Here we evaluate five atmospheric reanalyses in an Arctic gateway during late summer. The reanalyses include ERA5, ERA‐Interim, Japanese 55 year Re‐Analysis (JRA‐55), Climate Forecasting System ...Reanalysis‐version 2 (CFSv2), and Modern Era Retrospective analysis for Research and Applications‐version 2 (MERRA‐2). We use observations from 50 radiosondes launched in the Fram Strait around 79‐80°N, between 25 August and 11 September 2017. Crucially, data from 27 radiosondes were not transmitted to the Global Telecommunications System and therefore not assimilated into any reanalysis. In most reanalyses, the magnitude of wind speed and humidity errors is similar for profiles with and without data assimilation. In cases without data assimilation, correlation coefficients (R) exceed 0.88 for temperature, wind speed, and specific humidity, in all reanalyses. Overall, the newly released ERA5 has higher correlation coefficients than any other reanalyses as well as smaller biases and root‐mean‐square errors, for all three variables. The largest improvements identified in ERA5 are in its representation of the wind field, and temperature profiles over warm water.
Plain Language Summary
The Arctic is undergoing rapid and ongoing changes. However, due to the harsh environment, there are relatively few observations from this region. To understand the drivers of these changes, we rely heavily on atmospheric reanalyses. Reanalyses are our best guess at the state of the atmosphere at a given time. Reanalyses are generated by assimilating all available atmospheric observations into a weather forecast model. A key question within the scientific community is how accurate reanalyses are in the Arctic. One problem with answering this question is that most observations used to test the performance of reanalyses were ingested in to the model and are therefore not an independent data set. Here we present a new set of balloon‐borne atmospheric observations from the Fram Strait, between Svalbard and Greenland. Many of these data were not assimilated in to any reanalyses, providing a rare opportunity to evaluate their performance in this important Arctic gateway. We test five products, including the newly released ERA5 from the European Centre for Medium Ranged Weather Forecasting. All products simulate the temperature, humidity, and wind fields well, even without data assimilation. Overall, the newly released ERA5 performs best, with the largest improvements in the wind and temperature fields.
Key Points
In situ Arctic observations: 27 atmospheric profiles from radiosondes in Fram Strait (August–Septmber 2017) were not transmitted to GTS
ERA5 simulates observed atmospheric profiles more accurately than ERA‐Interim, JRA‐55, CFSv2, and MERRA‐2
Largest improvements are found in ERA5 for wind and temperature profiles over warmer eastern Fram Strait
Many of the devastating pandemics and outbreaks of the 20th and 21st centuries have involved enveloped viruses, including influenza, HIV, SARS, MERS, and Ebola. However, little is known about the ...presence and fate of enveloped viruses in municipal wastewater. Here, we compared the survival and partitioning behavior of two model enveloped viruses (MHV and ϕ6) and two nonenveloped bacteriophages (MS2 and T3) in raw wastewater samples. We showed that MHV and ϕ6 remained infective on the time scale of days. Up to 26% of the two enveloped viruses adsorbed to the solid fraction of wastewater compared to 6% of the two nonenveloped viruses. Based on this partitioning behavior, we assessed and optimized methods for recovering enveloped viruses from wastewater. Our optimized ultrafiltration method resulted in mean recoveries (±SD) of 25.1% (±3.6%) and 18.2% (±9.5%) for the enveloped MHV and ϕ6, respectively, and mean recoveries of 55.6% (±16.7%) and 85.5% (±24.5%) for the nonenveloped MS2 and T3, respectively. A maximum of 3.7% of MHV and 2% of MS2 could be recovered from the solids. These results shed light on the environmental fate of an important group of viruses and the presented methods will enable future research on enveloped viruses in water environments.
The giant, single-celled organism Stentor coeruleus has a long history as a model system for studying pattern formation and regeneration in single cells. Stentor 1, 2 is a heterotrichous ciliate ...distantly related to familiar ciliate models, such as Tetrahymena or Paramecium. The primary distinguishing feature of Stentor is its incredible size: a single cell is 1 mm long. Early developmental biologists, including T.H. Morgan 3, were attracted to the system because of its regenerative abilities—if large portions of a cell are surgically removed, the remnant reorganizes into a normal-looking but smaller cell with correct proportionality 2, 3. These biologists were also drawn to Stentor because it exhibits a rich repertoire of behaviors, including light avoidance, mechanosensitive contraction, food selection, and even the ability to habituate to touch, a simple form of learning usually seen in higher organisms 4. While early microsurgical approaches demonstrated a startling array of regenerative and morphogenetic processes in this single-celled organism, Stentor was never developed as a molecular model system. We report the sequencing of the Stentor coeruleus macronuclear genome and reveal key features of the genome. First, we find that Stentor uses the standard genetic code, suggesting that ciliate-specific genetic codes arose after Stentor branched from other ciliates. We also discover that ploidy correlates with Stentor’s cell size. Finally, in the Stentor genome, we discover the smallest spliceosomal introns reported for any species. The sequenced genome opens the door to molecular analysis of single-cell regeneration in Stentor.
•The introns of Stentor coeruleus, a giant ciliate, are 15–16 nt long•The short introns of Stentor are the shortest spliceosomal introns yet reported•Stentor uses a standard genetic code, unlike other characterized ciliates•The ploidy of the Stentor macronucleus is proportional to the volume of the cell
Stentor coeruleus is a giant single-celled organism that can regenerate after being cut in half. Slabodnick et al. describe the Stentor genome, a key tool for future experiments to understand regeneration in a single cell. The genome is unusual in that it contains extremely small introns.
Oncolytic viruses represent a novel drug class in which native or modified viruses mediate tumor regression through selective replication within and lysis of tumor cells as well as induction of ...systemic antitumor immunity capable of eradicating tumor at distant, uninjected sites. Talimogene laherparepvec (TVEC) is a type I herpes simplex virus genetically modified to preferentially replicate in tumor cells, enhance antigen loading of MHC class I molecules and express granulocyte-macrophage colony-stimulating factor to increase tumor-antigen presentation by dendritic cells. It is presently the only oncolytic virus approved by the FDA with an indication for advanced melanoma based upon improved durable response rate in a randomized, phase III trial. Clinical trials are underway in melanoma investigating TVEC as neoadjuvant monotherapy and in combination with checkpoint inhibitors for unresectable disease as well as in an array of other malignancies. It is appropriate to review TVEC's biology mechanism of action, clinical indication and future directions as a prototype of the burgeoning class of oncolytic viruses.
Gastric Cancer as Preventable Disease Rugge, Massimo; Genta, Robert M; Di Mario, Francesco ...
Clinical gastroenterology and hepatology,
12/2017, Volume:
15, Issue:
12
Journal Article
Peer reviewed
Open access
Gastric cancer, 1 of the 5 most common causes of cancer death, is associated with a 5-year overall survival rate less than 30%. A minority of cancers occurs as part of syndromic diseases; more than ...90% of adenocarcinomas are considered as the ultimate consequence of a longstanding mucosal inflammation. Helicobacter pylori infection is the leading etiology of non-self-limiting gastritis, which may result in atrophy of the gastric mucosa and impaired acid secretion. Gastric atrophy establishes a field of cancerization prone to further molecular and phenotypic changes, possibly resulting in cancer growth. This well-understood natural history provides the clinicopathologic rationale for primary and secondary cancer prevention strategies. A large body of evidence demonstrates that combined primary (H pylori eradication) and secondary (mainly endoscopy) prevention efforts may prevent or limit the progression of gastric oncogenesis. This approach, which is tailored to different country-specific gastric cancer incidence, socioeconomic, and cultural factors, requires that the complementary competences of gastroenterologists, oncologists, and pathologists be amalgamated into a common strategy of health policy.
Operative link on gastritis assessment (OLGA) staging for gastritis ranks the risk for gastric cancer (GC) in progressive stages (0-IV). This prospective study aimed at quantifying the cancer risk ...associated with each gastritis stage.
A cohort of 1755 consecutive patients with dyspepsia underwent initial (T-0) oesophagogastroduodenoscopy with mapped gastric biopsies, OLGA staging and assessment of
infection. Patients were followed for 55 months (median); patients with stages II III and IV underwent a second endoscopy/restaging (T-1), and those with stages 0 and I were followed clinically and through in-depth clinical and record checking. Endpoints were OLGA stage at T-1 and development of gastric epithelial neoplasia.
At T-0, 77.6% of patients had stage 0, 14.4% stage I, 5.1% stage II, 2.1% stage III and 0.85% stage IV.
infection was detected in 603 patients at T-0 and successfully eradicated in 602 of them; 220 had a documented history of
eradication; and 932 were
naïve-negative. Incident neoplastic lesions (prevalence=0.4%; low-grade intraepithelial neoplasia (IEN)=4; high-grade IEN=1; GC=2) developed exclusively in patients with stages III-IV. The risk for epithelial neoplasia was null in patients at stages 0, I and II (95% CI 0 to 0.4), 36.5 per 1000 person-years in patients at stage III (95% CI 13.7 to 97.4) and 63.1 per 1000 person-years in patients at stage IV (95% CI 20.3 to 195.6).
This prospective study confirms that OLGA staging reliably predicts the risk for development of gastric epithelial neoplasia. Although no neoplastic lesions arose in
naïve patients, the
eradication in subjects with advanced stages (III-IV) did not abolish the risk for neoplastic progression.
Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases.
To assess inhibition of interleukins 4 and 13 with dupilumab ...in patients with chronic sinusitis and nasal polyposis.
A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up.
Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks.
Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0-110; higher scores indicating worse quality of life; minimal clinically important difference ≥8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety.
Among the 60 patients who were randomized (mean SD age, 48.4 years 9.4 years; 34 men 56.7%; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was -0.3 (95% CI, -1.0 to 0.4) with placebo and -1.9 (95% CI, -2.5 to -1.2) with dupilumab (LS mean difference, -1.6 95% CI, -2.4 to -0.7; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was -8.8 (95% CI, -11.1 to -6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, -18.1 95% CI, -25.6 to -10.6; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 95% CI, 10.9 to 18.7; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%).
Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications.
clinicaltrials.gov Identifier: NCT01920893.
Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange sites for ions, metabolites and energy substrates from the blood to the brain. They maintain endothelial tight junctions ...that form the blood-brain barrier (BBB) and release vasoactive molecules that regulate vascular tone. Malignant gliomas are highly invasive tumours that use the perivascular space for invasion and co-opt existing vessels as satellite tumour form. Here we use a clinically relevant mouse model of glioma and find that glioma cells, as they populate the perivascular space of preexisting vessels, displace astrocytic endfeet from endothelial or vascular smooth muscle cells. This causes a focal breach in the BBB. Furthermore, astrocyte-mediated gliovascular coupling is lost, and glioma cells seize control over the regulation of vascular tone through Ca(2+)-dependent release of K(+). These findings have important clinical implications regarding blood flow in the tumour-associated brain and the ability to locally deliver chemotherapeutic drugs in disease.
Near‐surface air temperatures close to 0°C were observed in situ over sea ice in the central Arctic during the last three winter seasons. Here we use in situ winter (December–March) temperature ...observations, such as those from Soviet North Pole drifting stations and ocean buoys, to determine how common Arctic winter warming events are. Observations of winter warming events exist over most of the Arctic Basin. Temperatures exceeding −5°C were observed during >30% of winters from 1954 to 2010 by North Pole drifting stations or ocean buoys. Using the ERA‐Interim record (1979–2016), we show that the North Pole (NP) region typically experiences 10 warming events (T2m > −10°C) per winter, compared with only five in the Pacific Central Arctic (PCA). There is a positive trend in the overall duration of winter warming events for both the NP region (4.25 days/decade) and PCA (1.16 days/decade), due to an increased number of events of longer duration.
Plain Language Summary
During the last three winter seasons, extreme warming events were observed over sea ice in the central Arctic Ocean. Each of these warming events were associated with temperatures close to or above 0°C, which lasted for between 1 and 3 days. Typically temperatures in the Arctic at this time of year are below −30°C. Here we study past temperature observations in the Arctic to investigate how common winter warming events are. We use time temperature observations from expeditions such as Fram (1893–1896) and manned Soviet North Pole drifting ice stations from 1937 to 1991. These historic temperature records show that winter warming events have been observed over most of the Arctic Ocean. Despite a thin network of observation sites, winter time temperatures above −5°C were directly observed approximately once every 3 years in the central Arctic Ocean between 1954 and 2010. Winter warming events are associated with storm systems originating in either the Atlantic or Pacific Oceans. Twice as many warming events originate from the Atlantic Ocean compared with the Pacific. These storms often penetrate across the North Pole. While observations of winter warming events date back to 1896, we find an increasing number of winter warming events in recent years.
Key Points
Arctic winter warming events are a normal part of the Arctic winter climate. Observations of these events date back to the Fram expedition
North Pole region typically experiences 10 distinct warming events per winter, compared with 5 in the Pacific Central Arctic
Positive trends in the number and duration of Arctic winter warming events (1980–2016), with strongest trends for North Pole domain
Rapid changes are occurring in the Arctic, including a
reduction in sea ice thickness and coverage and a shift towards younger and
thinner sea ice. Snow and sea ice models are often used to study ...these
ongoing changes in the Arctic, and are typically forced by atmospheric
reanalyses in absence of observations. ERA5 is a new global reanalysis that
will replace the widely used ERA-Interim (ERA-I). In this study, we compare
the 2 m air temperature (T2M), snowfall (SF) and total precipitation (TP)
from ERA-I and ERA5, and evaluate these products using buoy observations
from Arctic sea ice for the years 2010 to 2016. We further assess how biases in
reanalyses can influence the snow and sea ice evolution in the Arctic, when
used to force a thermodynamic sea ice model. We find that ERA5 is generally
warmer than ERA-I in winter and spring (0–1.2 ∘C), but colder
than ERA-I in summer and autumn (0–0.6 ∘C) over Arctic sea ice.
Both reanalyses have a warm bias over Arctic sea ice relative to buoy
observations. The warm bias is smaller in the warm season, and larger in the
cold season, especially when the T2M is below −25 ∘C in the
Atlantic and Pacific sectors. Interestingly, the warm bias for ERA-I and new
ERA5 is on average 3.4 and 5.4 ∘C (daily mean),
respectively, when T2M is lower than −25 ∘C. The TP and SF along
the buoy trajectories and over Arctic sea ice are consistently higher in ERA5
than in ERA-I. Over Arctic sea ice, the TP in ERA5 is typically less than 10 mm snow water equivalent (SWE) greater than in ERA-I in any of the seasons, while the SF in ERA5 can
be 50 mm SWE higher than in ERA-I in a season. The largest increase in
annual TP (40–100 mm) and SF (100–200 mm) in ERA5 occurs in the Atlantic
sector. The SF to TP ratio is larger in ERA5 than in ERA-I, on average 0.6
for ERA-I and 0.8 for ERA5 along the buoy trajectories. Thus, the
substantial anomalous Arctic rainfall in ERA-I is reduced in ERA5,
especially in summer and autumn. Simulations with a 1-D thermodynamic sea ice
model demonstrate that the warm bias in ERA5 acts to reduce thermodynamic
ice growth. The higher precipitation and snowfall in ERA5 results in a
thicker snowpack that allows less heat loss to the atmosphere. Thus, the
larger winter warm bias and higher precipitation in ERA5, compared with
ERA-I, result in thinner ice thickness at the end of the growth
season when using ERA5; however the effect is small during the freezing
period.
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