Krylov-Bellman boosting: Super-linear policy evaluation in general state spaces

We present and analyze the Krylov-Bellman Boosting (KBB) algorithm for policy evaluation in general state spaces. It alternates between fitting the Bellman residual using non-parametric regression (as in boosting), and estimating the value function via the least-squares temporal difference (LSTD) procedure applied with a feature set that grows adaptively over time. By exploiting the connection to Krylov methods, we equip this method with two attractive guarantees. First, we provide a general convergence bound that allows for separate estimation errors in residual fitting and LSTD computation. Consistent with our numerical experiments, this bound shows that convergence rates depend on the restricted spectral structure, and are typically super-linear. Second, by combining this meta-result with sample-size dependent guarantees for residual fitting and LSTD computation, we obtain concrete statistical guarantees that depend on the sample size along with the complexity of the function class used to fit the residuals. We illustrate the behavior of the KBB algorithm for various types of policy evaluation problems, and typically find large reductions in sample complexity relative to the standard approach of fitted value iterationn.Comment: 40 pages, 7 figure

Spinal Cord Compression Secondary to Metastatic Sinonasal Undifferentiated Carcinoma

Sinonasal undifferentiated carcinoma (SNUC) is a rare malignancy of the upper airways and anterior skull base that carries a poor prognosis. The tumor is known to be invasive into the surrounding structures of the skull base and brain. To date, there is only one existing case report documenting drop metastasis to the intradural extramedullary spinal cord. To the best of our knowledge, we present the second case of metastatic SNUC to the spine. This report describes a 59-year-old male with a history of head and neck SNUC who presented with thoracic back pain and bilateral lower extremity paresis. Neuroimaging demonstrated an extradural thoracic mass with severe spinal cord compression. The patient underwent thoracic laminectomy and fusion for decompression of the spinal cord and internal stabilization. The pathology returned as SNUC. The patient was subsequently lost to follow-up from our institution. Metastatic SNUC is rare. We discuss the relevant clinical imaging and review the literature. Such a malignancy portends a very poor prognosis

Correlación entre rasgos de personalidad y mediciones acústicas en el habla de individuos hispanoparlantes del río de la plata

The background of this study is presented in three sections: a) Motivation Theories and their relationship with brain structures, b) Psychometric studies of Primary Personality Factors (PPF) and c) The role of brain structures in the production of prosodic aspects of language. Its objective is to evaluate the combination of parameters and acoustic characteristics found in the speech of normal individuals (n = 23), previously grouped according to a psychometric study of their personality in order to sort out Primary Personality Factors (PPF) and improve our knowledge on Human Temperaments. Acoustic parameters under study were: fundamental frequency (F0), total maximum energy and total duration, normal constituents of prosodic information. A three-syllable same phrase was analyzed in all the cases. The subject´s emissions were registered on a Sony (WM – 6 × 320) recorder and the phrase studied for each individual (N = 22) was processed with the Anagraf speech acoustic analysis program. The acoustic characteristics more useful to discriminate between PPF groups are: a) F0 rank and b) energy differences between stressed syllables and those not stressed. Acoustic studies can complement psychometric ones in order to differentiate each PPF group.El fundamento de este estudio se presenta en 3 secciones: a) Teorías de la Motivación y su relación con estructuras cerebrales, b) estudios psicométricos para determinar Factores Primarios de la Personalidad (FPP) y c) el rol de las estructuras cerebrales en la producción de los aspectos prosódicos del lenguaje. Su objetivo es evaluar la combinación de parámetros y características acústicas encontradas en el habla de individuos normales (n = 23), previamente agrupados en base a estudios psicométricos de la personalidad y aumentar el conocimiento acerca de los temperamentos humanos. Los parámetros acústicos estudiados incluyeron: frecuencia fundamental, energía total y duración, constituyentes normales de la información prosódica. Una misma frase de tres sílabas fue analizada en todos los casos. Las emisiones vocales se registraron en un grabador Sony (WM – 6 × 320) y la frase estudiada en cada individuo (N = 22) fue procesada con Anagraf, programa de análisis acústico del habla. El análisis de las varianzas en los resultados obtenidos mostró que las características acústicas que más probablemente pueden discriminar cada uno de los grupos de FPP son dos: a) el rango de la frecuencia fundamental, y b) la energía individual usada en las sílabas acentuadas respecto de aquellas que no lo son. Los estudios acústicos pueden complementar a los psicométricos para diferenciar los individuos que corresponden a cada grupo según los FPP

Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>Traumatic brain injury (TBI) with its associated morbidity is a major area of unmet medical need that lacks effective therapies. TBI initiates a neuroinflammatory cascade characterized by activation of astrocytes and microglia, and increased production of immune mediators including proinflammatory cytokines and chemokines. This inflammatory response contributes both to the acute pathologic processes following TBI including cerebral edema, in addition to longer-term neuronal damage and cognitive impairment. However, activated glia also play a neuroprotective and reparative role in recovery from injury. Thus, potential therapeutic strategies targeting the neuroinflammatory cascade must use careful dosing considerations, such as amount of drug and timing of administration post injury, in order not to interfere with the reparative contribution of activated glia.</p> <p>Methods</p> <p>We tested the hypothesis that attenuation of the acute increase in proinflammatory cytokines and chemokines following TBI would decrease neurologic injury and improve functional neurologic outcome. We used the small molecule experimental therapeutic, Minozac (Mzc), to suppress TBI-induced up-regulation of glial activation and proinflammatory cytokines back towards basal levels. Mzc was administered in a clinically relevant time window post-injury in a murine closed-skull, cortical impact model of TBI. Mzc effects on the acute increase in brain cytokine and chemokine levels were measured as well as the effect on neuronal injury and neurobehavioral function.</p> <p>Results</p> <p>Administration of Mzc (5 mg/kg) at 3 h and 9 h post-TBI attenuates the acute increase in proinflammatory cytokine and chemokine levels, reduces astrocyte activation, and the longer term neurologic injury, and neurobehavioral deficits measured by Y maze performance over a 28-day recovery period. Mzc-treated animals also have no significant increase in brain water content (edema), a major cause of the neurologic morbidity associated with TBI.</p> <p>Conclusion</p> <p>These results support the hypothesis that proinflammatory cytokines contribute to a glial activation cycle that produces neuronal dysfunction or injury following TBI. The improvement in long-term functional neurologic outcome following suppression of cytokine upregulation in a clinically relevant therapeutic window indicates that selective targeting of neuroinflammation may lead to novel therapies for the major neurologic morbidities resulting from head injury, and indicates the potential of Mzc as a future therapeutic for TBI.</p

Resilient remediation:Addressing extreme weather and climate change, creating community value

Recent devastating hurricanes demonstrated that extreme weather and climate change can jeopardize contaminated land remediation and harm public health and the environment. Since early 2016, the Sustainable Remediation Forum (SURF) has led research and organized knowledge exchanges to examine (1) the impacts of climate change and extreme weather events on hazardous waste sites, and (2) how we can mitigate these impacts and create value for communities. The SURF team found that climate change and extreme weather events can undermine the effectiveness of the approved site remediation, and can also affect contaminant toxicity, exposure, organism sensitivity, fate and transport, long-term operations, management, and stewardship of remediation sites. Further, failure to consider social vulnerability to climate change could compromise remediation and adaptation strategies. SURF's recommendations for resilient remediation build on resources and drivers from state, national, and international sources, and marry the practices of sustainable remediation and climate change adaptation. They outline both general principles and site-specific protocols and provide global examples of mitigation and adaptation strategies. Opportunities for synergy include vulnerability assessments that benefit and build on established hazardous waste management law, policy, and practices. SURF's recommendations can guide owners and project managers in developing a site resiliency strategy. Resilient remediation can help expedite cleanup and redevelopment, decrease public health risks, and create jobs, parks, wetlands, and resilient energy sources. Resilient remediation and redevelopment can also positively contribute to achieving international goals for sustainable land management, climate action, clean energy, and sustainable cities

Evaluation of General Large Language Models in Contextually Assessing Semantic Concepts Extracted from Adult Critical Care Electronic Health Record Notes

The field of healthcare has increasingly turned its focus towards Large Language Models (LLMs) due to their remarkable performance. However, their performance in actual clinical applications has been underexplored. Traditional evaluations based on question-answering tasks don't fully capture the nuanced contexts. This gap highlights the need for more in-depth and practical assessments of LLMs in real-world healthcare settings. Objective: We sought to evaluate the performance of LLMs in the complex clinical context of adult critical care medicine using systematic and comprehensible analytic methods, including clinician annotation and adjudication. Methods: We investigated the performance of three general LLMs in understanding and processing real-world clinical notes. Concepts from 150 clinical notes were identified by MetaMap and then labeled by 9 clinicians. Each LLM's proficiency was evaluated by identifying the temporality and negation of these concepts using different prompts for an in-depth analysis. Results: GPT-4 showed overall superior performance compared to other LLMs. In contrast, both GPT-3.5 and text-davinci-003 exhibit enhanced performance when the appropriate prompting strategies are employed. The GPT family models have demonstrated considerable efficiency, evidenced by their cost-effectiveness and time-saving capabilities. Conclusion: A comprehensive qualitative performance evaluation framework for LLMs is developed and operationalized. This framework goes beyond singular performance aspects. With expert annotations, this methodology not only validates LLMs' capabilities in processing complex medical data but also establishes a benchmark for future LLM evaluations across specialized domains

A distributed national stored collection: Testing the possibilities

This paper reports on a study of the holdings of a single discipline (Design) by a single institution (RMIT University Library) in order to test for the possibility of a form of distributed national storage in Australia. The study was undertaken using OCLC Collection Analysis software and the WorldCat database. The collection of RMIT University Library is compared with two ‘groups’ of libraries, the first consisting of seven Victorian academic library collections, and the second of three Melbourne-based non-academic libraries considered to have strong Design collections. Conclusions indicate that for this discipline a form of distributed storage is already in place, with the RMIT University Library collection making a considerable and complementary contribution to the state wide holdings

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research, and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 datasets containing 38 802 European-ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analyzed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis1) with qualifying unpublished data were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction, and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalizable, but must be of modest effect size and only observable in limited situations

Genome-wide ultraconserved elements exhibit higher phylogenetic informativeness than traditional gene markers in percomorph fishes

Ultraconserved elements (UCEs) have become popular markers in phylogenetic studies because of their cost effectiveness in phylogenomic analyses and because of their potential to resolve problematic phylogenetic questions such as interspecific relationships within the rayfinned fishes. Although UCE datasets typically contain a much larger number of loci and sites than more traditional datasets of PCR-amplified, single-copy, protein coding genes, a fraction of UCE sites are expected to be part of a nearly invariant core, and the relative performance of UCE datasets versus protein coding gene datasets is poorly understood. Here we use phylogenetic informativeness (PI) to compare the resolving power of multi-locus and UCE datasets in a sample of percomorph fishes with sequenced genomes (genome-enabled). We compare three data sets: UCE core regions, flanking sequence adjacent to the UCE core and a set of ten protein coding genes commonly used in fish systematics. We found the net informativeness of UCE core and flank regions to be roughly ten-fold and 100-fold more informative than that of the protein coding genes. On a per locus basis UCEs and protein coding genes exhibited similar levels of phylogenetic informativeness. Our results suggest that UCEs offer enormous potential for resolving relationships across the percomorph tree of life

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms