233 results on '"Brown RP"'
Search Results
2. Exposure to unethical career events: effects on decision making, climate, and socialization.
- Author
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Mumford MD, Waples EP, Antes AL, Murphy ST, Connelly S, Brown RP, and Devenport LD
- Abstract
An implicit goal of many interventions intended to enhance integrity is to minimize peoples' exposure to unethical events. The intent of the present effort was to examine if exposure to unethical practices in the course of one's work is related to ethical decision making. Accordingly, 248 doctoral students in the biological, health, and social sciences were asked to complete a field appropriate measure of ethical decision making. In addition, they were asked to complete measures examining the perceived acceptability of unethical events and a measure examining perceptions of ethical climate. When these criterion measures were correlated with a measure examining the frequency with which they had been exposed to unethical events in their day-to-day work, it was found that event exposure was strongly related to ethical decision making but less strongly related to climate perceptions and perceptions of event acceptability. However, these relationships were moderated by level of experience. The implications of these findings for practices intended to improve ethics are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2009
3. A meta-analysis of ethics instruction effectiveness in the sciences.
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Antes AL, Murphy ST, Waples EP, Mumford MD, Brown RP, Connelly S, and Devenport LD
- Abstract
Scholars have proposed a number of courses and programs intended to improve the ethical behavior of scientists in an attempt to maintain the integrity of the scientific enterprise. In the present study, we conducted a quantitative meta-analysis based on 26 previous ethics program evaluation efforts, and the results showed that the overall effectiveness of ethics instruction was modest. The effects of ethics instruction, however, were related to a number of instructional program factors, such as course content and delivery methods, in addition to factors of the evaluation study itself, such as the field of investigator and criterion measure utilized. An examination of the characteristics contributing to the relative effectiveness of instructional programs revealed that more successful programs were conducted as seminars separate from the standard curricula rather than being embedded in existing courses. Furthermore, more successful programs were case based and interactive, and they allowed participants to learn and practice the application of real-world ethical decision-making skills. The implications of these findings for future course development and evaluation are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2009
4. Field and experience influences on ethical decision making in the sciences.
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Mumford MD, Connelly S, Murphy ST, Devenport LD, Antes AL, Brown RP, Hill JH, and Waples EP
- Abstract
Differences across fields and experience levels are frequently considered in discussions of ethical decision making and ethical behavior. In the present study, doctoral students in the health, biological, and social sciences completed measures of ethical decision making. The effects of field and level of experience with respect to ethical decision making, metacognitive reasoning strategies, social-behavioral responses, and exposure to unethical events were examined. Social and biological scientists performed better than health scientists with respect to ethical decision making. Furthermore, the ethical decision making of health science students decreased as experience increased. Moreover, these effects appeared to be linked to the specific strategies underlying participants' ethical decision making. The implications of these findings for ethical decision making are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2009
5. A sensemaking approach to ethics training for scientists: preliminary evidence of training effectiveness.
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Mumford MD, Connelly S, Brown RP, Murphy ST, Hill JH, Antes AL, Waples EP, and Devenport LD
- Abstract
In recent years, we have seen a new concern with ethics training for research and development professionals. Although ethics training has become more common, the effectiveness of the training being provided is open to question. In the present effort, a new ethics training course was developed that stresses the importance of the strategies people apply to make sense of ethical problems. The effectiveness of this training was assessed in a sample of 59 doctoral students working in the biological and social sciences using a pre-post design with follow-up and a series of ethical decision-making measures serving as the outcome variable. Results showed not only that this training led to sizable gains in ethical decision making but also that these gains were maintained over time. The implications of these findings for ethics training in the sciences are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2008
6. Environmental influences on ethical decision making: climate and environmental predictors of research integrity.
- Author
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Mumford MD, Murphy ST, Connelly S, Hill JH, Antes AL, Brown RP, and Devenport LD
- Abstract
It is commonly held that early career experiences influence ethical behavior. One way early career experiences might operate is to influence the decisions people make when presented with problems that raise ethical concerns. To test this proposition, 102 first-year doctoral students were asked to complete a series of measures examining ethical decision making along with a series of measures examining environmental experiences and climate perceptions. Factoring of the environmental measure yielded five dimensions: professional leadership, poor coping, lack of rewards, limited competitive pressure, and poor career direction. Factoring of the climate inventory yielded four dimensions: equity, interpersonal conflict, occupational engagement, and work commitment. When these dimensions were used to predict performance on the ethical decision-making task, it was found that the environmental dimensions were better predictors than the climate dimensions. The implications of these findings for research on ethical conduct are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2007
7. Validation of ethical decision making measures: evidence for a new set of measures.
- Author
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Mumford MD, Devenport LD, Brown RP, Connelly S, Murphy ST, Hill JH, and Antes AL
- Abstract
Ethical decision making measures are widely applied as the principal dependent variable used in studies of research integrity. However, evidence bearing on the internal and external validity of these measures is not available. In this study, ethical decision making measures were administered to 102 graduate students in the biological, health, and social sciences, along with measures examining exposure to ethical breaches and the severity of punishments recommended. The ethical decision making measure was found to be related to exposure to ethical events and the severity of punishments awarded. The implications of these findings for the application of ethical decision making measures are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2006
8. Sudarshan Kriya yogic breathing in the treatment of stress, anxiety, and depression: part II -- clinical applications and guidelines.
- Author
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Brown RP and Gerbarg PL
- Abstract
Yogic breathing is a unique method for balancing the autonomic nervous system and influencing psychologic and stress-related disorders. Part I of this series presented a neurophysiologic theory of the effects of Sudarshan Kriya Yoga (SKY). Part II will review clinical studies, our own clinical observations, and guidelines for the safe and effective use of yoga breath techniques in a wide range of clinical conditions. Although more clinical studies are needed to document the benefits of programs that combine pranayama (yogic breathing) asanas (yoga postures), and meditation, there is sufficient evidence to consider Sudarshan Kriya Yoga to be a beneficial, low-risk, low-cost adjunct to the treatment of stress, anxiety, post-traumatic stress disorder (PTSD), depression, stress-related medical illnesses, substance abuse, and rehabilitation of criminal offenders. SKY has been used as a public health intervention to alleviate PTSD in survivors of mass disasters. Yoga techniques enhance well-being, mood, attention, mental focus, and stress tolerance. Proper training by a skilled teacher and a 30-minute practice every day will maximize the benefits. Health care providers play a crucial role in encouraging patients to maintain their yoga practices. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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9. Sudarshan Kriya yogic breathing in the treatment of stress, anxiety, and depression: part I -- neurophysiologic model [corrected] [published erratum appears in J ALTERN COMPLEMENT MED 2005 Apr;11(2):383-4].
- Author
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Brown RP and Gerbarg PL
- Abstract
Mind-body interventions are beneficial in stress-related mental and physical disorders. Current research is finding associations between emotional disorders and vagal tone as indicated by heart rate variability. A neurophysiologic model of yogic breathing proposes to integrate research on yoga with polyvagal theory, vagal stimulation, hyperventilation, and clinical observations. Yogic breathing is a unique method for balancing the autonomic nervous system and influencing psychologic and stress-related disorders. Many studies demonstrate effects of yogic breathing on brain function and physiologic parameters, but the mechanisms have not been clarified. Sudarshan Kriya yoga (SKY), a sequence of specific breathing techniques (ujjayi, bhastrika, and Sudarshan Kriya) can alleviate anxiety, depression, everyday stress, post-traumatic stress, and stress-related medical illnesses. Mechanisms contributing to a state of calm alertness include increased parasympathetic drive, calming of stress response systems, neuroendocrine release of hormones, and thalamic generators. This model has heuristic value, research implications, and clinical applications. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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10. Rhodiola rosea: a phytomedicinal overview.
- Author
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Brown RP, Gerbarg PL, and Ramazanov Z
- Abstract
Rhodiola has been used for centuries in Northern Europe, yet, despite decades of study, it remains largely unknown. This overview summarizes much of the available information about traditional and modern uses of the versitile Rhodiola rosea. [ABSTRACT FROM AUTHOR]
- Published
- 2002
11. Historical volcanism and within-island genetic divergence in the Tenerife skink (Squamata: Scincidae)
- Author
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Brown, RP, Woods, M, and Thorpe, RS
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QL ,GE ,QH ,QH426 - Abstract
This study examines the genetic diversity of the Tenerife skink (Chalcides viridanus) within the context that Tenerife is now thought to have arisen as a single island as opposed to two/three precursor islands. DNA sequences were obtained from two mitochondrial regions and five nuclear loci. MtDNA divergence was substantial with four geographical clusters being detected. Two of these corresponded to two ancient areas that have undergone little recent eruptive activity (Anaga, Teno), while two further clusters were found within the more volcanically active central region. Nuclear divergence was low and revealed no strong geographical pattern. Estimated divergence of the Anaga group was 0.4-2.1 Ma ago (95% posterior interval), while the divergence time of the Teno cluster was 0.1-1.2 Ma ago. Phylogeographic distributions correspond well with ancient edifices, but divergence times postdate those expected under the previous ‘unification of ancient islands’ geological scenario. There is evidence of a major recent expansion of the central group following a decline in eruptive activity in this region, which also fits well with current geological hypotheses. Previously-described within-island evolutionary patterns in other Tenerife species also need to examined within this new geological context.
12. GEOGRAPHIC-VARIATION AND POPULATION SYSTEMATICS - DISTINGUISHING BETWEEN ECOGENETICS AND PHYLOGENETICS
- Author
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Thorpe, Rs, Brown, Rp, and Malhotra, A.
13. Conservation Genomics of Endangered Alpine Ichthyofauna
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Ilardo, B, Brown, RP, Nichols, H, Micheletti, D, and Gandolfi, A
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GE ,QK - Abstract
The recent discovery of a pike species, Esox flaviae of Esox cisalpinus ("Italian pike") native to the Italian region has fuelled debate on the conservation status of this prized game fish and apex predator. Introgressive hybridization with allochthonous Northern pike (Esox lucius, here "European pike") is one of the main threats to the genetic identity of the newly described pike. We aim to understand the underlying genomic adaptations of this species to its environment, its population structure and evolutionary relationship with European pike, through a Whole Genome Sequencing (WGS) approach.
14. Skull morphological variation in a British stranded population of false killer whale (Pseudorca crassidens, Owen 1846): a 3D geometric morphometric approach
- Author
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Vicari, D, Sabin, RC, Brown, RP, Lambert, O, Bianucci, G, and Meloro, C
- Subjects
QH301 ,QL ,GE - Abstract
The false killer whale (Pseudorca crassidens (Owen, 1846)) is a globally distributed delphinid that shows geographical differentiation in its skull morphology. We explored cranial morphological variation in a sample of 85 skulls belonging to a mixed sex population stranded in the Moray Firth, Scotland, in 1927. A three-dimensional digitizer (Microscribe 2GX) was used to record 37 anatomical landmarks on the cranium and 25 on the mandible to investigate size and shape variation and to explore sexual dimorphism using geometric morphometric. Males showed greater overall skull size than females, whereas no sexual dimorphism could be identified in cranial and mandibular shape. Allometric skull changes occurred in parallel for both males and females, supporting the lack of sexual shape dimorphism for this particular sample. Also, fluctuating asymmetry did not differ between crania of males and females. This study confirms the absence of sexual shape dimorphism and the presence of a sexual size dimorphism in this false killer whale population.
15. Is there an association between Boletus lignicola and Phaeolus schweinitzii?
- Author
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Brown, RP, primary
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- 1985
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16. More on Metoclopramide and Tardive Dyskinesia
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Brown Rp and Mahler Jc
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Pediatrics ,medicine.medical_specialty ,Metoclopramide ,business.industry ,medicine ,General Medicine ,business ,Tardive dyskinesia ,medicine.disease ,medicine.drug - Published
- 1987
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17. Clinical roundup: how do you treat chronic fatigue syndrome in your practice? Using an integrative approach.
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Brown RP
- Published
- 2008
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18. Images in cardiology: neovascularisation of giant left atrial myxoma visualised on angiography.
- Author
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Yan BPY, Aggarwal A, Brown RP, Ajani AE, Yan, B P Y, Aggarwal, A, Brown, R P, and Ajani, A E
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- 2005
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19. Evaluating effects of community-based social healing model on Ubuntu, mental health and psychosocial functioning in post-genocide Rwanda: protocol for cluster randomized control trial.
- Author
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Jansen S, Niyonzima JB, Gerbarg P, Brown RP, Nsengiyumva A, Niyonsenga J, and Nsabimana E
- Subjects
- Humans, Rwanda, Randomized Controlled Trials as Topic, Treatment Outcome, Female, Male, Time Factors, Adult, Mental Health, Genocide psychology, Stress Disorders, Post-Traumatic psychology, Stress Disorders, Post-Traumatic therapy, Psychosocial Functioning
- Abstract
Background: The community-based social healing (CBSH) model, developed by Ubuntu Centre for Peace, aims to support individuals with traumatic experiences and mental health challenges in achieving better mental health. CBSH combines BREATH-BODY-MIND™ (BBM) practices with collective narrative and rituals, facilitated by Community Healing Assistants in therapeutic groups. A previous pilot study involving 1889 Rwandan CBSH participants showed significant mental health improvements, including reductions in depression, anxiety, and PTSD, along with enhanced work productivity, and decreased intimate partner violence. The trial investigates the CBSH model's impact on Ubuntu and mental health. Ubuntu, a concept that encompasses humanness, compassion, and interconnectedness, is deeply rooted in the African philosophy., Methods/design: This cluster randomized controlled trial will involve 54 villages randomly selected in the Kirehe district, with 1080 participants randomly allocated equally to the CBSH intervention or a wait-list control group. While the trial will be conducted at the village (cluster) level, both primary and secondary outcomes will be measured individually for participants within each cluster. The Primary outcome "Ubuntu" will be measured using a context-adapted Ubuntu measurement scale. Secondary outcomes include psychosocial indicators which will be assessed through standardized tools such as the Patient Health Questionnaire for depression (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), Warwick-Edinburgh Mental Wellbeing scale (WEMWS), Connor-Davidson Resilience scale (CD-RISK-10), Somatic Symptom Severity Scale (PHQ-15), Revised Conflict Tactics scale (CTS2S), and Adapted Social Capital Assessment Tool (SASCAT)., Conclusion: This trial aims to evaluate the CBSH model's impacts on Ubuntu, mental health, and social functioning among trauma-affected Rwandans, including those impacted by the 1994 Genocide against the Tutsi, mass killings, sexual abuse, and domestic violence. The findings could be of value to the Ubuntu Centre for Peace, policymakers, healthcare practitioners, and other stakeholders, by highlighting the significance of promoting Ubuntu as a foundation for addressing mental health challenges and the consequences of psychosocial trauma., Trial Registration: ISRCTN ISRCTN17659369. Registered on February 09, 2024., Competing Interests: Declarations Ethics approval and consent to participate The Institutional Review Board of the College of Medicine and Health Sciences at the University of Rwanda has granted ethical approval to this trial (No 111/CMHS IRB/2024). The trial has already been registered with ISRCTN (ISRCTN17659369, registered on February 09, 2024). Eligible participants will be given an explanation of the study, including potential risks and benefits, and will sign informed consent forms prior to participating. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)
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- 2024
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20. Three-dimensional geometric morphometric analyses of humerus ecomorphology: New perspectives for paleohabitat reconstruction in carnivorans and ungulates.
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Serio C, Brown RP, Clauss M, and Meloro C
- Abstract
Long bone ecomorphology has proven effective for paleohabitat reconstructions across a wide range of mammalian clades. Still, there is no comprehensive framework to allow interpretation of long bone morphological variation within and between different monophyletic groups. Here, we investigated the use of humerus morphometry to classify living members of the orders Carnivora and ungulates based on their preferred habitats. Using geometric morphometrics, we extracted three different kinds of humerus shape data describing interspecific variation with and without accounting for evolutionary allometry and phylogenetic signal. The traditional a priori categorization of species in open, mixed, and closed habitats was employed in combination with selected subsets of shape variables to identify the best-predictive models for habitat adaptation. These were identified based on the statistical performance of phylogenetic and non-phylogenetic discriminant analyses and then applied to predict habitats on a subsample of fossil species. Size-free shape data combined with phylogenetic discriminant analyses showed the highest rate of accuracy in habitat classification for a combined sample of carnivorans and ungulates. Conversely, when the two groups were investigated separately, traditional shape data analyzed with phylogenetic discriminant function analyses provided models with the greatest predictive power. By combining carnivorans and ungulates within the same methodological framework we identified common adaptive features in closed habitat-adapted species that show compressed epiphyses, while open habitat-adapted species have expanded epiphyses. These morphologies evolved to allow significant degree of direction switches during locomotion in closed habitats compared to open habitat-adapted species whose forelimb joints evolved to stabilize articulations for increasing speed., (© 2024 The Author(s). The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)
- Published
- 2024
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21. Preliminary Validation of Two Brief Measures of Masculine and Feminine Honor Endorsement.
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Bock JE, Brown RP, Pomerantz AL, and Raj A
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- Humans, Female, Adult, Male, Reproducibility of Results, Young Adult, Middle Aged, Masculinity, Femininity, Adolescent, Surveys and Questionnaires, Psychometrics
- Abstract
Researchers have developed numerous individual differences measures to assess people's endorsement of honor ideology (i.e., beliefs regarding the importance of honor and reputation) with most ranging from 12-36 items in length. Despite having great utility, the length of these measures magnifies the costs associated with survey research, especially in research contexts that use large, representative samples (e.g., health surveys). The present study aimed to develop and validate single-item measures that assess participants' agreement with gender-specific honor prototypes, as well as short-form versions of the honor ideology for manhood (HIM) and honor ideology for womanhood (HIW) scales. An initial sample of participants ( N = 879) completed single-item honor prototype measures, a battery of previously validated honor measures (including the HIM and HIW), and measures of constructs previously shown to be related to the dynamics of honor (e.g., aggression, firearm ownership). A second sample of participants ( N = 100) completed the new measures, as well as an abbreviated battery of honor measures, to examine test-retest reliability. Results indicated that the new, brief measures were strongly correlated with both the original HIM and HIW as well as several other established honor measures. Moreover, the associations between these new measures and honor-related outcomes were nearly identical to those found with the original HIM and HIW. Our new measures also demonstrated acceptable test-retest reliability, despite being single-item scales. Overall, the present work provides preliminary support for several brief measures of honor endorsement that researchers can use when longer scales are not feasible.
- Published
- 2024
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22. Breath-Body-Mind Core Techniques to Manage Medical Student Stress.
- Author
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Gerbarg PL, Cruz-Cordero YL, Conte VA, García ME, Braña A, Estape ES, and Brown RP
- Abstract
Objectives: This pilot study evaluated the feasibility of a live, interactive, synchronous, online, manualized intervention, Breath-Body-Mind Introductory Course (BBM-IC), for medical students. BBM-IC includes breathing, movement, and attention-focus techniques for stress management and better emotion regulation, energy, sleep, and mental focus., Methods: Medical students attending a 2-h BBM demonstration were invited to participate in the 12-h BBM-IC and weekly 45-min 6-week group practice. Measures were obtained using Survey Monkey: patient health questionnaire (PHQ9), generalized anxiety disorder-7 (GAD-7), exercise-induced feeling inventory (EFI), sleep quality scale (SQS), and body perception questionnaire-short form (BPQ-SF) at pre-BBM-IC (T1), post-BBM-IC (T2), and 6 weeks post (T3). Perceived stress scale (PSS) and meditation practices questionnaire (MPQ) were measured at baseline (T1) only., Results: Twelve medical students participated in BBM-IC 4-h daily for 3 days. Six attended practice sessions and completed 6-week post-tests. Mean scores comparison identified two variable sets with significant improvements: EFI tranquility ( p < .005) and supradiaphragmatic reactivity ( p < .040). Two measures reached near significance: SQS ( p ≤ .060) and PHQ9 ( p ≤ .078)., Conclusion: This pilot study provided preliminary evidence that BBM-IC may reduce stress and anxiety symptoms while improving mood, energy, mental focus, and other correlates of psychophysiological state in medical students. Taking time for self-care is challenging for medical students, as reflected in the small study enrollment. Designating time for BBM as a requirement within the medical curriculum would probably enable more students to participate and acquire skills to reduce the effects of stress on their physical and psychological health, as well as the health of their patients., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)
- Published
- 2023
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23. Habitat-associated Genomic Variation in a Wall Lizard from an Oceanic Island.
- Author
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Brown RP, Sun H, Jin Y, and Meloro C
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- Humans, Animals, Gene Frequency, Ecosystem, Gene Flow, Genomics, Genetics, Population, Lizards genetics
- Abstract
The lizard Teira dugesii exhibits morphological divergence between beach and inland habitats in the face of gene flow, within the volcanic island of Madeira, Portugal. Here, we analyzed genomic data obtained by genotyping-by-sequencing, which provided 16,378 single nucleotide polymorphisms (SNPs) from 94 individuals sampled from 15 sites across Madeira. Ancient within-island divergence in allopatry appears to have mediated divergence in similar species within other Atlantic islands, but this hypothesis was not supported for T. dugesii. Across all samples, a total of 168 SNPs were classified as statistical outliers using pcadapt and OutFLANK. Redundancy analysis (RDA) revealed that 17 of these outliers were associated with beach/inland habitats. The SNPs were located within 16 sequence tags and 15 of these were homologous with sequences in a 31 Mb region on chromosome 3 of a reference wall lizard genome (the remaining tag could not be associated with any chromosome). We further investigated outliers through contingency analyses of allele frequencies at each of four pairs of adjacent beach-inland sites. The majority of the outliers detected by the RDA were confirmed at two pairs of these matched sites. These analyses also suggested some parallel divergence at different localities. Six other outliers were associated with site elevation, four of which were located on chromosome 5 of the reference genome. Our study lends support to a previous hypothesis that divergent selection between gray shingle beaches and inland regions overcomes gene flow and leads to the observed morphological divergence between populations in these adjacent habitats., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)
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- 2023
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24. Veteran suicide rates mirror, but do not account for, elevated suicide rates among the general population in US cultures of honor.
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Bock JE, Tucker RP, Brown RP, Foster S, and Anestis MD
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- Humans, United States epidemiology, Risk Factors, Ownership, Suicide, Firearms, Veterans
- Abstract
Introduction: Veteran total and firearm suicide rates are higher compared to the general population. Among the general population, total and firearm suicide rates are higher in US states deemed cultures of honor compared to non-honor states, likely because honor states have higher firearm ownership rates and fewer firearm laws. Considering that veterans tend to live in states with fewer firearm laws and that veteran population rates predict both statewide total and firearm suicide rates, it is possible that the elevated suicide rates seen in honor states in part due to those states having a greater presence of veterans compared to non-honor states., Method: Publicly available databases were used to obtain total and firearm suicide rates (per 100 k) for veterans and non-veterans, as well as our covariates (e.g., rurality)., Results: Veteran population proportions were higher in honor states than non-honor states. Veteran and non-veteran total and firearm suicide rates were higher in honor states compared to non-honor states. Statewide differences in all four suicide rates were indirectly explained by honor states having higher firearm ownership than non-honor states., Conclusions: These findings add to a growing body of literature showing that enacting firearm regulations may be a viable public health approach for preventing suicide., (© 2023 American Association of Suicidology.)
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- 2023
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25. Barriers to chimpanzee gene flow at the south-east edge of their distribution.
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Bonnin N, Piel AK, Brown RP, Li Y, Connell AJ, Avitto AN, Boubli JP, Chitayat A, Giles J, Gundlapally MS, Lipende I, Lonsdorf EV, Mjungu D, Mwacha D, Pintea L, Pusey AE, Raphael J, Wich SA, Wilson ML, Wroblewski EE, Hahn BH, and Stewart FA
- Subjects
- Animals, Ecosystem, Pan troglodytes genetics, Gene Flow, Microsatellite Repeats genetics, Haplotypes genetics, Genetics, Population, Genetic Variation genetics
- Abstract
Populations on the edge of a species' distribution may represent an important source of adaptive diversity, yet these populations tend to be more fragmented and are more likely to be geographically isolated. Lack of genetic exchanges between such populations, due to barriers to animal movement, can not only compromise adaptive potential but also lead to the fixation of deleterious alleles. The south-eastern edge of chimpanzee distribution is particularly fragmented, and conflicting hypotheses have been proposed about population connectivity and viability. To address this uncertainty, we generated both mitochondrial and MiSeq-based microsatellite genotypes for 290 individuals ranging across western Tanzania. While shared mitochondrial haplotypes confirmed historical gene flow, our microsatellite analyses revealed two distinct clusters, suggesting two populations currently isolated from one another. However, we found evidence of high levels of gene flow maintained within each of these clusters, one of which covers an 18,000 km
2 ecosystem. Landscape genetic analyses confirmed the presence of barriers to gene flow with rivers and bare habitats highly restricting chimpanzee movement. Our study demonstrates how advances in sequencing technologies, combined with the development of landscape genetics approaches, can resolve ambiguities in the genetic history of critical populations and better inform conservation efforts of endangered species., (© 2023 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)- Published
- 2023
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26. Breath-centered virtual mind-body medicine reduces COVID-related stress in women healthcare workers of the Regional Integrated Support for Education in Northern Ireland: a single group study.
- Author
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Gerbarg PL, Dickson F, Conte VA, and Brown RP
- Abstract
Background: During the COVID-19 pandemic, healthcare workers endured prolonged stress affecting their psychological well-being. Objectives: (1) Evaluate the effects of the Breath-Body-Mind Introductory Course (BBMIC) on COVID-related stress among employees of the Regional Integrated Support for Education, Northern Ireland, (2) Reduce the risk of adverse effects from COVID-related stress, and (3) Evaluate the effects of BBMIC on indicators of psychophysiological states and the consistency with hypothesized mechanisms of action., Methods: In this single group study, a convenience sample of 39 female healthcare workers completed informed consent and baseline measures: Perceived Stress Scale (PSS), Stress Overload Scale-Short (SOS-S), and Exercise-Induced Feelings Inventory (EFI). Following the online BBMIC 4 h/day for 3 days and the 6 week solo (20 min/day) and group practice (45 min weekly), repeat testing plus the Indicators of Psychophysiological State (IPSS) and Program Evaluation were obtained., Results: Baseline (T1) mean PSS score was significantly elevated compared to a normative sample: PSS = 18.2 vs. 13.7 ( p < 0.001) and improved significantly 11 weeks post-BBMIC (T4). SOS-S mean score declined from 10.7(T1) to 9.7 at 6 week post-test (T3). The SOS-S proportion of High Risk scores found in 22/29 participants (T1), dropped to 7/29 (T3). EFI mean subscale scores improved significantly from T1 to T2 and T3 for Revitalization ( p < 0.001); Exhaustion ( p < 0.002); and Tranquility ( p < 0.001); but not Engagement ( p < 0.289)., Conclusion: Among RISE NI healthcare workers affected by COVID-related stress, participation in the BBMIC significantly reduced scores for Perceived Stress, Stress Overload, and Exhaustion. EFI Revitalization and Tranquility scores significantly improved. More than 60% of participants reported moderate to very strong improvements in 22 indicators of psychophysiological state, e.g., tension, mood, sleep, mental focus, anger, connectedness, awareness, hopefulness, and empathy. These results are consistent with the hypothesized mechanisms of action whereby voluntarily regulated breathing exercises change interoceptive messaging to brain regulatory networks that shift psychophysiological states of distress and defense to states of calmness and connection. These positive findings warrant validation in larger, controlled studies to extend the understanding of how breath-centered Mind-body Medicine practices could mitigate adverse effects of stress., Competing Interests: PG and RB have written books and book chapters about Complementary and Integrative Medicine, including breath-centered mind-body practices. They sometimes receive financial remuneration or honoraria for teaching mind-body practices. They are Co-Founders and members of the Board of Directors of the Breath-Body-Mind Foundation, a not-for-profit 501(c)3 that provides pro bono crisis relief programs for survivors of mass disasters, scholarships for applicants who cannot afford to pay for training, and grants for research projects. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gerbarg, Dickson, Conte and Brown.)
- Published
- 2023
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27. A patient-centered nurse-supported primary care-based collaborative care program to treat opioid use disorder and depression: Design and protocol for the MI-CARE randomized controlled trial.
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DeBar LL, Bushey MA, Kroenke K, Bobb JF, Schoenbaum M, Thompson EE, Justice M, Zatzick D, Hamilton LK, McMullen CK, Hallgren KA, Benes LL, Forman DP, Caldeiro RM, Brown RP, Campbell NL, Anderson ML, Son S, Haggstrom DA, Whiteside L, Schleyer TKL, and Bradley KA
- Subjects
- Adult, Humans, Depression drug therapy, Depression diagnosis, Patient-Centered Care, Randomized Controlled Trials as Topic, Motivational Interviewing, Opioid-Related Disorders drug therapy, Buprenorphine therapeutic use
- Abstract
Background: Opioid use disorder (OUD) contributes to rising morbidity and mortality. Life-saving OUD treatments can be provided in primary care but most patients with OUD don't receive treatment. Comorbid depression and other conditions complicate OUD management, especially in primary care. The MI-CARE trial is a pragmatic randomized encouragement (Zelen) trial testing whether offering collaborative care (CC) to patients with OUD and clinically-significant depressive symptoms increases OUD medication treatment with buprenorphine and improves depression outcomes compared to usual care., Methods: Adult primary care patients with OUD and depressive symptoms (n ≥ 800) from two statewide health systems: Kaiser Permanente Washington and Indiana University Health are identified with computer algorithms from electronic Health record (EHR) data and automatically enrolled. A random sub-sample (50%) of eligible patients is offered the MI-CARE intervention: a 12-month nurse-driven CC intervention that includes motivational interviewing and behavioral activation. The remaining 50% of the study cohort comprise the usual care comparison group and is never contacted. The primary outcome is days of buprenorphine treatment provided during the intervention period. The powered secondary outcome is change in Patient Health Questionnaire (PHQ)-9 depression scores. Both outcomes are obtained from secondary electronic healthcare sources and compared in "intent-to-treat" analyses., Conclusion: MI-CARE addresses the need for rigorous encouragement trials to evaluate benefits of offering CC to generalizable samples of patients with OUD and mental health conditions identified from EHRs, as they would be in practice, and comparing outcomes to usual primary care. We describe the design and implementation of the trial, currently underway., Trial Registration: ClinicalTrials.gov Identifier: NCT05122676. Clinical trial registration date: November 17, 2021., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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28. Life on a beach leads to phenotypic divergence despite gene flow for an island lizard.
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Brown RP, Jin Y, Thomas J, and Meloro C
- Subjects
- Animals, Gene Flow, Bayes Theorem, Ecosystem, Genetic Variation, Lizards genetics, Lizards anatomy & histology
- Abstract
Limited spatial separation within small islands suggests that observed population divergence may occur due to habitat differences without interruption to gene flow but strong evidence of this is scarce. The wall lizard Teira dugesii lives in starkly contrasting shingle beach and inland habitats on the island of Madeira. We used a matched pairs sampling design to examine morphological and genomic divergence between four beach and adjacent (<1 km) inland areas. Beach populations are significantly darker than corresponding inland populations. Geometric morphometric analyses reveal divergence in head morphology: beach lizards have generally wider snouts. Genotyping-by-sequencing allows the rejection of the hypothesis that beach populations form a distinct lineage. Bayesian analyses provide strong support for models that incorporate gene flow, relative to those that do not, replicated at all pairs of matched sites. Madeiran lizards show morphological divergence between habitats in the face of gene flow, revealing how divergence may originate within small islands., (© 2023. The Author(s).)
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- 2023
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29. Accurate modeling of replication rates in genome-wide association studies by accounting for Winner's Curse and study-specific heterogeneity.
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Zou J, Zhou J, Faller S, Brown RP, Sankararaman SS, and Eskin E
- Subjects
- Humans, Multifactorial Inheritance, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide
- Abstract
Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex human traits, but only a fraction of variants identified in discovery studies achieve significance in replication studies. Replication in genome-wide association studies has been well-studied in the context of Winner's Curse, which is the inflation of effect size estimates for significant variants due to statistical chance. However, Winner's Curse is often not sufficient to explain lack of replication. Another reason why studies fail to replicate is that there are fundamental differences between the discovery and replication studies. A confounding factor can create the appearance of a significant finding while actually being an artifact that will not replicate in future studies. We propose a statistical framework that utilizes genome-wide association studies and replication studies to jointly model Winner's Curse and study-specific heterogeneity due to confounding factors. We apply this framework to 100 genome-wide association studies from the Human Genome-Wide Association Studies Catalog and observe that there is a large range in the level of estimated confounding. We demonstrate how this framework can be used to distinguish when studies fail to replicate due to statistical noise and when they fail due to confounding., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)
- Published
- 2022
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30. Skull ecomorphological variation of narwhals (Monodon monoceros, Linnaeus 1758) and belugas (Delphinapterus leucas, Pallas 1776) reveals phenotype of their hybrids.
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Vicari D, Lorenzen ED, Skovrind M, Szpak P, Louis M, Olsen MT, Brown RP, Lambert O, Bianucci G, Sabin RC, and Meloro C
- Subjects
- Animals, Cetacea, Female, Gelatin, Male, Phenotype, Skull, Beluga Whale
- Abstract
Narwhals and belugas are toothed whales belonging to the Monodontidae. Belugas have a circumpolar Arctic and sub-Artic distribution while narwhals are restricted to the Atlantic Arctic. Their geographical ranges overlap during winter migrations in the Baffin Bay area (Canada/West Greenland) and successful interbreeding may occur. Here, we employed geometric morphometrics on museum specimens to explore the cranium and mandible morphology of a known hybrid (NHMD MCE 1356) and the cranium morphology of a putative hybrid (NHMD 1963.44.1.4) relative to skull morphological variation in the parental species. Specifically, we used 3D models of skulls from 69 belugas, 86 narwhals, and the two known/putative hybrids and 2D left hemi-mandibles from 20 belugas, 64 narwhals and the known hybrid. Skull shape analyses allowed clear discrimination between species. Narwhals are characterised by a relatively short rostrum and wide neurocranium while belugas show a more elongated and narrower cranium. Sexual size dimorphism was detected in narwhals, with males larger than females, but no sexual shape dimorphism was detected in either species (excluding presence/absence of tusks in narwhals). Morphological skull variation was also dependent on different allometric slopes between species and sexes in narwhals. Our analyses showed that the cranium of the known hybrid was phenotypically close to belugas but its 2D hemi-mandible had a narwhal shape and size morphology. Both cranium and mandible were strongly correlated, with the pattern of covariation being similar to belugas. The putative hybrid was a pure male narwhal with extruded teeth. Comparison of genomic DNA supported this result, and stable carbon and nitrogen isotope values suggested that the putative hybrid had a more benthic foraging strategy compared to narwhals. This work demonstrates that although the known hybrid could be discriminated from narwhals and belugas, detection of its affinities with these parental species was dependent on the part of the skull analysed., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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31. Functional correlates of skull shape in Chiroptera: feeding and echolocation adaptations.
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Giacomini G, Herrel A, Chaverri G, Brown RP, Russo D, Scaravelli D, and Meloro C
- Subjects
- Animals, Biological Evolution, Humans, Phylogeny, Skull anatomy & histology, Chiroptera physiology, Echolocation physiology
- Abstract
Morphological, functional, and behavioral adaptations of bats are among the most diverse within mammals. A strong association between bat skull morphology and feeding behavior has been suggested previously. However, morphological variation related to other drivers of adaptation, in particular echolocation, remains understudied. We assessed variation in skull morphology with respect to ecology (diet and emission type) and function (bite force, masticatory muscles and echolocation characteristics) using geometric morphometrics and comparative methods. Our study suggests that variation in skull shape of 10 bat families is the result of adaptations to broad dietary categories and sound emission types (oral or nasal). Skull shape correlates with echolocation parameters only in a subsample of insectivorous species, possibly because they (almost) entirely rely on this sensory system for locating and capturing prey. Insectivores emitting low frequencies are characterized by a ventrally tilted rostrum, a trait not associated with feeding parameters. This result questions the validity of a trade-off between feeding and echolocation function. Our study advances understanding of the relationship between skull morphology and specific features of echolocation and suggests that evolutionary constraints due to echolocation may differ between different groups within the Chiroptera., (© 2021 The Authors. Integrative Zoology published by International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)
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- 2022
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32. Factors contributing to honor-endorsing men's suicide capability: Firearm ownership, practical capability, and exposure to painful and provocative events.
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Bock JE, Tucker RP, Brown RP, Harrington EE, Bauer BW, Daruwala SE, Capron DW, and Anestis MD
- Subjects
- Adult, Aged, Humans, Male, Motivation, Ownership, Risk Factors, United States, Young Adult, Firearms, Suicide
- Abstract
Objective: White men in U.S. cultures of honor die by suicide at greater rates than other demographic groups. This finding has been attributed to factors such as the prevalence and use of firearms in men's suicide in honor states, as well as motivational risk factors (e.g., thwarted belongingness). Other features of honor cultures (e.g., physical aggression, risk-taking behaviors) suggest that honor-endorsing men may frequently experience painful and provocative events (PPEs), which, in turn, may facilitate practical capability for suicide. The present work tested this hypothesis and honor ideology's relationship to firearm ownership and storage practices., Method: In two samples of mostly White U.S. men-one undergraduate sample (N = 472, M
age = 19.76) and one middle- to older adult sample (N = 419, Mage = 65.17)-we assessed honor ideology endorsement, PPEs, practical capability for suicide, and firearm-related outcomes., Results: Honor endorsement was greater among firearm owners (particularly self-protective owners), but it was unrelated to storage practices. Honor endorsement was positively associated with PPEs and practical capability. Additionally, the relationship between honor ideology and practical capability was indirectly explained by PPE exposure., Conclusions: Results highlight multiple avenues-PPEs, practical capability for suicide, (self-protective) firearm ownership-by which masculine honor norms may place men at risk for suicide., (© 2021 The American Association of Suicidology.)- Published
- 2021
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33. Genomic signatures of drift and selection driven by predation and human pressure in an insular lizard.
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Bassitta M, Brown RP, Pérez-Cembranos A, Pérez-Mellado V, Castro JA, Picornell A, and Ramon C
- Subjects
- Adaptation, Physiological, Animals, Genome, Predatory Behavior, Spain, Genetic Drift, Genetic Variation, Lizards genetics, Selection, Genetic
- Abstract
Genomic divergence was studied in 10 small insular populations of the endangered Balearic Islands lizard (Podarcis lilfordi) using double digest restriction-site associated DNA sequencing. The objectives were to establish levels of divergence among populations, investigate the impact of population size on genetic variability and to evaluate the role of different environmental factors on local adaptation. Analyses of 72,846 SNPs supported a highly differentiated genetic structure, being the populations with the lowest population size (Porros, Foradada and Esclatasang islets) the most divergent, indicative of greater genetic drift. Outlier tests identified ~ 2% of loci as candidates for selection. Genomic divergence-Enviroment Association analyses were performed using redundancy analyses based on SNPs putatively under selection, detecting predation and human pressure as the environmental variables with the greatest explanatory power. Geographical distributions of populations and environmental factors appear to be fundamental drivers of divergence. These results support the combined role of genetic drift and divergent selection in shaping the genetic structure of these endemic island lizard populations.
- Published
- 2021
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34. Subspecies hybridization as a potential conservation tool in species reintroductions.
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Zecherle LJ, Nichols HJ, Bar-David S, Brown RP, Hipperson H, Horsburgh GJ, and Templeton AR
- Abstract
Reintroductions are a powerful tool for the recovery of endangered species. However, their long-term success is strongly influenced by the genetic diversity of the reintroduced population. The chances of population persistence can be improved by enhancing the population's adaptive ability through the mixing of individuals from different sources. However, where source populations are too diverse the reintroduced population could also suffer from outbreeding depression or unsuccessful admixture due to behavioural or genetic barriers. For the reintroduction of Asiatic wild ass Equus hemionus ssp. in Israel, a breeding core was created from individuals of two different subspecies ( E. h. onager & E. h. kulan ). Today the population comprises approximately 300 individuals and displays no signs of outbreeding depression. The aim of this study was a population genomic evaluation of this conservation reintroduction protocol. We used maximum likelihood methods and genetic clustering analyses to investigate subspecies admixture and test for spatial autocorrelation based on subspecies ancestry. Further, we analysed heterozygosity and effective population sizes in the breeding core prior to release and the current wild population. We discovered high levels of subspecies admixture in the breeding core and wild population, consistent with a significant heterozygote excess in the breeding core. Furthermore, we found no signs of spatial autocorrelation associated with subspecies ancestry in the wild population. Inbreeding and variance effective population size estimates were low. Our results indicate no genetic or behavioural barriers to admixture between the subspecies and suggest that their hybridization has led to greater genetic diversity in the reintroduced population. The study provides rare empirical evidence of the successful application of subspecies hybridization in a reintroduction. It supports use of intraspecific hybridization as a tool to increase genetic diversity in conservation translocations., Competing Interests: None declared., (© 2021 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)
- Published
- 2021
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35. Survey of public attitudes towards imminent death donation in the United States.
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Washburn L, Galván NTN, Moolchandani P, Price MB, Rath S, Ackah R, Myers KA, Wood RP, Parsons S, Brown RP, Ranova E, Goss M, Rana A, and Goss JA
- Subjects
- Adolescent, Adult, Attitude, Cross-Sectional Studies, Humans, Public Opinion, United States, Death, Tissue and Organ Procurement
- Abstract
Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient. Although IDD was ethically justified by United Network for Organ Sharing, the concept remains controversial due to presumed lack of public support. The aim of this study was to evaluate the public's attitudes towards IDD. A cross-sectional survey was conducted of US adults age >18 years (n = 2644). The survey included a case scenario of a patient with a devastating brain injury. Responses were assessed on a 5-point Likert scale. Results showed that 68% - 74% of participants agreed or strongly agreed with IDD when posed as a general question and in relation to the case scenario. Participants were concerned about "recovery after a devastating brain injury" (34%), and that "doctors would not try as hard to save a patient's life" (33%). Only 9% of participants would be less likely to trust the organ donation process. In conclusion, our study demonstrates strong public support for IDD in the case of a patient with a devastating brain injury. Notably, participants were not largely concerned with losing trust in the organ donation process. These results justify policy change towards imminent death donation., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2021
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36. Dorsal Pigmentation and Its Association with Functional Variation in MC1R in a Lizard from Different Elevations on the Qinghai-Tibetan Plateau.
- Author
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Jin Y, Tong H, Shao G, Li J, Lv Y, Wo Y, Brown RP, and Fu C
- Subjects
- Animals, Female, Lizards metabolism, Male, Polymorphism, Single Nucleotide, Signal Transduction, Tibet, Altitude, Lizards genetics, Pigmentation genetics, Receptor, Melanocortin, Type 1 genetics
- Abstract
Identification of the role of the MC1R gene has provided major insights into variation in skin pigmentation in several organisms, including humans, but the evolutionary genetics of this variation is less well established. Variation in this gene and its relationship with degree of melanism was analyzed in one of the world's highest-elevation lizards, Phrynocephalus theobaldi from the Qinghai-Tibetan Plateau. Individuals from the low-elevation group were shown to have darker dorsal pigmentation than individuals from a high-elevation group. The existence of climatic variation across these elevations was quantified, with lower elevations exhibiting higher air pressure, temperatures, and humidity, but less wind and insolation. Analysis of the MC1R gene in 214 individuals revealed amino acid differences at five sites between intraspecific sister lineages from different elevations, with two sites showing distinct fixed residues at low elevations. Three of the four single-nucleotide polymorphisms that underpinned these amino acid differences were highly significant outliers, relative to the generalized MC1R population structuring, suggestive of selection. Transfection of cells with an MC1R allele from a lighter high-elevation population caused a 43% reduction in agonist-induced cyclic AMP accumulation, and hence lowered melanin synthesis, relative to transfection with an allele from a darker low-elevation population. The high-elevation allele led to less efficient integration of the MC1R protein into melanocyte membranes. Our study identifies variation in the degree of melanism that can be explained by four or fewer MC1R substitutions. We establish a functional link between these substitutions and melanin synthesis and demonstrate elevation-associated shifts in their frequencies., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
- Published
- 2020
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37. Assessment of primary care practitioners' attitudes and interest in pharmacogenomic testing.
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Smith DM, Namvar T, Brown RP, Springfield TB, Peshkin BN, Walsh RJ, Welsh JC, Levin B, Brandt N, and Swain SM
- Subjects
- Female, Humans, Male, Nurse Practitioners psychology, Pharmacogenetics methods, Physician Assistants psychology, Physicians, Primary Care psychology, Precision Medicine psychology, Attitude of Health Personnel, Health Personnel psychology, Pharmacogenomic Testing methods, Primary Health Care methods, Surveys and Questionnaires
- Abstract
Aims: Identify the attitudes and interests of primary care providers (PCPs) in applying clinical pharmacogenomics (PGx) test results. Materials & methods: A questionnaire was designed and then disseminated to PCPs across the MedStar Health System. Results: Ninety of 312 (29%) PCPs responded and were included in analyses. Seventy-six (84%) had heard of PGx and 12 (13%) previously ordered PGx testing. Most, 68 (76%), believed PGx can improve care; however, a minority, 23 (26%), reported confidence in using PGx in prescribing decisions. Sixty-four (70%) wanted a pharmacist consultation. PCPs desired PGx for antidepressants (75%), proton pump inhibitors (72%) and other medications. Conclusion: Most PCPs felt unprepared to interpret PGx results and desired pharmacist consultations. These data can inform future PGx implementations with PCPs.
- Published
- 2020
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38. Analytical evaluation of the clonoSEQ Assay for establishing measurable (minimal) residual disease in acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma.
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Ching T, Duncan ME, Newman-Eerkes T, McWhorter MME, Tracy JM, Steen MS, Brown RP, Venkatasubbarao S, Akers NK, Vignali M, Moorhead ME, Watson D, Emerson RO, Mann TP, Cimler BM, Swatkowski PL, Kirsch IR, Sang C, Robins HS, Howie B, and Sherwood A
- Subjects
- Bone Marrow pathology, Cyclin D1 genetics, Gene Rearrangement, Humans, Immunoglobulin Heavy Chains genetics, Immunoglobulin lambda-Chains genetics, Immunoglobulins genetics, Leukemia, Lymphocytic, Chronic, B-Cell blood, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Limit of Detection, Multiple Myeloma blood, Multiple Myeloma genetics, Multiple Myeloma therapy, Neoplasm, Residual, Precursor Cell Lymphoblastic Leukemia-Lymphoma blood, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Proto-Oncogene Proteins c-bcl-2 genetics, Translocation, Genetic, High-Throughput Nucleotide Sequencing instrumentation, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Multiple Myeloma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Reagent Kits, Diagnostic
- Abstract
Background: The clonoSEQ® Assay (Adaptive Biotechnologies Corporation, Seattle, USA) identifies and tracks unique disease-associated immunoglobulin (Ig) sequences by next-generation sequencing of IgH, IgK, and IgL rearrangements and IgH-BCL1/2 translocations in malignant B cells. Here, we describe studies to validate the analytical performance of the assay using patient samples and cell lines., Methods: Sensitivity and specificity were established by defining the limit of detection (LoD), limit of quantitation (LoQ) and limit of blank (LoB) in genomic DNA (gDNA) from 66 patients with multiple myeloma (MM), acute lymphoblastic leukemia (ALL), or chronic lymphocytic leukemia (CLL), and three cell lines. Healthy donor gDNA was used as a diluent to contrive samples with specific DNA masses and malignant-cell frequencies. Precision was validated using a range of samples contrived from patient gDNA, healthy donor gDNA, and 9 cell lines to generate measurable residual disease (MRD) frequencies spanning clinically relevant thresholds. Linearity was determined using samples contrived from cell line gDNA spiked into healthy gDNA to generate 11 MRD frequencies for each DNA input, then confirmed using clinical samples. Quantitation accuracy was assessed by (1) comparing clonoSEQ and multiparametric flow cytometry (mpFC) measurements of ALL and MM cell lines diluted in healthy mononuclear cells, and (2) analyzing precision study data for bias between clonoSEQ MRD results in diluted gDNA and those expected from mpFC based on original, undiluted samples. Repeatability of nucleotide base calls was assessed via the assay's ability to recover malignant clonotype sequences across several replicates, process features, and MRD levels., Results: LoD and LoQ were estimated at 1.903 cells and 2.390 malignant cells, respectively. LoB was zero in healthy donor gDNA. Precision ranged from 18% CV (coefficient of variation) at higher DNA inputs to 68% CV near the LoD. Variance component analysis showed MRD results were robust, with expected laboratory process variations contributing ≤3% CV. Linearity and accuracy were demonstrated for each disease across orders of magnitude of clonal frequencies. Nucleotide sequence error rates were extremely low., Conclusions: These studies validate the analytical performance of the clonoSEQ Assay and demonstrate its potential as a highly sensitive diagnostic tool for selected lymphoid malignancies.
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- 2020
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39. Pharmacogenetics in Practice: Estimating the Clinical Actionability of Pharmacogenetic Testing in Perioperative and Ambulatory Settings.
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Smith DM, Peshkin BN, Springfield TB, Brown RP, Hwang E, Kmiecik S, Shapiro R, Eldadah Z, Lundergan C, McAlduff J, Levin B, and Swain SM
- Subjects
- Aged, Ambulatory Care standards, District of Columbia, Female, Humans, Male, Maryland, Middle Aged, Perioperative Care standards, Pharmacogenomic Testing standards, Pilot Projects, Practice Guidelines as Topic, Practice Patterns, Physicians' standards, Precision Medicine methods, Precision Medicine standards, Retrospective Studies, United States, United States Food and Drug Administration standards, Ambulatory Care statistics & numerical data, Perioperative Care statistics & numerical data, Pharmacogenomic Testing statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data, Precision Medicine statistics & numerical data
- Abstract
Most literature describing pharmacogenetic implementations are within academic medical centers and use single-gene tests. Our objective was to describe the results and lessons learned from a multisite pharmacogenetic pilot that utilized panel-based testing in academic and nonacademic settings. This was a retrospective analysis of 667 patients from a pilot in 4 perioperative and 5 outpatient cardiology clinics. Recommendations related to 12 genes and 65 drugs were classified as actionable or not actionable. They were ascertained from Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines and US Food and Drug Administration (FDA) labeling. Patients displayed a high prevalence of actionable results (88%, 99%) and use of medications (28%, 46%) with FDA or CPIC recommendations, respectively. Sixteen percent of patients had an actionable result for a current medication per CPIC compared with 5% per FDA labeling. A systematic approach by a health system may be beneficial given the quantity and diversity of patients affected., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)
- Published
- 2020
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40. Thalamic Gamma Aminobutyric Acid Level Changes in Major Depressive Disorder After a 12-Week Iyengar Yoga and Coherent Breathing Intervention.
- Author
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Streeter CC, Gerbarg PL, Brown RP, Scott TM, Nielsen GH, Owen L, Sakai O, Sneider JT, Nyer MB, and Silveri MM
- Subjects
- Adult, Anxiety, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Thalamus chemistry, Thalamus diagnostic imaging, Young Adult, gamma-Aminobutyric Acid metabolism, Breathing Exercises, Depressive Disorder, Major diagnostic imaging, Depressive Disorder, Major metabolism, Depressive Disorder, Major therapy, Thalamus metabolism, Yoga, gamma-Aminobutyric Acid analysis
- Abstract
Objective: To determine if a 12-week yoga intervention (YI) was associated with increased gamma aminobutyric acid (GABA) levels and decreased depressive symptoms in participants with major depressive disorder (MDD). Methods : Subjects were randomized to a high-dose group (HDG) of three YIs a week and a low-dose group (LDG) of two YIs a week. Thalamic GABA levels were obtained using magnetic resonance spectroscopy at Scan-1 before randomization. After the assigned 12-week intervention, Scan-2 was obtained, immediately followed by a YI and Scan-3. Beck Depression Inventory II (BDI-II) scores were obtained before Scan-1 and Scan-3. Settings/Location: Screenings and interventions occurred at the Boston University Medical Center. Imaging occurred at McLean Hospital. Subjects: Subjects met criteria for MDD. Intervention: Ninety minutes of Iyengar yoga and coherent breathing at five breaths per minute plus homework. Outcome measures: GABA levels and the BDI-II. Results: BDI-II scores improved significantly in both groups. GABA levels from Scan-1 to Scan-3 and from Scan-2 to Scan-3 were significantly increased in the LDG ( n = 15) and showed a trend in the total cohort. Post hoc , participants were divided into two groups based on having an increase in GABA levels at Scan-2. Increases in Scan-2 GABA levels were observed in participants whose mean time between their last YI and Scan-2 was 3.93 ± 2.92 standard deviation (SD) days, but not in those whose mean time between their last YI and Scan-2 was 7.83 ± 6.88 SD. Conclusions: This study tentatively supports the hypothesis that one of the mechanisms through which yoga improves mood is by increasing the activity of the GABA system. The observed increase in GABA levels following a YI that was no longer observed 8 days after a YI suggests that the associated increase in GABA after a YI is time limited such that at least one YI a week may be necessary to maintain the elevated GABA levels.
- Published
- 2020
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41. Psychological Function, Iyengar Yoga, and Coherent Breathing: A Randomized Controlled Dosing Study.
- Author
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Scott TM, Gerbarg PL, Silveri MM, Nielsen GH, Owen L, Nyer M, Brown RP, and Streeter CC
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Time Factors, Treatment Outcome, Young Adult, Depressive Disorder, Major psychology, Quality of Life psychology, Respiration, Yoga psychology
- Abstract
Background: Evidence suggests that yoga may be an effective treatment for major depressive disorder (MDD). Studies evaluating the "dosing" of yoga treatment and efficacy for MDD are needed. The goal of this study was to assess the effects of an intervention combining Iyengar yoga and coherent breathing in participants with MDD and determine the optimal intervention dose., Methods: Thirty-two participants (18 to 65 y of age) diagnosed with MDD were randomized to a high-dose group (HDG) or a low-dose group (LDG) of yoga and coherent breathing for 12 weeks. The HDG (n=15) involved three 90-minute yoga classes and four 30-minute homework sessions per week. The LDG (n=15) involved two 90-minute yoga classes and three 30-minute homework sessions per week. Participants were evaluated at baseline, week 4, week 8, and week 12 with the following instruments: Positivity Self-Test, Spielberger State Anxiety Inventory, Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index, and Exercise-induced Feeling Inventory. Data were analyzed using intent-to-treat methods., Results: Significant improvements in all outcome measures were found for both groups, with acute and cumulative benefits. Although the HDG showed greater improvements on all scales, between-group differences did not reach significance, possibly due to lack of power because of the small sample size. Cumulative yoga minutes were correlated with improvement in outcome measures., Limitation: This dosing study did not include a non-yoga control., Conclusions: Improvement in psychological symptoms correlated with cumulative yoga practice. Both interventions reduced symptoms of depression and anxiety and increased feelings of positivity. The time commitment for yoga practice needs to be weighed against benefits when designing yoga interventions.
- Published
- 2019
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42. Morphological species and discordant mtDNA: A genomic analysis of Phrynocephalus lizard lineages on the Qinghai-Tibetan Plateau.
- Author
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Jin Y and Brown RP
- Subjects
- Animals, Bayes Theorem, China, Ecosystem, Gene Flow, Genetic Variation, Genomics, Lakes, Tibet, DNA, Mitochondrial genetics, Genome genetics, Lizards classification, Lizards genetics, Phylogeny
- Abstract
Many species have been established on the basis of morphology, with markers such as mtDNA used to confirm the existence of independent historical lineages. Discordance between morphology and gene trees makes this less straightforward. Genotyping by sequencing (GBS) was used to analyse general genomic divergence across two recognized high altitude lizard species found in the eastern Qinghai-Tibetan Plateau. One of the species (Phyrnocephalus guinanensis) is found on a large area of sand dune habitat and distinguished from the other (P. putjatia) by morphology. We found that the primary pattern of genomic divergence is discordant with these morphological species: northern P. putjatia populations from around the large saline Qinghai lake are genomically distinct from P. putjatia and P. guinanensis populations located south of the Qinghai South and Riyue Mountains. Two competing historical scenarios were assessed using approximate Bayesian computation which unequivocally favoured a split between populations separated by the Qinghai South and Riyue mountains over a split between morphological species. The findings indicate that historical vicariance due to geographical features underpins the phylogenetic split rather than ecology-mediated divergence between sand dune and non-sand areas which i) is predicted by the mtDNA tree (showing the utility of this marker in species delimitation) and ii) demonstrates the unsuitability of the morphology-based taxonomy (indicating that large morphological differences do not always reflect historical lineages). In addition, we found a clear signal of isolation-by-distance around the periphery of Qinghai lake which suggests: i) a high level of resolution by GBS for detecting local divergence and ii) restricted gene flow over relatively short geographic distances. Overall, we show how morphological variation can mislead taxonomic conclusions and the utility of GBS for resolving these issues., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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43. Predicting Plasma Free Hemoglobin Levels in Patients Due to Medical Device-Related Hemolysis.
- Author
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Saylor DM, Buehler PW, Brown RP, and Malinauskas RA
- Subjects
- Adult, Animals, Humans, Male, Equipment and Supplies adverse effects, Hemoglobins metabolism, Hemolysis, Models, Cardiovascular
- Abstract
Blood passage through medical devices can cause hemolysis and increased levels of plasma free hemoglobin (pfH) that may lead to adverse effects such as vasoconstriction and renal tubule injury. Although the hemolytic potential of devices is typically characterized in vitro using animal blood, the results can be impacted by various blood parameters, such as donor species. Moreover, it is unclear how to relate measured in vitro hemolysis levels to clinical performance because pfH accumulation in vivo depends on both hemolysis rate and availability of plasma haptoglobin (Hpt) that can bind and safely eliminate pfH. To help to address these uncertainties, we developed a biokinetic model linking in vivo hemolysis rates to time-dependent pfH and Hpt concentrations. The model was initially parameterized using studies that characterized baseline levels and evolution of pfH and Hpt after introduction of excess pfH in humans. With the biokinetic parameters specified, the model was applied to predict hemolysis rates in three patient groups undergoing cardiopulmonary bypass surgery. The congruity of the model with these clinical data suggests that it can infer in vivo hemolysis rates and provide insight into pfH levels that may cause concern. The model was subsequently used to evaluate acceptance threshold hemolysis values proposed in the literature for chronic circulatory assist blood pumps and to assess the impact of patient weight on pfH accumulation using simple scaling arguments, which suggested that identical hemolysis index values may increase pfH levels nearly threefold in 10 kg pediatric patients compared with 80 kg adults.
- Published
- 2019
- Full Text
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44. Synthesis and Degradation of Cadmium-Free InP and InPZn/ZnS Quantum Dots in Solution.
- Author
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Brown RP, Gallagher MJ, Fairbrother DH, and Rosenzweig Z
- Subjects
- Cadmium chemistry, Chemistry Techniques, Synthetic, Luminescence, Models, Molecular, Molecular Conformation, Nanotechnology, Solutions, Stearic Acids chemistry, Indium chemistry, Phosphines chemistry, Quantum Dots chemistry, Sulfides chemistry, Zinc Compounds chemistry
- Abstract
This study advances the chemical research community toward the goal of replacing toxic cadmium-containing quantum dots (QDs) with environmentally benign InP QDs. The InP QD synthesis uniquely combines the previously reported use of InP magic-sized clusters (MSCs) as a single-source precursor for indium and phosphorus to form InP QDs, with zinc incorporation and subsequent ZnS shelling, to form InPZn/ZnS QDs with luminescence properties comparable to those of commonly used cadmium-containing luminescent QDs. The resulting InPZn/ZnS QDs have an emission quantum yield of about 50% across a broad range of emission peak wavelengths and emission peaks averaging 50 nm fwhm. The emission peak wavelength can be easily tuned by varying the Zn/In ratio in the reaction mixture. The strategy of using zinc stearate to tune the emission properties is advantageous as it does not lead to a loss of emission quantum yield or emission peak broadening. Although the initial optical properties of InP and InPZn/ZnS QDs are promising, thermal stability measurements of InPZn QDs show significant degradation in the absence of a shell compared to the CdSe QDs particularly at increased temperature in the presence of oxygen, which is indicative of thermal oxidation. There is no significant difference in the degradation rate of InP QDs made from molecular precursors and from MSCs. Additionally, the emission intensity and quantum yield of InPZn/ZnS QDs when purified and diluted in organic solvents under ambient conditions decrease significantly compared to those of CdSe/ZnS QDs. This indicates instability of the ZnS shell when prepared by common literature methods. This must be improved to realize high-quality, robust Cd-free QDs with the capability of replacing CdSe QDs in QD technologies.
- Published
- 2018
- Full Text
- View/download PDF
45. Renal Toxicodynamic Effects of Extracellular Hemoglobin After Acute Exposure.
- Author
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Baek JH, Yalamanoglu A, Brown RP, Saylor DM, Malinauskas RA, and Buehler PW
- Subjects
- Acute Kidney Injury blood, Acute Kidney Injury metabolism, Acute Kidney Injury pathology, Animals, Biomarkers metabolism, Dose-Response Relationship, Drug, Guinea Pigs, Hemoglobins administration & dosage, Hepatitis A Virus Cellular Receptor 1 metabolism, Humans, Iron metabolism, Kidney metabolism, Kidney pathology, Kidney Function Tests, Lipocalin-2 metabolism, Male, Models, Biological, Oxidative Stress drug effects, Toxicokinetics, Acute Kidney Injury chemically induced, Hemoglobins pharmacokinetics, Hemoglobins toxicity, Kidney drug effects
- Abstract
Plasma hemoglobin (Hb) is elevated in some hematologic disease states, during exposures to certain toxicants, and with the use of some medical devices. Exposure to free Hb can precipitate oxidative reactions within tissues and alter the normal physiological function of critical organ systems. As kidney structures can be highly sensitive to Hb exposures, we evaluated the acute dose dependent renal toxicologic response to purified Hb isolated from RBCs. Male Hartley guinea pigs (n = 5 per group) were dosed with 0.9% saline (2 ml), 15, 75, 150, or 300 mg of purified Hb, infused over a 2-h period. The primary endpoints of this study were to define toxicokinetic parameters after increasing doses of purified Hb, identify clinically recognized and experimental markers of acute kidney injury (AKI), and determine relevant toxicological parameters and potential causes of renal toxicity in this model. Experimental findings demonstrated a dose dependent increase in Cmax after a 2-h infusion, which correlated with an elevation in serum creatinine, renal Kim-1 mRNA expression and increased urinary Kim-1. Renal NGAL mRNA expression and urinary NGAL excretion were also increased in several groups, but these parameters did not correlate with exposure. Iron increased in the renal cortex as Hb exposure increased and its deposition colocalized with 4-hydroxy-nonenal and 8-Oxo-2-deoxyguanosine immune reactivity, suggesting oxidative stressors may contribute to AKI in animals exposed to Hb. The results presented here suggest that Cmax may effectively predict the risk of AKI in normal healthy animals exposed to Hb.
- Published
- 2018
- Full Text
- View/download PDF
46. Partition number, rate priors and unreliable divergence times in Bayesian phylogenetic dating.
- Author
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Jin Y and Brown RP
- Abstract
More loci/partitions should improve Bayesian estimation of divergence times on phylogenies but it has recently been shown that this can lead to surprisingly poor estimation due to the way it affects the prior on mean substitution rate. Here we consider the likely impact of partition number on divergence time analyses carried out using the program BEAST. Mitochondrial genome data from toad-headed lizards (genus Phrynocephalus) from the Qinghai-Tibetan Plateau were used to examine this effect. Under increased partitioning of the sequences, BEAST posterior divergence times became unreasonably narrow and downwardly biased due to misspecification of the mean substitution rate prior. This effect was detectable when relatively few partitions were used (i.e. between four and eight), but became very acute for 27-86 partitions. Fortunately, a correction that adjusts the standard deviation of the mean of locus rates led to results that were equivalent to those obtained using the latest version of the program MCMCtree, which implements a new gamma-Dirichlet prior to overcome this problem. A review of the literature shows that a substantial number of BEAST dating studies are likely to have been affected by this misspecification of the rate prior., (© The Willi Hennig Society 2017.)
- Published
- 2018
- Full Text
- View/download PDF
47. Adverse Interactions of Luminescent Semiconductor Quantum Dots with Liposomes and Shewanella oneidensis .
- Author
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Williams DN, Pramanik S, Brown RP, Zhi B, McIntire E, Hudson-Smith NV, Haynes CL, and Rosenzweig Z
- Abstract
Cadmium-containing luminescent quantum dots (QD) are increasingly used in display, bioimaging, and energy technologies; however, significant concerns have been raised about their potentially adverse impact on human health and the environment. This study makes use of a broad toolkit of analytical methods to investigate and increase our understanding of the interactions of luminescent cadmium-containing (CdSe) and cadmium-free (ZnSe) QD, with and without a passivating higher bandgap energy ZnS shell, with phospholipid vesicles (liposomes), which model bacterial membranes, and with Shewanella oneidensis MR-1, an environmentally relevant bacteria. A unique feature of this study is that all QD types have the same surface chemistry, being capped with uncharged poly(ethylene glycol) ligands. This enables focusing the study on the impact of the QD core on liposomes and bacterial cells. The study reveals that QD association with liposome and bacterial cell membranes is imperative for their adverse impact on liposomes and bacterial cells. The QD' concentration-dependent association with liposomes and bacterial cells destabilizes the membranes mechanically, which leads to membrane disruption and lysis in liposomes and to bacterial cell death. The study also shows that cadmium-containing QD exhibit a higher level of membrane disruption in bacterial cells than cadmium-free QD. ZnSe QD have low membrane impact, and coating them with a ZnS shell decreases their membrane disruption activity. In contrast, CdSe QD exhibit a high level of membrane impact, and coating them with a ZnS shell does not decrease, but in fact further increases, their membrane disruption activity. This behavior might be attributed to higher affinity and association of CdSe/ZnS QD with liposomes and bacterial cells and to a contribution of dissolved zinc ions from the ZnS shell to increased membrane disruption activity., Competing Interests: The authors declare no competing financial interest.
- Published
- 2018
- Full Text
- View/download PDF
48. Method-specific and unexplained reactivity in automated solid-phase testing and their association with specific antibodies.
- Author
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Harach ME, Gould JM, Brown RP, Sanders T, and Herman JH
- Subjects
- Automation, Laboratory, Humans, Immunologic Tests, Polyethylene Glycols, Retrospective Studies, Antibodies analysis
- Abstract
Conclusions: The inherent tradeoff between sensitivity and specificity in the detection of unexplained antibodies has been the objective of many studies, editorials, and journal articles. Many publications note that no method is capable of detecting all clinically significant antibodies while avoiding all clinically insignificant antibodies. This study describes the frequency of nonspecific reactivity and unexplained reactivity in solid-phase testing, along with the subsequent development of specific antibodies (Abs). In this study, nonspecific reactivity (NS) is defined as method-specific panreactivity detected by solid-phase testing only, with no reactivity in other methods. Unexplained reactivity (UR) is defined as reactivity present and detectable in all test methods after all clinically significant antibodies were ruled out following a standard antibody identification algorithm using selected cell panels. This retrospective study evaluated antibody detection tests of patients at a single center for 2 years using two automated solid-phase instruments that used the same three-cell antibody detection test. Antibody identification was performed with solid-phase panels supplemented with a polyethylene glycol tube method as needed. Of the 1934 (5%) samples with a positive antibody detection test, 29 had unavailable work-up data, leaving 1905 (98.5%) samples eligible for inclusion in the study. The data revealed the following: Ab only 999 (52.4%); UR only 429 (22.5%); Ab and UR 227 (11.9%); NS only 206 (10.8%); Ab and NS 24 (1.3%); UR and NS 14 (0.7%); and Ab, UR, and NS 6 (0.3%). Patients with a positive follow-up antibody detection test had UR and NS replaced with a specific Ab in 23 of 656 UR (3%) and 8 of 230 NS (3%) cases, respectively. Additionally, six patients with UR developed a specific Ab along with persistent UR, and no patients with persistent NS developed a specific Ab. The study concluded that both UR and NS can be encountered in solid-phase testing, and both UR and NS can persist in follow-up testing. Specific Ab was observed to replace UR in a few patients.
- Published
- 2018
49. Geometric morphometric analyses of sexual dimorphism and allometry in two sympatric snakes: Natrix helvetica (Natricidae) and Vipera berus (Viperidae).
- Author
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Tamagnini D, Stephenson J, Brown RP, and Meloro C
- Subjects
- Animals, Body Size, Female, Head, Male, Sex Characteristics, Sympatry, Colubridae physiology, Viperidae physiology
- Abstract
The non-venomous grass snake (Natrix helvetica) and the venomous adder (Vipera berus) are two native species that are often found in sympatry in Great Britain and Europe. They occupy partially overlapping ecological niches and prey on small vertebrates, but use different feeding strategies. Here, we investigated the morphologies of grass snakes and adders from Dorset (UK) using two-dimensional geometric morphometrics to assess the degree of sexual dimorphism in size and shape together with the relative impact of allometry and general body dimensions on head shape. Both species showed significant sexual dimorphism in head size, but not in head shape. We found a clear allometric pattern in N. helvetica, whereas allometry in V. berus was generally less pronounced. Body dimensions were strongly correlated with head shape in the grass snake, but not in the adder. The fact that V. berus is venomous appears to explain the lack of allometric patterns and the lack of an association between body dimensions and head shape. The high degree of size dimorphism identified in both species could originate from the advantages of reduced intraspecific competition that are conveyed by a partial differentiation in feeding morphology., (Copyright © 2018 Elsevier GmbH. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
50. Malic Acid Carbon Dots: From Super-resolution Live-Cell Imaging to Highly Efficient Separation.
- Author
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Zhi B, Cui Y, Wang S, Frank BP, Williams DN, Brown RP, Melby ES, Hamers RJ, Rosenzweig Z, Fairbrother DH, Orr G, and Haynes CL
- Abstract
As-synthesized malic acid carbon dots are found to possess photoblinking properties that are outstanding and superior compared to those of conventional dyes. Considering their excellent biocompatibility, malic acid carbon dots are suitable for super-resolution fluorescence localization microscopy under a variety of conditions, as we demonstrate in fixed and live trout gill epithelial cells. In addition, during imaging experiments, the so-called "excitation wavelength-dependent" emission was not observed for individual as-made malic acid carbon dots, which motivated us to develop a time-saving and high-throughput separation technique to isolate malic acid carbon dots into fractions of different particle size distributions using C
18 reversed-phase silica gel column chromatography. This post-treatment allowed us to determine how particle size distribution influences the optical properties of malic acid carbon dot fractions, that is, optical band gap energies and photoluminescence behaviors.- Published
- 2018
- Full Text
- View/download PDF
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