Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis

In addition to motor neurone degeneration, up to 50% of amyotrophic lateral sclerosis (ALS) patients present with cognitive decline. Understanding the neurobiological changes underlying these cognitive deficits is critical, as cognitively impaired patients exhibit a shorter survival time from symptom onset. Given the pathogenic role of synapse loss in other neurodegenerative diseases in which cognitive decline is apparent, such as Alzheimer's disease, we aimed to assess synaptic integrity in the ALS brain. Here, we have applied a unique combination of high-resolution imaging of post-mortem tissue with neuropathology, genetic screening and cognitive profiling of ALS cases. Analyses of more than 1 million synapses using two complimentary high-resolution techniques (electron microscopy and array tomography) revealed a loss of synapses from the prefrontal cortex of ALS patients. Importantly, synapse loss was significantly greater in cognitively impaired cases and was not due to cortical atrophy, nor associated with dementia-associated neuropathology. Interestingly, we found a trend between pTDP-43 pathology and synapse loss in the frontal cortex and discovered pTDP-43 puncta at a subset of synapses in the ALS brains. From these data, we postulate that synapse loss in the prefrontal cortex represents an underlying neurobiological substrate of cognitive decline in ALS

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Impact of Eastern Redcedar Proliferation on Water Resources in the Great Plains USA—Current State of Knowledge

In the Great Plains of the central United States, water resources for human and aquatic life rely primarily on surface runoff and local recharge from rangelands that are under rapid transformation to woodland by the encroachment of Eastern redcedar (redcedar; Juniperus virginiana) trees. In this synthesis, the current understanding and impact of redcedar encroachment on the water budget and water resources available for non-ecosystem use are reviewed. Existing studies concluded that the conversion from herbaceous-dominated rangeland to redcedar woodland increases precipitation loss to canopy interception and vegetation transpiration. The decrease of soil moisture, particularly for the subsurface soil layer, is widely documented. The depletion of soil moisture is directly related to the observed decrease in surface runoff, and the potential of deep recharge for redcedar encroached watersheds. Model simulations suggest that complete conversion of the rangelands to redcedar woodland at the watershed and basin scale in the South-central Great Plains would lead to reduced streamflow throughout the year, with the reductions of streamflow between 20 to 40% depending on the aridity of the climate of the watershed. Recommended topics for future studies include: (i) The spatial dynamics of redcedar proliferation and its impact on water budget across a regional hydrologic network; (ii) the temporal dynamics of precipitation interception by the herbaceous canopy; (iii) the impact of redcedar infilling into deciduous forests such as the Cross Timbers and its impact on water budget and water availability for non-ecosystem use; (iv) land surface and climate interaction and cross-scale hydrological modeling and forecasting; (v) impact of redcedar encroachment on sediment production and water quality; and (vi) assessment and efficacy of different redcedar control measures in restoring hydrological functions of watershed

Global data set of long-term summertime vertical temperature profiles in 153 lakes

Measurement(s) : temperature of water, temperature profile Technology Type(s) : digital curation Factor Type(s) : lake location, temporal interval Sample Characteristic - Environment : lake, reservoir Sample Characteristic - Location : global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14619009Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change

Global data set of long-term summertime vertical temperature profiles in 153 lakes

Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change

Impact of Eastern Redcedar Proliferation on Water Resources in the Great Plains USA—Current State of Knowledge

In the Great Plains of the central United States, water resources for human and aquatic life rely primarily on surface runoff and local recharge from rangelands that are under rapid transformation to woodland by the encroachment of Eastern redcedar (redcedar; Juniperus virginiana) trees. In this synthesis, the current understanding and impact of redcedar encroachment on the water budget and water resources available for non-ecosystem use are reviewed. Existing studies concluded that the conversion from herbaceous-dominated rangeland to redcedar woodland increases precipitation loss to canopy interception and vegetation transpiration. The decrease of soil moisture, particularly for the subsurface soil layer, is widely documented. The depletion of soil moisture is directly related to the observed decrease in surface runoff, and the potential of deep recharge for redcedar encroached watersheds. Model simulations suggest that complete conversion of the rangelands to redcedar woodland at the watershed and basin scale in the South-central Great Plains would lead to reduced streamflow throughout the year, with the reductions of streamflow between 20 to 40% depending on the aridity of the climate of the watershed. Recommended topics for future studies include: (i) The spatial dynamics of redcedar proliferation and its impact on water budget across a regional hydrologic network; (ii) the temporal dynamics of precipitation interception by the herbaceous canopy; (iii) the impact of redcedar infilling into deciduous forests such as the Cross Timbers and its impact on water budget and water availability for non-ecosystem use; (iv) land surface and climate interaction and cross-scale hydrological modeling and forecasting; (v) impact of redcedar encroachment on sediment production and water quality; and (vi) assessment and efficacy of different redcedar control measures in restoring hydrological functions of watershed

Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials

Abstract Background The comparative efficacy of inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) triple therapy administered via single or multiple inhalers in patients with chronic obstructive pulmonary disease (COPD) has not been evaluated comprehensively. We conducted two replicate trials comparing single- with multiple-inhaler ICS/LAMA/LABA combination in COPD. Methods 207608 and 207609 were Phase IV, 12-week, randomized, double-blind, triple-dummy non-inferiority trials comparing once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg via Ellipta inhaler, with twice-daily budesonide/formoterol (BUD/FOR) 400/12 μg via metered-dose inhaler plus once-daily tiotropium (TIO) 18 μg via HandiHaler. Patients had symptomatic COPD and forced expiratory volume in 1 s (FEV1) &lt; 50% predicted, or FEV1 &lt; 80% predicted and ≥ 2 moderate or 1 severe exacerbations in the prior year. The primary endpoint in both trials was weighted mean change from baseline (wmCFB) in 0–24-h FEV1 at Week 12. Secondary endpoints included CFB in trough FEV1 at Day 84 and 85. Other endpoints included serial FEV1 and health status outcomes at Week 12. Safety was evaluated descriptively. Results The modified per-protocol population included 720 and 711 patients in studies 207608 and 207609 (intent-to-treat population: 728 and 732). FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0–24-h FEV1 at Week 12 (Study 207608 treatment difference [95% confidence interval]: 15 mL [− 13, 43]; Study 207609: 11 mL [− 20, 41]). FF/UMEC/VI improved trough FEV1 CFB versus BUD/FOR+TIO at Day 84 and 85 (Day 85 treatment difference: Study 207608: 38 mL [10, 66]; Study 207609: 51 mL [21, 82]) and FEV1 at 12 and 24 h post-morning dose at Week 12 in both studies. No treatment differences were seen in health status outcomes. Safety profiles were similar between treatments; pneumonia occurred in 7 (&lt; 1%) patients with FF/UMEC/VI and 9 (1%) patients with BUD/FOR+TIO, across both studies. Conclusions FF/UMEC/VI was non-inferior to BUD/FOR+TIO for wmCFB in 0–24-h FEV1 at Week 12 in patients with COPD. Greater improvements in trough and serial FEV1 measurements at Week 12 with FF/UMEC/VI versus BUD/FOR+TIO, together with similar health status improvements and safety outcomes including the incidence of pneumonia, suggest that once-daily single-inhaler FF/UMEC/VI triple therapy is a viable option for patients looking to simplify their treatment regimen. Trial registration GSK (207608/207609; NCT03478683/NCT03478696). </jats:sec