1,097 results on '"Kari L"'
Search Results
2. Transthyretin Amyloid Cardiomyopathy Risk Evaluation in a Cohort of Patients With Heart Failure
- Author
-
Angie A Suh, Paul B Shaw, Mark Y Jeong, Kari L Olson, and Thomas Delate
- Subjects
General Medicine - Published
- 2023
3. Development and psychometric properties of self-reported job interview skills and job interview anxiety for autistic transition-age youth
- Author
-
Helen M. Genova, Michael A. Kallen, Kari L. Sherwood, Leann DaWalt, Lauren Bishop, David Telfer, Cheryl Brown, Barbara Sanchez, and Matthew J. Smith
- Subjects
Occupational Therapy ,Rehabilitation - Abstract
BACKGROUND: The study of job interview training is an emerging area among transition-age autistic youth who face significant challenges when navigating job interviews. The autism field has limited measures that have undergone rigorous psychometric evaluation. OBJECTIVE: We sought to evaluate the psychometric properties of adapted self-report measures assessing job interview skills and job interview anxiety. METHODS: As part of two parent randomized controlled trials, eighty-five transition-age autistic youth completed measures related to the strength of their job interview skills and their level of job interview anxiety. We conducted classical test theory analyses, exploratory and confirmatory factor analyses, and Rasch model analytic and calibration analyses. Pearson correlations were used to establish concurrent, divergent, and criterion validity by correlating these scales with measures of social challenges, depressive symptoms, behaviors, neuropsychological functioning, and work history. RESULTS: Our analyses yielded two brief and reliable scales: Measure of Job Interview Skills (MOJO-iSkills) and Measure of Job Interview Anxiety (MOJO-iAnxiety), which demonstrated initial concurrent, divergent, and criterion validities when correlated with measures of depressive symptoms, social challenges, internalizing and externalizing behavior, and work history. CONCLUSION: This study presents initial evidence that MOJO-iSkills and MOJO-iAnxiety have acceptable psychometric properties supporting they can be used to reliably and validly assess job interview skills and interview anxiety.
- Published
- 2023
4. Neoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma
- Author
-
Sapna P. Patel, Megan Othus, Yuanbin Chen, G. Paul Wright, Kathleen J. Yost, John R. Hyngstrom, Siwen Hu-Lieskovan, Christopher D. Lao, Leslie A. Fecher, Thach-Giao Truong, Jennifer L. Eisenstein, Sunandana Chandra, Jeffrey A. Sosman, Kari L. Kendra, Richard C. Wu, Craig E. Devoe, Gary B. Deutsch, Aparna Hegde, Maya Khalil, Ankit Mangla, Amy M. Reese, Merrick I. Ross, Andrew S. Poklepovic, Giao Q. Phan, Adedayo A. Onitilo, Demet G. Yasar, Benjamin C. Powers, Gary C. Doolittle, Gino K. In, Niels Kokot, Geoffrey T. Gibney, Michael B. Atkins, Montaser Shaheen, James A. Warneke, Alexandra Ikeguchi, Jose E. Najera, Bartosz Chmielowski, Joseph G. Crompton, Justin D. Floyd, Eddy Hsueh, Kim A. Margolin, Warren A. Chow, Kenneth F. Grossmann, Eliana Dietrich, Victor G. Prieto, Michael C. Lowe, Elizabeth I. Buchbinder, John M. Kirkwood, Larissa Korde, James Moon, Elad Sharon, Vernon K. Sondak, and Antoni Ribas
- Subjects
General Medicine - Published
- 2023
5. Altered dendritic morphology in dorsolateral prefrontal cortex of nonhuman primates prenatally exposed to maternal immune activation
- Author
-
Kari L. Hanson, Ruth K. Weir, Ana-Maria Iosif, Judy Van de Water, Cameron S. Carter, A. Kimberley McAllister, Melissa D. Bauman, and Cynthia M. Schumann
- Subjects
Male ,Autism ,Neuroimmunology ,Immunology ,Prefrontal Cortex ,NHP ,Reproductive health and childbirth ,Basic Behavioral and Social Science ,Article ,Behavioral Neuroscience ,Dorsolateral Prefrontal Cortex ,Pregnancy ,Behavioral and Social Science ,Golgi ,Maternal immune activation ,Animals ,Humans ,Psychology ,Animal model ,Pediatric ,Behavior ,Neurology & Neurosurgery ,Animal ,Endocrine and Autonomic Systems ,Mental Disorders ,Neurosciences ,Brain ,Brain Disorders ,Neuroanatomy ,Poly I-C ,Poly IC ,Mental Health ,Maternal Exposure ,Prenatal Exposure Delayed Effects ,Disease Models ,Neurological ,Schizophrenia ,Female - Abstract
Women who contract a viral or bacterial infection during pregnancy have an increased risk of giving birth to a child with a neurodevelopmental or psychiatric disorder. The effects of maternal infection are likely mediated by the maternal immune response, as preclinical animal models have confirmed that maternal immune activation (MIA) leads to long lasting changes in offspring brain and behavior development. The present study sought to determine the impact of MIA-exposure during the first or second trimester on neuronal morphology in dorsolateral prefrontal cortex (DLPFC) and hippocampus from brain tissue obtained from MIA-exposed and control male rhesus monkey (Macaca mulatta) during late adolescence. MIA-exposed offspring display increased neuronal dendritic branching in pyramidal cells in DLPFC infra- and supragranular layers relative to controls, with no significant differences observed between offspring exposed to maternal infection in the first and second trimester. In addition, the diameter of apical dendrites in DLPFC infragranular layer is significantly decreased in MIA-exposed offspring relative to controls, irrespective of trimester exposure. In contrast, alterations in hippocampal neuronal morphology of MIA-exposed offspring were not evident. These findings demonstrate that a maternal immune challenge during pregnancy has long-term consequences for primate offspring dendritic structure, selectively in a brain region vital for socioemotional and cognitive development.
- Published
- 2023
6. Pediatric Chemotherapy Infusions in Outpatient Examination Rooms: A Novel Patient Care Approach
- Author
-
Tami K. Omdahl, Janelle L. Stenzel, Marsha L. Pike, Patricia M. Conlon, Tracy A. Barry, Tanya M. Brown, Kari L. Cambern, Kadi M. Davis, Kelly A. Fjerstad, Kevin K. Graner, Alexis K. Kuhn, Alison P. Larson, Amir B. Orandi, Emily L. Smith, Scott A. Soefje, and Alan M. Janssen
- Subjects
Advanced and Specialized Nursing ,Oncology (nursing) ,General Medicine ,Pediatrics - Abstract
Background: Many health care organizations offer pediatric infusions in outpatient infusion centers or, as in our organization, in a hospital-based outpatient Pediatric Infusion Therapy Center (PITC). When restrictions related to the COVID-19 pandemic decreased our PITC appointment capacity by 40%, other patient and family satisfaction issues were exacerbated. We implemented a new approach to pediatric infusions with the aim of improving patient and family satisfaction and reducing the amount of time in an appointment itinerary without negatively affecting patient safety. Methods: Our team used a phased approach to pilot the administration of short chemotherapy infusions in the same outpatient clinic examination rooms where consultation and routine office visits were conducted. Patients saw their specialist for an examination and, if clinically indicated, their infusion was administered in the same room. Appointment itineraries were then completed. The team tracked efficiency, satisfaction, and safety metrics related to the new process. Results: All efficiency metrics improved. No harm came to the 49 unique patients who received a total of 184 infusions. Patient appointment itineraries were shortened by an average of 1.03 hr. Satisfaction survey responses indicated a clear preference (93%) for the new process. Discussion: The novel approach of offering short infusions in outpatient clinic examination rooms provides an opportunity to ease capacity constraints and further increase patient and family satisfaction. This method may be especially helpful for health care organizations when external influences (e.g., lack of physical space, challenging patient volumes, and pandemics) necessitate a change.
- Published
- 2023
7. Effects of Exercise and Dietary Modifications on Hidradenitis Suppurativa: A Systematic Review
- Author
-
Isaac Weber, Josie Giefer, and Kari L. Martin
- Subjects
Dermatology ,General Medicine - Published
- 2023
8. A Creative Approach to Promoting Survey Response 1
- Author
-
Charles F. Brady and Kari L. Klinedinst
- Published
- 2023
9. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial—ECOG-ACRIN EA6134
- Author
-
Michael B. Atkins, Sandra J. Lee, Bartosz Chmielowski, Ahmad A. Tarhini, Gary I. Cohen, Thach-Giao Truong, Helen H. Moon, Diwakar Davar, Mark O'Rourke, Joseph J. Stephenson, Brendan D. Curti, Walter J. Urba, Joanna M. Brell, Pauline Funchain, Kari L. Kendra, Alexandra P. Ikeguchi, Anthony Jaslowski, Charles L. Bane, Mark A. Taylor, Madhuri Bajaj, Robert M. Conry, Robert J. Ellis, Theodore F. Logan, Noel Laudi, Jeffrey A. Sosman, David G. Crockett, Andrew L. Pecora, Ian J. Okazaki, Sowjanya Reganti, Sunandana Chandra, Samantha Guild, Helen X. Chen, Howard Z. Streicher, Jedd D. Wolchok, Antoni Ribas, and John M. Kirkwood
- Subjects
Cancer Research ,Oncology - Abstract
PURPOSE Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4–blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with BRAFV600-mutant metastatic melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy. PATIENTS AND METHODS In a phase III trial, patients with treatment-naive BRAFV600-mutant metastatic melanoma were randomly assigned to receive either combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and at disease progression were enrolled in step 2 to receive the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D). The primary end point was 2-year overall survival (OS). Secondary end points were 3-year OS, objective response rate, response duration, progression-free survival, crossover feasibility, and safety. RESULTS A total of 265 patients were enrolled, with 73 going onto step 2 (27 in arm C and 46 in arm D). The study was stopped early by the independent Data Safety Monitoring Committee because of a clinically significant end point being achieved. The 2-year OS for those starting on arm A was 71.8% (95% CI, 62.5 to 79.1) and arm B 51.5% (95% CI, 41.7 to 60.4; log-rank P = .010). Step 1 progression-free survival favored arm A ( P = .054). Objective response rates were arm A: 46.0%; arm B: 43.0%; arm C: 47.8%; and arm D: 29.6%. Median duration of response was not reached for arm A and 12.7 months for arm B ( P < .001). Crossover occurred in 52% of patients with documented disease progression. Grade ≥ 3 toxicities occurred with similar frequency between arms, and regimen toxicity profiles were as anticipated. CONCLUSION Combination nivolumab/ipilimumab followed by BRAF and MEK inhibitor therapy, if necessary, should be the preferred treatment sequence for a large majority of patients.
- Published
- 2023
10. A Special Issue on Contemporary Veteran Voices: A Literary Exposition of the Human Experience in Military Service and War
- Author
-
Eugenia L. Weiss, Kari L. Fletcher, and Kate Hendricks Thomas
- Published
- 2023
11. Dose-Dependent Dissociation of Pro-cognitive Effects of Donepezil on Attention and Cognitive Flexibility in Rhesus Monkeys
- Author
-
Adam Neumann, Seyed Alireza Hassani, Sofia Lendor, Kanchan Sinha Roy, Thilo Womelsdorf, Kianoush Banaie Boroujeni, Janusz Pawliszyn, and Kari L. Hoffman
- Subjects
business.industry ,Perseveration ,Cognitive flexibility ,Attentional control ,Cognition ,Striatum ,General Medicine ,Neurochemical ,mental disorders ,Medicine ,medicine.symptom ,business ,Donepezil ,Prefrontal cortex ,Neuroscience ,medicine.drug - Abstract
BACKGROUNDDonepezil exerts pro-cognitive effects by non-selectively enhancing acetylcholine (ACh) across multiple brain systems. The brain systems that mediate pro-cognitive effects of attentional control and cognitive flexibility are the prefrontal cortex and the anterior striatum which have different pharmacokinetic sensitivities to ACh modulation. We speculated that these area-specific ACh profiles lead to distinct optimal dose-ranges for donepezil to enhance the cognitive domains of attention and flexible learning.METHODSTo test for dose-specific effects of donepezil on different cognitive domains we devised a multi-task paradigm for nonhuman primates (NHPs) that assessed attention and cognitive flexibility. NHPs received either vehicle or variable doses of donepezil prior to task performance. We measured donepezil intracerebral and how strong it prevented the breakdown of ACh within prefrontal cortex and anterior striatum using solid-phase-microextraction neurochemistry.RESULTSThe highest administered donepezil dose improved attention and made subjects more robust against distractor interference, but it did not improve flexible learning. In contrast, only a lower dose range of donepezil improved flexible learning and reduced perseveration, but without distractor-dependent attentional improvement. Neurochemical measurements confirmed a dose-dependent increase of extracellular donepezil and decreases in choline within the prefrontal cortex and the striatum.CONCLUSIONSThe donepezil dose for maximally improving attention functions differed from the dose range that enhanced cognitive flexibility despite the availability of the drug in the major brain systems supporting these cognitive functions. Thus, the non-selective acetylcholine esterase inhibitor donepezil inherently trades improvement in the attention domain for improvement in the cognitive flexibility domain at a given dose range.
- Published
- 2023
12. Pediatric Allergic Contact Dermatitis Registry patch testing results from 2016 to 2022: A retrospective study of age-related differences
- Author
-
Katherine Young, Reid W. Collis, David Sheinbein, Chelsea Shope, Tara Suresh, Idy Tam, Alan Snyder, Colleen Cotton, Raegan Hunt, Alina Goldenberg, Ari Goldminz, Aida Lugo-Somolinos, Eric Grisham, Kari L. Martin, Mandeep Sandhu, Dawn Z. Eichenfield, Jessica Sprague, Elana P. Kleinman, Katie Sum, Jennifer K. Chen, Joyce Teng, Marcella R. Aquino, John Plante, Katlein Franca, Alejandra Onate, Patricia Udrizar, Walter Liszewski, and JiaDe Yu
- Subjects
Dermatology - Published
- 2023
13. Nonlinear Analyses Distinguish Load Carriage Dynamics in Walking and Standing: A Systematic Review
- Author
-
Kolby J, Brink, Kari L, McKenzie, and Aaron D, Likens
- Subjects
Nonlinear Dynamics ,Movement ,Entropy ,Standing Position ,Rehabilitation ,Biophysics ,Humans ,Orthopedics and Sports Medicine ,Walking - Abstract
Load carriage experiments are typically performed from a linear perspective that assumes that movement variability is equivalent to error or noise in the neuromuscular system. A complimentary, nonlinear perspective that treats variability as the object of study has generated important results in movement science outside load carriage settings. To date, no systematic review has yet been conducted to understand how load carriage dynamics change from a nonlinear perspective. The goal of this systematic review is to fill that need. Relevant literature was extracted and reviewed for general trends involving nonlinear perspectives on load carriage. Nonlinear analyses that were used in the reviewed studies included sample, multiscale, and approximate entropy; the Lyapunov exponent; fractal analysis; and relative phase. In general, nonlinear tools successfully distinguish between unloaded and loaded conditions in standing and walking, although not in a consistent manner. The Lyapunov exponent and entropy were the most used nonlinear methods. Two noteworthy findings are that entropy in quiet standing studies tends to decrease, whereas the Lyapunov exponent in walking studies tends to increase, both due to added load. Thus, nonlinear analyses reveal altered load carriage dynamics, demonstrating promise in applying a nonlinear perspective to load carriage while also underscoring the need for more research.
- Published
- 2022
14. Endometrial Hyperplasia
- Author
-
Kari L. Ring, Anne M. Mills, and Susan C. Modesitt
- Subjects
Obstetrics and Gynecology - Published
- 2022
15. Eligibility of out-of-hospital cardiac arrest patients for extracorporeal cardiopulmonary resuscitation in the United States: A geographic information system model
- Author
-
Adam L. Gottula, Christopher R. Shaw, Kari L. Gorder, Bennett H. Lane, Jennifer Latessa, Man Qi, Amy Koshoffer, Rabab Al-Araji, Wesley Young, Jordan Bonomo, James R. Langabeer, Demetris Yannopoulos, Timothy D. Henry, Cindy H. Hsu, and Justin L. Benoit
- Subjects
Emergency Medicine ,Emergency Nursing ,Cardiology and Cardiovascular Medicine - Abstract
Recent evidence suggest that extracorporeal cardiopulmonary resuscitation (ECPR) may improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). Eligibility criteria for ECPR are often based on patient age, clinical variables, and facility capabilities. Expanding access to ECPR across the U.S. requires a better understanding of how these factors interact with transport time to ECPR centers.We constructed a Geographic Information System (GIS) model to estimate the number of ECPR candidates in the U.S. We utilized a Resuscitation Outcome Consortium (ROC) database to model time-dependent rates of ECPR eligibility and the Cardiac Arrest Registry to Enhance Survival (CARES) registry to determine the total number of OHCA patients who meet pre-specified ECPR criteria within designated transportation times. The combined model was used to estimate the total number of ECPR candidates.There were 588,203 OHCA patients in the CARES registry from 2013 to 2020. After applying clinical eligibility criteria, 22,104 (3.76%) OHCA patients were deemed eligible for ECPR. The rate of ROSC increased with longer resuscitation time, which resulted in fewer ECPR candidates. The proportion of OHCA patients eligible for ECPR increased with older age cutoffs. Only 1.68% (9,889/588,203) of OHCA patients in the U.S. were eligible for ECPR based on a 45-minute transportation time to an ECMO-ready center model.Less than 2% of OHCA patients are eligible for ECPR in the U.S. GIS models can identify the impact of clinical criteria, transportation time, and hospital capabilities on ECPR eligibility to inform future implementation strategies.
- Published
- 2022
16. Retrosplenial and Hippocampal Synchrony during Retrieval of Old Memories in Macaques
- Author
-
Ahmed T. Hussin, Saman Abbaspoor, and Kari L. Hoffman
- Subjects
General Neuroscience ,Mental Recall ,Animals ,Brain ,Female ,Macaca mulatta ,Hippocampus ,Gyrus Cinguli - Abstract
Memory for events from the distant past relies on multiple brain regions, but little is known about the underlying neural dynamics that give rise to such abilities. We recorded neural activity in the hippocampus and retrosplenial cortex of two female rhesus macaques as they visually selected targets in year-old and newly acquired object-scene associations. Whereas hippocampal activity was unchanging with memory age, the retrosplenial cortex responded with greater magnitude alpha oscillations (10–15 Hz) and greater phase locking to memory-guided eye movements during retrieval of old events. A similar old-memory enhancement was observed in the anterior cingulate cortex but in a beta2/gamma band (28–35 Hz). In contrast, remote retrieval was associated with decreased gamma-band synchrony between the hippocampus and each neocortical area. The increasing retrosplenial alpha oscillation and decreasing hippocampocortical synchrony with memory age may signify a shift in frank memory allocation or, alternatively, changes in selection among distributed memory representations in the primate brain.SIGNIFICANCE STATEMENTMemory depends on multiple brain regions, whose involvement is thought to change with time. Here, we recorded neuronal population activity from the hippocampus and retrosplenial cortex as nonhuman primates searched for objects embedded in scenes. These memoranda were either newly presented or a year old. Remembering old material drove stronger oscillations in the retrosplenial cortex and led to a greater locking of neural activity to search movements. Remembering new material revealed stronger oscillatory synchrony between the hippocampus and retrosplenial cortex. These results suggest that with age, memories may come to rely more exclusively on neocortical oscillations for retrieval and search guidance and less on long-range coupling with the hippocampus.
- Published
- 2022
17. Atopic Dermatitis in the Adult Population
- Author
-
Baumann John R, Groneck Andrew D, and Martin Kari L
- Subjects
General Medicine - Published
- 2023
18. Determination of Stretching Frequencies by Isotopic Substitution Using Infrared Spectroscopy: An Upper-Level Undergraduate Experiment for an In-Person or Online Laboratory
- Author
-
Sarah E. Shaner and Kari L. Stone
- Subjects
General Chemistry ,Education - Published
- 2023
19. Theta- and gamma-band oscillatory uncoupling in the macaque hippocampus
- Author
-
Saman Abbaspoor, Ahmed T Hussin, and Kari L Hoffman
- Subjects
General Immunology and Microbiology ,General Neuroscience ,General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
Nested hippocampal oscillations in the rodent give rise to temporal dynamics that may underlie learning, memory, and decision making. Although theta/gamma coupling in rodent CA1 occurs during exploration and sharp-wave ripples emerge in quiescence, it is less clear that these oscillatory regimes extend to primates. We therefore sought to identify correspondences in frequency bands, nesting, and behavioral coupling of oscillations taken from macaque hippocampus. We found that, in contrast to rodent oscillations, theta and gamma frequency bands in macaque CA1 were segregated by behavioral states. In both stationary and freely moving designs, beta2/gamma (15–70 Hz) had greater power during visual search whereas the theta band (3–10 Hz; peak ~8 Hz) dominated during quiescence and early sleep. Moreover, theta-band amplitude was strongest when beta2/slow gamma (20–35 Hz) amplitude was weakest, instead occurring along with higher frequencies (60–150 Hz). Spike-field coherence was most frequently seen in these three bands (3–10 Hz, 20–35 Hz, and 60–150 Hz); however, the theta-band coherence was largely due to spurious coupling during sharp-wave ripples. Accordingly, no intrinsic theta spiking rhythmicity was apparent. These results support a role for beta2/slow gamma modulation in CA1 during active exploration in the primate that is decoupled from theta oscillations. The apparent difference to the rodent oscillatory canon calls for a shift in focus of frequency when considering the primate hippocampus.
- Published
- 2023
20. A Framework for Evidentiary Reasoning in Biology: Insights from Laboratory Courses Focused on Evolutionary Tree-thinking
- Author
-
Shiyao Liu, Chaonan Liu, Ala Samarapungavan, Stephanie M. Gardner, Kari L. Clase, and Nancy J. Pelaez
- Subjects
Education - Published
- 2023
21. Detrusor underactivity is associated with metabolic syndrome in aged primates
- Author
-
Natalia P. Biscola, Petra M. Bartmeyer, Kari L. Christe, Ricki J. Colman, and Leif A. Havton
- Subjects
Multidisciplinary - Abstract
Lower urinary tract (LUT) dysfunction is prevalent in the elderly population, and clinical manifestations include urinary retention, incontinence, and recurrent urinary tract infections. Age-associated LUT dysfunction is responsible for significant morbidity, compromised quality of life, and rising healthcare costs in older adults, but its pathophysiology is not well understood. We aimed to investigate the effects of aging on LUT function by urodynamic studies and metabolic markers in non-human primates. Adult (n = 27) and aged (n = 20) female rhesus macaques were evaluated by urodynamic and metabolic studies. Cystometry showed detrusor underactivity (DU) with increased bladder capacity and compliance in aged subjects. Metabolic syndrome indicators were present in the aged subjects, including increased weight, triglycerides, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and high sensitivity C-reactive protein (hsCRP), whereas aspartate aminotransferase (AST) was unaffected and the AST/ALT ratio reduced. Principal component analysis and paired correlations showed a strong association between DU and metabolic syndrome markers in aged primates with DU but not in aged primates without DU. The findings were unaffected by prior pregnancies, parity, and menopause. Our findings provide insights into possible mechanisms for age-associated DU and may guide new strategies to prevent and treat LUT dysfunction in older adults.
- Published
- 2023
22. Risk Factors for Immune Checkpoint Inhibitor Immunotherapy Toxicity Among Older Adults with Cancer
- Author
-
Andrew C Johns, Mike Yang, Lai Wei, Madison Grogan, Daniel Spakowicz, Sandipkumar H Patel, Mingjia Li, Marium Husain, Kari L Kendra, Gregory A Otterson, Ashley E Rosko, Barbara L Andersen, David P Carbone, Dwight H Owen, and Carolyn J Presley
- Subjects
Cancer Research ,Oncology - Abstract
Objectives Immune checkpoint inhibitor immunotherapy (IO) is revolutionizing cancer care but can lead to significant toxicity. This study seeks to describe potential risk factors for immune-related adverse events (irAEs) specifically among older adults. Materials and Methods This was a retrospective study at a single academic comprehensive cancer center based on chart review data abstracted by physicians. For patients aged ≥70 years, frequency, type, and grade of irAEs and their association with baseline patient demographics, comorbidities, mobility, and functional status were characterized using bivariate analysis. Based on those results, multivariable logistic regressions were constructed to model the association between these characteristics with any grade and grade 3 or higher irAEs. Results Data were analyzed for 238 patients aged ≥70 years who received IO for mostly (≥90%) advanced cancer between 2011 and 2018. Thirty-nine percent of older adults experienced an irAE and 13% experienced one that was grade 3 or higher. In the multivariable analysis, depression was associated with an increased incidence of any grade irAE, while decreased life-space mobility was associated with an increased incidence of grade ≥3 irAEs. Conclusion Most characteristics of special interest among older adults, include fall risk, weight loss, cognitive limitations, and hearing loss, were not associated with irAEs in our study. However, decreased life-space mobility and depression are potential risk factors for IO toxicity among older adults with advanced cancer. Interventions designed to evaluate and mitigate modifiable risk factors for treatment-related toxicity are needed, and the results of this study may be useful for guiding those efforts.
- Published
- 2023
23. Supplementary Table 5 from A Multicenter Phase I Study of Pazopanib in Combination with Paclitaxel in First-Line Treatment of Patients with Advanced Solid Tumors
- Author
-
Miguel A. Villalona-Calero, Lone H. Ottesen, Chun-Fang Xu, Natalie Compton, A. Benjamin Suttle, Elaine M. Paul, Mary E. R. O'Brien, Ravi Salgia, Ruth Plummer, and Kari L. Kendra
- Abstract
Investigator-assessed best confirmed response to treatment with pazopanib and paclitaxel
- Published
- 2023
24. Supplementary Table 3 from A Multicenter Phase I Study of Pazopanib in Combination with Paclitaxel in First-Line Treatment of Patients with Advanced Solid Tumors
- Author
-
Miguel A. Villalona-Calero, Lone H. Ottesen, Chun-Fang Xu, Natalie Compton, A. Benjamin Suttle, Elaine M. Paul, Mary E. R. O'Brien, Ravi Salgia, Ruth Plummer, and Kari L. Kendra
- Abstract
Drug exposure for paclitaxel and pazopanib
- Published
- 2023
25. Supplementary Table 1 from A Multicenter Phase I Study of Pazopanib in Combination with Paclitaxel in First-Line Treatment of Patients with Advanced Solid Tumors
- Author
-
Miguel A. Villalona-Calero, Lone H. Ottesen, Chun-Fang Xu, Natalie Compton, A. Benjamin Suttle, Elaine M. Paul, Mary E. R. O'Brien, Ravi Salgia, Ruth Plummer, and Kari L. Kendra
- Abstract
Liver function tests for a cohort 1 patient with a hepatotoxicity dose-limiting toxicity
- Published
- 2023
26. Supplementary Table 2 from A Multicenter Phase I Study of Pazopanib in Combination with Paclitaxel in First-Line Treatment of Patients with Advanced Solid Tumors
- Author
-
Miguel A. Villalona-Calero, Lone H. Ottesen, Chun-Fang Xu, Natalie Compton, A. Benjamin Suttle, Elaine M. Paul, Mary E. R. O'Brien, Ravi Salgia, Ruth Plummer, and Kari L. Kendra
- Abstract
Pharmacokinetic data for a cohort 1 patient with hepatotoxicity dose-limiting toxicity
- Published
- 2023
27. Supplementary Table 4 from A Multicenter Phase I Study of Pazopanib in Combination with Paclitaxel in First-Line Treatment of Patients with Advanced Solid Tumors
- Author
-
Miguel A. Villalona-Calero, Lone H. Ottesen, Chun-Fang Xu, Natalie Compton, A. Benjamin Suttle, Elaine M. Paul, Mary E. R. O'Brien, Ravi Salgia, Ruth Plummer, and Kari L. Kendra
- Abstract
Summary of paclitaxel pharmacokinetic parameters
- Published
- 2023
28. Developmental pyrethroid exposure causes a neurodevelopmental disorder phenotype in mice
- Author
-
Melissa A Curtis, Rohan K Dhamsania, Rachel C Branco, Ji-Dong Guo, Justin Creeden, Kari L Neifer, Carlie A Black, Emily J Winokur, Elissar Andari, Brian G Dias, Robert C Liu, Shannon L Gourley, Gary W Miller, and James P Burkett
- Abstract
Neurodevelopmental disorders (NDDs) are a widespread and growing public health challenge, affecting as many as 17% of children in the United States. Recent epidemiological studies have implicated ambient exposure to pyrethroid pesticides during pregnancy in the risk for NDDs in the unborn child. Using a litter-based, independent discovery–replication cohort design, we exposed mouse dams orally during pregnancy and lactation to the Environmental Protection Agency's reference pyrethroid, deltamethrin, at 3 mg/kg, a concentration well below the benchmark dose used for regulatory guidance. The resulting offspring were tested using behavioral and molecular methods targeting behavioral phenotypes relevant to autism and NDD, as well as changes to the striatal dopamine system. Low-dose developmental exposure to the pyrethroid deltamethrin (DPE) decreased pup vocalizations, increased repetitive behaviors, and impaired both fear conditioning and operant conditioning. Compared with control mice, DPE mice had greater total striatal dopamine, dopamine metabolites, and stimulated dopamine release, but no difference in vesicular dopamine capacity or protein markers of dopamine vesicles. Dopamine transporter protein levels were increased in DPE mice, but not temporal dopamine reuptake. Striatal medium spiny neurons showed changes in electrophysiological properties consistent with a compensatory decrease in neuronal excitability. Combined with previous findings, these results implicate DPE as a direct cause of an NDD-relevant behavioral phenotype and striatal dopamine dysfunction in mice and implicate the cytosolic compartment as the location of excess striatal dopamine.
- Published
- 2023
29. Hormonal Suppression in Female Rhesus Macaques (Macaca mulatta) Implanted Subcutaneously with Deslorelin
- Author
-
Kelsey E Carroll, Alexis L Mackiewicz, Amir Ardeshir, Susan A Alber, and Kari L Christe
- Subjects
Animal Science and Zoology - Abstract
Providing effective contraception for nonhuman primates (NHP) is challenging. Deslorelin acetate is a commercially available gonadotropin-releasing hormone (GnRH) agonist that may provide a relatively noninvasive, long-lasting, and potentially reversible alternative to standard NHP contraception methods. This study evaluated the duration of suppression of progesterone and estradiol in 6 adult female rhesus macaques (Macaca mulatta) that received a single subcutaneous 4.7 mg deslorelin implant. We hypothesized that deslorelin would suppress production of these hormones for 6 mo with a correspond- ing cessation of menses. Prior to implantation, blood was collected over 1 mo for baseline hormone analyses. Macaques were sedated at the onset of the next menstrual cycle and a 4.7 mg deslorelin implant was placed in the interscapular region. Blood was collected over the subsequent month at the same intervals used for the baseline collection schedule, and then every 7 d thereafter. Results showed that estradiol and progesterone transiently increased 1 to 3 d after implantation, then fell to basal levels within 6 d of implantation. The duration of hormone suppression (progesterone
- Published
- 2022
30. Supplementary Figure 1 from Involvement of RNA Helicases p68 and p72 in Colon Cancer
- Author
-
Ralf Janknecht, Joseph P. Grande, Kari L. Rossow, and Sook Shin
- Abstract
Supplementary Figure 1 from Involvement of RNA Helicases p68 and p72 in Colon Cancer
- Published
- 2023
31. Data from Involvement of RNA Helicases p68 and p72 in Colon Cancer
- Author
-
Ralf Janknecht, Joseph P. Grande, Kari L. Rossow, and Sook Shin
- Abstract
The homologous proteins p68 and p72 are members of the DEAD box family of RNA helicases. Here, we show that expression of both of these helicases strongly increases during the polyp→adenoma→adenocarcinoma transition in the colon. Furthermore, p68 and p72 form complexes with β-catenin and promote the ability of β-catenin to activate gene transcription. Conversely, simultaneous knockdown of p68 and p72 leads to reduced expression of the β-catenin–regulated genes, c-Myc, cyclin D1, c-jun, and fra-1, all of which are proto-oncogenes. Moreover, transcription of the cell cycle inhibitor p21WAF1/CIP1, whose expression is suppressed by c-Myc, is enhanced on p68/p72 knockdown. Thus, p68/p72 may contribute to colon cancer formation by directly up-regulating proto-oncogenes and indirectly by down-regulating the growth suppressor p21WAF1/CIP1. Accordingly, knockdown of p68 and p72 in colon cancer cells inhibits their proliferation and diminishes their ability to form tumors in vivo. Altogether, these results suggest that p68/p72 overexpression is not only a potential marker of colon cancer but is also causally linked to this disease. Therefore, p68 and p72 may be novel targets in the combat against colon cancer. [Cancer Res 2007;67(16):7572–8]
- Published
- 2023
32. Supplementary Figure 1 Legend from Involvement of RNA Helicases p68 and p72 in Colon Cancer
- Author
-
Ralf Janknecht, Joseph P. Grande, Kari L. Rossow, and Sook Shin
- Abstract
Supplementary Figure 1 Legend from Involvement of RNA Helicases p68 and p72 in Colon Cancer
- Published
- 2023
33. Optimizing Short-format Training: an International Consensus on Effective, Inclusive, and Career-spanning Professional Development in the Life Sciences and Beyond
- Author
-
Jason J. Williams, Rochelle E. Tractenberg, Bérénice Batut, Erin A. Becker, Anne M. Brown, Melissa L. Burke, Ben Busby, Nisha K. Cooch, Allissa A. Dillman, Samuel S. Donovan, Maria A. Doyle, Celia W.G. van Gelder, Christina R. Hall, Kate L. Hertweck, Kari L. Jordan, John R. Jungck, Ainsley R. Latour, Jessica M. Lindvall, Marta Lloret-Llinares, Gary S. McDowell, Rana Morris, Teresa Mourad, Amy Nisselle, Patricia Ordóñez, Lisanna Paladin, Patricia M. Palagi, Mahadeo A. Sukhai, Tracy K. Teal, and Louise Woodley
- Abstract
Science, technology, engineering, mathematics, and medicine (STEMM) fields change rapidly and are increasingly interdisciplinary. Commonly, STEMM practitioners use short-format training (SFT) such as workshops and short courses for upskilling and reskilling, but unaddressed challenges limit SFT’s effectiveness and inclusiveness. Prior work, including the NSF 2026 Reinventing Scientific Talent proposal, called for addressing SFT challenges, and a diverse international group of experts in education, accessibility, and life sciences came together to do so. This paper describes the phenomenography and content analyses that produced a set of 14 actionable recommendations to systematically strengthen SFT. Recommendations were derived from findings in the educational sciences and the experiences of several of the largest life science SFT programs. Recommendations cover the breadth of SFT contexts and stakeholder groups and include actions for instructors (e.g., make equity and inclusion an ethical obligation), programs (e.g., centralize infrastructure for assessment and evaluation), as well as organizations and funders (e.g., professionalize training SFT instructors; deploy SFT to counter inequity). Recommendations are aligned into a purpose-built framework— “The Bicycle Principles”—that prioritizes evidenced-based teaching, inclusiveness, and equity, as well as the ability to scale, share, and sustain SFT. We also describe how the Bicycle Principles and recommendations are consistent with educational change theories and can overcome systemic barriers to delivering consistently effective, inclusive, and career-spanning SFT.SIGNIFICANCE STATEMENTSTEMM practitioners need sustained and customized professional development to keep up with innovations. Short-format training (SFT) such as workshops and short-courses are relied upon widely but have unaddressed limitations. This project generated principles and recommendations to make SFT consistently effective, inclusive, and career-spanning. Optimizing SFT could broaden participation in STEMM by preparing practitioners more equitably with transformative skills. Better SFT would also serve members of the STEMM workforce who have several decades of productivity ahead, but who may not benefit from education reforms that predominantly focus on undergraduate STEMM. The Bicycle Principles and accompanying recommendations apply to any SFT instruction and may be especially useful in rapidly evolving and multidisciplinary fields such as artificial intelligence, genomics, and precision medicine.
- Published
- 2023
34. Goal-Congruity Theory Predicts Students' Sense of Belonging in Computing Across Racial/Ethnic Groups
- Author
-
Kathleen Isenegger, Kari L. George, Paul Bruno, and Colleen M. Lewis
- Published
- 2023
35. Updates in gynecologic care for individuals with lynch syndrome
- Author
-
Kaylee A. Underkofler and Kari L. Ring
- Subjects
Cancer Research ,Oncology - Abstract
Lynch syndrome is an autosomal dominant hereditary cancer syndrome caused by germline pathogenic variants (PVs) in DNA mismatch repair genes (MLH1, MSH2, PMS2, MSH6) or the EPCAM gene. It is estimated to affect 1 in 300 individuals and confers a lifetime risk of cancer of 10-90%, depending on the specific variant and type of cancer. Lynch syndrome is the most common cause of inherited colorectal cancer, but for women, endometrial cancer is more likely to be the sentinel cancer. There is also evidence that certain PVs causing Lynch syndrome confer an increased risk of ovarian cancer, while the risk of ovarian cancer in others is not well defined. Given this, it is essential for the practicing gynecologist and gynecologic oncologist to remain up to date on the latest techniques in identification and diagnosis of individuals with Lynch syndrome as well as evidence-based screening and risk reduction recommendations for those impacted. Furthermore, as the landscape of gynecologic cancer treatment shifts towards treatment based on molecular classification of tumors, knowledge of targeted therapies well-suited for mismatch repair deficient Lynch tumors will be crucial. The objective of this review is to highlight recent updates in the literature regarding identification and management of individuals with Lynch syndrome as it pertains to endometrial and ovarian cancers to allow gynecologic providers the opportunity to both prevent and identify Lynch-associated cancers earlier, thereby reducing the morbidity and mortality of the syndrome.
- Published
- 2023
36. Building Financial Capability and Assets for All
- Author
-
Elena Delavega, Kari L. Fletcher, and Melissa Hirschi
- Published
- 2023
37. Websites about, not for, adolescents? A systematic analysis of online fertility preservation information for adolescent and young adult cancer patients
- Author
-
Sienna Ruiz, Rachel Mintz, Amela Sijecic, Michelle Eggers, Aubri S. Hoffman, Terri Woodard, Kari L. Bjornard, Holly Hoefgen, Taryn Sandheinrich, Kenan Omurtag, and Ashley J. Housten
- Subjects
Oncology ,Oncology (nursing) - Abstract
Purpose Fertility preservation is an increasingly important topic in adolescent and young adult cancer survivorship, yet treatments remain under-utilized, possibly due to lack of awareness and understanding. The internet is widely used by adolescents and young adults and has been proposed to fill knowledge gaps and advance high-quality, more equitable care. As a first step, this study analyzed the quality of current fertility preservation resources online and identified opportunities for improvement. Methods We conducted a systematic analysis of 500 websites to assess the quality, readability, and desirability of website features, and the inclusion of clinically relevant topics. Results The majority of the 68 eligible websites were low quality, written at college reading levels, and included few features that younger patients find desirable. Websites mentioned more common fertility preservation treatments than promising experimental treatments, and could be improved with cost information, socioemotional impacts, and other equity-related fertility topics. Conclusions Currently, the majority of fertility preservation websites are about, but not for, adolescent and young adult patients. High-quality educational websites are needed that address outcomes that matter to teens and young adults, with a priority on solutions that prioritize equity. Implications for Cancer Survivors: Adolescent and young adult survivors have limited access to high-quality fertility preservation websites that are designed for their needs. There is a need for the development of fertility preservation websites that are clinically comprehensive, written at appropriate reading levels, inclusive, and desirable. We include specific recommendations that future researchers can use to develop websites that could better address AYA populations and improve the fertility preservation decision making process.
- Published
- 2023
38. Association of medical comorbidities and cardiovascular disease with toxicity and survival among patients receiving checkpoint inhibitor immunotherapy
- Author
-
Andrew C. Johns, Mike Yang, Lai Wei, Madison Grogan, Sandipkumar H. Patel, Mingjia Li, Marium Husain, Kari L. Kendra, Gregory A. Otterson, Jarred T. Burkart, Daniel Spakowicz, Rebecca Hoyd, Dwight H. Owen, and Carolyn J. Presley
- Subjects
Cancer Research ,Oncology ,Immunology ,Immunology and Allergy - Published
- 2023
39. Muscle Activation During Single-Legged Squat Is Affected by Position of the Nonstance Limb
- Author
-
Anne Khuu, Kari L. Loverro, and Cara L. Lewis
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Posture ,Physical Therapy, Sports Therapy and Rehabilitation ,Context (language use) ,Quadriceps Muscle ,Young Adult ,Physical medicine and rehabilitation ,medicine ,Humans ,Orthopedics and Sports Medicine ,Knee ,Muscle activity ,Gluteal muscles ,Muscle, Skeletal ,Rehabilitation ,biology ,business.industry ,Electromyography ,Biomechanics ,Muscle activation ,General Medicine ,biology.organism_classification ,Medius ,medicine.anatomical_structure ,Buttocks ,Single leg squat ,Female ,business - Abstract
Context The single-legged squat (SLS) is appropriate for targeting activation, strengthening, and neuromuscular retraining of the gluteus maximus, gluteus medius, and quadriceps. However, the effects of different nonstance-limb positions on muscle activity have not been fully evaluated. Objective To compare the muscle activity of selected stance-limb hip muscles during the SLS using 3 nonstance-limb positions: in front (SLS-Front), in the middle (SLS-Middle), and in back (SLS-Back). Design Controlled laboratory study. Setting Biomechanics laboratory. Patients or Other Participants A total of 17 healthy adults (8 men, 9 women; age = 22.6 ± 3.6 years, height = 173.3 ± 10.7 cm, mass = 71.2 ± 11.0 kg) participated. Main Outcome Measure(s) Surface electromyographic data of the gluteus maximus, gluteus medius, lateral hamstrings, medial hamstrings, rectus femoris, and tensor fascia lata (TFL) as well as kinetic data of the hip and knee were collected while participants performed the 3 SLS tasks. Mean muscle-activation levels during the descent and ascent phases for the selected hip muscles and hip and knee kinetics in all 3 planes were compared for the 3 tasks. Each variable of interest was analyzed using a separate linear regression model with a generalized estimating equations correction. Results Muscle-activation levels of the gluteus maximus, gluteus medius, medial hamstrings, rectus femoris, and TFL for the stance limb during descent (P ≤ .04) and the medial hamstrings and TFL during ascent (P ≤ .002) were different among the SLS tasks. The greatest number of differences occurred between SLS-Front and SLS-Back. During descent, gluteal muscle activity was greater in SLS-Front (P ≤ .03) and SLS-Middle (P = .03) than in SLS-Back. For both phases, TFL activity was greater during SLS-Front than during both SLS-Middle and SLS-Back (P ≤ .006). Kinetic differences at the hip and knee between SLS tasks were also observed (P values ≤ .02). Conclusions The 3 SLS tasks had different muscle-activation and kinetic profiles. Clinicians and researchers can vary nonstance-limb position during the SLS to manipulate muscle-activation levels and tailor the exercise to assist with goals at different stages of rehabilitation.
- Published
- 2023
40. Characterizing Relationships Among the Cognitive, Physical, Social-emotional, and Health-related Traits of Military Personnel
- Author
-
Grace E Giles, Ester Navarro, Seth Elkin-Frankston, Tad T Brunyé, Wade R Elmore, Joseph F Seay, Kari L McKenzie, Kevin S O’Fallon, Stephanie A Brown, Joseph L Parham, Todd N Garlie, Linda DeSimone, Jose D Villa, Hyegjoo E Choi-Rokas, K Blake Mitchell, Kenneth Racicot, Jason W Soares, Christina Caruso, Debra Anderson, Julie A Cantelon, Aaron L Gardony, Tracey J Smith, J Philip Karl, Julianna M Jayne, John J Christopher, Maria K Talarico, Jennifer Neugebauer Sperlein, Angela C Boynton, Andrew Jensen, John W Ramsay, and Marianna D Eddy
- Subjects
Public Health, Environmental and Occupational Health ,General Medicine - Abstract
Introduction Personnel engaged in high-stakes occupations, such as military personnel, law enforcement, and emergency first responders, must sustain performance through a range of environmental stressors. To maximize the effectiveness of military personnel, an a priori understanding of traits can help predict their physical and cognitive performance under stress and adversity. This work developed and assessed a suite of measures that have the potential to predict performance during operational scenarios. These measures were designed to characterize four specific trait–based domains: cognitive, health, physical, and social-emotional. Materials and Methods One hundred and ninety-one active duty U.S. Army soldiers completed interleaved questionnaire–based, seated task–based, and physical task–based measures over a period of 3-5 days. Redundancy analysis, dimensionality reduction, and network analyses revealed several patterns of interest. Results First, unique variable analysis revealed a minimally redundant battery of instruments. Second, principal component analysis showed that metrics tended to cluster together in three to five components within each domain. Finally, analyses of cross-domain associations using network analysis illustrated that cognitive, health, physical, and social-emotional domains showed strong construct solidarity. Conclusions The present battery of metrics presents a fieldable toolkit that may be used to predict operational performance that can be clustered into separate components or used independently. It will aid predictive algorithm development aimed to identify critical predictors of individual military personnel and small-unit performance outcomes.
- Published
- 2023
41. Endometrial hyperplasia, estrogen therapy, and the prevention of endometrial cancer
- Author
-
Kari L. Ring, JoAnn V. Pinkerton, Lisa M. Landrum, Rosemary E. Zuna, and Linda R. Duska
- Published
- 2023
42. Contributors
- Author
-
Floor J. Backes, Lindsey B. Beffa, Caroline C. Billingsley, Michael J. Birrer, Kristin Bixel, Teresa K.L. Boitano, Wendy R. Brewster, Dana M. Chase, Shaina Bruce, Angelena Crown, Christina S. Chu, Daniel L. Clarke-Pearson, Robert A. Ross, Brian Crosland, Joshua G. Cohen, Robert L. Coleman, Paul A. DiSilvestro, Oliver Dorigo, Linda R. Duska, Ramez Nassef Eskander, Mary L. Gemignani, Camille Catherine Gunderson, Andrea R. Hagemann, Thomas J. Herzog, Travis R. Korenaga, Warner K. Huh, Lindsay Kuroki, Katherine Kurnit, Robert S. Mannel, L. Stewart Massad, Cara A. Mathews, David S. Miller, Bradley J. Monk, David G. Mutch, Rachita Nikam, JoAnn V. Pinkerton, Matthew Powell, Dominique L. Rash, Lisa M. Landrum, Kari L. Ring, Malte Renz, Brandon Roane, Stephen C. Rubin, Ritu Salani, Jane Satero, Anil K. Sood, John T. Soper, Elizabeth Christina Stock, C. James Sung, Krishnansu Sujata Tewari, Michael D. Toboni, Katherine Tucker, Joan L. Walker, Jaclyn A. Wall, Christina Washington, Lari B. Wenzel, Shannon N. Westin, Catheryn M. Yashar, William T. Creasman, and Rosemary E. Zuna
- Published
- 2023
43. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134
- Author
-
Atkins, Michael B, Lee, Sandra J, Chmielowski, Bartosz, Tarhini, Ahmad A, Cohen, Gary I, Truong, Thach-Giao, Moon, Helen H, Davar, Diwakar, O'Rourke, Mark, Stephenson, Joseph J, Curti, Brendan D, Urba, Walter J, Brell, Joanna M, Funchain, Pauline, Kendra, Kari L, Ikeguchi, Alexandra P, Jaslowski, Anthony, Bane, Charles L, Taylor, Mark A, Bajaj, Madhuri, Conry, Robert M, Ellis, Robert J, Logan, Theodore F, Laudi, Noel, Sosman, Jeffrey A, Crockett, David G, Pecora, Andrew L, Okazaki, Ian J, Reganti, Sowjanya, Chandra, Sunandana, Guild, Samantha, Chen, Helen X, Streicher, Howard Z, Wolchok, Jedd D, Ribas, Antoni, and Kirkwood, John M
- Subjects
Proto-Oncogene Proteins B-raf ,Mitogen-Activated Protein Kinase Kinases ,Skin Neoplasms ,Pyridones ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Oncology and Carcinogenesis ,Evaluation of treatments and therapeutic interventions ,Ipilimumab ,Nivolumab ,Clinical Research ,6.1 Pharmaceuticals ,Oximes ,Antineoplastic Combined Chemotherapy Protocols ,Mutation ,Disease Progression ,Humans ,Prospective Studies ,Patient Safety ,Oncology & Carcinogenesis ,Melanoma ,6.2 Cellular and gene therapies ,Cancer - Abstract
PurposeCombination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with BRAFV600-mutant metastatic melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy.Patients and methodsIn a phase III trial, patients with treatment-naive BRAFV600-mutant metastatic melanoma were randomly assigned to receive either combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and at disease progression were enrolled in step 2 to receive the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D). The primary end point was 2-year overall survival (OS). Secondary end points were 3-year OS, objective response rate, response duration, progression-free survival, crossover feasibility, and safety.ResultsA total of 265 patients were enrolled, with 73 going onto step 2 (27 in arm C and 46 in arm D). The study was stopped early by the independent Data Safety Monitoring Committee because of a clinically significant end point being achieved. The 2-year OS for those starting on arm A was 71.8% (95% CI, 62.5 to 79.1) and arm B 51.5% (95% CI, 41.7 to 60.4; log-rank P = .010). Step 1 progression-free survival favored arm A (P = .054). Objective response rates were arm A: 46.0%; arm B: 43.0%; arm C: 47.8%; and arm D: 29.6%. Median duration of response was not reached for arm A and 12.7 months for arm B (P < .001). Crossover occurred in 52% of patients with documented disease progression. Grade ≥ 3 toxicities occurred with similar frequency between arms, and regimen toxicity profiles were as anticipated.ConclusionCombination nivolumab/ipilimumab followed by BRAF and MEK inhibitor therapy, if necessary, should be the preferred treatment sequence for a large majority of patients.
- Published
- 2023
44. Using pharmacy technicians and electronic health record capabilities to improve outcomes for patients with cardiovascular disease
- Author
-
Cari R. Friesleben, Stephanie M. Campbell, Jessica M. Stine, Jennifer J. Schimmer, Kari L. Olson, Jessica Angleson, and Sheila L. Stadler
- Subjects
Male ,medicine.medical_specialty ,Pharmacy Technicians ,Pharmacology (nursing) ,Pharmacy ,Diabetes mellitus ,medicine ,Electronic Health Records ,Humans ,media_common.cataloged_instance ,Aged ,Retrospective Studies ,media_common ,Aged, 80 and over ,Pharmacology ,business.industry ,Retrospective cohort study ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,Clinical pharmacy ,Blood pressure ,Cardiovascular Diseases ,Emergency medicine ,Ambulatory ,Female ,business ,Pharmacy technician ,Dyslipidemia - Abstract
OBJECTIVE This study aimed to compare lipid and blood pressure (BP) control before and after implementing a certified pharmacy technician (CPhT) protocol that optimized electronic health record (EHR) capabilities and shifted work from clinical pharmacy specialists (CPSs) to CPhT. SETTING Kaiser Permanente Colorado's pharmacist-managed cardiac risk reduction service (which manages dyslipidemia, hypertension, and diabetes for all patients with atherosclerotic cardiovascular disease). PRACTICE DESCRIPTION In 2019, a protocol that optimized EHR capabilities and allowed work to be offloaded from CPS to CPhT was implemented. Filtered views within the EHR were created that bucketed patients with specific lipid results criteria. The CPhT protocol provided guidance to CPhT on determining whether patients were at low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein (non-HDL) goals, on appropriate statin intensity, adherent to medications, and whether the most recent BP was controlled. The CPhT notified CPS of uncontrolled patients who would assess and manage these patients, as necessary. The CPhT notified controlled patients of their results. PRACTICE INNOVATION Data on the outcomes of incorporating pharmacy technicians to support CPS clinical activities in ambulatory clinical pharmacy are limited. EVALUATION METHODS This retrospective study compared a "Pharmacist-Driven" (index date: January 1, 2016) with a "Tech-Enhanced" (index date: January 1, 2019) group. The primary outcome was the proportion of patients at all goals defined as LDL-C < 70 mg/dL, non-HDL
- Published
- 2022
45. Use of serial testing to interrupt a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) outbreak on a hospital medical floor—Minnesota, October–December 2020
- Author
-
Rajesh M. Prabhu, Melanie J. Firestone, Kari L. Bergman, Amanda L. Beaudoin, Tammy Hale, Alexandra J. Lorentz, Jacob Garfin, Xiong Wang, and Stacy M. Holzbauer
- Subjects
Microbiology (medical) ,Infectious Diseases ,Epidemiology - Abstract
Objective:Describe a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) hospital outbreak and the role of serial testing of patients and healthcare personnel (HCP) in interrupting SARS-CoV-2 transmission.Design:Outbreak investigation.Setting:Medical floor of a tertiary-care center in Minnesota.Methods:Serial testing for SARS-CoV-2 and whole-genome sequencing (WGS) of positive specimens from HCP and patients were used. An outbreak-associated case was defined as a positive SARS-CoV-2 molecular test in an HCP who worked on the floor prior to testing positive or in a patient who was hospitalized on the medical floor bewteen October 27 and December 1, 2020. WGS was used to determine potential routes of transmission.Results:The outbreak was detected after a patient hospitalized for 12 days tested positive for SARS-CoV-2. Serial testing of patients and HCP was conducted in response. Overall, 247 HCP and 41 patients participated in serial SARS-CoV-2 testing; 52 HCP (21%) and 19 hospitalized patients (46%) tested positive. One additional HCP tested positive outside serial testing. The WGS of specimens from 27 (51%) HCP and 15 (79%) patients identified 3 distinct transmission clusters. WGS and epidemiologic evidence suggested intrafacility transmission. The proportions of asymptomatic and presymptomatic patients who tested positive (63%) and HCP who worked during their infectious period (75%) highlight the need for serial testing of asymptomatic patients and HCP during outbreaks.Conclusions:Coupled with preventive measures such as personal protective equipment use and physical distancing, serial testing of HCP and patients could help detect and prevent transmission within healthcare facilities during outbreaks and when nosocomial transmission is suspected.
- Published
- 2022
46. Targeting immune checkpoints in gynecologic cancer: updates & perspectives for pathologists
- Author
-
Kari L. Ring, Timothy N. J. Bullock, and Anne M. Mills
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,B7-H1 Antigen ,Pathology and Forensic Medicine ,Immune system ,TIGIT ,Neoplasms ,Internal medicine ,MHC class I ,Biomarkers, Tumor ,Humans ,Medicine ,CD134 ,biology ,business.industry ,CD137 ,Microsatellite instability ,Immunotherapy ,Mismatch Repair Protein ,medicine.disease ,Immunohistochemistry ,Pathologists ,biology.protein ,Female ,Microsatellite Instability ,business - Abstract
Checkpoint inhibitor-based immunotherapy is increasingly used in the treatment of gynecologic cancers, and most often targets the PD-1/PD-L1 axis. Pathologists should be familiar with the biomarkers required to determine candidacy for these treatments based on existing FDA approvals, including mismatch repair protein immunohistochemistry, microsatellite instability testing, tumor mutation burden testing, and PD-L1 immunohistochemistry. This review summarizes the rationale behind these treatments and their associated biomarkers and delivers guidance on how to utilize and readout these tests. It also introduces additional biomarkers which may provide information regarding immunotherapeutic vulnerability in the future such as neoantigen load; POLE mutation status; and immunohistochemical expression of immunosuppressive checkpoints like LAG-3, TIM-3, TIGIT, and VISTA; immune-activating checkpoints such as CD27, CD40, CD134, and CD137; enzymes such as IDO-1 and adenosine-related compounds; and MHC class I.
- Published
- 2022
47. The Tech Trajectory: Examining the Role of College Environments in Shaping Students’ Interest in Computing Careers
- Author
-
Kari L. George, Linda J. Sax, Annie M. Wofford, and Sarayu Sundar
- Subjects
Education - Published
- 2022
48. Impella in Transport: Physiology, Mechanics, Complications, and Transport Considerations
- Author
-
Jordan Bonomo, Jonathan Chuko, Kari L. Gorder, Christopher R. Shaw, Saad Ahmad, William R. Hinckley, Michael J. Lauria, Amy Swiencki, Justine Milligan, and Adam L. Gottula
- Subjects
Coronary angiography ,medicine.medical_specialty ,Critical Care ,business.industry ,Cardiogenic shock ,Transport medicine ,Hemodynamics ,Shock, Cardiogenic ,Conventional treatment ,Emergency Nursing ,medicine.disease ,Patient support ,Patient population ,Treatment Outcome ,Emergency Medicine ,medicine ,Humans ,Heart-Assist Devices ,business ,Intensive care medicine ,Impella - Abstract
Cardiogenic shock (CS) represents a spectrum of hemodynamic deficits in which the cardiac output is insufficient to provide adequate tissue perfusion. The Impella (Abiomed Inc, Danvers, MA) device, a contemporary percutaneous ventricular support, is most often indicated for classic, deteriorating, and extremis Society for Coronary Angiography and Intervention stages of CS, which describe CS that is not responsive to optimal medical management and conventional treatment measures. Impella devices are an evolving field of mechanical support that is used with increasing frequency. Critical care transport medicine crews are required to transport patient support by the Impella device with increasing frequency. It is important that critical care transport medicine crews are familiar with the Impella device and are able to troubleshoot complications that may arise in the transport environment. This article reviews many aspects of the Impella device critical to the transport of this complex patient population.
- Published
- 2022
49. Transition Services Utilization Among US Women Veterans: A Secondary Analysis of a National Survey
- Author
-
Kari L. Fletcher, Justin T. McDaniel, Kate Hendricks Thomas, Majorie J. Scaffa, David L. Albright, Mohammed Alsheri, and Jennifer Anthony
- Published
- 2022
50. Relative Brain Volume of Carnivorans Has Evolved in Correlation with Environmental and Dietary Variables Differentially among Clades
- Author
-
Leigha M, Lynch and Kari L, Allen
- Subjects
Primates ,Behavioral Neuroscience ,Developmental Neuroscience ,Carnivora ,Animals ,Brain ,Organ Size ,Biological Evolution ,Phylogeny ,Diet - Abstract
Carnivorans possess relatively large brains compared to most other mammalian clades. Factors like environmental complexity (Cognitive Buffer Hypothesis) and diet quality (Expensive-Tissue Hypothesis) have been proposed as mechanisms for encephalization in other large-brained clades. We examine whether the Cognitive Buffer and Expensive-Tissue Hypotheses account for brain size variation within Carnivora. Under these hypotheses, we predict a positive correlation between brain size and environmental complexity or protein consumption. Relative endocranial volume (phylogenetic generalized least-squares residual from species’ mean body mass) and 9 environmental and dietary variables were collected from the literature for 148 species of terrestrial and marine carnivorans. We found that the correlation between relative brain volume and environment and diet differed among clades, a trend consistent with other larger brained vertebrates (i.e., Primates, Aves). Mustelidae and Procyonidae demonstrate larger brains in species with higher-quality diets, consistent with the Expensive-Tissue Hypothesis, while in Herpestidae, correlations between relative brain size and environment are consistent with the Cognitive Buffer Hypothesis. Our results indicate that carnivorans may have evolved relatively larger brains under similar selective pressures as primates despite the considerable differences in life history and behavior between these two clades.
- Published
- 2022
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.