A Unifying Model of Genome Evolution Under Parsimony

We present a data structure called a history graph that offers a practical basis for the analysis of genome evolution. It conceptually simplifies the study of parsimonious evolutionary histories by representing both substitutions and double cut and join (DCJ) rearrangements in the presence of duplications. The problem of constructing parsimonious history graphs thus subsumes related maximum parsimony problems in the fields of phylogenetic reconstruction and genome rearrangement. We show that tractable functions can be used to define upper and lower bounds on the minimum number of substitutions and DCJ rearrangements needed to explain any history graph. These bounds become tight for a special type of unambiguous history graph called an ancestral variation graph (AVG), which constrains in its combinatorial structure the number of operations required. We finally demonstrate that for a given history graph $G$, a finite set of AVGs describe all parsimonious interpretations of $G$, and this set can be explored with a few sampling moves.Comment: 52 pages, 24 figure

Quantification of human C1 esterase inhibitor protein using an automated turbidimetric immunoassay

BACKGROUND: Impaired levels or function of C1 inhibitor (C1-INH) results in angioedema due to increased bradykinin. It is important to distinguish between angioedema related to C1-INH deficiency and that caused by other mechanisms, as treatment options are different. In hereditary (HAE) and acquired (AAE) angioedema, C1-INH concentration is measured to aid patient diagnosis. Here, we describe an automated turbidimetric assay to measure C1-INH concentration on the Optilite® analyzer. METHODS: Linearity, precision, and interference were established over a range of C1-INH concentrations. The 95th percentile reference interval was generated from 120 healthy adult donors. To compare the Optilite C1-INH assay with a predicate assay used in a clinical laboratory, samples sent for C1-INH investigation were used. The predicate results were provided to allow comparison. RESULTS: The Optilite C1-INH assay was linear across the measuring range at the standard sample dilution. Intra and interassay variability was <6%. The 95th percentile adult reference interval for the assay was 0.21-0.38 g/L. There was a strong correlation between the Optilite concentrations and those generated with the predicate assay (R2 = 0.94, P < 0.0001, slope y = 0.83x). All patients with Type I HAE (n = 24) and AAE (n = 3) tested had concentrations below the measuring range in both assays, while all patients with unspecified angioedema (UAE), not diagnosed with HAE or AAE had values within the reference range. CONCLUSION: The Optilite assay allows the automated and precise quantification of C1-INH concentrations in patient samples. It could therefore be used as a tool to aid the investigation of patients with angioedema

A major root architecture QTL responding to water limitation in durum wheat

The optimal root system architecture (RSA) of a crop is context dependent and critical for efficient resource capture in the soil. Narrow root growth angle promoting deeper root growth is often associated with improved access to water and nutrients in deep soils during terminal drought. RSA, therefore is a drought-adaptive trait that could minimize yield losses in regions with limited rainfall. Here, GWAS for seminal root angle (SRA) identified seven marker-trait associations clustered on chromosome 6A, representing a major quantitative trait locus (qSRA-6A) which also displayed high levels of pairwise LD (r2 = 0.67). Subsequent haplotype analysis revealed significant differences between major groups. Candidate gene analysis revealed loci related to gravitropism, polar growth and hormonal signaling. No differences were observed for root biomass between lines carrying hap1 and hap2 for qSRA-6A, highlighting the opportunity to perform marker-assisted selection for the qSRA-6A locus and directly select for wide or narrow RSA, without influencing root biomass. Our study revealed that the genetic predisposition for deep rooting was best expressed under water-limitation, yet the root system displayed plasticity producing root growth in response to water availability in upper soil layers. We discuss the potential to deploy root architectural traits in cultivars to enhance yield stability in environments that experience limited rainfall

The role of the alloy structure in the magnetic behavior of granular systems

The effect of grain size, easy magnetization axis and anisotropy constant distributions in the irreversible magnetic behavior of granular alloys is considered. A simulated granular alloy is used to provide a realistic grain structure for the Monte Carlo simulation of the ZFC-FC curves. The effect of annealing and external field is also studied. The simulation curves are in good agreement with the FC and ZFC magnetization curves measured on melt spun Cu-Co ribbons.Comment: 13 pages, 10 figures, submitted to PR

Interventions for preventing oral mucositis for patients with cancer receiving treatment

Interventions for preventing oral mucositis for patients with cancer receiving treatmentTreatment for cancer (including bone marrow transplant) can cause oral mucositis (severe ulcers in the mouth). This painful condition can cause difficulties in eating, drinking and swallowing, and may also be associated with infections which may require the patient to stay longer in hospital. Different strategies are used to try and prevent this condition, and the review of trials found that some of these are effective. Two interventions, cryotherapy (ice chips) and keratinocyte growth factor (palifermin®) showed some benefit in preventing mucositis. Sucralfate is effective in reducing the severity of mucositis, and a further seven interventions, aloe vera, amifostine, intravenous glutamine, granulocyte‐colony stimulating factor (G‐CSF), honey, laser and antibiotic lozenges containing polymixin/tobramycin/amphotericin (PTA) showed weaker evidence of benefit. These were evaluated in patients with different types of cancer, undergoing different types of cancer treatment. Benefits may be restricted to the disease and treatment combinations evaluated

Relocating civil society in a politics of civic-driven change

Politics is central to development discourse, yet remains peripheral. Over some twenty years, a civil-society narrative has not fulfilled its potential to 'bring politics back in'. Reasons can be found in conceptual confusion, in selectivity in donor thinking, in policies towards civil society and in the growth-driven political economy of NGO-ism. Remedies for the political lacunae are being sought through a focus on rights, citizenship and leadership that show valuable focused progress. This article examines a comprehensive complement to such efforts referred to as civic-driven change (CDC). Originating in a grounded empirical approach, the constituent principles and elements of CDC offer a lens that can both sharpen and deepen insights and advance analysis of socio-political processes. © The Authors 2013. Development Policy Revie

Genomic prediction in CIMMYT maize and wheat breeding programs

Genomic selection (GS) has been implemented in animal and plant species, and is regarded as a useful tool for accelerating genetic gains. Varying levels of genomic prediction accuracy have been obtained in plants, depending on the prediction problem assessed and on several other factors, such as trait heritability, the relationship between the individuals to be predicted and those used to train the models for prediction, number of markers, sample size and genotype × environment interaction (GE). The main objective of this article is to describe the results of genomic prediction in International Maize and Wheat Improvement Center's (CIMMYT's) maize and wheat breeding programs, from the initial assessment of the predictive ability of different models using pedigree and marker information to the present, when methods for implementing GS in practical global maize and wheat breeding programs are being studied and investigated. Results show that pedigree (population structure) accounts for a sizeable proportion of the prediction accuracy when a global population is the prediction problem to be assessed. However, when the prediction uses unrelated populations to train the prediction equations, prediction accuracy becomes negligible. When genomic prediction includes modeling GE, an increase in prediction accuracy can be achieved by borrowing information from correlated environments. Several questions on how to incorporate GS into CIMMYT's maize and wheat programs remain unanswered and subject to further investigation, for example, prediction within and between related bi-parental crosses. Further research on the quantification of breeding value components for GS in plant breeding populations is required.J Crossa, P Pérez, J Hickey, J Burgueño, L Ornella, J Cerón-Rojas, X Zhang, S Dreisigacker, R Babu, Y Li, D Bonnett and K Mathew

Methods for selecting the best evidence to inform a NICE technology appraisal on selective internal radiation therapies for hepatocellular carcinoma

Background: Systematic reviews of medical devices are particularly challenging as the quality of evidence tends to be more limited than evidence on pharmaceutical products. This article describes the methods used to identify, select and critically appraise the best available evidence on selective internal radiation therapy devices for treating hepatocellular carcinoma, to inform a technology appraisal for the National Institute for Health and Care Excellence. Methods: A comprehensive search of ten medical databases and six grey literature sources was undertaken to identify studies of three devices (TheraSphere®, SIR-Spheres® and QuiremSpheres®) for treating hepatocellular carcinoma. The large evidence base was scoped before deciding what level of evidence to include for data extraction and critical appraisal. The methodological quality of the included studies was assessed using criteria relevant to each study design. Results: Electronic searches identified 4755 records; over 1000 met eligibility criteria after screening titles and abstracts. A hierarchical process was used to scope these records, prioritising comparative studies over non-comparative studies, where available. 194 full papers were ordered; 64 met the eligibility criteria. For each intervention, studies were prioritised by study design and applicability to current UK practice, resulting in 20 studies subjected to critical appraisal and data extraction. Only two trials had a low overall risk of bias. In view of the poor quality of the research evidence, our technology appraisal focused on the two higher quality trials, including a thorough critique of their reliability and generalisability to current UK practice. The 18 poorer quality studies were briefly summarised; many were very small and results were often contradictory. No definitive conclusions could be drawn from the poorer quality research evidence available. Conclusions: A systematic, pragmatic process was used to select and critically appraise the vast quantity of research evidence available in order to present the most reliable evidence on which to develop recommendations

A major root architecture QTL responding to water limitation in durum wheat

The optimal root system architecture (RSA) of a crop is context dependent and critical for efficient resource capture in the soil. Narrow root growth angle promoting deeper root growth is often associated with improved access to water and nutrients in deep soils during terminal drought. RSA, therefore is a drought-adaptive trait that could minimize yield losses in regions with limited rainfall. Here, GWAS for seminal root angle (SRA) identified seven marker-trait associations clustered on chromosome 6A, representing a major quantitative trait locus (qSRA-6A) which also displayed high levels of pairwise LD (r 2 = 0.67). Subsequent haplotype analysis revealed significant differences between major groups. Candidate gene analysis revealed loci related to gravitropism, polar growth and hormonal signaling. No differences were observed for root biomass between lines carrying hap1 and hap2 for qSRA-6A, highlighting the opportunity to perform marker-assisted selection for the qSRA-6A locus and directly select for wide or narrow RSA, without influencing root biomass. Our study revealed that the genetic predisposition for deep rooting was best expressed under water-limitation, yet the root system displayed plasticity producing root growth in response to water availability in upper soil layers. We discuss the potential to deploy root architectural traits in cultivars to enhance yield stability in environments that experience limited rainfall.Samir Alahmad, Khaoula El Hassouni, Filippo M. Bassi, Eric Dinglasan, Chvan Youssef, Georgia Quarry, Alpaslan Aksoy, Elisabetta Mazzucotelli, Angéla Juhász, Jason A. Able, Jack Christopher, Kai P. Voss-Fels and Lee T. Hicke