Ticagrelor versus clopidogrel dual antiplatelet therapy for unruptured intracranial aneurysms treated with flowdiverter.

BACKGROUND AND PURPOSE: Antiplatelet therapy (APT) is a key element limiting the risk of thromboembolic events (TEE) in neuroendovascular procedures, including aneurysm treatment with flowdiverter. Clopidogrel combined with aspirin is the mostly reported dual APT (DAPT). However, resistance phenomenon and intraindividual efficacy fluctuation are identified limitations. In recent years, ticagrelor has been increasingly used in this indication. We compared these two DAPT regimens for intracranial aneurysm treated with flowdiverter. METHODS: We conducted a multicentric retrospective study from prospectively maintained databases in two high volume centers extracting consecutive patients presenting unruptured intracranial aneurysm treated with flowdiverter and receiving DAPT (May 2015 to December 2019).  Two groups were compared according to their DAPT regimen: "ticagrelor+aspirin" and "clopidogrel+aspirin". Clopidogrel group was systematically checked with platelet test inhibition before endovascular procedure. The primary endpoint was composite, defined as any thrombo-embolic event (TEE) or major hemorrhagic event occurring the first 6 months during and after embolization RESULTS: 260 patients met our inclusion criteria. Baseline patients and aneurysms characteristics were comparable between groups, except for aneurysm location, median size and pre-treatment modified Rankin scale. No significant difference was observed regarding the primary composite outcome: 11.5% (12/104) in the ticagrelor group versus 10.9% (17/156) in the clopidogrel group (p = 1.000). There was also no significant difference in secondary outcomes including TEE (10.5 vs 9.0%; p = 0.673), major hemorrhage (0.9 vs 1.2%; p = 0.651) and clinical outcome (at least 1-point mRS worsening during follow up: 6.7% vs 8.3%; p = 0.813). CONCLUSION: First-line DAPT with ticagrelor+aspirin seems as safe and effective as clopidogrel+aspirin regimen.

Stereotactic Radiosurgery for Intraventricular Metastases: A Multicenter Study.

BACKGROUND: Intraventricular metastases (IVMs) are uncommon, and their optimal management remains debatable. OBJECTIVE: To define the safety and efficacy of stereotactic radiosurgery (SRS) in the treatment of IVMs. METHODS: This retrospective, multicenter study included patients managed with SRS for IVMs. SRS-induced adverse events, local tumor or intracranial progression, and the frequency of new-onset hydrocephalus or leptomeningeal spread were documented. Analyses of variables related to patient neuroimaging or clinical outcomes were also performed. RESULTS: The cohort included 160 patients from 11 centers who underwent SRS for treatment of 1045 intracranial metastases, of which 196 were IVMs. The median survival from SRS was 10 months. Of the 154 patients and 190 IVMs with imaging follow-up, 94 patients (61%) experienced distant intracranial disease progression and 16 IVMs (8.4%) progressed locally. The 12- and 24-month local IVM control rates were 91.4% and 86.1%, respectively. Sixteen (10%) and 27 (17.5%) patients developed hydrocephalus and leptomeningeal dissemination post-SRS, respectively. Adverse radiation effects were documented in 24 patients (15%). Eleven patients (6.9%) died because of intracranial disease progression. CONCLUSION: SRS is an effective treatment option for IVMs, with a local IVM control rate comparable with SRS for parenchymal brain metastases. Leptomeningeal spread and hydrocephalus in patients with IVM occur in a minority of patients, but these patients warrant careful follow-up to detect these changes.

MRI Outcomes Achieved by Simple Flow Blockage Technique in Symptomatic Carotid Artery Stenosis Stenting.

In this study, we aimed to determine the frequency and clinical impact of new ischemic lesions detected with diffusion-weighted-imaging-MRI (DWI-MRI) as well as the clinical outcomes after carotid artery stenting (CAS) using the simple flow blockage technique (SFB). This is a retrospective study with data extraction from a monocentric prospective clinical registry (from 2017 to 2019) of consecutive patients admitted for symptomatic cervical ICA stenosis or web. Herein, patients benefited from DWI-MRI before and within 48 h of CAS for symptomatic ICA stenosis or web. The primary endpoint was the frequency of new DWI-MRI ischemic lesions and the secondary (composite) endpoint was the rate of mortality, symptomatic stroke or acute coronary syndrome within 30 days of the procedure. All of the 82 CAS procedures were successfully performed. Among the 33 patients (40.2%) with new DWI-MRI ischemic lesions, 30 patients were asymptomatic (90.9%). Irregular carotid plaque surface with (n = 13, 44.8%) or without ulceration (n = 12, 60.0%) was associated with higher rates of new DWI-MRI lesions by comparison to patients with a regular plaque (n = 7, 25%) (p = 0.048) using the univariate analysis. Less than half of this CAS cohort using the SFB technique had new ischemic lesions detected with DWI-MRI. Among these patients, more than 90% were asymptomatic. Irregularity of the plaque seems to increase the risk of peri-procedural DWI-MRI lesions.

Radiological and clinical outcomes of stereotactic radiosurgery for gangliogliomas: an international multicenter study.

OBJECTIVE: The optimal treatment for recurrent and residual gangliogliomas remains unclear. The aim of this study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of patients with recurrent or residual intracranial ganglioglioma. METHODS: This retrospective multicenter study involved patients managed with SRS for ganglioglioma. The study endpoints included local tumor control and tumor- or SRS-related neurological morbidity following treatment. Factors associated with tumor progression and neurological morbidity were also analyzed. RESULTS: The cohort included 20 patients (11 males [55%]) with a median age of 24.5 (IQR 14) years who had been managed with SRS for ganglioglioma. Five-year radiological progression-free survival was 85.6%. After SRS, 2 patients (10%) experienced transient neurological deterioration. At a median clinical follow-up of 88.5 (IQR 112.5) months, 1 patient (5%) experienced seizure worsening and 1 (5%) required further resection of the tumor because of radiological progression. No mortality was noted in this series. CONCLUSIONS: SRS appears to be a safe and effective treatment option for surgically inaccessible, recurrent, and residual gangliogliomas. In this series, the 5-year progression-free survival rate after SRS was 85.6%. Gross-total resection remains the primary treatment of choice for patients with newly diagnosed or recurrent ganglioglioma. SRS may be considered for patients unfit for surgery and those with surgically inaccessible newly diagnosed, residual, and recurrent lesions.

Intergenerational inequities in exposure to climate extremes.

Young generations are severely threatened by climate change.

Early Holocene greening of the Sahara requires Mediterranean winter rainfall.

The greening of the Sahara, associated with the African Humid Period (AHP) between ca. 14,500 and 5,000 y ago, is arguably the largest climate-induced environmental change in the Holocene; it is usually explained by the strengthening and northward expansion of the African monsoon in response to orbital forcing. However, the strengthened monsoon in Early to Middle Holocene climate model simulations cannot sustain vegetation in the Sahara or account for the increased humidity in the Mediterranean region. Here, we present an 18,500-y pollen and leaf-wax δD record from Lake Tislit (32° N) in Morocco, which provides quantitative reconstruction of winter and summer precipitation in northern Africa. The record from Lake Tislit shows that the northern Sahara and the Mediterranean region were wetter in the AHP because of increased winter precipitation and were not influenced by the monsoon. The increased seasonal contrast of insolation led to an intensification and southward shift of the Mediterranean winter precipitation system in addition to the intensified summer monsoon. Therefore, a winter rainfall zone must have met and possibly overlapped the monsoonal zone in the Sahara. Using a mechanistic vegetation model in Early Holocene conditions, we show that this seasonal distribution of rainfall is more efficient than the increased monsoon alone in generating a green Sahara vegetation cover, in agreement with observed vegetation. This conceptual framework should be taken into consideration in Earth system paleoclimate simulations used to explore the mechanisms of African climatic and environmental sensitivity.

Large potential for crop production adaptation depends on available future varieties.

Climate change affects global agricultural production and threatens food security. Faster phenological development of crops due to climate warming is one of the main drivers for potential future yield reductions. To counter the effect of faster maturity, adapted varieties would require more heat units to regain the previous growing period length. In this study, we investigate the effects of variety adaptation on global caloric production under four different future climate change scenarios for maize, rice, soybean, and wheat. Thereby, we empirically identify areas that could require new varieties and areas where variety adaptation could be achieved by shifting existing varieties into new regions. The study uses an ensemble of seven global gridded crop models and five CMIP6 climate models. We found that 39% (SSP5-8.5) of global cropland could require new crop varieties to avoid yield loss from climate change by the end of the century. At low levels of warming (SSP1-2.6), 85% of currently cultivated land can draw from existing varieties to shift within an agro-ecological zone for adaptation. The assumptions on available varieties for adaptation have major impacts on the effectiveness of variety adaptation, which could more than half in SSP5-8.5. The results highlight that region-specific breeding efforts are required to allow for a successful adaptation to climate change.

Deterministic modelling of seed dispersal based on observed behaviours of an endemic primate in Brazil.

Plant species models are among the available tools to predict the future of ecosystems threatened by climate change, habitat loss, and degradation. However, they suffer from low to no inclusion of plant dispersal, which is necessary to predict ecosystem evolution. A variety of seed dispersal models have been conceived for anemochorous and zoochorous plant species, but the coupling between vegetation models and seed dispersal processes remains rare. The main challenge in modelling zoochoric dispersal is simulating animal movements in their complex habitat. Recent developments allow straightforward applications of hidden Markov modelling (HMM) to animal movements, which could ease generalizations when modelling zoochoric seed dispersal. We tested the use of HMM to model seed dispersal by an endangered primate in the Brazilian Atlantic forest, to demonstrate its potential simplicity to simulate seed dispersal processes. We also discuss how to adapt it to other species. We collected information on movement, fruit consumption, deposition, and habitat use of Leontopithecus chrysomelas. We analysed daily trajectories using HMM and built a deterministic Model Of Seed Transfer (MOST), which replicated, with good approximation, the primate's movement and seed deposition patterns as observed in the field. Our results suggest that the dispersal behaviour and short daily-trajectories of L. chrysomelas restrict the species' role in large-scale forest regeneration, but contribute to the prevalence of resource tree species locally, and potentially maintaining tree diversity by preventing local extinction. However, it may be possible to accurately simulate dispersal in an area, without necessarily quantifying variables that influence movement, if the movement can be broken down to step-length and turning angles, and parametrised along with the distribution of gut-transit times. For future objectives, coupling MOST with a DVM could be used to test hypotheses on tree species survival in various scenarios, simulating regeneration and growth at regional scales by including data on main dispersal agents over the area of interest, distribution of tree species, and land use data. The principal advantage of the MOST model is its functionality with data available from the literature as the variables are easy to parametrise. We suggest using the coupled model to perform experiments using only available information, but varying the numbers and species of seed dispersers, or modifying land cover or configuration to test for possible thresholds preventing the extinction of selected tree species.

Angiographic Patterns and Outcomes Achieved by Proximal Balloon Occlusion in Symptomatic Carotid Artery Stenosis Stenting.

BACKGROUND AND PURPOSE: The best embolic protection strategy has not yet been established for carotid artery stenting (CAS). This article reports a new simplified approach using a balloon guide catheter inspired by stroke therapy, in patients harboring a symptomatic ICA atherosclerotic stenosis or web. In addition, the three angiographic patterns and clinical outcomes associated with this technique, called the simple flow blockage (SFB) technique are described. MATERIAL AND METHODS: This was a retrospective study with data extraction from a monocentric prospective clinical registry of consecutive patients admitted for symptomatic ICA stenosis or web. The primary study outcome (composite endpoint) was the rate of occurrence of death, symptomatic stroke or acute coronary syndrome within 30 days of the intervention. RESULTS: In this study 75 symptomatic patients with >50% carotid artery atherosclerotic stenosis or web were included. All procedures were successfully performed. The composite endpoint occurred in 3 patients (4.0%, 95% confidence interval, CI, 0.0-11.3): 1 had symptomatic ischemic stroke, 1 had reperfusion syndrome with symptomatic intracranial hemorrhage and 1 had acute coronary syndrome. After proximal balloon inflation three angiographic patterns were observed: complete contrast column stagnation in the ICA (38.7%), retrograde washout of the ICA from the intracranial circulation towards the external carotid artery (35.5%) and antegrade washout of contrast medium towards the intracranial circulation (25.8%). The median procedure length was 40 min. New asymptomatic ischemic lesions were observed in 22.5% on DWI-MRI. CONCLUSION: The SFB technique enables fast and safe procedures in CAS. A favorable angiographic pattern after proximal balloon inflation was observed in 74.2% of cases.

Brazilian montane rainforest expansion induced by Heinrich Stadial 1 event.

The origin of modern disjunct plant distributions in the Brazilian Highlands with strong floristic affinities to distant montane rainforests of isolated mountaintops in the northeast and northern Amazonia and the Guyana Shield remains unknown. We tested the hypothesis that these unexplained biogeographical patterns reflect former ecosystem rearrangements sustained by widespread plant migrations possibly due to climatic patterns that are very dissimilar from present-day conditions. To address this issue, we mapped the presence of the montane arboreal taxa Araucaria, Podocarpus, Drimys, Hedyosmum, Ilex, Myrsine, Symplocos, and Weinmannia, and cool-adapted plants in the families Myrtaceae, Ericaceae, and Arecaceae (palms) in 29 palynological records during Heinrich Stadial 1 Event, encompassing a latitudinal range of 30°S to 0°S. In addition, Principal Component Analysis and Species Distribution Modelling were used to represent past and modern habitat suitability for Podocarpus and Araucaria. The data reveals two long-distance patterns of plant migration connecting south/southeast to northeastern Brazil and Amazonia with a third short route extending from one of them. Their paleofloristic compositions suggest a climatic scenario of abundant rainfall and relative lower continental surface temperatures, possibly intensified by the effects of polar air incursions forming cold fronts into the Brazilian Highlands. Although these taxa are sensitive to changes in temperature, the combined pollen and speleothems proxy data indicate that this montane rainforest expansion during Heinrich Stadial 1 Event was triggered mainly by a less seasonal rainfall regime from the subtropics to the equatorial region.

State-of-the-art global models underestimate impacts from climate extremes.

Global impact models represent process-level understanding of how natural and human systems may be affected by climate change. Their projections are used in integrated assessments of climate change. Here we test, for the first time, systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions. Using the 2003 European heat wave and drought as a historical analogue for comparable events in the future, we find that a majority of models underestimate the extremeness of impacts in important sectors such as agriculture, terrestrial ecosystems, and heat-related human mortality, while impacts on water resources and hydropower are overestimated in some river basins; and the spread across models is often large. This has important implications for economic assessments of climate change impacts that rely on these models. It also means that societal risks from future extreme events may be greater than previously thought.

Tree mortality submodels drive simulated long-term forest dynamics: assessing 15 models from the stand to global scale.

Models are pivotal for assessing future forest dynamics under the impacts of changing climate and management practices, incorporating representations of tree growth, mortality, and regeneration. Quantitative studies on the importance of mortality submodels are scarce. We evaluated 15 dynamic vegetation models (DVMs) regarding their sensitivity to different formulations of tree mortality under different degrees of climate change. The set of models comprised eight DVMs at the stand scale, three at the landscape scale, and four typically applied at the continental to global scale. Some incorporate empirically derived mortality models, and others are based on experimental data, whereas still others are based on theoretical reasoning. Each DVM was run with at least two alternative mortality submodels. Model behavior was evaluated against empirical time series data, and then, the models were subjected to different scenarios of climate change. Most DVMs matched empirical data quite well, irrespective of the mortality submodel that was used. However, mortality submodels that performed in a very similar manner against past data often led to sharply different trajectories of forest dynamics under future climate change. Most DVMs featured high sensitivity to the mortality submodel, with deviations of basal area and stem numbers on the order of 10-40% per century under current climate and 20-170% under climate change. The sensitivity of a given DVM to scenarios of climate change, however, was typically lower by a factor of two to three. We conclude that (1) mortality is one of the most uncertain processes when it comes to assessing forest response to climate change, and (2) more data and a better process understanding of tree mortality are needed to improve the robustness of simulated future forest dynamics. Our study highlights that comparing several alternative mortality formulations in DVMs provides valuable insights into the effects of process uncertainties on simulated future forest dynamics.

Pig empire under infectious threat: risk of African swine fever introduction into the People's Republic of China.

Pig production and pork consumption are very important to the People's Republic of China for both economic and cultural reasons. The incursion and spread of a disease such as African swine fever (ASF), which emerged in Eastern Europe in 2007, could have devastating socioeconomic consequences for both the Chinese and the global pig industry. The Chinese government consequently attributes a very high priority to ASF and is actively seeking to improve its preparedness. This paper discusses different drivers and pathways of potential emergence of ASF in China in light of the country's specificities, including international movements of people, pigs and pig products, swill feeding practices and wild boar populations. It suggests that effective ASF risk management in China will require a comprehensive and integrated approach linking science and policy and will need to involve all relevant stakeholders to develop realistic policies.

The obstructive sleep apnoea syndrome in adolescents.

BACKGROUND: The obstructive sleep apnoea syndrome (OSAS) results from a combination of structural and neuromotor factors; however, the relative contributions of these factors have not been studied during the important developmental phase of adolescence. We hypothesised that adenotonsillar volume (ATV), nasopharyngeal airway volume (NPAV), upper airway critical closing pressure (Pcrit) in the hypotonic and activated neuromotor states, upper airway electromyographic response to subatmospheric pressure and the ventilatory response to CO2 during sleep would be major predictors of OSAS risk. METHODS: 42 obese adolescents with OSAS and 37 weight-matched controls underwent upper airway MRI, measurements of Pcrit, genioglossal electromyography and ventilatory response to CO2 during wakefulness and sleep. RESULTS: ATV, NPAV, activated and hypotonic Pcrit, genioglossal electromyography and ventilatory response to CO2 during sleep were all associated with OSAS risk. Multivariate models adjusted for age, gender, body mass index and race indicated that ATV, NPAV and activated Pcrit each independently affected apnoea risk in adolescents; genioglossal electromyography was independently associated in a reduced sample. There was significant interaction between NPAV and activated Pcrit (p=0.021), with activated Pcrit more strongly associated with OSAS in adolescents with larger NPAVs and NPAV more strongly associated with OSAS in adolescents with more negative activated closing pressure. CONCLUSIONS: OSAS in adolescents is mediated by a combination of anatomic (ATV, NPAV) and neuromotor factors (activated Pcrit). This may have important implications for the management of OSAS in adolescents.

MERS-CoV at the Animal-Human Interface: Inputs on Exposure Pathways from an Expert-Opinion Elicitation.

Nearly 4 years after the first report of the emergence of Middle-East respiratory syndrome Coronavirus (MERS-CoV) and nearly 1800 human cases later, the ecology of MERS-CoV, its epidemiology, and more than risk factors of MERS-CoV transmission between camels are poorly understood. Knowledge about the pathways and mechanisms of transmission from animals to humans is limited; as of yet, transmission risks have not been quantified. Moreover the divergent sanitary situations and exposures to animals among populations in the Arabian Peninsula, where human primary cases appear to dominate, vs. other regions in the Middle East and Africa, with no reported human clinical cases and where the virus has been detected only in dromedaries, represents huge scientific and health challenges. Here, we have used expert-opinion elicitation in order to obtain ideas on relative importance of MERS-CoV risk factors and estimates of transmission risks from various types of contact between humans and dromedaries. Fourteen experts with diverse and extensive experience in MERS-CoV relevant fields were enrolled and completed an online questionnaire that examined pathways based on several scenarios, e.g., camels-camels, camels-human, bats/other species to camels/humans, and the role of diverse biological substances (milk, urine, etc.) and potential fomites. Experts believed that dromedary camels play the largest role in MERS-CoV infection of other dromedaries; however, they also indicated a significant influence of the season (i.e. calving or weaning periods) on transmission risk. All experts thought that MERS-CoV-infected dromedaries and asymptomatic humans play the most important role in infection of humans, with bats and other species presenting a possible, but yet undefined, risk. Direct and indirect contact of humans with dromedary camels were identified as the most risky types of contact, when compared to consumption of various camel products, with estimated "most likely" incidence risks of at least 22 and 13% for direct and indirect contact, respectively. The results of our study are consistent with available, yet very limited, published data regarding the potential pathways of transmission of MERS-CoV at the animal-human interface. These results identify key knowledge gaps and highlight the need for more comprehensive, yet focused research to be conducted to better understand transmission between dromedaries and humans.