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Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.
Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial.
In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS).
MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance.
Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.
It is a truth universally acknowledged that every ambitious twenty-first century trade agreement is in want of a chapter on electronic commerce. One of the most politically sensitive and technically challenging issues is personal privacy, including cross-border transfer of information by electronic means, use and location of computing facilities, and personal information protection. States are learning to solve the problem of state responsibility for something that does not respect their borders while still allowing twenty-first century commerce to develop. A comparison of the Canada–European Union Comprehensive Economic and Trade Agreement (CETA) and the Trans-Pacific Partnership (TPP) allows us to see the evolution of the issues thought necessary for an e-commerce chapter, since both include Canada, and to see the differing priorities of the US and the EU, since they are each signatory to one of the agreements, but not of the other. I conclude by seeking generalizations about why we see a mix of aspirational and obligatory provisions in free trade agreements. I suggest that the reasons are that governments are learning how to work with each other in a new domain, and learning about the trade implications of these issues.
State-owned enterprises (SOEs) are a major force in the Chinese economy and a growing presence in international trade and investment. The challenge to the WTO legal regime is commercial, given the size of SOEs and their share of Chinese output, and political, given worries that trade and investment by SOEs may be driven by public policy goals. And both challenges may be exacerbated by the murky world of Chinese SOEs. In this article, I first review whether Chinese SOEs are a problem for the WTO, and whether more sunshine on their operations might be a useful discipline. I then ask what we know about SOEs inside the WTO, including in the Trade Policy Review Mechanism. Since the answer is, not much, I consider whether mega-regional trade negotiations offer a better approach. My answer being negative, I finally consider whether an attempt to negotiate a WTO Reference Paper on SOEs might help. I conclude that transparency is likely to be a better discipline on the spillovers associated with SOEs than a search for binding rules, while also helping everyone better understand the efficiency effects.
OBJECTIVES/SPECIFIC AIMS: This study will assess the effect of essential amino acid (EAA) supplementation on plasma triglyceride (TG) in elderly adults. We will also explore the mechanisms mediating EAA mediated changes in fat metabolism and to suggest promising routes to refine therapy of hypertriglyceridemia. METHODS/STUDY POPULATION: In total, 7 nondiabetic male and female subjects ages 50–75 years with elevated plasma TG levels (130–500 mg/dL) were recruited to participate in an acute (5 h) and long-term (8 wk) EAA supplementation study. We measured changes in regional and whole body fat metabolism, including changes in body composition, plasma TG levels, whole body fat metabolic rates, tissue mitochondrial respiratory capacity, and metabolomic profiles before and after supplementation. RESULTS/ANTICIPATED RESULTS: Long-term EAA supplementation decreased fasted plasma TG levels by 19% (p<0.01). Metabolomics of skeletal muscle found acute EAA supplementation resulted in increased EAA metabolic products while long-term supplementation resulted in increased anaplerosis [flux into the tricarboxylic acid cycle (TCA) intermediate pool] and anaplerotic substrates [propionyl (p<0.01) and succinyl (p<0.01) carnitine] and intermediates of long-chain fatty acid metabolism [stearoyl (p<0.01) and myristoyl (p<0.05) carnitine]. However, tissue level respiratory capacity appeared to be unaffected by EAA supplementation. DISCUSSION/SIGNIFICANCE OF IMPACT: EAA supplementation has potential to improve lipid metabolism and plasma TG levels in non-diabetic older adults. Mitochondrial metabolomics suggest that insufficient TCA pool size may limit tissue fatty acid oxidation and may provide an additional route for nutritional therapy.
Private standards are increasing in number, and they affect trade, but their status in the WTO remains problematic. Standards-takers are typically countries with little bargaining power, who cannot affect their terms of trade, and, thus, even if they possess domestic antitrust laws, will find it hard to persuade standard-setters to take account of their interests. Our concern is to bring more of these standards within the normative framework of the trade regime – that is, we worry that these private forms of social order can conflict with the fundamental norms of transparency and non-discrimination. The WTO membership has consumed itself in endless discussions regarding mundane, legalistic issues, and has not moved at all towards addressing the real concerns of developing countries. We discuss one aspect of the problem: How reclusive should the WTO allow product standards to be? We argue that the WTO should adopt a ‘Reference Paper’ that would encourage its members to apply WTO rules for adopting those standards that already come under the aegis of the WTO to private standards. In the absence of centralized enforcement, utopia in the WTO legal paradigm, transparency disciplines imposed on standard-setters is the best the WTO could offer to those who are negatively affected by private standards.
The Amsterdam glacial basin was a major sedimentary sink from late Saalian until late Eemian (Picea zone, E6) times. The basin’s exemplary record makes it a potential reference area for the last interglacial stage. The cored Amsterdam-Terminal borehole was drilled in 1997 to provide a record throughout the Eemian interglacial. Integrated facies analysis has resulted in a detailed reconstruction of the sedimentary history.
After the Saalian ice mass had disappeared from the area, a large, deep lake had come into being, fed by the Rhine river. At the end of the glacial, the lake became smaller because it was cut off from the river-water supply, and eventually only a number of shallow pools remained in the Amsterdam basin. During the early Eemian (Betula zone, El), a seepage lake existed at the site. The lake deepened under the influence of a steadily rising sea level and finally evolved into a silled lagoon (late Quercus zone, E3). Initially, the lagoon water had fairly stable stratification, but as the sea level continued to rise the sill lost its significance, the lagoon becoming well mixed by the middle of the Corylus/Taxus zone (E4b). The phase of free exchange with the open sea ended in the early Carpinus zone (E5), when barriers developed in the sill area causing the lagoon to become stratified again. During the Late Eemian (late E5), a more dynamic system developed. The sandy barriers that had obstructed exchange with the open sea were no longer effective, and a tidally-influenced coastal lagoon formed.
The Eemian sedimentary history shown in the Amsterdam-Terminal borehole is intimately connected with the sea-level history. Because the site includes both a high-resolution pollen signal and a record of sea-level change, it has potential for correlation on various scales. Palaeomagnetic results show that the sediments predate the Blake Event, which confirms that this reversal excursion is relatively young. The U/Th age of the uppermost part of the Eemian sequence is 118.2±6.3 ka.
To summarize the best available evidence regarding the short- and long-term health effects of cow’s milk intake in healthy, full-term infants up to 3 years of age.
We conducted a systematic review and meta-analysis.
We searched MEDLINE (via PubMed), EMBASE and the Cochrane Library between 1960 and July 2013 and manually reviewed reference lists of pertinent articles. Two researchers independently reviewed abstracts and full-text articles and extracted relevant data.
We included (randomized/non-randomized) controlled trials and observational studies.
We included data from twenty-three studies (one randomized controlled trial, four non-randomized controlled trials, eight case–control studies and ten cohort studies) for the evidence synthesis. Pooled results of four studies revealed a higher risk of Fe-deficiency anaemia for infants consuming cow’s milk compared with those consuming follow-on formula (relative risk=3·76; 95 % CI 2·73, 5·19). For type 1 diabetes mellitus, six out of seven case–control studies did not show a difference in the risk of developing this disease based on the age of introduction of cow’s milk. We did not find negative associations for other health effects.
Cow’s milk consumption in infancy is associated with an increased risk of developing Fe-deficiency anaemia. Limiting cow’s milk consumption may be important to ensure an adequate Fe intake for infants and toddlers. High-quality patient information for caregivers is needed on how infants’ Fe requirements can be met.
The commonplace tendency is to blame the difficulties of the Doha Round of multilateral trade negotiations on the World Trade Organization (WTO) itself. In contrast, I suggest in the first section of this article that exogenous structural factors, especially changing commodity prices and trade flows, fatally undermined the Round. In the second section, I discount the significance of endogenous institutional factors such as the number of participants, the size of the agenda, or the Single Undertaking, although design failures, notably in the ‘modalities’ for negotiation, did hurt. But what hurt even more was the way the WTO, in common with most multilateral organizations, has not caught up with the shifting centre of gravity in global governance. The trading system is no longer a transatlantic bargain. The regulatory issues on the twenty-first century trade policy agenda will inevitably be negotiated in Geneva, but only after a new trans-Pacific accommodation recognizes China's central role.
This paper shows that the two most common impedance transformation networks for power amplifiers (PAs) can be designed to achieve optimum transformation at two frequencies. Hence, a larger bandwidth for the required impedance transformation ratio is achieved. A design procedure is proposed, which takes imperfections like losses into account. Furthermore, an analysis method is presented to estimate the maximum uncompressed output power of a PA with respect to frequency. Based on these results, a fully integrated PA with a dual-band impedance transformation network is designed and its functionality is proven by large signal measurement results. The amplifier covers the frequency band from 450 MHz to 1.2 GHz (3 dB bandwidth of the output power and efficiency), corresponding to a relative bandwidth of more than 100%. It delivers 23.7 dBm output power in the 1 dB compression point, having a power-added efficiency of 33%.
Fossil fuel subsidies undermine efforts to mitigate climate change, and they damage the trading system. Multilateral discussion is hampered by inconsistent definitions and incomplete data, which could increase the risks of WTO disputes. Members do not notify such subsidies as much as they should under the Agreement on Subsidies and Countervailing Measures (ASCM), which limits the usefulness of the SCM Committee. The reports of the Trade Policy Review Mechanism on individual countries and on the trading system draw on a wider range of sources, creating an opportunity for non-governmental organizations (NGOs) to provide the missing data from publicly available sources. We suggest a new template that could be used for such third-party notifications. The objective is to shine a light on all fossil fuel subsidies that cause market distortions, especially trade distortions. The result should be better, more comparable data for the Secretariat, governments, and researchers, providing the basis for better-informed discussion of the incidence of fossil fuel subsidies and rationale for their use.
An overview about the German cluster project Cool Silicon aiming at increasing the energy efficiency for semiconductors, communications, sensors and software is presented. Examples for achievements are: 1000 times reduced gate leakage in transistors using high-fc (HKMG) materials compared to conventional poly-gate (SiON) devices at the same technology node; 700 V transistors integrated in standard 0.35 μm CMOS; solar cell efficiencies above 19% at < 200 W/m2 irradiation; 0.99 power factor, 87% efficiency and 0.088 distortion factor for dc supplies; 1 ns synchronization resolution via Ethernet; database accelerators allowing 85% energy savings for servers; adaptive software yielding energy reduction of 73% for e-Commerce applications; processors and corresponding data links with 40% and 70% energy savings, respectively, by adaption of clock frequency and supply voltage in less than 20 ns; clock generator chip with tunable frequency from 83-666 MHz and 0.62-1.6 mW dc power; 90 Gb/s on-chip link over 6 mm and efficiency of 174 fJ/mm; dynamic biasing system doubling efficiency in power amplifiers; 60 GHz BiCMOS frontends with dc power to bandwidth ratio of 0.17 mW/MHz; driver assistance systems reducing energy consumption by 10% in cars
We present a design strategy for a buck converter, which fulfills the high dynamic requirements of efficient envelope amplifier needed by modern efficiency enhancement techniques for power amplifiers. The proposed DC–DC converter has an innovative control system, which makes it fast, robust, and resource saving. A mathematical model describes its dynamic behavior and is used to find a setup, which gives an optimal compromise between the dynamic performance and efficiency. The approach is applicable to various state-of-the-art communication standards. As an example, an envelope following (EF) power amplifier (PA) for the wideband code-division-multiple-access (W-CDMA) modulation scheme is treated. The corresponding buck converter is implemented in a monolithic chip (except the inductor and the capacitor of the output filter). The measurements with an industry standard W-CDMA PA (RMPA2265) match very well with the forecast of the model and confirm doubling of the average efficiency.
The determination of whether increased dietary protein can positively affect health outcomes is hindered by the absence of prospective, randomized trials directly addressing this issue in which all pertinent variables are controlled. Consequently, we can only address the question deductively by considering the support for the rationale underlying the notion of a beneficial effect of increased dietary protein intake. With regard to health outcomes, we have focused on older individuals. Muscle mass and function are progressively lost with aging, so that by the age of 60 many individuals have reached a threshold where function begins to be affected. An association between reduced muscle mass and strength and unfavourable health outcomes is more likely to be revealed in individuals who have significant decrements in muscle mass and strength. In this article support for the rationale underlying the notion of a beneficial effect of increased dietary protein intake is considered. Dietary protein intake, and the resulting increased availability of plasma amino acids, stimulates muscle protein synthesis. If all other variables are controlled, increased muscle protein synthesis leads to improved muscle mass, strength and function over time. Increased muscle mass, strength and function are related to improved health outcomes in older individuals. Since adverse effects of reasonable increases in protein intake above the recommended dietary allowance (RDA) of 0·8 g protein/kg/day have not been reported, it is reasonable to conclude that the optimal protein intake for an older individual is greater than the RDA.