Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
186
result(s) for
"Patrick Fagan"
Sort by:
RIPK1-mediated induction of mitophagy compromises the viability of extracellular-matrix-detached cells
For cancer cells to survive during extracellular matrix (ECM) detachment, they must inhibit anoikis and rectify metabolic deficiencies that cause non-apoptotic cell death. Previous studies in ECM-detached cells have linked non-apoptotic cell death to reactive oxygen species (ROS) generation, although the mechanistic underpinnings of this link remain poorly defined. Here, we uncover a role for receptor-interacting protein kinase 1 (RIPK1) in the modulation of ROS and cell viability during ECM detachment. We find that RIPK1 activation during ECM detachment results in mitophagy induction through a mechanism dependent on the mitochondrial phosphatase PGAM5. As a consequence of mitophagy, ECM-detached cells experience diminished NADPH production in the mitochondria, and the subsequent elevation in ROS levels leads to non-apoptotic death. Furthermore, we find that antagonizing RIPK1/PGAM5 enhances tumour formation in vivo. Thus, RIPK1-mediated induction of mitophagy may be an efficacious target for therapeutics aimed at eliminating ECM-detached cancer cells.
Hawk et al. show that RIPK1 activation during extracellular matrix detachment induces mitophagy through mitochondrial phosphatase PGAM5 to increase reactive oxygen species and non-apoptotic cell death, and that antagonizing RIPK1/PGAM5 enhances tumour formation.
Journal Article
High-Frequency Fractional Predictions and Spatial Distribution of the Magnetic Loss in a Grain-Oriented Magnetic Steel Lamination
Grain-oriented silicon steel (GO FeSi) laminations are vital components for efficient energy conversion in electromagnetic devices. While traditionally optimized for power frequencies of 50/60 Hz, the pursuit of higher frequency operation (f ≥ 200 Hz) promises enhanced power density. This paper introduces a model for estimating GO FeSi laminations’ magnetic behavior under these elevated operational frequencies. The proposed model combines the Maxwell diffusion equation and a material law derived from a fractional differential equation, capturing the viscoelastic characteristics of the magnetization process. Remarkably, the model’s dynamical contribution, characterized by only two parameters, achieves a notable 4.8% Euclidean relative distance error across the frequency spectrum from 50 Hz to 1 kHz. The paper’s initial section offers an exhaustive description of the model, featuring comprehensive comparisons between simulated and measured data. Subsequently, a methodology is presented for the localized segregation of magnetic losses into three conventional categories: hysteresis, classical, and excess, delineated across various tested frequencies. Further leveraging the model’s predictive capabilities, the study extends to investigating the very high-frequency regime, elucidating the spatial distribution of loss contributions. The application of proportional–iterative learning control facilitates the model’s adaptation to standard characterization conditions, employing sinusoidal imposed flux density. The paper deliberates on the implications of GO FeSi behavior under extreme operational conditions, offering insights and reflections essential for understanding and optimizing magnetic core performance in high-frequency applications.
Journal Article
A Qualitative Study on Challenges Faced and Strategies Used by African American Men in Senior Leadership
This generic qualitative descriptive study explored the experiences and challenges faced by African American men in top leadership positions in the United States. Despite strides in civil rights, the professional advancement of Black leaders continues to be hindered, and the research literature is lacking regarding some factors that may contribute to this gap. I sought to address this gap by employing a generic qualitative descriptive approach to explore the experiences of African American men in top leadership positions. Braun and Clarke’s thematic analysis framework was used to analyze the data, guided by Lent et al.’s social cognitive career theory. The purpose of the research was to answer the question: “How do African American men in top leadership positions describe their challenges and the strategies they use to overcome barriers to top leadership positions?” Purposive sampling was used to recruit 15 participants with in-depth knowledge of the career development of male African American senior leaders. Six themes emerged from the findings: (a) racism, discrimination, and segregation; (b) lack of support and code-switching; (c) workplace and interpersonal problems; (d) transformational leadership style; (e) personal growth and skill acquisition; and (f) networking and building relationships, all of which were reported by African American participants. Participants also felt less support to effectively nurture their career progression. The men found it difficult to assert themselves in the workplace due to competition and noncooperation from other employees and management. The participants adopted transformational leadership strategies to overcome identified barriers. They overcame barriers through transformational leadership, personal growth, networking, and nurturing relationships; these findings demonstrate the need for Black leaders to take bold steps to inspire and pave the way for others in senior management.
Dissertation
Paroxysmal Hypertension in Congenital Hypothyroidism: An Unusual Case of Pheochromocytoma
Pheochromocytomas are rare tumors arising from the chromaffin cells of the adrenal medulla that result in the secretion of excessive catecholamines. They are an uncommon cause of hypertension in the pediatric population. We present a case of a six-year-old male with hypertension, rapid weight loss, palpitations, excessive sweating, and vomiting. Their previous medical history was significant for congenital hypothyroidism, and upon the emergence of his symptoms, his levothyroxine dosing was reduced to half. Presenting symptoms and initial history were suspicious for thyroid-related disease; however, imaging showed a complex right adrenal mass in the setting of elevated plasma catecholamine levels. A diagnosis of pheochromocytoma was made, and a right adrenalectomy was performed. The patient tolerated the procedure well, with complete resolution of symptoms. Three years later, his symptoms re-emerged and were concerning for tumor recurrence. This case highlights the diagnosis of this rare cause of pediatric hypertension and the importance of remaining vigilant against anchoring bias.
Journal Article
Familia y Educación
El objetivo de este trabajo es examinar la relación íntima entre la familia y la educación y revelar las implicaciones sociales y educativas subyacentes del primero sobre el segundo, en concreto en la unión parental, participación de los padres, la estructura familiar (es decir, la composición del hogar, definida por la presencia o no presencia de la figura del padre y de la madre), y la práctica religiosa. Esta revisión considera estas categorías relacionadas entre sí y como los principales factores determinantes del éxito o el fracaso escolar de los niños. A partir de la revisión de la literatura, dibujamos cuatro observaciones principales: (1) las familias protectoras representan el mejor de todos los resultados educativos medibles, (2) la participación de padres, declarada en una fuerte unidad parental, mejora fuertemente los resultados educativos y la conducta, (3) los niños de familias biológicas de dos padres casados poseen un mejor rendimiento académico en todo el espectro, y (4) la práctica religiosa, mediada a través de la familia, protege y mejora el nivel de educación de los niños. En conjunto, estos datos suponen un ejemplo convincente para la estrecha relación entre la educación y la familia.
Journal Article
Familia y educacion
The aim of this paper is to examine the intimate link between family and education and reveal the underlying social and educational implications of the former on the latter, concentrating on parental union, parental involvement, family structure (i.e. the composition of a household, defined by the presence or non-presence of father and mother figures), and religious practice. This review considers these categories as interrelated and as major determinants of children's educational success or failure. From our review of the literature, we draw four major observations: (1) intact families perform the best on all measurable educational outcomes; (2) parental involvement, predicated on strong parental unity, strongly improves educational outcomes and behavior; (3) the children of married two-parent biological family perform best academically across the spectrum; and (4) religious practice, mediated through the family, protects and improves the educational attainment of children. Together, these data make a compelling case for the close connection between education and family.
Journal Article
Family and Education/Familia y Educación
The aim of this paper is to examine the intimate link between family and education and reveal the underlying social and educational implications of the former on the latter, concentrating on parental union, parental involvement, family structure (i.e. the composition of a household, defined by the presence or non-presence of father and mother figures), and religious practice. This review considers these categories as interrelated and as major determinants of children's educational success or failure. From our review of the literature, we draw four major observations: (1) intact families perform the best on all measurable educational outcomes; (2) parental involvement, predicated on strong parental unity, strongly improves educational outcomes and behavior; (3) the children of married two-parent biological family perform best academically across the spectrum; and (4) religious practice, mediated through the family, protects and improves the educational attainment of children. Together, these data make a compelling case for the close connection between education and family. [PUBLICATION ABSTRACT]
Journal Article
Evaluation of an Intravenous Acetaminophen Protocol in the Emergency Department
Acute pain is a leading reason for Emergency Department (ED) evaluation, accounting for nearly half of all ED visits. Therefore, providing effective non-opioid analgesics in the ED is critical. Oral acetaminophen (APAP) is commonly administered in the ED but is limited to patients tolerating oral intake. Intravenous (IV) APAP provides significant pain reduction parenterally. The purpose of this quality assessment project was to evaluate the frequency of opioid use in patients receiving IV APAP, the safety of IV APAP, and compliance with an ED IV APAP protocol.
This study included all patients who received IV APAP in the ED of a tertiary care, level I trauma center, during a three-month period. The protocol required ED patients to be NPO (nil per os), 18 years or older, and administered with a single 1000 mg dose. The adverse reactions within 24 hours post-IV APAP, ED length of stay (LOS), and opioid administration within four hours post-IV APAP were assessed.
Ninety-four patients received IV APAP. All patients received a 1000 mg dose. One patient received more than one dose, but this patient had a 22-hour ED LOS. Two patients received oral medications within one hour of IV APAP (one received an antacid, and the other received carbamazepine and lamotrigine). An opioid was administered to 22 of the 94 (23.4%) patients during the four-hour protocol period. There were no reports of adverse reactions.
The results show excellent compliance with the protocol. IV APAP was safe and well-tolerated. Notably, most patients did not receive an opioid within four hours of IV APAP. IV APAP can be safely and effectively utilized as an analgesic and lessen ED opioid use.
Journal Article
PARIS and SPARTA: Finding the Achilles’ Heel of SARS-CoV-2
Determining reinfection rates and correlates of protection against SARS-CoV-2 infection induced by both natural infection and vaccination is of high significance for the prevention and control of coronavirus disease 2019 (COVID-19). Furthermore, understanding reinfections or infection after vaccination and the role immune escape plays in these scenarios will inform the need for updates of the current SARS-CoV-2 vaccines and help update guidelines suitable for the postpandemic world. To understand reinfection rates and correlates of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we established eight different longitudinal cohorts in 2020 under the umbrella of the PARIS (Protection Associated with Rapid Immunity to SARS-CoV-2)/SPARTA (SARS SeroPrevalence And Respiratory Tract Assessment) studies. Here, we describe the PARIS/SPARTA cohorts, the harmonized assays and analysis that are performed across the cohorts, as well as case definitions for SARS-CoV-2 infection and reinfection that have been established by the team of PARIS/SPARTA investigators. IMPORTANCE Determining reinfection rates and correlates of protection against SARS-CoV-2 infection induced by both natural infection and vaccination is of high significance for the prevention and control of coronavirus disease 2019 (COVID-19). Furthermore, understanding reinfections or infection after vaccination and the role immune escape plays in these scenarios will inform the need for updates of the current SARS-CoV-2 vaccines and help update guidelines suitable for the postpandemic world.
Journal Article