Subjective utility moderates bidirectional effects of conflicting motivations on pain perception

Minimizing pain and maximizing pleasure are conflicting motivations when pain and reward co-occur. Decisions to prioritize reward consumption or pain avoidance are assumed to lead to pain inhibition or facilitation, respectively. Such decisions are a function of the subjective utility of the stimuli involved, i.e. the relative value assigned to the stimuli to compare the potential outcomes of a decision. To test perceptual pain modulation by varying degrees of motivational conflicts and the role of subjective utility, we implemented a task in which healthy volunteers had to decide between accepting a reward at the cost of receiving a nociceptive electrocutaneous stimulus or rejecting both. Subjective utility of the stimuli was assessed by a matching task between the stimuli. Accepting reward coupled to a nociceptive stimulus resulted in decreased perceived intensity, while rejecting the reward to avoid pain resulted in increased perceived intensity, but in both cases only if a high motivational conflict was present. Subjective utility of the stimuli involved moderated these bidirectional perceptual effects: the more a person valued money over pain, the more perceived intensity increased or decreased. These findings demonstrate pain modulation when pain and reward are simultaneously present and highlight the importance of subjective utility for such modulation

A genome scan for milk production traits in dairy goats reveals two new mutations in <i>Dgat1</i> reducing milk fat content

The quantity of milk and milk fat and proteins are particularly important traits in dairy livestock. However, little is known about the regions of the genome that influence these traits in goats. We conducted a genome wide association study in French goats and identified 109 regions associated with dairy traits. For a major region on chromosome 14 closely associated with fat content, the Diacylglycerol O-Acyltransferase 1 (DGAT1) gene turned out to be a functional and positional candidate gene. The caprine reference sequence of this gene was completed and 29 polymorphisms were found in the gene sequence, including two novel exonic mutations: R251L and R396W, leading to substitutions in the protein sequence. The R251L mutation was found in the Saanen breed at a frequency of 3.5% and the R396W mutation both in the Saanen and Alpine breeds at a frequencies of 13% and 7% respectively. The R396W mutation explained 46% of the genetic variance of the trait, and the R251L mutation 6%. Both mutations were associated with a notable decrease in milk fat content. Their causality was then demonstrated by a functional test. These results provide new knowledge on the genetic basis of milk synthesis and will help improve the management of the French dairy goat breeding program

Language use in kindergarten science lessons:Language production and academic language during a video feedback coaching intervention in kindergarten science lessons

This paper aims to gain insight into language production and academic language of 4- and 5-year-old students and their teachers in the course of a teacher intervention during kindergarten science education. The study is based on videotaped classroom observations, and specifically focuses on the academic language use of students (Nintervention = 18, Ncontrols = 26) and teachers (Nintervention = 5, Ncontrols = 5). The results suggest that this general teacher intervention yields interesting changes in language use and production. Patterns of change over time confirm the idiosyncratic and non-linear nature of these changes. Science lessons represent an appropriate context in which to acquaint students with academic language, which can be used as a basis to build upon more sophisticated language skills

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden

Euthanasia: from the perspective of HIV infected persons in Europe.

BACKGROUND: In the debate about legalization of euthanasia very little attention has so far been given to the opinion of the patient. OBJECTIVE: To assess the opinion of persons with HIV infection in Europe. METHODS: A cross-sectional survey of persons with HIV infection attending HIV/AIDS treatment centres or HIV support organizations in 11 European Union Member States was performed. A total of 2751 anonymous patient self-administered questionnaires were distributed between August 1996 and September 1997. The questionnaire contained 108 questions concerning a variety of topics about HIV care, including five questions on euthanasia. RESULTS: One thousand three hundred and seventy-one people with HIV infection completed the questionnaire, of whom 1341 (98%) responded to the questions concerning euthanasia. Seventy-eight percent of respondents agreed with the legalization of euthanasia in case of severe physical suffering, 47% if there was severe psychological suffering and 24% simply at the patient's request. For physical suffering and at a clear patient's request, accepted practices were: alleviation of pain with double effect (81%), medical euthanasia (62%) and physician assisted suicide (45%). Fifty percent would consider euthanasia for themselves if all treatment options were exhausted. Social indicators such as educational level and employment seemed to play a more significant role in determining attitudes towards legalization, and personal interest in, euthanasia than indicators related to disease status. CONCLUSION: In this study a majority of HIV infected persons in Europe favoured the legalization of euthanasia

Financial situation of people living with HIV in Europe.

The objective was to investigate the financial situation of people living with HIV in Europe. Two surveys using an anonymous questionnaire were organized in Europe among people living with HIV, the first in 1996-97 and the second in 1998-99. One thousand one hundred and sixty-one people from the 1996-97 survey and 899 from the 1998-99 survey were included. Four hundred and fifty-seven (42%) of the 1996-97 participants reported that their income had decreased since HIV diagnosis. The latter participants reported significantly more often difficulties in paying for housing (27% vs 20%), food (18% vs 12%) and transport (17% vs 12%) compared to 1998-99 participants. In multiple regression analysis, severity of HIV disease, not being on highly active antiretroviral therapy (HAART), younger age, lower education level and living in the South of Europe were associated with having financial difficulties. We concluded that since the introduction of HAART, the financial situation of persons living with HIV in Europe has improved, but a relatively large percentage of them still have financial difficulties

Antiretroviral treatments used among adults with HIV infection in Europe.

International guidelines for the treatment of human immunodeficiency virus (HIV) infection change rapidly. They are mainly based on results from large-scale randomized clinical trials, but also on hypotheses. The objective of the study was to look at the use of antiretrovirals (ARVs) in different HIV treatment centres in Europe. Between August 1996 and September 1997 self-administered anonymous questionnaires were distributed to persons with HIV infection at inpatient and outpatient departments in 11 European countries; 1,366 people completed the questionnaire. Important differences in use of ARVs were noted between different centres. Zidovudine was the drug that was used predominantly in all countries and by 77% of all patients; the use of didanosine, zalcitabine and stavudine differed widely. Use of ARVs was found to be lower for people who reported intravenous drug use (compared to homosexual transmission), people with a low education level, and those with a monthly income lower than 992 Euro. The use of a protease inhibitor containing ARV treatment regimen was significantly lower in the centres in the south of Europe. Between 1996 and 1997, many persons with HIV infection in Europe received a suboptimal ARV treatment regimen. Use of ARVs should be improved for intravenous drug users, persons with lower educational level and lower income

In silico regenerative medicine: how computational tools allow regulatory and financial challenges to be addressed in a volatile market

The cell therapy market is a highly volatile one, due to the use of disruptive technologies, the current economic situation and the small size of the market. In such a market, companies as well as academic research institutes are in need of tools to advance their understanding and, at the same time, reduce their R&D costs, increase product quality and productivity, and reduce the time to market. An additional difficulty is the regulatory path that needs to be followed, which is challenging in the case of cell-based therapeutic products and should rely on the implementation of quality by design (QbD) principles. In silico modelling is a tool that allows the above-mentioned challenges to be addressed in the field of regenerative medicine. This review discusses such in silico models and focuses more specifically on the bioprocess. Three (clusters of) examples related to this subject are discussed. The first example comes from the pharmaceutical engineering field where QbD principles and their implementation through the use of in silico models are both a regulatory and economic necessity. The second example is related to the production of red blood cells. The described in silico model is mainly used to investigate the manufacturing process of the cell-therapeutic product, and pays special attention to the economic viability of the process. Finally, we describe the set-up of a model capturing essential events in the development of a tissue-engineered combination product in the context of bone tissue engineering. For each of the examples, a short introduction to some economic aspects is given, followed by a description of the in silico tool or tools that have been developed to allow the implementation of QbD principles and optimal design.status: publishe

In silico regenerative medicine: how computational tools allow regulatory and financial challenges to be addressed in a volatile market.

The cell therapy market is a highly volatile one, due to the use of disruptive technologies, the current economic situation and the small size of the market. In such a market, companies as well as academic research institutes are in need of tools to advance their understanding and, at the same time, reduce their R&D costs, increase product quality and productivity, and reduce the time to market. An additional difficulty is the regulatory path that needs to be followed, which is challenging in the case of cell-based therapeutic products and should rely on the implementation of quality by design (QbD) principles. In silico modelling is a tool that allows the above-mentioned challenges to be addressed in the field of regenerative medicine. This review discusses such in silico models and focuses more specifically on the bioprocess. Three (clusters of) examples related to this subject are discussed. The first example comes from the pharmaceutical engineering field where QbD principles and their implementation through the use of in silico models are both a regulatory and economic necessity. The second example is related to the production of red blood cells. The described in silico model is mainly used to investigate the manufacturing process of the cell-therapeutic product, and pays special attention to the economic viability of the process. Finally, we describe the set-up of a model capturing essential events in the development of a tissue-engineered combination product in the context of bone tissue engineering. For each of the examples, a short introduction to some economic aspects is given, followed by a description of the in silico tool or tools that have been developed to allow the implementation of QbD principles and optimal design