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    Diderot

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    Because of his public leadership of the philosophe party in eighteenth-century France, Voltaire stands today as the iconic example of the French Enlightenment philosopher. Denis Diderot (1713–1784) is often seen as Voltaire’s second in that role since it was around both men that the Enlightenment philosophes rallied as a movement after 1750. The epochal project, which Diderot jointly pursued with Jean le Rond D’Alembert, to “change the common way of thinking” through a comprehensive Encyclopedia, or Reasoned Dictionary of the Arts, Sciences, and Trades provided the emergent philosophe movement with the cause around which they would coalesce. Diderot also fought vigorously with Voltaire on behalf of the Encyclopédie project and its principles, becoming as a result a public leader of the Enlightenment philosophical party in France alongside Voltaire. He also worked, like Voltaire, as a writer and critical intellectual who willingly positioned himself against the grain of established authority, and one who used philosophy as a vehicle for political and social activism. Yet Diderot’s philosophy pursued many more agendas and dimensions than Voltaire’s. He also left behind a corpus of philosophical writings that marks him out as arguably the most sophisticated of all the Enlightenment philosophes, and as one of the great philosophical thinkers of the eighteenth-century. Despite the obvious sophistication of Diderot’s philosophy, his legacy has suffered because of the historical differences separating his writings from the discipline of philosophy as it is practiced today. Enlightenment philosophie was something very different from what professional academic philosophers mean by that term today, and Diderot’s writings are often ignored by modern philosophers because they do not appear to be philosophy as they know it. Like many Enlightenment philosophes, Diderot also worked as an homme de lettres first and foremost, and only as a philosopher narrowly construed in certain instances. He also never authored any recognizable work of “systematic philosophy” if by that term we mean writing in the vein of his contemporaries such as David Hume in his Treatise or Immanuel Kant in his Critiques. Yet Diderot made important contributions to modern philosophy, and if they are to be grasped, the historical differences separating his writing from philosophy today must be transcended, and his eclectic manner of working accepted and embraced. Diderot wrote works that we recognize today as philosophy, but he also wrote a great deal more than that, and the challenge presented by his eighteenth-century philosophie is to see the modern philosophy contained in all of it. For Diderot did not simply write plays, art criticism, prose fictions, and highly imaginative works of literature alongside his work in philosophy; he pursued philosophie through these ostensibly literary works as well. He experimented with genres, including philosophical genres, when crafting his thought, and his writing overall is redolent with a self-consciousness that makes any easy separation of his explicitly philosophical writings from his literary work well-nigh impossible. His publishing habits were similarly complex, for as a writer who suffered personally under censorship that made the traffic in illicit ideas a prosecutable offense in Old Regime France, Diderot often had very good reason to leave his work unpublished—and very often did. At the same time, censorship alone does not explain the peculiar mix of published and unpublished writings found in Diderot’s oeuvre. This historical complexity has given rise to some difficulty in assessing Diderot’s writings according to the disciplinary canon of modern philosophy. Condillac, Helvétius, and d’Holbach are the Enlightenment philosophes most commonly studied within philosophy departments because their writings appear to conform better with conventional understandings of what philosophy should look like as a genre and a linguistic idiom. By contrast, the works of Diderot tend to be studied only in literature or history departments. This is unfortunate, for the treatment of Diderot’s philosophie as something different from modern philosophy has cut contemporary philosophers off from the work of one of the most sophisticated, subtle, and complex philosophical thinkers of the eighteenth century. To some extent, the way in which Diderot’s philosophical work employs different genres but also, challenges the idea of genre itself, has made it seem (perhaps too easily) congenial to a more “Continental” philosophical tradition, and foreign to a more formally oriented “analytic” tradition. But that would ignore Diderot’s naturalistic commitments and the role the Encyclopédie played, e.g., in the self-image of philosophers of science in the Vienna Circle. Our entry seeks to go beyond such oppositions in dealing with Diderot as a philosopher. Neither perspective alone fully grasps the richness of Diderot’s contributions to modern philosophy, so in order to fully situate his philosophie within philosophy writ large, a flexible and reflexive attitude regarding his writings must be adopted. Every text in Diderot’s oeuvre needs to be treated as a participant in both his philosophie and his philosophical work, and our conventional understanding of the boundaries isolating art and literature from science and philosophy also needs to be suspended because very often these modern distinctions do not apply in Diderot’s case. He also manifests an awareness of the new and emergent disciplinary taxonomy arising at the time, targeting his philosophie on many occasions at an interrogation of these developing epistemological divisions. This reflexivity often makes his thought even more relevant today than it was when it was written. To capture the complexity of Diderot’s philosophie as philosophy, this article adopts this reflexive approach. It will proceed in two parts. An overview of Diderot’s life and major texts is offered in Part I so as to present his work and writings as particular episodes in a coherent eighteenth-century life and career. To simplify the reading of this biography, the text is offered in a two-level presentation. A short overview of the highlights of Diderot’s life and work is offered in Section 1 to give readers a schematic overview, but a more extensive presentation of his biography is available in the Biographical Supplement. A comprehensive analysis of Diderot’s major philosophical preoccupations as revealed in his writings is then offered in Section 2 so as to outline the contours of Diderot’s place within Enlightenment philosophie and modern philosophy overall. This is followed by brief concluding remarks in Section 3

    Antiretroviral Therapy outcomes among adolescents and youth in rural Zimbabwe

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    Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents) 15.1-19 years (adolescents), 19.1-24 years (young adults) and 24.1-29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35). Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults

    Evaluation of the utilization of the preanaesthetic clinics in a University teaching hospital

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    BACKGROUND: Dedicated out-patient preanaesthetic clinics are relatively recent phenomenon and information is sparse from developing world. This study attempted to evaluate the utilization of adult and paediatric preanaesthetic clinics and its impact on the cancellations of surgery in Trinidad. METHODS: All patients scheduled to have elective surgery during the period of twelve weeks were enrolled for prospective collection of data including demographics, the admitting diagnoses, surgical procedure, category of surgery and specialty, and the patients' attendance to preanaesthetic clinics. Cancellations on the day of surgery along with reasons were recorded. The difference between patients who attended and did not attend the clinic was analysed. RESULTS: Of 424 patients scheduled for procedures during the study period, 213 were adults and 211 were children. Overall 39% of adults and 46% of the children scheduled for surgery had previously attended the preanaesthetic clinic. Among adults, general surgery patients were the largest majority to attend the preanaesthetic clinic. The paediatric preanaesthetic clinic was mostly utilized by paediatric general surgery. Overall 30% of procedures in adults and 26% of those in children were cancelled. There was a statistically significant difference in cancellations between patients who attended and did not attend the preanaesthetic clinic (p = 0.004). There was a 52% more chance of the procedure getting cancelled if the patient did not attend the clinic. CONCLUSION: The study highlights the inadequate use of the preanaesthetic clinics and the impact of the clinics on last-minute cancellations

    Carer subjective burden after first-episode psychosis: Types and predictors. A multilevel statistical approach

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    Background: Carer burden at first-episode psychosis is common and adds to the multiple other psychiatric and psychological problems that beset new carers; yet, knowledge of the factors that predict carer burden is limited. Aim: This study sought to investigate the types and predictors of carer burden at first-episode psychosis in the largest, most ethnically diverse and comprehensively characterised sample to date. Method: This study involved a cross-sectional survey of carers of people with first-episode psychosis presenting to Harrow and Hillingdon Early Intervention in Psychosis service between 2011 and 2017. Carers completed self-report measures assessing their illness beliefs, coping styles and caregiving experiences (i.e. burden). Thirty carer and patient sociodemographic and clinical factors were also collected. Mixed effects linear regression modelling was conducted to account for clustering of carers by patient, with carer burden (and its 8 subtypes) investigated as dependent variables. Results: The sample included data on 254 carers (aged 18–74 years) and 198 patients (aged 14–36 years). Regression modelling identified 35 significant predictors of carer burden and its subtypes at first-episode psychosis. Higher total burden was independently predicted by perceiving greater negative consequences of the illness for the patient (B = .014, p < .001, 95% CI: [.010–.018]) and the carer (B = .008, p = .002, 95% CI: [.003–.013]), and engaging in avoidant-focussed coping (B = .010, p = .006, 95% CI: [.003–.016]). Lower burden was independently predicted by patients being in a relationship (B = −.075, p = .047, 95% CI: [−.149 to −.001]). Predictors of the eight burden subtypes (difficult behaviours, negative symptoms, stigma, problems with services, effects on family, dependency, loss and need to backup) are also included in the article. Conclusion: Findings can be used to inform the identification of carers ‘at-risk’ of experiencing burden and highlight potential targets for theraputic intervention to lower carer buden

    Interactions between downslope flows and a developing cold-air pool

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    A numerical model has been used to characterize the development of a region of enhanced cooling in an alpine valley with a width of order (Formula presented.) km, under decoupled stable conditions. The region of enhanced cooling develops largely as a region of relatively dry air which partitions the valley atmosphere dynamics into two volumes, with airflow partially trapped within the valley by a developing elevated inversion. Complex interactions between the region of enhanced cooling and the downslope flows are quantified. The cooling within the region of enhanced cooling and the elevated inversion is almost equally partitioned between radiative and dynamic effects. By the end of the simulation, the different valley atmospheric regions approach a state of thermal equilibrium with one another, though this cannot be said of the valley atmosphere and its external environment.Peer reviewe

    A random cell motility gradient downstream of FGF controls elongation of amniote embryos

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    Vertebrate embryos are characterized by an elongated antero-posterior (AP) body axis, which forms by progressive cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of cell motility and directionality in the PSM. We tracked the movement of the PSM extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells. After subtraction, cell motility remained graded but lacked directionality, indicating that the posterior cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of cell motion along the PSM parallels the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK) gradient1, which has been implicated in the control of cell motility in this tissue2. Both FGF signalling gain- and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with cell movement inhibitors (blebbistatin or RhoK inhibitor), but not cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements

    A Cross-Sectional Survey on Knowledge and Perceptions of Health Risks Associated with Arsenic and Mercury Contamination from Artisanal Gold mining in Tanzania.

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    An estimated 0.5 to 1.5 million informal miners, of whom 30-50% are women, rely on artisanal mining for their livelihood in Tanzania. Mercury, used in the processing gold ore, and arsenic, which is a constituent of some ores, are common occupational exposures that frequently result in widespread environmental contamination. Frequently, the mining activities are conducted haphazardly without regard for environmental, occupational, or community exposure. The primary objective of this study was to assess community risk knowledge and perception of potential mercury and arsenic toxicity and/or exposure from artisanal gold mining in Rwamagasa in northwestern Tanzania. A cross-sectional survey of respondents in five sub-villages in the Rwamagasa Village located in Geita District in northwestern Tanzania near Lake Victoria was conducted. This area has a history of artisanal gold mining and many of the population continue to work as miners. Using a clustered random selection approach for recruitment, a total of 160 individuals over 18 years of age completed a structured interview. The interviews revealed wide variations in knowledge and risk perceptions concerning mercury and arsenic exposure, with 40.6% (n=65) and 89.4% (n=143) not aware of the health effects of mercury and arsenic exposure respectively. Males were significantly more knowledgeable (n=59, 36.9%) than females (n=36, 22.5%) with regard to mercury (x²=3.99, p<0.05). An individual's occupation category was associated with level of knowledge (x²=22.82, p=<0.001). Individuals involved in mining (n=63, 73.2%) were more knowledgeable about the negative health effects of mercury than individuals in other occupations. Of the few individuals (n=17, 10.6%) who knew about arsenic toxicity, the majority (n=10, 58.8%) were miners. The knowledge of individuals living in Rwamagasa, Tanzania, an area with a history of artisanal gold mining, varied widely with regard to the health hazards of mercury and arsenic. In these communities there was limited awareness of the threats to health associated with exposure to mercury and arsenic. This lack of knowledge, combined with minimal environmental monitoring and controlled waste management practices, highlights the need for health education, surveillance, and policy changes

    Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

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    In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.

    Mosquito Abundance, Bed net Coverage and Other Factors Associated with Variations in Sporozoite Infectivity Rates in Four Villages of Rural Tanzania.

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    Entomological surveys are of great importance in decision-making processes regarding malaria control strategies because they help to identify associations between vector abundance both species-specific ecology and disease intervention factors associated with malaria transmission. Sporozoite infectivity rates, mosquito host blood meal source, bed net coverage and mosquito abundance were assessed in this study. A longitudinal survey was conducted in four villages in two regions of Tanzania. Malaria vectors were sampled using the CDC light trap and pyrethrum spray catch methods. In each village, ten paired houses were selected for mosquitoes sampling. Sampling was done in fortnight case and study was undertaken for six months in both Kilimanjaro (Northern Tanzania) and Dodoma (Central Tanzania) regions. A total of 6,883 mosquitoes were collected including: 5,628 (81.8%) Anopheles arabiensis, 1,100 (15.9%) Culex quinquefasciatus, 89 (1.4%) Anopheles funestus, and 66 (0.9%) Anopheles gambiae s.s. Of the total mosquitoes collected 3,861 were captured by CDC light trap and 3,022 by the pyrethrum spray catch method. The overall light trap: spray catch ratio was 1.3:1. Mosquito densities per room were 96.5 and 75.5 for light trap and pyrethrum spray catch respectively. Mosquito infectivity rates between villages that have high proportion of bed net owners and those without bed nets was significant (P < 0.001) and there was a significant difference in sporozoite rates between households with and without bed nets in these four villages (P < 0.001). Malaria remains a major problem in the study areas characterized as low transmission sites. Further studies are required to establish the annual entomological inoculation rates and to observe the annual parasitaemia dynamics in these communities. Outdoor mosquitoes collection should also be considered

    Ethics for an uninhabited planet

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    Some authors argue that we have a moral obligation to leave Mars the way it is, even if it does not harbour any life. This claim is usually based on an assumption that Mars has intrinsic value. The problem with this concept is that different authors use it differently. In this chapter, I investigate different ways in which an uninhabited Mars is said to have intrinsic value. First, I investigate whether the planet can have moral standing. I find that this is not a plausible assumption. I then investigate different combinations of objective value and end value. I find that there is no way we can know whether an uninhabited Mars has objective end value and even if it does, this does not seem to imply any moral obligations on us. I then investigate whether an uninhabited Mars can have subjective end value. I conclude that this is very plausible. I also investigate whether an uninhabited Mars can have objective instrumental value in relation to some other, non-Mars related end value. I find also this very plausible. It is also highly plausible, however, that spreading (human or other) life to a presently uninhabited Mars can also have subjective end value, as well as objective instrumental value. I mention shortly two ways of prioritising between these values: (1) The utilitarian method of counting the number of sentient beings who entertain each value and determining the strength of the values to them. (2) Finding a compromise that allows colonisation on parts of the planet while leaving other parts untouched. These methods should be seen as examples, not as an exhaustive list. Also, I do not take a definitive stand in favour of any of the two approaches, though it seems at least prima facie that the second approach may have a better chance of actually leading to a constructive result
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