336 research outputs found

    The Extirpation of Idolatry in Peru

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    Long recognized as a classic account of the early Spanish efforts to convert the Indians of Peru, Father De Arriaga’s book, originally published in 1621, has become comparatively rare even in its Spanish editions. This translation now makes available for the first time in English a unique record of the customs and religious practices that prevailed after the Spanish conquest. In his book, which was designed as a manual for the rooting out of paganism, De Arriaga sets down plainly and methodically what he found among the Indians—their objects of worship, their priests and sorcerers, their festivals and sacrifices, and their superstitions—and how these things are to be recognized and combated. Moreover, he evinces a steady awareness of the hold of custom and of the plight of the Indians who are torn between the demands of their old life and their new masters. The Extirpation of Idolatry in Peru is an invaluable source for historians and anthropologists. L. Clark Keating is professor of modern languages at the University of Kentucky.https://uknowledge.uky.edu/upk_latin_american_history/1004/thumbnail.jp

    The effect of rotavirus vaccine on diarrhoea mortality

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    Background Approximately 39% of the global diarrhoea deaths in children aged 5 years may be attributable to rotavirus infection. Two rotavirus vaccines were recently introduced to the market, with evidence of efficacy in the USA, Europe and Latin America. We sought to estimate the effectiveness of these vaccines against rotavirus morbidity and mortality

    The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

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    Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

    Many body physics from a quantum information perspective

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    The quantum information approach to many body physics has been very successful in giving new insight and novel numerical methods. In these lecture notes we take a vertical view of the subject, starting from general concepts and at each step delving into applications or consequences of a particular topic. We first review some general quantum information concepts like entanglement and entanglement measures, which leads us to entanglement area laws. We then continue with one of the most famous examples of area-law abiding states: matrix product states, and tensor product states in general. Of these, we choose one example (classical superposition states) to introduce recent developments on a novel quantum many body approach: quantum kinetic Ising models. We conclude with a brief outlook of the field.Comment: Lectures from the Les Houches School on "Modern theories of correlated electron systems". Improved version new references adde

    The Retrohoming of Linear Group II Intron RNAs in Drosophila melanogaster Occurs by Both DNA Ligase 4–Dependent and –Independent Mechanisms

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    Mobile group II introns are bacterial retrotransposons that are thought to have invaded early eukaryotes and evolved into introns and retroelements in higher organisms. In bacteria, group II introns typically retrohome via full reverse splicing of an excised intron lariat RNA into a DNA site, where it is reverse transcribed by the intron-encoded protein. Recently, we showed that linear group II intron RNAs, which can result from hydrolytic splicing or debranching of lariat RNAs, can retrohome in eukaryotes by performing only the first step of reverse splicing, ligating their 3′ end to the downstream DNA exon. Reverse transcription then yields an intron cDNA, whose free end is linked to the upstream DNA exon by an error-prone process that yields junctions similar to those formed by non-homologous end joining (NHEJ). Here, by using Drosophila melanogaster NHEJ mutants, we show that linear intron RNA retrohoming occurs by major Lig4-dependent and minor Lig4-independent mechanisms, which appear to be related to classical and alternate NHEJ, respectively. The DNA repair polymerase θ plays a crucial role in both pathways. Surprisingly, however, mutations in Ku70, which functions in capping chromosome ends during NHEJ, have only moderate, possibly indirect effects, suggesting that both Lig4 and the alternate end-joining ligase act in some retrohoming events independently of Ku. Another potential Lig4-independent mechanism, reverse transcriptase template switching from the intron RNA to the upstream exon DNA, occurs in vitro, but gives junctions differing from the majority in vivo. Our results show that group II introns can utilize cellular NHEJ enzymes for retromobility in higher organisms, possibly exploiting mechanisms that contribute to retrotransposition and mitigate DNA damage by resident retrotransposons. Additionally, our results reveal novel activities of group II intron reverse transcriptases, with implications for retrohoming mechanisms and potential biotechnological applications

    Knowledge-Driven Analysis Identifies a Gene–Gene Interaction Affecting High-Density Lipoprotein Cholesterol Levels in Multi-Ethnic Populations

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    Total cholesterol, low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C) levels are among the most important risk factors for coronary artery disease. We tested for gene–gene interactions affecting the level of these four lipids based on prior knowledge of established genome-wide association study (GWAS) hits, protein–protein interactions, and pathway information. Using genotype data from 9,713 European Americans from the Atherosclerosis Risk in Communities (ARIC) study, we identified an interaction between HMGCR and a locus near LIPC in their effect on HDL-C levels (Bonferroni corrected Pc = 0.002). Using an adaptive locus-based validation procedure, we successfully validated this gene–gene interaction in the European American cohorts from the Framingham Heart Study (Pc = 0.002) and the Multi-Ethnic Study of Atherosclerosis (MESA; Pc = 0.006). The interaction between these two loci is also significant in the African American sample from ARIC (Pc = 0.004) and in the Hispanic American sample from MESA (Pc = 0.04). Both HMGCR and LIPC are involved in the metabolism of lipids, and genome-wide association studies have previously identified LIPC as associated with levels of HDL-C. However, the effect on HDL-C of the novel gene–gene interaction reported here is twice as pronounced as that predicted by the sum of the marginal effects of the two loci. In conclusion, based on a knowledge-driven analysis of epistasis, together with a new locus-based validation method, we successfully identified and validated an interaction affecting a complex trait in multi-ethnic populations

    How is the New Public Management applied in the occupational health care system? - decision-makers' and OH personnel's views in Finland

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    <p>Abstract</p> <p>Background</p> <p>In many countries occupational health care system is in change. Occupational health studies are mainly focused on occupational health substance and content. This study offers new perspectives on municipal OHS and its operations from management perspective.</p> <p>Aim</p> <p>The aim of this study is to analyse how New Public Management (NPM) doctrines are applied in the Finnish occupational health care system (OHS). The main focus is to describe and compare the views of decision-makers' and OH workers within the framework of NPM.</p> <p>Methods</p> <p>The data were collected by semi-structured interviews from 17 municipal decision-makers' and 26 municipal OH workers. Data was analyzed by examining coded data in a theory-driven way according to Hood's doctrine of NPM.</p> <p>Results</p> <p>The doctrines were not as compatible with the OH personnel view as with the decision-makers' view. Decision-makers and OH personnel highlighted the strict criteria required for operation evaluation. Moreover, decision-makers strongly accentuated professional management in the public sector and the reorganization of public sector units. These were not equally relevant in OH personnel views. In OH personnel views, other doctrines (more attention to performance and accomplishments, emphasizing and augmentation of the competition and better control of public expense and means test) were not similarly in evidence, only weak evidence was observed when their importance viewed as medium by decision-makers. Neither of the respondents group kept the doctrine of management models of the private sector relevant.</p> <p>Conclusions</p> <p>The NPM and Hoods doctrine fitted well with OH research. The doctrine brought out view differences and similarities between decision-makers and OH personnel. For example, policymakers highlighted more strongly the structural change by emphasizing professional management compared to OH personnel. The need for reorganization of municipal OH, regardless of different operational preconditions, was obvious for both decision-makers and OH personnel. The adaptation of more clarify management to a municipal context is not trouble-free. The municipality systemic structure, complex operational environment, and reconciliation of political and officer authority set challenges to management of municipalities.</p

    Interaction of Pyrrolobenzodiazepine (PBD) Ligands with Parallel Intermolecular G-Quadruplex Complex Using Spectroscopy and ESI-MS

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    Studies on ligand interaction with quadruplex DNA, and their role in stabilizing the complex at concentration prevailing under physiological condition, has attained high interest. Electrospray ionization mass spectrometry (ESI-MS) and spectroscopic studies in solution were used to evaluate the interaction of PBD and TMPyP4 ligands, stoichiometry and selectivity to G-quadruplex DNA. Two synthetic ligands from PBD family, namely pyrene-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrid (PBD1), mixed imine-amide pyrrolobenzodiazepine dimer (PBD2) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) were studied. G-rich single-stranded oligonucleotide d(5′GGGGTTGGGG3′) designated as d(T2G8), from the telomeric region of Tetrahymena Glaucoma, was considered for the interaction with ligands. ESI-MS and spectroscopic methods viz., circular dichroism (CD), UV-Visible, and fluorescence were employed to investigate the G-quadruplex structures formed by d(T2G8) sequence and its interaction with PBD and TMPyP4 ligands. From ESI-MS spectra, it is evident that the majority of quadruplexes exist as d(T2G8)2 and d(T2G8)4 forms possessing two to ten cations in the centre, thereby stabilizing the complex. CD band of PBD1 and PBD2 showed hypo and hyperchromicity, on interaction with quadruplex DNA, indicating unfolding and stabilization of quadruplex DNA complex, respectively. UV-Visible and fluorescence experiments suggest that PBD1 bind externally where as PBD2 intercalate moderately and bind externally to G-quadruplex DNA. Further, melting experiments using SYBR Green indicate that PBD1 unfolds and PBD2 stabilizes the G-quadruplex complex. ITC experiments using d(T2G8) quadruplex with PBD ligands reveal that PBD1 and PBD2 prefer external/loop binding and external/intercalative binding to quadruplex DNA, respectively. From experimental results it is clear that the interaction of PBD2 and TMPyP4 impart higher stability to the quadruplex complex

    Prospective Monitoring Reveals Dynamic Levels of T Cell Immunity to Mycobacterium Tuberculosis in HIV Infected Individuals

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    Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3–21 months. 62% of RD1-Elispot negative individuals were positive by cultured Elispot. Fluctuations in T cell response were observed with rates of change ranging from −150 to +153 spot-forming cells (SFC)/200,000 PBMC in a 3-month period. To validate these responses we used an RD1-specific real time quantitative PCR assay for monokine-induced by IFN-γ (MIG) and IFN-γ inducible protein-10 (IP10) (MIG: r = 0.6527, p = 0.0114; IP-10: r = 0.6967, p = 0.0056; IP-10+MIG: r = 0.7055, p = 0.0048). During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB. Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB. The RD1-Elispot appears to have limited value in this setting
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