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Search Results: 1 - 10 of 10131 matches for " Carol Fabian and Jennifer Klemp "
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Cardiorespiratory fitness in breast cancer survivors
David Burnett, Patricia Kluding, Charles Porter, Carol Fabian and Jennifer Klemp
SpringerPlus , 2013, DOI: 10.1186/2193-1801-2-68
Abstract: Maximal oxygen uptake (VO2max) has been used to assess risk for all-cause mortality and cardiovascular disease (CVD), and low VO2max has recently been associated with increased mortality from breast cancer. The purpose of this study was to determine the proportion of breast cancer survivors with 2 or more risk factors for CVD exhibiting a low VO2max and to determine whether sub-maximal endpoints which could be applied more readily to intervention research would correlate with the maximal treadmill test. We performed a single VO2max test on a treadmill with 30 breast cancer survivors age 30--60 (mean age 50.5 +/- 5.6 years) who had 2 or more cardiac risk factors for CVD not related to treatment and who had received systemic therapy and or left chest radiation. Submaximal VO2 endpoints were assessed during the VO2max treadmill test and on an Arc trainer. Resting left ventricular ejection fraction (LVEF) was also assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA). A majority (23/30) of women had a VO2max below the 20th percentile based on their predicted normal values. The group mean resting LVEF was 60.5 +/- 5.0%. Submaximal VO2 measures were strongly correlated with the maximal test including; 1) 85% age predicted maximum heart rate VO2 on treadmill, (r = .89; p < 0.001), 2) treadmill VO2 at anaerobic threshold (AT), (r = .83; p < 0.001), and 3) Arc VO2 at AT, (r = .80; p < 0.001). Breast cancer survivors with 2 or more CVD risk factors but normal LVEF had a low cardiorespiratory fitness level compared to normative values in the healthy population placing them at increased risk for breast cancer and cardiovascular mortality. Submaximal VO2 exercise testing endpoints showed a strong correlation with the VO2max test in breast cancer survivors and is a good candidate for testing interventions to improve cardiorespiratory fitness.
Surrogates are just surrogates, but helpful just the same
Carol Fabian
Breast Cancer Research , 2007, DOI: 10.1186/bcr1816
Abstract: To be credible, an SEB must have biological plausibility and a strong association with ultimate outcome. To be used for prevention, an SEB should be identified as being causally related to the development of precancer and cancer. Modulation of the SEB through an intervention should predict outcome. The SEB should be reproducible and reliable. Reproducibility is generally maximized with a quantitative biomarker. Optimally, both risk and response SEBs should be prospectively validated in a clinical trial in which the nonsurrogate outcome is also being evaluated [1,2].SEBs are used in clinical trials to identify effective new strategies faster and more economically with fewer patients. They may also offer insight into why or why not a particular therapy does not work. In the patient care setting, SEBs are used to determine whether and when to change the therapeutic plan.In the metastatic setting, typically the same surrogate markers are measured repeatedly to assess response or progression often by imaging and/or physical examination. Two surrogate markers can independently predict the same outcome, but results at any single point in time may be discordant. Consequently, it is important to understand the biology that underlies the surrogate in order to avoid making inappropriate clinical decisions.In the neoadjuvant setting, a low Ki-67 a few weeks after initiation of treatment and pathological response after several months of treatment both predict long-term disease-free survival [3-5]. Both biomarkers are currently used in the research setting, and pathological stage after neoadjuvant treatment is used clinically to estimate distant disease-free survival. It is probable that, in the near future, early reduction in breast proliferation will be used along with clinical indices to determine whether to switch antihormonal or chemotherapeutic treatment during the neoadjuvant period. Pathological response after neoadjuvant chemotherapy will also probably be used to determi
Breast cancer chemoprevention: beyond tamoxifen
Carol J Fabian
Breast Cancer Research , 2000, DOI: 10.1186/bcr279
Abstract: The demonstration by the National Surgical Adjuvant Breast and Bowel Project that tamoxifen reduces breast cancer risk by approximately 50% for at least some groups of high-risk women was a milestone in the chemoprevention of breast cancer [1]. However, other than women with a prior diagnosis of atypical hyperplasia, in situ or invasive cancer, it is not clear what groups of women receive enough benefit to offset the potential side effects. These side effects include increased risk of menstrual abnormalities and bone loss in young pre-menopausal women, and increased risk of hot flashes, sexual dysfunction, cataracts, uterine cancer, and thromboembolic phenomena in perimenopausal and post-menopausal women [1,2,3]. Concerns about the risk:benefit ratio, particularly in women over 50, have led to the recommendation that this group not receive tamoxifen unless their short-term risk approaches 1% per year for women with a uterus and 0.5% per year for women without a uterus [4]. In the USA, many women are not given the option of simultaneous tamoxifen and hormone replacement for fear of increasing thromboembolic risk [1,5]. Furthermore, it is clear that the incidence of estrogen receptor (ER)-negative cancers is not reduced with preventive tamoxifen therapy and that some ER-positive precancerous lesions might be resistant to tamoxifen [1].Important priorities for breast cancer prevention are to develop a variety of new prevention agents that have fewer side effects or a different side effect profile from that of tamoxifen, that are compatible with hormone replacement therapy (HRT), and that are effective in ER-negative as well as in tamoxifen-resistant ER-positive precancerous tissue.To develop new drugs in a short period and at reasonable cost, more efficient clinical testing models are being developed for phase I and II prevention trials. These models use potentially reversible morphological and molecular biomarkers that will enhance short-term risk prediction, that wil
Population Genetics of the Aquatic Fungus Tetracladium marchalianum over Space and Time
Jennifer L. Anderson,Carol A. Shearer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015908
Abstract: Aquatic hyphomycete fungi are fundamental mediators of energy flow and nutrient spiraling in rivers. These microscopic fungi are primarily dispersed in river currents, undergo substantial annual fluctuations in abundance, and reproduce either predominantly or exclusively asexually. These aspects of aquatic hyphomycete biology are expected to influence levels and distributions of genetic diversity over both spatial and temporal scales. In this study, we investigated the spatiotemporal distribution of genotypic diversity in the representative aquatic hyphomycete Tetracladium marchalianum. We sampled populations of this fungus from seven sites, three sites each in two rivers in Illinois, USA, and one site in a Wisconsin river, USA, and repeatedly sampled one population over two years to track population genetic parameters through two seasonal cycles. The resulting fungal isolates (N = 391) were genotyped at eight polymorphic microsatellite loci. In spite of seasonal reductions in the abundance of this species, genotypic diversity was consistently very high and allele frequencies remarkably stable over time. Likewise, genotypic diversity was very high at all sites. Genetic differentiation was only observed between the most distant rivers (~450 km). Clear evidence that T. marchalianum reproduces sexually in nature was not observed. Additionally, we used phylogenetic analysis of partial β-tubulin gene sequences to confirm that the fungal isolates studied here represent a single species. These results suggest that populations of T. marchalianum may be very large and highly connected at local scales. We speculate that large population sizes and colonization of alternate substrates in both terrestrial and aquatic environments may effectively buffer the aquatic populations from in-stream population fluctuations and facilitate stability in allele frequencies over time. These data also suggest that overland dispersal is more important for structuring populations of T. marchalianum over geographic scales than expected.
Advances in the WRF model for convection-resolving forecasting
J. B. Klemp
Advances in Geosciences (ADGEO) , 2006,
Abstract: The Weather Research and Forecasting (WRF) Model has been designed to be an efficient and flexible simulation system for use across a broad range of weather-forecast and idealized-research applications. Of particular interest is the use of WRF in nonhydrostatic applications in which moist-convective processes are treated explicitly, thereby avoiding the ambiguities of cumulus parameterization. To evaluate the capabilities of WRF for convection-resolving applications, real-time forecasting experiments have been conducted with 4 km horizontal mesh spacing for both convective systems in the central U.S. and for hurricanes approaching landfall in the southeastern U.S. These forecasts demonstrate a good potential for improving the forecast accuracy of the timing and location of these systems, as well as providing more detailed information on their structure and evolution that is not available in current coarser resolution operational forecast models.
Radiation Pattern Analysis of Antenna Systems for MIMO and Diversity Configurations
O. Klemp,H. Eul
Advances in Radio Science : Kleinheubacher Berichte , 2005,
Abstract: Multiple-input multiple-output (MIMO) antenna systems and antenna configurations for wideband multimode diversity rank among the emerging key technologies in next generation wireless communication systems. The analysis of such transmission systems usually neglects the influences of real antenna radiation characteristics as well as the influences of mutual coupling in a multielement antenna arrangement. Nevertheless, to achieve a detailed description of diversity gain and channel capacity by using several transmit- and receive antennas in a wireless link, it is essential to take all those effects into account. The expansion of the radiation fields in terms of spherical eigenmodes allows an analytical description of the antenna radiation characteristics and accounts for all the coupling effects in multielement antenna configurations. Therefore the radiation pattern analysis by spherical eigenmode expansion provides an efficient alternative to establish an analytical approach in the calculation of envelope correlation or channel capacity.
Ovarian steroid hormones: what's hot in the stem cell pool?
Diana M Cittelly, Jennifer K Richer, Carol A Sartorius
Breast Cancer Research , 2010, DOI: 10.1186/bcr2627
Abstract: Lifetime exposure to circulating steroid hormones via the number of menstrual cycles, menopausal hormone therapy, and perhaps pregnancy all increase breast cancer risk [1]. The details underlying this increased risk, however, have long remained elusive. The re-emergence of the cancer stem cell (CSC) theory since its original inception over a century ago [2] has popularized mammary stem cells (MaSCs) as putative cells of origin for breast cancers. Since the MaSCs reside within the steroid receptor-negative basal epithelial compartment [3], it was presumed that steroid hormone signaling would have little impact on their regulation. This presumption was despite earlier work demonstrating that estrogen receptor (ER)-positive and progesterone receptor (PR)-positive luminal cells in the normal breast use a paracrine mechanism to instruct neighboring ER-negative/PR-negative cells to proliferate [4]. Two seminal papers now uncover a critical role for steroid hormones in controlling both the number and the regenerative function of MaSCs in the normal murine mammary gland. These exciting findings promise to revolutionize our perception of how the female sex steroid hormones regulate the differentiation state of the breast and influence the risk of breast disease [5,6].Asselin-Labat and colleagues establish that steroid hormone deprivation via ovariectomized or aromatasedeficient mice significantly reduces the ability of MaSCs (CD29hiCD24+) to repopulate a mammary gland in the cleared fat pad of syngeneic recipient mice [5]. A combination of 17β-estradiol plus progesterone, but not 17β-estradiol or progesterone alone, in ovariectomized mice restores the repopulating frequency of MaSCs. Blockade of either 17β-estradiol (letrozole) or progesterone (RU486) did not affect MaSC numbers, but did reduce their repopulating ability and ductal outgrowth formation, respectively - indicating that MaSCs rely on the luminal compartment for functional signals. Interestingly, the hormonal sta
Hypoadrenalism in patients with fatigue and rheumatic disease
Dimitra Methiniti,Jennifer Hamilton,Vadivelu Saravanan,Carol Heycock
Rheumatology Reports , 2009, DOI: 10.4081/rr.2009.e13
Abstract: Many patients with rheumatic disease complain of fatigue. Clinicians may interpret this as part of the disease process in the absence of anaemia or hypothyroidism, and sometimes respond with the empiric addition of steroids to therapy. The possibility of true hypoadrenalism is only occasionally considered, and little data exists on the frequency with which it coexists with rheumatic disease. Random serum cortisol may be requested by clinicians to help exclude hypoadrenalism as a factor in fatigue. We undertook a survey to assess how frequently this test was of clinical relevance, what was done in patients with low results, and which patients were most likely to have true adrenal failure. All random cortisol assays requested by the members of a rheumatological team over one year were identified and the notes examined retrospectively. The indication for the request, the result, the ultimate clinical diagnosis and all prior diagnoses were recorded. Where further investigations were undertaken, these too were noted. The results were compared to those in an age and gender matched population of patients with general medical conditions (excluding endocrine disorders) for whom cortisol assays had also been requested. Random cortisol was requested by a team of four consultants in 74 patients with a variety of rheumatic disorders over 12 months, usually because of unexplained fatigue. Among the control group of 75 medical patients, the commonest reasons for requesting cortisol assay were fatigue, low sodium and unexplained anaemia. Mean cortisol levels were significantly higher in medical patients (512 nmol/L) than those with rheumatic disease (351 nmol/L) [P=0.04]. The results were low (<200 nmol/L) in 14 rheumatic patients and 7 medical patients. Among these 21 individuals, synacthen tests were performed in 16 and were indicative of hypoadrenalism in 6 cases. Further investigations revealed primary hypoadrenalism in 3 patients, with tertiary adrenal suppression from oral steroids in three others. All six of these patients had underlying rheumatic disorders, usually RA (3) or systemic lupus erythematosus (SLE) (2). None of the medical patients had an abnormal synacthen test. Fatigue in patients with rheumatic disease may be a presenting feature of hypoadrenalism. Although adrenal failure is rare in medical patients with anaemia, hyponatraemia or fatigue, patients with rheumatic disease and unexplained fatigue merit a random cortisol. If this is low, synacthen testing may be appropriate. Steroids should not be commenced empirically in such patients until hypoadre
From Precocious Puberty to Infertility: Metabolic Control of the Reproductive Function
Jennifer W. Hill,Meenakshi Alreja,Carol F. Elias
Frontiers in Endocrinology , 2013, DOI: 10.3389/fendo.2013.00043
Controlling Meiotic Recombinational Repair – Specifying the Roles of ZMMs, Sgs1 and Mus81/Mms4 in Crossover Formation
Ashwini Oke,Carol M. Anderson,Phoebe Yam,Jennifer C. Fung
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004690
Abstract: Crossovers (COs) play a critical role in ensuring proper alignment and segregation of homologous chromosomes during meiosis. How the cell balances recombination between CO vs. noncrossover (NCO) outcomes is not completely understood. Further lacking is what constrains the extent of DNA repair such that multiple events do not arise from a single double-strand break (DSB). Here, by interpreting signatures that result from recombination genome-wide, we find that synaptonemal complex proteins promote crossing over in distinct ways. Our results suggest that Zip3 (RNF212) promotes biased cutting of the double Holliday-junction (dHJ) intermediate whereas surprisingly Msh4 does not. Moreover, detailed examination of conversion tracts in sgs1 and mms4-md mutants reveal distinct aberrant recombination events involving multiple chromatid invasions. In sgs1 mutants, these multiple invasions are generally multichromatid involving 3–4 chromatids; in mms4-md mutants the multiple invasions preferentially resolve into one or two chromatids. Our analysis suggests that Mus81/Mms4 (Eme1), rather than just being a minor resolvase for COs is crucial for both COs and NCOs in preventing chromosome entanglements by removing 3′- flaps to promote second-end capture. Together our results force a reevaluation of how key recombination enzymes collaborate to specify the outcome of meiotic DNA repair.
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