On Uniformly Most Powerful Decentralized Detection

The theory behind Uniformly Most Powerful (UMP) composite binary hypothesis testing is mature and well defined in centralized detection where all observations are directly accessible at one central node. However, within the area of decentralized detection, UMP tests have not been researched, even though tests of this nature have properties that are highly desirable. The purpose of this research is to extend the UMP concept into decentralized detection, which we define as UMP decentralized detection (UMP-DD). First, the standard parallel decentralized detection model with conditionally independent observations will be explored. This section will introduce theorems and corollaries that define when UMP-DD exists and provide counterintuitive examples where UMP-DD tests do not exist. Second, we explore UMP-DD for directed single-rooted trees of bounded height. We will show that a binary relay tree achieves a Type II error probability exponent that is equivalent to the parallel structure even if all the observations are not identically distributed. We then show that the optimal configuration can also achieve UMP-DD performance, while the tandem configuration does not achieve UMP-DD performance. Finally, we relax the assumption of conditional independence and show under specific constraints that both the parallel and binary relay tree configurations can still be UMP-DD. Throughout, examples will be provided that tie this theoretical work together with current research in fields such as Cognitive Radio

Asynchronous accretion can mimic diverse white dwarf pollutants II: water content

Volatiles, notably water, are key to the habitability of rocky planets. The presence of water in planetary material can be inferred from the atmospheric oxygen abundances of polluted white dwarfs, but this interpretation is often complex. We study the accretion process, and find that ices may sublimate and accrete before more refractory minerals reach the star. As a result, a white dwarf's relative photospheric abundances may vary with time during a single accretion event, and do not necessarily reflect the bulk composition of a pollutant. We offer two testable predictions for this hypothesis: 1. cooler stars will more often be inferred to have accreted wet pollutants, and 2. there will be rare occurrences of accretion events with inferred volatile levels far exceeding those of pristine comets. To observationally test these predictions, we statistically constrain the water content of white dwarf pollutants. We find that in the current sample, only three stars show statistically significant evidence of water at the 2$\sigma$ level, due to large typical uncertainties in atmospheric abundances and accretion states. In the future, an expanded sample of polluted white dwarfs with hydrogen-dominated atmospheres will allow for the corroboration of our theoretical predictions. Our work also shows the importance of interpreting pollutant compositions statistically, and emphasizes the requirement to reduce uncertainties on measured abundances to allow for statistically significant constraints on their water content.Comment: Accepted for publication in MNRAS. Part two of a series of two papers. Comments and questions welcom

The paradoxical signals of two TrkC receptor isoforms supports a rationale for novel therapeutic strategies in ALS

Full length TrkC (TrkC-FL) is a receptor tyrosine kinase whose mRNA can be spliced to a truncated TrkC.T1 isoform lacking the kinase domain. Neurotrophin-3 (NT-3) activates TrkC-FL to maintain motor neuron health and function and TrkC.T1 to produce neurotoxic TNF-α; hence resulting in opposing pathways. In mouse and human ALS spinal cord, the reduction of miR-128 that destabilizes TrkC.T1 mRNA results in up-regulated TrkC.T1 and TNF-α in astrocytes. We exploited conformational differences to develop an agonistic mAb 2B7 that selectively activates TrkC-FL, to circumvent TrkC.T1 activation. In mouse ALS,2B7 activates spinal cord TrkC-FL signals, improves spinal cord motor neuron phenotype and function, and significantly prolongs life-span. Our results elucidate biological paradoxes of receptor isoforms and their role in disease progression, validate the concept of selectively targeting conformational epitopes in naturally occurring isoforms, and may guide the development of pro-neuroprotective (TrkC-FL) and anti-neurotoxic (TrkC.T1) therapeutic strategies.Fil: Brahimi, Fouad. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Maira, Mario. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Barcelona, Pablo Federico. Mc Gill University. Lady Davis Research Intitute; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Galan, Alba. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Aboulkassim, Tahar. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Teske, Katrina. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Rogers, Mary Louise. Flinders University, Department Of Human Physiology; AustraliaFil: Bertram, Lisa. University of British Columbia; CanadáFil: Wang, Jing. University of British Columbia; CanadáFil: Yousefi, Masoud. University of British Columbia; CanadáFil: Rush, Robert. Flinders University, Department Of Human Physiology; AustraliaFil: Fabian, Marc. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Cashman, Neil. University of British Columbia; CanadáFil: Saragovi, H. Uri. Mc Gill University. Lady Davis Research Intitute; Canad

Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells

Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found to be critically important for the maintenance of tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the tumor from which they are identified, and are drivers of recurrence in numerous cancers. In this study, telomerase enzymatic activity was directly measured and inhibited to assess the therapeutic potential of targeting telomerase. Telomerase repeat amplification protocol (TRAP) (n = 36) and C-circle assay/telomere FISH/ATRX staining (n = 76) were performed on primary ependymomas to determine the prevalence and prognostic potential of telomerase activity or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms, respectively. Imetelstat, a phase 2 telomerase inhibitor, was used to elucidate the effect of telomerase inhibition on proliferation and tumorigenicity in established cell lines (BXD-1425EPN, R254), a primary TIC line (E520) and xenograft models of pediatric ependymoma. Over 60 % of pediatric ependymomas were found to rely on telomerase activity to maintain telomeres, while no ependymomas showed evidence of ALT. Children with telomerase-active tumors had reduced 5-year progression-free survival (29 +/- A 11 vs 64 +/- A 18 %; p = 0.03) and overall survival (58 +/- A 12 vs 83 +/- A 15 %; p = 0.05) rates compared to those with tumors lacking telomerase activity. Imetelstat inhibited proliferation and self-renewal by shortening telomeres and inducing senescence in vitro. In vivo, Imetelstat significantly reduced subcutaneous xenograft growth by 40 % (p = 0.03) and completely abolished the tumorigenicity of pediatric ependymoma TICs in an orthotopic xenograft model. Telomerase inhibition represents a promising therapeutic approach for telomerase-active pediatric ependymomas found to characterize high-risk ependymomas.Canadian Institutes of Health Research [MOP 82727]info:eu-repo/semantics/publishedVersio

Standardized Definitions for Bioprosthetic Valve Dysfunction Following Aortic or Mitral Valve Replacement: JACC State-of-the-Art Review.

peer reviewedBioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF) may be caused by structural or nonstructural valve dysfunction. Both surgical and transcatheter bioprosthetic valves have limited durability because of structural valve deterioration. The main objective of this summary of experts participating in a virtual workshop was to propose standardized definitions for nonstructural and structural BVD and BVF following aortic or mitral biological valve replacement with the goal of facilitating research reporting and implementation of these terms in clinical practice. Definitions of structural BVF, based on valve reintervention or death, underestimate the true incidence of BVF. However, definitions solely based on the presence of high transprosthetic gradient at a given echocardiogram during follow-up overestimate the incidence of structural BVD and BVF. Definitions of aortic or mitral structural BVD must therefore include the confirmation by imaging of permanent structural changes to the leaflets alongside evidence of deterioration in valve hemodynamic function at echocardiography follow-up

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

On the Performance of Decentralized Detection Under Transmission Constraints

We consider the problem of distributed detection in a wireless network consisting of a large number of sensors having either ideal or non-ideal communication links to their respective fusion or relay node. The detection performance is characterized under a Neyman-Pearson framework using a parallel configuration and a single-rooted tree with bounded height, where only the leaves are sensors. We show that with conditionally independent observations across sensors, the Type II error exponent for a single-rooted tree of uniform height two can be equivalent to that of a parallel configuration under certain conditions. These conditions include the ability to group sensors into sub-classes, where the observations within a class are conditionally independent and identically distributed, and with binary decision throughout. We then show that a single rooted tree can achieve improved detection performance versus the parallel configuration with the same number of nodes under multipath fading communication links and a constrained transmit power budget in the non-asymptotic regime

Uniformly Most Powerful Distributed Detection and its Application in Cooperative Spectrum Sensing

In this paper, a special class of distributed composite binary hypothesis testing problem with monotonic likelihood ratio is investigated. The sensor observations are assumed to be conditionally independent given a fixed but unknown parameter θ where θ ∈ Θ1 under the H1 hypothesis and θ = θ0 under the H0 hypothesis. The optimal form of sensor decision rule is established under both the Neyman-Pearson and Bayesian criteria. As an illustrative example, the design of an optimal cognitive radio rule for cooperative spectrum sensing is established