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Secant pile walls (SPWs) are frequently employed as temporary excavation support systems in urban areas; thus, they are useless once permanent foundations and basements have been constructed. Recently, attempts have been made to employ these walls to bear axial loads and lateral earth pressure, which may have significant potential benefits. Unfortunately, the shortage of research that recognizes them as bearing elements, especially numerical studies, has prevented this approach from reaching the final design and implementation stage. Thus, the primary objective of this research was to calibrate a finite element model to depict the performance of axially loaded SPW and extend the finite element analysis by including key factors and additional trials that may impact the performance of the axially loaded SPW. This research investigated various aspects to describe SPW behavior, including the maximum axial capacity of the SPW (Pmax), normalized horizontal deflection (δh/Ht%), normalized ground settlement (δvg/Ht%), the normalized vertical deflection of the SPW (δvw/Ht%), the normalized pivot point location (ε′/He) and settlement influence zone (Do). Several parameters, such as normalized penetration depth (He/Hc), sand relative density (Dr), surcharge load density (Wsur), and wall rigidity (Ht/Dp), were studied and examined in relation to these aspects. Additionally, 224 axially loaded SPW trails were performed as part of a parametric study. The findings demonstrated that the proposed FEM could depict the performance of the experimental model with fair accuracy under the effect of the axial and lateral loads. The effects of the investigated aspects on the Pmax were also discussed in detail. Also, using linear and non-linear regression analysis, the data from the parametric analysis was utilized to create rational relations between the various parameters. The best-achieved mathematical models for predicting the Pmax were also represented in graphical forms. Moreover, these graphs can be a useful and fast tool for civil and geotechnical engineers to predict the maximum axial capacity of an SPW according to the different variables. [ABSTRACT FROM AUTHOR]

In urban environments, temporary excavation support systems (ESSs) are intensively recommended during the construction process of structures with underground levels to preserve nearby structures and maintain the excavation sides. Once the foundations and basements are constructed, these systems are rendered useless. As a result, integrating the temporary ESS into the building foundation may have significant benefits. Therefore, the main aim of this paper was to investigate the behavior of Secant Pile Walls (SPWs) through fifteen model tests with an acceptable scale on an axially loaded SPW embedded in medium and dense sand. This study considered several factors to define wall behavior, such as normalized lateral deflection (δh/Ht%), the vertical deflection of the SPW (δvw/Ht%), vertical ground settlement (δv/Ht%), and settlement influence zone (Do). These factors were investigated and analyzed under the influence of a set of parameters including normalized penetration depth (He/Hc), sand relative density (Dr), and surcharge load density (Wsur). The findings demonstrated that SPWs had structural and overall stability features to withstand lateral earth pressures as well as applied axial loads. Generally, increasing the He/Hc ratio further than a limit value of 2.0 for the same surcharge load had a limited impact on the ultimate axial capacity, particularly in the case of dense sand. The location of the pivot point (ε′) extended from 0.24 to 0.41He from the wall tip, with a mean value of 0.34He and 0.29He for the values of Dr = 80 ± 2%, and 60 ± 2%, respectively. Other issues were also discussed for selected samples, including an analysis of the wall's bending moments and any potential wall buckling. Finally, to correlate the experimental data with the theoretical values, a modification factor for the pile static formula was developed by using nonlinear regression analysis with a significant prediction accuracy with an R2 of 0.94. [ABSTRACT FROM AUTHOR]

Background: International guidelines recommend nintedanib (OFEV®) as an option for the treatment of idiopathic pulmonary fibrosis (IPF).Objective: The objective of this study was to assess the cost effectiveness of nintedanib versus pirfenidone, N-acetylcysteine and best supportive care (BSC) for the treatment of IPF from a UK payer's perspective.Methods: A Markov model was designed to capture the changes in the condition of adults with IPF. Efficacy outcomes included mortality, lung function decline and acute exacerbations. Treatment safety (serious adverse events) and tolerability (overall discontinuation) were also considered. The baseline risk of these events was derived from patient-level data from the placebo arms of nintedanib clinical trials (TOMORROW, INPULSIS-1, INPULSIS-2). A network meta-analysis (NMA) was conducted to estimate the relative effectiveness of the comparator treatments. Quality of life and healthcare resource use data from the clinical trials were also incorporated in the economic model.Results: Nintedanib showed statistically significant differences against placebo on acute exacerbation events avoided and lung function decline. In the cost-effectiveness analysis, the results were split between two treatments with relative low costs and modest effectiveness (BSC and N-acetylcysteine) and two that showed improved effectiveness (lung function) and higher costs (nintedanib and pirfenidone). All comparators were assumed to have similar projected survival and the difference in quality-adjusted life-years (QALYs) was driven by the acute exacerbations and lung function estimates. In the base-case deterministic pairwise comparison with pirfenidone, nintedanib was found to have fewer acute exacerbations and resulted in less costs and more QALYs gained.Conclusions: Compared with BSC (placebo), nintedanib and pirfenidone were the only treatments to show statistical significance in the efficacy parameters. We found substantial uncertainty in the overall cost-effectiveness results between nintedanib and pirfenidone. N-Acetylcysteine was largely similar to BSC but with a worse survival profile. INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477. [ABSTRACT FROM AUTHOR]

The pentane extract of the Peruvian plant, Lepidium meyenii (Maca), has been demonstrated to possess neuroprotective activity in previous in vitro and in vivo studies (Pino-Figueroa et al. in Ann N Y Acad Sci 1199:77-85, 2010; Pino-Figueroa et al. in Am J Neuroprot Neuroregener 3:87-92, 2011). This extract contains a number of macamides that may act on the endocannabinoid system (Pino-Figueroa et al. in Ann N Y Acad Sci 1199:77-85, 2010; Pino-Figueroa et al., 2011; Dini et al. in Food Chem 49:347-349, 1994). The aim of this study was to characterize the inhibitory activity of four of these maccamides (N-benzylstearamide, N-benzyloleamide, N-benzyloctadeca-9Z,12Z-dienamide, and N-benzyloctadeca-9Z,12Z,15Z-trienamide) on fatty acid amide hydrolase (FAAH), an enzyme that is responsible for endocannabinoid degradation in the nervous system (Kumar et al. in Anaesthesia 56:1059-1068, 2001). The four compounds were tested at concentrations between 1 and 100 μM, utilizing an FAAH inhibitor screening assay. The results demonstrated concentration-dependent FAAH inhibitory activities for the four macamides tested. N-Benzyloctadeca-9Z,12Z-dienamide demonstrated the highest FAAH inhibitory activity whereas N-benzylstearamide had the lowest inhibitory activity. In addition, N-benzylstearamide, N-benzyloleamide, and N-benzyloctadeca-9Z,12Z-dienamide demonstrated time-dependent inhibition when tested after a pre-incubation period, indicating that the mechanism of inhibition for these compounds most likely is irreversible. Of interest, unsaturation in the fatty acid moiety resulted in greater FAAH inhibitory activity. LC/MS/MS analysis demonstrated that FAAH was able to hydrolyze N-benzyloctadeca-9Z,12Z-dienamide, suggesting that N-benzyloctadeca-9Z,12Z-dienamide is also a slow substrate for FAAH. These results provide useful information about the mechanism of action of Lepidium meyenii and may help with the development of new compounds with FAAH inhibitory or modulatory activity. [ABSTRACT FROM AUTHOR]

The dorsal metacarpal veins are frequently cannulated. Cannulation success is determined by several variable anatomic features. The objective of this study is to classify, for the first time, the anatomic variants of the dorsal metacarpal veins. In this cross-sectional study, 520 university students and staff were conveniently recruited. The dorsal metacarpal veins in 1040 hands were studied. Venous visibility was enhanced by either tourniquet application or near-infrared illumination. Variant patterns of the dorsal metacarpal veins were classified. The final analysis included 726 hands, for an exclusion rate of 30 %. Eight pattern types were identified. Three anatomic features informed the variation. Bilateral symmetry of the dorsal metacarpal veins was present in 352 participants (83 % of the total). The overall frequency distribution of variants in both hands was similar (P = 0.8). The frequency distribution of variants was subject to sexual dimorphism (P = 0.001), ethnic variation (P < 0.001), and technical variation (P < 0.001). The anatomic variants of the dorsal metacarpal veins were sorted into decreasingly frequent primary, secondary, and tertiary groups. The groups may signify a progressive increase in difficulty of peripheral cannulation, in the mentioned order. As such, primary patterns are the most common and likely the easiest to cannulate, while tertiary patterns are the least common and likely the most difficult to cannulate. The preceding premise, in tandem with the bilateral asymmetry of the veins, is clinically significant. With cannulation difficulty likely signifying an underlying tertiary pattern, the contralateral dorsal metacarpal veins are probabilistically characterized by a primary pattern and are, as such, the easier option for peripheral venous cannulation. [ABSTRACT FROM AUTHOR]

The design methods currently used for earth reinforcement are mostly based on deterministic properties of both the soil and the construction materials used. Nowadays, however, the general trend is designing at a specific degree of reliability. This is even more true where the raw data such as soil properties exhibit significant variation. Deterministic solutions, in this case, may not suffice. Therefore, this paper will attempt to use probabilistic formulations thereby modifying the existing design procedure of reinforced earth retaining walls to account for uncertainties and variabilities. Through a first order Taylor's series expansion about the mean, the mean and variance of the strip reinforcing components, namely width and length, are derived in terms of the variations in the soil properties. Design charts that enable estimation of both mean and variance are developed to avoid extensive partial differentiation involved in the computations. Using appropriate probability distributions along with the mean and variance, the final design outputs are determined for a selected failure probability by introducing what is refered to as 'risk index'. The results indicate that the risk index increases with an increase in the coefficient of variations and a decrease in failure probability. Furthermore, it is shown that in some cases, depending on the variabilities of the soil properties, the classical design technique produced a relatively high failure probability. [ABSTRACT FROM AUTHOR]

'Fen-phen' refers to the off-label combination of the appetite suppressants fenfluramine and phentermine. The rationale for the fen-phen combination was that the two drugs exerted independent actions on brain satiety mechanisms so that it was possible to use lower doses of each drug and yet retain a common action on suppressing appetite while minimizing adverse drug effects. The focus of the present review is to consider whether fenfluramine and phentermine exert actions that are additive in nature or whether these two drugs exhibit drug-drug synergism. The fen-phen combination results in synergism for the suppression of appetite and body weight, the reduction of brain serotonin levels, pulmonary vasoconstriction and valve disease. Fen-phen synergism may reflect changes in the pharmacokinetics of drug distribution, common actions on membrane ion currents, or interactions between neuronal release and reuptake mechanisms with MAO-mediated transmitter degradation. The synergism between fenfluramine and phentermine highlights the need to more completely understand the pharmacology and neurochemistry of appetite suppressants prior to use in combination pharmacotherapy for the treatment of obesity. [ABSTRACT FROM AUTHOR]

Studies the reasons how and why journalists avoid connecting environmental degradation to population growth. Significance of news coverage; Indifference of world leaders to the problem; Impact of social taboos in the Catholic Church; Framework of environmental causality; Identification of population-influenced disruptions.

PHOTOPLETHYSMOGRAPHY (PPG) has been recently introduced into the field of non-invasive assessment of venous function. Direct venous pressure measurements show a close correlation with post-exercise venous recovery obtained when using the PPG (Abramowitz et al, 1979). The PPG is also reputed to demonstrate a difference in recovery time among patients with primary and secondary varicose veins (Barnes et al, 1978). This prospective controlled trial studied patients before and after surgery or injection aclerotherapy used for patients with all types of venous diseases. We have shown that treatment of primary varicose veins and patients with postphlebitic syndrome results in improvement in post-exercise venous recovery times and a PPG value that returns towards a normal range. We conclude that this technique provides a useful non - invasive assessment of venous function and requires further evaluation as a simple objective follow-up for these patients. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated the ability of tyrosine (TYR), the amino acid precursor of catecholamines, to increase blood pressure in rats made hypotensive by haemorrhage. Other studies have shown that supplementation of the diet with TYR can reverse certain neurochemical and behavioural consequences associated with acute stress. Such studies demonstrate that during conditions of enhanced neuronal firing catecholamine synthesis is accelerated when additional precursor TYR is made available. In these situations the rate-limiting enzyme of catecholamine synthesis, tyrosine hydroxylase, activated via phosphorylation, becomes responsive to additional TYR. Our experiments were designed to study the ability of dietary TYR (3.7%, or 4 X the normal amount), to prevent the rapid fall in blood pressure observed during acute haemorrhage. Rats consuming the high TYR diet (5 days) maintained arterial blood pressure (systolic, diastolic and mean) at significantly greater values during the period of acute haemorrhagic insult than animals maintained on a control diet. Rats fed the high TYR diet had significantly greater levels of the amino acid in the heart, adrenal glands, liver, kidney, brainstem, spleen and semimembranosus pars caudalis muscle. We conclude that TYR can be stored and most likely utilized in the synthesis of catecholamines for the maintenance of arterial blood pressure during acute haemorrhage. These results are of particular importance in light of the fact that most total parenteral nutrition solutions contain very little if any TYR. [ABSTRACT FROM AUTHOR]

Plasma large neutral amino acid concentrations were measured in thirty-seven subjects before and after completing the Boston Marathon. Concentrations of tyrosine, phenylalanine, and methionine increased, as did their 'plasma ratios' (i.e., the ratio of each amino acid's concentration to the summed plasma concentrations of the other large neutral amino acids which compete with it for brain uptake). No changes were noted in the plasma concentrations of tryptophan, leucine, isoleucine, nor valine; however, the 'plasma ratios' of valine, leucine, and isoleucine all decreased. These changes in plasma amino acid patterns may influence neurotransmitter synthesis. [ABSTRACT FROM AUTHOR]

All aspartame does given to humans cause greater elevations in plasma (and, presumably, brain) phenylalanine than in plasma tyrosine. In contrast, doses of aspartame usually used in experiments on rodents preferentially elevate tyrosine. Since phenylalanine can inhibit brain catecholamine synthesis while tyrosine is the antidote for this effect, we determined the aspartame dose that would be needed to elevate phenylalanine more than tyrosine in rodents, using published data. In general rodents need 60 times as much aspartame, on a mg/kg basis, as humans to obtain comparable elevations in phenylalanine with respect to tyrosine. [ABSTRACT FROM AUTHOR]

We examined the effect of tyrosine (10-200 mg/kg given intravenously) or placebo on blood pressure (BP) in dogs made hypotensive (systolic BP=50 mm Hg) by bleeding one hour previously. Animals which, prior to induction of hypotension, had been normotensive (mean arterial pressures, [MAP]≦145 mm Hg) subsequently exhibited a dose-related increase in BP after tyrosine administration. In contrast, dogs which had been hypertensive prior to bleeding exhibited a fall in BP after tyrosine. These observations indicated that prior cardiovascular status may be an important factor influencing responses to exogenous tyrosine, and to endogenous catecholamines produced from the tyrosine. [ABSTRACT FROM AUTHOR]