Sequential Extensions of Causal and Evidential Decision Theory

Moving beyond the dualistic view in AI where agent and environment are separated incurs new challenges for decision making, as calculation of expected utility is no longer straightforward. The non-dualistic decision theory literature is split between causal decision theory and evidential decision theory. We extend these decision algorithms to the sequential setting where the agent alternates between taking actions and observing their consequences. We find that evidential decision theory has two natural extensions while causal decision theory only has one.Comment: ADT 201

Living with myotonic dystrophy; what can be learned from couples? a qualitative study

Contains fulltext : 96062.pdf (publisher's version ) (Open Access)BACKGROUND: Myotonic dystrophy type 1 (MD1) is one of the most prevalent neuromuscular diseases, yet very little is known about how MD1 affects the lives of couples and how they themselves manage individually and together. To better match health care to their problems, concerns and needs, it is important to understand their perspective of living with this hereditary, systemic disease. METHODS: A qualitative study was carried out with a purposive sample of five middle-aged couples, including three men and two women with MD1 and their partners. Fifteen in-depth interviews with persons with MD1, with their partners and with both of them as a couple took place in the homes of the couples in two cities and three villages in the Netherlands in 2009. Results : People with MD1 associate this progressive, neuromuscular condition with decreasing abilities, describing physical, cognitive and psychosocial barriers to everyday activities and social participation. Partners highlighted the increasing care giving burden, giving directions and using reminders to compensate for the lack of initiative and avoidant behaviour due to MD1. Couples portrayed the dilemmas and frustrations of renegotiating roles and responsibilities; stressing the importance of achieving a balance between individual and shared activities. All participants experienced a lack of understanding from relatives, friends, and society, including health care, leading to withdrawal and isolation. Health care was perceived as fragmentary, with specialists focusing on specific aspects of the disease rather than seeking to understand the implications of the systemic disorder on daily life. CONCLUSIONS: Learning from these couples has resulted in recommendations that challenge the tendency to treat MD1 as a condition with primarily physical impairments. It is vital to listen to couples, to elicit the impact of MD1, as a multisystem disorder that influences every aspect of their life together. Couple management, supporting the self-management skills of both partners is proposed as a way of reducing the mismatch between health services and health needs

A comparison of two methods for estimating odds ratios: Results from the National Health Survey

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Bottom up ethics - neuroenhancement in education and employment

Neuroenhancement involves the use of neurotechnologies to improve cognitive, affective or behavioural functioning, where these are not judged to be clinically impaired. Questions about enhancement have become one of the key topics of neuroethics over the past decade. The current study draws on in-depth public engagement activities in ten European countries giving a bottom-up perspective on the ethics and desirability of enhancement. This informed the design of an online contrastive vignette experiment that was administered to representative samples of 1000 respondents in the ten countries and the United States. The experiment investigated how the gender of the protagonist, his or her level of performance, the efficacy of the enhancer and the mode of enhancement affected support for neuroenhancement in both educational and employment contexts. Of these, higher efficacy and lower performance were found to increase willingness to support enhancement. A series of commonly articulated claims about the individual and societal dimensions of neuroenhancement were derived from the public engagement activities. Underlying these claims, multivariate analysis identified two social values. The Societal/Protective highlights counter normative consequences and opposes the use enhancers. The Individual/Proactionary highlights opportunities and supports use. For most respondents these values are not mutually exclusive. This suggests that for many neuroenhancement is viewed simultaneously as a source of both promise and concern

Algorithmic iteration for computational intelligence

Machine awareness is a disputed research topic, in some circles considered a crucial step in realising Artificial General Intelligence. Understanding what that is, under which conditions such feature could arise and how it can be controlled is still a matter of speculation. A more concrete object of theoretical analysis is algorithmic iteration for computational intelligence, intended as the theoretical and practical ability of algorithms to design other algorithms for actions aimed at solving well-specified tasks. We know this ability is already shown by current AIs, and understanding its limits is an essential step in qualifying claims about machine awareness and Super-AI. We propose a formal translation of algorithmic iteration in a fragment of modal logic, formulate principles of transparency and faithfulness across human and machine intelligence, and consider the relevance to theoretical research on (Super)-AI as well as the practical import of our results

Modulation of calcification of vascular smooth muscle cells in culture by calcium antagonists, statins, and their combination

Background Vascular calcification is an organized process in which vascular smooth muscle cells (VSMCs) are implicated primarily. The purpose of the present study was to assess the effects of calcium antagonists and statins on VSMC calcification in vitro. Methods VSMC calcification was stimulated by incubation in growth medium supplemented with 10 mmol/l β-glycerophosphate, 8 mmol/l CaCl2, 10 mmol/l sodium pyruvate, 1 μmol/l insulin, 50 μg/ml ascorbic acid, and 100 nmol/l dexamethasone (calcification medium). Calcification, proliferation, and apoptosis of VSMCs were quantified. Results Calcium deposition was stimulated dose-dependently by β-glycerophosphate, CaCl2, and ascorbic acid (all P < 0.01). Addition of amlodipine (0.01–1 μmol/l) to the calcification medium did not affect VSMC calcification. However, atorvastatin (2–50 μmol/l) stimulated calcium deposition dose-dependently. Combining treatments stimulated calcification to a degree similar to that observed with atorvastatin alone. Both atorvastatin and amlodipine inhibited VSMC proliferation at the highest concentration used. Only atorvastatin (50 μmol/l) induced considerable apoptosis of VSMCs. Conclusion In vitro calcification of VSMCs is not affected by amlodipine, but is stimulated by atorvastatin at concentrations ≥10 μmol/l, which could contribute to the plaque-stabilizing effect reported for statins

Homeobox transcription factor muscle segment homeobox 2 (Msx2) correlates with good prognosis in breast cancer patients and induces apoptosis in vitro

Introduction: The homeobox-containing transcription factor muscle segment homeobox 2 (Msx2) plays an important role in mammary gland development. However, the clinical implications of Msx2 expression in breast cancer are unclear. The aims of this study were to investigate the potential clinical value of Msx2 as a breast cancer biomarker and to clarify its functional role in vitro. Methods: Msx2 gene expression was first examined in a well-validated breast cancer transcriptomic dataset of 295 patients. Msx2 protein expression was then evaluated by immunohistochemistry in a tissue microarray (TMA) containing 281 invasive breast tumours. Finally, to assess the functional role of Msx2 in vitro, Msx2 was ectopically expressed in a highly invasive breast tumour cell line (MDA-MB-231) and an immortalised breast cell line (MCF10a), and these cell lines were examined for changes in growth rate, cell death and cell signalling. Results: Examination of Msx2 mRNA expression in a breast cancer transcriptomic dataset demonstrated that increased levels of Msx2 were associated with good prognosis (P = 0.011). Evaluation of Msx2 protein expression on a TMA revealed that Msx2 was detectable in both tumour cell nuclei and cytoplasm. Cytoplasmic Msx2 expression was associated with low grade tumours (P = 0.012) and Ki67 negativity (P = 0.018). Nuclear Msx2 correlated with low-grade tumours (P = 0.015), estrogen receptor positivity (P = 0.038), low Ki67 (P = 0.005) and high cyclin D1 expression (P = 0.037). Increased cytoplasmic Msx2 expression was associated with a prolonged breast cancer-specific survival (P = 0.049), recurrence-free survival (P = 0.029) and overall survival (P = 0.019). Ectopic expression of Msx2 in breast cell lines resulted in radically decreased cell viability mediated by induction of cell death via apoptosis. Further analysis of Msx2-expressing cells revealed increased levels of p21 and phosphorylated extracellular signal-regulated kinase (ERK) and decreased levels of Survivin and the 'split ends' (SPEN) protein family member RBM15. Conclusions: We conclude that increased Msx2 expression results in improved outcome for breast cancer patients, possibly by increasing the likelihood of tumour cell death by apoptosis

Mechanisms of MEOX1 and MEOX2 Regulation of the Cyclin Dependent Kinase Inhibitors p21CIP1/WAF1 and p16INK4a in Vascular Endothelial Cells

Senescence, the state of permanent cell cycle arrest, has been associated with endothelial cell dysfunction and atherosclerosis. The cyclin dependent kinase inhibitors p21CIP1/WAF1 and p16INK4a govern the G1/S cell cycle checkpoint and are essential for determining whether a cell enters into an arrested state. The homeodomain transcription factor MEOX2 is an important regulator of vascular cell proliferation and is a direct transcriptional activator of both p21CIP1/WAF1 and p16INK4a. MEOX1 and MEOX2 have been shown to be partially functionally redundant during development, suggesting that they regulate similar target genes in vivo. We compared the ability of MEOX1 and MEOX2 to activate p21CIP1/WAF1 and p16INK4a expression and induce endothelial cell cycle arrest. Our results demonstrate for the first time that MEOX1 regulates the MEOX2 target genes p21CIP1/WAF1 and p16INK4a. In addition, increased expression of either of the MEOX homeodomain transcription factors leads to cell cycle arrest and endothelial cell senescence. Furthermore, we show that the mechanism of transcriptional activation of these cyclin dependent kinase inhibitor genes by MEOX1 and MEOX2 is distinct. MEOX1 and MEOX2 activate p16INK4a in a DNA binding dependent manner, whereas they induce p21CIP1/WAF1 in a DNA binding independent manner

Association of Attitudes and Beliefs towards Antiretroviral Therapy with HIV-Seroprevalence in the General Population of Kisumu, Kenya

Since antiretroviral therapy (ART) became available in the developed world, the prevalence of unprotected sex and the incidence of sexually transmitted infections (STIs) and HIV have increased. We hypothesized that a similar phenomenon may be occurring in sub-Saharan Africa concomitant with the scale-up of HIV treatment.We conducted a general population-based survey in Kisumu, Kenya. Participants completed an interview that included demographics as well as ART-related attitudes and beliefs (AB) and then underwent HIV serological testing. Exploratory and confirmatory factor analyses of AB about ART indicated two factors: 1) ART-related risk compensation (increased sexual risk taking now that ART is available); and 2) a perception that HIV is more controllable now that ART is available. Logistic regression was used to determine associations of these factors with HIV-seroprevalence after controlling for age.1,655 (90%) of 1,844 people aged 15-49 contacted, including 749 men and 906 women, consented to participate in the study. Most participants (n = 1164; 71%) had heard of ART. Of those who had heard of ART, 23% believed ART was a cure for HIV. ART-related risk compensation (Adjusted (A)OR = 1.45, 95% CI 1.16-1.81), and a belief that ART cures HIV (AOR = 2.14, 95% CI 1.22-3.76) were associated with an increased HIV seroprevalence in men but not women after controlling for age. In particular, ART-related risk compensation was associated with an increased HIV-seroprevalence in young (aged 15-24 years) men (OR = 1.56; 95% CI 1.12-2.19).ART-related risk compensation and a belief that ART cures HIV were associated with an increased HIV seroprevalence among men but not women. HIV prevention programs in sub-Saharan Africa that target the general population should include educational messages about ART and address the changing beliefs about HIV in the era of greater ART availability

Ghrelin Attenuates the Osteoblastic Differentiation of Vascular Smooth Muscle Cells through the ERK Pathway

Vascular calcification results from osteoblastic differentiation of vascular smooth muscle cells (VSMCs) and is a major risk factor for cardiovascular events. Ghrelin is a newly discovered bioactive peptide that acts as a natural endogenous ligand of the growth hormone secretagog receptor (GHSR). Several studies have identified the protective effects of ghrelin on the cardiovascular system, however research on the effects and mechanisms of ghrelin on vascular calcification is still quite rare. In this study, we determined the effect of ghrelin on osteoblastic differentiation of VSMCs and investigated the mechanism involved using the two universally accepted calcifying models of calcifying vascular smooth muscle cells (CVSMCs) and beta-glycerophosphate (beta-GP)-induced VSMCs. Our data demonstrated that ghrelin inhibits osteoblastic differentiation and mineralization of VSMCs due to decreased alkaline phosphatase (ALP) activity, Runx2 expression, bone morphogenetic protein-2 (BMP-2) expression and calcium content. Further study demonstrated that ghrelin exerted this suppression effect via an extracellular signal-related kinase (ERK)-dependent pathway and that the suppression effect of ghrelin was time dependent and dose dependent. Furthermore, inhibition of the growth hormone secretagog receptor (GHSR), the ghrelin receptor, by siRNA significantly reversed the activation of ERK by ghrelin. In conclusion, our study suggests that ghrelin may inhibit osteoblastic differentiation of VSMCs through the GHSR/ERK pathway