Craig Goch Report No. 10 The effect of density on mortality in juvenile Atlantic salmon (Salmo salar L.)

Le Cren (1973) suggested that the most likely population-regulating process in salmonid populations is density-dependent territorial behaviour. Thus, in trout (Salmo trutta L.) populations aggressive territorial behaviour was manifested in density-dependent mortality and the size of the adult stock was largely dependent on the area of suitable rearing ground for the fry (Le Cren, 1973). Ricker (1954) also concluded that in most fish populations compensatory mortality in the juvenile stages, rather than in the mature stock, was of greatest importance as a regulator of population size. The nature of such regulating mechanisms in juvenile populations is, therefore, of fundamental importance in the understanding of the dynamics of fish populations and the implementation of management policies. This paper considers mortality rates of young Atlantic salmon (Salmo salar L.) in the upper catchment of the R. Wye over a two year period. The work forms part of a broader study of fish populations in the R. Wye

Influence of Co-Existing Atrial Fibrillation on the Efficacy of Atorvastatin Treatment in Patients With Dilated Cardiomyopathy: A Pilot Study

INTRODUCTION: The aim of the study was to assess the influence of co-existing atrial fibrillation (AF) on inflammatory condition factors, left ventricular function, clinical course and the efficacy of statin treatment of congestive heart failure in the course of dilated cardiomyopathy (DCM). MATERIAL AND METHODS: In a prospective, randomized, open-label study, 69 patients with DCM and left ventricular ejection fraction (LVEF) ≤40% were divided into two groups, with and without AF, who were treated according to the recommended standards. 68% of patients from the group with AF and 59% of patients from the group without AF were administered atorvastatin 40 mg daily for 8 weeks and 10 mg for next 4 months. Clinical examination with the assessment of body mass index (BMI) and waist size were followed by routine laboratory tests, measurement of concentration of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and IL-10 in blood plasma, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in blood serum, echocardiographic examination, and the assessment of exercise capacity in 6-minute walk test (6-MWT). After six months, morbidity rate and the number of heart failure hospitalizations were also observed. RESULTS: In the whole population of patients, a significantly higher concentration of NT-proBNP was observed in the AF group (2669 ± 2192 vs 1540 ± 1067, p = 0.02). After statin treatment, in patients with DCM and co-existing AF, higher values of NT-proBNP and IL-6 were observed compared to non-AF patients (1530 ± 1054 vs 1006 ± 1195, p = 0.04 and (14.16 ± 13.40 vs 6.74 ± 5.45, p = 0.02, respectively). CONCLUSION: In patients with DCM and co-existing AF, a weaker effect of atorvastatin concerning the reduction of IL-6 and NT-proBNP concentration was observed than in patients without atrial fibrillation. TRIALS REGISTRATION: (ClinialTrial.gov No.: NCT01015144

Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo-perceptual deficits.

BackgroundPeople with Parkinson's disease (PD) who develop visuo-perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo-perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo-perceptual deficits in PD.ObjectiveWe developed an online platform to test visuo-perceptual function. We hypothesised that (1) visuo-perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias.MethodsWe assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks.ResultsPeople with PD were worse than controls at object recognition, showing no deficits in other visuo-perceptual tests. Specifically, they were worse at identifying skewed images (P < .0001); at detecting hidden objects (P = .0039); at identifying objects in peripheral vision (P < .0001); and at detecting biological motion (P = .0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias.ConclusionsOnline tests can detect visuo-perceptual deficits in people with PD, with object recognition particularly affected. Ultimately, visuo-perceptual tests may be developed to identify at-risk patients for clinical trials to slow PD dementia. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Craig Goch Report No. 10 The effect of density on mortality in juvenile Atlantic salmon (Salmo salar L.)

Le Cren (1973) suggested that the most likely population-regulating process in salmonid populations is density-dependent territorial behaviour. Thus, in trout (Salmo trutta L.) populations aggressive territorial behaviour was manifested in density-dependent mortality and the size of the adult stock was largely dependent on the area of suitable rearing ground for the fry (Le Cren, 1973). Ricker (1954) also concluded that in most fish populations compensatory mortality in the juvenile stages, rather than in the mature stock, was of greatest importance as a regulator of population size. The nature of such regulating mechanisms in juvenile populations is, therefore, of fundamental importance in the understanding of the dynamics of fish populations and the implementation of management policies. This paper considers mortality rates of young Atlantic salmon (Salmo salar L.) in the upper catchment of the R. Wye over a two year period. The work forms part of a broader study of fish populations in the R. Wye

Assessing cognitive dysfunction in Parkinson's disease: an online tool to detect visuo-perceptual deficits

Background: People with Parkinson's disease (PD) who develop visuo‐perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo‐perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo‐perceptual deficits in PD. Objective: We developed an online platform to test visuo‐perceptual function. We hypothesised that (1) visuo‐perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias. Methods: We assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks. Results: People with PD were worse than controls at object recognition, showing no deficits in other visuo‐perceptual tests. Specifically, they were worse at identifying skewed images (P  < .0001); at detecting hidden objects (P  = .0039); at identifying objects in peripheral vision (P  < .0001); and at detecting biological motion (P  = .0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias. Conclusions: Online tests can detect visuo‐perceptual deficits in people with PD, with object recognition particularly affected. Ultimately, visuo‐perceptual tests may be developed to identify at‐risk patients for clinical trials to slow PD dementia. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

S100A1: A Multifaceted Therapeutic Target in Cardiovascular Disease

Cardiovascular disease is the leading cause of death worldwide, showing a dramatically growing prevalence. It is still associated with a poor clinical prognosis, indicating insufficient long-term treatment success of currently available therapeutic strategies. Investigations of the pathomechanisms underlying cardiovascular disorders uncovered the Ca2+ binding protein S100A1 as a critical regulator of both cardiac performance and vascular biology. In cardiomyocytes, S100A1 was found to interact with both the sarcoplasmic reticulum ATPase (SERCA2a) and the ryanodine receptor 2 (RyR2), resulting in substantially improved Ca2+ handling and contractile performance. Additionally, S100A1 has been described to target the cardiac sarcomere and mitochondria, leading to reduced pre-contractile passive tension as well as enhanced oxidative energy generation. In endothelial cells, molecular analyses revealed a stimulatory effect of S100A1 on endothelial NO production by increasing endothelial nitric oxide synthase activity. Emphasizing the pathophysiological relevance of S100A1, myocardial infarction in S100A1 knockout mice resulted in accelerated transition towards heart failure and excessive mortality in comparison with wild-type controls. Mice lacking S100A1 furthermore displayed significantly elevated blood pressure values with abrogated responsiveness to bradykinin. On the other hand, numerous studies in small and large animal heart failure models showed that S100A1 overexpression results in reversed maladaptive myocardial remodeling, long-term rescue of contractile performance, and superior survival in response to myocardial infarction, indicating the potential of S100A1-based therapeutic interventions. In summary, elaborate basic and translational research established S100A1 as a multifaceted therapeutic target in cardiovascular disease, providing a promising novel therapeutic strategy to future cardiologists

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

ZBO-evaluaties: verplicht, verzuimd, en veronachtzaamd?

Contains fulltext : 145510.pdf (publisher's version ) (Open Access)Dit artikel beschrijft onze kennis over prestaties van zelfstandige bestuursorganen (ZBO’s) op basis van jaarverslagen en evaluatierapporten. Er blijkt weinig geëvalueerd te worden, ook al is dat wettelijk verplicht. Rapporten zijn ook niet allemaal openbaar. De inhoud en kwaliteit van evaluatierapporten zijn niet altijd voldoende om duidelijke conclusies te kunnen trekken. Uit rapporten en jaarverslagen komt een wisselend tot licht positief beeld naar voren over ZBO-prestaties, en een negatief beeld over de relatie tussen ZBO’s en moederdepartementen. Evaluatierapporten worden slechts in enkele gevallen betrokken bij de politieke besluitvorming over ZBO’s. Dat roept de vraag op waarom politici zo weinig interesse hebben in ZBO-prestaties en -evaluaties, temeer daar er bij de oprichting van ZBO’s vaak zulke hoge verwachtingen zijn ten aanzien van de prestaties van deze organisaties.11 p