The sources of real agency: Kant on the metaphysics of freedom and life

The role of Kant’s Critique of Judgment in his overall theory of freedom has been largely confined to making room for the possibility of the realization of our ultimate moral goals in the world. While this is a central task Kant endeavoured to address with the third Critique, that work had a more overreaching impact in his general metaphysical picture of nature, which is instrumental in making sense of the core tenets of his theory of freedom. In this dissertation, I argue that Kant’s solution to what I term the real agency problem, namely, how actions that are determined by the laws of nature can be nevertheless said to be freely caused by agents, is riddled with problems unless we incorporate the requirements brought by the power of judgment into it. I argue that, according to Kant, judgment compels us to posit a purposive ground of nature that accounts for the necessity of empirical laws, and in such a way that the causality of organisms can be made possible. By doing so, we gain a warrant to judge human beings as intelligibly grounded. Insofar as humans exhibit rational behaviour, this opens a space to our judging them as having an intelligible character which grounds actions as freely caused. Thus, the new insights provided by the third Critique are instrumental in understanding Kant’s metaphysics of freedom

Can Kant tell us what to do? Intentions, dilemmas, and the long journey towards moral perfection

The “received view” on Kantian ethics holds that perfect duties enjoy absolute priority over imperfect duties. More recently, several Kantian scholars have reassessed this situation, arguing that imperfect duties may remain binding even if they imply breaching a perfect duty. In this article, I argue that both positions rely on a misunderstanding of the bindingness of Kantian duties. Genuine Kantian duties, I claim, remain binding even when they cannot be fulfilled. We must always strive for a total completion of our duties; what it means for us to strive for it, however, will vary depending on our peculiar situation

Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes

Endotips; Glomerulosclerosi segmentària focal; Resposta inflamatòriaEndotipos; Glomeruloesclerosis segmentaria focal; Respuesta inflamatoriaEndotypes; Focal segmental glomerulosclerosis; Inflammatory responseObjectives Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids. Methods This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFNγ), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed. Results A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4/16, 25%) than in CL1 (16/26, 72.7%) and CL3 (22/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14). Conclusions Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids

Left Ventricular Dysfunction and Plasmatic NT-proBNP Are Associated with Adverse Evolution in Respiratory Syncytial Virus Bronchiolitis

Aim: To investigate whether the presence of left ventricular myocardial dysfunction (LVMD) assessed by Tei index (LVTX) impacts the outcomes of healthy infants with Respiratory Syncytial Virus Bronchiolitis (RSVB). To explore whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) increases the accuracy of traditional clinical markers in predicting the outcomes. Methods: A single-centre, prospective, cohort study including healthy infants aged 1–12 months old admitted for RSVB between 1 October 2016 and 1 April 2017. All patients underwent clinical, laboratory and echocardiographic evaluation within 24 h of admission. Paediatric intensive care unit (PICU) admission was defined as severe disease. Results: We enrolled 50 cases of RSVB (median age of 2 (1–6.5) months; 40% female) and 50 age-matched controls. We observed higher values of LVTX in infants with RSVB than in controls (0.42 vs. 0.36; p = 0.008). Up to nine (18%) children presented with LVMD (LVTX > 0.5), with a higher incidence of PICU admission (89% vs. 5%; p < 0.001). The diagnostic performance of NT-proBNP in predicting LVMD was high (area under the receiver operator characteristic curve (AUC) 0.95, CI 95% 0.90–1). The diagnostic yield of the predictive model for PICU admission that included NT-proBNP was excellent (AUC 0.945, CI 95% 0.880–1), and significantly higher than the model without NT-proBNP (p = 0.026). Conclusions: LVMD could be present in healthy infants with RSVB who develop severe disease. NT-proBNP seems to improve traditional clinical markers for outcomes

Low-fat dairy consumption and reduced risk of hypertension: the Seguimiento Universidad de Navarra (SUN) cohort

BACKGROUND: Some observational studies have shown a beneficial effect of dairy consumption on blood pressure, especially in overweight and relatively young (<40 y) persons. However, no results from prospective studies conducted in a free-living population exist that show this association in middle-aged adults. OBJECTIVE: The aim of the present study was to assess whether total, low-fat, and whole-fat dairy consumption was associated prospectively with the risk of hypertension. DESIGN: This was a prospective study conducted in 5880 university graduates in Spain, aged >20 y in 2000 (mean age: 37 y), free of hypertension and cardiovascular disease at baseline, and followed-up with mailed questionnaires for a median of 27 mo. Dairy consumption was assessed with a previously validated semiquantitative food-frequency questionnaire. RESULTS: One hundred eighty new cases of hypertension were identified. The hazard ratio of hypertension between extreme quintiles of low-fat dairy product consumption was 0.46 (95% CI: 0.26, 0.84; P for trend = 0.02) after adjustment for the main known risk factors for hypertension and several dietary factors. No significant association between whole-fat dairy products or total calcium intake and incident hypertension was seen. CONCLUSION: In this Mediterranean cohort, low-fat dairy consumption, but not whole-fat dairy consumption, was associated with a lower risk of incident hypertension

Interfacial Self-Assembly to Spatially Organize Graphene Oxide Into Hierarchical and Bioactive Structures

Multicomponent self-assembly holds great promise for the generation of complex and functional biomaterials with hierarchical microstructure. Here, we describe the use of supramolecular co-assembly between an elastin-like recombinamer (ELR5) and a peptide amphiphile (PA) to organise graphene oxide (GO) flakes into bioactive structures across multiple scales. The process takes advantage of a reaction – diffusion mechanism to enable the incorporation and spatial organization of GO within multiple ELR5/PA layers. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and ImageJ software were used to demonstrate the hierarchical organisation of GO flakes within the ELR5/PA layers and the distribution profiles of GO throughout the ELR5/PA membranes. Furthermore,atomic force microscopy (AFM) revealed improved Young’s moduli of the ELR5/PA/GOmembranes compared to the ELR5/PA membranes. Lastly, we investigated biocompatibility of the ELR5/PA/GO membrane via various cell culture methods

Stochastic unit commitment in microgrids based on model predictive control

This article deals with the problem of Stochastic Unit Commitment (SUC), considering the stochastic nature of demand and meteorological phenomena. This paper shows the optimal operation of a hybrid microgrid composed of the following generation units: wind turbine (WT), photovoltaic solar panel (PV), diesel engine generator (DE), micro-turbine (MT), as well as storage devices such as Battery Energy Storage (BES), considering its constraints and the requirements of the reserve generation. For this purpose, a Model-based Predictive Control (MPC), which uses dynamic models of prediction of renewable power and demand in real time, is developed, allowing feedback at each step of time, which corrects the uncertainty of the models. A comparison with a classic UC formulation has been made. The results reach a lower cost solution

Validation of self reported diagnosis of hypertension in a cohort of university graduates in Spain

Background: The search for risk factors of hypertension requires the study of large populations. Sometimes, the only feasible way of studying these populations is to rely on self-reported data of the outcome. The objective of this study was to evaluate validity of self-reported diagnosis of hypertension in a cohort of university graduates in Spain. Methods: The Seguimiento Universidad de Navarra (SUN) Study is a cohort of more than 15,000 university graduates in Spain. We selected a random sample of 79 cohort participants who reported a diagnosis of hypertension and 48 participants who did not report such diagnosis (76% participation proportion). Then, we compared information on the self-reported diagnosis of hypertension and hypertension status as assessed through two personal blood pressure measurements and an interview. Additionally, we compared self-reported and measured blood pressure levels with intraclass correlation coefficients and the survival-agreement plot. Results: From those 79 reporting a diagnosis of hypertension, 65 (82.3%, 95% CI 2.8–92.8) were confirmed through conventional measurement of blood pressure and the interview. From those 48 that did not report a diagnosis of hypertension, 41 (85.4%, 95% CI 72.4–89.1) were confirmed as non hypertensives. Results were similar among men and women, but were worse for overweight and obese individuals, and for those with a family history of hypertension. The greement between self-reported and measured blood pressure levels (as a continuous variable), as estimated by the intraclass correlation coefficient, was 0.35 for both systolic and diastolic blood pressure. Conclusion: Self-reported hypertension among highly educated participants in a cohort study is a relatively valid tool to assess the hypertensive status of participants. However, the investigators should be cautious when using self-reported blood pressure values