A performance comparision between a novel tapered piezoprobe and the piezocone in Boston blue clay

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 1998.Includes bibliographical references (v. 2, leaves 265-268).by Amy Jeanne Varney.Ph.D

Differences between murine arylamine N-acetyltransferase type 1 and human arylamine N-acetyltransferase type 2 defined by substrate specificity and inhibitor binding

Background: The mouse has three arylamine N-acetyltransferase genes, (MOUSE)Nat1, (MOUSE)Nat2 and (MOUSE)Nat3. These are believed to correspond to (HUMAN)NAT1, (HUMAN)NAT2 and NATP in humans. (MOUSE)Nat3 encodes an enzyme with poor activity and human NATP is a pseudogene. (MOUSE)Nat2 is orthologous to (HUMAN)NAT1 and their corresponding proteins are functionally similar, but the relationship between (MOUSE)Nat1 and (HUMAN)NAT2 is less clear-cut. Methods: To determine whether the (MOUSE)NAT1 and (HUMAN)NAT2 enzymes are functionally equivalent, we expressed and purified (MOUSE)NAT1*1 and analysed its substrate specificity using a panel of arylamines and hydrazines. To understand how specific residues contribute to substrate selectivity, three site-directed mutants of (MOUSE)NAT2*1 were prepared: these were (MOUSE)NAT2_F125S, (MOUSE)NAT2_R127G and (MOUSE)NAT2_R127L. All three exhibited diminished activity towards “(MOUSE)NAT2-specific” arylamines but were more active against hydrazines than (MOUSE)NAT1*1. The inhibitory and colorimetric properties of a selective naphthoquinone inhibitor of (HUMAN)NAT1 and (MOUSE)NAT2 were investigated. Results: Comparing (MOUSE)NAT1*1 with other mammalian NAT enzymes demonstrated that the substrate profiles of (MOUSE)NAT1 and (HUMAN)NAT2 are less similar than previously believed. Three key residues (F125, R127 and Y129) in (HUMAN)NAT1*4 and (MOUSE)NAT2*1 were required for enzyme inhibition and the associated colour change on naphthoquinone binding. In silico modelling of selective ligands into the appropriate NAT active sites further implicated these residues in substrate and inhibitor specificity in mouse and human NAT isoenzymes. Conclusions: Three non-catalytic residues within (HUMAN)NAT1*4 (F125, R127 and Y129) contribute both to substrate recognition and inhibitor binding by participating in distinctive intermolecular interactions and maintaining the steric conformation of the catalytic pocket. These active site residues contribute to the definition of substrate and inhibitor selectivity, an understanding of which is essential for facilitating the design of second generation (HUMAN)NAT1-selective inhibitors for diagnostic, prognostic and therapeutic purposes. In particular, since the expression of (HUMAN)NAT1 is related to the development and progression of oestrogen-receptor-positive breast cancer, these structure-based tools will facilitate the ongoing design of candidate compounds for use in (HUMAN)NAT1-positive breast tumours. </p

The Effect of Medicare Eligibility on Spousal Insurance Coverage

A majority of married couples in the United States take advantage of the fact that employers often provide health insurance coverage to spouses. When the older spouses become eligible for Medicare, however, many of them can no longer provide their younger spouses with coverage. In this paper, we study how spousal eligibility for Medicare affects the health insurance and health care access of the younger spouse. We find spousal eligibility for Medicare results in the younger spouse having worse insurance coverage and reduced access to health care services

The Lantern, 2018-2019

The Treasure Buried in Ponce de Leon\u27s Fountain of Youth Archaeological Park • High Cards on the Low River • Sestina of a Vagina left in the microwave too long • Keeps on Tripping • The Auction • Nuclear Meltdown on Seedship C5B.6 • Cock Fight • An Interview with God • Minimum Wage • Star-Crossed Lovers • Romeo Echo Alpha • PM Entertainment, or Action Beats • The Gospel of Aggregates • Hel Hath no Fury • Crossing the Line • Mango de la hora • Stress Judgment • Perception (Part 2) • Rain Falling Up • Church: the Italian Market • Landscape with the Fall of Hillary • Forced to Ponder • Morally Upright • Adulthood • Migration in Tandem • Hospital Bed • To Autumn (After Keats) • Selected Tweets • Hidden Moments • Mysteries are Wrong • Jukebox Memory • Flames • A Simple Moment • The Farmhouse • Lord, Let Me Catch a Fish • Sun-Kissed • Five • The Thing • The Moons of Mars • You are Weak • You Kept Me Quiet • Offer Her a Seat • Sacraments • Cigar • The Lake George Mafia • Houses • Spun Out • To Romanticize the Restless • 12/25/17 • skylight • lanternflies • Goo Girls • Toi Le • Lovers, Thinkers, Rebels • home in paradise • Irreverence • The Fisherman • St Mary Episcopal Cathedral, Edinburgh • Mirror 2https://digitalcommons.ursinus.edu/lantern/1187/thumbnail.jp

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Small molecule inhibitors and substrate analyses of protein arginine methyltransferases

Chapter 1 introduces the Protein Arginine Methyltransferases (PRMTs) as epigenetic regulators that decorate peptidic arginine with methyl groups. Evidence for PRMT involvement in cancer pathogenesis is reviewed and their plausibility as therapeutic targets is introduced. The methylation patterns conferred by the PRMTs is described, and the existence of novel patterns is considered. Techniques for assaying PRMT activity are compared and contrasted and a discussion of current PRMT inhibitors is presented. The chapter concludes by outlining the aims of the thesis. Chapter 2 describes synthesis towards novel methylated arginine molecules that are fully protected for inclusion in peptides via solid phase peptide synthesis. Chapter 3 outlines the total synthesis of protected δ-monomethylated arginine for peptide synthesis. This methylation pattern is known in yeast but has not yet been identified in humans. Chapter 4 details a new mass spectrometry-based assay that can be applied for inhibitor and substrate analyses. Synthesis of a novel histone peptide containing the δ-monomethylated arginine, produced in Chapter 3, is also described and this is tested for relevance as a human epigenetic marker. Novel polymethylation patterns are also explored in a total of five histone peptides. This chapter concludes with discussion of possible methylation pattern rearrangements. Chapter 5 describes the synthesis and testing of two series of putative PRMT inhibitors based on previously identified scaffolds within this research group. Data obtained from three different assays, including that outlined in Chapter 4, are analysed and suggestions as to the direction of PRMT assay design are offered. Chapter 6 provides the experimental data to support Chapters 2-5, including all organic synthesis procedures, protein &amp; peptide syntheses and assay methodology.</p

Clinic Design, Key Practice Metrics, and Resident Satisfaction in Internal Medicine Continuity Clinics: Findings of the Educational Innovations Project Ambulatory Collaborative

BackgroundInternal medicine programs are redesigning ambulatory training to improve the resident experience and answer the challenges of conflicting clinical responsibilities. However, little is known about the effect of clinic redesign on residents' satisfaction.ObjectiveWe assessed residents' satisfaction with different resident continuity clinic models in programs participating in the Educational Innovations Project Ambulatory Collaborative (EPAC).MethodsA total of 713 internal medicine residents from 12 institutions in the EPAC participated in this cross-sectional study. Each program completed a detailed curriculum questionnaire and tracked practice metrics for participating residents. Residents completed a 3-part satisfaction survey based on the Veterans Affairs Learners' Perception Survey, with additional questions addressing residents' perceptions of the continuous healing relationship and conflicting duties across care settings.ResultsTHREE CLINIC MODELS WERE IDENTIFIED: traditional weekly experience, combination model with weekly experience plus concentrated ambulatory rotations, and a block model with distinct inpatient and ambulatory blocks. The satisfaction survey showed block models had less conflict between inpatient and outpatient duties than traditional and combination models. Residents' perceptions of the continuous healing relationship was higher in combination models. In secondary analyses, the continuity for physician measure was correlated with residents' perceptions of the continuous healing relationship. Panel size and workload did not have an effect on residents' overall personal experience.ConclusionsBlock models successfully minimize conflict across care settings without sacrificing overall resident satisfaction or resident perception of the continuous healing relationship. However, resident perception of the continuous healing relationship was higher in combination models

Determinants of Patient Satisfaction in Internal Medicine Resident Continuity Clinics: Findings of the Educational Innovations Project Ambulatory Collaborative

BackgroundMany internal medicine programs have reorganized their resident continuity clinics to improve the ambulatory care experience for residents. The effect of this redesign on patient satisfaction is largely unknown.MethodsOur multi-institutional, cross-sectional study included 569 internal medicine residents from 11 programs participating in the Educational Innovations Project Ambulatory Collaborative. An 11-item patient satisfaction survey from the Consumer Assessment of Healthcare Providers and Systems was used to assess patient satisfaction, comparing patient satisfaction in traditional models of weekly continuity clinic with 2 new clinic models. We then examined the relationship between patient satisfaction and other practice variables.ResultsPatient satisfaction responses related to resident listening and communication skills, knowledge of medical history, perception of adequate visit time, overall rating, and willingness to refer to family and friends were significantly better in the traditional and block continuity models than the combination model. Higher ambulatory workload was associated with reduced patient perception of respect shown by the physician. The percentage of diabetic patients with glycated hemoglobin &lt; 8% was positively correlated with number of visits, knowledge of medical history, perception of respect, and higher scores for recommending the physician to others. The percentage of diabetic patients with low density lipoprotein &lt; 100&nbsp;mg/dL was positively correlated with the physician showing respect.ConclusionsPatient satisfaction was similar in programs using block design and traditional models for continuity clinic, and both outperformed the combination model programs. There was a delicate balance between workload and patient perception of the physician showing respect. Care outcome measures for diabetic patients were associated with aspects of patient satisfaction