Contributing to regional development through project selection

The EIB finances a large number of projects in support of EU policies including social and economic cohesion, that is to reduce regional disparities in income. Since 1995, the EIB Evaluation Department has looked at over 100 projects where the Bank has been involved, normally along the lines of a particular theme (e.g. impact of the Banks projects in a specific sector or region). Inevitably, the information gathered is patchy because very few statistical series exist at a sufficient level of disaggregation to be used for ex-post project analysis. As any case-study work, their main value is to tell us whether a problem exists or not, rather than to assess the exact magnitude of the problem. A series of evaluations has been structured around a regional development theme. In the most recent study of 17 projects, 14 of them had some positive impact on regional development and in over half of these cases, the impact was a strong one. Can the Bank improve on this, or at least maintain the same record? Clearly, this requires an understanding of the type of projects that contribute most to regional development. The purpose of this paper is to discuss what has been learned so far on this subject

PRE‐dialysis survey on anaemia management

Background. The PRE‐dialysis survey on anaemia management (PRESAM) was designed to assess the care given to pre‐dialysis patients in the 12 months before haemodialysis or peritoneal dialysis, with emphasis on anaemia management. Methods. For this epidemiological study, a retrospective chart review was conducted for patients who started haemodialysis or peritoneal dialysis between 1 August, 1999 and 6 April, 2000. All adult patients who entered one of the 779 participating centres in 21 European countries, Israel or South Africa were included, except for patients who underwent dialysis only during an acute episode. In addition to demographic characteristics, the study examined the prevalence of anaemia, anaemia management including the use of iron supplementation and epoetin, source of referral to the dialysis centre, comorbidities and major clinical events. Results. A total of 4333 new dialysis patients were included in the survey. At the first visit to the dialysis centre, 68% of the patients had a haemoglobin (Hb) concentration ≤11.0 g/dl; Hb concentration was positively correlated with creatinine clearance rate (r=0.43, P<0.01). Patients who received epoetin had a mean Hb concentration of 8.8 g/dl at the start of epoetin treatment, and 96% of these patients had an Hb concentration ≤11.0 g/dl. Only 26.5% of the patients received epoetin before dialysis. The length of time under the care of a nephrologist was associated with meeting the European Best Practice Guidelines (EBPG) target Hb concentration, as well as receiving epoetin. Conclusions. Few pre‐dialysis patients met the EBPG target for Hb concentration, despite regular nephrology car

Ethical Risk and Energy

Defining ethical violations as acts or situations excluding individuals from choices, and ethical deterioration as an increase in intensity or number of ethical violations, the ethical risk is defined as the risk of ethical deterioration. Ethical deteriorations and improvements often coexist and share the same causes, and the net ethical impact is often difficult and controversial to assess. In the energy sector, the ethical risk appears to have five key determinants: (i) personal accountability, i.e. our responsibility in decisions and actions; (ii) fairness, i.e. the consequence on the choices of others; (iii) usage, i.e. the impact on the social and natural environment; (iv) addiction, i.e. the dependence that is created as energy is used over time and (v) danger, i.e. how the force of energy sources can be unexpectedly unleashed and what effort is made to mitigate these

The physiological variability of channel density in hippocampal CA1 pyramidal cells and interneurons explored using a unified data-driven modeling workflow

Every neuron is part of a network, exerting its function by transforming multiple spatiotemporal synaptic input patterns into a single spiking output. This function is specified by the particular shape and passive electrical properties of the neuronal membrane, and the composition and spatial distribution of ion channels across its processes. For a variety of physiological or pathological reasons, the intrinsic input/output function may change during a neuron’s lifetime. This process results in high variability in the peak specific conductance of ion channels in individual neurons. The mechanisms responsible for this variability are not well understood, although there are clear indications from experiment and modeling that degeneracy and correlation among multiple channels may be involved. Here, we studied this issue in biophysical models of hippocampal CA1 pyramidal neurons and interneurons. Using a unified data-driven simulation workflow and starting from a set of experimental recordings and morphological reconstructions obtained from rats, we built and analyzed several ensembles of morphologically and biophysically accurate single cell models with intrinsic electrophysiological properties consistent with experimental findings. The results suggest that the set of conductances expressed in any given hippocampal neuron may be considered as belonging to two groups: one subset is responsible for the major characteristics of the firing behavior in each population and the other responsible for a robust degeneracy. Analysis of the model neurons suggests several experimentally testable predictions related to the combination and relative proportion of the different conductances that should be expressed on the membrane of different types of neurons for them to fulfill their role in the hippocampus circuitry

Effect of long-term steroid withdrawal in renal transplant recipients: a retrospective cohort study

Background. Steroids are largely effective for the immunosuppressive treatment in renal transplant patients, but cause severe side effects. Whether steroid withdrawal confers long-term beneficial effects remains unclear

A universal workflow for creation, validation, and generalization of detailed neuronal models

\ua9 2023 The Author(s). Detailed single-neuron modeling is widely used to study neuronal functions. While cellular and functional diversity across the mammalian cortex is vast, most of the available computational tools focus on a limited set of specific features characteristic of a single neuron. Here, we present a generalized automated workflow for the creation of robust electrical models and illustrate its performance by building cell models for the rat somatosensory cortex. Each model is based on a 3D morphological reconstruction and a set of ionic mechanisms. We use an evolutionary algorithm to optimize neuronal parameters to match the electrophysiological features extracted from experimental data. Then we validate the optimized models against additional stimuli and assess their generalizability on a population of similar morphologies. Compared to the state-of-the-art canonical models, our models show 5-fold improved generalizability. This versatile approach can be used to build robust models of any neuronal type

Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression

BACKGROUND: The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR. However, the statistical method does not weigh the relative clinical importance of the end point components. A HCE accounts for the clinical importance of the end point components and enables combining dichotomous outcomes with continuous measures. METHODS: We developed and validated a new HCE for kidney disease progression, performing post hoc analyses of seven major Phase 3 placebo-controlled trials that assessed the effects of canagliflozin, dapagliflozin, finerenone, atrasentan, losartan, irbesartan, and aliskiren in patients with CKD. We calculated the win odds (WOs) for treatment effects on a kidney HCE, defined as a hierarchical composite of all-cause mortality; kidney failure; sustained 57%, 50%, and 40% GFR declines from baseline; and GFR slope. The WO describes the odds of a more favorable outcome for receiving the active compared with the control. We compared the WO with the hazard ratio (HR) of the primary kidney outcome of the original trials. RESULTS: In all trials, treatment effects calculated with the WO reflected a similar direction and magnitude of the treatment effect compared with the HR. Clinical trials incorporating the HCE would achieve increased statistical power compared with the established composite end point at equivalent sample sizes. CONCLUSIONS: In seven major kidney clinical trials, the WO and HR provided similar direction of treatment effect estimates with smaller HRs associated with larger WOs. The prioritization of clinical outcomes and inclusion of broader composite end points makes the HCE an attractive alternative to the established kidney end point