A multidisciplinary Spatial Data Infrastructure for the Mediterranean to support implementation of the Marine Strategy Framework Directive

29 páginas, 4 figuras, 2 tablas, 1 apéndice.The Marine Strategy Framework Directive (MSFD) adopted in 2008 aims to protect the marine environment through the holistic Ecosystem Approach (EA). The MSFD requires Member States to develop and implement cost-effective measures to achieve and/or maintain “Good Environmental Status” (GEnS). To this end, interested parties require a large amount of data and this data should be appropriately managed. This is particularly true for EA applications, where data can come from diverse sources, in diverse formats, and from several disciplines. Preliminary steps for supporting reliable multi-disciplinary analysis include data collection, data management, and the implementation of an interoperable sharing system. In an effort to implement this type of multidisciplinary analysis, a working group from the KnowSeas project (www.knowseas.com) created a Spatial Data Infrastructure for the Mediterranean Sea, designed to define and analyze the GEnS concept across various geographical scales. This article describes the implementation of this SDI, demonstrating how an interoperable system can provide strong support in implementing the MSFD under the EA, and how marine spatial planning can assist policymakers in the decision making process.This work was co-funded by the KnowSeas project (grant number 226675) and the EGIDA project (grant number 265124).Peer reviewe

Los Casos Piloto de Ordenación del Espacio Marítimo Transfronterizos y su Implicación en el Proceso Nacional en España

Maritime Spatial Planning processes are already being implemented in many parts of the world being Europe one of the hot spots due to the approval of the Directive 2014/89/EU of the European Parliament and of the Council of 23 July 2014 establishing a framework for maritime spatial planning, which oblige every coastal Member State to have approved plans by March 2021. This Directive does not allocate specific funds for the development of these plans but it supports national processes by funding Maritime Spatial Planning transboundary projects among neighbouring countries. These projects have mainly two benefits, one is to provide states with knowledge, capacity and methodologies to apply in MSP national processes, and another one is to facilitate the coherence along plans of neighbouring countries sharing a sea basin region. As biological and ecological processes in the marine environment are not limited by administrative borders, the transboundary component of Maritime Spatial Planning is of extremely importance to manage marine resources in a sustainable wayVersión del edito

A multidisciplinary Spatial Data Infrastructure for the Mediterranean to support implementation of the Marine Strategy Framework Directive

The Marine Strategy Framework Directive (MSFD) adopted in 2008 aims to protect the marine environment through the holistic Ecosystem Approach (EA). The MSFD requires Member States to develop and implement cost-effective measures to achieve and/or maintain “Good Environmental Status” (GEnS). To this end, interested parties require a large amount of data and this data should be appropriately managed. This is particularly true for EA applications, where data can come from diverse sources, in diverse formats, and from several disciplines. Preliminary steps for supporting reliable multi-disciplinary analysis include data collection, data management, and the implementation of an interoperable sharing system. In an effort to implement this type of multidisciplinary analysis, a working group from the KnowSeas project (www.knowseas.com) created a Spatial Data Infrastructure for the Mediterranean Sea, designed to define and analyze the GEnS concept across various geographical scales. This article describes the implementation of this SDI, demonstrating how an interoperable system can provide strong support in implementing the MSFD under the EA, and how marine spatial planning can assist policymakers in the decision making process

Sox-2 Positive Neural Progenitors in the Primate Striatum Undergo Dynamic Changes after Dopamine Denervation.

The existence of endogenous neural progenitors in the nigrostriatal system could represent a powerful tool for restorative therapies in Parkinson's disease. Sox-2 is a transcription factor expressed in pluripotent and adult stem cells, including neural progenitors. In the adult brain Sox-2 is expressed in the neurogenic niches. There is also widespread expression of Sox-2 in other brain regions, although the neurogenic potential outside the niches is uncertain. Here, we analyzed the presence of Sox-2+ cells in the adult primate (Macaca fascicularis) brain in naïve animals (N = 3) and in animals exposed to systemic administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine to render them parkinsonian (N = 8). Animals received bromodeoxyuridine (100 mg/kg once a day during five consecutive days) to label proliferating cells and their progeny. Using confocal and electron microscopy we analyzed the Sox-2+ cell population in the nigrostriatal system and investigated changes in the number, proliferation and neurogenic potential of Sox-2+ cells, in control conditions and at two time points after MPTP administration. We found Sox-2+ cells with self-renewal capacity in both the striatum and the substantia nigra. Importantly, only in the striatum Sox-2+ was expressed in some calretinin+ neurons. MPTP administration led to an increase in the proliferation of striatal Sox-2+ cells and to an acute, concomitant decrease in the percentage of Sox-2+/calretinin+ neurons, which recovered by 18 months. Given their potential capacity to differentiate into neurons and their responsiveness to dopamine neurotoxic insults, striatal Sox-2+ cells represent good candidates to harness endogenous repair mechanisms for regenerative approaches in Parkinson's disease

Steps toward a shared governance response for achieving Good Environmental Status in the Mediterranean Sea

The Mediterranean region is of fundamental importance to Europe given its strategic position. The responsibility for its overall ecosystem integrity is shared by European Union Member States (EU-MS) and other Mediterranean countries. A juxtaposition of overlapping governance instruments occurred recently in the region, with the implementation of both the Marine Strategy Framework Directive (MSFD) for EU-MS and the Ecosystem Approach Strategy (ECAP) for all Mediterranean countries, including EU-MS. Both MSFD and ECAP are structured around vision-driven processes to achieve Good Environmental Status and a Healthy Environment, respectively. These processes have clear ecosystem-based, integrated policy objectives to guarantee the preservation and integrity of Mediterranean marine ecosystem goods and services. However, adoption of these instruments, especially those related to the new EUMS directives on marine policy, could result in a governance gap in addition to the well-known economic gap between the EU and the non-EU political blocs. We identify two complementary requirements for effective implementation of both MSFD and ECAP that could work together to reduce this gap, to ensure a better alignment between MSFD and ECAP and better planning for stakeholder engagement. These are key issues for the future success of these instruments in a Mediterranean region where discrepancies between societal and ecological objectives may pose a challenge to these processes

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Correction: Sox-2 Positive Neural Progenitors in the Primate Striatum Undergo Dynamic Changes after Dopamine Denervation.

[This corrects the article on p. e66377 in vol. 8.]