291 research outputs found

    Stoics against stoics in Cudworth's "A Treatise of Freewill"

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    In his 'A Treatise of Freewill', Ralph Cudworth argues against Stoic determinism by drawing on what he takes to be other concepts found in Stoicism, notably the claim that some things are ‘up to us’ and that these things are the product of our choice. These concepts are central to the late Stoic Epictetus and it appears at first glance as if Cudworth is opposing late Stoic voluntarism against early Stoic determinism. This paper argues that in fact, despite his claim to be drawing on Stoic doctrine, Cudworth uses these terms with a meaning first articulated only later, by the Peripatetic commentator Alexander of Aphrodisias

    The status of health services in the 15 counties of Liberia

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    Aim: Liberia, situated at the West African coast, is composed of 15 counties with an economic gradient steeply decreasing from the Northwest to the Southeast. Health-related activities by government action in the 15 counties concentrate on the areas of family planning, antenatal and delivery care, as well as immunization, health workforce and infrastructure. The differences in this regard between the 15 Liberian counties will be reviewed. Methods: A narrative review is employed, making use of the recent international and national documents, relevant literature and available information from the following primary and secondary sources and databases. Results: The results point to gross differences between the 15 counties of Liberia in terms of health service provision. The overall readiness based on defined indicators for all 701 facilities was 59% with a range between facilities at the level of counties of 50% to 65%; for family planning services 88% (range 65% – 100%); for antenatal care 62% (range 55% – 100%); for immunization coverage 76% (range 66% – 86%). The health workforce of Liberia comprises 11.8 health workers per 10.000 population, WHO target is 23, the counties range from 8.0 to 15.7. Similarly, according to WHO standards, there should be 2 health facilities per 10.000 inhabitants, Liberia comes up to 1.9 however the counties range from 1.1 – 3.0 per 10.000. Conclusions: It is obvious that across almost all areas of women and child health and health services in general there exist large differences between counties, which points to considerable health inequities in this country. The government of Liberia should consider reallocating the available resources per number of population instead of accepting historical developments, however with a correction factor in favou of disadvantaged regions and population groups

    The status of health services in the 15 counties of Liberia

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    Aim: Liberia, situated at the West African coast, is composed of 15 counties with an economic gradient steeply decreasing from the Northwest to the Southeast. Health-related activities by government action in the 15 counties concentrate on the areas of family planning, antenatal and delivery care, as well as immunization, health workforce and infrastructure. The differences in this regard between the 15 Liberian counties will be reviewed.Methods: A narrative review is employed, making use of the recent international and national documents, relevant literature and available information from the following primary and secondary sources and databases.Results: The results point to gross differences between the 15 counties of Liberia in terms of health service provision. The overall readiness based on defined indicators for all 701 facilities was 59% with a range between facilities at the level of counties of 50% to 65%; for family planning services 88% (range 65% – 100%); for antenatal care 62% (range 55% – 100%); for immunization coverage 76% (range 66% – 86%). The health workforce of Liberia comprises 11.8 health workers per 10.000 population, WHO target is 23, the counties range from 8.0 to 15.7. Similarly, according to WHO standards, there should be 2 health facilities per 10.000 inhabitants, Liberia comes up to 1.9 however the counties range from 1.1 – 3.0 per 10.000.Conclusions: It is obvious that across almost all areas of women and child health and health services in general there exist large differences between counties, which points to considerable health inequities in this country. The government of Liberia should consider reallocating the available resources per number of population instead of accepting historical developments, however with a correction factor in favour of disadvantaged regions and population groups.  

    Quantitative trait loci mapping reveals candidate pathways regulating cell cycle duration in Plasmodium falciparum

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    <p>Abstract</p> <p>Background</p> <p>Elevated parasite biomass in the human red blood cells can lead to increased malaria morbidity. The genes and mechanisms regulating growth and development of <it>Plasmodium </it><it>falciparum </it>through its erythrocytic cycle are not well understood. We previously showed that strains HB3 and Dd2 diverge in their proliferation rates, and here use quantitative trait loci mapping in 34 progeny from a cross between these parent clones along with integrative bioinformatics to identify genetic loci and candidate genes that control divergences in cell cycle duration.</p> <p>Results</p> <p>Genetic mapping of cell cycle duration revealed a four-locus genetic model, including a major genetic effect on chromosome 12, which accounts for 75% of the inherited phenotype variation. These QTL span 165 genes, the majority of which have no predicted function based on homology. We present a method to systematically prioritize candidate genes using the extensive sequence and transcriptional information available for the parent lines. Putative functions were assigned to the prioritized genes based on protein interaction networks and expression eQTL from our earlier study. DNA metabolism or antigenic variation functional categories were enriched among our prioritized candidate genes. Genes were then analyzed to determine if they interact with cyclins or other proteins known to be involved in the regulation of cell cycle.</p> <p>Conclusions</p> <p>We show that the divergent proliferation rate between a drug resistant and drug sensitive parent clone is under genetic regulation and is segregating as a complex trait in 34 progeny. We map a major locus along with additional secondary effects, and use the wealth of genome data to identify key candidate genes. Of particular interest are a nucleosome assembly protein (PFL0185c), a Zinc finger transcription factor (PFL0465c) both on chromosome 12 and a ribosomal protein L7Ae-related on chromosome 4 (PFD0960c).</p

    Physio-chemical characterization of three-component co-amorphous systems generated by a melt-quench method

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    The purpose of this work was to evaluate the possibility of creating a ternary co-amorphous system and to determine how the properties of a co-amorphous material are altered by the addition of a selected third component. Piroxicam and indomethacin form a stable co-amorphous with the Tg above room temperature. The third component added was selected based on tendency to crystallise (benzamide, caffeine) or form amorphous (acetaminophen, clotrimazole) on cooling. Generated co-amorphous systems were characterised with TGA, HSM, DSC, FTIR, and XRD. Stable ternary co-amorphous systems were successfully generated, which was confirmed using XRD, DSC and FTIR analysis. In all cases, Tg of the ternary system was lower than the Tg of the binary system, although higher than that of the individual third compound. Upon storage for 4 weeks all created ternary systems showed significantly smaller variation in Tg compared to the binary system. Stable three-component co-amorphous systems can be generated via melt quench method using either a crystalline or amorphous third component. Addition of third component can alter the Tg of co-amorphous system and in all cases created more stable co-amorphous system upon storage. Physical parameters may not be sufficient in predicting the resulting Tg, therefore knowledge of chemical interaction must be brought into equation as well

    Predicting Crystallization of Amorphous Drugs with Terahertz Spectroscopy.

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    There is a controversy about the extent to which the primary and secondary dielectric relaxations influence the crystallization of amorphous organic compounds below the glass transition temperature. Recent studies also point to the importance of fast molecular dynamics on picosecond-to-nanosecond time scales with respect to the glass stability. In the present study we provide terahertz spectroscopy evidence on the crystallization of amorphous naproxen well below its glass transition temperature and confirm the direct role of Johari-Goldstein (JG) secondary relaxation as a facilitator of the crystallization. We determine the onset temperature Tβ above which the JG relaxation contributes to the fast molecular dynamics and analytically quantify the level of this contribution. We then show there is a strong correlation between the increase in the fast molecular dynamics and onset of crystallization in several chosen amorphous drugs. We believe that this technique has immediate applications to quantify the stability of amorphous drug materials.JS and JAZ would like to acknowledge the UK Engineering and Physical Sciences Research Council for funding (EP/J007803/1).This is the final version of the article. It first appeared from ACS at http://dx.doi.org/10.1021/acs.molpharmaceut.5b0033

    Protocol for a national, mixed-methods knowledge, attitudes and practices survey on non-communicable diseases

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    Background Mongolia is undergoing rapid epidemiological transition with increasing urbanisation and economic development. The lifestyle and health of Mongolians are changing as a result, shown by the 2005 and 2009 STEPS surveys (World Health Organization's STEPwise Approach to Chronic Disease Risk Factor Surveillance) that described a growing burden of Non-Communicable Diseases and injuries (NCDs). This study aimed to assess, describe and explore the knowledge, attitudes and practices of the Mongolian adult population around NCDs in order to better understand the drivers and therefore develop more appropriate solutions to this growing disease burden. In addition, it aimed to provide data for the evaluation of current public health programs and to assist in building effective, evidence-based health policy. Methods/design This national survey consisted of both quantitative and qualitative methods. A quantitative household-based questionnaire was conducted using a nationally representative sample of 3854 rural and urban households. Participants were selected using a multi-stage cluster sampling technique in 42 regions across Mongolia, including rural and urban sites. Permanent residents of sampled households were eligible for recruitment, if aged between 15-64 years. This quantitative arm was then complemented and triangulated with a qualitative component: twelve focus group discussions focusing on diet, exercise and alcohol consumption. Discussions took place in six sites across the country, facilitated by local, trained health workers. These six sites were chosen to reflect major Mongolian cultural and social groups. Discussion KAP surveys are well represented in the literature, but studies that aim to explore the knowledge, attitudes and practices of a population around NCDs remain scarce. This is despite the growing number of national epidemiological surveys, such as STEPS, which aim to quantify the burden of these diseases but do not explore the level of population-based awareness, understanding, risk-perception and possible motivation for change. Therefore this paper will contribute to building a knowledge base of NCD KAP survey methodology for future use in epidemiology and research worldwide

    Adjuvant radiotherapy for primary breast cancer in BRCA1 and BRCA2 mutation carriers and risk of contralateral breast cancer with special attention to patients irradiated at younger age

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    The purpose of this study was to estimate the influence of adjuvant radiotherapy for primary breast cancer (BC) on the risk of contralateral BC (CBC) in BRCA1 or BRCA2(BRCA1/2) mutation carriers, with special attention to patients irradiated at age younger than 40 years. Additionally, tendencies in locoregional treatments and rates of contralateral risk-reducing mastectomy over time were explored. In this retrospective cohort study, 691 BRCA1/2-associated BC patients treated between 1980 and 2013 were followed from diagnosis until CBC or censoring event including ipsilateral BC recurrence, distant metastasis, contralateral risk-reducing mastectomy, other invasive cancer diagnosis, death, or loss to follow up. Hazard ratios (HR) for CBC associated with radiotherapy were estimated using Cox regression. Median follow-up time was 8.6 years [range 0.3–34.3 years]. No association between radiotherapy for primary BC and risk of CBC was found, neither in the total population (HR 0.82, 95 % CI 0.45–1.49) nor in the subgroup of patients younger than 40 years at primary diagnosis (HR 1.36, 95 % CI 0.60–3.09). During follow-up, the number of patients at risk decreased substantially since a large proportion of patients were censored after contralateral risk-reducing mastectomy or BC recurrence. Over the years, increasing preference for mastectomy without radiotherapy compared to breast-conserving surgery with radiotherapy was found ranging from less than 30 % in 1995 to almost 50 % after 2010. The rate of contralateral risk-reducing mastectomy increased over the years from less than 40 % in 1995 to more than 60 % after 2010. In this cohort of BRCA1/2-associated BC patients, no association between radiotherapy for primary BC and risk of CBC was observed in the total group, nor in the patients irradiated before the age of 40 years. The number of patients at risk after 10 and 15 years of follow-up, however, was too small to definitively exclude harmful effects of adjuvant radiotherapy
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