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We defend, from a contractarian perspective, that the fair price of an insurance policy is the amount that the contracting parties agree when they are both equally uncertain about the insured event. Drawing on the approach developed by R. Sugden in The Community of Advantage, we answer two standard objections raised against contractarianism in the actuarial sciences: (1) people are not wise enough to assess their actuarial risks; (2) they are not rational enough to decide which insurance policy suits them better. We show under which circumstances people can make fair actuarial agreements, without presupposing any objective risk or rationality benchmarks.

In the last few years, the need of preventing classification biases due to race, gender, social status, etc. has increased the interest in designing fair clustering algorithms. The main idea is to ensure that the output of a cluster algorithm is not biased towards or against specific subgroups of the population. There is a growing specialized literature on this topic, dealing with the problem of clustering numerical data bases. Nevertheless, to our knowledge, there are no previous papers devoted to the problem of fair clustering of pure categorical attributes. In this paper, we show that the Multicluster methodology proposed by Santos and Heras (Interdiscip J Inf Knowl Manag 15:227–246, 2020. https://doi.org/10.28945/4643) for clustering categorical data, can be modified in order to increase the fairness of the clusters. Of course, there is a trade-off between fairness and efficiency, so that an increase in the fairness objective usually leads to a loss of classification efficiency. Yet it is possible to reach a reasonable compromise between these goals, since the methodology proposed by Santos and Heras (2020) can be easily adapted in order to get homogeneous and fair clusters.

Aim/Purpose: This article proposes a methodology for selecting the initial sets for clustering categorical data. The main idea is to combine all the different values of every single criterion or attribute, to form the first proposal of the so-called multiclusters, obtaining in this way the maximum number of clusters for the whole dataset. The multiclusters thus obtained, are themselves clustered in a second step, according to the desired final number of clusters. Background: Popular cluster methods for categorical data, such as the well-known K-Modes, usually select the initial sets by means of some random process. This fact introduces some randomness in the final results of the algorithms. We explore a different application of the clustering methodology for categorical data that overcomes the instability problems and ultimately provides a greater clustering efficiency. Methodology: For assessing the performance of the proposed algorithm and its comparison with K-Modes, we apply both of them to categorical databases where the response variable is known but not used in the analysis. In our examples, that response variable can be identified to the real clusters or classes to which the observations belong. With every data set, we perform a two-step analysis. In the first step we perform the clustering analysis on data where the response variable (the real clusters) has been omitted, and in the second step we use that omitted information to check the efficiency of the clustering algorithm (by comparing the real clusters to those given by the algorithm). Contribution: Simplicity, efficiency and stability are the main advantages of the multicluster method. Findings: The experimental results attained with real databases show that the multicluster algorithm has greater precision and a better grouping effect than the classical K-modes algorithm. Recommendations for Practitioners: The method can be useful for those researchers working with small and medium size datasets, allowing them to detect the underlying structure of the data in an intuitive and reasonable way. Recommendation for Researchers: The proposed algorithm is slower than K-Modes, since it devotes a lot of time to the calculation of the initial combinations of attributes. The reduction of the computing time is therefore an important research topic. Future Research: We are concerned with the scalability of the algorithm to large and complex data sets, as well as the application to mixed data sets with both quantitative and qualitative attributes.

Behavioral interventions have shown promising neuroprotective effects, but the cascade of molecular, brain and behavioral changes involved in these benefits remains poorly understood. Projecte Moviment is a 12-week (5 days per week – 45 min per day) multi-domain, single-blind, proof-of-concept randomized controlled trial examining the cognitive effect and underlying mechanisms of an aerobic exercise (AE), computerized cognitive training (CCT) and a combined (COMB) groups compared to a waitlist control group. Adherence was >80% for 82/109 participants recruited (62% female; age = 58.38 ± 5.47). In this study we report intervention-related changes in plasma biomarkers (BDNF, TNF-α, HGF, ICAM-1, SDF1-α) and structural-MRI (brain volume) and how they related to changes in physical activity and individual variables (age and sex) and their potential role as mediators in the cognitive changes. Our results show that although there were no significant changes in molecular biomarker concentrations in any intervention group, changes in ICAM-1 and SDF1-α were negatively associated with changes in physical activity outcomes in AE and COMB groups. Brain volume changes were found in the CCT showing a significant increase in precuneus volume. Sex moderated the brain volume change in the AE and COMB groups. Changes in molecular biomarkers and brain volumes did not significantly mediate the cognitive-related benefits found previously for any group. This study shows crucial initial molecular and brain volume changes related to lifestyle interventions at early stages and highlights the value of examining activity parameters, individual difference characteristics and using a multi-level analysis approach to address these questions.

IntroductionPeripheral arterial disease (PAD) is a marker of cardiovascular morbidity, causing disability, loss of mobility and poor quality of life, manifesting clinically in the form of intermittent claudication (IC). Physical exercise increases the distance walked and improves quality of life. The aim of our study will be increased walking distance prolonging the time of onset of pain in patients with symptomatic PAD (IC).Methods and analysisThis study will be performed in Mataró Hospital’s vascular surgery service and School of Health Sciences, TecnoCampus. This population comes from 15 primary healthcare centres ofNorth Barcelona, Spain (450 000 inhabitants).This study will be a four-group parallel, longitudinal, randomised controlled trial, blind to analysis.The main primary outcome of this study will be the improvement in pain-free walking distance. Others primary objectives are and improvement in functional status, quality of life and Ankle-Brachial Index (ABI). Secondary outcomes will be the analysis of cardiorespiratory fitness, evaluation of muscle fitness, determine the maintenance of primary objectives at 6 and 12 months.We will be included 124 patients (31 per group). The changes of the outcome (Barthel, SF-12, VascQOL-6, ABI) of the three intervention groups vs the control group at 3, 6 and 12 months will be compared, both continuously (linear regression) and categorically (logistic regression). A person who has not performed at least 75% of the training will be considered to have not completed the intervention.Ethics and disseminationThe study will be conducted according to the Declaration of Helsinki . It was approved by the Ethics Committee of the Research Institute Primary Health IDIAP Jordi Gol (20/035 P),Barcelona 6 October 2020. Informed consent will be obtained from all patients before the start of the study. We will disseminate results through academic papers and conference presentations.Trial registration numberNCT04578990.

Objective Cognitive impairment in multiple system atrophy (MSA) is common, but remain poorly characterized. We evaluated cognitive and behavioral features in MSA patients and assessed between‐group differences for MSA subtypes and the effect of orthostatic hypotension (OH) on cognition. Methods This retrospective study included 54 patients with clinical diagnosis of possible and probable MSA referred to the Department of Neurology at Medical University of Innsbruck between 2000 and 2018. Neurological work‐up included comprehensive neuropsychological testing including Consortium to Establish a Registry for Alzheimer's Disease (CERAD‐plus) test battery, Frontal Assessment Battery (FAB), digit span test (DST), clock drawing task (CLOX1), and Hospital Anxiety and Depression Scale (HADS‐D). Results The mean MMSE score was 27.6 points. Overall, slight to moderate cognitive impairment was noted in up to 40% of patients, with predominant impairment of executive function and verbal memory. Patients with the cerebellar variant performed significantly worse than patients with the parkinsonian type (P < 0.05) in a screening of executive functions (FAB) and in phonemic verbal fluency. Depression and anxiety scores were elevated in 28% and 22% of MSA patients, respectively. Cognitive profile, depression, and anxiety levels were comparable between patients with and without OH. Interpretation Cognitive deficits are relatively frequent in MSA and primarily affect executive functions and verbal memory. Future comparative studies including Parkinson dementia, Lewy body disease, and MSA cases with and without OH are required to elucidate disease‐specific cognitive profiles in these synucleinopathies and to examine the influence of cardiovascular autonomic dysfunction on cognitive function in MSA.

Background Recent epidemiological evidence has linked hypoxia with the development of Alzheimer disease (AD). A number of in vitro and in vivo studies have reported that hypoxia can induce amyloid-β peptide accumulation through various molecular mechanisms including the up-regulation of the amyloid-β precursor protein, the β-secretase Bace1, or the γγ-secretase complex components, as well as the down-regulation of Aβ-degrading enzymes. Objectives To investigate the effects of acute and chronic sustained hypoxia in Aβ generation in vivo. Methods 2–3 month-old C57/Bl6J wild-type mice were exposed to either normoxia (21% O2) or hypoxia (9% O2) for either 4 to 72 h (acute) or 21–30 days (chronic sustained) in a hermetic chamber. Brain mRNA levels of Aβ-related genes were measured by quantitative real-time PCR, whereas levels of Bace1 protein, full length AβPP, and its C-terminal fragments (C99/C88 ratio) were measured by Western blot. In addition, 8 and 14-month-old APP/PS1 transgenic mice were subjected to 9% O2 for 21 days and levels of Aβ40, Aβ42, full length AβPP, and soluble AβPPα (sAβPPα) were measured by ELISA or WB. Results Hypoxia (either acute or chronic sustained) did not impact the transcription of any of the Aβ-related genes in young wild-type mice. A significant reduction of Bace1 protein level was noted with acute hypoxia for 16 h but did not correlate with an increased level of full length AβPP or a decreased C99/C83 ratio. Chronic sustained hypoxia did not significantly alter the levels of Bace1, full length AβPP or the C99/C83 ratio. Last, chronic sustained hypoxia did not significantly change the levels of Aβ40, Aβ42, full length AβPP, or sAβPPα in either young or aged APP/PS1 mice. Discussion Our results argue against a hypoxia-induced shift of AβPP proteolysis from the non-amyloidogenic to the amyloidogenic pathways. We discuss the possible methodological caveats of previous in vivo studies.

Aim Pre-clinical studies in models of multiple sclerosis and other inflammatory disorders suggest that high-salt diet may induce activation of the immune system and potentiate inflammation. However, high-salt diet constitutes a common non-pharmacological intervention to treat autonomic problems in synucleinopathies such as Parkinson’s disease and multiple system atrophy. Since neuroinflammation plays an important pathogenic role in these neurodegenerative disorders, we asked here whether high-salt diet may aggravate the disease phenotype in a transgenic model of multiple system atrophy. Methods Nine-month-old PLP-hαSyn and matched wildtype mice received normal or high-salt diet for a period of 3 months. Behavioral, histological, and molecular analyses were performed to evaluate the effect of high-salt diet on motor decline, neuroinflammation, neurodegeneration, and α-synuclein accumulation in these mice. Results Brain subregion-specific molecular and histological analyses showed no deleterious effects of high-salt diet on the level of microglial activation. Moreover, neuroinflammation-related cytokines and chemokines, T cell recruitment or astrogliosis were unaffected by high-salt diet exposure. Behavioral testing showed no effect of diet on motor decline. High-salt diet was not related to the deterioration of neurodegeneration or α-synuclein accumulation in PLP-hαSyn mice. Conclusions Here, we demonstrate that high-salt diet does not aggravate neuroinflammation and neurodegeneration in PLP-hαSyn mice. Our findings discard a deleterious pro-neuroinflammatory effect of high-salt diet in multiple system atrophy.

[...]CRT may serve as an early and specific indicator for clinical deterioration. [...]in a cohort of deteriorating obstetric patients in which a rapid response team was activated, an altered CRT was an accurate predictor of ICU admission and enhanced the predictive capacity of commonly used clinical scores used for triage. Maharaj R, Raffaele I, Wendon J. Rapid response systems: a systematic review and meta-analysis.

Background Cilostazol has been associated with spontaneous reports of cardiovascular adverse events and serious bleeding. The objective of this study is to determine the relative risk of cardiovascular adverse events or haemorrhages in patients with peripheral artery disease treated with cilostazol in comparison to pentoxifylline users. Methods Population-based cohort study including all individuals older than 40 who initiated cilostazol or pentoxifylline during 2009–2011 in SIDIAP database. The two treatment groups were matched through propensity score (PS). Results Nine thousand one hundred twenty-nine patients met inclusion criteria and after PS matching, there were 2905 patients in each group. 76% of patients were men, with similar mean ages in both groups (68.8 for cilostazol and 69.4 for pentoxifylline). There were no differences in bleeding, cerebrovascular and cardiovascular events between both groups. Conclusions Patients treated with cilostazol were different from those treated with pentoxifylline at baseline, so they were matched through PS. We did not find differences between treatment groups in the incidence of bleeding or cardiovascular and cerebrovascular events. Cilostazol should be used with precaution in elderly polymedicated patients.