Effect of erythropoietin levels on mortality in old age: the Leiden 85-plus Study

BACKGROUND: The production of erythropoietin is triggered by impaired oxygen delivery to the kidney, either because of anemia or hypoxemia. High erythropoietin levels have been shown to predict the risk of death among patients with chronic heart failure. We investigated the prognostic value of elevated erythropoietin levels on mortality among very elderly people in the general population. METHODS: The Leiden 85-plus Study is a population-based prospective follow-up study involving 599 people aged 85 years in Leiden, the Netherlands, enrolled between September 1997 and September 1999. Erythropoietin levels were determined at age 86. For this analysis, we included 428 participants with a creatinine clearance of at least 30 mL/min. Mortality data, recorded until Feb. 1, 2008, were obtained from the municipal registry. RESULTS: During follow-up, 324 (75.7%) participants died. Compared with participants whose erythropoietin levels were in the lowest tertile (reference group), those whose levels were in the middle tertile had a 25% increased risk of death (hazard ratio [HR] 1.25, 95% confidence interval [CI] 0.95–1.64), and those whose levels were in the highest tertile had a 73% increased risk (HR 1.73, 95% CI 1.32–2.26) (p value for trend < 0.01). The association between erythropoietin levels and mortality remained largely unchanged after we adjusted for sex, creatinine clearance, hemoglobin level, comorbidity, smoking status and C-reactive protein level, and was similar for deaths from cardiovascular and noncardiovascular causes. INTERPRETATION: Among people aged 85 years and older, elevated erythropoietin levels were associated with an increased risk of death, independent of hemoglobin levels

Incorporating Baseline Outcome Data in Individual Participant Data Meta-Analysis of Non-randomized Studies

Background: In non-randomized studies (NRSs) where a continuous outcome variable (e.g., depressive symptoms) is assessed at baseline and follow-up, it is common to observe imbalance of the baseline values between the treatment/exposure group and control group. This may bias the study and consequently a meta-analysis (MA) estimate. These estimates may differ across statistical methods used to deal with this issue. Analysis of individual participant data (IPD) allows standardization of methods across studies. We aimed to identify methods used in published IPD-MAs of NRSs for continuous outcomes, and to compare different methods to account for baseline values of outcome variables in IPD-MA of NRSs using two empirical examples from the Thyroid Studies Collaboration (TSC). Methods: For the first aim we systematically searched in MEDLINE, EMBASE, and Cochrane from inception to February 2021 to identify published IPD-MAs of NRSs that adjusted for baseline outcome measures in the analysis of continuous outcomes. For the second aim, we applied analysis of covariance (ANCOVA), change score, propensity score and the naïve approach (ignores the baseline outcome data) in IPD-MA from NRSs on the association between subclinical hyperthyroidism and depressive symptoms and renal function. We estimated the study and meta-analytic mean difference (MD) and relative standard error (SE). We used both fixed- and random-effects MA. Results: Ten of 18 (56%) of the included studies used the change score method, seven (39%) studies used ANCOVA and one the propensity score (5%). The study estimates were similar across the methods in studies in which groups were balanced at baseline with regard to outcome variables but differed in studies with baseline imbalance. In our empirical examples, ANCOVA and change score showed study results on the same direction, not the propensity score. In our applications, ANCOVA provided more precise estimates, both at study and meta-analytical level, in comparison to other methods. Heterogeneity was higher when change score was used as outcome, moderate for ANCOVA and null with the propensity score. Conclusion: ANCOVA provided the most precise estimates at both study and meta-analytic level and thus seems preferable in the meta-analysis of IPD from non-randomized studies. For the studies that were well-balanced between groups, change score, and ANCOVA performed similarly

The impact of policy and model uncertainties on emissions projections of the Paris Agreement pledges

Tracking progress towards the Paris Agreement climate goal requires understanding the 2030 emission levels implied by countries' National Determined Contributions (NDCs). However, key uncertainties and assumptions impact greenhouse gas (GHG) emission projections implied by the NDCs. This study analyses this impact, both globally and for major emitting countries. We find that the assessed uncertainties markedly affect global GHG emission projections. Full achievement of NDC targets is estimated to result in a range of 46-60 GtCO2eq by 2030 (median estimate: 53 GtCO2eq). The uncertainty in measuring historical emissions, including land-use, as reflected by different datasets is the most important contributing factor. This is followed by two equally important factors globally: socio-economic baseline uncertainty and uncertainty about the emissions implied by current policies in case NDCs are less ambitious than these. Overall, the impact of policy uncertainty (i.e. uncertainty resulting from conditionality of or ranges in NDC targets and uncertainty in emissions resulting from current policies) is about equally important as model/technical uncertainty (i.e. uncertainty in historical emissions and socio-economic baseline variations). This new insight is important for decision makers and researchers because a larger share of the total uncertainty is now attributable to aspects that can be influenced by policy decisions compared to previous analyses of NDC uncertainty

Novel mutations in the voltage-gated sodium channel of pyrethroid-resistant Varroa destructor populations from the Southeastern USA

The parasitic mite Varroa destructor has a significant worldwide impact on bee colony health. In the absence of control measures, parasitized colonies invariably collapse within 3 years. The synthetic pyrethroids tau-fluvalinate and flumethrin have proven very effective at managing this mite within apiaries, but intensive control programs based mainly on one active ingredient have led to many reports of pyrethroid resistance. In Europe, a modification of leucine to valine at position 925 (L925V) of the V. destructor voltage-gated sodium channel was correlated with resistance, the mutation being found at high frequency exclusively in hives with a recent history of pyrethroid treatment. Here, we identify two novel mutations, L925M and L925I, in tau-fluvalinate resistant V. destructor collected at seven sites across Florida and Georgia in the Southeastern region of the USA. Using a multiplexed TaqMan® allelic discrimination assay, these mutations were found to be present in 98% of the mites surviving tau-fluvalinate treatment. The mutations were also found in 45% of the non-treated mites, suggesting a high potential for resistance evolution if selection pressure is applied. The results from a more extensive monitoring programme, using the Taqman® assay described here, would clearly help beekeepers with their decision making as to when to include or exclude pyrethroid control products and thereby facilitate more effective mite management programmes

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

A fresh look at instrumentation - an introduction

The theme of "instrumentation between science, state and industry" does not square well with the venerable discourse which opposes "science" and "technology" in social studies of science. In this discourse, "technology" stands for the contrary of "science"; it represents the practical uses of science in society at large and is understood as separate from the somehow autonomous sphere of "science" (Layton 1971a). This vocabulary, widespread as it may be, is not very useful for our purposes, and, for that matter, for any inquiry into the role of instruments. Technology, in the sense of technical instruments and the knowledge systems that go with them, pervades all societal systems. There are technologies of science, of industry, of state, and so forth, and it would be ill-advised to assume that, in the end, they all flow out of "science." But even if the crude opposition of science and technology has little analytic value, the dual problem remains: how to effectively conceive the dynamic relationship between scientific spheres and other societal spheres, and how to conceive the role that technological matters play in this relationship

Regaining momentum for international climate policy beyond Copenhagen

The 'Copenhagen Accord' fails to deliver the political framework for a fair, ambitious and legally-binding international climate agreement beyond 2012. The current climate policy regime dynamics are insufficient to reflect the realities of topical complexity, actor coalitions, as well as financial, legal and institutional challenges in the light of extreme time constraints to avoid 'dangerous' climate change of more than 2°C. In this paper we analyze these stumbling blocks for international climate policy and discuss alternatives in order to regain momentum for future negotiations