Damage to the prefrontal cortex increases utilitarian moral judgements

The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies1–11. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions12–14, produce an abnor- mally ‘utilitarian’ pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person’s life to save a number of other lives)7,8. In contrast, the VMPC patients’ judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements

Influence of topography on tide propagation and amplification in semi-enclosed basins

An idealized model for tide propagation and amplification in semi-enclosed rectangular basins is presented, accounting for depth differences by a combination of longitudinal and lateral topographic steps. The basin geometry is formed by several adjacent compartments of identical width, each having either a uniform depth or two depths separated by a transverse topographic step. The problem is forced by an incoming Kelvin wave at the open end, while allowing waves to radiate outward. The solution in each compartment is written as the superposition of (semi)-analytical wave solutions in an infinite channel, individually satisfying the depth-averaged linear shallow water equations on the f plane, including bottom friction. A collocation technique is employed to satisfy continuity of elevation and flux across the longitudinal topographic steps between the compartments. The model results show that the tidal wave in shallow parts displays slower propagation, enhanced dissipation and amplified amplitudes. This reveals a resonance mechanism, occurring when\ud the length of the shallow end is roughly an odd multiple of the quarter Kelvin wavelength. Alternatively, for sufficiently wide basins, also Poincaré waves may become resonant. A transverse step implies different wavelengths of the incoming and reflected Kelvin wave, leading to increased amplitudes in shallow regions and a shift of amphidromic points in the direction of the deeper part. Including the shallow parts near the basin’s closed end (thus capturing the Kelvin resonance mechanism) is essential to reproduce semi-diurnal and diurnal\ud tide observations in the Gulf of California, the Adriatic Sea and the Persian Gulf

Multiple uncontrolled conditions and blood pressure medication intensification: an observational study

Abstract Background Multiple uncontrolled medical conditions may act as competing demands for clinical decision making. We hypothesized that multiple uncontrolled cardiovascular risk factors would decrease blood pressure (BP) medication intensification among uncontrolled hypertensive patients. Methods We observed 946 encounters at two VA primary care clinics from May through August 2006. After each encounter, clinicians recorded BP medication intensification (BP medication was added or titrated). Demographic, clinical, and laboratory information were collected from the medical record. We examined BP medication intensification by presence and control of diabetes and/or hyperlipidemia. 'Uncontrolled' was defined as hemoglobin A1c ≥ for diabetes, BP ≥ 140/90 mmHg (≥ 130/80 mmHg if diabetes present) for hypertension, and low density lipoprotein cholesterol (LDL-c) ≥ 130 mg/dl (≥ 100 mg/dl if diabetes present) for hyperlipidemia. Hierarchical regression models accounted for patient clustering and adjusted medication intensification for age, systolic BP, and number of medications. Results Among 387 patients with uncontrolled hypertension, 51.4% had diabetes (25.3% were uncontrolled) and 73.4% had hyperlipidemia (22.7% were uncontrolled). The BP medication intensification rate was 34.9% overall, but higher in individuals with uncontrolled diabetes and uncontrolled hyperlipidemia: 52.8% overall and 70.6% if systolic BP ≥ 10 mmHg above goal. Intensification rates were lowest if diabetes or hyperlipidemia were controlled, lower than if diabetes or hyperlipidemia were not present. Multivariable adjustment yielded similar results. Conclusions The presence of uncontrolled diabetes and hyperlipidemia was associated with more guideline-concordant hypertension care, particularly if BP was far from goal. Efforts to understand and improve BP medication intensification in patients with controlled diabetes and/or hyperlipidemia are warranted.http://deepblue.lib.umich.edu/bitstream/2027.42/78266/1/1748-5908-5-55.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78266/2/1748-5908-5-55.pdfPeer Reviewe

Determinants of medication adherence to antihypertensive medications among a Chinese population using Morisky medication adherence scale

<b>Background and objectives</b> Poor adherence to medications is one of the major public health challenges. Only one-third of the population reported successful control of blood pressure, mostly caused by poor drug adherence. However, there are relatively few reports studying the adherence levels and their associated factors among Chinese patients. This study aimed to study the adherence profiles and the factors associated with antihypertensive drug adherence among Chinese patients.<p></p> <b>Methods</b> A cross-sectional study was conducted in an outpatient clinic located in the New Territories Region of Hong Kong. Adult patients who were currently taking at least one antihypertensive drug were invited to complete a self-administered questionnaire, consisting of basic socio-demographic profile, self-perceived health status, and self-reported medication adherence. The outcome measure was the Morisky Medication Adherence Scale (MMAS-8). Good adherence was defined as MMAS scores greater than 6 points (out of a total score of 8 points).<p></p> <b>Results</b> From 1114 patients, 725 (65.1%) had good adherence to antihypertensive agents. Binary logistic regression analysis was conducted. Younger age, shorter duration of antihypertensive agents used, job status being employed, and poor or very poor self-perceived health status were negatively associated with drug adherence.<p></p> <b>Conclusion</b> This study reported a high proportion of poor medication adherence among hypertensive subjects. Patients with factors associated with poor adherence should be more closely monitored to optimize their drug taking behavior

The contribution of a 9p21.3 variant, a KIF6 variant, and C-reactive protein to predicting risk of myocardial infarction in a prospective study

<p>Abstract</p> <p>Background</p> <p>Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD) in prospective and case-control studies. A variant of <it>KIF6 </it>(719Arg) has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or <it>KIF6 </it>variants) or a well-established non-genetic risk factor (C-reactive protein [CRP]) can improve risk prediction by the Framingham Risk Score (FRS) in the Cardiovascular Health Study (CHS)--a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older.</p> <p>Methods</p> <p>Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC) and by net reclassification improvement (NRI).</p> <p>Results</p> <p>Among white participants the FRS was improved by addition of <it>KIF6 </it>719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03) but not by NRI (NRI = 0.027, P = 0.32). Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02) and NRI (0.093, P = 0.008) in men, but not women (P ≥ 0.24).</p> <p>Conclusions</p> <p>While none of these risk markers individually or in combination improved risk prediction among women, a combination of <it>KIF6 </it>719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.</p

Institutional difference and outward FDI: Evidence from China

This paper investigates the impact of institutional difference on China’s outward foreign direct investment (OFDI) through a gravity model. Our estimations are based on a large panel of 150 countries over the period 2003-2015. The results show that the institutional differences of government effectiveness and control of corruption between China and a host country have a statistically significant negative effect on China’s OFDI. In addition, our empirical evidence suggests that the ‘One Belt One Road’ policy does not have the expected positive effect on China’s OFDI. Consistent results are obtained from a set of robustness tests. Our findings provide a reasonable guideline for countries aiming to attract Chinese OFDI or seeking factors to boost it

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089

Cruel to be kind but not cruel for cash : harm aversion in the dictator game

People regularly take prosocial actions, making individual sacrifices for the greater good. Similarly, people generally avoid causing harm to others. These twin desires to do good and avoid harm often align, but sometimes they can diverge, creating situations of moral conflict. Here, we examined this moral conflict using a modified dictator game. Participants chose how much money to allocate away from a recipient who was designated as an orphan, creating a sense of harm. This money was then reallocated to either the participant or a charity. People were strongly prosocial: they allocated more money away from the orphan for charity than for themselves. Furthermore, people left more money with the orphan when the harm was framed as a means (taking) than as a side effect (splitting). As is predicted by dual-process theories of moral decision making, response times were longer with the take action and were positively correlated with the amount taken from the orphan. We concluded that just as people take positive actions for the greater good, they are similarly more willing to cause harm when it benefits others rather than themselves

Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene

Mutations in PROP1 are a common genetic cause of multiple pituitary hormone deficiency (MPHD). We used a comparative genomics approach to predict the transcriptional regulatory domains of Prop1 and tested them in cell culture and mice. A BAC transgene containing Prop1 completely rescues the Prop1 mutant phenotype, demonstrating that the regulatory elements necessary for proper PROP1 transcription are contained within the BAC. We generated DNA sequences from the PROP1 genes in lemur, pig, and five different primate species. Comparison of these with available human and mouse PROP1 sequences identified three putative regulatory sequences that are highly conserved. These are located in the PROP1 promoter proximal region, within the first intron of PROP1, and downstream of PROP1. Each of the conserved elements elicited orientation-specific enhancer activity in the context of the Drosophila alcohol dehydrogenase minimal promoter in both heterologous and pituitary-derived cells lines. The intronic element is sufficient to confer dorsal expansion of the pituitary expression domain of a transgene, suggesting that this element is important for the normal spatial expression of endogenous Prop1 during pituitary development. This study illustrates the usefulness of a comparative genomics approach in the identification of regulatory elements that may be the site of mutations responsible for some cases of MPHD