3,118 research outputs found
Prenatal origin of childhood AML occurs less frequently than in childhood ALL
Background While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. Methods We analysed Guthrie cards of 12 ALL patients aged 2β6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1β14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1β3 positive cells were present in the neonatal blood spot. Results In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. Conclusion In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases
The Impact and Cost of Scaling up GeneXpert MTB/RIF in South Africa
We estimated the incremental cost and impact on diagnosis and treatment uptake of national rollout of Xpert MTB/RIF technology (Xpert) for the diagnosis of pulmonary TB above the cost of current guidelines for the years 2011 to 2016 in South Africa.We parameterised a population-level decision model with data from national-level TB databases (nβ=β199,511) and implementation studies. The model follows cohorts of TB suspects from diagnosis to treatment under current diagnostic guidelines or an algorithm that includes Xpert. Assumptions include the number of TB suspects, symptom prevalence of 5.5%, annual suspect growth rate of 10%, and 2010 public-sector salaries and drug and service delivery costs. Xpert test costs are based on data from an in-country pilot evaluation and assumptions about when global volumes allowing cartridge discounts will be reached.At full scale, Xpert will increase the number of TB cases diagnosed per year by 30%-37% and the number of MDR-TB cases diagnosed by 69%-71%. It will diagnose 81% of patients after the first visit, compared to 46% currently. The cost of TB diagnosis per suspect will increase by 55% to USD 60-61 and the cost of diagnosis and treatment per TB case treated by 8% to USD 797-873. The incremental capital cost of the Xpert scale-up will be USD 22 million and the incremental recurrent cost USD 287-316 million over six years.Xpert will increase both the number of TB cases diagnosed and treated and the cost of TB diagnosis. These results do not include savings due to reduced transmission of TB as a result of earlier diagnosis and treatment initiation
The Decline of University Patenting and the End of the Bayh-Dole Effect
University patenting has been heralded as a symbol of changing relations
between universities and their social environments. The Bayh-Dole Act of 1980
in the USA was eagerly promoted by the OECD as a recipe for the
commercialization of university research, and the law was imitated by a number
of national governments. However, since the 2000s university patenting in the
most advanced economies has been on the decline both as a percentage and in
absolute terms. We suggest that the institutional incentives for university
patenting have disappeared with the new regime of university ranking. Patents
and spin-offs are not counted in university rankings. In the new arrangements
of university-industry-government relations, universities have become very
responsive to changes in their relevant environments
Negative parental responses to coming out and family functioning in a sample of lesbian and gay young adults
Parental responses to youths' coming out (CO) are crucial to the subsequent adjustment of children and family. The present study investigated the negative parental reaction to the disclosure of same-sex attraction and the differences between maternal
and paternal responses, as reported by their homosexual daughters and sons. Participants' perceptions of their parents' reactions (evaluated through the Perceived Parental Reactions Scale, PPRS), age at coming out, gender, parental political
orientation, and religiosity involvement, the family functioning (assessed through the Family Adaptability and Cohesion Evaluation Scales, FACES IV), were assessed in 164 Italian gay and lesbian young adults. Pearson correlation coefficients were calculated to assess the relation between family functioning and parental reaction to CO. The paired sample t-test was used to compare mothers and fathers' scores on the PPRS. Hierarchical multiple regression was conducted to analyze the relevance of each variable. No differences were found between mothers and fathers in their reaction to the disclosure. The analysis showed that a negative reaction to coming out was predicted by parents' right-wing political conservatism, strong religious beliefs, and
higher scores in the scales Rigid and Enmeshed. Findings confirm that a negative parental reaction is the result of poor family resources to face a stressful situation and a strong belief in traditional values. These results have important implications in both clinical and social fields
Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.
Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity
Persistent Intersection Homology for the Analysis of Discrete Data
Topological data analysis is becoming increasingly relevant to support the
analysis of unstructured data sets. A common assumption in data analysis is
that the data set is a sample---not necessarily a uniform one---of some
high-dimensional manifold. In such cases, persistent homology can be
successfully employed to extract features, remove noise, and compare data sets.
The underlying problems in some application domains, however, turn out to
represent multiple manifolds with different dimensions. Algebraic topology
typically analyzes such problems using intersection homology, an extension of
homology that is capable of handling configurations with singularities. In this
paper, we describe how the persistent variant of intersection homology can be
used to assist data analysis in visualization. We point out potential pitfalls
in approximating data sets with singularities and give strategies for resolving
them.Comment: Topology-based Methods in Visualization 201
Antiepileptic drugsβ tolerability and safety β a systematic review and meta-analysis of adverse effects in dogs
<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016.Β </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /
Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle
Background
Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals.
Results
Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle.
Conclusions
This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought
The metagenomics RAST server β a public resource for the automatic phylogenetic and functional analysis of metagenomes
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