Angiotensin II blockade and aortic-root dilation in Marfan's syndrome

Background: Progressive enlargement of the aortic root, leading to dissection, is the main cause of premature death in patients with Marfan's syndrome. Recent data from mouse models of Marfan's syndrome suggest that aortic-root enlargement is caused by excessive signaling by transforming growth factor (beta) (TGF-(beta)) that can be mitigated by treatment with TGF-(beta) antagonists, including angiotensin II-receptor blockers (ARBs). We evaluated the clinical response to ARBs in pediatric patients with Marfan's syndrome who had severe aortic-root enlargement. Methods: We identified 18 pediatric patients with Marfan's syndrome who had been followed during 12 to 47 months of therapy with ARBs after other medical therapy had failed to prevent progressive aortic-root enlargement. The ARB was losartan in 17 patients and irbesartan in 1 patient. We evaluated the efficacy of ARB therapy by comparing the rates of change in aortic-root diameter before and after the initiation of treatment with ARBs. Results: The mean (+/-SD) rate of change in aortic-root diameter decreased significantly from 3.54+/-2.87 mm per year during previous medical therapy to 0.46+/-0.62 mm per year during ARB therapy (P<0.001). The deviation of aortic-root enlargement from normal, as expressed by the rate of change in z scores, was reduced by a mean difference of 1.47 z scores per year (95% confidence interval, 0.70 to 2.24; P<0.001) after the initiation of ARB therapy. The sinotubular junction, which is prone to dilation in Marfan's syndrome as well, also showed a reduced rate of change in diameter during ARB therapy (P<0.05), whereas the distal ascending aorta, which does not normally become dilated in Marfan's syndrome, was not affected by ARB therapy. Conclusions: In a small cohort study, the use of ARB therapy in patients with Marfan's syndrome significantly slowed the rate of progressive aortic-root dilation. These findings require confirmation in a randomized trial

Impact of Vegetative Treatment Systems on Multiple Measures of Antibiotic Resistance in Agricultural Wastewater

Wastewater is an important vector of antibiotic resistant bacteria and antibiotic resistance genes (ARB/G). While there is broad agreement that ARB/G from agricultural (ag) wastewaters can be transported through the environment and may contribute to untreatable infectious disease in humans and animals, there remain large knowledge gaps surrounding applied details on the types and amounts of ARB/G associated with different agricultural wastewater treatment options and different ag production systems. This study evaluates a vegetative treatment system (VTS) built to treat the wastewater from a beef cattle feedlot. Samples were collected for three years, and plated on multiple media types to enumerate tetracycline and cefotaxime-resistant bacteria. Enterobacteriaceae isolates (n = 822) were characterized for carriage of tetracycline resistance genes, and E. coli isolates (n = 673) were phenotyped to determine multi-drug resistance (MDR) profiles. Tetracycline resistance in feedlot runoff wastewater was 2-to-3 orders of magnitude higher compared to rainfall runoff from the VTS fields, indicating efficacy of the VTA for reducing ARB over time following wastewater application. Clear differences in MDR profiles were observed based on the specific media on which a sample was plated. This result highlights the importance of method, especially in the context of isolate-based surveillance and monitoring of ARB in agricultural wastewaters

On the correlation of shear band formation and texture evolution in α\alpha-brass during accumulative roll bonding

We studied the microstructural evolution of the low stacking fault energy $\alpha$-brass alloy CuZn15 during accumulative roll bonding (ARB). Most notably, the typical brass-type texture was clearly observed after four ARB passes (approx. 93.8 % total thickness reduction), before significant shear localization set in. This observation contradicts the widely accepted idea that shear band formation is a necessary prerequisite for the development of the brass type texture, indicating that the two phenomena, shear banding and development of the brass texture, are only correlated in ARB, and that their order of appearance can be switched depending on experimental parameters.Comment: 4 pages, 2 figure

The impact of antibiotic use on transmission of resistant bacteria in hospitals: Insights from an agent-based model

Extensive antibiotic use over the years has led to the emergence and spread of antibiotic resistant bacteria (ARB). Antibiotic resistance poses a major threat to public health since for many infections antibiotic treatment is no longer effective. Hospitals are focal points for ARB spread. Antibiotic use in hospitals exerts selective pressure, accelerating the spread of ARB. We used an agent-based model to explore the impact of antibiotics on the transmission dynamics and to examine the potential of stewardship interventions in limiting ARB spread in a hospital. Agents in the model consist of patients and health care workers (HCW). The transmission of ARB occurs through contacts between patients and HCW and between adjacent patients. In the model, antibiotic use affects the risk of transmission by increasing the vulnerability of susceptible patients and the contagiousness of colonized patients who are treated with antibiotics. The model shows that increasing the proportion of patients receiving antibiotics increases the rate of acquisition non-linearly. The effect of antibiotics on the spread of resistance depends on characteristics of the antibiotic agent and the density of antibiotic use. Antibiotic's impact on the spread increases when the bacterial strain is more transmissible, and decreases as resistance prevalence rises. The individual risk for acquiring ARB increases in parallel with antibiotic density both for patients treated and not treated with antibiotics. Antibiotic treatment in the hospital setting plays an important role in determining the spread of resistance. Interventions to limit antibiotic use have the potential to reduce the spread of resistance, mainly by choosing an agent with a favorable profile in terms of its impact on patient's vulnerability and contagiousness. Methods to measure these impacts of antibiotics should be developed, standardized, and incorporated into drug development programs and approval packages

Losartan/Hydrochlorothiazide Combination Therapy Surpasses High-dose Angiotensin Receptor Blocker in the Reduction of Morning Home Blood Pressure in Patients with Morning Hypertension

Angiotensin receptor blockers (ARBs) are the first-line antihypertensive agents. In clinical practice, it is often difficult to achieve the recommended blood pressure level by ARBs in their ordinal dosages alone. This study examined the practical efficacy of a combination therapy of ARB with thiazide diuretics for lowering morning home blood pressure (MHBP) in comparison to high-dose ARB therapy in patients with morning hypertension administered an ordinal dosage of ARB. This study was performed in a prospective, randomized, open-labeled and blind-endpoint fashion. Patients were considered to have morning hypertension when their self-measured systolic MHBPs were 135mmHg or higher, irrespective of their diastolic MHBP and office blood pressures (OBPs). Forty-eight outpatients with morning hypertension receiving the ordinal dosage of ARB were given either losartan/hydrochlorothiazide (n＝26) or high-dose ARB (n＝22) in place of their previously prescribed ARB. No change in any medication was permitted during this period. Decreases of both systolic and diastolic MHBP after 3 months of treatment were significantly greater in the losartan/hydrochlorothiazide group than in the high-dose ARB group (p＜0.05, respectively). The ratio of adverse events was somewhat high (23.1% in the losartan/hydrochlorothiazide group, 9.1% in the high-dose ARB group, respectively). However, there were no significant differences in any particular adverse event between groups. This study suggested losartan/hydrochlorothiazide might be superior to high-dose ARB for reducing morning home blood pressure

Precedent and Control in Investment Treaty Arbitration

This Article\u27s thesis is that, although arbitrators in investment treaty arbitration are not formally bound by precedent in the same manner as common-law judges, there is an informal, but powerful, system of precedent that constrains arbitrators to account for prior published awards and to stabilize international investment law. This informal system, however, imperfectly supports the relevant policy goals. It is additionally being tested by an increasing diversity of arbitrators, who are themselves facing pressures from investors and host States to meet conflicting demands. This Article proposes that the structure of investment treaty arbitration can absorb such stresses if: (a) the system of precedent is clarified and publicized to enable the global community to appraise awards and the arbitrators who render them; (b) investors and States exercise care in their selection of arbitrators; and (c) the community of international arbitrators exercises sufficient informal self-regulation and self-selection. This thesis is developed in three Parts. Part I discusses the concept and policies of precedent as it has developed in courts. Part II examines the extent to which these policies apply to investment treaty arbitration, and whether investment treaty arbitration has a system of precedent that promotes the relevant policy goals. Part III makes recommendations to further refine the system of precedent in response to emerging global trends, such as the economic growth of the People\u27s Republic of China and an increasing diversity of arbitrators from both developed and developing States

Resonant spike propagation in coupled neurons with subthreshold activity

Màster en Biofísica, curs 2006-2007Chemical coupling between neurons is only active when the presynaptic neuron is firing, and thus it does not allow for the propagation of subthreshold activity. Electrical coupling via gap junctions, on the other hand, is also ubiquitous and, due to its diffusive nature, transmits both subthreshold and suprathreshold activity between neurons. We study theoretically the propagation of spikes between two neurons that exhibit subthreshold oscillations, and which are coupled via both chemical synapses and gap junctions. Due to the electrical coupling, the periodic subthreshold activity is synchronized in the two neurons, and affects propagation of spikes in such a way that for certain values of the delay in the synaptic coupling, propagation is not possible. This effect could provide a mechanism for the modulation of information transmission in neuronal networks

Future changes in tropical cyclone activity in the North Indian Ocean projected by high-resolution MRI-AGCMs

Open Access at publisher's web site: http://www.springerlink.com/content/b682734237171631

Streamlining the Corruption Defense: A Proposed Framework for FCPA-ICSID Interaction

Over the past decade, the number of Foreign Corrupt Practices Act (FCPA) enforcement actions has soared, as has the number of cases before the International Centre for Settlement of Investment Disputes (ICSID). At the same time, events have demonstrated that two problems may arise from the lack of coordination between anticorruption investigations and ICSID arbitration proceedings. First, anticorruption investigations may reveal arbitral decisions to be incorrect due to a lack of evidence regarding corruption in the formation of investment contracts. Second, the corruption defense —an emerging affirmative defense that allows host states to invoke corruption in the formation of investment contracts as an absolute bar to liability—creates a perverse incentive that encourages states to expropriate investors\u27 assets, or to renegotiate for burdensome new terms, following FCPA investigations. This Note explores the characteristics of the corruption defense as applied by ICSID tribunals, including the evidentiary burden placed upon the host state to assert the defense. It then proposes a framework for FCPA-ICSID interaction designed to strengthen the defense and to further the goal of eradicating global corruption. It proposes using tools such as waiver and disgorgement, contract cure, and communication between FCPA enforcement authorities and ICSID tribunals to remedy the problems identified above