285 research outputs found

    Holographic Anomalous Conductivities and the Chiral Magnetic Effect

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    We calculate anomaly induced conductivities from a holographic gauge theory model using Kubo formulas, making a clear conceptual distinction between thermodynamic state variables such as chemical potentials and external background fields. This allows us to pinpoint ambiguities in previous holographic calculations of the chiral magnetic conductivity. We also calculate the corresponding anomalous current three-point functions in special kinematic regimes. We compare the holographic results to weak coupling calculations using both dimensional regularization and cutoff regularization. In order to reproduce the weak coupling results it is necessary to allow for singular holographic gauge field configurations when a chiral chemical potential is introduced for a chiral charge defined through a gauge invariant but non-conserved chiral density. We argue that this is appropriate for actually addressing charge separation due to the chiral magnetic effect.Comment: 17 pages, 1 figure. v2: 18 pages, 1 figure, discussion clarified throughout the text, references added, version accepted for publication in JHE

    Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

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    Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

    Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

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    We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

    Hierarchy Theory of Evolution and the Extended Evolutionary Synthesis: Some Epistemic Bridges, Some Conceptual Rifts

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    Contemporary evolutionary biology comprises a plural landscape of multiple co-existent conceptual frameworks and strenuous voices that disagree on the nature and scope of evolutionary theory. Since the mid-eighties, some of these conceptual frameworks have denounced the ontologies of the Modern Synthesis and of the updated Standard Theory of Evolution as unfinished or even flawed. In this paper, we analyze and compare two of those conceptual frameworks, namely Niles Eldredge’s Hierarchy Theory of Evolution (with its extended ontology of evolutionary entities) and the Extended Evolutionary Synthesis (with its proposal of an extended ontology of evolutionary processes), in an attempt to map some epistemic bridges (e.g. compatible views of causation; niche construction) and some conceptual rifts (e.g. extra-genetic inheritance; different perspectives on macroevolution; contrasting standpoints held in the “externalism–internalism” debate) that exist between them. This paper seeks to encourage theoretical, philosophical and historiographical discussions about pluralism or the possible unification of contemporary evolutionary biology

    Knowledge, perceived stigma, and care-seeking experiences for sexually transmitted infections: a qualitative study from the perspective of public clinic attendees in Rio de Janeiro, Brazil

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    BACKGROUND: An estimated 12 million sexually transmitted infections (STIs) are documented in Brazil per year. Given the scope of this public health challenge and the importance of prompt treatment and follow-up counseling to reduce future STI/HIV-related risk behavior, we sought to qualitatively explore STI clinic experiences among individuals diagnosed with STIs via public clinics in Rio de Janeiro, Brazil. The study focused on eliciting the perspective of clinic users with regard to those factors influencing their STI care-seeking decisions and the health education and counseling which they received during their clinic visit. METHODS: Thirty semi-structured interviews were conducted with heterosexual men and women and men who have sex with men presenting with STIs at two public clinics. Content analysis was conducted by coding transcripts of audio-taped interviews for key domains of interest and comparing and synthesizing code output across participants and sub-groups. Thematic narratives were then developed per each of the study sub-groups. RESULTS: Salient themes that emerged from participant narratives included the importance of low STI-related knowledge and high perceived stigma, both STI-related and other types of social stigma, on STI care-seeking delays. However, there are indications in the data that the level of STI-related knowledge and the amount and types of stigma experienced vary across the study sub-groups suggesting the need for further research on the significance and program relevance of these potential differences. Interview findings also suggest that such barriers to care seeking are not adequately addressed through ongoing health education and counseling efforts at public STI clinics and in turn critical opportunities for STI/HIV prevention are currently being missed. CONCLUSION: Information, communication and education regarding early recognition and prompt care-seeking for STIs should be developed, with consideration given to the possibility of tailoring messages tailored to specific sub-groups. To promote prompt treatment-seeking, interventions must also address both STI-specific and other forms of social stigma which may limit access to care. Efforts to further assess and respond to barriers related to the delivery of quality health education and counseling within the context of public STI clinics are also needed

    Deterministic and stochastic P systems for modelling cellular processes

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    This paper presents two approaches based on metabolic and stochastic P systems, together with their associated analysis methods, for modelling biological sys- tems and illustrates their use through two case studies.Kingdom's Engineering and Physical Sciences Research Council EP/ E017215/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/D019613/1Biotechnology and Biological Sciences Research Council/United Kingdom BB/F01855X/

    Follow-up study on lead exposure in children living in a smelter community in northern Mexico

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    <p>Abstract</p> <p>Background</p> <p>To study the changes of children lead exposure in the city of Torreon during the last five years, after environmental and public health interventions, using the timeline of lead in blood concentration as the biomarker of exposure and its relation to lead in soil concentrations.</p> <p>Methods</p> <p>This follow-up study started in 2001 and consisted of 232 children living in nine neighborhoods in Torreon. Children were tested at 0, 6, 12 and 60 months. Lead in blood concentrations, Hemoglobin, Zinc-Protoporphyrin, anthropometric measures and socioeconomic status questionnaire was supplied to the parents.</p> <p>Results</p> <p>Median and range of lead in blood concentrations obtained at 0, 6, 12, 60 months were: 10.12 μg/dl (1.9 - 43.8), 8.75 μg/dl (1.85 - 41.45), 8.4 μg/dl (1.7 - 35.8) and 4.4 μg/dl (1.3 - 30.3), respectively. The decrease of lead in blood levels was significantly related to ages 0, 6, 12 and 60 months of the follow-up study. The timeline of B-Pb was associated with the timeline of lead in soil concentrations.</p> <p>Conclusions</p> <p>B-Pb levels have significantly decreased in the group of children studied. This could be explained by a) environmental interventions by authorities and the smelter companies, b) normal changes in hygienic habits as children age and c) lead redistribution from blood to hard tissues.</p

    The EG95 Antigen of Echinococcus spp. Contains Positively Selected Amino Acids, which May Influence Host Specificity and Vaccine Efficacy

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    Echinococcosis is a worldwide zoonotic parasitic disease of humans and various herbivorous domestic animals (intermediate hosts) transmitted by the contact with wild and domestic carnivores (definitive hosts), mainly foxes and dogs. Recently, a vaccine was developed showing high levels of protection against one parasite haplotype (G1) of Echinococcus granulosus, and its potential efficacy against distinct parasite variants or species is still unclear. Interestingly, the EG95 vaccine antigen is a secreted glycosylphosphatydilinositol (GPI)-anchored protein containing a fibronectin type III domain, which is ubiquitous in modular proteins involved in cell adhesion. EG95 is highly expressed in oncospheres, the parasite life cycle stage which actively invades the intermediate hosts. After amplifying and sequencing the complete CDS of 57 Echinococcus isolates belonging to 7 distinct species, we uncovered a large amount of genetic variability, which may influence protein folding. Two positively selected sites are outside the vaccine epitopes, but are predicted to alter protein conformation. Moreover, phylogenetic analyses indicate that EG95 isoform evolution is convergent with regard to the number of beta-sheets and alpha-helices. We conclude that having a variety of EG95 isoforms is adaptive for Echinococcus parasites, in terms of their ability to invade different hosts, and we propose that a mixture of isoforms could possibly maximize vaccine efficacy

    Prognostic factors in left-sided endocarditis: results from the andalusian multicenter cohort

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    <p>Abstract</p> <p>Background</p> <p>Despite medical advances, mortality in infective endocarditis (IE) is still very high. Previous studies on prognosis in IE have observed conflicting results. The aim of this study was to identify predictors of in-hospital mortality in a large multicenter cohort of left-sided IE.</p> <p>Methods</p> <p>An observational multicenter study was conducted from January 1984 to December 2006 in seven hospitals in Andalusia, Spain. Seven hundred and five left-side IE patients were included. The main outcome measure was in-hospital mortality. Several prognostic factors were analysed by univariate tests and then by multilogistic regression model.</p> <p>Results</p> <p>The overall mortality was 29.5% (25.5% from 1984 to 1995 and 31.9% from 1996 to 2006; Odds Ratio 1.25; 95% Confidence Interval: 0.97-1.60; p = 0.07). In univariate analysis, age, comorbidity, especially chronic liver disease, prosthetic valve, virulent microorganism such as <it>Staphylococcus aureus</it>, <it>Streptococcus agalactiae </it>and fungi, and complications (septic shock, severe heart failure, renal insufficiency, neurologic manifestations and perivalvular extension) were related with higher mortality. Independent factors for mortality in multivariate analysis were: Charlson comorbidity score (OR: 1.2; 95% CI: 1.1-1.3), prosthetic endocarditis (OR: 1.9; CI: 1.2-3.1), <it>Staphylococcus aureus </it>aetiology (OR: 2.1; CI: 1.3-3.5), severe heart failure (OR: 5.4; CI: 3.3-8.8), neurologic manifestations (OR: 1.9; CI: 1.2-2.9), septic shock (OR: 4.2; CI: 2.3-7.7), perivalvular extension (OR: 2.4; CI: 1.3-4.5) and acute renal failure (OR: 1.69; CI: 1.0-2.6). Conversely, <it>Streptococcus viridans </it>group etiology (OR: 0.4; CI: 0.2-0.7) and surgical treatment (OR: 0.5; CI: 0.3-0.8) were protective factors.</p> <p>Conclusions</p> <p>Several characteristics of left-sided endocarditis enable selection of a patient group at higher risk of mortality. This group may benefit from more specialised attention in referral centers and should help to identify those patients who might benefit from more aggressive diagnostic and/or therapeutic procedures.</p

    Alloxan-Induced Diabetes Triggers the Development of Periodontal Disease in Rats

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    BACKGROUND: Periodontal disease in diabetic patients presents higher severity and prevalence; and increased severity of ligature-induced periodontal disease has been verified in diabetic rats. However, in absence of aggressive stimuli such as ligatures, the influence of diabetes on rat periodontal tissues is incompletely explored. The aim of this study was to evaluate the establishment and progression of periodontal diseases in rats only with diabetes induction. METHODOLOGY/PRINCIPAL FINDINGS: Diabetes was induced in Wistar rats (n = 25) by intravenous administration of alloxan (42 mg/kg) and were analyzed at 1, 3, 6, 9 and 12 months after diabetes induction. The hemimandibles were removed and submitted to radiographical and histopathological procedures. A significant reduction was observed in height of bone crest in diabetic animals at 3, 6, 9 and 12 months, which was associated with increased numbers of osteoclasts and inflammatory cells. The histopathological analyses of diabetic rats also showed a reduction in density of collagen fibers, fibroblasts and blood vessels. Severe caries were also detected in the diabetic group. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that diabetes induction triggers, or even co-induces the onset of alterations which are typical of periodontal diseases even in the absence of aggressive factors such as ligatures. Therefore, diabetes induction renders a previously resistant host into a susceptible phenotype, and hence diabetes can be considered a very important risk factor to the development of periodontal disease
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