2,228 research outputs found

    The Selection of Choice of Law Provisions in International Commercial Arbitration: A Case for Contractual Depeҫage

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    One additional advantage of arbitration, the parties\u27 ability to predetermine the law governing the resolution of the dispute, has gained growing recognition in recent years. This recognition, however, has been myopic to some extent. Some commentators see choice of law options confined either to the selection of one national legal system from several possibilities or to the selection of a single national, international, or anational legal system. Such a self-imposed limitation of the applicable law to one system of law often denies parties many of the benefits and powers allowed them in international commercial arbitration. As an alternative, an agreement may direct an arbitrator to apply different systems of law to different areas of the dispute

    Addition of a dairy fraction rich in milk fat globule membrane to a high-saturated fat meal reduces the postprandial insulinaemic and inflammatory response in overweight and obese adults.

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    Meals high in SFA, particularly palmitate, are associated with postprandial inflammation and insulin resistance. Milk fat globule membrane (MFGM) has anti-inflammatory properties that may attenuate the negative effects of SFA-rich meals. Our objective was to examine the postprandial metabolic and inflammatory response to a high-fat meal composed of palm oil (PO) compared with PO with an added dairy fraction rich in MFGM (PO+MFGM) in overweight and obese men and women (n 36) in a randomised, double-blinded, cross-over trial. Participants consumed two isoenergetic high-fat meals composed of a smoothie enriched with PO with v. without a cream-derived complex milk lipid fraction ( dairy fraction rich in MFGM) separated by a washout of 1-2 weeks. Serum cytokines, adhesion molecules, cortisol and markers of inflammation were measured at fasting, and at 1, 3 and 6 h postprandially. Glucose, insulin and lipid profiles were analysed in plasma. Consumption of the PO + MFGM v. PO meal resulted in lower total cholesterol (P = 0·021), LDL-cholesterol (P = 0·046), soluble intracellular adhesion molecule (P = 0·005) and insulin (P = 0·005) incremental AUC, and increased IL-10 (P = 0·013). Individuals with high baseline C-reactive protein (CRP) concentrations (≥3 mg/l, n 17) had higher (P = 0·030) insulin at 1 h after the PO meal than individuals with CRP concentrations <3 mg/l (n 19). The addition of MFGM attenuated this difference between CRP groups. The addition of a dairy fraction rich in MFGM attenuated the negative effects of a high-SFA meal by reducing postprandial cholesterol, inflammatory markers and insulin response in overweight and obese individuals, particularly in those with elevated CRP

    Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

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    Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P < 0·05) without a decrease by 6 h. The incremental AUC (iAUC) for CRP was significantly lower (P < 0·05) in response to the cheese compared with the vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633

    Monoallelic deletion of the microRNA biogenesis gene Dgcr8 produces deficits in the development of excitatory synaptic transmission in the prefrontal cortex

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    Abstract Background Neuronal phenotypes associated with hemizygosity of individual genes within the 22q11.2 deletion syndrome locus hold potential towards understanding the pathogenesis of schizophrenia and autism. Included among these genes is Dgcr8, which encodes an RNA-binding protein required for microRNA biogenesis. Dgcr8 haploinsufficient mice (Dgcr8+/-) have reduced expression of microRNAs in brain and display cognitive deficits, but how microRNA deficiency affects the development and function of neurons in the cerebral cortex is not fully understood. Results In this study, we show that Dgcr8+/- mice display reduced expression of a subset of microRNAs in the prefrontal cortex, a deficit that emerges over postnatal development. Layer V pyramidal neurons in the medial prefrontal cortex of Dgcr8+/- mice have altered electrical properties, decreased complexity of basal dendrites, and reduced excitatory synaptic transmission. Conclusions These findings demonstrate that precise microRNA expression is critical for the postnatal development of prefrontal cortical circuitry. Similar defects in neuronal maturation resulting from microRNA deficiency could represent endophenotypes of certain neuropsychiatric diseases of developmental onset

    Pulmonary hypertension is a manifestation of congestive heart failure and left ventricular diastolic dysfunction in octogenarians with severe aortic stenosis

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    Previous studies have suggested that pulmonary hypertension (PH) in severe aortic stenosis (AS) is a risk factor for operative mortality with aortic valve replacement (AVR). Conversely, others have shown that patients with AS and PH extract a large symptomatic and survival benefit from AVR compared with those patients not treated surgically. We sought to evaluate the prevalence, severity, and mechanism of PH in an elderly patient cohort with severe AS. We prospectively evaluated 41 patients aged ≥80 years with severe AS. All patients underwent cardiac catheterization and transthoracic echocardiography within 24 hours. We found that PH was common in this cohort: 32 patients (78%) had PH; however, the predominant mechanism of PH was left heart congestion. Patients with PH had nearly double the pulmonary artery wedge pressure of patients without PH (23 vs. 13 mmHg; P ≤ 0.001). In patients with PH compared with those without, pulmonary vascular resistance was higher yet still under 3 Wood units (WU; 2.9 vs. 1.5 WU; P = 0.001), and the transpulmonary gradient (11 vs. 7 mmHg; P = 0.01) and diastolic pulmonary gradient (DPG; 3.0 vs. 2.7 mmHg; P = 0.74) were in normal range. Left ventricular diastolic abnormalities were more common in patients with severe AS and PH. Right ventricular (RV) dysfunction was common (13/41 patients, 32%), but the PH and non-PH groups had similar tricuspid annular plane systolic excursion (2.0 vs. 2.3 cm; P = 0.15). Only 2 subjects had both RV dysfunction and an elevated DPG. In conclusion, PH is common in elderly patients with severe AS. This occurs largely due to left heart congestion, with a relative absence of pulmonary vascular disease and RV dysfunction, and as such, PH may serve as a heart failure equivalent in these patients

    Why growth equals power - and why it shouldn't : constructing visions of China

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    When discussing the success of China's transition from socialism, there is a tendency to focus on growth figures as an indication of performance. Whilst these figures are indeed impressive, we should not confuse growth with development and assume that the former necessarily automatically generates the latter. Much has been done to reduce poverty in China, but the task is not as complete as some observers would suggest; particularly in terms of access to health, education and welfare, and also in dealing with relative (rather than absolute) depravation and poverty. Visions of China have been constructed that exaggerate Chinese development and power in the global system partly to serve political interests, but partly due to the failure to consider the relationship between growth and development, partly due to the failure to disaggregate who gets what in China, and partly due to the persistence of inter-national conceptions of globalised production, trade, and financial flows

    Tubular gelatinase A (MMP-2) and its tissue inhibitors in polycystic kidney disease in the Han:SPRD rat

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    Tubular gelatinase A (MMP-2) and its tissue inhibitors in polycystic kidney disease in the Han:SPRD rat. Thickening of the tubular basement membrane is one of the hallmarks of polycystic kidney disease (PKD). The present study was conducted to investigate the potential role of the matrix metalloproteinase-2 (MMP-2) and its specific tissue inhibitors (TIMP-1 and TIMP-2) in the accumulation of matrix components in PKD. As a model of PKD, two-month-old heterozygous Han:SPRD rats, which are at an early stage of cystogenesis, were used. MMP-2, but not MMP-9 (gelatinase B) nor MMP-3 (stromelysin) could be detected in proximal tubules of the normal rat kidney. The presence of the inhibitors TIMP-1 and TIMP-2 was confirmed on the mRNA level. In tubules from PKD rats MMP-2 activity was lower (31 ± 8 vs. 58 ± 7 U/prep., N = 9, P < 0.05), mRNA of MMP-2 was reduced 4.2 ± 0.6-fold (N = 4, P < 0.05) and enzyme protein was depressed 3.8 ± 0.8-fold (N = 4, P < 0.05). By contrast, TIMP-1 mRNA was 9.0 ± 1.1-fold and TIMP-2 mRNA 3.8 ± 0.7-fold (N = 4, P < 0.05) elevated over controls. Cyst fluid from homozygous rats contained MMP-2 protein and activity. These findings indicate that tubular MMP-2 activity is reduced in PKD, due to down-regulation of MMP-2, up-regulation of TIMP-1 and TIMP-2, and luminal secretion of the enzyme. It is conceivable that these alterations relate to the enhanced matrix accumulation observed in the evolution of PKD
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