Snow-vegetation-atmosphere interactions in alpine tundra

The interannual variability of snow cover in alpine areas is increasing, which may affect the tightly coupled cycles of carbon and water through snow-vegetation-atmosphere interactions across a range of spatio-temporal scales. To explore the role of snow cover for the land-atmosphere exchange of CO2 and water vapor in alpine tundra ecosystems, we combined three years (2019&ndash;2021) of continuous eddy covariance flux measurements of net ecosystem exchange of CO2 (NEE) and evapotranspiration (ET) from the Finse site in alpine Norway (1210 m a.s.l.) with a ground-based ecosystem-type classification and satellite imagery from Sentinel-2, Landsat 8, and MODIS. While the snow conditions in 2019 and 2021 can be described as site-typical, 2020 features an extreme snow accumulation associated with a strong negative phase of the Scandinavian Pattern of the synoptic atmospheric circulation during spring. This extreme snow accumulation caused a one-month delay in melt-out date, which falls on the 92nd-percentile in the distribution of yearly melt-out dates in the period 2001&ndash;2021. The melt-out dates follow a consistent fine-scale spatial relationship with ecosystem types across years. Mountain and lichen heathlands melt out more heterogeneously than fens and flood plains, while late snowbeds melt out up to one month later than the other ecosystem types. While the summertime average Normalized Difference Vegetation Index (NDVI) was reduced considerably during the extreme snow year 2020, it reached the same maximum as in the other years for all but one the ecosystem type (late snowbeds), indicating that the delayed onset of vegetation growth is compensated to the same maximum productivity. Eddy covariance estimates of NEE and ET are gap-filled separately for two wind sectors using a random forest regression model to account for complex and nonlinear ecohydrological interactions. While the two wind sectors differ markedly in vegetation composition and flux magnitudes, their flux response is controlled by the same drivers as estimated by the predictor importance of the random forest model as well as the high correlation of flux magnitudes (correlation coefficient r = 0.92 for NEE and r = 0.89 for ET) between both areas. The one-month delay of the start of the snow-free season in 2020 reduced the total annual ET by 50 % compared to 2019 and 2021, and reduced the growing season carbon assimilation to turn the ecosystem from a moderate annual carbon sink (&minus;31 to &minus;6 gC m&minus;2 yr&minus;1) to a source (34 to 20 gC m&minus;2 yr&minus;1). These results underpin the strong dependence of ecosystem structure and functioning on snow dynamics, whose anomalies can result in important ecological extreme events for alpine ecosystems.</p

Benefit of second-line therapy for advanced esophageal squamous cell carcinoma: a tri-center propensity score analysis

BACKGROUND: The level of evidence for palliative second-line therapy in advanced esophageal squamous cell carcinoma (aESCC) is limited. This is the first study that reports efficacy data comparing second-line therapy + active symptom control (ASC) versus ASC alone in aESCC. METHODS: We conducted a tri-center retrospective cohort study (n = 166) including patients with aESCC who had experienced disease progression on palliative first-line therapy. A propensity score model using inverse probability of treatment weighting (IPTW) was implemented for comparative efficacy analysis of overall survival (OS) in patients with second-line + ASC (n = 92, 55%) versus ASC alone (n = 74, 45%). RESULTS: The most frequent second-line regimens used were docetaxel (36%) and paclitaxel (18%). In unadjusted primary endpoint analysis, second-line + ASC was associated with significantly longer OS compared with ASC alone [hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.35–0.69, p < 0.0001]. However, patients in the second-line + ASC group were characterized by more favorable baseline features including a better Eastern Cooperative Oncology Group (ECOG) performance status, a longer first-line treatment duration and lower C-reactive protein levels. After rigorous adjusting for baseline confounders by re-weighting the data with the IPTW the favorable association between second-line and longer OS weakened but prevailed. The median OS was 6.1 months in the second-line + ASC group and 3.2 months in the ASC group, respectively (IPTW-adjusted HR = 0.40, 95% CI: 0.24–0.69, p = 0.001). Importantly, the benefit of second-line was consistent across several clinical subgroups, including patients with ECOG performance status ⩾1 and age ⩾65 years. The most common grade 3 or 4 adverse events associated with palliative second-line therapy were hematological toxicities. CONCLUSION: This real-world study supports the concept that systemic second-line therapy prolongs survival in patients with aESCC

Climate–ecosystem modelling made easy: The Land Sites Platform

Dynamic Global Vegetation Models (DGVMs) provide a state-of-the-art process-based approach to study the complex interplay between vegetation and its physical environment. For example, they help to predict how terrestrial plants interact with climate, soils, disturbance and competition for resources. We argue that there is untapped potential for the use of DGVMs in ecological and ecophysiological research. One fundamental barrier to realize this potential is that many researchers with relevant expertize (ecology, plant physiology, soil science, etc.) lack access to the technical resources or awareness of the research potential of DGVMs. Here we present the Land Sites Platform (LSP): new software that facilitates single-site simulations with the Functionally Assembled Terrestrial Ecosystem Simulator, an advanced DGVM coupled with the Community Land Model. The LSP includes a Graphical User Interface and an Application Programming Interface, which improve the user experience and lower the technical thresholds for installing these model architectures and setting up model experiments. The software is distributed via version-controlled containers; researchers and students can run simulations directly on their personal computers or servers, with relatively low hardware requirements, and on different operating systems. Version 1.0 of the LSP supports site-level simulations. We provide input data for 20 established geo-ecological observation sites in Norway and workflows to add generic sites from public global datasets. The LSP makes standard model experiments with default data easily achievable (e.g., for educational or introductory purposes) while retaining flexibility for more advanced scientific uses. We further provide tools to visualize the model input and output, including simple examples to relate predictions to local observations. The LSP improves access to land surface and DGVM modelling as a building block of community cyberinfrastructure that may inspire new avenues for mechanistic ecosystem research across disciplines.publishedVersio

Towards real-time cardiovascular magnetic resonance guided transarterial CoreValve implantation: in vivo evaluation in swine

<p>Abstract</p> <p>Background</p> <p>Real-time cardiovascular magnetic resonance (rtCMR) is considered attractive for guiding TAVI. Owing to an unlimited scan plane orientation and an unsurpassed soft-tissue contrast with simultaneous device visualization, rtCMR is presumed to allow safe device navigation and to offer optimal orientation for precise axial positioning. We sought to evaluate the preclinical feasibility of rtCMR-guided transarterial aortic valve implatation (TAVI) using the nitinol-based Medtronic CoreValve bioprosthesis.</p> <p>Methods</p> <p>rtCMR-guided transfemoral (n = 2) and transsubclavian (n = 6) TAVI was performed in 8 swine using the original CoreValve prosthesis and a modified, CMR-compatible delivery catheter without ferromagnetic components.</p> <p>Results</p> <p>rtCMR using TrueFISP sequences provided reliable imaging guidance during TAVI, which was successful in 6 swine. One transfemoral attempt failed due to unsuccessful aortic arch passage and one pericardial tamponade with subsequent death occurred as a result of ventricular perforation by the device tip due to an operating error, this complication being detected without delay by rtCMR. rtCMR allowed for a detailed, simultaneous visualization of the delivery system with the mounted stent-valve and the surrounding anatomy, resulting in improved visualization during navigation through the vasculature, passage of the aortic valve, and during placement and deployment of the stent-valve. Post-interventional success could be confirmed using ECG-triggered time-resolved cine-TrueFISP and flow-sensitive phase-contrast sequences. Intended valve position was confirmed by ex-vivo histology.</p> <p>Conclusions</p> <p>Our study shows that rtCMR-guided TAVI using the commercial CoreValve prosthesis in conjunction with a modified delivery system is feasible in swine, allowing improved procedural guidance including immediate detection of complications and direct functional assessment with reduction of radiation and omission of contrast media.</p

Patients' experiences and perceived causes of persisting discomfort following day surgery

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to describe patients' experiences and perceived causes of persisting discomfort following day surgery. Earlier research has mainly covered symptoms and signs during a recovery period of up to one month, and not dealt with patients' perceptions of what causes persisting, longer-term discomfort.</p> <p>Methods</p> <p>This study is a part from a study carried out during the period May 2006 to May 2007 with a total of 298 day surgery patients. Answers were completed by 118 patients at 48 hours, 110 at seven days and 46 at three months to one open-ended question related to discomfort after day surgery constructed as follows: <it>If you are still experiencing discomfort related to the surgery, what is the reason, in your opinion</it>? Data was processed, quantitatively and qualitatively. Descriptive, inferential, correlation and content analyses were performed.</p> <p>Results</p> <p>The results suggest that patients suffer from remaining discomfort e.g. pain and wound problem, with effects on daily life following day surgery up to three months. Among patients' perceptions of <it>factors leading to discomfort </it>may be <it>wrongful or suboptimal treatment</it>, <it>type of surgery </it>or <it>insufficient access to provider/information.</it></p> <p>Conclusions</p> <p>The results have important implications for preventing and managing discomfort at home following day surgery, and for nursing interventions to help patients handle the recovery period better.</p

Biallelic ADAM22 pathogenic variants cause progressive encephalopathy and infantile-onset refractory epilepsy

Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harboring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20), delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: defective cell membrane expression (1), impaired LGI1-binding (2), and/or impaired interaction with the postsynaptic density protein PSD-95 (3). We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics

Biallelic ADAM22 pathogenic variants cause progressive encephalopathy and infantile-onset refractory epilepsy

Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harbouring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20) and delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: (i) defective cell membrane expression; (ii) impaired LGI1-binding; and/or (iii) impaired interaction with the postsynaptic density protein PSD-95. We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics. Van der Knoop et al. describe the clinical features of 21 individuals with biallelic pathogenic variants in ADAM22 and confirm the deleteriousness of the variants with functional studies. Clinical hallmarks of this rare disorder comprise progressive encephalopathy and infantile-onset refractory epilepsy.Peer reviewe

Myeloid Cells Restrict MCMV and Drive Stress-Induced Extramedullary Hematopoiesis through STAT1

Cytomegalovirus (CMV) has a high prevalence worldwide, is often fatal for immunocompromised patients, and causes bone marrow suppression. Deficiency of signal transducer and activator of transcription 1 (STAT1) results in severely impaired antiviral immunity. We have used cell-type restricted deletion of Stat1 to determine the importance of myeloid cell activity for the defense against murine CMV (MCMV). We show that myeloid STAT1 limits MCMV burden and infection-associated pathology in the spleen but does not affect ultimate clearance of infection. Unexpectedly, we found an essential role of myeloid STAT1 in the induction of extramedullary hematopoiesis (EMH). The EMH-promoting function of STAT1 was not restricted to MCMV infection but was also observed during CpG oligodeoxynucleotide-induced sterile inflammation. Collectively, we provide genetic evidence that signaling through STAT1 in myeloid cells is required to restrict MCMV at early time points post-infection and to induce compensatory hematopoiesis in the spleen