380 research outputs found

    How well do structured abstracts reflect the articles they summerize?

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    Background: evidence-based medicine requires critical appraisal of published research. This is often done by reading the abstracts alone of published papers. This study examined how well structured abstracts reflect the articles they summarize in medical journals.Methods: a total of 20 papers reporting original randomized trials were obtained from four general medical journals. Key study details, results, and conclusions were extracted from the full articles. Abstracts were examined to see what information from the article was included, and they were scrutinized for inaccuracies, data not presented in the main body, and ambiguous statements.Results: nineteen abstracts (95%; 95% CI 75 to 100%) correctly stated the primary outcome. Eight abstracts (40%; 19% to 64%) were deficient in some way. Three (15%; 3% to 38%) contained incorrect or inconsistent figures or data. Six abstracts (30%; 12% to 54%) contained data not present in the full article.Discussion: almost half of the abstracts studied contained some data inconsistent with the full article, or missing altogether. Authors and editors need to ensure that abstracts are of a high quality and accurately reflect the papers they are summarizing. CONSORT guidelines provide helpful indications as to what should be included in abstracts reporting clinical trial

    Infection Parameters in the Sand Fly Vector That Predict Transmission of Leishmania major

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    To identify parameters of Leishmania infection within a population of infected sand flies that reliably predict subsequent transmission to the mammalian host, we sampled groups of infected flies and compared infection intensity and degree of metacyclogenesis with the frequency of transmission. The percentage of parasites within the midgut that were metacyclic promastigotes had the highest correlation with the frequency of transmission. Meta-analysis of multiple transmission experiments allowed us to establish a percent-metacyclic “cutoff” value that predicted transmission competence. Sand fly infections initiated with variable doses of parasites resulted in correspondingly altered percentages of metacyclic promastigotes, resulting in altered transmission frequency and disease severity. Lastly, alteration of sand fly oviposition status and environmental conditions at the time of transmission also influenced transmission frequency. These observations have implications for transmission of Leishmania by the sand fly vector in both the laboratory and in nature, including how the number of organisms acquired by the sand fly from an infection reservoir may influence the clinical outcome of infection following transmission by bite

    Theoretical Risk of Genetic Reassortment Should Not Impede Development of Live, Attenuated Rift Valley Fever (RVF) Vaccines Commentary on the Draft WHO RVF Target Product Profile

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    In November 2019, The World Health Organization (WHO) issued a draft set of Target Product Profiles (TPPs) describing optimal and minimally acceptable targets for vaccines against Rift Valley fever (RVF), a Phlebovirus with a three segmented genome, in both humans and ruminants. The TPPs contained rigid requirements to protect against genomic reassortment of live, attenuated vaccines (LAVs) with wild-type RVF virus (RVFV), which place undue constraints on development and regulatory approval of LAVs. We review the current LAVs in use and in development, and conclude that there is no evidence that reassortment between LAVs and wild-type RVFV has occurred during field use, that such a reassortment event if it occurred would have no untoward consequence, and that the TPPs should be revised to provide a more balanced assessment of the benefits versus the theoretical risks of reassortment

    Modeling biomedical experimental processes with OBI

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    BACKGROUND: Experimental descriptions are typically stored as free text without using standardized terminology, creating challenges in comparison, reproduction and analysis. These difficulties impose limitations on data exchange and information retrieval. RESULTS: The Ontology for Biomedical Investigations (OBI), developed as a global, cross-community effort, provides a resource that represents biomedical investigations in an explicit and integrative framework. Here we detail three real-world applications of OBI, provide detailed modeling information and explain how to use OBI. CONCLUSION: We demonstrate how OBI can be applied to different biomedical investigations to both facilitate interpretation of the experimental process and increase the computational processing and integration within the Semantic Web. The logical definitions of the entities involved allow computers to unambiguously understand and integrate different biological experimental processes and their relevant components. AVAILABILITY: OBI is available at http://purl.obolibrary.org/obo/obi/2009-11-02/obi.ow

    Gene content evolution in the arthropods

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    Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

    The age, origin and emplacement of the Tsiknias Ophiolite, Tinos, Greece

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    The Tsiknias Ophiolite, exposed at the highest structural levels of Tinos, Greece, represents a thrust sheet of Tethyan oceanic crust and upper mantle emplaced onto the Attic‐Cycladic Massif. We present new field observations and a new geological map of Tinos, integrated with petrology, THERMOCALC phase diagram modelling, U–Pb geochronology and whole rock geochemistry, resulting in a tectono‐thermal model that describes the formation and emplacement of the Tsiknias Ophiolite and newly identified underlying metamorphic sole. The ophiolite comprises a succession of partially dismembered and structurally repeated ultramafic and gabbroic rocks that represent the Moho Transition Zone. A plagiogranite dated by U‐Pb zircon at 161.9 ± 2.8 Ma, reveals that the Tsiknias Ophiolite formed in a supra‐subduction zone setting, comparable to the “East‐Vardar Ophiolites”, and was intruded by gabbros at 144.4 ± 5.6 Ma. Strongly sheared metamorphic sole rocks show a condensed and inverted metamorphic gradient, from partially anatectic amphibolites at P–T conditions of ca. 8.5 kbar 850‐600 °C, down‐structural section to greenschist‐facies oceanic metasediments over ~250 m. Leucosomes generated by partial melting of the uppermost sole amphibolite, yielded a U–Pb zircon protolith age of ca. 190 Ma and a high‐grade metamorphic‐anatectic age of 74.0 ± 3.5 Ma associated with ophiolite emplacement. The Tsiknias Ophiolite was therefore obducted ~90 Myrs after it formed during initiation of a NE‐dipping intra‐oceanic subduction zone to the northeast of the Cyclades that coincides with Africa's plate motion changing from transcurrent to convergent. Continued subduction resulted in high‐pressure metamorphism of the Cycladic continental margin ~25 Myrs later

    KSAC, a Defined Leishmania Antigen, plus Adjuvant Protects against the Virulence of L. major Transmitted by Its Natural Vector Phlebotomus duboscqi

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    Leishmaniasis is a neglected disease caused by the Leishmania parasite and transmitted by the bite of an infective sand fly. Despite the importance of this disease there is no vaccine available for humans. Studies have shown that vector-transmitted infections are more virulent, promoting parasite establishment and abrogating protection observed against needle-injected parasites in vaccinated mice. KSAC and L110f, derived from Leishmania-based polyproteins, protected mice against the needle-injected parasites. Here, we tested the two molecules for their capacity to protect mice against cutaneous leishmaniasis transmitted by an infective sand fly. Our results show that KSAC, but not L110f, confers protection against Leishmania transmitted by sand fly bites where protection was correlated to a strong immune response to Leishmania antigens by memory T cells before and after sand fly transmission of the parasite. This is the first report of a Leishmania-based vaccine that confers protection against a virulent sand fly challenge. Our results support the importance of screening Leishmania vaccine candidates using infective sand flies before moving forward with the costly steps of vaccine development

    The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16

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    Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently results in renal fallure due to progressive cyst development. The major locus, PKD1, maps to 16p13.3. We identified a chromosome translocation associated with ADPKD that disrupts a gene (PBP) encoding a 14 kb transcript in the PKD1 candidate region. Further mutations of the PBP gene were found in PKD1 patients, two deletions (one a de novo event) and a splicing defect, confirming that PBP is the PKD1 gene. This gene is located adjacent to the TSC2 locus in a genomic region that is reiterated more proximally on 16p. The duplicate area encodes three transcripts substantially homologous to the PKD1 transcript. Partial sequence analysis of the PKD1 transcript shows that it encodes a novel protein whose function is at present unknown

    Vector Transmission of Leishmania Abrogates Vaccine-Induced Protective Immunity

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    Numerous experimental vaccines have been developed to protect against the cutaneous and visceral forms of leishmaniasis caused by infection with the obligate intracellular protozoan Leishmania, but a human vaccine still does not exist. Remarkably, the efficacy of anti-Leishmania vaccines has never been fully evaluated under experimental conditions following natural vector transmission by infected sand fly bite. The only immunization strategy known to protect humans against natural exposure is “leishmanization,” in which viable L. major parasites are intentionally inoculated into a selected site in the skin. We employed mice with healed L. major infections to mimic leishmanization, and found tissue-seeking, cytokine-producing CD4+ T cells specific for Leishmania at the site of challenge by infected sand fly bite within 24 hours, and these mice were highly resistant to sand fly transmitted infection. In contrast, mice vaccinated with a killed vaccine comprised of autoclaved L. major antigen (ALM)+CpG oligodeoxynucleotides that protected against needle inoculation of parasites, showed delayed expression of protective immunity and failed to protect against infected sand fly challenge. Two-photon intra-vital microscopy and flow cytometric analysis revealed that sand fly, but not needle challenge, resulted in the maintenance of a localized neutrophilic response at the inoculation site, and removal of neutrophils following vector transmission led to increased parasite-specific immune responses and promoted the efficacy of the killed vaccine. These observations identify the critical immunological factors influencing vaccine efficacy following natural transmission of Leishmania
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