100 results on '"Lewis NL"'
Search Results
2. A metabolic approach towards optimising equine in vitro maturation
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Lewis, NL, McGowan, Cathy, Brison, Daniel, Hinrichs, Katrin, Argo, caroline, Peffers, mandy, and grove white, dai
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- 2019
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3. Strabismus in infants of opiate-dependent mothers
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Gill, AC, primary, Oei, J, additional, Lewis, NL, additional, Younan, N, additional, Kennedy, I, additional, and Lui, K, additional
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- 2007
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4. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2.
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Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S, Leong S, O'Bryant C, Chow LQ, Serkova NJ, Meropol NJ, Lewis NL, Chiorean EG, Fox F, Youssoufian H, Rowinsky EK, Eckhardt SG, Spratlin, Jennifer L, Cohen, Roger B, and Eadens, Matthew
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- 2010
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5. Phase I study of the safety, tolerability, and pharmacokinetics of oral CP-868,596, a highly specific platelet-derived growth factor receptor tyrosine kinase inhibitor in patients with advanced cancers.
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Lewis NL, Lewis LD, Eder JP, Reddy NJ, Guo F, Pierce KJ, Olszanski AJ, Cohen RB, Lewis, Nancy L, Lewis, Lionel D, Eder, Joseph P, Reddy, Nandi J, Guo, Feng, Pierce, Kristen J, Olszanski, Anthony J, and Cohen, Roger B
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- 2009
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6. Effects of food on the relative bioavailability of lapatinib in cancer patients.
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Koch KM, Reddy NJ, Cohen RB, Lewis NL, Whitehead B, Mackay K, Stead A, Beelen AP, Lewis LD, Koch, Kevin M, Reddy, Nandi J, Cohen, Roger B, Lewis, Nancy L, Whitehead, Bonnie, Mackay, Kathleen, Stead, Andrew, Beelen, Andrew P, and Lewis, Lionel D
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- 2009
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7. Long-term care of the elderly: public policy issues.
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Lewis NL
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- 1986
8. Recipe for fatigue: sleep, work patterns, and well-being of galley workers on surface ships of the US Navy.
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Shattuck NL and Matsangas P
- Abstract
Study Objectives: The purpose of the study was to compare the fatigue levels, work/rest patterns, health-related behaviors, and well-being of galley workers with other sailors on US Navy ships while underway., Methods: Analysis was based on a retrospective comparison of data from 3 fit-for-duty groups of sailors: 67 galley workers, 192 non-watchstanders, and 466 watchstanders. Participants completed questionnaires (Epworth Sleepiness Scale [ESS], Insomnia Severity Index [ISI], Pittsburgh Sleep Quality Index [PSQI], and Profile of Mood States [POMS]) and activity logs, and wore actigraphs., Results: Galley workers slept MD = 6.57 (IQR = 1.42) h/d and worked MD = 12.8 (IQR = 2.42) h/d. Approximately 84% of the galley workers were classified as poor sleepers, ~57% reported having excessive daytime sleepiness (EDS), and ~38% reported elevated insomnia symptoms. Compared to non-watchstanders, galley workers had worse scores on POMS (total mood disturbance, tension-anxiety, depression, anger-hostility, fatigue, and confusion-bewilderment), ESS, ISI, and PSQI. Compared to non-watchstanders, galley workers had a higher risk for symptoms of EDS (75%), symptoms of clinically relevant insomnia (126%), and for being classified as poor sleepers (27%). Galley workers slept less and worked on average 2 h/d more than non-watchstanders. Compared to watchstanders, galley workers had worse ESS, ISI, and anger-hostility scores. More watchstanders napped compared to galley workers., Conclusions: Although they are considered day workers, the sleep patterns, fatigue levels, and mood of galley workers are comparable to, or worse than, watchstanders or other non-watchstanders. To ameliorate the effects of long work hours on sailor well-being, ship leadership should consider adopting strategies to improve galley workers' well-being., (Published by Oxford University Press on behalf of Sleep Research Society 2024.)
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- 2024
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9. Building Resilience Among Nursing Students.
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Liljestrand RL, Chandler GE, Devine CA, Pérez JR, Mchenga NL, and Kalmakis KA
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- Humans, Nursing Education Research, Education, Nursing, Baccalaureate organization & administration, Students, Nursing psychology, Resilience, Psychological
- Abstract
Competing Interests: The authors declare no conflicts of interest.
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- 2024
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10. Sleepy and grumpy go hand in hand for US Navy Sailors.
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McClernon CK, Matsangas P, and Shattuck NL
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Study Objectives: The study explores how sleep, sleep-related practices, and behaviors, in addition to various demographic and occupational characteristics, are related to overall mood of US Navy sailors when they are underway., Methods: Longitudinal assessment of US Navy sailors performing their underway duties ( N = 873, 79.2% males, median age 25 years). Participants completed standardized questionnaires, wore wrist-worn actigraphs, and completed daily activity logs., Results: Sailors who reported worse profile of mood states (POMS) total mood disturbance scores had shorter sleep duration, worse sleep quality, and more episodes of split sleep. The group with worse mood also reported more symptoms of excessive daytime sleepiness as well as more symptoms of insomnia. In addition to sleep results, sailors with worse mood also tended to be younger, more likely to use nicotine and tobacco products, and less likely to have an exercise routine when compared to sailors with better POMS scores. Finally, the group with worse POMS scores included more enlisted personnel, tended to work more hours per day, and were more likely to stand watch-especially on rotating watch schedules., Conclusions: The results found significant associations between the sleep practices and mood of sailors aboard US Navy ships. Numerous other demographic and occupational factors were also strongly associated with mood. This paper is part of the Sleep and Circadian Rhythms: Management of Fatigue in Occupational Settings Collection., (Published by Oxford University Press on behalf of Sleep Research Society 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
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- 2024
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11. Chromatic fusion: Generative multimodal neuroimaging data fusion provides multi-informed insights into schizophrenia.
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Geenjaar EPT, Lewis NL, Fedorov A, Wu L, Ford JM, Preda A, Plis SM, and Calhoun VD
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- Humans, Magnetic Resonance Imaging methods, Brain diagnostic imaging, Neuroimaging, Diffusion Magnetic Resonance Imaging, Schizophrenia diagnostic imaging
- Abstract
This work proposes a novel generative multimodal approach to jointly analyze multimodal data while linking the multimodal information to colors. We apply our proposed framework, which disentangles multimodal data into private and shared sets of features from pairs of structural (sMRI), functional (sFNC and ICA), and diffusion MRI data (FA maps). With our approach, we find that heterogeneity in schizophrenia is potentially a function of modality pairs. Results show (1) schizophrenia is highly multimodal and includes changes in specific networks, (2) non-linear relationships with schizophrenia are observed when interpolating among shared latent dimensions, and (3) we observe a decrease in the modularity of functional connectivity and decreased visual-sensorimotor connectivity for schizophrenia patients for the FA-sFNC and sMRI-sFNC modality pairs, respectively. Additionally, our results generally indicate decreased fractional corpus callosum anisotropy, and decreased spatial ICA map and voxel-based morphometry strength in the superior frontal lobe as found in the FA-sFNC, sMRI-FA, and sMRI-ICA modality pair clusters. In sum, we introduce a powerful new multimodal neuroimaging framework designed to provide a rich and intuitive understanding of the data which we hope challenges the reader to think differently about how modalities interact., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
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- 2023
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12. Edwardsiella tarda Isolated from a Kidney Mass in a Common Loon (Gavia immer).
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Lewis NL, Ware C, and Griffin MJ
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- Animals, Kidney, Autopsy veterinary, New Jersey, Edwardsiella tarda, Birds
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A Common Loon (Gavia immer) was found recumbent at Island Beach State Park, New Jersey, US, and euthanized. Necropsy revealed a caseous mass in the kidney, from which bacteria were isolated and phenotypically and molecularly identified as Edwardsiella tarda., (© Wildlife Disease Association 2023.)
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- 2023
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13. Persistent MALT Lymphoma With Plasmacytic Differentiation Following Treatment With Rituximab.
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Moumen M, Bowers NL, DeSilverio R Jr, and Sangueza OP
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- Humans, Rituximab therapeutic use, Lymphoma, B-Cell, Marginal Zone drug therapy, Lymphoma, B-Cell, Marginal Zone pathology, Stomach Neoplasms
- Abstract
Competing Interests: The authors declare no conflicts of interest.
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- 2023
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14. Using Light to Facilitate Circadian Entrainment from Day to Night Flights.
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Shattuck NL, Matsangas P, Reily J, McDonough M, and Giles KB
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- Humans, Sleepiness, Work Schedule Tolerance, Circadian Rhythm, Sleep, Melatonin
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BACKGROUND: As part of a larger project to provide recommendations regarding limitations and best practices for shifting aviators from day to night operations, a study was conducted to assess the efficacy of high energy visible (HEV) light to shift the circadian rhythm in humans. The study attempted to replicate the patterns of military aviators who could be required to shift abruptly from day to night flight operations. METHODS: Simulated flight performance and salivary melatonin levels of 10 U.S. military aviators were collected over a 3-night period using a within-subject dim light melatonin onset (DLMO) study design. Data were collected in a laboratory with participants returning home to sleep following each of the three evenings/nights of data collection. Light treatment included a single 4-h exposure of blue-enriched white light (∼1000 lux) on night 2. Data collected included melatonin levels, light exposure, sleepiness, cognitive workload, and simulated flight performance. RESULTS: The average delay in melatonin onset was 1.32 ± 0.37 h (range: 53 min to 1 h 56 min). Sleepiness ( P = 0.044) and cognitive workload ( P = 0.081) improved the night following the light treatment compared to the baseline. No systematic differences were identified in flight performance. DISCUSSION: The HEV light treatment successfully delayed the circadian phase of all participants even though participants' ambient light levels (including daylight) outside the laboratory were not controlled. These findings were used to develop circadian synchronization plans for aviators who are asked to transition from day to night operations. These plans will be assessed in a follow-on study in an operational unit. Shattuck NL, Matsangas P, Reily J, McDonough M, Giles KB. Using light to facilitate circadian entrainment from day to night flights . Aerosp Med Hum Perform. 2023; 94(2):66-73.
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- 2023
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15. Casualty Evacuation (CASEVAC) Platform Review and Case Series of US Military Enroute Critical Care Team With Contract Personnel Recovery Services in an Austere Environment.
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Boyer NL, Mazarella JA, Thronson EE, and Brillhart DB
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- Critical Care, Humans, Resuscitation, Retrospective Studies, Military Medicine, Military Personnel
- Abstract
In a rapidly changing operational environment, in which there has been an emphasis on prolonged field care and limited evacuation platforms, military providers must practice to the full scope of their training to maximize outcomes. In addition to pushing military providers further into combat zones, the Department of Defense has relied on contracted personnel to help treat and evacuate servicemembers. This article is a retrospective review on the interoperability of the expeditionary resuscitative surgical team (ERST) and a contracted personnel recovery (CPR) team in a far-forward austere environment and will discuss actual patient transport case reviews that used multiple evacuation platforms across thousands of miles of terrain. To effectively incorporate CPR personnel into a military transport team model, we recommend including cross-training on equipment and formularies, familiarization with CPR evacuation platforms, and mass casualty (MASCAL) exercises that incorporate the different platforms available., (2021.)
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- 2021
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16. Guiding principles for determining work shift duration and addressing the effects of work shift duration on performance, safety, and health: guidance from the American Academy of Sleep Medicine and the Sleep Research Society.
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Gurubhagavatula I, Barger LK, Barnes CM, Basner M, Boivin DB, Dawson D, Drake CL, Flynn-Evans EE, Mysliwiec V, Patterson PD, Reid KJ, Samuels C, Shattuck NL, Kazmi U, Carandang G, Heald JL, and Van Dongen HPA
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- Fatigue etiology, Humans, Personnel Staffing and Scheduling, Sleep physiology, United States, Sleep Disorders, Circadian Rhythm complications, Work Schedule Tolerance physiology
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Risks associated with fatigue that accumulates during work shifts have historically been managed through working time arrangements that specify fixed maximum durations of work shifts and minimum durations of time off. By themselves, such arrangements are not sufficient to curb risks to performance, safety, and health caused by misalignment between work schedules and the biological regulation of waking alertness and sleep. Science-based approaches for determining shift duration and mitigating associated risks, while addressing operational needs, require: (1) a recognition of the factors contributing to fatigue and fatigue-related risks; (2) an understanding of evidence-based countermeasures that may reduce fatigue and/or fatigue-related risks; and (3) an informed approach to selecting workplace-specific strategies for managing work hours. We propose a series of guiding principles to assist stakeholders with designing a shift duration decision-making process that effectively balances the need to meet operational demands with the need to manage fatigue-related risks., (© This article has been co-published with permission in SLEEP® and JOURNAL OF CLINICAL SLEEP MEDICINE. All rights reserved in respect of SLEEP®, © Sleep Research Society 2021, and in respect of JOURNAL OF CLINICAL SLEEP MEDICINE, © American Academy of Sleep Medicine 2021. The articles are identical except for minor differences in keeping with each journal’s style. Either citation can be used when citing this article. Published by Oxford University Press on behalf of the Sleep Research Society. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2021
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17. Myxozoan parasites vary in river herring according to life history stage and habitat.
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Friend SE, Lewis NL, and Lovy J
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- Animals, Ecosystem, Fishes, Life Cycle Stages, Rivers, Fish Diseases epidemiology, Parasites
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Anadromous river herring have declined in many parts of their range, leading to fisheries management efforts to help repopulate this species by improving connectivity of rivers and restoring populations by fish transfers. With data lacking on parasites in these species, this study sought to better understand myxozoans across various life stages and habitats in river herring populations in New Jersey, USA. We compared fish from riverine habitats during early-life growth and adults returning to spawn, marine-phase fish, and landlocked Alewife populations. Three myxozoan species were identified in young-of-the-year (YOY) anadromous river herring, including Kudoa clupeidae in the skeletal musculature, Myxobolus mauriensis in the rib cartilage, and an uncharacterized coelozoic myxozoan within the lumen of mesonephric tubules. In YOY river herring, Blueback Herring were 2 times more likely to be infected by K. clupeidae than Alewife (p = 0.019) and in the Maurice River, fish were 4 times more likely to be infected with M. mauriensis than fish from Great Egg Harbor River (p = 0.000) and 11 times more likely than the Delaware River (p = 0.001). Spawning adult river herring were infected with a previously undescribed myxozoan parasite infecting the kidney. Sequencing the 18S rDNA indicated this species is closely related to Ortholinea species. Myxobolus mauriensis and the Ortholinea-like species were absent from marine-phase river herring indicating that infections were linked to river environments occurring during early-life growth and spawning, respectively. No myxozoans were present in landlocked Alewife, showing that similar infections occurring in rivers were absent in lake environments in the region., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2021
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18. My Experience With Ptyalism Gravidarum During the COVID-19 Pandemic.
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Mchenga NL
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- Female, Humans, Pandemics, Pregnancy, Pregnancy Complications, SARS-CoV-2, Sialorrhea psychology, COVID-19, Hyperemesis Gravidarum, Sialorrhea etiology
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An immigrant woman and nurse describes her experience of ptyalism gravidarum in the United States during the COVID-19 pandemic., (Copyright © 2021 AWHONN. Published by Elsevier Inc. All rights reserved.)
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- 2021
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19. Habitability in Berthing Compartments and Well-Being of Sailors Working on U.S. Navy Surface Ships.
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Matsangas P and Shattuck NL
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- Fatigue epidemiology, Humans, Longitudinal Studies, Sleep, Military Personnel, Ships
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Objective: The study had two objectives: (a) to assess the prevalence of sleep-related habitability concerns in the berthing compartments of U.S. Navy surface ships and (b) to assess whether habitability issues in berthing compartments affected the sleep and well-being of crew members., Background: The importance of habitability for human well-being is recognized. Little is known, however, about the association between habitability factors in the sleeping/berthing compartments and sailor well-being in operational conditions., Method: Fit-for-duty sailors ( N = 1,269; from six ships) participated in this naturalistic and longitudinal study. Sailors reported habitability factors affecting their sleep and completed four standardized questionnaires to assess daytime sleepiness, insomnia, sleep quality, and mood. Sleep was assessed through wrist-worn actigraphy and activity logs., Results: Noise, ambient temperature, poor bedding conditions, and ambient light were the most frequently reported factors of concern. Compared to their peers with fewer complaints, sailors with more habitability-related complaints were more likely to have elevated daytime sleepiness (by 23%) and to report insomnia symptoms (145%) and lower sleep quality (21%). Sailors who reported more habitability-related issues also tended to sleep longer. Individuals with more complaints about habitability also tended to report worse mood (total mood disturbance, tension/anxiety, depression, fatigue, and confusion/bewilderment)., Conclusion: Habitability-related complaints are associated with sailor well-being and sleep. Future studies should expound on the various detrimental factors that degrade conditions in berthing compartments and negatively impact crew well-being., Application: Habitability in berthing compartments of surface ships is associated with sailors' daytime sleepiness, insomnia severity, mood, and sleep attributes. Ship designers should take these findings into consideration and investigate viable and cost-effective methods to mitigate the problems we identified.
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- 2021
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20. Eating behaviors in sailors of the United States Navy: Meal-to-sleep intervals.
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Shattuck NL and Matsangas P
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- Adult, Circadian Rhythm, Female, Humans, Male, Personnel Staffing and Scheduling, Time Factors, United States, Feeding Behavior, Meals, Military Personnel, Sleep
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Background: Due to their long workdays and erratic watch schedules, sailors on United States Navy (USN) ships often eat meals close to their bedtime, which may contribute to sleep disruption., Aim: To assess the duration of meal-to-sleep (M-S) intervals in relation to timing of sailor workdays and watch schedules., Methods: Longitudinal field assessment of USN sailors performing their underway duties ( N = 234). Participants completed questionnaires, wore actigraphs, and completed activity logs., Results: Approximately 35% of M-S intervals were <3 h in duration. M-S interval duration was associated with watchstanding status ( p < 0.001) and the number of sections in the watchstanding schedule ( p < 0.001). Sailors on the two-section watch schedule had, on average, the shortest M-S intervals (55 min) compared to sailors on three- or four-section watchbills (∼4 h) and to non-watchstanders (4.85 h)., Conclusion: Sailors on two-section watchbills often eat quite close to bedtime. To provide appropriate recommendations regarding healthy dietary patterns, we will continue assessing dietary behaviors and food choices of sailors while underway, especially as they relate to sailor work hours, circadian rhythms, and sleep practices.
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- 2021
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21. ER stress preconditioning ameliorates liver damage after hemorrhagic shock and reperfusion.
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Obert DP, Wolpert AK, Grimm NL, and Korff S
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The mismatch of oxygen supply and demand during hemorrhagic shock disturbs endoplasmic reticulum (ER) homeostasis. The resulting accumulation of unfolded proteins in the ER lumen, which is a condition that is defined as ER stress, triggers the unfolded protein response (UPR). Since the UPR influences the extent of organ damage following hemorrhagic shock/reperfusion (HS/R) and mediates the protective effects of stress preconditioning before ischemia-reperfusion injury, the current study investigated the mechanisms of ER stress preconditioning and its impact on post-hemorrhagic liver damage. Male C56BL/6-mice were injected intraperitoneally with the ER stress inductor tunicamycin (TM) or its drug vehicle 48 h prior to being subjected to a 90 min pressure-controlled hemorrhagic shock (30±5 mmHg). A period of 14 h after hemorrhagic shock induction, mice were sacrificed. Hepatocellular damage was quantified by analyzing hepatic transaminases and hematoxylin-eosin stained liver tissue sections. Additionally, the topographic expression patterns of the ER stress marker binding immunoglobulin protein (BiP), UPR signaling pathways, and the autophagy marker Beclin1 were evaluated. TM injection significantly increased BiP expression and modified the topographic expression patterns of the UPR signaling proteins. In addition, immunohistochemical analysis of Beclin1 revealed an increased pericentral staining intensity following TM pretreatment. The histologic analysis of hepatocellular damage demonstrated a significant reduction in cell death areas in HS/R+TM (P=0.024). ER stress preconditioning influences the UPR and alleviates post-hemorrhagic liver damage. The beneficial effects were, at least partially, mediated by the upregulation of BiP and autophagy induction. These results underscore the importance of the UPR in the context of HS/R and may help identify novel therapeutic targets., (Copyright: © Obert et al.)
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- 2021
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22. Using Lean Six Sigma techniques to improve efficiency in outpatient ophthalmology clinics.
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Kam AW, Collins S, Park T, Mihail M, Stanaway FF, Lewis NL, Polya D, Fraser-Bell S, Roberts TV, and Smith JEH
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- Ambulatory Care Facilities, Appointments and Schedules, Efficiency, Organizational, Humans, Outpatients, Ophthalmology standards, Total Quality Management
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Background: Increasing patient numbers, complexity of patient management, and healthcare resource limitations have resulted in prolonged patient wait times, decreased quality of service, and decreased patient satisfaction in many outpatient services worldwide. This study investigated the impact of Lean Six Sigma, a service improvement methodology originally from manufacturing, in reducing patient wait times and increasing service capacity in a publicly-funded, tertiary referral outpatient ophthalmology clinic., Methods: This quality improvement study compared results from two five-months audits of operational data pre- and post-implementation of Lean Six Sigma. A baseline audit was conducted to determine duration and variability of patient in-clinic time and number of patients seen per clinic session. Staff interviews and a time-in-motion study were conducted to identify issues reducing clinic service efficiency. Solutions were developed to address these root causes including: clinic schedule amendments, creation of dedicated postoperative clinics, and clear documentation templates. A post-implementation audit was conducted, and the results compared with baseline audit data. Significant differences in patient in-clinic time pre- and post-solution implementation were assessed using Mann-Whitney test. Differences in variability of patient in-clinic times were assessed using Brown-Forsythe test. Differences in numbers of patients seen per clinic session were assessed using Student's t-test., Results: During the baseline audit period, 19.4 patients were seen per 240-minute clinic session. Median patient in-clinic time was 131 minutes with an interquartile range of 133 minutes (84-217 minutes, quartile 1- quartile 3). Targeted low/negligible cost solutions were implemented to reduce in-clinic times. During the post-implementation audit period, the number of patients seen per session increased 9% to 21.1 (p = 0.016). There was significant reduction in duration (p < 0.001) and variability (p < 0.001) of patient in-clinic time (median 107 minutes, interquartile range 91 minutes [71-162 minutes])., Conclusions: Lean Six Sigma techniques may be used to reduce duration and variability of patient in-clinic time and increase service capacity in outpatient ophthalmology clinics without additional resource input.
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- 2021
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23. Sleep quality, occupational factors, and psychomotor vigilance performance in the U.S. Navy sailors.
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Matsangas P and Shattuck NL
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- Adult, Female, Humans, Male, Psychomotor Performance, Reaction Time, Sleep, Surveys and Questionnaires, Wakefulness, Military Personnel
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Study Objectives: This field study (a) assessed sleep quality of sailors on the U.S. Navy (USN) ships while underway, (b) investigated whether the Pittsburgh Sleep Quality Index (PSQI) scores were affected by occupational factors and sleep attributes, and (c) assessed whether the PSQI could predict impaired psychomotor vigilance performance., Methods: Longitudinal field assessment of fit-for-duty USN sailors performing their underway duties (N = 944, 79.0% males, median age 26 years). Participants completed questionnaires, wore actigraphs, completed logs, and performed the wrist-worn 3-min Psychomotor Vigilance Task (PVT)., Results: Sailors slept on average 6.60 ± 1.01 h/day with 86.9% splitting their sleep into more than one episode/day. The median PSQI Global score was 8 (interquartile range [IQR] = 5); 80.4% of the population were classified as "poor sleepers" with PSQI scores >5. PSQI scores were affected by sailor occupational group, rank, daily sleep duration, and number of sleep episodes/day. Sleep quality showed a U-shape association with daily sleep duration due to the confounding effect of split sleep. Sailors with PSQI scores >9 had 21.1% slower reaction times (p < 0.001) and 32.8%-61.5% more lapses combined with false starts (all p < 0.001) than sailors with PSQI scores ≤9. Compared to males and officers, females and enlisted personnel had 86% and 23% higher risk, respectively, of having PSQI scores >9. Sailors in the PSQI > 9 group had more pronounced split sleep., Conclusions: Working on Navy ships is associated with elevated PSQI scores, a high incidence of poor sleep, and degraded psychomotor vigilance performance. The widely used PSQI score>5 criterion should be further validated in active-duty service member populations., (Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2020.)
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- 2020
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24. Does the quality of life differ for shift workers compared to day workers?
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Shattuck NL and Matsangas P
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- Circadian Rhythm, Female, Humans, Male, Quality of Life, Sleep, United States, Disorders of Excessive Somnolence, Sleep Initiation and Maintenance Disorders
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It is often assumed the quality of life of dayworkers is better than that of shiftworkers. Our findings from United States Navy (USN) sailors (N = 804, 78.4% males) showed dayworkers slept better, were less sleepy, and reported greater vigor and reduced fatigue (Profile of Mood States) than shiftworkers. Nevertheless, ~25% of dayworkers slept <6.5 h/d, ~62% had split sleep, 31% reported excessive daytime sleepiness (EDS), and ~64% were poor sleepers (Pittsburgh Sleep Quality Index). The two groups had similar sleep-related behaviors, rates of insomnia, comorbid EDS/insomnia, and scores on total mood disturbance, tension/anxiety, depression, anger/hostility, and confusion/bewilderment. The findings of our study indicate shipboard sleep-related issues are prevalent among USN sailors.
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- 2020
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25. Hand-Held and Wrist-Worn Field-Based PVT Devices vs. the Standardized Laptop PVT.
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Matsangas P and Shattuck NL
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- Actigraphy, Adult, Hand physiology, Humans, Middle Aged, Sleep physiology, Smartphone, Wearable Electronic Devices, Wrist physiology, Young Adult, Psychometrics instrumentation, Psychometrics methods, Psychomotor Performance
- Abstract
BACKGROUND: Given the challenges of collecting reliable Psychomotor Vigilance Task (PVT) data in the field, this study compared a 3-min PVT on a hand-held device and wrist-worn device vs. a standardized laptop. METHODS: The experiment utilized a randomized, repeated-measures design. Subjects ( N = 36) performed the PVT on a touch-screen, hand-held device (HHD), a wrist-worn device (WWD), and a standardized laptop (L). Sleep was assessed using wrist-worn actigraphy. RESULTS: Compared to the L, the HHD was slower on average (∼50% longer reaction times; ∼34% slower response speeds; ∼600% more lapses in attention combined with false starts) and introduced a proportional bias that decreased the range of response speeds by 60%. Compared to the L, the WWD with the backlight on was faster on average (reaction time: ∼6%; response speed: ∼13%), but equivalent in lapses combined with false starts, and introduced a proportional bias that increased the range of responses by 60%. DISCUSSION: Compared to the L PVT, using a hand-held, touch screen interface to collect PVT data may introduce a large constant bias and a proportional bias that decreases the range of response speed. However, performance on the WWD closely mirrors performance on the L PVT and the proportional bias tends to be in favor of detecting individuals with slower responses. Researchers should avoid comparing PVT metrics between different device types. Reliability of PVT data from a WWD or HHD may be degraded when used in an operational setting with unpredictable environmental movement (such as a surface maritime setting). Matsangas P, Shattuck NL. Hand-held and wrist-worn field-based PVT devices vs. the standardized laptop PVT . Aerosp Med Hum Perform. 2020; 91(5):409-415.
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- 2020
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26. Sleep-Related Practices, Behaviors, and Sleep-Related Difficulties in Deployed Active-Duty Service Members Performing Security Duties.
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Matsangas P, Shattuck NL, and Saitzyk A
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- Adult, Female, Humans, Male, Young Adult, Military Personnel psychology, Sleep Initiation and Maintenance Disorders psychology
- Abstract
Objective : To assess sleep-related difficulties (e.g., trouble staying asleep, oversleeping, falling asleep while on duty, disturbing dreams, sleep paralysis) and behavioral patterns of active-duty service members (ADSMs) performing security duties. Participants : The participants were 1,169 ADSMs (20-44 years of age). Methods : ADSMs completed an online survey (67.3% response rate) with items assessing demographics, the occupational environment, sleep-related attributes, habits, or difficulties, factors affecting sleep, aids and techniques used to improve sleep, and the use of sleep-related products. Results : ADSMs reported sleeping ~6.5 hr/day (~56% reported sleeping < 6 hr). Sleep-related difficulties were reported by ~72% of the ADSMs (i.e., 55.1% had problems staying asleep, 33.1% reported experiencing sleep paralysis, 25.6% reported oversleeping, 21.6% had disturbing dreams, and 4.79% reported falling asleep while on duty). Daily sleep duration and quality, occupational factors (shift work, operational commitments, collateral duties, habitability, taking antimalarial medication, years deployed), and personal factors or behaviors (history of sleep problems, problems in personal life, late exercise times, altering sleep schedule to talk or text with family or friends) were associated with sleep-related difficulties. Some ADSMs reported using alcohol (~14%) or exercising prior to bedtime (~34%) in an attempt to fall sleep faster. Conclusions : We identified a high prevalence of sleep-related difficulties in our military sample. Even though most ADSMs used sleep hygiene practices to improve their sleep, some ADSMs used methods not recommended. Improving ADSMs' daily schedule (to include periods for exercising, and protected sleep periods), and further emphasis on sleep hygiene practices may be viable methods to reinforce behaviors promoting healthy sleep and improve performance.
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- 2020
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27. Developing a Hospital-Based Postpartum Depression Education Intervention for Perinatal Nurses.
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Lewis NL
- Subjects
- Adult, Aged, Depression, Postpartum psychology, Education, Nursing, Continuing trends, Educational Measurement methods, Female, Georgia, Humans, Middle Aged, Neonatal Nursing methods, Surveys and Questionnaires, Depression, Postpartum therapy, Education, Nursing, Continuing methods, Neonatal Nursing education
- Abstract
Perinatal nurses in the hospital setting have prolonged contact with new mothers and are in a vital position to provide postpartum depression patient education. This study describes the development and implementation of an education intervention that led to nurses' increased knowledge and provision of postpartum depression patient education. The framework can be utilized by nursing professional development practitioners to develop staff education programs to improve patient education in various clinical settings.
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- 2020
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28. Clinical significance of T cell receptor excision circle (TREC) quantitation after allogenic HSCT.
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Mikhael NL and Elsorady M
- Abstract
Background: Hematopoietic stem cell transplantation (HSCT) is a well-established treatment modality for a variety of diseases. Immune reconstitution is an important event that determines outcomes. The immune recovery of T cells relies on peripheral expansion of mature graft cells, followed by differentiation of donor-derived hematopoietic stem cells. The formation of new T cells occurs in the thymus and as a byproduct, T cell receptor excision circles (TRECs) are released. Detection of TRECs by PCR is a reliable method for estimating the amount of newly formed T cells in the circulation and, indirectly, for estimating thymic function. The aim of this study was to determine the role of TREC quantitation in predicting outcomes of human leucocyte antigen (HLA) identical allogenic HSCT., Methods: The study was conducted on 100 patients receiving allogenic HSCT from an HLA identical sibling. TREC quantification was done by real time PCR using a standard curve., Results: TREC levels were inversely related to age ( P =0.005) and were significantly lower in patients with malignant diseases than in those with benign diseases ( P =0.038). TREC levels could predict relapse as an outcome but not graft versus host disease (GvHD) and infections., Conclusion: Age and nature of disease determine the TREC levels, which are related to relapse., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported., (© 2019 Korean Society of Hematology.)
- Published
- 2019
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29. Seasonal intestinal coccidiosis in wild bluegill Lepomis macrochirus is associated with a spring bacterial epizootic.
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Lovy J, Friend SE, and Lewis NL
- Subjects
- Animals, Bacteremia mortality, Bacteremia veterinary, Coccidiosis microbiology, Coccidiosis pathology, Cold Temperature, Fish Diseases mortality, Intestinal Diseases, Parasitic diagnosis, Intestinal Diseases, Parasitic microbiology, Perciformes microbiology, Pseudomonas pathogenicity, Pseudomonas Infections mortality, Pseudomonas Infections parasitology, Coccidiosis diagnosis, Fish Diseases microbiology, Fish Diseases parasitology, Intestinal Diseases, Parasitic veterinary, Perciformes parasitology, Pseudomonas Infections veterinary, Seasons
- Abstract
Wild bluegill, Lepomis macrochirus Rafinesque, succumb to seasonal mortality in the early spring during cool water temperatures, shown previously to be related to bacteraemia caused by a psychrotrophic bacterium, Pseudomonas mandelii. In the study herein, intestinal coccidiosis in wild bluegill had seasonal prevalence causing heavy intestinal infections and sloughing of intestinal epithelium occurring in late winter/early spring. Infections were predominantly related to two different species, Goussia washuti n. sp., an epicellular coccidium, and a coccidium closely resembling Goussia desseri Molnár 1996, previously only described in percid fish in Europe. In 2019, co-infections of bacteraemia and intestinal coccidiosis occurred in bluegills. Evaluating coccidium infection intensity by fresh parasite examination and histology, an association was observed in which fish with moderate-to-heavy intestinal coccidiosis were 8-12 times more likely to have bacteraemia compared to fish with no or light coccidiosis. The association of these co-infections suggests that intestinal coccidiosis could contribute to seasonal bacterial epizootics of wild bluegill., (© 2019 John Wiley & Sons Ltd.)
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- 2019
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30. Discriminating Between Fatigue and Sleepiness in the Naval Operational Environment.
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Matsangas P and Shattuck NL
- Subjects
- Adult, Disorders of Excessive Somnolence epidemiology, Female, Humans, Male, Retrospective Studies, Surveys and Questionnaires, Disorders of Excessive Somnolence etiology, Fatigue etiology, Military Personnel psychology, Sleepiness
- Abstract
Objective: To assess the similarities and differences between reported levels of fatigue and sleepiness as a consequence of working at sea., Participants: 767 crewmembers of a U.S. Navy ship., Methods: Retrospective analysis of a survey to include questions about demographics, caffeine consumption, sleep adequacy, the Epworth Sleepiness Scale (ESS), and the Fatigue Severity Scale (FSS)., Results: ESS scores (8.41 ± 4.66) indicated that 32% of the participants had excessive daytime sleepiness (ESS score > 10), while approximately 7% had an ESS score of 16 or more. FSS scores (average FSS = 3.01 ± 1.37) indicated that 28% of the participants had elevated fatigue (FSS score ≥ 4). Even though ESS and FSS scores were correlated (r = 0.39), their association explained only 15% of the variability observed. In terms of behavioral and lifestyle patterns, crewmembers with elevated fatigue (FSS ≥ 4) reported getting less exercise than those reporting less fatigue. Individuals with excessive sleepiness (ESS > 10) reported higher caffeine consumption. Crewmembers with elevated fatigue and comorbid sleepiness (FSS ≥ 4 and ESS > 10) reported receiving less sleep than other crew members., Conclusions: These results suggest that subjective fatigue and subjective sleepiness, as measured by the FSS and ESS scales, are distinct constructs and both are consequences of working at sea. The scores on the two scales correlate differentially with behavioral and lifestyle patterns of the crewmembers.
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- 2018
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31. Preliminary validation study of the 3-min wrist-worn psychomotor vigilance test.
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Matsangas P, Shattuck NL, and Brown S
- Subjects
- Adult, Data Collection instrumentation, Female, Humans, Male, Microcomputers, Young Adult, Arousal physiology, Monitoring, Ambulatory instrumentation, Psychomotor Performance physiology, Reaction Time physiology, Wrist
- Abstract
The 10-min psychomotor vigilance test (PVT) is a widely used tool to assess behavioral alertness. In operational environments, however, the 3-min version of the PVT is more practicable. Under controlled laboratory conditions, we compared performance on the 3-min PVT on a wrist-worn device with the 3-min PVT on a laptop computer. We conducted two repeated measures experiments (72 participants) to assess the effects of PVT device type (laptop or wrist-worn), backlight on the wrist-worn device (on or off), ambient light (low or normal levels), and interstimulus interval (ISI). First, we compared the wrist-worn PVT (ISI of 2-10 s) with the laptop-based PVT (ISI of 1-4 s). Participants performed six PVT trials counterbalanced for order of ambient light and device type. In both ambient-lighting conditions, the median differences in PVT metrics (reaction time, response speed, and percentage of 355-ms or 500-ms lapses combined with false starts) between the laptop and the wrist-worn PVT with the backlight on were less than 4.5 %. Specifically, the median difference in reaction times was less than 10 ms. However, the standard deviation in most metrics using the wrist-worn PVT was twice that of the laptop. In a second experiment, we compared the wrist-worn and laptop PVTs with the same ISIs (1-4 s) in normal light conditions. The results suggest that PVT data can be collected reliably in the field using the wrist-worn device with the backlight on and an ISI of 2-10 s.
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- 2017
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32. Operational assessment of the 5-h on/10-h off watchstanding schedule on a US Navy ship: sleep patterns, mood and psychomotor vigilance performance of crewmembers in the nuclear reactor department.
- Author
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Shattuck NL and Matsangas P
- Subjects
- Adult, Fatigue physiopathology, Female, Humans, Job Satisfaction, Male, Nuclear Reactors, Personnel Staffing and Scheduling, Reaction Time, Ships, Surveys and Questionnaires, Young Adult, Affect, Arousal, Military Personnel, Psychomotor Performance, Sleep, Sleep Deprivation physiopathology, Sleep Disorders, Circadian Rhythm physiopathology, Work Schedule Tolerance
- Abstract
We assessed sleep patterns, psychomotor vigilance performance, work demands and mood of 77 crewmembers of USS NIMITZ (CVN-68) on the rotating 5-h on/10-h off (5/10) watchstanding schedule. Within the 3-day cycle of the 5/10, sleep occurred at distinctly different times each day. On two of these days, sailors typically received only brief, 4-h sleep episodes followed by periods of sustained wakefulness (approximately 22 and 20 h). Crewmembers received approximately seven hours of sleep daily, but reported excessive fatigue and dissatisfaction with their schedule. Crewmembers' mood worsened significantly over the course of the underway phase. Psychomotor vigilance performance (reaction times, lapses) was significantly degraded compared to performance when working circadian-aligned schedules. Overall, standing watch on the 5/10 schedule, combined with other work duties, resulted in poor sleep hygiene. Crewmembers on the 5/10 experienced periodic bouts of sustained wakefulness and accrued a significant sleep debt due to extended workdays and circadian-misaligned sleep. Practitioner summary: We assessed crewmembers' sleep patterns, psychomotor vigilance performance and work demands when working a rotating 5-h on/10-h off (5/10) watchstanding schedule. The 5/10, combined with other work duties, resulted in poor sleep hygiene. Crewmembers experienced periodic bouts of sustained wakefulness and accrued a significant sleep debt due to extended workdays and circadian-misaligned sleep.
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- 2016
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33. Comparison of Two Watch Schedules for Personnel at the White House Military Office President's Emergency Operations Center.
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Shattuck NL, Matsangas P, Eriksen E, and Kulubis S
- Subjects
- Adult, Affect, Female, Humans, Male, Sleep Deprivation, Sleep Disorders, Circadian Rhythm, United States, Military Personnel, Morale, Personnel Staffing and Scheduling, Sleep, Work Schedule Tolerance
- Abstract
Objective: The aim of this study was to assess effectiveness of an alternative, 24-hr-on/72-hr-off watchstanding schedule on sleep and morale of personnel assigned to the President's Emergency Operations Center (PEOC)., Background: As part of the White House Military Office, PEOC personnel historically worked a 12-hr "Panama" watch schedule. Personnel reported experiencing chronic insufficient and disrupted sleep patterns and sought advice for improving their watchstanding schedule., Method: Participants (N = 14 active-duty military members, ages 29 to 42 years) completed the Profile of Mood State (POMS) three times: before, during, and after switching to the alternative schedule with 5-hr sleep periods built into their workday. Participants completed a poststudy questionnaire to assess individual schedule preferences. Sleep was measured actigraphically, supplemented by activity logs., Results: As indicated by POMS scores, mood improved significantly on the new schedule. Although average total sleep amount did not change substantively, the timing of sleep was more consistent on the new schedule, resulting in better sleep hygiene. PEOC personnel overwhelmingly preferred the new schedule, reporting not only that they felt more rested but that the new schedule was more conducive to the demands of family life., Conclusions: Demands of family life and time spent commuting were found to be critical factors for acceptance of the alternative schedule. This new schedule will be most effective if personnel adhere to the scheduled rest periods assigned during their 24-hr duty., Application: A successful schedule should avoid conflicts between social life and operational demands. Results may lead to changes in the work schedules of other departments with similar 24/7 responsibilities., (© 2015, Human Factors and Ergonomics Society.)
- Published
- 2015
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34. A 6-month assessment of sleep during naval deployment: a case study of a commanding officer.
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Shattuck NL and Matsangas P
- Subjects
- Actigraphy, Adult, Humans, Male, Wakefulness, Work Schedule Tolerance, Fatigue physiopathology, Military Personnel, Occupational Diseases physiopathology, Ships, Sleep Deprivation physiopathology
- Abstract
Background: Sleep deprivation is known to be a common problem in the U.S. Navy and has been documented using wrist-worn actigraphy in various operational studies that typically span 2 to 4 wk in duration. However, sleep patterns over an extended period of time have not been objectively measured., Case Report: This 6-mo study used actigraphy and the Fatigue Avoidance Scheduling Tool (FAST) to quantify the sleep patterns of a 39-yr-old Commanding Officer (CO) of an Arleigh Burke class destroyer while the ship was forward-deployed. On average, the CO received 5.2 h of sleep daily and averaged 6 h time in bed each day. The participant received more than 8 h of sleep for only 2% (N = 3) of the study days; for 17% (N = 27) of the days, he received less than 4 h of daily sleep. For 15% of waking time, the CO had a predicted effectiveness of less than 70% on the FAST scale, equating to a blood alcohol equivalent of 0.08%-or legally drunk. The CO's predicted effectiveness was below 65% approximately 10% of waking time., Discussion: Results from this study are aligned with earlier research showing that crewmembers on U.S. Navy ships suffer from chronic sleep restriction. During a typical deployment, personnel accrue a considerable sleep debt even during normal operations. Should critical events with additional sleep restriction occur, the ship has limited reserve capacity, potentially placing her crew and their mission in grave jeopardy.
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- 2015
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35. Psychomotor vigilance performance predicted by Epworth Sleepiness Scale scores in an operational setting with the United States Navy.
- Author
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Shattuck NL and Matsangas P
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Reaction Time physiology, Time Factors, United States, Young Adult, Attention physiology, Military Personnel psychology, Psychomotor Performance physiology, Sleep Deprivation diagnosis, Sleep Deprivation physiopathology, Sleep Stages physiology
- Abstract
It is critical in operational environments to identify individuals who are at higher risk of psychomotor performance impairments. This study assesses the utility of the Epworth Sleepiness Scale for predicting degraded psychomotor vigilance performance in an operational environment. Active duty crewmembers of a USA Navy destroyer (N = 69, age 21-54 years) completed the Epworth Sleepiness Scale at the beginning of the data collection period. Participants wore actigraphs and completed sleep diaries for 11 days. Psychomotor vigilance tests were administered throughout the data collection period using a 3-min version of the psychomotor vigilance test on the actigraphs. Crewmembers with elevated scores on the Epworth Sleepiness Scale (i.e. Epworth Sleepiness Scale >10) had 60% slower reaction times on average, and experienced at least 60% more lapses and false starts compared with individuals with normal Epworth Sleepiness Scale scores (i.e. Epworth Sleepiness Scale ≤ 10). Epworth Sleepiness Scale scores were correlated with daily time in bed (P < 0.01), sleep (P < 0.05), mean reaction time (P < 0.001), response speed 1/reaction time (P < 0.05), slowest 10% of response speed (P < 0.001), lapses (P < 0.01), and the sum of lapses and false starts (P < 0.001). In this chronically sleep-deprived population, elevated Epworth Sleepiness Scale scores identified that subset of the population who experienced degraded psychomotor vigilance performance. We theorize that Epworth Sleepiness Scale scores are an indication of personal sleep debt that varies depending on one's individual sleep requirement. In the absence of direct performance metrics, we also advocate that the Epworth Sleepiness Scale can be used to determine the prevalence of excessive sleepiness (and thereby assess the risk of performance decrements)., (© 2014 European Sleep Research Society.)
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- 2015
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36. A phase II trial of the proteasome inhibitor bortezomib in patients with advanced biliary tract cancers.
- Author
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Denlinger CS, Meropol NJ, Li T, Lewis NL, Engstrom PF, Weiner LM, Cheng JD, Alpaugh RK, Cooper H, Wright JJ, and Cohen SJ
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma pathology, Adult, Aged, Antineoplastic Agents adverse effects, Antineoplastic Agents therapeutic use, Bile Duct Neoplasms pathology, Bile Ducts, Intrahepatic pathology, Boronic Acids adverse effects, Bortezomib, Cholangiocarcinoma drug therapy, Cholangiocarcinoma pathology, Disease Progression, Female, Follow-Up Studies, Gallbladder Neoplasms pathology, Humans, Male, Middle Aged, Proteasome Inhibitors adverse effects, Pyrazines adverse effects, Survival Rate, Time Factors, Treatment Outcome, Bile Duct Neoplasms drug therapy, Boronic Acids therapeutic use, Gallbladder Neoplasms drug therapy, Proteasome Inhibitors therapeutic use, Pyrazines therapeutic use
- Abstract
Background: Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest that proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers., Patients and Methods: Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0 to 2 previous therapies received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 of a 21-day cycle. The primary end point was objective response rate. A Simon 2-stage design was used (null response rate of < 5% and response rate of ≥ 20% of interest)., Results: Twenty patients enrolled (bile duct/gallbladder cancer [14/6] and previous treatments 0/1/2 [10/6/3]). The trial was discontinued early because of lack of confirmed partial responses. No unanticipated adverse events were noted. There was 1 unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% confidence interval [CI], 0.7-77.6 months). Median survival was 9 months (95% CI, 4.6-18.5 months). The 6-month and 1-year survival rates were 70% and 38%, respectively. There was no difference in survival based on primary disease site., Conclusion: Single-agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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37. A Phase I trial of the kinesin spindle protein (Eg5) inhibitor AZD4877 in patients with solid and lymphoid malignancies.
- Author
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Gerecitano JF, Stephenson JJ, Lewis NL, Osmukhina A, Li J, Wu K, You Z, Huszar D, Skolnik JM, and Schwartz GK
- Subjects
- Adult, Aged, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Infusions, Intravenous, Male, Maximum Tolerated Dose, Middle Aged, Prognosis, Tissue Distribution, Benzamides pharmacokinetics, Benzamides therapeutic use, Kinesins antagonists & inhibitors, Lymphoma, B-Cell drug therapy, Neoplasms drug therapy, Pyrimidinones pharmacokinetics, Pyrimidinones therapeutic use
- Abstract
Background: This Phase I study assessed the safety and maximum tolerated dose (MTD) of the kinesin spindle protein inhibitor AZD4877 in patients with relapsed/refractory solid tumors and lymphoma., Methods: In this multicenter study, a standard 3 + 3 dose-escalation design was used. AZD4877 was given as an intravenous infusion on days 1, 4, 8 and 11 of each 21-day cycle. Responses were assessed with CT scans +/- PET after 6 and 12 weeks, then every 12 weeks while on therapy. An additional four patients with lymphoma were enrolled at the MTD., Results: 29 patients were enrolled and 22 patients received at least one dose of AZD4877 and were evaluable for safety. The MTD was 11 mg. Dose-limiting toxicity was neutropenia (n = 2 patients, 15 mg cohort). The most common adverse events were grade 1/2 fatigue, nausea, neutropenia and dyspnea. AZD4877 exposure generally increased with dose, with mean elimination half-life approximately 16 h at the MTD. Pharmacodynamic analyses demonstrated moderate correlation between plasma drug concentrations at 6 or 24 h and monoaster formation in peripheral blood mononuclear cells (PBMCs)., Conclusions: AZD4877 is generally well-tolerated with pharmacodynamic evidence of target inhibition in circulating PBMCs.
- Published
- 2013
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38. A Phase I, open-label, dose escalation study of afatinib, in a 3-week-on/1-week-off schedule in patients with advanced solid tumors.
- Author
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Marshall J, Hwang J, Eskens FA, Burger H, Malik S, Uttenreuther-Fischer M, Stopfer P, Ould-Kaci M, Cohen RB, and Lewis NL
- Subjects
- Afatinib, Aged, Aged, 80 and over, Cohort Studies, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Male, Maximum Tolerated Dose, Middle Aged, Prognosis, Tissue Distribution, Lymphoma, B-Cell drug therapy, Neoplasms drug therapy, Quinazolines pharmacokinetics, Quinazolines therapeutic use
- Abstract
Background: A Phase I study to determine the maximum tolerated dose (MTD) and pharmacokinetics of afatinib (BIBW 2992), a novel irreversible ErbB Family Blocker, administered orally once daily in a 3-week-on/1-week-off dosing schedule., Methods: Patients with advanced solid tumors received single-agent afatinib at 10, 20, 40, 55 or 65 mg/day. Safety, antitumor activity, pharmacokinetics and pharmacodynamic modulation of biomarkers were assessed., Results: Forty-three patients were enrolled. Dose-limiting toxicities (DLTs) occurred in five patients in the dose escalation phase (1/8 at 40 mg/day; 1/6 at 55 mg/day; 3/6 at 65 mg/day). The MTD was established at 55 mg/day. In the expansion cohort at the MTD, 6 patients experienced a DLT in the first 28-day treatment period. The most frequent DLT was diarrhea. The most common adverse events were diarrhea, rash, nausea, vomiting and fatigue. Overall, the afatinib safety profile in a 3-week-on/1-week-off dose schedule was similar to that of our daily-continuous schedule. Afatinib displayed dose-dependent pharmacokinetics at doses up to and including 55 mg/day, with a terminal half-life suitable for once-daily dosing. Signs of clinical antitumor activity were observed. In biopsies taken from clinically normal forearm skin, afatinib caused a reduced proliferation rate, with a concomitant increase in differentiation of epidermal keratinocytes., Conclusion: Afatinib in a 3-week-on/1-week-off schedule showed a good safety profile. The MTD was 55 mg/day, although excess DLTs in the expansion cohort indicated that the 40 mg/day dose would have an acceptable safety profile for future studies. Dose cohorts between 40 and 55 mg/day were not examined in this study.
- Published
- 2013
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39. Tacrolimus-associated thrombotic microangiopathy in a lung transplant recipient.
- Author
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Boyer NL, Niven A, and Edelman J
- Subjects
- Adult, Cystic Fibrosis surgery, Female, Humans, Lung Transplantation, Immunosuppressive Agents adverse effects, Tacrolimus adverse effects, Thrombotic Microangiopathies chemically induced
- Abstract
A 25-year-old woman with a history of bilateral lung transplant secondary to cystic fibrosis presented with non-specific abdominal complaints and was found to have acute kidney injury, thrombocytopaenia and laboratory findings consistent with a microangiopathic haemolytic anaemia. Her thrombotic microangiopathy (TMA) was attributed to tacrolimus, which was discontinued and replaced with cyclosporine with resolution of her TMA and no subsequent complications. This is the fifth reported case of TMA associated with tacrolimus use in a lung transplant patient, and the third to be successfully managed with cyclosporine substitution. Clinicians must be aware of this uncommon, but likely under-reported complication of tacrolimus therapy in lung transplant recipients. Cyclosporine replacement may be used as a successful therapy to treat tacrolimus-associated TMA without increasing the risk of acute rejection that may be associated with other treatment strategies.
- Published
- 2013
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40. Wounded in action: what the sleep community can learn from sleep disorders of US military service members.
- Author
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Shattuck NL and Brown SA
- Subjects
- Female, Humans, Male, Military Personnel statistics & numerical data, Sleep Wake Disorders epidemiology
- Published
- 2013
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41. A phase 1b study of humanized KS-interleukin-2 (huKS-IL2) immunocytokine with cyclophosphamide in patients with EpCAM-positive advanced solid tumors.
- Author
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Connor JP, Cristea MC, Lewis NL, Lewis LD, Komarnitsky PB, Mattiacci MR, Felder M, Stewart S, Harter J, Henslee-Downey J, Kramer D, Neugebauer R, and Stupp R
- Subjects
- Aged, Antigens, Neoplasm, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cell Adhesion Molecules metabolism, Dose-Response Relationship, Drug, Epithelial Cell Adhesion Molecule, Female, Humans, Interleukin-2 administration & dosage, Interleukin-2 adverse effects, Interleukin-2 pharmacokinetics, Male, Maximum Tolerated Dose, Middle Aged, Neoplasms immunology, Neoplasms metabolism, Survival Analysis, Antineoplastic Agents administration & dosage, Cyclophosphamide administration & dosage, Interleukin-2 analogs & derivatives, Neoplasms drug therapy
- Abstract
Background: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent., Methods: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated., Results: Twenty-seven patients were treated for up to 6 cycles; 26 were evaluable for response. The MTD of huKS-IL2 in combination with 300 mg/m2 cyclophosphamide was 3.0 mg/m2. At higher doses, myelosuppression was dose-limiting. Transient lymphopenia was the most common grade 3/4 adverse event (AE). Other significant AEs included hypotension, hypophosphatemia, and increase in serum creatinine. All patients recovered from these AEs. The huKS-IL2 exposure was dose-dependent, but not dose-proportional, accumulation was negligible, and elimination half-life and systemic clearance were independent of dose and time. Most patients had a transient immune response to huKS-IL2. Immunologic activity was observed at all doses. Ten patients (38%) had stable disease as best response, lasting for ≥ 4 cycles in 3 patients., Conclusion: The combination of huKS-IL2 with low-dose cyclophosphamide was well tolerated. Although no objective responses were observed, the combination showed evidence of immunologic activity and 3 patients showed stable disease for ≥ 4 cycles.
- Published
- 2013
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42. Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring.
- Author
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Lovy J, Lewis NL, Hershberger PK, Bennett W, Meyers TR, and Garver KA
- Subjects
- Animals, Fishes, Hemorrhagic Septicemia, Viral mortality, Kidney pathology, Kidney virology, Spleen pathology, Spleen virology, Time Factors, Viral Load, Hemorrhagic Septicemia, Viral pathology, Hemorrhagic Septicemia, Viral virology, Novirhabdovirus physiology, Viral Tropism
- Abstract
Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring., (Published by Elsevier B.V.)
- Published
- 2012
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43. Accommodating adolescent sleep-wake patterns: the effects of shifting the timing of sleep on training effectiveness.
- Author
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Miller NL, Tvaryanas AP, and Shattuck LG
- Subjects
- Actigraphy, Adolescent, Affect, Demography, Fatigue epidemiology, Fatigue physiopathology, Female, Firearms, Humans, Male, Mental Health statistics & numerical data, Missouri epidemiology, Physical Fitness, Sleep Wake Disorders epidemiology, Sleep Wake Disorders physiopathology, Time Factors, Learning, Military Personnel psychology, Psychomotor Performance physiology, Sleep physiology, Wakefulness physiology
- Abstract
Study Objective: This study evaluated the effect of accommodating adolescent sleep-wake patterns by altering the timing of the major sleep period of US Army recruits., Design: The quasi-experimental study compared recruits assigned to one of two training companies: one with a customary sleep regimen (20:30 to 04:30) while the other employed a phase-delayed sleep regimen (23:00 to 07:00), the latter aligning better with biologically driven sleep-wake patterns of adolescents., Setting: The study was conducted during Basic Combat Training (BCT) at Fort Leonard Wood, Missouri. TRAINEES: The study included 392 trainees: 209 received the intervention, while 183 composed the Comparison group., Measurements and Results: Demographic and psychophysiological measures were collected on all trainees. Weekly assessments of subjective fatigue and mood, periodic physical fitness, marksmanship scores, and attrition rates from BCT were studied. Actigraphy was collected on approximately 24% of trainees. Based on actigraphy, trainees on the phase-delayed sleep schedule obtained 31 m more sleep/night than trainees on the customary sleep schedule. The Intervention group reported less total mood disturbance relative to baseline. Improvements in marksmanship correlated positively with average nightly sleep during the preceding week when basic marksmanship skills were taught. No differences were seen in physical fitness or attrition rates. In contrast to the Intervention group, the Comparison group was 2.3 times more likely to experience occupationally significant fatigue and 5.5 times more likely to report poor sleep quality., Conclusions: Accommodating adolescent sleep patterns significantly improves mental health and performance in the training environment.
- Published
- 2012
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44. Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer.
- Author
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Michaelson MD, Bellmunt J, Hudes GR, Goel S, Lee RJ, Kantoff PW, Stein CA, Lardelli P, Pardos I, Kahatt C, Nieto A, Cullell-Young M, Lewis NL, and Smith MR
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Agents, Alkylating therapeutic use, Cohort Studies, Dioxoles adverse effects, Humans, Male, Middle Aged, Neoplasm Metastasis, Orchiectomy, Prostatic Neoplasms pathology, Prostatic Neoplasms surgery, Sarcoma pathology, Sarcoma surgery, Tetrahydroisoquinolines adverse effects, Trabectedin, Treatment Failure, Treatment Outcome, Dioxoles therapeutic use, Prostatic Neoplasms drug therapy, Sarcoma drug therapy, Tetrahydroisoquinolines therapeutic use
- Abstract
Background: This multicenter phase II trial evaluated the efficacy and safety of trabectedin in metastatic castration-resistant prostate cancer (CRPC)., Patients and Methods: Two schedules were evaluated in three cohorts: weekly as 3-h i.v. infusion at 0.58 mg/m(2) for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m(2) (Cohort B1, n = 5) and 1.2 mg/m(2) (Cohort B2, n = 20). The primary end point was prostate-specific antigen (PSA) response; secondary end points included safety, tolerability and time to progression (TTP)., Results: Trabectedin resulted in PSA declines ≥ 50% in 12.5% (Cohort A) and 10.5% (Cohort B2) of patients. Among men pretreated with taxane-based chemotherapy, PSA response was 13.6% (Cohort A) and 15.4% (Cohort B2). PSA responses lasted 4.1-8.6 months, and median TTP was 1.5 months (Cohort A) and 1.9 months (Cohort B2). The dose of 1.5 mg/m(2) (approved for soft tissue sarcoma) given as 24-h infusion q3wk was not tolerable in these patients. At 1.2 mg/m(2) q3wk and 0.58 mg/m(2) weekly, the most common adverse events were nausea, fatigue and transient neutropenia and transaminase increase., Conclusions: Two different trabectedin schedules showed modest activity in metastatic CRPC. Further studies may require identification of predictive factors of response in prostate cancer.
- Published
- 2012
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45. KREPB6, KREPB7, and KREPB8 are important for editing endonuclease function in Trypanosoma brucei.
- Author
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Guo X, Carnes J, Ernst NL, Winkler M, and Stuart K
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- Gene Knockdown Techniques methods, Mutagenesis, Insertional, Promoter Regions, Genetic, RNA, Messenger genetics, RNA, Mitochondrial, RNA, Protozoan genetics, Trypanosoma brucei brucei enzymology, Trypanosoma brucei brucei growth & development, Uridine metabolism, Endonucleases genetics, Endonucleases metabolism, Protozoan Proteins genetics, Protozoan Proteins metabolism, RNA Editing, Trypanosoma brucei brucei genetics, Trypanosoma brucei brucei metabolism
- Abstract
Three distinct editosomes are required for the uridine insertion/deletion editing that creates translatable mitochondrial mRNAs in Trypanosoma brucei. They contain KREPB6, KREPB7, or KREPB8 proteins and their respective endonucleases KREN3, KREN2, or KREN1. RNAi knockdowns of KREPB6, KREPB7, and KREPB8 variably affect growth and RNA editing. KREPB6 and KREPB7 knockdowns substantially reduced in vitro insertion site cleavage activity of their respective editosomes, while KREPB8 knockdown did not affect its editosome deletion site cleavage activity despite inhibition of growth and editing. KREPB6, KREPB7, and KREPB8 knockdowns disrupted tagged KREN3, KREN2, or KREN1 editosomes, respectively, to varying degrees, and in the case of KREN1 editosomes, the deletion editing site cleavage activity shifted to a smaller S value. The varying effects correlate with a combination of the relative abundances of the KREPB6-8 proteins and of the different insertion and deletion sites. Tagged KREPB6-8 were physically associated with deletion subcomplexes upon knockdown of the centrally interactive KREPA3 protein, while KREN1-3 endonucleases were associated with insertion subcomplexes. The results indicate that KREPB6-8 occupy similar positions in editosomes and are important for the activity and specificity of their respective endonucleases. This suggests that they contribute to the accurate recognition of the numerous similar but diverse editing site substrates.
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- 2012
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46. Sleep and fatigue issues in continuous operations: a survey of U.S. Army officers.
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Miller NL, Shattuck LG, and Matsangas P
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- Adult, Female, Humans, Judgment, Male, Policy, Sleep, Sleep Deprivation psychology, Surveys and Questionnaires, United States, Warfare, Workload, Young Adult, Fatigue psychology, Military Personnel psychology, Sleep Deprivation complications
- Abstract
Forty-nine U.S. Army officers with recent combat experience were surveyed to assess their units' sleep patterns and to determine the tactics, techniques, and procedures used to counter the effects of sleep deprivation in their units. Despite Army policy requiring units to develop and implement sleep management plans, nearly 80% of the participants reported they had not been briefed on a sleep management plan during their most recent deployment. Over one half of the respondents reported that fatigue was a problem in their units. During high operational tempo (OPTEMPO), which occupied nearly half of their time in combat, participants report receiving only 4 hr of sleep daily. The vast majority of respondents (82.6%) reported feeling sleep-deprived at least occasionally while at high OPTEMPO. These findings have important implications for the operational readiness of all military units deployed to combat environments.
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- 2011
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47. Longitudinal study of sleep patterns of United States Military Academy cadets.
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Miller NL, Shattuck LG, and Matsangas P
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- Adolescent, Age Factors, Female, Humans, Longitudinal Studies, Male, Military Personnel education, Seasons, Sex Factors, Sleep Deprivation physiopathology, Sleep Deprivation psychology, United States, Young Adult, Military Personnel psychology, Sleep Deprivation epidemiology, Students psychology
- Abstract
Study Objectives: The study provided an opportunity to observe sleep patterns in a college-age population attending the United States Military Academy., Design: This 4-year longitudinal study investigated sleep patterns of cadets. A stratified sample of 80 cadets had sleep patterns monitored using actigraphy for 8 months: one month in both fall and spring academic semesters over a 4-year period., Setting: Data were collected at the United States Military Academy, West Point, NY., Participants: Participants were members of the class of 2007 (n˜1300) ranging in age from 17 to 22 when entering USMA., Measurements and Results: A sample of the class (n=80) wore wrist activity monitors and completed activity logs for one month in fall and spring academic semesters for the 4-year period. On average over the 4 years, cadets slept<5.5 h on school nights. Cadets napped extensively, perhaps in an attempt to compensate for chronic sleep debt. Cadets slept more during fall than spring semesters. Male and female cadet sleep patterns varied dramatically, with males consistently receiving less sleep than females (˜21 m for nighttime sleep and ˜23 m for daily sleep)., Conclusions: Cadet sleep at USMA is related to academic year, semester, season, sex, school day or weekend, and day of the week. These students suffer from chronic sleep debt. Restrictions imposed by the military academy limit the generalizability of the findings to other college age populations.
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- 2010
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48. The zinc-fingers of KREPA3 are essential for the complete editing of mitochondrial mRNAs in Trypanosoma brucei.
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Guo X, Ernst NL, Carnes J, and Stuart KD
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- Animals, Mutation, Protozoan Proteins chemistry, Reverse Transcriptase Polymerase Chain Reaction, Ribonucleoproteins chemistry, Mitochondria genetics, Protozoan Proteins genetics, RNA Editing, RNA, Messenger genetics, Ribonucleoproteins genetics, Trypanosoma brucei brucei genetics, Zinc Fingers
- Abstract
Most mitochondrial mRNAs in trypanosomes undergo uridine insertion/deletion editing that is catalyzed by approximately 20S editosomes. The editosome component KREPA3 is essential for editosome structural integrity and its two zinc finger (ZF) motifs are essential for editing in vivo but not in vitro. KREPA3 function was further explored by examining the consequence of mutation of its N- and C-terminal ZFs (ZF1 and ZF2, respectively). Exclusively expressed myc-tagged KREPA3 with ZF2 mutation resulted in lower KREPA3 abundance and a relative increase in KREPA2 and KREL1 proteins. Detailed analysis of edited RNA products revealed the accumulation of partially edited mRNAs with less insertion editing compared to the partially edited mRNAs found in the cells with wild type KREPA3 expression. Mutation of ZF1 in TAP-tagged KREPA3 also resulted in accumulation of partially edited mRNAs that were shorter and only edited in the 3'-terminal editing region. Mutation of both ZFs essentially eliminated partially edited mRNA. The mutations did not affect gRNA abundance. These data indicate that both ZFs are essential for the progression of editing and perhaps its accuracy, which suggests that KREPA3 plays roles in the editing process via its ZFs interaction with editosome proteins and/or RNA substrates.
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- 2010
- Full Text
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49. Differential functions of two editosome exoUases in Trypanosoma brucei.
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Ernst NL, Panicucci B, Carnes J, and Stuart K
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- Animals, Gene Knockdown Techniques, RNA Interference, Trypanosoma brucei brucei metabolism, Uridine metabolism, Exonucleases metabolism, RNA Editing, Trypanosoma brucei brucei enzymology
- Abstract
Mitochondrial RNAs in trypanosomes are edited by the insertion and deletion of uridine (U) nucleotides to form translatable mRNAs. Editing is catalyzed by three distinct editosomes that contain two related U-specific exonucleases (exoUases), KREX1 and KREX2, with the former present exclusively in KREN1 editosomes and the latter present in all editosomes. We show here that repression of KREX1 expression leads to a concomitant reduction of KREN1 in approximately 20S editosomes, whereas KREX2 repression results in reductions of KREPA2 and KREL1 in approximately 20S editosomes. Knockdown of KREX1 results in reduced cell viability, reduction of some edited RNA in vivo, and a significant reduction in deletion but not insertion endonuclease activity in vitro. In contrast, KREX2 knockdown does not affect cell growth or editing in vivo but results in modest reductions of both insertion and deletion endonuclease activities and a significant reduction of U removal in vitro. Simultaneous knockdown of both proteins leads to a more severe inhibition of cell growth and editing in vivo and an additive effect on endonuclease cleavage in vitro. Taken together, these results indicate that both KREX1 and KREX2 are important for retention of other proteins in editosomes, and suggest that the reduction in cell viability upon KREX1 knockdown is likely a consequence of KREN1 loss. Furthermore, although KREX2 appears dispensable for cell growth, the increased inhibition of editing and parasite viability upon knockdown of both KREX1 and KREX2 together suggests that both proteins have roles in editing.
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- 2009
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50. The effect of stretching on muscle responses and postural sway responses during computerized dynamic posturography in women and men.
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Lewis NL, Brismée JM, James CR, Sizer PS, and Sawyer SF
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- Adult, Analysis of Variance, Female, Humans, Male, Postural Balance physiology, Reference Values, Muscle Stretching Exercises, Muscle, Skeletal physiology, Posture physiology, Proprioception physiology
- Abstract
Objective: To evaluate the effect of stretching on the parameters of postural sway and on the kinematic variables associated with balance control in women and men., Design: Mixed repeated measures design with 2 levels., Setting: Research laboratory., Participants: Fifteen women and fifteen men (mean age 23.4+/-2.2)., Intervention: Two separate sessions of (1) lower extremity stretching and (2) no-stretching, immediately prior to balance testing with simultaneous surface electromyographic (EMG) recordings of muscle responses., Main Outcome Measures: EMG latencies and average amplitudes for 4 lower extremity muscles for the preferred stance limb during computerized dynamic posturography (CDP) tests, specifically the Postural Evoked Response Test, Adaptation Test, Motor Control Test, Sensory Organization Test, and Unilateral Stance Test., Results: Analyses of variance indicated no significant main effect for stretching and 2 significant main effects for gender for the Motor Control Test (P=.021) and latency of tibialis anterior (P=.009). Analyses of covariance with covariants of height and active knee extension revealed no significant main effect of stretching or of gender on muscles responses or CDP performance., Conclusions: In both women and men, lower extremity stretching did not significantly affect muscle responses or performance during CDP.
- Published
- 2009
- Full Text
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