Extensive biological and clinical evidence supports the notion many CRC tumors are addicted to EGFR/KRAS/MAPK signaling. For example, mutations in KRAS, BRAF and other MAPK pathway components confer intrinsic or acquired resistance to... more
Extensive biological and clinical evidence supports the notion many CRC tumors are addicted to EGFR/KRAS/MAPK signaling. For example, mutations in KRAS, BRAF and other MAPK pathway components confer intrinsic or acquired resistance to anti-EGFR therapy. However, a significant proportion of acquired resistance cases have remained unexplained. ARID1A mutations are found in approximately 11% of CRC tumors, but a connection between ARID1A mutations and EGFR/MAPK signaling activation in CRC has not been previously suspected. By leveraging the genomic biomarker data collected from 333 patients at baseline and at progression who participated in the CALGB/SWOG 80405 trial, we found that mutations in ARID1A, a key component of SWI/SNF complex, were enriched in the cell free DNA of 6/16 of the patients whose tumors had become resistant to anti-EGFR therapy with ARID1A mutations detected at either timepoint (adj. p = 0.03, OR = 0.09, two-tailed fisher's exact test). In contrast, there was ...
Research Interests:
Research Interests:
BackgroundSTING pathway agonism has emerged as a potential therapeutic mechanism to stimulate an innate anti-tumor immune response. While in principle systemic administration of a STING agonist would have many therapeutic benefits,... more
BackgroundSTING pathway agonism has emerged as a potential therapeutic mechanism to stimulate an innate anti-tumor immune response. While in principle systemic administration of a STING agonist would have many therapeutic benefits, including the delivery of STING to all tumor lesions, such an approach may be limited by toxicity. Antibody-drug conjugates (ADCs) constitute a proven therapeutic modality that is ideally suited to allow systemic administration while stimulating the innate immunity in a targeted manner. We have previously demonstrated that targeted delivery of a STING agonist with an ADC induces robust anti-tumor immune responses.MethodsHerein we investigated the mechanism of action of tumor cell-targeted STING agonist ADCs. We evaluated STING pathway activation and anti-tumor activity elicited by ADCs harboring either wild type (wt) or mutant Fc deficient in Fcγ receptor (FcγR) binding in wt or STING knockout (ko) cancer cell mono-cultures, immune cell co-cultures, and i...
Research Interests:
Research Interests:
Objective To assess the ability of 2nd-year students to identify normal and abnormal findings during cardiac and lung auscultation using high-fidelity manikin simulators and standardized patients. A secondary objective was to assess... more
Objective To assess the ability of 2nd-year students to identify normal and abnormal findings during cardiac and lung auscultation using high-fidelity manikin simulators and standardized patients. A secondary objective was to assess students' perceived competence and confidence in their abilities. Methods This was a descriptive pilot study of randomly selected 2nd-year students at 1 chiropractic training program. Participants were asked to perform cardiac and lung auscultation on high-fidelity manikins (2 stations) and standardized human patients (2 stations) with normal and abnormal auscultation sounds. Participants described the auscultated sound as “abnormal” or “normal” and were also asked to score their confidence in describing the sound and competence in performing auscultation on a 100-mm visual analog scale. Descriptive statistics were calculated for all study variables. Results Thirty-two students (23 women and 9 men) were included. For lung auscultation, 15.6% were inc...
Background The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein... more
Background The Coronavirus disease-2019 (COVID-19) is a global pandemic. Acute respiratory compromise and systemic coagulopathy cause significant morbidity and mortality. Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as arterial thromboembolism (ATE), which includes stroke, are common sequelae described in this patient population. COVID-19 coagulopathy is attributed to severe inflammation and endothelial dysfunction resulting in a prothrombotic state. COVID-19 related treatment has focused on targeting the unregulated inflammatory state in an attempt to decrease incidence of COVID-19 related complications, such as thrombosis. Prophylactic anticoagulation is recommended, and many suggest intermediate to therapeutic anticoagulation in severe COVID-19. However, there is no clear data showing impact of anticoagulation on morbidity and mortality in patients with COVID-19. Methods A retrospective analysis was performed...
Research Interests:
In recent years, more and more countries have paid close attention to energy and environmental issues [...]
Research Interests:
Two texts inscribed on a large statue base shaft from Aphrodisias in Caria record repairs made to »the statues of the Cyclops« that originally stood on top of the base. While the inscriptions themselves have been well studied, the missing... more
Two texts inscribed on a large statue base shaft from Aphrodisias in Caria record repairs made to »the statues of the Cyclops« that originally stood on top of the base. While the inscriptions themselves have been well studied, the missing Cyclops statue group has received rather less attention. In this article, the iconography and original display context of this group are investigated for the first time. A series of statue and statuette fragments from Aphrodisias are presented to support the hypothesis that the base once supported an arresting Hellenistic-style statue group depicting Polyphemos eviscerating a companion of Odysseus. It is argued that this statue group was originally set up in a public space in Aphrodisias, plausibly the large urban park known today as the South Agora. This contextualisation permits a consideration of the factors that led to Cyclops statue groups being erected as public monuments in the cities of Greece and Asia Minor during the 1st and 2nd centuries...
Research Interests:
Research Interests:
Research Interests:
Investigating all forces exerted on the patient’s body during high-velocity, low-amplitude spinal manipulative therapy (SMT) remains fundamental to elucidate how these may contribute to SMT’s effects. Previous conflicting findings... more
Investigating all forces exerted on the patient’s body during high-velocity, low-amplitude spinal manipulative therapy (SMT) remains fundamental to elucidate how these may contribute to SMT’s effects. Previous conflicting findings preclude our understanding of the relationship between SMT forces acting at the clinician–patient and patient–table interfaces. This study aimed to quantify forces at the clinician–participant and participant–table interfaces during thoracic SMT in asymptnomatic adults. An experienced clinician provided a posterior to anterior SMT centered to T7 transverse processes using predetermined force–time characteristics to 40 asymptomatic volunteers (20 females; average age = 27.2 [4.9] y). Forces at the clinician–participant interface were recorded by triaxial load cells; whereas, forces at the participant–table interface were recorded by the force-sensing table technology. Preload force, total peak force, time to peak, and loading rate at each interface were ana...
Research Interests:
Research Interests:
e12518Background: Oncotype dx is a 21 gene breast cancer assay that helps predict benefit of chemotherapy in early-stage hormone receptor positive (HR+), HER2 negative, 0 to 3 node positive breast ...
Research Interests:
Finding facial component in face images is a significant arrangement for various facial image-understanding applications. The face detection is a process of detecting a region of the face from a picture, or image of one or multiple... more
Finding facial component in face images is a significant arrangement for various facial image-understanding applications. The face detection is a process of detecting a region of the face from a picture, or image of one or multiple objects together. In this paper, we introduce Adaboost, viola-Jones, and Haar algorithms to detect faces either through mobile phone interface or from desktop computer UI. The application of the work has extended into an automated classroom attendance system using a handheld device. The results have shown the effectiveness of the proposed model.
Research Interests:
Some have claimed that human life is inevitably meaningless because we are mortal. Others have claimed the opposite: that life would be meaningless if we never died, and our being mortal is actually an essential condition for our lives to... more
Some have claimed that human life is inevitably meaningless because we are mortal. Others have claimed the opposite: that life would be meaningless if we never died, and our being mortal is actually an essential condition for our lives to have any meaning at all. The aim of this thesis is to evaluate the arguments that have or could be used to support these claims, and come to a conclusion about which position, if either, is correct. Part One provides an introduction to the problem and an overview of various accounts of meaningfulness which can be found in the literature before outlining a broader and more defensible amalgam theory of meaningfulness. According to this theory, a life is ideally meaningful if and only if, and to the extent that, it contains sufficient degrees of purposefulness, significance, and coherence. In Part Two, the thesis moves on to systematically consider arguments that immortal life would be meaningless because it would lack each of these three essential in...
Research Interests:
N.K.Y., P.C., & P.R.Y. contributed equally to this study Introduction: Many studies have concluded that active cancer patients infected with SARS-CoV-2 have a more complicated infection course and worse outcomes compared to the general... more
N.K.Y., P.C., & P.R.Y. contributed equally to this study Introduction: Many studies have concluded that active cancer patients infected with SARS-CoV-2 have a more complicated infection course and worse outcomes compared to the general patient population hospitalized with COVID-19. However, little evidence exists whether having a history of cancer plays a significant role in these observations. Patients with hematologic malignancy (HM) might have worse prognosis among all cancer patients but the reason remains unclear. Our objective is to evaluate outcomes and severity of COVID-19 in patients with Hematological Malignancy (HM) versus Solid-tumors (ST) in different clinical settings and also compare these outcomes within the group of patients with hematological malignancies. Methods: This retrospective study examines risk factors and outcomes of COVID-19 in patients with a history of cancer and laboratory-confirmed COVID-19 diagnosis between March 1 st, 2020, and December 31 st, 2020...
Research Interests:
Research Interests:
Research Interests:
Background COVID-19 has disrupted medical education in the United Kingdom (UK). The pandemic may result in a long-term disproportionate negative impact to students applying to Medical School from a low-socioeconomic background. In... more
Background COVID-19 has disrupted medical education in the United Kingdom (UK). The pandemic may result in a long-term disproportionate negative impact to students applying to Medical School from a low-socioeconomic background. In addition, the upsurge in Medical School applications increases the likelihood of stricter University entry criteria over the coming years. There is no current research to determine how widening participation of Medicine to students from low-socioeconomic backgrounds can be improved virtually. The aim of this study is to establish the impact of COVID-19 on students enrolled in UK widening access schemes and the role of virtual student led initiatives in widening participation. Methods A voluntary online survey was distributed to UK Sixth Form students (N = 31) enrolled in a widening access scheme who attended Sheffield Neuroscience Society International Virtual Conference in February 2021. The event was free to attend. The five-domain survey consisted of qu...
Research Interests:
Rural, economically disadvantaged communities face a bigger challenge than urban communities in recruiting and retaining high school (HS) students in science, technology, engineering, and mathematics (STEM) because many of these students... more
Rural, economically disadvantaged communities face a bigger challenge than urban communities in recruiting and retaining high school (HS) students in science, technology, engineering, and mathematics (STEM) because many of these students do not have access to high-quality STEM opportunities. In this article, we describe a mentoring program we developed as part of a larger New York State education grant. This program was implemented in a rural community to connect undergraduate STEM students with HS students to increase HS students’ interest in these fields. In this program, HS students visited colleges, explored their interests in STEM, and learned about opportunities available to them in college and beyond. Here, we share the challenges and the successful strategies in implementing a mentoring program in a rural, economically disadvantaged region. The ideas described in the article were designed so other educators can gain insight on how to set up successful mentoring programs to a...
Research Interests:
Antibody-drug conjugates (ADCs) represent a promising drug class that relies on monoclonal antibody recognition of specific cancer-associated antigens for targeted delivery of chemotherapeutic agents. Fleximer® ADCs utilize a... more
Antibody-drug conjugates (ADCs) represent a promising drug class that relies on monoclonal antibody recognition of specific cancer-associated antigens for targeted delivery of chemotherapeutic agents. Fleximer® ADCs utilize a polymer-based conjugation platform to enable high drug-antibody ratios (DAR) and significantly greater anti-tumor potency compared to ADCs with DAR 3-4. We previously showed that trastuzumab-dolaflexin (T-dolaflexin), a HER2-targeted ADC comprised of the antibody trastuzumab conjugated to ∼15 proprietary auristatin molecules via Fleximer, has excellent pharmacokinetics and efficacy in mouse models (AACR 2014 Abstract #2645). T-dolaflexin is efficacious at a single dose of 0.67 mg/kg in mouse xenograft models, and achieves prolonged tumor-free survival after a single 2 mg/kg dose in a low HER2-expressing model that is insensitive to ado-trastuzumab emtansine (T-DM1). We sought to test the tolerability of T-dolaflexin in exploratory mouse, rat and non-human prima...
Research Interests:
Introduction: Application of research methods to medical research is a key skill that students should acquire during medical school. The value of a mandatory research module for students in terms of their understanding of medical research... more
Introduction: Application of research methods to medical research is a key skill that students should acquire during medical school. The value of a mandatory research module for students in terms of their understanding of medical research and the academic outputs that arise from the module are yet to be evaluated, especially compared to research undertaken through different avenues. Method: Sheffield Medical Students were invited to complete a questionnaire on their thoughts of the research module, any academic outputs that arose from the module and any further research that they had undertaken outside the module. Ordinal regression analysis was used to assess for differences between groups’ answers to the Likert scales. Results: 101 students answered the questionnaire. 72.3% of students agreed that the module increased their knowledge of medical research, while fewer students agreed that it increased their interest in research and desire to undertake further research. Undergraduate...
Research Interests:
Abstract:Our understanding of the importance for, and the influence on the American philosophical tradition of Native American thought has been usefully extended in a number of ways in recent decades. With a few notable exceptions,... more
Abstract:Our understanding of the importance for, and the influence on the American philosophical tradition of Native American thought has been usefully extended in a number of ways in recent decades. With a few notable exceptions, however, scant attention has been paid to the unique contribution to the history of American thought made by Black Elk, the preeminent wicasa wakan, or holy man, of the first reservation generation of the Oglala Lakota. Scholarship on Black Elk's religious life has struggled between two interpretive possibilities. Traditionalists are concerned to preserve the image of Black Elk as fully native and traditional, a member of the resistance, if not exactly an open insurrectionist. By contrast, the Catholic camp is concerned to claim Black Elk for the Church, championing him as a great conversion success story. Holler has pointed out that both camps fail to overcome their respective burdens of proof with regard to claims of exclusive observance, however. Thus, he hypothesizes that Black Elk comfortably practiced "dual participation," contending that the fundamental, relevant religious category for the Lakota was sacred power, not propositional truth. An orientation toward sacred power alone is inadequate to account for Black Elk's dual participation, however; it may illuminate a necessary condition for Black Elk's dual participation, but it does little to explain the particular form his dual participation took. To that end, this essay argues there are at least two specific, novel and creative hermeneutic strategies—reverse typology and remythologization—developed and deployed by Black Elk as partial means of harmonizing traditional Lakota religion and Catholicism. Taken together with the basic orientation toward power rather than truth, these strategies not only provide us with a fuller understanding of the theological basis of Black Elk's particular form of dual participation, but also recommend Black Elk as a far more sophisticated and significant intellectual figure than he generally receives credit for being.
Research Interests:
A parchment codex of the early sixth century a.d., now in Vienna, contains a remarkable series of nearly 400 full-page illustrations of individual botanical species. These illustrations accompany an alphabetical recension of a... more
A parchment codex of the early sixth century a.d., now in Vienna, contains a remarkable series of nearly 400 full-page illustrations of individual botanical species. These illustrations accompany an alphabetical recension of a pharmacological treatise on the medicinal properties of plants written by Dioskourides of Anazarbos, a Greek author of the first century a.d. Both the date of the codex and the style of its botanical illustrations have encouraged suggestions that the latter were modelled somehow on classical archetypes. This article presents new observations in support of the classical archetypes theory, but questions the traditional view that these archetypes were transmitted by ‘illustrated texts’ or ‘pattern books’ executed in papyrus or parchment. What follows is a new hypothesis concerning the nature of the artistic intermediaries used by painters, mosaicists and sculptors during antiquity.
Research Interests:
Research Interests:
Research Interests: Medicine and Circulation
To design feedback control systems for vibration suppression and high precision pointing, an accurate model is imperative, especially if using modern analytical design approaches, e.g., pole placement/observer designs or Linear Quadratic... more
To design feedback control systems for vibration suppression and high precision pointing, an accurate model is imperative, especially if using modern analytical design approaches, e.g., pole placement/observer designs or Linear Quadratic Gaussian (LQG). For complex systems, such as flexible space structures, models developed using dynamics and kinematics approaches or finite element techniques often do not have the fidelity to design control systems for achieving performance goals. An alternate approach to model development is system identification (ID), which is the process of collecting experimental input and output data and numerically computing the parameters of a model. A problem encountered in system ID is that experimentally measured data will be corrupted with noise that can be from disturbance signals or errors in measurements. The main thrust of this paper is two-fold: (1) to present a frequency domain least squares system identification technique to produce linear, time-invariant (LTI), discrete transfer function models that can be used to design digital controllers;
Research Interests:
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The application of biodegradable polymers to antibody-drug conjugate (ADC) design can provide numerous advantages, including significantly higher drug-antibody ratios,... more
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The application of biodegradable polymers to antibody-drug conjugate (ADC) design can provide numerous advantages, including significantly higher drug-antibody ratios, the use of alternative payloads with potencies considered insufficient for direct conjugation, the improvement of ADC physico-chemical properties, especially for highly hydrophobic payloads, and the potential expansion of protein recognition scaffolds beyond the commonly used IgGs. The basis of the novel polymer-based conjugation system described herein is a hydrophilic, fully biodegradable polyacetal carrier, (poly(1-hydroxymethylethylene hydroxymethylformal) or PHF) modified with chemically orthogonal linkers. A bioconjugation linker is used for efficient covalent attachment of a targeting moiety to the PHF scaffold, while a second, chemically distinct linker is used to attach multiple copies of a drug payload to the polymer to control the mechanism and rate of drug release. Utilizing multiple copies of a proprietary dolastatin derivative chemically conjugated to PHF, we have developed a potent and effective drug conjugation platform for ADC application, which has been named Dolaflexin™. Here, we report the preparation and characterization of a novel trastuzumab DolaflexinTM ADC, employing a maleimide-based bioconjugation approach. The resulting ADC, with a drug-antibody ratio of 20, exhibits enhanced stability and improved pharmacokinetics, with a prolonged plasma half-life and tumor-specific accumulation. Active drug release and accumulation in tumor tissue was also confirmed by LC/MS/MS methods. The activity of this novel trastuzumab-dolaflexin ADC was evaluated in multiple tumor xenograft models with significant variations in target antigen expression levels. Models including BT474 breast cancer, NCI-N87 gastric cancer, and JIMT1 breast cancer models were utilized, and comparisons to a variety of controls and ADC reference standards were made. Significant advantages of the polyacetal polymer-based ADCs in comparison to conventional ADCs, particularly in models with low target antigen expression, were observed. Details of these studies and potential applications for the development of new ADC therapeutics based on this approach will be presented. Citation Format: Alex Yurkovetskiy, Natalya Bodyak, Mao Yin, Joshua D. Thomas, Patrick Conlon, Cheri A. Stevenson, Alex Uttard, LiuLiang Qin, Dmitry R. Gumerov, Elena Ter-Ovaneysan, Venu R. Gurijala, Dennis McGillicuddy, Roberta E. Glynn, Michael DeVit, Laura L. Poling, Peter U. Park, Timothy B. Lowinger. Advantages of polyacetal polymer-based ADCs: Application to low expression targets. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2645. doi:10.1158/1538-7445.AM2014-2645
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Background Coronavirus disease-2019 (COVID-19) has become a global pandemic causing respiratory compromise, coagulopathy and renal failure in severe cases. Studies demonstrate a high incidence of venous thromboembolism (VTE), up to 69% in... more
Background Coronavirus disease-2019 (COVID-19) has become a global pandemic causing respiratory compromise, coagulopathy and renal failure in severe cases. Studies demonstrate a high incidence of venous thromboembolism (VTE), up to 69% in patients with severe COVID-19 infection. Coagulopathy in COVID-19 patients is attributed to excessive inflammation and endotheliopathy. Pregnant patients have approximately a 4-fold increase of VTE incidence. This is in part due to an increase in clotting factors and fibrinogen and a decrease in fibrinolytic activity and protein S. Increased stasis and the presence of acquired and inherited thrombophilias can contribute to increased VTE incidence during pregnancy and postpartum period (PP). Risk factors for thrombosis in pregnancy include African American race, heart disease, diabetes, smoking, multiparity, age >35 years, and obesity. Pregnancy/PP state and COVID-19 infection independently increase the risk of VTE which raises concern for an eve...
Research Interests:
Research Interests:
Horizontal gene transfer via plasmids could favour cooperation in bacteria, because transfer of a cooperative gene turns non-cooperative cheats into cooperators. This hypothesis has received support from both theoretical and genomic... more
Horizontal gene transfer via plasmids could favour cooperation in bacteria, because transfer of a cooperative gene turns non-cooperative cheats into cooperators. This hypothesis has received support from both theoretical and genomic analyses. In contrast, with a comparative analysis across 51 diverse species, we found that genes for extracellular proteins, which are likely to act as cooperative ‘public goods’, were not more likely to be carried on either: (i) plasmids compared to chromosomes; or (ii) plasmids that transfer at higher rates. Our results were supported by theoretical modelling which showed that while horizontal gene transfer can help cooperative genes initially invade a population, it does not favour the longer-term maintenance of cooperation. Instead, we found that genes for extracellular proteins were more likely to be on plasmids when they coded for pathogenic virulence traits, in pathogenic bacteria with a broad host-range. Taken together, these results support an ...
Research Interests:
<p>The Hellenistic period witnessed striking new developments in art, literature, and science. This volume addresses a particularly vibrant area of innovation: the study of animals and the natural world. While Aristotle and his... more
<p>The Hellenistic period witnessed striking new developments in art, literature, and science. This volume addresses a particularly vibrant area of innovation: the study of animals and the natural world. While Aristotle and his followers had revolutionized fields such as zoology and botany during the fourth century BC, these disciplines took on exciting new directions during Hellenistic times. Kings imported exotic species into their royal capitals from faraway lands. Travel writers described unusual creatures that they had never previously encountered. And buyers from a range of social levels chose works of art featuring animals and plants to decorate their palaces, houses and tombs. While textual sources shed some light on these developments, the central premise of <italic>Art, Science, and the Natural World in the Ancient Mediterranean</italic> is that our surviving artistic evidence permits an even fuller understanding. Accordingly, the study brings together a rich body of visual material that invites new observations on how and why knowledge of the natural world increased in importance during this period. It is suggested that this cultural phenomenon affected many different groups in society: from kings in Alexandria and Pergamon to provincial aristocrats in the Levant, and from the Julio-Claudian imperial family to prosperous homeowners in Pompeii. By analysing the works of art produced for these individuals, a vivid picture emerges of this significant aspect of ancient culture.</p>
Research Interests:
In this paper we analyse a set of 33 optical spectra, which were acquired with the ARCES echelle spectrograph (R = 38,000) on the 3.5-m telescope at the Apache Point Observatory. We examine the Hα profile in each of these observations in... more
In this paper we analyse a set of 33 optical spectra, which were acquired with the ARCES echelle spectrograph (R = 38,000) on the 3.5-m telescope at the Apache Point Observatory. We examine the Hα profile in each of these observations in order to determine the geometry and velocity structure of the previously discovered bipolar jet, which originates from the secondary star of HD 44179 located at the centre of the Red Rectangle nebula. Using a 3D geometric model we are able to determine the orbital coverage during which the jet occults the primary star. During the occultation, part of the Hα line profile appears in absorption. The velocity structure of the jet was determined by modelling the absorption line profile using the Sobolev approximation for each orbital phase during which we have observations. The results indicate the presence of a wide angle jet, likely responsible for observed biconical structure of the outer nebula. Furthermore, we were able to determine a likely velocit...
Research Interests:
<jats:p> <jats:bold>Background.</jats:bold> Recent studies have suggested that scar volume is one of the predictors of ICD utilization. We hypothesized that noninvasive ECG predictors of myocardial scar (number of leads... more
<jats:p> <jats:bold>Background.</jats:bold> Recent studies have suggested that scar volume is one of the predictors of ICD utilization. We hypothesized that noninvasive ECG predictors of myocardial scar (number of leads with Q waves and/or fragmented QRS complexes, fQRS) would correlate with infarct size and could predict patients with a depressed ejection fraction that would be the most likely to benefit from imaging scar volume. </jats:p> <jats:p> <jats:bold>Methods.</jats:bold> Patients with ischemic cardiomyopathy eligible for an ICD for the primary prevention of sudden death underwent PET imaging (n=78). Scar volume (% LV) was quantified from <jats:sup>18</jats:sup> FDG uptake during insulin stimulation and <jats:sup>13</jats:sup> N-ammonia flow using a validated algorithm (MyoPC, Ottawa Heart Institute). Pathologic Q waves and fQRS (RSR morphology or notching in R or S waves) on the 12-lead ECG were assessed by consensus of three blinded readers. </jats:p> <jats:p> <jats:bold>Results.</jats:bold> Subjects were 67 ± 12 years of age and 87% male. Average ejection fraction was 28 ± 10%. Myocardial scar encompassed 17.1 ± 7.3% of the left ventricle, with a very wide range among subjects (1.9 to 34.4%). In patients with a QRS duration &lt;120 msec (n=47), there was very poor correlation between scar volume and the number of leads with Q waves, fQRS or both (R <jats:sup>2</jats:sup> =0.01– 0.06, Table <jats:xref ref-type="table" /> ). Furthermore, patients with a wide QRS (&gt;120 msec) did not have an increase in scar volume (Table <jats:xref ref-type="table" /> ). </jats:p> <jats:p> <jats:bold>Conclusions.</jats:bold> These results indicate that 1.) The volume of scar varies widely in patients with ischemic cardiomyopathy that are eligible to receive an ICD for primary prevention and 2.) Infarct volume is independent of electrocardiographic indices of scar. Thus, imaging is necessary to stratify risk for SCD as a function of scar volume. </jats:p> <jats:p> <jats:table-wrap orientation="portrait" position="anchor"> <jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" orientation="portrait" position="float" xlink:href="2419T1.jpeg" /> </jats:table-wrap> </jats:p>
Research Interests:
IMPROVEMENT IN DYE SENSITIZED SOLAR CELL EFFICIENCY THROUGH FUNCTIONALIZATION OF REDOX MEDIATORS AND PASSIVATION OF THE PHOTOANODE USING A HOME-BUILT ATOMIC LAYER DEPOSITION SYSTEM The efficiency of dye sensitized solar cells (DSSCs) is... more
IMPROVEMENT IN DYE SENSITIZED SOLAR CELL EFFICIENCY THROUGH FUNCTIONALIZATION OF REDOX MEDIATORS AND PASSIVATION OF THE PHOTOANODE USING A HOME-BUILT ATOMIC LAYER DEPOSITION SYSTEM The efficiency of dye sensitized solar cells (DSSCs) is driven based on the contributions of a vast array of kinetic and thermodynamic processes which must all function in sync with one another. The redox mediator factors into a majority of these processes and thus its proper function is vital to adequate function of the DSSC as a whole. The function of the redox mediator can be altered in two ways: changing the identity of the redox couple used and modifying one of the components which the redox couple is interacting with. Herein, both methods have been performed to optimize the properties and processes involved in efficient DSSC function. Several cobalt bipyridine coordination complex type mediators have been synthesized and differentiated through the modification of the ligand structure. The purpose of...
Introducción: El siguiente artículo recupera el quehacer universitario vinculado con infancias, adolescencias y juventudes desde dos de sus tres áreas sustantivas: la Acción Social y la Investigación. Objetivo: Analizar los proyectos... more
Introducción: El siguiente artículo recupera el quehacer universitario vinculado con infancias, adolescencias y juventudes desde dos de sus tres áreas sustantivas: la Acción Social y la Investigación. Objetivo: Analizar los proyectos de Acción Social e Investigación vinculados con niñas, niños, adolescentes y jóvenes de la Universidad de Costa Rica vigentes a marzo 2021, a la luz del Atlas de Desarrollo Humano Cantonal 2020; con el fin de generar líneas orientadoras de trabajo con la población que contribuyan a la promoción de sus derechos. Método: Partiendo del Enfoque de Derechos Humanos y de Juventudes, se llevó a cabo una recuperación de proyectos de Acción Social e Investigación vigentes a marzo 2021. Posterior a ello, se clasificaron según ejes temáticos y su ubicación geográfica; información que posteriormente fue triangulada con el Índice de Desarrollo Humano Cantonal. Resultados: Se presenta una mayor concentración de proyectos en la provincia de San José y en cant...
Research Interests:
The RhK/Mo2C catalyst exhibited remarkable selectivity for higher alcohols synthesis from syngas under mild reaction conditions owing to the interface sites between Rh and Mo2C promoted by K, which greatly facilitated CO insertion.
SummaryThe circadian clock times cellular processes to the day/night cycle via a Transcription-Translation negative Feedback Loop (TTFL). However, a mechanistic understanding of the negative arm in both the timing of the TTFL and its... more
SummaryThe circadian clock times cellular processes to the day/night cycle via a Transcription-Translation negative Feedback Loop (TTFL). However, a mechanistic understanding of the negative arm in both the timing of the TTFL and its control of output is lacking. We posited that the formation of negative-arm protein complexes was fundamental to clock regulation stemming from the negative arm. Using a modified peptide microarray approach termed Linear motif discovery using rational design (LOCATE), we characterized the interaction of the disordered negative-arm clock protein FREQUENCY to its partner protein FREQUENCY-Interacting RNA helicase. LOCATE identified a specific Short Linear Motif (SLiM) and interaction “hotspot” as well as positively charged “islands” that mediate electrostatic interactions, suggesting a model where negative arm proteins form a “fuzzy” complex essential for clock timing and robustness. Further analysis revealed that the positively charged islands were an ev...
Research Interests:
Graft-versus-host disease (GVHD) is a rare complication after solid organ transplant. We present a case of GVHD after simultaneous pancreas kidney transplant. The patient was diagnosed with a cutaneous biopsy after developing the classic... more
Graft-versus-host disease (GVHD) is a rare complication after solid organ transplant. We present a case of GVHD after simultaneous pancreas kidney transplant. The patient was diagnosed with a cutaneous biopsy after developing the classic symptoms of maculopapular rash, diarrhea, and pancytopenia. However, this patient had unexplained elevations in donor-derived cell-free DNA (dd-cfDNA) for months before the onset of GVHD symptoms. We hypothesize that GVHD may be associated with elevated dd-cfDNA as a result of massive donor lymphocyte proliferation and turnover. Further investigation is warranted because earlier diagnosis and treatment could improve outcomes in an otherwise lethal disease.
Research Interests:
Philosophers, archeologists, and other heritage professionals often take a rather negative view of heritage reconstruction, holding that it is inappropriate or even impermissible. In this essay, we argue that taking such hardline... more
Philosophers, archeologists, and other heritage professionals often take a rather negative view of heritage reconstruction, holding that it is inappropriate or even impermissible. In this essay, we argue that taking such hardline attitudes toward the reconstruction of heritage is unjustified. To the contrary, we believe that the reconstruction of heritage can be both permissible and beneficial, all things considered. In other words, sometimes we have good reasons, on balance, to pursue reconstructions, and doing so can be morally acceptable. In defending this claim, we discern a number of arguments made against heritage reconstruction and demonstrate that these arguments are either exaggerated or lack support.