169 research outputs found

    A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

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    In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

    Emotional Engineers: Toward Morally Responsible Design

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    Engineers are normally seen as the archetype of people who make decisions in a rational and quantitative way. However, technological design is not value neutral. The way a technology is designed determines its possibilities, which can, for better or for worse, have consequences for human wellbeing. This leads various scholars to the claim that engineers should explicitly take into account ethical considerations. They are at the cradle of new technological developments and can thereby influence the possible risks and benefits more directly than anybody else. I have argued elsewhere that emotions are an indispensable source of ethical insight into ethical aspects of risk. In this paper I will argue that this means that engineers should also include emotional reflection into their work. This requires a new understanding of the competencies of engineers: they should not be unemotional calculators; quite the opposite, they should work to cultivate their moral emotions and sensitivity, in order to be engaged in morally responsible engineering

    Reproductive Behaviour Evolves Rapidly When Intralocus Sexual Conflict Is Removed

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    Background Intralocus sexual conflict can inhibit the evolution of each sex towards its own fitness optimum. In a previous study, we confirmed this prediction through the experimental removal of female selection pressures in Drosophila melanogaster, achieved by limiting the expression of all major chromosomes to males. Compared to the control populations (C1-4) where the genomes are exposed to selection in both sexes, the populations with male-limited genomes (ML1-4) showed rapid increases in male fitness, whereas the fitness of females expressing ML-evolved chromosomes decreased [1]. Methodology/Principal Findings Here we examine the behavioural phenotype underlying this sexual antagonism. We show that males expressing the ML genomes have a reduced courtship level but acquire the same number of matings. On the other hand, our data suggest that females expressing the ML genomes had reduced attractiveness, stimulating a lower rate of courtship from males. Moreover, females expressing ML genomes tend to display reduced yeast-feeding behaviour, which is probably linked to the reduction of their fecundity. Conclusion/Significance These results suggest that reproductive behaviour is shaped by opposing selection on males and females, and that loci influencing attractiveness and foraging were polymorphic for alleles with sexually antagonistic expression patterns prior to ML selection. Hence, intralocus sexual conflict appears to play a role in the evolution of a wide range of fitness-related traits and may be a powerful mechanism for the maintenance of genetic variation in fitness

    Pain in platin-induced neuropathies: A systematic review and meta-analysis

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    INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment

    On the predictive utility of animal models of osteoarthritis

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    Raynaud's phenomenon, vibration-induced white finger, and difficulties in hearing

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    Background: An association has previously been reported between finger blanching and hearing difficulties, but only in workers with exposure to noise and hand transmitted vibration (HTV).Aims: To explore the association in a community sample, including cases who lacked occupational exposure to noise or HTV.Method: A questionnaire was mailed to 12 606 subjects aged 35–64 years, chosen at random from the age–sex registers of 34 British general practices. Inquiry was made about years of employment in noisy jobs, lifetime exposure to HTV, hearing difficulties and tinnitus, and lifetime history of cold induced finger blanching. Subjects were classed as having severe hearing difficulty if they used a hearing aid or found it difficult or impossible to hear conversation in a quiet room. Associations of finger blanching with hearing difficulties and tinnitus were analysed by logistic regression.Results: Among 8193 respondents were 185 who reported severe hearing difficulty and 1151 who reported finger blanching. After adjustment for age and years of work in noisy jobs, hearing difficulty was about twice as common in men and women who reported finger blanching, including those who had never been importantly exposed to noise and in those never exposed to HTV.Conclusions: These data support an association between finger blanching and hearing loss, which is not explained by confounding occupational exposure to noise, and suggest that it may extend to causes of blanching other than vibration induced white finger. Further investigations are warranted to confirm the association and explore possible mechanisms, such as sympathetic vasoconstriction in the cochlea

    Joints

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