Rivals for the crown: Reply to Opthof and Leydesdorff

We reply to the criticism of Opthof and Leydesdorff [arXiv:1002.2769] on the way in which our institute applies journal and field normalizations to citation counts. We point out why we believe most of the criticism is unjustified, but we also indicate where we think Opthof and Leydesdorff raise a valid point

Towards a new crown indicator: Some theoretical considerations

The crown indicator is a well-known bibliometric indicator of research performance developed by our institute. The indicator aims to normalize citation counts for differences among fields. We critically examine the theoretical basis of the normalization mechanism applied in the crown indicator. We also make a comparison with an alternative normalization mechanism. The alternative mechanism turns out to have more satisfactory properties than the mechanism applied in the crown indicator. In particular, the alternative mechanism has a so-called consistency property. The mechanism applied in the crown indicator lacks this important property. As a consequence of our findings, we are currently moving towards a new crown indicator, which relies on the alternative normalization mechanism

The Leiden Ranking 2011/2012: Data collection, indicators, and interpretation

The Leiden Ranking 2011/2012 is a ranking of universities based on bibliometric indicators of publication output, citation impact, and scientific collaboration. The ranking includes 500 major universities from 41 different countries. This paper provides an extensive discussion of the Leiden Ranking 2011/2012. The ranking is compared with other global university rankings, in particular the Academic Ranking of World Universities (commonly known as the Shanghai Ranking) and the Times Higher Education World University Rankings. Also, a detailed description is offered of the data collection methodology of the Leiden Ranking 2011/2012 and of the indicators used in the ranking. Various innovations in the Leiden Ranking 2011/2012 are presented. These innovations include (1) an indicator based on counting a university's highly cited publications, (2) indicators based on fractional rather than full counting of collaborative publications, (3) the possibility of excluding non-English language publications, and (4) the use of stability intervals. Finally, some comments are made on the interpretation of the ranking, and a number of limitations of the ranking are pointed out

Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF)

Aims: Inhibition of sodium–glucose co-transporter 2 (SGLT2) reduces the risk of death and heart failure (HF) admissions in patients with chronic HF. However, safety and clinical efficacy of SGLT2 inhibitors in patients with acute decompensated HF are unknown. Methods and results: In this randomized, placebo-controlled, double-blind, parallel group, multicentre pilot study, we randomized 80 acute HF patients with and without diabetes to either empagliflozin 10 mg/day or placebo for 30 days. The primary outcomes were change in visual analogue scale (VAS) dyspnoea score, diuretic response (weight change per 40 mg furosemide), change in N-terminal pro brain natriuretic peptide (NT-proBNP), and length of stay. Secondary outcomes included safety and clinical endpoints. Mean age was 76 years, 33% were female, 47% had de novo HF and median NT-proBNP was 5236 pg/mL. No difference was observed in VAS dyspnoea score, diuretic response, length of stay, or change in NT-proBNP between empagliflozin and placebo. Empagliflozin reduced a combined endpoint of in-hospital worsening HF, rehospitalization for HF or death at 60 days compared with placebo [4 (10%) vs. 13 (33%); P = 0.014]. Urinary output up until day 4 was significantly greater with empagliflozin vs. placebo [difference 3449 (95% confidence interval 578–6321) mL; P < 0.01]. Empagliflozin was safe, well tolerated, and had no adverse effects on blood pressure or renal function. Conclusions: In patients with acute HF, treatment with empagliflozin had no effect on change in VAS dyspnoea, diuretic response, NT-proBNP, and length of hospital stay, but was safe, increased urinary output and reduced a combined endpoint of worsening HF, rehospitalization for HF or death at 60 days

On the correlation between bibliometric indicators and peer review: reply to Opthof and Leydesdorff

Opthof and Leydesdorff (Scientometrics, 2011) reanalyze data reported by Van Raan (Scientometrics 67(3):491–502, 2006) and conclude that there is no significant correlation between on the one hand average citation scores measured using the CPP/FCSm indicator and on the other hand the quality judgment of peers. We point out that Opthof and Leydesdorff draw their conclusions based on a very limited amount of data. We also criticize the statistical methodology used by Opthof and Leydesdorff. Using a larger amount of data and a more appropriate statistical methodology, we do find a significant correlation between the CPP/FCSm indicator and peer judgment

Towards a new crown indicator: an empirical analysis

We present an empirical comparison between two normalization mechanisms for citation-based indicators of research performance. These mechanisms aim to normalize citation counts for the field and the year in which a publication was published. One mechanism is applied in the current so-called crown indicator of our institute. The other mechanism is applied in the new crown indicator that our institute is currently exploring. We find that at high aggregation levels, such as at the level of large research institutions or at the level of countries, the differences between the two mechanisms are very small. At lower aggregation levels, such as at the level of research groups or at the level of journals, the differences between the two mechanisms are somewhat larger. We pay special attention to the way in which recent publications are handled. These publications typically have very low citation counts and should therefore be handled with special care

PRMT3 inhibitor SGC707 reduces triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice

Protein arginine methyltransferase 3 (PRMT3) is a co-activator of liver X receptor capable of selectively modulating hepatic triglyceride synthesis. Here we investigated whether pharmacological PRMT3 inhibition can diminish the hepatic steatosis extent and lower plasma lipid levels and atherosclerosis susceptibility. Hereto, male hyperlipidemic low-density lipoprotein receptor knockout mice were fed an atherogenic Western-type diet and injected 3 times per week intraperitoneally with PRMT3 inhibitor SGC707 or solvent control. Three weeks into the study, SGC707-treated mice developed severe pruritus and scratching-associated skin lesions, leading to early study termination. SGC707-treated mice exhibited 50% lower liver triglyceride stores as well as 32% lower plasma triglyceride levels. Atherosclerotic lesions were virtually absent in all experimental mice. Plasma metabolite analysis revealed that levels of taurine-conjugated bile acids were ~ threefold increased (P < 0.001) in response to SGC707 treatment, which was paralleled by systemically higher bile acid receptor TGR5 signalling. In conclusion, we have shown that SGC707 treatment reduces hepatic steatosis and plasma triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice. These findings suggest that pharmacological PRMT3 inhibition can serve as therapeutic approach to treat non-alcoholic fatty liver disease and dyslipidemia/atherosclerosis, when unwanted effects on cholesterol and bile acid metabolism can be effectively tackled

PRMT3 inhibitor SGC707 reduces triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice

Protein arginine methyltransferase 3 (PRMT3) is a co-activator of liver X receptor capable of selectively modulating hepatic triglyceride synthesis. Here we investigated whether pharmacological PRMT3 inhibition can diminish the hepatic steatosis extent and lower plasma lipid levels and atherosclerosis susceptibility. Hereto, male hyperlipidemic low-density lipoprotein receptor knockout mice were fed an atherogenic Western-type diet and injected 3 times per week intraperitoneally with PRMT3 inhibitor SGC707 or solvent control. Three weeks into the study, SGC707-treated mice developed severe pruritus and scratching-associated skin lesions, leading to early study termination. SGC707-treated mice exhibited 50% lower liver triglyceride stores as well as 32% lower plasma triglyceride levels. Atherosclerotic lesions were virtually absent in all experimental mice. Plasma metabolite analysis revealed that levels of taurine-conjugated bile acids were ~ threefold increased (P < 0.001) in response to SGC707 treatment, which was paralleled by systemically higher bile acid receptor TGR5 signalling. In conclusion, we have shown that SGC707 treatment reduces hepatic steatosis and plasma triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice. These findings suggest that pharmacological PRMT3 inhibition can serve as therapeutic approach to treat non-alcoholic fatty liver disease and dyslipidemia/atherosclerosis, when unwanted effects on cholesterol and bile acid metabolism can be effectively tackled.Analytical BioScience

Cortisol and alpha-Amylase Secretion Patterns between and within Depressed and Non-Depressed Individuals

ObjectivesAssociations between biological stress markers and depression are inconsistent across studies. We assessed whether inter- and intra-individual variability explain these inconsistencies.MethodsPair-matched depressed and non-depressed participants (N = 30) collected saliva thrice a day for 30 days, resulting in 90 measurements per individual. The relationships between measures of stress-system function and depression were examined at the group level by means of mixed model analyses, and at the individual level by means of pair-matched comparisons. The analyses were repeated after adjusting for time-varying lifestyle factors by means of time-series regression analyses.ResultsCortisol and α-amylase levels were higher, the α-amylase/cortisol ratio larger, and the daily cortisol slope steeper in the depressed compared to the non-depressed group. Adjusting for lifestyle factors and antidepressant use reduced the associations under study. In 40%-60% of the matched comparisons, depressed individuals had higher cortisol and α-amylase levels, a larger α-amylase/cortisol ratio, and a steeper daily slope than their non-depressed match, regardless of adjustment.ConclusionsOur group-level findings were mostly in line with the literature but generalization to individuals appeared troublesome. Findings of studies on this topic should be interpreted with care, because in clinical practice the focus is on individuals instead of groups