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Search Results: 1 - 10 of 462259 matches for " Debra A. Fleischman "
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Faster cognitive decline in the years prior to MR imaging is associated with smaller hippocampal volumes in cognitively healthy older persons
Debra A. Fleischman,Lei Yu,Konstantinos Arfanakis,S. Duke Han,Patricia A. Boyle,David A. Bennett
Frontiers in Aging Neuroscience , 2013, DOI: 10.3389/fnagi.2013.00021
Abstract: Early identification of persons at risk for cognitive decline in aging is critical to optimizing treatment to delay or avoid a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). To accomplish early identification, it is essential that trajectories of cognitive change be characterized and associations with established biomarkers of MCI and AD be examined during the phase in which older persons are considered cognitively healthy. Here we examined the association of rate of cognitive decline in the years leading up to structural magnetic resonance imaging with an established biomarker, hippocampal volume. The sample comprised 211 participants of the Rush Memory and Aging Project who had an average of 5.5 years of cognitive data prior to structural scanning. Results showed that there was significant variability in the trajectories of cognitive change prior to imaging and that faster cognitive decline was associated with smaller hippocampal volumes. Domain-specific analyses suggested that this association was primarily driven by decline in working memory. The results emphasize the importance of closely examining cognitive change and its association with brain structure during the years in which older persons are considered cognitively healthy.
Systemic Inflammation in Non-Demented Elderly Human Subjects: Brain Microstructure and Cognition
Konstantinos Arfanakis, Debra A. Fleischman, Giorgia Grisot, Christopher M. Barth, Anna Varentsova, Martha C. Morris, Lisa L. Barnes, David A. Bennett
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073107
Abstract: The purpose of this study was to test the hypothesis that higher levels of systemic inflammation in a community sample of non-demented subjects older than seventy years of age are associated with reduced diffusion anisotropy in brain white matter and lower cognition. Ninety-five older persons without dementia underwent detailed clinical and cognitive evaluation and magnetic resonance imaging, including diffusion tensor imaging. Systemic inflammation was assessed with a composite measure of commonly used circulating inflammatory markers (C-reactive protein and tumor necrosis factor-alpha). Tract-based spatial statistics analyses demonstrated that diffusion anisotropy in the body and isthmus of the corpus callosum was negatively correlated with the composite measure of systemic inflammation, controlling for demographic, clinical and radiologic factors. Visuospatial ability was negatively correlated with systemic inflammation, and diffusion anisotropy in the body and isthmus of the corpus callosum was shown to mediate this association. The findings of the present study suggest that higher levels of systemic inflammation may be associated with lower microstructural integrity in the corpus callosum of non-demented elderly individuals, and this may partially explain the finding of reduced higher-order visual cognition in aging.
A Real-World Observational Study of Patients with Advanced Melanoma Receiving First-Line Ipilimumab in a Community Practice Setting  [PDF]
Debra A. Patt, Debra Rembert, Menaka Bhor, Debajyoti Bhowmik, Sumati A. Rao
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.512110
Abstract: Background: Following approval of ipilimumab, this observational cohort study (CA184-332) was initiated to describe patient and disease characteristics, patterns of care, survival, and adverse events (AEs) in advanced melanoma (AM) patients treated with first-line ipilimumab in realworld US community practice. Methods: Adult patients with treatment-naive AM who received ≥1 dose of ipilimumab 3 mg/kg between April 2011 and September 2012 were retrospectively identified at US Oncology sites. Clinical data were abstracted from patient medical records. Results: Median age of the 157 patient cohorts was 66 years (range 21 - 91). 68.2% were male, and 90.5% had a cutaneous primary site. At ipilimumab initiation, 80.9% of patients had an ECOG performance status of 0 or 1; 54.1% were stage M1c; 34.4% had brain metastases; 24.8% had elevated lactate dehydrogenase, and 13.4% were positive for BRAF mutation. All 4 cycles of ipilimumab were completed by 55.8% of patients. At a median follow-up of 8.5 months (range 2.9 - 15.0), median overall survival was 11.5 months (95% CI: 8.9 - 16.6) and 1-year survival was 46.7% (95% CI: 38.1 - 54.9). During ipilimumab treatment, AEs were experienced by 63.7% of patients. The most frequent AEs were gastrointestinal (41.4%; diarrhea in 19.1%) and skin-related (28.0%; rash in 17.8%); 17.8% of patients had an AE that led to ipilimumab discontinuation. Conclusions: These real-world results are consistent with those from clinical trials and provide evidence supporting the effectiveness and safety of first-line ipilimumab 3 mg/kg monotherapy in patients with AM treated in a community practice setting.
Prevention of breast cancer by recapitulation of pregnancy hormone levels
Debra A Tonetti
Breast Cancer Research , 2003, DOI: 10.1186/bcr750
Abstract: Numerous epidemiologic studies have demonstrated the protective effect of a full-term pregnancy before age 20 years on the risk for developing breast cancer, as compared with women who have never had a full-term pregnancy. Rodent models can replicate the protective effect of pregnancy against the development of carcinogen-induced mammary cancer. Most intriguing is the ability to prevent mammary cancers in these rodent models by recreating the hormonal milieu of pregnancy by providing estradiol and progesterone to achieve pregnancy levels, either before or after the carcinogenic insult. In this issue of Breast Cancer Research, Rajkumar and coworkers [1] take a step further in recapitulating the protective effect of pregnancy. They demonstrate that both natural and synthetic estrogens in combination with progestins at lower doses and with shorter durations of treatment are capable of providing the protective effect. These studies are compelling because this hormonal regimen may be applicable to the prevention of human breast cancer. However, this approach, despite impressive preclinical studies, may be difficult to translate into a clinical trial.The protective effect afforded by full-term pregnancy in women who are 20 years old or younger, as compared with nulliparous women, is recognized among all ethnic groups, but the mechanism of this effect is not fully understood. Rodent models have been extensively utilized to demonstrate the role of pregnancy [2,3] and hormones simulating pregnancy [4,5] in preventing mammary carcinogenesis. Actually, two separate models have been used to demonstrate the protective effects of parity: a pretreatment model and a post-treatment model [6]. In the pretreatment model the hormonal treatment is given before the carcinogen, whereas in the post-treatment model the carcinogen is given first, followed by the hormone treatment. The latter is the model used by Rajkumar and coworkers [1]. The fact that the timing of hormonal treatment – bef
Sex differences in stress-related receptors: ″micro″ differences with ″macro″ implications for mood and anxiety disorders
Bangasser Debra A
Biology of Sex Differences , 2013, DOI: 10.1186/2042-6410-4-2
Abstract: Stress-related psychiatric disorders, such as unipolar depression and post-traumatic stress disorder (PTSD), occur more frequently in women than in men. Emerging research suggests that sex differences in receptors for the stress hormones, corticotropin releasing factor (CRF) and glucocorticoids, contribute to this disparity. For example, sex differences in CRF receptor binding in the amygdala of rats may predispose females to greater anxiety following stressful events. Additionally, sex differences in CRF receptor signaling and trafficking in the locus coeruleus arousal center combine to make females more sensitive to low levels of CRF, and less adaptable to high levels. These receptor differences in females could lead to hyperarousal, a dysregulated state associated with symptoms of depression and PTSD. Similar to the sex differences observed in CRF receptors, sex differences in glucocorticoid receptor (GR) function also appear to make females more susceptible to dysregulation after a stressful event. Following hypothalamic pituitary adrenal axis activation, GRs are critical to the negative feedback process that inhibits additional glucocorticoid release. Compared to males, female rats have fewer GRs and impaired GR translocation following chronic adolescent stress, effects linked to slower glucocorticoid negative feedback. Thus, under conditions of chronic stress, attenuated negative feedback in females would result in hypercortisolemia, an endocrine state thought to cause depression. Together, these studies suggest that sex differences in stress-related receptors shift females more easily into a dysregulated state of stress reactivity, linked to the development of mood and anxiety disorders. The implications of these receptor sex differences for the development of novel pharmacotherapies are also discussed.
Disturbance, Response, and Persistence in Self-Organized Forested Communities: Analysis of Robustness and Resilience in Five Communities in Southern Indiana
Forrest D. Fleischman,Kinga Boenning,Gustavo A. Garcia-Lopez,Sarah Mincey
Ecology and Society , 2010,
Abstract: We develop an analytic framework for the analysis of robustness in social-ecological systems (SESs) over time. We argue that social robustness is affected by the disturbances that communities face and the way they respond to them. Using Ostrom's ontological framework for SESs, we classify the major factors influencing the disturbances and responses faced by five Indiana intentional communities over a 15-year time frame. Our empirical results indicate that operational and collective-choice rules, leadership and entrepreneurship, monitoring and sanctioning, economic values, number of users, and norms/social capital are key variables that need to be at the core of future theoretical work on robustness of self-organized systems.
The Social Determinants of Organ Trafficking: A Reflection of Social Inequity
Debra A. Budiani,Kabir Karim
Social Medicine , 2008,
Abstract: Organ trafficking has become evident in its global scope and consequences. Poverty, vulnerability, destitution and a system of exploitative transplant practices are social determinants for commercial living organ donation. Guided by the WHO resolution on organ transplants and the Istanbul Declaration, transplant practices can advanced standards of greater social equality rather than exploit social determinants of poverty, vulnerability and destitution by way of exploitative health systems.
Early-type Stars: Most Favorable Targets for Astrometrically Detectable Planets in the Habitable Zone
Andrew Gould,Debra A. Fischer
Physics , 2003, DOI: 10.1086/377147
Abstract: Early-type stars appear to be a difficult place to look for planets astrometrically. First, they are relatively heavy, and for fixed planetary mass the astrometric signal falls inversely as the stellar mass. Second, they are relatively rare (and so tend to be more distant), and for fixed orbital separation the astrometric signal falls inversely as the distance. Nevertheless, because early-type stars are relatively more luminous, their habitable zones are at larger semi-major axis. Since astrometric signal scales directly as orbital size, this gives early-type stars a strong advantage, which more than compensates for the other two factors. Using the Hipparcos catalog, we show that early-type stars constitute the majority of viable targets for astrometric searches for planets in the habitable zone. We contrast this characteristic to transit searches, which are primarily sensitive to habitable planets around late-type stars.
Revealing A Universal Planet-Metallicity Correlation For Planets of Different Sizes Around Solar-Type Stars
Ji Wang,Debra A. Fischer
Physics , 2013,
Abstract: The metallicity of exoplanet systems serves as a critical diagnostic of planet formation mechanisms. Previous studies have demonstrated the planet-metallicity correlation for large planets ($R_P\ \geq\ 4\ R_E$); however, a correlation has not been found for smaller planets. With a sample of 406 $Kepler$ Objects of Interest whose stellar properties are determined spectroscopically, we reveal a universal planet-metallicity correlation: not only gas-giant planets ($3.9\ R_E\ < R_P\ \leq\ 22.0\ R_E$) but also gas-dwarf ($1.7\ R_E\ < R_P\ \leq\ 3.9\ R_E$) and terrestrial planets ($R_P\ \leq\ 1.7\ R_E$) occur more frequently in metal-rich stars. The planet occurrence rates of gas-giant planets, gas-dwarf planets, and terrestrial planets are $9.30^{+5.62}_{-3.04}$, $2.03^{+0.29}_{-0.26}$, and $1.72^{+0.19}_{-0.17}$ times higher for metal-rich stars than for metal-poor stars, respectively.
Questioning the Ubiquity of Neofunctionalization
Todd A. Gibson ,Debra S. Goldberg
PLOS Computational Biology , 2009, DOI: 10.1371/journal.pcbi.1000252
Abstract: Gene duplication provides much of the raw material from which functional diversity evolves. Two evolutionary mechanisms have been proposed that generate functional diversity: neofunctionalization, the de novo acquisition of function by one duplicate, and subfunctionalization, the partitioning of ancestral functions between gene duplicates. With protein interactions as a surrogate for protein functions, evidence of prodigious neofunctionalization and subfunctionalization has been identified in analyses of empirical protein interactions and evolutionary models of protein interactions. However, we have identified three phenomena that have contributed to neofunctionalization being erroneously identified as a significant factor in protein interaction network evolution. First, self-interacting proteins are underreported in interaction data due to biological artifacts and design limitations in the two most common high-throughput protein interaction assays. Second, evolutionary inferences have been drawn from paralog analysis without consideration for concurrent and subsequent duplication events. Third, the theoretical model of prodigious neofunctionalization is unable to reproduce empirical network clustering and relies on untenable parameter requirements. In light of these findings, we believe that protein interaction evolution is more persuasively characterized by subfunctionalization and self-interactions.
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