The Downward Influence of Sudden Stratospheric Warmings: Association with Tropospheric Precursors

Tropospheric features preceding sudden stratospheric warming events (SSWs) are identified using a large compendium of events obtained from a chemistryclimate model. In agreement with recent observational studies, it is found that approximately one-third of SSWs are preceded by extreme episodes of wave activity in the lower troposphere. The relationship becomes stronger in the lower stratosphere, where ~60% of SSWs are preceded by extreme wave activity at 100 hPa. Additional analysis characterizes events that do or do not appear to subsequently impact the troposphere, referred to as downward and non-downward propagating SSWs, respectively. On average, tropospheric wave activity is larger preceding downward-propagating SSWs compared to non-downward propagating events, and associated in particular with a doubly strengthened Siberian high. Of the SSWs that were preceded by extreme lower-tropospheric wave activity, ~2/3 propagated down to the troposphere, and hence the presence of extreme lower-tropospheric wave activity can only be used probabilistically to predict a slight increase or decrease at the onset, of the likelihood of tropospheric impacts to follow. However, a large number of downward and non-downward propagating SSWs must be considered (>35), before the difference becomes statistically significant. The precursors are also robust upon comparison with composites consisting of randomly selected tropospheric northern annular mode (NAM) events. The downward influence and precursors to split and displacement events are also examined. It is found that anomalous upward wave-1 fluxes precede both cases. Splits exhibit a near instantaneous, barotropic response in the stratosphere and troposphere, while displacements have a stronger long-term influence

Attitudes and expectations of patients on home parenteral nutrition towards eHealth: A multicenter survey.

BACKGROUND & AIMS Advances in technology enable patients on home parenteral nutrition (HPN) to manage their treatment more independently and safely. eHealth is a promising application of electronic means in healthcare, aimed at improving and simplifying processes and connecting the different parties involved. A thorough understanding of the attitudes and expectations of patients on HPN towards eHealth is a prerequisite for a successful implementation. However, to the best of our knowledge, such a survey preceding the implementation of HPN specific eHealth care has never been conducted. The objective of this preliminary survey is the acquisition of insights on the attitudes and expectations of patients on HPN towards eHealth. Resulting findings then serve as the basis for the design of an eHealth platform to facilitate communication among those involved in HPN care, improve the HPN management, and safeguard and monitor the treatment. METHODS We conducted a survey on the attitudes and expectations of patients towards an envisioned eHealth platform for HPN. Patients were recruited from large Swiss hospitals by their treating physician or directly by the research team. The surveys were conducted between September 2020 and October 2021 by structured personal interviews based on a questionnaire. RESULTS We included 35 patients on HPN (21 [60%] females) treated in ambulant care of 4 hospitals. They had a median (interquartile range) age of 55 (18) years and a median (interquartile range) duration of parenteral nutrition of 1.3 (3.1) years. Most patients (n = 30, 86%) were equipped with a smartphone, tablet, or computer and 22 (63%) used apps and rated themselves as proficient with the corresponding digital device. A majority of patients rated the following aspects and features of the platform as important: Data collection and storage (n = 29, 83%), checklists for PN, catheter, and infusion pump handling (n = 28, 80%), video instructions (n = 27, 77%), and videoconferencing with physicians (n = 25, 71%). Most patients (n = 26, 74%) were willing to enter data into the platform themselves. The type of data to be entered should be defined on an individual basis. CONCLUSIONS Patients on HPN are open to videoconference consultations and using an eHealth platform. Two-thirds have the necessary technical skills including suitable digital devices for an eHealth care. We identified key features of an eHealth platform to improve HPN management

A post-transcriptional regulatory landscape of aging in the female mouse hippocampus

Aging is associated with substantial physiological changes and constitutes a major risk factor for neurological disorders including dementia. Alterations in gene expression upon aging have been extensively studied; however, an in-depth characterization of post-transcriptional regulatory events remains elusive. Here, we profiled the age-related changes of the transcriptome and translatome in the female mouse hippocampus by RNA sequencing of total RNA and polysome preparations at four ages (3-, 6-, 12-, 20-month-old); and we implemented a variety of bioinformatics approaches to unravel alterations in transcript abundance, alternative splicing, and polyadenylation site selection. We observed mostly well-coordinated transcriptome and translatome expression signatures across age including upregulation of transcripts related to immune system processes and neuroinflammation, though transcripts encoding ribonucleoproteins or associated with mitochondrial functions, calcium signaling and the cell-cycle displayed substantial discordant profiles, suggesting translational control associated with age-related deficits in hippocampal-dependent behavior. By contrast, alternative splicing was less preserved, increased with age and was associated with distinct functionally-related transcripts encoding proteins acting at synapses/dendrites, RNA-binding proteins; thereby predicting regulatory roles for RBM3 and CIRBP. Only minor changes in polyadenylation site selection were identified, indicating pivotal 3′-end selection in young adults compared to older groups. Overall, our study provides a comprehensive resource of age-associated post-transcriptional regulatory events in the mouse hippocampus, enabling further examination of the molecular features underlying age-associated neurological diseases

Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors

BACKGROUND Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors. METHODS Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR). RESULTS As of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3-79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16-49) for all patients. In all patients, the 24-week disease control rate was 73% (95% CI: 54-87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45-100), 56% (95% CI: 38-74), and 85% (95% CI: 71-99), respectively. Median time to response was 1.9 months (range 1.0-3.8 months). Duration of treatment ranged from 1.2-31.3+ months. Treatment-related adverse events were reported for 20 patients, with Grade 3-4 in 3 patients. No new safety signals were identified. CONCLUSIONS In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile

Explaining Institutional Change: Why Elected Politicians Implement Direct Democracy

In existing models of direct democratic institutions, the median voter benefits, but representative politicians are harmed since their policy choices can be overridden. This is a puzzle, since representative politicians were instrumental in creating these institutions. I build a model of direct democracy that explains why a representative might benefit from tying his or her own hands in this way. The key features are (1) that voters are uncertain about their representative's preferences; (2) that direct and representative elections are complementary ways for voters to control outcomes. The model shows that some politicians benefit from the introduction of direct democracy, since they are more likely to survive representative elections: direct democracy credibly prevents politicians from realising extreme outcomes. Historical evidence from the introduction of the initiative, referendum and recall in America broadly supports the theory, which also explains two empirical results that have puzzled scholars: legislators are trusted less, but reelected more, in US states with direct democracy. I conclude by discussing the potential for incomplete information and signaling models to improve our understanding of institutional change more generally

Tissue Type-Specific Expression of the dsRNA-Binding Protein 76 and Genome-Wide Elucidation of Its Target mRNAs

Background: RNA-binding proteins accompany all steps in the life of mRNAs and provide dynamic gene regulatory functions for rapid adjustment to changing extra-or intracellular conditions. The association of RNA-binding proteins with their targets is regulated through changing subcellular distribution, post-translational modification or association with other proteins. Methodology: We demonstrate that the dsRNA binding protein 76 (DRBP76), synonymous with nuclear factor 90, displays inherently distinct tissue type-specific subcellular distribution in the normal human central nervous system and in malignant brain tumors of glial origin. Altered subcellular localization and isoform distribution in malignant glioma indicate that tumor-specific changes in DRBP76-related gene products and their regulatory functions may contribute to the formation and/or maintenance of these tumors. To identify endogenous mRNA targets of DRBP76, we performed RNA-immunoprecipitation and genome-wide microarray analyses in HEK293 cells, and identified specific classes of transcripts encoding critical functions in cellular metabolism. Significance: Our data suggest that physiologic DRBP76 expression, isoform distribution and subcellular localization are profoundly altered upon malignant transformation. Thus, the functional role of DRBP76 in co- or post-transcriptional gene regulation may contribute to the neoplastic phenotype

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis