John Rawls between two enlightenments

John Rawls shares the Enlightenment's commitment to finding moral and political principles which can be reflectively endorsed by all individuals autonomously. He usually presents reflective autonomy in Kantian, rationalist terms: autonomy is identified with the exercise of reason, and principles of justice must be constructed which are acceptable to all on the basis of reason alone. Yet David Hume, Adam Smith and many other Enlightenment thinkers rejected such rationalism, searching instead for principles which can be endorsed by all on the basis of all the faculties of the human psyche, emotion and imagination included. The influence of these sentimentalists on Rawls is clearest in his descriptive moral psychology, but I argue that it is also present in Rawls's understanding of the sources of normativity. Although this debt is obscured by Rawls's explicit "Kantianism," his theory would be strengthened by a greater understanding of its debts to the sentimentalist Enlightenment

Measuring attitudes, behaviours, and influences in inner city victims of interpersonal violence (VIVs) - a Swiss emergency room pilot study

Background Switzerland is confronted with the problem of interpersonal violence. Violence is in the increase and the potential for aggression seems to be rising. Observations by hospitals discern an appalling increase of the severity of the injuries. The aim of this study is to collect accurate information about the social environment, the motivation and possible reasons for violence. We also intend to investigate whether sociocultural, or ethnic differences among male victims exist. Materials and methods For the first time in Switzerland, this survey employed a validated questionnaire from the division of violence prevention, Atlanta, Georgia. The first part of the questionnaire addressed social and demographic factors which could influence the risk of violence: age, gender, duration of stay in Switzerland, nationality and educational level. Beside these social structural factors, the questionnaire included questions on experience of violent offences in the past, information about the most recent violent offence and intra and interpersonal facts. The questionnaire itself consists of 27 questions, translated into German and French. In a pilot study, the questionnaire was checked with adolescents for feasibility and comprehensibility. Results 69 male VIVs were interviewed at two hospitals in the Canton of Bern. Most of the adolescents emphasised that weapons were not used during their confrontations. It is astonishing that all of the young men considered themselves to be victims. Most of the brawls were incited after an exchange of verbal abuse and provocations with unfamiliar individuals. The rivals could neither be classified with the help of ethnic categories nor identifiable groups of the youth scenes. The incidents took place in scenes, where violence was more likely to happen. Interestingly and contrary to a general perception the offenders are well integrated into sport and leisure clubs. A further surprising result of our research is that the attitude towards religion differs between young men with experience of violence and non-violent men. Discussion Youth violence is a health issue, which concerns us globally. The human and economic toll of violence on victims and offenders, their families, and on society in general is high. The economic costs associated with violence-related illness and disability is estimated to be millions of Swiss francs each year. Physicians and psychologists are compelled to identify the factors, which cause young people to be violent, to find out which interventions prove to be successful, and to design effective prevention programs. The identification of effective programs depends on the availability of reliable and valid measures to assess changes in violence-related attitudes. In our efforts to create healthier communities, we need to investigate; document and do research on the causes and circumstances of youth violence

Mendelian adult-onset leukodystrophy genes in Alzheimer´s disease. Critical influence of CSF1R and NOTCH3

Mendelian adult-onset leukodystrophies are a spectrum of rare inherited progressive neurodegenerative disorders affecting the white matter of the central nervous system. Among these, Cerebral Autosomal Dominant and Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL and CARASIL), Cerebroretinal vasculopathy (CRV), Metachromatic leukodystrophy (MLD), Hereditary diffuse Leukoencephalopathy with spheroids (HDLS), Vanishing white matter disease (VWM) present with rapidly progressive dementia as dominant feature and are caused by mutations in NOTCH3, HTRA1, TREX1, ARSA, CSF1R, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, respectively. Given the rare incidence of these disorders and the lack of unequivocally diagnostic features, leukodystrophies are frequently misdiagnosed with common sporadic dementing diseases such as Alzheimer’s disease (AD), raising the question of whether these overlapping phenotypes may be explained by shared genetic risk factors. To investigate this intriguing hypothesis, we have combined gene expression analysis 1) in 6 different AD mouse strains (APPPS1, HOTASTPM, HETASTPM, TPM, TAS10 and TAU), at 5 different developmental stages (Embryo [E15], 2 months, 4 months, 8 months and 18 months), 2) in APPPS1 primary cortical neurons under stress conditions (oxygen-glucose deprivation) and single-variant and single-gene (c-alpha and SKAT tests) based genetic screening in a cohort composed of 332 Caucasian late-onset AD patients and 676 Caucasian elderly controls. Csf1r was significantly overexpressed (Log2FC>1, adj. p-val<0.05) in the cortex and hippocampus of aged HOTASTPM mice with extensive Aβ core dense plaque pathology. We identified 3 likely pathogenic mutations in CSF1R TK domain (p.L868R, p.Q691H and p.H703Y) in our discovery and validation cohort, composed of 465 AD and MCI Caucasian patients from the UK. Moreover, NOTCH3 was a significant hit in the c-alpha test (adj p-val = 0.01). Adult onset Mendelian leukodystrophy genes are not common factors implicated in AD. Nevertheless, our study suggests a potential pathogenic link between NOTCH3, CSF1R and sporadic LOAD, that warrants further investigation

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass

Enzyme-Polymer Conjugates to Enhance Enzyme Shelf Life in a Liquid Detergent Formulation

Herein, the synthesis of enzyme–polymer conjugates is reported. Four different activated polymers (mPEG-aldehyde, mPEG-NHS, maltodextrin-aldehyde, carboxymethyl cellulose aldehyde) are conjugated to the surface of protease, α-amylase, and lipase using two different strategies (reductive amination and alkylation with NHS-activated acid). Although the chemical modification of the enzymes is accompanied by losses in enzyme activity (maximum loss 40%), the covalent attachment of polymers increases the thermal stability and the stability in a standard detergent formulation compared to the unmodified enzymes. The enzyme–polymer conjugates are characterized by asymmetrical-flow field-flow fractionation and differential scanning microcalorimetry. Furthermore, it is demonstrated that conjugated enzymes still show performance in a real washing process. Enzyme–polymer conjugates show a potential as a stabilizing system for enzymes in detergents