Drought as an Inciting Mortality Factor in Scots Pine Stands of the Valais, Switzerland

During the 20th century, high mortality rates of Scots pine (Pinus silvestris L.) have been observed over large areas in the Rhône valley (Valais, Switzerland) and in other dry valleys of the European Alps. In this study, we evaluated drought as a possible inciting factor of Scots pine decline in the Valais. Averaged tree-ring widths, standardized tree-ring series, and estimated annual mortality risks were related to a drought index. Correlations between drought indices and standardized tree-ring series from 11 sites showed a moderate association. Several drought years and drought periods could be detected since 1864 that coincided with decreased growth. Although single, extreme drought years had generally a short-term, reversible effect on tree growth, multi-year drought initiated prolonged growth decreases that increased a tree's long-term risk of death. Tree death occurred generally several years or even decades after the drought. In conclusion, drought has a limiting effect on tree growth and acts as a bottleneck event in triggering Scots pine decline in the Valai

Eurasian contribution to the last glacial dust cycle:how are loess sequences built?

International audienceThe last 130 000 years have been marked by pronounced millennial-scale climate variability, which strongly impacted the terrestrial environments of the Northern Hemisphere, especially at middle latitudes. Identifying the trigger of these variations, which are most likely associated with strong couplings between the ocean and the atmosphere, still remains a key question. Here, we show that the analysis of δ 18 O and dust in the Greenland ice cores, and a critical study of their source variations, reconciles these records with those observed on the Eurasian continent. We demonstrate the link between European and Chinese loess sequences, dust records in Greenland, and variations in the North Atlantic sea ice extent. The sources of the emitted and transported dust material are variable and relate to different environments corresponding to present desert areas, but also hidden regions related to lower sea level stands, dry rivers, or zones close to the frontal moraines of the main Northern Hemisphere ice sheets. We anticipate our study to be at the origin of more sophisticated and elaborated investigations of millennial and sub-millennial continental climate variability in the Northern Hemisphere

Therapeutic Management of Anomalous Coronary Arteries Originating From the Opposite Sinus of Valsalva: Current Evidence, Proposed Approach, and the Unknowing.

Anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS) are a challenge because of their various anatomic and clinical presentation. Although the prevalence is low, the absolute numbers of detected ACAOS are increasing because of the growing use of noninvasive anatomical imaging for ruling out coronary artery disease. As evidence-based guidelines are lacking, treating physicians are left in uncertainty for the optimal management of such patients. The sole presence of ACAOS does not justify surgical correction, and therefore a thorough anatomic and hemodynamic assessment is warranted. Invasive and noninvasive multimodality imaging provides information to the clinical question whether the presence of ACAOS is an innocent coincidental finding, is responsible for the patient's symptoms, or even might be a risk for sudden cardiac death. Based on recent clinical data, focusing on the pathophysiology of patients with ACAOS, myocardial ischemia is dependent on both the extent of fixed and dynamic components, represented by anatomic high-risk features. These varying combinations should be considered individually in the decision making for the different therapeutic options. This state-of-the-art review focuses on the advantages and limitations of the common contemporary surgical, interventional, and medical therapy with regard to the anatomy and pathophysiology of ACAOS. Further, we propose a therapeutic management algorithm based on current evidence on multimodality invasive and noninvasive imaging findings and highlight remaining gaps of knowledge

Inverse stochastic-dynamic models for high-resolution Greenland ice core records

Proxy records from Greenland ice cores have been studied for several decades, yet many open questions remain regarding the climate variability encoded therein. Here, we use a Bayesian framework for inferring inverse, stochastic–dynamic models from δ¹⁸O and dust records of unprecedented, subdecadal temporal resolution. The records stem from the North Greenland Ice Core Project (NGRIP), and we focus on the time interval 59–22 ka b2k. Our model reproduces the dynamical characteristics of both the δ¹⁸O and dust proxy records, including the millennial-scale Dansgaard–Oeschger variability, as well as statistical properties such as probability density functions, waiting times and power spectra, with no need for any external forcing. The crucial ingredients for capturing these properties are (i) high-resolution training data, (ii) cubic drift terms, (iii) nonlinear coupling terms between the δ¹⁸O and dust time series, and (iv) non-Markovian contributions that represent short-term memory effects

Torcetrapib impairs endothelial function in hypertension

Aims A marked increase in HDL notwithstanding, the cholesterol ester transfer protein (CETP) inhibitor torcetrapib was associated with an increase in all-cause mortality in the ILLUMINATE trial. As underlying mechanisms remain elusive, the present study was designed to delineate potential off-target effects of torcetrapib. Methods and results Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were treated with torcetrapib (100 mg/kg/day; SHR-T and WKY-T) or placebo (SHR-P and WKY-P) for 3 weeks. Blood pressure transiently increased during the first 3 days of torcetrapib administration in SHRs and returned to baseline thereafter despite continued drug administration. Acetylcholine-induced endothelium-dependent relaxations of aortic rings were markedly impaired, and endothelial nitric oxide synthase (eNOS) mRNA and protein were down-regulated after 3 weeks of torcetrapib treatment in SHR (P < 0.0001, <0.01, and <0.05, resp. vs. SHR-P). Torcetrapib reduced NO release in cultured aortic endothelial cells (P < 0.01 vs. vehicle-treated cells) and increased generation of reactive oxygen species in aortas of SHR-T (P < 0.05, vs. SHR-P). Vascular reactivity to endothelin-1 (ET-1) and aortic ET-1 tissue content were increased in SHR-T (P < 0.05 vs. SHR-P). Importantly, the ET-1 receptor A/B (ETA/B) antagonist bosentan normalized endothelial function in SHR-T (P < 0.05). Conclusion Torcetrapib induces a sustained impairment of endothelial function, decreases eNOS mRNA, protein as well as NO release, stimulates vascular ROS and ET production, an effect that is prevented by chronic ETA/B-receptor blockade. These unexpected off-target effects of torcetrapib need to be ruled out in the clinical development of novel CETP inhibitors, particularly before a large patient population at increased cardiovascular risk is exposed to these compound

Coronary CT FFR vs Invasive Adenosine and Dobutamine FFR in a Right Anomalous Coronary Artery.

We present the management of an anomalous coronary artery originating from the opposite sinus of Valsalva with comprehensive diagnostic workup including noninvasive coronary computed tomography (CT) derived fractional flow reserve (FFR) and invasive dobutamine-volume challenge-FFR/intravascular ultrasound. After surgical operation, treatment success was quantified by anatomical and functional analysis in postoperative CT. (Level of Difficulty: Advanced.)

Decadal-scale progression of Dansgaard-Oeschger warming events

During the last glacial period, proxy records throughout the Northern Hemisphere document a succession of rapid millennial-scale warming events, called Dansgaard–Oeschger (DO) events. A range of different mechanisms has been proposed that can produce similar warming in model experiments; however, the progression and ultimate trigger of the events are still unknown. Because of their fast nature, the progression is challenging to reconstruct from paleoclimate data due to the limited temporal resolution achievable in many archives and cross-dating uncertainties between records. Here, we use new high-resolution multi-proxy records of sea-salt (derived from sea spray and sea ice over the North Atlantic) and terrestrial (derived from the central Asian deserts) aerosol concentrations over the period 10–60 ka from the North Greenland Ice Core Project (NGRIP) and North Greenland Eemian Ice Drilling (NEEM) ice cores in conjunction with local precipitation and temperature proxies from the NGRIP ice core to investigate the progression of environmental changes at the onset of the warming events at annual to multi-annual resolution. Our results show on average a small lead of the changes in both local precipitation and terrestrial dust aerosol concentrations over the change in sea-salt aerosol concentrations and local temperature of approximately one decade. This suggests that, connected to the reinvigoration of the Atlantic meridional overturning circulation and the warming in the North Atlantic, both synoptic and hemispheric atmospheric circulation changes at the onset of the DO warming, affecting both the moisture transport to Greenland and the Asian monsoon systems. Taken at face value, this suggests that a collapse of the sea-ice cover may not have been the initial trigger for the DO warming

A North Atlantic tephrostratigraphical framework for 130-60 ka b2k:new tephra discoveries, marine-based correlations, and future challenges

Building chronological frameworks for proxy sequences spanning 130–60 ka b2k is plagued by difficulties and uncertainties. Recent developments in the North Atlantic region, however, affirm the potential offered by tephrochronology and specifically the search for cryptotephra. Here we review the potential offered by tephrostratigraphy for sequences spanning 130–60 ka b2k. We combine newly identified cryptotephra deposits from the NGRIP ice-core and a marine core from the Iceland Basin with previously published data from the ice and marine realms to construct the first tephrostratigraphical framework for this time-interval. Forty-three tephra or cryptotephra deposits are incorporated into this framework; twenty three tephra deposits are found in the Greenland ice-cores, including nine new NGRIP tephras, and twenty separate deposits are preserved in various North Atlantic marine sequences. Major, minor and trace element results are presented for the new NGRIP horizons together with age estimates based on their position within the ice-core record. Basaltic tephras of Icelandic origin dominate the framework with only eight tephras of rhyolitic composition found. New results from marine core MD99-2253 also illustrate some of the complexities and challenges of assessing the depositional integrity of marine cryptotephra deposits. Tephra-based correlations in the marine environment provide independent tie-points for this time-interval and highlight the potential of widening the application of tephrochronology. Further investigations, however, are required, that combine robust geochemical fingerprinting and a rigorous assessment of tephra depositional processes, in order to trace coeval events between the two depositional realms

Frequency of serological non-responders and false-negative RT-PCR results in SARS-CoV-2 testing: a population-based study.

Objectives The sensitivity of molecular and serological methods for COVID-19 testing in an epidemiological setting is not well described. The aim of the study was to determine the frequency of negative RT-PCR results at first clinical presentation as well as negative serological results after a follow-up of at least 3 weeks. Methods Among all patients seen for suspected COVID-19 in Liechtenstein (n=1921), we included initially RT-PCR positive index patients (n=85) as well as initially RT-PCR negative (n=66) for follow-up with SARS-CoV-2 antibody testing. Antibodies were detected with seven different commercially available immunoassays. Frequencies of negative RT-PCR and serology results in individuals with COVID-19 were determined and compared to those observed in a validation cohort of Swiss patients (n=211). Results Among COVID-19 patients in Liechtenstein, false-negative RT-PCR at initial presentation was seen in 18% (12/66), whereas negative serology in COVID-19 patients was 4% (3/85). The validation cohort showed similar frequencies: 2/66 (3%) for negative serology, and 16/155 (10%) for false negative RT-PCR. COVID-19 patients with negative follow-up serology tended to have a longer disease duration (p=0.05) and more clinical symptoms than other patients with COVID-19 (p<0.05). The antibody titer from quantitative immunoassays was positively associated with the number of disease symptoms and disease duration (p<0.001). Conclusions RT-PCR at initial presentation in patients with suspected COVID-19 can miss infected patients. Antibody titers of SARS-CoV-2 assays are linked to the number of disease symptoms and the duration of disease. One in 25 patients with RT-PCR-positive COVID-19 does not develop antibodies detectable with frequently employed and commercially available immunoassays

Characterization of a Pan-Immunoglobulin Assay Quantifying Antibodies Directed against the Receptor Binding Domain of the SARS-CoV-2 S1-Subunit of the Spike Protein: A Population-Based Study.

Pan-immunoglobulin assays can simultaneously detect IgG, IgM and IgA directed against the receptor binding domain (RBD) of the S1 subunit of the spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 S1-RBD Ig). In this work, we aim to evaluate a quantitative SARS-CoV-2 S1-RBD Ig electrochemiluminescence immunoassay (ECLIA) regarding analytical, diagnostic, operational and clinical characteristics. Our work takes the form of a population-based study in the principality of Liechtenstein, including 125 cases with clinically well-described and laboratory confirmed SARS-CoV-2 infection and 1159 individuals without evidence of coronavirus disease 2019 (COVID-19). SARS-CoV-2 cases were tested for antibodies in sera taken with a median of 48 days (interquartile range, IQR, 43-52) and 139 days (IQR, 129-144) after symptom onset. Sera were also tested with other assays targeting antibodies against non-RBD-S1 and -S1/S2 epitopes. Sensitivity was 97.6% (95% confidence interval, CI, 93.2-99.1), whereas specificity was 99.8% (95% CI, 99.4-99.9). Antibody levels linearly decreased from hospitalized patients to symptomatic outpatients and SARS-CoV-2 infection without symptoms (p < 0.001). Among cases with SARS-CoV-2 infection, smokers had lower antibody levels than non-smokers (p = 0.04), and patients with fever had higher antibody levels than patients without fever (p = 0.001). Pan-SARS-CoV-2 S1-RBD Ig in SARS-CoV-2 infection cases significantly increased from first to second follow-up (p < 0.001). A substantial proportion of individuals without evidence of past SARS-CoV-2 infection displayed non-S1-RBD antibody reactivities (248/1159, i.e., 21.4%, 95% CI, 19.1-23.4). In conclusion, a quantitative SARS-CoV-2 S1-RBD Ig assay offers favorable and sustained assay characteristics allowing the determination of quantitative associations between clinical characteristics (e.g., disease severity, smoking or fever) and antibody levels. The assay could also help to identify individuals with antibodies of non-S1-RBD specificity with potential clinical cross-reactivity to SARS-CoV-2