International Right and Kant's World Federation

Recent interpretations of Kant’s international political philosophy have argued that the formation of a coercive world-state (Völkerstaat) is morally required. While these interpretations highlight the importance of a strong world government, they ignore Kant’s alternative to a Völkerstaat, a world-federation (Völkerbund). For both theoretical and practical reasons, the Völkerbund plays a crucial role in cosmopolitan right, and Kant can only justifiably reject the formation of the Völkerstaat because of the structure of the Völkerbund. This article explains the constitution and functions of the Völkerbund, and thereby shows why Kant was not ultimately committed to supporting a coercive world-state

A Mooring for Ethical Life

Since G.A. Cohen’s influential criticism, John Rawls’s focus on the basic structure of society has fallen out of favor in moral and political philosophy. The most prominent defenses of this focus has argued from particular conceptions of justice or from a moral division of labor. In this dissertation, I instead argue for the Rawlsian focus from the ways in which social institutions establish new obligations, rights and powers. I argue that full evaluation of individual conduct requires that we evaluate the practices within which an individual’s actions occur. Likewise, full evaluation of practices often requires evaluating the systems within which actions occur. I argue that we should treat the basic structure of society as a moral subject because the full evaluation of the various institutions that constitute the basic structure requires that we evaluate the basic structure as a whole. This argument shows the advantages of the Rawlsian approach even when we do not accept contractualism, constructivism or the two principles of justice. We need only accept the view that the major social institutions establish obligations, rights, and powers for individuals as members of society

A Mooring for Ethical Life: Assessing the Basic Structure of Society

In order to articulate a political philosophy that applies beyond state action, John Rawls took the the basic structure of society as the first subject of justice. In this dissertation, I explain both what the basic structure of society is and why it is an appropriate subject in moral theory. As the set of institutions that specify our valid claims as members of society, the basic structure has a profound influence on the content of ethical life; shaping our values, virtues, relationships, and obligations. In order to adequately assess this influential set of institutions, we should treat the the basic structure as a fundamental moral concern

Clinical predictors of outcome in survivors of out-of-hospital cardiac arrest treated with hypothermia

AbstractBackgroundOut-of-hospital cardiac arrest (OHCA) is a leading cause of death and severe neurological disability. The objective of this study was to identify clinical predictors of early neurological outcome in survivors of OHCA managed according to recent recommendations for OHCA care.MethodsData from survivors of OHCA, admitted to a tertiary cardiac intensive care unit and treated with hypothermia in a 22 months period (n=46, age 60±13 years, 74% males) were retrospectively evaluated. At 1-month follow-up, patients were classified according to the best achieved Glasgow–Pittsburgh cerebral performance categories (CPC 1–5) and factors affecting the outcome were analysed.ResultsAt 1-month follow-up, 23 patients (50%) had favourable outcome (CPC 1–2), while 23 patients (50%) had poor outcome (CPC 3–5), including 19 with in-hospital death (41% of total). Patients with good outcome were younger (55±13 years vs. 66±10 years; P=0.003), had more often myocardial infarction as the cause of arrest (63% vs. 30%; P=0.018) and ventricular fibrillation/tachycardia as an initial rhythm (78% vs. 39%; P=0.007). Both groups differed by lactate level on admission (4.0±4.6 vs. 7.3±4.1mmol/l, P=0.02), after 12h (2.5±1.1 vs. 4.3±3.2mmol/l, P=0.04) and after 24h (1.9±1.2 vs. 3.2±1.9mmol/l, P=0.04). Logistic regression revealed the following independent outcome predictors: age, acute myocardial infarction and admission lactate level.ConclusionFavourable outcome was observed in a half of OHCA survivors. Young age, acute myocardial infarction as underlying aetiology of cardiac arrest, and low lactate level on admission were the best predictors of favourable outcome

Dynamic changes and prognostic value of pulmonary congestion by lung ultrasound in acute and chronic heart failure: a systematic review

Aims: Pulmonary congestion is an important finding in patients with heart failure (HF) that can be quantified by lung ultrasound (LUS). We conducted a systematic review to describe dynamic changes in LUS findings of pulmonary congestion (B-lines) in HF and to examine the prognostic utility of B-lines in HF. Methods and results: We searched online databases for studies conducted in patients with chronic or acute HF that used LUS to assess dynamic changes or the prognostic value of pulmonary congestion. We included studies in adult populations, published in English, and conducted in ≥25 patients. Of 1327 identified studies, 13 (25–290 patients) met the inclusion criteria: six reported on dynamic changes in LUS findings (438 patients) and seven on the prognostic value of B-lines in HF (953 patients). In acute HF, B-line number changed within as few as 3 h of HF treatment. In acute HF, ≥15 B-lines on 28-zone LUS at discharge identified patients at a more than five-fold risk for HF readmission or death. Similarly, in ambulatory patients with chronic HF, ≥3 B-lines on five- or eight-zone LUS marked those at a nearly four-fold risk for 6-month HF hospitalization or death. Conclusions: Lung ultrasound findings change rapidly in response to HF therapy. This technique may represent a useful and non-invasive method to track dynamic changes in pulmonary congestion. Furthermore, residual congestion at the time of discharge in acute HF or in ambulatory patients with chronic HF may identify those at high risk for adverse events

Left atrial rather than left ventricular impaired mechanics are associated with the pro-fibrotic ST2 marker and outcomes in heart failure with preserved ejection fraction.

AIMS: Left ventricular (LV) mechanics have been extensively investigated in heart failure with preserved ejection fraction (HFpEF) overshadowing for a long time the potential role of left atrium (LA) in that setting. Soluble suppression of tumorigenicity-2 receptor (ST2) is a novel biomarker of pro-fibrotic burden in HF. We hypothesized that due to the thinner LA wall, the fibrotic myocardial changes in HFpEF as indicated by elevated ST2 levels might more readily be reflected by impairments in the LA rather than the LV performance. METHODS AND RESULTS: In 86 patients with HFpEF, enrolled in the Karolinska Rennes (KaRen) biomarker prospective substudy, global LA strain (GL-LS) along with other echocardiographic as well as haemodynamic parameters and ST2 levels were measured. ST2 levels were inversely associated with LA-GS (r = -0.30, P = 0.009), but not with LA size, LV geometry, systolic or diastolic LV function (P > 0.05 for all). Furthermore, symptom severity correlated with ST2 and LA-GS, but not with LV structural or functional indices. Finally, during a median 18-month follow-up, LA-GS independently predicted the composite endpoint of HF hospitalization and all-cause mortality, even after adjustment for potential clinical and cardiac mechanical confounders, including LV global longitudinal strain and filling pressures (odds ratio: 4.15; confidence interval: 1.2-14, P = 0.023). CONCLUSIONS: Reduced LA-GS but not LV functional systolic and diastolic parameters were associated with the pro-fibrotic ST2 marker, HF symptoms and outcome in HFpEF

Clinical and humoral determinants of congestion in heart failure. potential role of adiponectin

Background: Some patients with heart failure (HF) are more prone to systemic congestion than others. The goal of this study was to identify clinical and humoral factors linked to congestion and its prognostic impact in HF patients. Methods: A total of 371 advanced HF patients underwent physical examination, echocardiography, right heart catheterization, blood samplings, and Minnesota Living with HF Questionnaire. Subjects were followed-up for adverse events (death, urgent transplantation, or assist device implantation without heart transplantation). Results: Thirty-one percent of patients were classified as prone to congestion. During a median follow-up of 1,093 days, 159 (43%) patients had an adverse event. In the Cox analysis, the congestion-prone (CP) status was associated with a 43% higher event risk. The CP status was strongly (p ? 0.001) associated with body weight loss, right ventricular dysfunction (RVD), dilated inferior vena cava (IVC), diuretics, and beta-blockers prescription and the majority of tested hormones in the univariate analysis. In the multivariate analysis, the only independent variables associated with the CP status were adiponectin, albumin, IVC diameter, and RVD. Adiponectin by itself was predictive of adverse events. In a multivariate model, CP status was no longer predictive of adverse events, in contrast to adiponectin. Conclusions: CP patients experienced more severe symptoms and had shorter survival. Potential role of adiponectin, a new independent predictor of CP status, should be further examined

B-type natriuretic peptide: powerful predictor of endstage chronic heart failure in individuals with systolic dysfunction of the systemic right ventricle

Aim To assess whether B-type natriuretic peptide (BNP) can serve as a predictor of end-stage chronic heart failure (CHF) in patients with severe systolic dysfunction of the systemic right ventricle (SRV). Methods We performed a retrospective analysis in 28 patients with severe systolic dysfunction of the SRV (ejection fraction 23 ± 6%) who were evaluated as heart transplant (HTx) candidates between May 2007 and October 2014. The primary endpoints of the study (end-stage CHF) were progressive CHF, urgent HTx, and ventricular assist device (VAD) implantation. Plasma BNP levels were measured using a chemiluminescent immunoassay. Results During median follow-up of 29 months (interquartile range, 9-50), 3 patients died of progressive CHF, 5 patients required an urgent HTx, and 6 patients underwent VAD implantation. BNP was a strong predictor of end-stage CHF (hazard ratio per 100 ng/L: 1.079, 95% confidence interval, 1.042-1.117, P<0.001). The following variables with corresponding areas under the curve (AUC) were identified as the most significant predictors of end-stage CHF: BNP (AUC 1.00), New York Heart Association functional class class III or IV (AUC 0.98), decompensated CHF in the last year (AUC 0.96), and systolic dysfunction of the subpulmonal ventricle (AUC 0.96). Conclusion BNP is a powerful predictor of end-stage CHF in individuals with systolic dysfunction of the SRV

Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2

<p>Abstract</p> <p>Background</p> <p>Chronic hemodynamic overloading leads to heart failure (HF) due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF) and sham-operated rats harvested at the advanced, decompensated stage of HF.</p> <p>Methods</p> <p>We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip.</p> <p>Results</p> <p>In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs.</p> <p>Conclusions</p> <p>The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy.</p

Pulse wave analysis during supine rest may identify subjects with recurrent vasovagal syncope A B S T R A C T

In the present study, we studied whether analysis of the FAP (finger arterial pressure) waveform during supine rest discriminates subjects with recurrent VVS (vasovagal syncope) from healthy controls. Signal-averaged FAP waveforms (Finapres) were obtained in 32 head-up tilt-test-positive subjects with recurrent VVS (35 + − 13 years) and in 32 sex-and age-matched healthy controls. The DT (time delay) between the systolic and diastolic peaks of the FAP waveform was measured and large artery SI (stiffness index) was calculated as a ratio of body height and DT. VVS patients had significantly shorter DT compared with controls (303 + − 31 compared with 329 + − 18 ms; P &lt; 0.001) and higher SI (5.79 + − 0.70 compared with 5.20 + − 0.36 m/s; P &lt; 0.001). The differences were independent of heart rate and blood pressure. SI &gt; 5.45 m/s identified subjects with syncope with a sensitivity of 72 % and a specificity of 84 %. Age-corrected DT (cDT = DT + age − 350) identified subjects with syncope with a sensitivity of 75 % and a specificity of 84 %. Combined use of cDT &lt; 0 ms and SI &gt; 5.45 m/s increased sensitivity and specificity to 81 % and 96 % respectively. The discriminative power of FAP descriptors improved further when younger subjects were excluded. In subjects aged &gt; 30 years (median age), the combination of cDT and SI identified subjects with syncope with a sensitivity of 93 % and a specificity of 100 %. These results suggest that FAP descriptors during supine rest might be useful in the diagnosis of VVS in middle-aged subjects