Search

Your search keyword '"SHARKEY, P. M."' showing total 238 results
Start Over Author "SHARKEY, P. M."
238 results on '"SHARKEY, P. M."'

2. Ubiquilin-2 regulates pathological alpha-synuclein

Author

Sandoval-Pistorius, Stephanie S., Gerson, Julia E., Liggans, Nyjerus, Ryou, Jaimie H., Oak, Kulin, Li, Xingli, Negron-Rios, Keyshla Y., Fischer, Svetlana, Barsh, Henry, Crowley, Emily V., Skinner, Mary E., Sharkey, Lisa M., Barmada, Sami J., and Paulson, Henry L.

Published
2023
Full Text
View/download PDF

4. Deconvolution of octahedral Pt3Ni nanoparticle growth pathway from in situ characterizations.

Author

Shen, Xiaochen, Zhang, Changlin, Zhang, Shuyi, Dai, Sheng, Zhang, Guanghui, Ge, Mingyuan, Pan, Yanbo, Sharkey, Stephen M, Graham, George W, Hunt, Adrian, Waluyo, Iradwikanari, Miller, Jeffrey T, Pan, Xiaoqing, and Peng, Zhenmeng

Subjects
MD Multidisciplinary
Abstract

Understanding the growth pathway of faceted alloy nanoparticles at the atomic level is crucial to morphology control and property tuning. Yet, it remains a challenge due to complexity of the growth process and technical limits of modern characterization tools. We report a combinational use of multiple cutting-edge in situ techniques to study the growth process of octahedral Pt3Ni nanoparticles, which reveal the particle growth and facet formation mechanisms. Our studies confirm the formation of octahedral Pt3Ni initiates from Pt nuclei generation, which is followed by continuous Pt reduction that simultaneously catalyzes Ni reduction, resulting in mixed alloy formation with moderate elemental segregation. Carbon monoxide molecules serve as a facet formation modulator and induce Ni segregation to the surface, which inhibits the (111) facet growth and causes the particle shape to evolve from a spherical cluster to an octahedron as the (001) facet continues to grow.

Published
2018

5. Phase I/II Trial of Labetuzumab Govitecan (Anti-CEACAM5/SN-38 Antibody-Drug Conjugate) in Patients With Refractory or Relapsing Metastatic Colorectal Cancer

Author

Dotan, Efrat, Cohen, Steven J, Starodub, Alexander N, Lieu, Christopher H, Messersmith, Wells A, Simpson, Pamela S, Guarino, Michael J, Marshall, John L, Goldberg, Richard M, Hecht, J Randolph, Wegener, William A, Sharkey, Robert M, Govindan, Serengulam V, Goldenberg, David M, and Berlin, Jordan D

Subjects
Cancer, Clinical Research, Clinical Trials and Supportive Activities, Colo-Rectal Cancer, Digestive Diseases, 5.1 Pharmaceuticals, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, Evaluation of treatments and therapeutic interventions, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Camptothecin, Colorectal Neoplasms, Disease Progression, Disease-Free Survival, Drug Administration Schedule, Drug Resistance, Neoplasm, Female, Half-Life, Humans, Infusions, Intravenous, Irinotecan, Male, Middle Aged, Neoplasm Metastasis, Survival Analysis, Treatment Outcome, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Purpose The objectives were to evaluate dosing schedules of labetuzumab govitecan, an antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for tumor delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with relapsed or refractory metastatic colorectal cancer. Patients and Methods Eligible patients with at least one prior irinotecan-containing therapy received labetuzumab govitecan once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles. End points were safety, response, pharmacokinetics, and immunogenicity. Results Eighty-six patients who had undergone a median of five prior therapies (range, one to 13) were each enrolled into one of the four cohorts. On the basis of Response Evaluation Criteria in Solid Tumors 1.1, 38% of these patients had a tumor as well as plasma carcinoembryonic antigen reduction from baseline after labetuzumab govitecan treatment; one patient achieved a partial response with a sustained response spanning > 2 years, whereas 42 patients had stable disease as the best overall response. Median progression-free survival and overall survival were 3.6 and 6.9 months, respectively. The major toxicities (grade ≥ 3) among all cohorts were neutropenia (16%), leukopenia (11%), anemia (9%), and diarrhea (7%). The antibody-drug conjugate's mean half-life was 16.5 hours for the four cohorts. Anti-drug/anti-antibody antibodies were not detected. The two once-weekly dose schedules, showing comparable toxicity and efficacy, were chosen for further study. Conclusion Monotherapy with labetuzumab govitecan demonstrated a manageable safety profile and therapeutic activity in heavily pretreated patients with metastatic colorectal cancer, all with prior irinotecan therapy. Further studies of labetuzumab govitecan treatment alone or in combination with other therapies in earlier settings are indicated.

Published
2017

6. Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study

Author

Touchefeu, Y., Bailly, C., Frampas, E., Eugène, T., Rousseau, C., Bourgeois, M., Bossard, C., Faivre-Chauvet, A., Rauscher, A., Masson, D., David, A., Cerato, E., Carlier, T., Sharkey, R. M., Goldenberg, D. M., Barbet, J., Kraeber-Bodere, F., and Bodet-Milin, C.

Published
2021
Full Text
View/download PDF

14. Illness Uncertainty and Illness Intrusiveness as Predictors of Depressive and Anxious Symptomology in College Students with Chronic Illnesses

Author

Mullins, Alexandria J., Gamwell, Kaitlyn L., Sharkey, Christina M., Bakula, Dana M., Tackett, Alayna P., Suorsa, Kristina I., Chaney, John M., and Mullins, Larry L.

Abstract

Objective: To examine predictors of psychological functioning in college students with chronic illnesses. Participants: Participants (N = 1413) included 364 students with self-reported diagnoses of asthma or allergies, 148 students with other chronic illnesses (eg, epilepsy, type 1 diabetes), and 901 healthy students. Data were collected between November 2013 and May 2015. Methods: Participants completed online measures of psychosocial functioning, including illness uncertainty, illness intrusiveness, depression, and anxiety. Results: Students with chronic illnesses other than asthma or allergies evidenced the greatest levels of anxious (p <0.05), but not depressive symptomology. Additionally, this group reported greater illness uncertainty and intrusiveness (p <0.05) compared to their peers. Uncertainty and intrusiveness independently predicted depressive and anxious symptoms for students in both illness groups. Conclusions: Compared to peers with asthma or allergies, college students with other chronic illnesses reported higher levels of anxious symptoms. Illness uncertainty and intrusiveness appear to be predictors of psychological distress, regardless of illness.

Published
2017
Full Text
View/download PDF

16. PRODUCT LIABILITY AND ONLINE MARKETPLACES: COMPARISON AND REFORM

Author

Fairgrieve, Duncan, Busch, Christoph, Büyüksagis, Erdem, Garrett, Zachary G., Straetmans, Gert, Karaiskos, Antonios, Linley, Robin D., Markou, Christiana, Paterson, Jeannie Marie, and Sharkey, Catherine M.

Abstract

AbstractThis article analyses the challenges that online marketplaces and e-commerce pose to traditional product liability doctrines. It uses a comparative perspective to examine whether an online platform can be liable to a consumer for a defective product purchased on its platform, and the adaption of product liability law to this challenge in a series of jurisdictions. It reflects on the role of litigation and regulation, focusing on Europe and the United States, and considers reform in a number of jurisdictions in this area. It concludes with proposals for increasing the accountability of online marketplaces for products sold on their websites.

Published
2024
Full Text
View/download PDF

18. Single-cell reconstruction of the early maternal–fetal interface in humans

Author

Vento-Tormo, Roser, Efremova, Mirjana, Botting, Rachel A., Turco, Margherita Y., Vento-Tormo, Miquel, Meyer, Kerstin B., Park, Jong-Eun, Stephenson, Emily, Polański, Krzysztof, Goncalves, Angela, Gardner, Lucy, Holmqvist, Staffan, Henriksson, Johan, Zou, Angela, Sharkey, Andrew M., Millar, Ben, Innes, Barbara, Wood, Laura, Wilbrey-Clark, Anna, Payne, Rebecca P., Ivarsson, Martin A., Lisgo, Steve, Filby, Andrew, Rowitch, David H., Bulmer, Judith N., Wright, Gavin J., Stubbington, Michael J. T., Haniffa, Muzlifah, Moffett, Ashley, and Teichmann, Sarah A.

Published
2018
Full Text
View/download PDF

19. Predictors of Rapid Aortic Root Dilation and Referral for Aortic Surgery in Marfan Syndrome

Author

Hoskoppal, Arvind, Menon, Shaji, Trachtenberg, Felicia, Burns, Kristin M., De Backer, Julie, Gelb, Bruce D., Gleason, Marie, James, Jeanne, Lai, Wyman W., Liou, Aimee, Mahony, Lynn, Olson, Aaron K., Pyeritz, Reed E., Sharkey, Angela M., Stylianou, Mario, Wechsler, Stephanie Burns, Young, Luciana, Levine, Jami C., Tierney, Elif Seda Selamet, Lacro, Ronald V., Bradley, Timothy J., and Pediatric Heart Network Investigators

Published
2018
Full Text
View/download PDF

27. Wild-type and pathogenic forms of ubiquilin 2 differentially modulate components of the autophagy-lysosome pathways

Author

Idera, Akiko, Sharkey, Lisa M., Kurauchi, Yuki, Kadoyama, Keiichi, Paulson, Henry L., Katsuki, Hiroshi, and Seki, Takahiro

Abstract

Missense mutations of ubiquilin 2 (UBQLN2) have been identified to cause X-linked amyotrophic lateral sclerosis (ALS). Proteasome-mediated protein degradation is reported to be impaired by ALS-associated mutations of UBQLN2. However, it remains unknown how these mutations affect autophagy-lysosome protein degradation, which consists of macroautophagy (MA), microautophagy (mA), and chaperone-mediated autophagy (CMA). Using a CMA/mA fluorescence reporter we found that overexpression of wild-type UBQLN2 impairs CMA. Conversely, knockdown of endogenous UBQLN2 increases CMA activity, suggesting that normally UBQLN2 negatively regulates CMA. ALS-associated mutant forms of UBQLN2 exacerbate this impairment of CMA. Using cells stably transfected with wild-type or ALS-associated mutant UBQLN2, we further determined that wild-type UBQLN2 increased the ratio of LAMP2A (a CMA-related protein) to LAMP1 (a lysosomal protein). This could represent a compensatory reaction to the impairment of CMA by wild-type UBQLN2. However, ALS-associated mutant UBQLN2 failed to show this compensation, exacerbating the impairment of CMA by mutant UBQLN2. We further demonstrated that ALS-associated mutant forms of UBQLN2 also impair MA, but wild-type UBQLN2 does not. These results support the view that ALS-associated mutant forms of UBQLN2 impair both CMA and MA which may contribute to the neurodegeneration observed in patients with UBQLN2-mediated ALS.

Published
2023
Full Text
View/download PDF

29. Quality of Life in Adolescents and Young Adults With a Chronic Medical Condition: The Role of Perceived Maturity and Transition Readiness.

Author

Dattilo, Taylor M., Fisher, Rachel S., Roberts, Caroline M., Sharkey, Christina M., Clawson, Ashley, Chaney, John M., and Mullins, Larry L.

Abstract

Adolescents and young adults (AYA) with a chronic medical condition (CMC) attending college must learn to manage their own healthcare (i.e., transition readiness). Maturity has been linked to positive outcomes in AYAs. Research has established a positive relationship between transition readiness and quality of life. The current study aimed to examine a model of perceived maturityàtransition readinessàmental and physical quality of life. AYA (N = 153) with a CMC completed self-report questionnaires. The perceived maturity→transition readiness→mental quality of life indirect path was significant (ab = 1.96, 95% CI = 0.53 to 3.62). The perceived maturity→transition readiness→physical quality of life direct and indirect paths were not significant. Results showed that maturity and transition readiness are positively associated. Transition readiness may be one mechanism by which maturity results in enhanced quality of life. Findings highlight the value of enhancing strengths such as maturity to promote AYA independence/autonomy. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

40. Insomnia and Other Sleep Disorders in Older Adults

Author

Cohen, Zachary L., Eigenberger, Paul M., Sharkey, Katherine M., Conroy, Michelle L., and Wilkins, Kirsten M.

Abstract

Sleep disruption is common in older adults and is associated with many poor health outcomes. It is vital for providers to understand insomnia and other sleep disorders in this population. This article outlines age-related changes in sleep, and medical, psychiatric, environmental, and psychosocial factors that may impact sleep. It addresses the evaluation of sleep symptoms and diagnosis of sleep disorders. It aims to examine the evidence for non-pharmacological and pharmacologic treatment options for insomnia while weighing factors particularly germane to the aging adult..

Published
2022
Full Text
View/download PDF

41. Products Liability in the Digital Age: Online Platforms as “Cheapest Cost Avoiders”.

Author

SHARKEY, CATHERINE M.

Subjects
PRODUCT liability, ELECTRONIC commerce, CONSUMERS, CROSS-border e-commerce, COMMON law
Abstract

Products liability in the digital age entails reckoning with the transformative shift away from in-person purchases at brick-and-mortar stores to digital purchases from e-commerce platforms. The epochal rise of the online storefront has vastly expanded the prevalence of direct-to-consumer sales, implicating complex questions of how liability rules should respond when those consumers are harmed by the products they buy, especially in this age of international e-commerce and cross-border sales. Imposing liability on online platforms on grounds of their superior ability to prevent harms from newly emergent risks, i.e., their status as “cheapest cost avoiders,” reveals courts’ efforts to vindicate the regulatory needs of society, and hence pin responsibility on entities in the best position to have readily avoided harm arising from the imposition of excessive risks. Products liability is a microcosm of how the common law evolves over time, specifically, here, to respond to new societal risks—posed by the automobile, mass-produced goods, and now, digital e-commerce. At each juncture in the development of products liability law, judges have relied explicitly on deterrence, or prevention of harm, rationales to address new forms of risks and prevent them from materializing into harms, and in doing so, have recognized new harms and/or expanded tort liability. [ABSTRACT FROM AUTHOR]

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results