes. Systematic review registration PROSPERO CRD42016052762

Resumen: Se presenta el caso de un paciente al que se le implanta una prótesis transcatéter en posición tricúspide vía vena yugular interna sobre una bioprótesis disfuncionante demostrando que es una alternativa terapéutica válida a la reintervención en esos enfermos de alto riesgo quirúrgico. Abstract: The case is presented of a patient who received an implant with a transcatheter prosthesis in tricuspid position through the internal jugular vein on a dysfunctional bioprosthesis, demonstrating that it is a valid therapeutic alternative to re-operation in these patients with high surgical risk. Palabras clave: Implantación de prótesis transcatéter, Posición tricúspide, Disfunción de bioprótesis, Keywords: Transcatheter prosthesis implantation, Tricuspid position, Bioprosthesis dysfunction

In this work we focus on the Alboran Sea (western Mediterranean) to relate wind field and ocean velocity variability with chlorophyll a (Chl a) behaviour, using a 2-km resolution, coupled 3D ocean circulation-NPZD model (ROMS). The analysis is done in three steps. First, we split the seasonal and residual contribution for the fields under study. Second, we calculate the corresponding empirical orthogonal functions (EOFs) for the seasonal and residual parts. Finally, we relate each pair of variables for both seasonal and residual contribution EOFs. The results reported here allow the links between wind and Chl a to be quantified. We explain these links in terms of the ocean velocity field acting as a driver of Chl a variability. The results show that, although the seasonal part of the Chl a field is modulated by the vertical velocity, the residual component is modulated by the horizontal velocity components. Vertical velocities are responsible, through coastal upwelling, for Chl a bloom enhancement, while horizontal velocities spread coastal Chl a surface blooms off-shore.

La llegada de nuevos medicamentos al mercado exige muchos años de investigación previa junto con la evaluación continua de sus resultados durante toda la vida del medicamento. Ello justifica la necesidad de la investigación farmacoepidemiológica, entendida como el estudio del uso y los efectos de los medicamentos en grandes poblaciones. En la actualidad, este tipo de investigación parece más factible que nunca, habida cuenta de la expansión que han experimentado de las fuentes de información por la incorporación masiva de datos, (por ejemplo, registros clínicos de pacientes o historia clínica electrónica). No obstante, ante el entusiasmo que suscita el “Big Data”, se debe tener en cuenta el riesgo de sobreinformación, de evidencia fragmentada y que su naturaleza mayoritariamente observacional está sujeta a sesgos y confusión. La utilización de los métodos epidemiológicos en este escenario se antoja fundamental para su análisis. En definitiva, el manejo y aprovechamiento de estas fuentes de información en expansión para generar información útil constituye el próximo desafío para la aplicación de los métodos de investigación en la farmacoepidemiología moderna.

Las nuevas recomendaciones respecto a la utilización de estatinas potentes y/o dosis altas (terapia intensiva) para el tratamiento de la enfermedad cardiovascular se han basado en la extrapolación de los resultados de los ensayos clínicos. El objetivo fue describir el perfil clínico-epidemiológico de los pacientes que inician tratamiento con estatinas para la prevención secundaria en España y estudiar qué factores determinan la utilización de estatinas en terapia intensiva. Métodos: Estudio transversal a partir de 88.751 pacientes ≥45 años con enfermedad cardiovascular que iniciaron tratamiento con estatinas (enero 2007-diciembre 2011). Los tratamientos con dosis superiores a 40 mg/día de simvastatina (o estatina equipotente) se consideraron terapia intensiva. Se construyeron modelos de regresión logística multivariante con el fin de examinar la asociación de las variables relacionadas con la prescripción de terapia intensiva respecto al uso de la terapia moderada. Resultados: Se identificó a 16.857 personas adultas que iniciaron tratamiento con estatinas para la prevención secundaria. Los factores predictores para el inicio de terapia intensiva fueron el año de prescripción, sexo masculino (odds ratio ajustada: 1,70; IC95%: 1,44-2,00), edad >75 años (1,39; 1,15-1,69), historia previa de enfermedad isquémica coronaria (1,71; 1,44-2,04), accidente isquémico transitorio de cualquier localización (1,24; 0,97-1,59), tabaquismo (1,62; 1,34-1,95), hipertensión (1,41; 1,20-1,65) y tratamiento reciente con fibratos (2,32; 1,27-4,26). Conclusiones: La utilización de terapia intensiva con estatinas está determinada por el tipo de evento vascular previo y con la edad (>75 años, en los que el balance beneficio-riesgo podría ser discutible). No se encuentran diferencias estadísticamente significativas en función del c-LDL.

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents.We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution.Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008.

Diatoms, a major component of the large-sized phytoplankton, are able to produce and release polyunsaturated aldehydes after cell disruption (potential PUAs or pPUA). These organisms are dominant in the large phytoplankton fraction (>10 µm) in the Strait of Gibraltar, the only connection between the Mediterranean Sea and the Atlantic Ocean. In this area, the hydrodynamics exerts a strong control on the composition and physiological state of the phytoplankton. This environment offers a great opportunity to analyze and compare the little known distribution of larger sized PUA producers in nature and, moreover, to study how environmental variables could affect the ranges and potential distribution of these compounds. Our results showed that, at both tidal regimes studied (Spring and Neap tides), diatoms in the Strait of Gibraltar are able to produce three aldehydes: Heptadienal, Octadienal and Decadienal, with a significant dominance of Decadienal production. The PUA released by mechanical cell disruption of large-sized collected cells (pPUA) ranged from 0.01 to 12.3 pmol from cells in 1 L, and from 0.1 to 9.8 fmol cell−1. Tidal regime affected the abundance, distribution and the level of physiological stress of diatoms in the Strait. During Spring tides, diatoms were more abundant, usually grouped nearer the coastal basin and showed less physiological stress than during Neap tides. Our results suggest a significant general increase in the pPUA productivity with increasing physiological stress for the cell also significantly associated to low nitrate availability.

Fundamentos: Trabajos previos han sugerido que el bloqueo dual con inhibidores del sistema renina-angiotensina (SRA) estaría asociado a un incremento de efectos adversos comparado con la monoterapia. Se reexamina la seguridad del doble bloqueo del SRA, especialmente en pacientes de riesgo y se explora la estabilidad de la evidencia acumulada a lo largo de los años. Método: Revisión sistemática con metaanálisis de efectos aleatorios. Se revisaron 15 metaanálisis publicados anteriormente como punto de partida. Se realizó una búsqueda en PubMed/Medline de estudios observacionales y de ensayos clínicos controlados recientes. Las variables dependientes estudiadas fueron: mortalidad (general y cardiovascular), hiperpotasemia, hipotensión, insuficiencia renal, accidente cerebrovascular y la retirada del tratamiento por efectos adversos. Se calcularon los riesgos relativos (RR) y su intervalo de confianza (IC95%)Resultados: El bloqueo dual del SRA no se asoció con una reducción del RR de la mortalidad general (RR:1,00; IC95%: 0,96-1,05; 21 estudios), ni de la mortalidad cardiovascular (RR:1,01; 0,94-1,09; 13 estudios) ni del riesgo de accidente cerebrovascular (RR:1,02; 0,94-1,11; 11 estudios) en comparación con la monoterapia. El bloqueo dual se asoció a un riesgo aumentado de hiperpotasemia (RR:1,58; 1,37-1,81; 34 estudios), hipotensión (RR:1,66; 1,41-1,95; 25 estudios), daño renal (1,52; 1,28-1,81; 29 estudios) y retirada del tratamiento por efectos adversos (RR:1,26; 1,22-1,30; 37 estudios). Los resultados fueron consistentes en las cohortes de pacientes con diabetes mellitus, enfermedad renal o insuficiencia cardiaca. Conclusiones: El bloqueo dual del SRA vs monoterapia incrementa los riesgos de hiperpotasemia, hipotensión, insuficiencia renal e interrupción del tratamiento por efectos adversos. Además no ofrece beneficios adicionales por reducción de la mortalidad general, mortalidad cardiovascular o accidente cerebrovascular. Estos hallazgos son consistentes a lo largo del tiempo.

Very few mass stranding events of invertebrates have been reported. In this paper, we report a mass stranding of multiple benthic organisms occurred at Punta Umbría beach (S Spain) after the passage of storm Emma (28 February to 5 March 2018). The most abundant organisms were identified, and exceptional meteorological and oceanographic events were analyzed, as a basis to understand the causes of stranding. The morphodynamic changes affecting the beach profile during the storm were inferred using a cross shore depth-integrated and time averaged numerical model (CSHORE). Among the stranded species, decapods (Upogebia spp., Atelecyclus undecimdentatus), sipunculids (Sipunculus nudus), starfish (Astropecten sp.), and sessile tunicates were dominant. Storm Emma involved extreme significant wave heights of up to 7.27 m, low pressures, strong SW winds, precipitations and spring tides that modified the seabed elevation to depth as deep as −10 m. Simulations suggest that benthic organisms living at a water depth between −10 to −0.3 m were buried under a layer of sediment of up to ca. 10 cm deposited during the storm. This burial preceded the transport of intertidal and subtidal benthic organisms to the dry beach, causing their stranding. Impacts on the quality of habitat, biodiversity and the productivity of coastal ecosystems are discussed.

Vertical distributions of turbulent energy dissipation rates and fluorescence were measured simultaneously with a high-resolution micro-profiler in four different oceanographic regions, from temperate to polar and from coastal to open waters settings. High fluorescence values, forming a deep chlorophyll maximum (DCM), were often located in weakly stratified portions of the upper water column, just below layers with maximum levels of turbulent energy dissipation rate. In the vicinity of the DCM, a significant negative relationship between fluorescence and turbulent energy dissipation rate was found. We discuss the mechanisms that may explain the observed patterns of planktonic biomass distribution within the ocean mixed layer, including a vertically variable diffusion coefficient and the alteration of the cells’ sinking velocity by turbulent motion. These findings provide further insight into the processes controlling the vertical distribution of the pelagic community and position of the DCM.

de los grupos farmacológicos más prescritos en la mayoría de países des- arrollados. El objetivo principal del presente trabajo fue explorar el patrón de uso de ansiolíticos e hipnóticos en España durante el período 2000-2011 y comparar su incremento con el de cinco países europeos. Método: Estudio ecológico descriptivo del consumo en España a partir de datos de medicamentos dispensados en oficina de farmacia y facturados a través de receta oficial con cargo al Sistema Nacional de Salud. El consumo anual y total se expresó en dosis diarias definidas por 1.000 habitantes y día (DDD/1.000 hab/día) en cada subgrupo terapéutico, principio activo y aten- diendo a la semivida plasmática. También se establecieron comparaciones aproximativas con otros países. Resultados: El uso de ansiolíticos e hipnóticos fue de 56,7 DDD/1.000 hab/día en el año 2000 y 82,9 DDD/1.000 hab/día en el año 2011 (incremen- to del 46,1% en el período). Lorazepam y alprazolam fueron los ansiolíticos más consumidos (20,5 y 15,6 DDD/1.000 hab/día en 2011, respectivamente), mientras que lormetazepam lo fue del grupo de los hipnóticos (18,3 DDD/1.000 hab./día en 2011). En términos relativos, lormetazepam y zolpi- dem fueron los hipnóticos que más incrementaron su uso (103,3% y 85,1%, respectivamente) mientras que lorazepam e hidroxicina lo fueron entre los ansiolíticos (75,1% y 72,8%, respectivamente). En España (período 2003- 2010), el incremento total en el consumo de ansiolíticos e hipnóticos fue de +34,3%, siendo del +24,0% para Portugal, +4,0% para Italia y -6,1% para Francia. Conclusiones: Durante el período estudiado, el consumo de ansiolíticos e hipnóticos se incrementó en España, siendo el incremento superior incluso al reportado en otros países europeos..

BackgroundMedications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes.Methods and findingsEligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke-singly and as a composite endpoint, major cardiovascular outcome-and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality-singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90-1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79-1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96-1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73-1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90-1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72-1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65-1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78-1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies. Potential inconsistency was identified in network meta-analyses of stroke and angina pectoris, limiting the conclusiveness of findings for these single endpoints.ConclusionsIn adults with diabetes, comparisons of different RAS blockers showed similar effects of ACE inhibitors and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies, the combination of an ACE inhibitor and an ARB failed to provide significant benefits on major outcomes. Clinicians should discuss the balance between benefits, costs, and potential harms with individual diabetes patients before starting treatment.Review registrationPROSPERO CRD42014014404.

The Strait of Gibraltar replenishes the Mediterranean with Atlantic waters through an intense eastward current known as the Atlantic Jet (AJ). The AJ fertilizes the southwestern Mediterranean and is considered to be the ultimate factor responsible for the comparatively high fish production of this region. Here, we perform an analysis of the available historical catches and catch per unit effort (CPUE), together with a long series of surface currents, kinetic energy and chlorophyll concentration. We show that the high kinetic energy of the AJ increases primary production but also negatively impacts the recruitment of anchovy. We contend that anchovy recruitment in the region is inhibited by the advection and dispersion of larvae and post-larvae during periods of strong advection by the AJ. The inhibitory impact of kinetic energy on anchovy landings is not a transient but rather a persistent state of the system. An exceptional combination of events creates an outbreak of this species in the Alboran Sea. These events depend on the Mediterranean-Atlantic exchange of water masses and, therefore, are highly sensitive to climate changes that are projected, though not always negatively, for fish landings.

Climate change is affecting marine ecosystems altering the distribution and abundance of organisms, with implications for fisheries and food security. This warming-induced reshuffle in species abundance could bring threats and opportunities to the fisheries, but needs to be assessed to promote effective actions and to foster resilience. We analyzed the density and distribution patterns of deep-sea rose shrimp (Parapenaeus longirostris), as well as identified the main environmental have identified the environmental drivers shaping its habitat along the western Mediterranean (Iberian Peninsula) during the period 2001–2020. Using spatial distribution models developed concurrently with an ensemble of four Regional Climate Models (RCMs), we have projected the density of this species during the next century under two climate scenarios (RCP4.5 and RCP8.5). Bathymetry and sea bottom temperature drove the density of the species, leading to a marked northward expansion during the last two decades. Our results projected an increase in its distribution and especially in density throughout the area along the 21st century, mirroring the effect of global warming. Consequently, the most distant period (i.e. 2100s) and the warmest scenario (RCP8.5) presented also the highest densities and low internal variability of the ensemble. We discussed the power of assessing uncertainties using a RCM ensemble, particularly under complex oceanographic features, to bring robust information for an effective scientific advice to fisheries management.