Enhancing legal certainty is one of the main values that are sought in the investor–state dispute settlement system. The importance of legal certainty is strengthened in the case of renewable energy ...investments, which are in the global public interest, long-term and capital-intensive up-front. The first part of the paper presents the importance of legal certainty in investment arbitration in general, its limits and its importance in the context of the green energy transition. In addition, it addresses the special features of renewable energy investments. The second part of the paper analyses from the perspective of legal certainty the Spanish renewable energy cases initiated under the Energy Charter Treaty (ECT), which deal with similar factual and legal issues. In this respect, the paper presents the varying weight tribunals gave to the important facts that led them further to conclude whether Spain breached the fair and equitable treatment standard, and if so, whether the investor was entitled to full compensation or a reasonable rate of return. In addition, it presents different approaches to perceiving the stability provision of Article 10 (1) of the ECT. The paper concludes that it remains uncertain to what extent RE investors will be protected under the ECT’s stability condition in the case of fundamental or small-scale changes. Although one group of arbitrators may argue that the fundamental change triggers per se a breach of a stability condition, others may argue that for the breach to be established, the host state’s measures must be arbitrary, unreasonable or discriminatory. Moreover, the threat to legal certainty might not only be the vague provisions of the ECT but also the significant discretion tribunals have towards the interpretation of facts, leading to different outcomes. Indeed, it is at the discretion of arbitrators to consider whether the timing of investment, presence of evidence indicating possible regulatory changes, and the reasonable rate of return prescribed in Spain’s domestic law will be relevant or irrelevant.
Hyperglycemia has detrimental effect on ischemic myocardium, but the impact of acute hyperglycemia on the myocardium in asymptomatic diabetic patients has not been fully elucidated. Thus, this ...follow-up study was aimed to investigate the effects and reversibility of acute hyperglycemia on regional contractile function of left ventricle (LV) in diabetic patients without cardiovascular disease.
The two-dimensional speckle tracking echocardiography (2D-STE), including multilayer strain analysis, was used for evaluation of global and regional LV function in asymptomatic, normotensive patients with uncomplicated diabetes, with acute hyperglycemia ( ≥ 11.1 mmol/l) (Group A, n = 67), or with optimal metabolic control (fasting plasma glucose < 7 mmol/l and HbA1c < 7%) (Group B, n = 20), while 20 healthy individuals served as controls (Group C). In group A, after 72 h of i.v. continuous insulin treatment (at the time euglycemia was achieved) (second examination) and after 3 months following acute hyperglycemia (third examination) 2D-STE was repeated.
Global longitudinal strain (GLS) (- 19.6 ± 0.4%) in Group A was significantly lower in comparison to both groups B (- 21.3 ± 0.4%; p < 0.05) and C (- 21.9 ± 0.4%; p < 0.01) at baseline, while we could not detect the differences between groups B and C. Peak systolic longitudinal endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) layer strain were significantly lower in group A at baseline compared to both groups B and C. Deterioration in peak systolic circumferential strain was observed at basal LV level, in all three layers (Endo, Mid and Epi) and in mid-cavity LV level in Epi layer in group A in comparison to group C. Moreover, in group A, after euglycemia was achieved (at second and third examination) GLS, as well as peak longitudinal and circumferential strain remain the same.
Acute hyperglycemia in asymptomatic diabetic patients has significant negative effects on systolic LV myocardial mechanics primarily by reducing GLS and multilayer peak systolic longitudinal and circumferential strain which was not reversible after three months of good glycemic control.
This study was aimed at investigating daily fluctuation of PAI-1 levels in relation to insulin resistance (IR) and daily profile of plasma insulin and glucose levels in 26 type 2 diabetic (T2D) ...patients with coronary artery disease (CAD) (group A), 10 T2D patients without CAD (group B), 12 nondiabetics with CAD (group C), and 12 healthy controls (group D). The percentage of PAI-1 decrease was lower in group A versus group B (4.4 ± 2.7 versus 35.0 ± 5.4%; P<0.05) and in C versus D (14.0 ± 5.8 versus 44.7 ± 3.1%; P<0.001). HOMA-IR was higher in group A versus group B (P<0.05) and in C versus D (P<0.01). Simultaneously, AUCs of PAI-1 and insulin were higher in group A versus group B (P<0.05) and in C versus D (P<0.01), while AUC of glucose did not differ between groups. In multiple regression analysis waist-to-hip ratio and AUC of insulin were independent determinants of decrease in PAI-1. The altered diurnal fluctuation of PAI-1, especially in T2D with CAD, might be strongly influenced by a prolonged exposure to hyperinsulinemia in the settings of increased IR and abdominal obesity, facilitating altogether an accelerated atherosclerosis.
Summary
Background
: Previous studies have indicated that high sensitivity C-reactive protein (hs-CRP) is a risk factor for the peripheral arterial disease (PAD) in diabetes. This study aimed to ...evaluate the possible predictive significance of hs-CRP for the development and progression of PAD in patients with type 2 diabetes (T2D).
Methods
: The study included 80 patients previously diagnosed with T2D, aged 45–70 years, divided into
group A
(T2D patients with PAD; n=38) and
group B
(T2D patients without PAD; n=42). After five years, all the patients were re-examined and divided into subgroups depending on
de novo
development of PAD or progression of previously diagnosed PAD. Ankle-Brachial Index (ABI) measurement was used for PAD diagnosis and hs-CRP was determined by nephelometry.
Results
: We found significantly higher hs-CRP levels in group A compared to group B, but only at baseline. Among the patients in group A, those with later progression of PAD (subgroup A1) had the highest levels of hs-CRP at baseline, although not significantly different from those in subgroup A2 (non-progressors). In contrast, hs-CRP level was significantly higher in subgroup B1 (progressors) in comparison to subgroup B2 (non-progressors) at both the first and second exam. Of all the investigated metabolic parameters, hs-CRP was the only independent predictor of PAD progression (OR=0.456, 95% CI=0.267–0.7815, p=0.004). The cut-off point for hs-CRP was 2.5 mg/L (specificity 75% and sensitivity 73.3%) with the relative risk for PAD of 2.93 (95% CI=1.351–6.3629).
Conclusions
: Our study implies that hs-CRP can be used as a reliable predictor for the progression of PAD in patients with T2D.
Despite the use of statins, familial hypercholesterolemia (FH) patients often have increased LDL-cholesterol (Ch) and high risk for atherosclerotic cardiovascular disease (ASCVD). This study aimed to ...analyze the effect of statin therapy on attainment of LDL-Ch treatment targets and appearance of new ASCVD and diabetes in FH patients.
This study is a retrospective analysis of data from medical records of 302 FH patients treated continuously with statins during 3 years. At baseline and once yearly, anthropometric measurements, lipids (total Ch, LDL-Ch, HDL-Ch, triglycerides, apoliporotein A1 and B), fasting plasma glucose, and insulin were determined.
In FH patients, high intensity statin was prescribed only in 17.9% of cases. LDL-Ch levels were significantly lower after 3 years of statin treatment (3.61 ± 1.19 mmol/l) vs. baseline (4.51 ± 1.69 mmol/l; p < 0.01), but only 6.9% of FH patients reached the recommended ≥50% LDL-Ch reduction and 16.2% attained the LDL-Ch <2.6 mmol/l target. Simultaneously, 9.6% of FH patients developed new ASCVD, with lower HDL-Ch after 3 years of statin treatment than in those who remained free of ASCVD. In addition, we observed new onset diabetes in 6.4% of FH patients who were more obese, older and with higher fasting glucose at baseline than FH patients free of diabetes, regardless of the type of statin.
These results imply that only a small proportion of FH patients achieved the recommended LDL-Ch treatment targets, mostly due to the use of low statin dose and infrequent implementation of high-intensity statin treatment, which altogether could not prevent the increase in residual cardiovascular risk.
•A small proportion of familial hypercholesterolemia (FH) patients achieved the recommended LDL-Ch treatment targets.•High intensity statin was prescribed in only 17.9% of FH patients.•9.6% of FH patients developed new atherosclerotic cardiovascular disease (ASCVD) during the 3 years of statin treatment.•New onset diabetes was diagnosed in 6.4% of statin treated FH patients.
Disertacija se bavi leksičko-semantičkom analizom grupe glagola sa osnovnim značenjem ’udariti’ u norveškom i srpskom jeziku, a osnovnim ciljevima istraživanja se mogu smatrati detaljan ...leksičko-semantički opis ove grupe glagola u pomenutim jezicima, utvrđivanje paradigmatskih odnosa u okviru grupe, kao i međujezičko kontrastiranje rezultata analize. Sekundarni cilj rada bi bio utvrđivanje korelacija značenjskih i sintaksičkih elemenata i stepena njihove međuzavisnosti na planu semantičko-sintaksičkog interfejsa analizirane grupe glagola.U teorijskom i metodološkom okviru rad je koncipiran na temeljima kognitivne lingvistike, pre svega na teoriji dinamike sile i pristupima proisteklim iz ovog shvatanja, teoriji prototipa, kao i na analizi semantičkih uloga. Istraživanje je sprovedeno na građi prikupljenoj iz elektronskih korpusa norveškog i srpskog jezika, jednojezičnih rečnika oba jezika, kao i iz rečnika sinonima.Kao prvi korak u analizi nametnulo se bliže određenje samog pojma glagola udaranja i pokušaj razgraničavanja grupe glagola udaranja u odnosu na susedne, odn. srodne grupe glagola. Budući da leksičko-semantičku grupu glagola shvatamo kao kategoriju sa stožerom u prototipnom predstavniku, najpre smo utvrdili osnovne semantičke i sintaksičke osobenosti centralnog glagola grupe u norveškom i srpskom jeziku. Detaljno smo opisali i događaj udaranja i izdvojili elemente koji su mu inherentni (izvor udarca, kretanje izvora udarca, naglost, sila, primalac udaraca i kontakt ostvaren između izvora i primaoca udarca), kao i elemente koji nisu obavezno prisutni pri jezičkom kodiranju radnje udaranja (eksterno sredstvo udarca, kretanje primaoca udarca i posledica udarca). Poređenjem karakteristika svih ekscerpiranih glagola sa utvrđenim osobenostima prototipnog glagola i događaja udaranja, oformljena je leksičko-semantička grupa glagola udaranja u norveškom i srpskom jeziku. Posebna pažnja posvećena je rubnim zonama kategorije jer smatramo da upravo analiza prepletaja elemenata koji jesukarakteristični za događaj udaranja, ali i onih koji to nisu, u semantici jednog istog glagola, može pružiti koristan uvid u konceptualizaciju udaranja kod govornika norveškog i srpskog jezika.
The internal capsule and basal nuclei are supplied by perforating branches of the anterior cerebral artery (ACA), Heubner's artery, middle cerebral artery (MCA), internal carotid artery (ICA) and ...anterior choroidal artery (AChA). Some of the mentioned perforators vascularize both the internal capsule and basal nuclei, while some of them also perfuse the adjacent brain structures. Dorsal part of the anterior limb, knee and posterior limb of the internal capsule are commonly supplied by lateral MCA perforators. The intermediate part of the anterior limb is perfused by medial MCA perforators, while its ventral part is nourished by ACA perforators and Heubner's artery. The intermediate part of the knee is supplied by medial MCA perforators, while its ventral part is mostly vascularized by ICA and proximal AChA perforators. The intermediate part of the posterior limb is perfused by medial MCA perforators anteriorly and the proximal AChA perforators posteriorly. The ventral part is supplied by AChA perforators. The retrolenticular and sublenticular portions of the internal capsule are mainly nourished by distal AChA perforators. The caudate nucleus is supplied by perforators of the ACA, MCA and AChA, as well as by branches of the lateral posterior choroidal artery. Most of the putamen is vascularized by MCA perforators, and smaller parts by ACA and AChA perforators. The lateral segment of the globus pallidus is perfused by MCA perforators and partially by Heubner's artery and ACA, while its medial segment is supplied by ICA and AChA perforators. The ACA perforators, that most often originate from the initial 5.9 mm of the A1 segment, range in number from 1 to 5 (mean, 2.2) and in diameter between 80 pm and 710 pm (average, 295 microm). Heubner's artery, which most often arises close to the anterior communicating artery, can be singular (72.5%), double (23%) or triple (4.5%). It varies in diameter from 190 microm to 1,600 pm (average, 750 microm) and in length between 11 mm and 36 mm (mean, 22.4 mm). The MCA perforators, that most frequently originate from M1 segment (90.7%) and leptomeningeal branches (62.6%), range in number between 2 and 13 (mean, 8.1) and in diameter from 80 microm to 1,300 microm (mean, 520 microm). Many perforators arise as individual vessels, and some of them with common trunks (70.8%). Medial and lateral group of these perforators can be distinguished. The ICA perforators, which more often arise close to the AChA originating site (35.4%) than from the ICA bifurcation point (10.4%), vary in number from 1 to 5 (average, 3) and in diameter between 70 microm and 500 microm (mean, 236 microm). The AChA perforators that originate from its cisternal segment, range in number from 2 to 9 (mean, 4.5) and in diameter from 90 microm to 600 pm (mean, 325 microm).
•Coronary ED is associated with insulin resistance.•Coronary ED is also associated with impairments in insulin secretory response.•Decreases in LDL particle size, not the total LDL-Ch, influences ...coronary ED.•Coronary ED is also influenced by impaired fibrinolysis.
This study was aimed to compare insulin sensitivity and secretion response, lipoprotein and plasminogen activator inhibitor 1 (PAI-1) levels between the subjects with and without coronary artery endothelial dysfunction (ED).
ED was detected by intracoronary injection of acetylcholine (ACh) in 47 nondiabetes subjects without stenotic coronary arteries, selected from 316 consecutive patients with coronary angiography performed for suspected coronary artery disease. The subjects were divided into two groups: presence of ACh-induced coronary spasm (group ED+, N = 30) and absence of ACh-induced coronary spasm (group ED−, N = 17). Insulin sensitivity (Si) was evaluated by frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis and by HOMA-IR, insulin secretion by acute insulin response (AIR) (calculated from the first 8 min of FSIGTT) and by disposition index (DI) (Si × AIR). Lipids and PAI-1 levels were determined enzymatically, and LDL particle size by gradient gel electrophoresis.
Si was significantly lower (4.22 ± 0.62 vs 6.98 ± 1.47 min−1/mU/l × 104; p < 0.05) while HOMA-IR was significantly higher in ED + group vs ED− group (2.8 ± 0.3 vs 1.7 ± 0.2; p < 0.05). Simultaneously, AIR and DI was significantly lower in ED + vs ED− groups (p < 0.05 and p < 0.01, respectively). Investigated groups did not differ in fasting lipid levels but ED+ group had significantly smaller LDL particles (p < 0.01) and higher PAI-1 levels (p < 0.05). Regression analysis shown that DI was a strong independent predictor of appearance of ED, together with PAI-1 and LDL particle size.
Both insulin resistance and impairment in insulin secretion response strongly correlate with coronary ED in subjects without diabetes.
To investigate the influence of low glomerular filtration rate, as well as of systolic and diastolic hypertension, on microalbuminuria in patients with type 1 diabetes mellitus.
Twenty seven patients ...with type 1 diabetes mellitus (18 males, 9 females) were studied. All of the patients were below 50 years of age. In 93% of the cases, the duration of diabetes was less than 15 years. GFR was determined, after intravenous injection in the lying position, by using a 99m-Tc-DTPA, while microalbuminuria was calculated for the 24-hour urine using the nephelometric immunoassay (30-300 mg/24 h). The patients were divided into 3 groups according to the value of GFR. The values ranged from 90 to 125 ml/min/1.73 m2 were considered normal (in 63% of the patients in group 1), those above that range were considered as hyperfiltration (in 22.2% of the patients in group 2), while those below that range were considered as hypofiltration (in 13.8% of the patient in group 3).
Data analyzed with the one-way ANOVA, indicated a significant statistical difference between the 3 groups in the duration of diabetes (p < 0.05), micro-albuminuria (p < 0.01), systolic BP (p < 0.01), diastolic BP (p < 0.05), fructosamine (p = 0.50), urea (p < 0.05), creatinine (p = 0.05), and uric acid (p < 0.05). Microalbuminuria correlated with the age of patients (p <0.05) (Spearman's rho), diabetes mellitus duration (p < 0.01), systolic BP (p < 0.05), diastolic BP (p < 0.05), LDL-cholesterol (p < 0.05). There was no statistically significant correlation between GFR and the other parameters. Hypertension, microalbuminuria, and the duration of diabetes correlated positively with the reduction of GFR, revealing the most frequent reduction of GFR in the patients with more than 15-year duration of diabetes.
Hypertension and low GFR were associated with microalbuminuria in type 1 diabetes, while the duration of diabetes was shown to be the independent risk factor for the development of microalbuminuria.
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