THE EARTHCARE SATELLITE Illingworth, A. J.; Barker, H. W.; Beljaars, A. ...
Bulletin of the American Meteorological Society,
08/2015, Letnik:
96, Številka:
8
Journal Article
Recenzirano
Odprti dostop
The collective representation within global models of aerosol, cloud, precipitation, and their radiative properties remains unsatisfactory. They constitute the largest source of uncertainty in ...predictions of climatic change and hamper the ability of numerical weather prediction models to forecast high-impact weather events. The joint European Space Agency (ESA)–Japan Aerospace Exploration Agency (JAXA) Earth Clouds, Aerosol and Radiation Explorer (EarthCARE) satellite mission, scheduled for launch in 2018, will help to resolve these weaknesses by providing global profiles of cloud, aerosol, precipitation, and associated radiative properties inferred from a combination of measurements made by its collocated active and passive sensors. EarthCARE will improve our understanding of cloud and aerosol processes by extending the invaluable dataset acquired by the A-Train satellitesCloudSat, Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), andAqua. Specifically, EarthCARE’s cloud profiling radar, with 7 dB more sensitivity thanCloudSat, will detect more thin clouds and its Doppler capability will provide novel information on convection, precipitating ice particle, and raindrop fall speeds. EarthCARE’s 355-nm high-spectral-resolution lidar will measure directly and accurately cloud and aerosol extinction and optical depth. Combining this with backscatter and polarization information should lead to an unprecedented ability to identify aerosol type. The multispectral imager will provide a context for, and the ability to construct, the cloud and aerosol distribution in 3D domains around the narrow 2D retrieved cross section. The consistency of the retrievals will be assessed to within a target of ±10 W m−2on the (10 km)² scale by comparing the multiview broadband radiometer observations to the top-of-atmosphere fluxes estimated by 3D radiative transfer models acting on retrieved 3D domains.
Summary
Background
There are limited long‐term, ‘real‐world’ data on ustekinumab, or the effect of dose adjustment in suboptimal responders.
Objectives
We describe 52‐week data from TRANSIT, which ...initiated ustekinumab by licensed regimen and investigated exploratory dose adjustment.
Methods
Patients with moderate‐to‐severe psoriasis and inadequate methotrexate response received ustekinumab, with immediate or gradual methotrexate withdrawal. Outcomes were similar between treatment arms at week 12 (primary endpoint), so week 52 data were pooled. Patients weighing ≤ 100 kg or > 100 kg were administered ustekinumab 45 or 90 mg, respectively. Patients weighing ≤ 100 kg without 75% improvement in Psoriasis Area and Severity Index (PASI 75) response at weeks 28 or 40 received a dose adjustment to 90 mg. The primary analysis used observed data.
Results
Overall, 391 and 98 patients received ustekinumab 45 and 90 mg, respectively. Forty‐four patients (9%) discontinued before week 52 (0·4% due to adverse events). At week 52 (in the overall population), 369 patients (83%) achieved a PASI score ≤ 5, and 341 patients (77%) achieved PASI 75; the median PASI score decreased from 15 at baseline to 1·8. At weeks 28 and 40, 84 and 31 patients, respectively, did not achieve PASI 75 and received a dose adjustment; by week 52, 35/82 (43%) and 15/31 (48%) of these patients, respectively, achieved PASI 75 (two discontinued between weeks 28 and 40).
Conclusions
Ustekinumab showed sustained 1‐year efficacy and was well tolerated when initially administered according to label. Adjusting the ustekinumab dose to 90 mg may result in clinically meaningful improvement in response in patients weighing ≤ 100 kg with suboptimal initial response.
What's already known about this topic?
The TRANSIT trial showed that ustekinumab was effective within 12 weeks in patients with an inadequate response to methotrexate.
There was no difference in the safety profile irrespective of whether methotrexate was withdrawn abruptly or gradually.
What does this study add?
Ustekinumab showed sustained efficacy after 1 year of treatment according to European label in patients who had experienced inadequate response to methotrexate, and safety was consistent with the known profile of ustekinumab.
A Psoriasis Area and Severity Index (PASI) 75 response was achieved at week 52 in 43–48% of patients weighing ≤ 100 kg who underwent dose adjustment from 45 to 90 mg at week 28 or 40 for lack of PASI 75 response at these time points.
Nearly all animal species have utilized photoperiod to cue seasonal behaviours and life history traits. We investigated photoperiod responses in keystone species, Daphnia magna, to identify molecular ...processes underlying ecologically important behaviours and traits using functional transcriptomic analyses. Daphnia magna were photoperiod‐entrained immediately posthatch to a standard control photoperiod of 16 light/ 8 dark hours (16L:8D) relative to shorter (4L:20D, 8L:16D, 12L:12L) and longer (20L:4D) day length photoperiods. Short‐day photoperiods induced significantly increased light‐avoidance behaviours relative to controls. Correspondingly, significant differential transcript expression for genes involved in glutamate signalling was observed, a critical signalling pathway in arthropod light‐avoidance behaviour. Additionally, period circadian protein and proteins coding F‐box/LRR‐repeat domains were differentially expressed which are recognized to establish circadian rhythms in arthropods. Indicators of metabolic rate increased in short‐day photoperiods which corresponded with broadscale changes in transcriptional expression across system‐level energy metabolism pathways. The most striking observations included significantly decreased neonate production at the shortest day length photoperiod (4L:20D) and significantly increased male production across short‐day and equinox photoperiods (4L:20D, 8L:16D and 12L:12D). Transcriptional expression consistent with putative mechanisms of male production was observed including photoperiod‐dependent expression of transformer‐2 sex‐determining protein and small nuclear ribonucleoprotein particles (snRNPs) which control splice variant expression for genes like transformer. Finally, increased transcriptional expression of glutamate has also been shown to induce male production in Daphnia pulex via photoperiod‐sensitive mechanisms. Overall, photoperiod entrainment affected molecular pathways that underpin critical behavioural and life history traits in D. magna providing fundamental insights into biological responses to this primary environmental cue.
Summary
Background
Limited data exist on transitioning patients with psoriasis from conventional systemic agents to biologics.
Objectives
The TRANSIT study aimed to assess the efficacy and safety of ...two methotrexate‐to‐ustekinumab transition strategies.
Methods
Patients with moderate‐to‐severe psoriasis and inadequate methotrexate response were randomized 1 : 1 to receive ustekinumab with immediate (arm 1) or 4‐week gradual (arm 2) methotrexate withdrawal. Patients weighing ≤ 100 kg or > 100 kg received ustekinumab 45 mg or 90 mg, respectively. The primary endpoint was the frequency of adverse events (AEs) at week 12. Secondary endpoints included additional safety, efficacy and patient‐reported outcomes. We report the 12‐week efficacy and safety results.
Results
Overall, 244 patients in arm 1 and 245 in arm 2 were randomized and received ustekinumab. Four patients per arm discontinued the trial by week 12. At week 12 in arms 1 and 2, respectively, 61% and 65% of patients experienced an AE, 2·9% and 2·4% had a serious AE, and 1·2% and 0·4% had an AE leading to ustekinumab discontinuation. In arms 1 and 2, respectively, median Psoriasis Area and Severity Index (PASI) score decreased from 15·2 and 15·4 at baseline to 2·9 and 2·8 at week 12; 58% and 62% of patients achieved a 75% reduction from baseline in PASI score (PASI 75) at week 12; median baseline Dermatology Life Quality Index fell from 8 and 9 at baseline to 1 (both arms) at week 16.
Conclusions
Ustekinumab was well tolerated and effective in patients who had an inadequate response to methotrexate. Both transition strategies resulted in similar week 12 safety and efficacy outcomes.
What's already known about this topic?
In patients with moderate‐to‐severe psoriasis, biologics are recommended for use after conventional systemic agents have failed, or in patients for whom they are not suitable.
There are limited data on how to transition patients from conventional systemic treatment to biologics.
What does this study add?
In patients with an inadequate response to methotrexate, similar efficacy and safety/tolerability outcomes were observed at week 12 after initiating ustekinumab, irrespective of whether methotrexate was immediately or gradually withdrawn. Therefore, immediate transitioning from methotrexate to ustekinumab can be recommended and a washout period is not needed.
No adverse safety or efficacy effects were noted after overlapping ustekinumab and methotrexate treatment for up to 1 month.
OBJECTIVE To investigate associations between recovery of locomotion and putative prognostic factors in dogs with loss of deep pain perception in the pelvic limbs caused by intervertebral disk ...herniation (IVDH). DESIGN Prospective cohort study. ANIMALS 78 client-owned dogs evaluated for IVDH that underwent spinal decompression surgery. PROCEDURES Dogs with complete loss of deep pain perception in the pelvic limbs and tail underwent routine examinations, advanced imaging, and spinal decompression surgery in accordance with standards of practice and owner consent. For each dog, information was prospectively collected on duration of clinical signs prior to onset of paraplegia; delay between onset of paraplegia and initial referral evaluation; date of recovery of locomotion, death, or euthanasia (3-month follow-up period); and whether dogs had received corticosteroid drugs before surgery. Severity of spinal cord compression at the lesion epicenter was measured via CT or MRI. RESULTS 45 of 78 (58%) of dogs recovered the ability to ambulate independently within 3 months after spinal decompression surgery. No evidence of prognostic value was identified for any of the investigated factors; importantly, a greater delay between onset of paraplegia and referral evaluation was not associated with a poorer prognosis. CONCLUSIONS AND CLINICAL RELEVANCE In this group of dogs with IVDH, immediacy of surgical treatment had no apparent association with outcome. The prognosis for recovery may instead be strongly influenced by the precise nature of the initiating injury.
The zoonotic transmission of hantaviruses from their rodent hosts to humans in North and South America is associated with a severe and frequently fatal respiratory disease, hantavirus pulmonary ...syndrome (HPS)
. No specific antiviral treatments for HPS are available, and no molecular determinants of in vivo susceptibility to hantavirus infection and HPS are known. Here we identify the human asthma-associated gene protocadherin-1 (PCDH1)
as an essential determinant of entry and infection in pulmonary endothelial cells by two hantaviruses that cause HPS, Andes virus (ANDV) and Sin Nombre virus (SNV). In vitro, we show that the surface glycoproteins of ANDV and SNV directly recognize the outermost extracellular repeat domain of PCDH1-a member of the cadherin superfamily
-to exploit PCDH1 for entry. In vivo, genetic ablation of PCDH1 renders Syrian golden hamsters highly resistant to a usually lethal ANDV challenge. Targeting PCDH1 could provide strategies to reduce infection and disease caused by New World hantaviruses.
Here, we bind the sodium dependent amino acid transporter on nitrilotriacetic acid/polyethylene glycol functionalized gold sensors in detergents and perform a detergent-lipid exchange with ...phosphatidylcholine. We characterize the LeuT structure in the adsorbed film by magnetic contrast neutron reflection using the predicted model from molecular dynamic simulations.
Abstract only
Background:
Outcomes after subarachnoid hemorrhage (SAH) have been rarely examined in large cohorts.
Methods:
This is an extension of the International Stroke Outcomes Study (INSTRUCT) ...pooling 13 ‘ideal’ stroke incidence studies (n=657 with SAH from 1993-2017, median age 56 years; 46% men). The primary outcomes were mortality and functional outcome (mRS score 3-5). Harmonized study factors included age, sex, behaviors (current smoking, alcohol intake), comorbidities (history of hypertension, ischemic heart disease, atrial fibrillation), stroke severity (e.g. NIHSS score) and year of stroke. In the pooled dataset, we estimated predictors of mortality using Poisson regression, to estimate incidence rate ratio (IRR) at 1 month (11 studies), 1 year (12 studies) and 5 years (7 studies). Generalized equation estimates in the log-binomial family were used to calculate risk ratios (RRs) for predictors of poor functional outcome at 1 month (5 studies) and 1 year (8 studies).
Results:
Mortality was 33% at 1 month, 43% at 1 year, and 47% at 5 years (Fig 1). Poor functional outcome was 25% at 1 month and 15% at 1 year (Fig 1). In multivariable analysis, age and stroke severity were associated with mortality at all time points, together with current smoking at 1 and 5 years, and history of hypertension at 5 years (Fig 2). Poor functional outcome was predicted by age (RR 1.03; 95% CI 1.01-1.04) at 1 month and by age (RR 1.04; 95% CI 1.00-1.08) and stroke severity (RR 1.94; 95% CI 1.02-2.87) at 1 year.
Conclusion:
Risk factors that predict SAH incidence including hypertension and smoking make outcomes worse. Better management of older patients and those with severe strokes could improve outcomes after SAH.
Abstract
Omic BON is a thematic Biodiversity Observation Network under the Group on Earth Observations Biodiversity Observation Network (GEO BON), focused on coordinating the observation of ...biomolecules in organisms and the environment. Our founding partners include representatives from national, regional, and global observing systems; standards organizations; and data and sample management infrastructures. By coordinating observing strategies, methods, and data flows, Omic BON will facilitate the co-creation of a global omics meta-observatory to generate actionable knowledge. Here, we present key elements of Omic BON's founding charter and first activities.
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