2,086 research outputs found
Social Links from Latent Topics in Microblogs
Language use is overlaid on a network of social con-nections, which exerts an influence on both the top-ics of discussion and the ways that these topics can be expressed (Halliday, 1978). In the past, efforts t
The Effect of High Dose Total Body Irradiation on ACTH, Corticosterone, and Catecholamines in the Rat
Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic–pituitary–adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study assessed HPA axis function in rats undergoing TBI. Using a head-shielded model of TBI, we found an enhanced response to corticotropin-releasing hormone (CRH) in vitro in pituitaries from irradiated compared with nonirradiated rats at both 8 and 70 days after 10-Gy single fraction TBI. At 70, but not 8 days, plasma adrenocorticotrophic hormone (ACTH) and corticosterone levels were increased significantly in irradiated compared with nonirradiated rats. Plasma aldosterone was not affected by TBI at either time point, whereas plasma renin activity was decreased in irradiated rats at 8 days. Basal and stimulated adrenal steroid synthesis in vitro was not affected by TBI. In addition, plasma epinephrine was decreased at 70 days after TBI. The hypothalamic expression of CRH messenger RNA (mRNA) and hippocampal expression of glucocorticoid receptor mRNA were unchanged by irradiation. We conclude that the hypertension of radiation nephropathy is not aldosterone or catecholamine-dependent but that there is an abscopal activation of the HPA axis after 10 Gy TBI. This activation was attributable at least partially to enhanced pituitary ACTH production
Exforge® (amlodipine/valsartan combination) in hypertension: the evidence of its therapeutic impact
peer reviewedAbstract
Introduction: Hypertension is an important risk factor for cardiovascular disease and its management requires improvement.
New treatment strategies are needed.
Aims: This review analyses one of these strategies, which is the development of effective and safe combination therapy. Indeed, at least
two antihypertensive agents are often needed to achieve blood pressure control. Exforge® (Novartis) is a new drug combination of the
calcium channel blocker, amlodipine, and the angiotensin II receptor blocker, valsartan.
Evidence review: The amlodipine/valsartan combination is an association of two well-known antihypertensive products with specific
targets in cardiovascular protection, namely calcium channel blockade and antagonism of the renin-angiotensin-aldosterone system. This
kind of association, with neutral metabolic properties and significant antihypertensive efficacy, could be a useful new antihypertensive
product. Currently available data have shown that this new combination is well-tolerated and effective even in severe hypertension.
Clinical value: Clinical trials are ongoing for further assessment of the efficacy, compliance, and safety of this combination and its
congeners. No data exist to prove that the amlodipine/valsartan combination is better than other antihypertensive strategies for
cardiovascular or renal protection, but some trials with other combination therapies show such potential advantage
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Prediction of Treatment Response to Neoadjuvant Chemotherapy for Breast Cancer via Early Changes in Tumor Heterogeneity Captured by DCE-MRI Registration.
We analyzed DCE-MR images from 132 women with locally advanced breast cancer from the I-SPY1 trial to evaluate changes of intra-tumor heterogeneity for augmenting early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) after neoadjuvant chemotherapy (NAC). Utilizing image registration, voxel-wise changes including tumor deformations and changes in DCE-MRI kinetic features were computed to characterize heterogeneous changes within the tumor. Using five-fold cross-validation, logistic regression and Cox regression were performed to model pCR and RFS, respectively. The extracted imaging features were evaluated in augmenting established predictors, including functional tumor volume (FTV) and histopathologic and demographic factors, using the area under the curve (AUC) and the C-statistic as performance measures. The extracted voxel-wise features were also compared to analogous conventional aggregated features to evaluate the potential advantage of voxel-wise analysis. Voxel-wise features improved prediction of pCR (AUC = 0.78 (±0.03) vs 0.71 (±0.04), p < 0.05 and RFS (C-statistic = 0.76 ( ± 0.05), vs 0.63 ( ± 0.01)), p < 0.05, while models based on analogous aggregate imaging features did not show appreciable performance changes (p > 0.05). Furthermore, all selected voxel-wise features demonstrated significant association with outcome (p < 0.05). Thus, precise measures of voxel-wise changes in tumor heterogeneity extracted from registered DCE-MRI scans can improve early prediction of neoadjuvant treatment outcomes in locally advanced breast cancer
Deformations and dilations of chaotic billiards, dissipation rate, and quasi-orthogonality of the boundary wavefunctions
We consider chaotic billiards in d dimensions, and study the matrix elements
M_{nm} corresponding to general deformations of the boundary. We analyze the
dependence of |M_{nm}|^2 on \omega = (E_n-E_m)/\hbar using semiclassical
considerations. This relates to an estimate of the energy dissipation rate when
the deformation is periodic at frequency \omega. We show that for dilations and
translations of the boundary, |M_{nm}|^2 vanishes like \omega^4 as \omega -> 0,
for rotations like \omega^2, whereas for generic deformations it goes to a
constant. Such special cases lead to quasi-orthogonality of the eigenstates on
the boundary.Comment: 4 pages, 3 figure
Scaling of dynamical susceptibility at the onset of rigidity for disordered viscoelastic matter
The onset of rigidity in interacting liquids, as they undergo a transition to
a disordered solid, is associated with a dramatic rearrangement of the
low-frequency vibrational spectrum. In this letter, we derive scaling forms for
the singular dynamical response of disordered viscoelastic networks near both
jamming and rigidity percolation. Using effective-medium theory, we extract
critical exponents, invariant scaling combinations and analytical formulas for
universal scaling functions near these transitions. Our scaling forms describe
the behavior in space and time near the various onsets of rigidity, for rigid
and floppy phases and the crossover region, including diverging length and time
scales at the transitions. We expect that these behaviors can be measured in
systems ranging from colloidal suspensions to anomalous charge-density
fluctuations of "strange" metals.Comment: 6 pages, 3 figure
Role of Motility and the \u3cem\u3eflhDC\u3c/em\u3e Operon in \u3cem\u3eEscherichia coli\u3c/em\u3e MG1655 Colonization of the Mouse Intestine
Previously, we reported that the mouse intestine selected mutants of Escherichia coli MG1655 that have improved colonizing ability (M. P. Leatham et al., Infect. Immun. 73:8039-8049, 2005). These mutants grew 10 to 20% faster than their parent in mouse cecal mucus in vitro and 15 to 30% faster on several sugars found in the mouse intestine. The mutants were nonmotile and had deletions of various lengths beginning immediately downstream of an IS1 element located within the regulatory region of the flhDC operon, which encodes the master regulator of flagellum biosynthesis, FlhD4C2. Here we show that during intestinal colonization by wild-type E. coli strain MG1655, 45 to 50% of the cells became nonmotile by day 3 after feeding of the strain to mice and between 80 and 90% of the cells were nonmotile by day 15 after feeding. Ten nonmotile mutants isolated from mice were sequenced, and all were found to have flhDC deletions of various lengths. Despite this strong selection, 10 to 20% of the E. coli MG1655 cells remained motile over a 15-day period, suggesting that there is an as-yet-undefined intestinal niche in which motility is an advantage. The deletions appear to be selected in the intestine for two reasons. First, genes unrelated to motility that are normally either directly or indirectly repressed by FlhD4C2 but can contribute to maximum colonizing ability are released from repression. Second, energy normally used to synthesize flagella and turn the flagellar motor is redirected to growth
Role of Motility and the \u3cem\u3eflhDC\u3c/em\u3e Operon in \u3cem\u3eEscherichia coli\u3c/em\u3e MG1655 Colonization of the Mouse Intestine
Previously, we reported that the mouse intestine selected mutants of Escherichia coli MG1655 that have improved colonizing ability (M. P. Leatham et al., Infect. Immun. 73:8039-8049, 2005). These mutants grew 10 to 20% faster than their parent in mouse cecal mucus in vitro and 15 to 30% faster on several sugars found in the mouse intestine. The mutants were nonmotile and had deletions of various lengths beginning immediately downstream of an IS1 element located within the regulatory region of the flhDC operon, which encodes the master regulator of flagellum biosynthesis, FlhD4C2. Here we show that during intestinal colonization by wild-type E. coli strain MG1655, 45 to 50% of the cells became nonmotile by day 3 after feeding of the strain to mice and between 80 and 90% of the cells were nonmotile by day 15 after feeding. Ten nonmotile mutants isolated from mice were sequenced, and all were found to have flhDC deletions of various lengths. Despite this strong selection, 10 to 20% of the E. coli MG1655 cells remained motile over a 15-day period, suggesting that there is an as-yet-undefined intestinal niche in which motility is an advantage. The deletions appear to be selected in the intestine for two reasons. First, genes unrelated to motility that are normally either directly or indirectly repressed by FlhD4C2 but can contribute to maximum colonizing ability are released from repression. Second, energy normally used to synthesize flagella and turn the flagellar motor is redirected to growth
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