1,637 research outputs found

    That\u27s Why You Came Back To Me

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    https://digitalcommons.library.umaine.edu/mmb-vp/6505/thumbnail.jp

    A gendered analysis of the role of authority in argumentation

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    The first part of this paper will look at how essential features of power and authority affect the credibility of arguments. Empirical evidence from communication studies and feminist writings, such Sue Campbell, and Robin Lakoff, shows that there is inherent disparity in the reception of arguments when presented by men and women. The second part will aim to elucidate how this problem of lack of authority is not addressed by the ad verecundiam fallacy

    Then You\u27ll Come Back To Me

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    https://digitalcommons.library.umaine.edu/mmb-vp/6253/thumbnail.jp

    A multicenter retrospective study of patients treated in the thalamus with responsive neurostimulation

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    INTRODUCTION: For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy. METHODS: This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and \u3e 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed. RESULTS: Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at \u3e2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale. DISCUSSION: Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores

    Comparison of surface chlorophyll, primary production, and satellite imagery in hydrographically different sounds off southern New England

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    Block Island Sound (BIS) and Rhode Island Sound (RIS) are adjacent inner continental shelf ecosystems with contrasting hydrographic regimes. BIS exhibits more energetic tidal mixing, and water column stratification remains weak but persists year-round due to nearby estuarine exchange flow; RIS is less influenced by estuaries, and more seasonal with strong stratification in summer. We compared annual cycles of phytoplankton biomass and primary production in BIS and RIS using measurements (surface chlorophyll, 14C primary production), primary production models (Webb/Platt and BZE models), and satellite ocean color products. During 22 mo of sampling, measured surface chlorophyll was not significantly different between BIS (mean = 1.86 mg m-3) and RIS (1.69 mg m-3), and bimodal peaks of phytoplankton biomass and production occurred concurrently in both Sounds. In contrast, a 12 yr ocean-color based chlorophyll time series indicated higher long-term average surface chlorophyll in the more well-mixed system (BIS, mean = 1.50 mg m-3; RIS, mean = 0.86 mg m-3). BIS annual primary production (318 to 329 g C m-2 yr-1) was higher than RIS (239 to 256 g C m-2 yr-1; p \u3c 0.001). These differences were most apparent during the summer, concurrent with the largest differences in water column stratification. Phytoplankton bloom phenology was driven by physical processes, with chlorophyll significantly related to water column stratification (r = -0.51, p = 0.01), depth of the euphotic zone (r = -0.54, p = 0.05), and surface water salinity (r = 0.54, p = 0.04). Primary production was correlated with surface water temperature (r = 0.57, p = 0.03) but the mechanisms underlying production differences between the Sounds remain unresolved. We hypothesize that different hydrographies give rise to different productivity between the Sounds

    Responsive neurostimulation for people with drug-resistant epilepsy and autism spectrum disorder

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    PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System. METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis. RESULTS: Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a \u3e50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction \u3e90%). For the super responders, two of the four patients had the device implanted for \u3e2 years. The response rate was 70% for those in whom the device was implanted for \u3e2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported. CONCLUSIONS: Based on the authors\u27 experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD-DRE

    Priorities to promote participant engagement in the Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network

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    BACKGROUND: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network\u27s research. METHODS: PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network\u27s research priorities in participant engagement: (i) a brainstorming exercise to elicit potential priorities; (ii) a 2-day virtual meeting to discuss priorities; (iii) recommendations from the PE-CGS External Advisory Panel to refine priorities; and (iv) a virtual meeting to set priorities. RESULTS: Nearly 150 PE-CGS stakeholders engaged in the process. Five priorities were set: (i) tailor education and communication materials for participants throughout the research process; (ii) identify measures of participant engagement; (iii) identify optimal participant engagement strategies; (iv) understand cancer disparities in the context of cancer genomics research; and (v) personalize the return of genomics findings to participants. CONCLUSIONS: PE-CGS is pursuing these priorities to meaningfully engage diverse and underrepresented patients with cancer and posttreatment cancer survivors as participants in cancer genomics research and, subsequently, generate new discoveries. IMPACT: Data from PE-CGS will be shared with the broader scientific community in a manner consistent with participant informed consent and community agreement

    Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment

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    BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors. METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient\u27s hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual\u27s TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor. RESULTS: Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth. CONCLUSIONS: Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing

    Regeneration of Aged DMF for Use in Solid-Phase Peptide Synthesis

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    DMF, which is still the most commonly used solvent for Fmoc-SPPS, has the potential for degradation over time on exposure to air (and water vapour) and storage, to give dimethylamine and formic acid impurities. In particular, dimethylamine can lead to unwanted deprotection of the Fmoc group during for example the initial loading of Fmoc amino acids in SPPS, which leads reduced calculated loading values. We have found that treatment of such aged DMF by simple sparging with an inert gas (N2), or vacuum sonication, can regenerate the DMF in order to restore loading levels back to those found for newer, fresh, DMF samples
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