Exploring the ability of the variable-resolution Community Earth System Model to simulate cryospheric–hydrological variables in High Mountain Asia

Earth system models (ESMs) can help to improve the understanding of climate-induced cryospheric–hydrological impacts in complex mountain regions, such as High Mountain Asia (HMA). Coarse ESM grids, however, have difficulties in representing cryospheric–hydrological processes that vary over short distances in complex mountainous environments. Variable-resolution (VR) ESMs can help to overcome these limitations through targeted grid refinement. This study investigates the ability of the VR Community Earth System Model (VR-CESM) to simulate cryospheric–hydrological variables such as the glacier surface mass balance (SMB) over HMA. To this end, a new VR grid is generated, with a regional grid refinement up to 7 km over HMA. Two coupled atmosphere–land simulations are run for the period 1979–1998. The second simulation is performed with an updated glacier cover dataset and includes snow and glacier model modifications. Comparisons are made to gridded outputs derived from a globally uniform 1∘ CESM grid, observation-, reanalysis-, and satellite-based datasets, and a glacier model forced by a regional climate model (RCM). Climatological biases are generally reduced compared to the coarse-resolution CESM grid, but the glacier SMB is too negative relative to observation-based glaciological and geodetic mass balances, as well as the RCM-forced glacier model output. In the second simulation, the SMB is improved but is still underestimated due to cloud cover and temperature biases, missing model physics, and incomplete land–atmosphere coupling. The outcomes suggest that VR-CESM could be a useful tool to simulate cryospheric–hydrological variables and to study climate change in mountainous environments, but further developments are needed to better simulate the SMB of mountain glaciers.</p

Exploring the ability of the variable-resolution Community Earth System Model to simulate cryospheric–hydrological variables in High Mountain Asia

Earth system models (ESMs) can help to improve the understanding of climate-induced cryospheric–hydrological impacts in complex mountain regions, such as High Mountain Asia (HMA). Coarse ESM grids, however, have difficulties in representing cryospheric–hydrological processes that vary over short distances in complex mountainous environments. Variable-resolution (VR) ESMs can help to overcome these limitations through targeted grid refinement. This study investigates the ability of the VR Community Earth System Model (VR-CESM) to simulate cryospheric–hydrological variables such as the glacier surface mass balance (SMB) over HMA. To this end, a new VR grid is generated, with a regional grid refinement up to 7 km over HMA. Two coupled atmosphere–land simulations are run for the period 1979–1998. The second simulation is performed with an updated glacier cover dataset and includes snow and glacier model modifications. Comparisons are made to gridded outputs derived from a globally uniform 1∘ CESM grid, observation-, reanalysis-, and satellite-based datasets, and a glacier model forced by a regional climate model (RCM). Climatological biases are generally reduced compared to the coarse-resolution CESM grid, but the glacier SMB is too negative relative to observation-based glaciological and geodetic mass balances, as well as the RCM-forced glacier model output. In the second simulation, the SMB is improved but is still underestimated due to cloud cover and temperature biases, missing model physics, and incomplete land–atmosphere coupling. The outcomes suggest that VR-CESM could be a useful tool to simulate cryospheric–hydrological variables and to study climate change in mountainous environments, but further developments are needed to better simulate the SMB of mountain glaciers

Importance of snow and glacier meltwater for agriculture on the Indo-Gangetic Plain

Densely populated floodplains downstream of Asia’s mountain ranges depend heavily on mountain water resources, in particular for irrigation. An intensive and complex multi-cropping irrigated agricultural system has developed here to optimize the use of these mountain water resources in conjunction with monsoonal rainfall. Snow and glacier melt thereby modulate the seasonal pattern of river flows and, together with groundwater, provide water when rainfall is scarce. Climate change is expected to weaken this modulating effect, with potentially strong effects on food production in one of the world’s breadbaskets. Here we quantify the space-, time- and crop-specific dependence of agriculture in the Indo-Gangetic Plains on mountain water resources, using a coupled state-of-the-art, high-resolution, cryosphere–hydrology–crop model. We show that dependence varies strongly in space and time and is highest in the Indus basin, where in the pre-monsoon season up to 60% of the total irrigation withdrawals originate from mountain snow and glacier melt, and that it contributes an additional 11% to total crop production. Although dependence in the floodplains of the Ganges is comparatively lower, meltwater is still essential during the dry season, in particular for crops such as sugar cane. The dependency on meltwater in the Brahmaputra is negligible. In total, 129 million farmers in the Indus and Ganges substantially depend on snow and glacier melt for their livelihoods. Snow and glacier melt provides enough water to grow food crops to sustain a balanced diet for 38 million people. These findings provide important information for agricultural and climate change adaptation policies in a climate change hot spot where shifts in water availability and demand are projected as a result of climate change and socio-economic growth

Syndromic surveillance of influenza-like illness in Scotland during the influenza A H1N1v pandemic and beyond

Syndromic surveillance refers to the rapid monitoring of syndromic data to highlight and follow outbreaks of infectious diseases, increasing situational awareness. Such systems are based upon statistical models to described routinely collected health data. We describe a working exception reporting system (ERS) currently used in Scotland to monitor calls received to the NHS telephone helpline, NHS24. We demonstrate the utility of the system to describe the time series data from NHS24 both at an aggregated Scotland level and at the individual health board level for two case studies, firstly during the initial phase of the 2009 Influenza A H1N1v and secondly for the emergence of seasonal influenza in each winter season from 2006/07 and 2010/11. In particular, we focus on a localised cluster of infection in the Highland health board and the ability of the system to highlight this outbreak. Caveats of the system, including the effect of media reporting of the pandemic on the results and the associated statistical issues, will be discussed. We discuss the adaptability and timeliness of the system and how this continues to form part of a suite of surveillance used to give early warnings to public health decision makers

Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol

BACKGROUND Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. METHODS We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540. RESULTS A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (SD) LDL cholesterol levels at baseline were 104.738.3 mg per deciliter (2.710.99 mmol per liter) and 105.539.1 mg per deciliter (2.731.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P&lt;0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent. CONCLUSIONS Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo

Repeated Endovascular Thrombectomy in Patients With Acute Ischemic Stroke: Results From a Nationwide Multicenter Database

Background and Purpose- Patients with acute ischemic stroke treated with endovascular thrombectomy may be treated with repeat endovascular thrombectomy (rEVT) in case of recurrent large vessel occlusion. Data on safety and efficacy of these interventions is scarce. Our aim is to report on frequency, timing, and outcome of rEVT in a large nation-wide multicenter registry. Methods- In the Netherlands, all patients with endovascular thrombectomy have been registered since 2002 (MR CLEAN Pretrial registry, MR CLEAN Trial [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands], and MR CLEAN Registry). We retrospectively reviewed these databases for anterior circulation rEVT cases. Patient characteristics, procedural data, and functional outcome (modified Rankin Scale at 90 days) were analyzed. Results- Of 3928 patients treated between 2002 and 2017, 27 (0.7%) underwent rEVT. Median time between first and second procedure was 78 (1-1122) days; 11/27 patients were re-treated within 30 days. Cardioembolism was the most common etiology (18 patients [67%]). In 19 patients (70%), recurrent occlusion occurred ipsilateral to previous occlusion. At 90 days after rEVT procedure, 44% of the patients had achieved functional independence (modified Rankin Scale score of 0-2), and 33% had died. Adverse events were 2/27 (7.4%) intracranial hemorrhage, 1/27 (3.7%) stroke progression, and 1/27 (3.7%) pneumonia. Conclusions- In this large nationwide cohort of patients with acute ischemic stroke treated with endovascular thrombectomy, rEVT was rare. Stroke cause was mainly cardio-embolic, and most recurrent large vessel occlusions in which rEVT was performed occurred ipsilateral. Although there probably is a selection bias on repeated treatment in case of recurrent large vessel occlusion, rEVT appears safe, with similar outcome as in single-treated cases

Assessment of collateral status by dynamic ct angiography in acute mca stroke: Timing of acquisition and relationship with final infarct volume

BACKGROUND AND PURPOSE: Dynamic CTA is a promising technique for visualization of collateral filling in patients with acute ischemic stroke. Our aim was to describe collateral filling with dynamic CTA and assess the relationship with infarct volume at follow-up. MATERIALS AND METHODS: We selected patients with acute ischemic stroke due to proximal MCA occlusion. Patients underwent NCCT, single-phase CTA, and whole-brain CT perfusion/dynamic CTA within 9 hours after stroke onset. For each patient, a detailed assessment of the extent and velocity of arterial filling was obtained. Poor radiologic outcome was defined as an infarct volume of\70 mL. The association between collateral score and follow-up infarct volume was analyzed with Poisson regression. RESULTS: Sixty-one patients with a mean age of 67 years were included. For all patients combined, the interval that contained the peak of arterial filling in both hemispheres was between 11 and 21 seconds after ICA contrast entry. Poor collateral status as assessed with dynamic CTA was more strongly associated with infarct volume of 70 mL (risk ratio, 1.9; 95% CI, 1.3-2.9) than with single-phase CTA (risk ratio, 1.4; 95% CI, 0.8-2.5). Four subgroups (good-versus-poor and fast-versus-sl

White Matter Lesions and Outcomes After Endovascular Treatment for Acute Ischemic Stroke:MR CLEAN Registry Results

BACKGROUND: Cerebral white matter lesions (WMLs) have been associated with a greater risk of poor functional outcome after ischemic stroke. We assessed the relations between WML burden and radiological and clinical outcomes in patients treated with endovascular treatment in routine practice. METHODS: We analyzed data from the MR CLEAN Registry (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands)-a prospective, multicenter, observational cohort study of patients treated with endovascular treatment in the Netherlands. WMLs were graded on baseline noncontrast computed tomography using a visual grading scale. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included early neurological recovery, successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b), futile recanalization (modified Rankin Scale score ≥3 despite successful reperfusion), and occurrence of symptomatic intracranial hemorrhage. We used multivariable logistic regression models to assess associations between WML severity and outcomes, taking the absence of WML on noncontrast computed tomography as the reference category. RESULTS: Of 3180 patients included in the MR CLEAN Registry between March 2014 and November 2017, WMLs were graded for 3046 patients and categorized as none (n=1855; 61%), mild (n=608; 20%), or moderate to severe (n=588; 19%). Favorable outcome (modified Rankin Scale score, 0-2) was achieved in 838 patients (49%) without WML, 192 patients (34%) with mild WML, and 130 patients (24%) with moderate-to-severe WML. Increasing WML grades were associated with a shift toward poorer functional outcome in a dose-dependent manner (adjusted common odds ratio, 1.34 [95% CI, 1.13-1.60] for mild WML and 1.67 [95% CI, 1.39-2.01] for moderate-to-severe WML; Ptrend, <0.001). Increasing WML grades were associated with futile recanalization (Ptrend, <0.001) and were inversely associated with early neurological recovery (Ptrend, 0.041) but not with the probability of successful reperfusion or symptomatic intracranial hemorrhage. CONCLUSIONS: An increasing burden of WML at baseline is associated with poorer clinical outcomes after endovascular treatment for acute ischemic stroke but not with the probability of successful reperfusion or symptomatic intracranial hemorrhage

Endovascular Treatment for Acute Ischemic Stroke in Patients on Oral Anticoagulants: Results from the MR CLEAN Registry

Background and Purpose - The use of oral anticoagulants (OAC) is considered a contra-indication for intravenous thrombolytics as acute treatment of ischemic stroke. However, little is known about the risks and benefits of endovascular treatment in patients on prior OAC. We aim to compare outcomes after endovascular treatment between patients with and without prior use of OAC. Methods - Data of patients with acute ischemic stroke caused by an intracranial anterior circulation occlusion, included in the nationwide, prospective, MR CLEAN Registry between March 2014 and November 2017, were analyzed. Outcomes of interest included symptomatic intracranial hemorrhage and functional outcome at 90 days (modified Rankin Scale score). Outcomes between groups were compared with (ordinal) logistic regression analyses, adjusted for prognostic factors. Results - Three thousand one hundred sixty-two patients were included in this study, of whom 502 (16%) used OAC. There was no significant difference in the occurrence of symptomatic intracranial hemorrhage between patients with and without prior OACs (5% versus 6%; adjusted odds ratio, 0.63 [95% CI, 0.38-1.06]). Patients on OACs had worse functional outcomes than patients without OACs (common odds ratio, 0.57 [95% CI, 0.47-0.66]). However, this observed difference in functional outcome disappeared after adjustment for prognostic factors (adjusted common odds ratio, 0.91 [95% CI, 0.74-1.13]). Conclusions - Prior OAC use in patients treated with endovascular treatment for ischemic stroke is not associated with an increased risk of symptomatic intracranial hemorrhage or worse functional outcome compared with no prior OAC use. Therefore, prior OAC use should not be a contra-indication for endovascular treatment