Genetic linkage mapping of economically important traits in cultivated tetraploid potato (<i>Solanum tuberosum</i> L.)

The objective of this study was to construct a single nucleotide polymorphism (SNP)-based genetic map at the cultivated tetraploid level to locate quantitative trait loci (QTL) contributing to economically important traits in potato (Solanum tuberosum L.). The 156 F(1) progeny and parents of a cross (MSL603) between “Jacqueline Lee” and “MSG227-2” were genotyped using the Infinium 8303 Potato Array. Furthermore, the progeny and parents were evaluated for foliar late blight reaction to isolates of the US-8 genotype of Phytophthora infestans (Mont.) de Bary and vine maturity. Linkage analyses and QTL mapping were performed using a novel approach that incorporates allele dosage information. The resulting genetic maps contained 1972 SNP markers with an average density of 1.36 marker per cM. QTL mapping identified the major source of late blight resistance in “Jacqueline Lee.” The best SNP marker mapped ∼0.54 Mb from a resistance hotspot on the long arm of chromosome 9. For vine maturity, the major-effect QTL was located on chromosome 5 with allelic effects from both parents. A candidate SNP marker for this trait mapped ∼0.25 Mb from the StCDF1 gene, which is a candidate gene for the maturity trait. The identification of markers for P. infestans resistance will enable the introgression of multiple sources of resistance through marker-assisted selection. Moreover, the discovery of a QTL for late blight resistance not linked to the QTL for vine maturity provides the opportunity to use marker-assisted selection for resistance independent of the selection for vine maturity classifications

Engineered Swine Models of Cancer

Over the past decade, the technology to engineer genetically modified swine has seen many advancements, and because their physiology is remarkably similar to that of humans, swine models of cancer may be extremely valuable for preclinical safety studies as well as toxicity testing of pharmaceuticals prior to the start of human clinical trials. Hence, the benefits of using swine as a large animal model in cancer research and the potential applications and future opportunities of utilizing pigs in cancer modeling are immense. In this review, we discuss how pigs have been and can be used as a biomedical models for cancer research, with an emphasis on current technologies. We have focused on applications of precision genetics that can provide models that mimic human cancer predisposition syndromes. In particular, we describe the advantages of targeted gene-editing using custom endonucleases, specifically TALENs and CRISPRs, and transposon systems, to make novel pig models of cancer with broad preclinical applications

Meningococcal disease in children in Merseyside, England:a 31 year descriptive study

Meningococcal disease (MCD) is the leading infectious cause of death in early childhood in the United Kingdom, making it a public health priority. MCD most commonly presents as meningococcal meningitis (MM), septicaemia (MS), or as a combination of the two syndromes (MM/MS). We describe the changing epidemiology and clinical presentation of MCD, and explore associations with socioeconomic status and other risk factors. A hospital-based study of children admitted to a tertiary children's centre, Alder Hey Children's Foundation Trust, with MCD, was undertaken between 1977 to 2007 (n = 1157). Demographics, clinical presentations, microbiological confirmation and measures of deprivation were described. The majority of cases occurred in the 1-4 year age group and there was a dramatic fall in serogroup C cases observed with the introduction of the meningococcal C conjugate (MCC) vaccine. The proportion of MS cases increased over the study period, from 11% in the first quarter to 35% in the final quarter. Presentation with MS (compared to MM) and serogroup C disease (compared to serogroup B) were demonstrated to be independent risk factors for mortality, with odds ratios of 3.5 (95% CI 1.18 to 10.08) and 2.18 (95% CI 1.26 to 3.80) respectively. Cases admitted to Alder Hey were from a relatively more deprived population (mean Townsend score 1.25, 95% CI 1.09 to 1.41) than the Merseyside reference population. Our findings represent one of the largest single-centre studies of MCD. The presentation of MS is confirmed to be a risk factor of mortality from MCD. Our study supports the association between social deprivation and MCD

Positive practices : solution-focused and narrative therapeutic techniques with children with sexually harmful behaviours

This article explores the use of solution-focused and Narrative Therapeutic approaches with a boy who had sexually harmful behaviours. The paper will highlight the practical challenges of working with someone who is 'problem-saturated' through institutionalisation and who is also subjected to powerful discourses claiming the 'truth' about him. The use of solution-focused and Narrative Therapeutic principles and approaches will be demonstrated in the work described, in a way that allows the reader to reflect on how these may differ from modernist understandings and responses to this behaviour

Factors affecting formulation and efficacy of a sheep ectoparasiticide

This research thesis, FACTORS AFFECTING FORMULATION AND EFFICACY OF A SHEEP ECTOPARASITICIDE used six experimental formulations containing a range of excipients and a novel ectoparasiticide, AHC-2013. The project was conducted at Yarrandoo R&D Centre, Novartis Animal Health Australasia Pty Limited (NAH), Kemps Creek, Australia. The project utilized resources and personnel approved by NAH management, e.g. animals, animal facilities, scientific analytical equipment and technical support. Three in vivo studies in sheep were conducted to investigate efficacy, drug migration in the fleece and around the body (from the site of deposition), and the scourability of an incorporated dye from the wool – each of these associated with potential production losses of meat from louse infestation or of wool from residues. The efficacy study found no formulation fully controlled the louse populations on the sheep for the 20 week period required for regulatory approval (Holdsworth et al., 2006). Despite this, several formulations displayed efficacy above 95%; these formulations, FD 0184-sol-31, FD 0184-sol-32, FD 0184-sol-33 should be the preferred formulations considered for optimization and evaluation at equivalent and higher doses. At the evaluated dose it was demonstrated that even at the application site with the highest chemical concentrations there were small residual populations of lice. Larger populations of lice were found as concentrations declined rapidly away from the application site along the backline. Mean louse counts within the control group were reduced by 31.8% 14 days after shearing, 52.2% 28 days from shearing and peaking at 52.5% on day 56 post-shearing. The decline in mean louse count started to stabilize by day 42 (51.5%) with further subtle declines up to day 56. This trend of population decline stopped at day 70 post-shearing when an increase in the mean louse population was observed. It is probable this reversal in trend was due to a resumption of the surviving parasite’s breeding cycle, and an increase in wool length and therefore the louse habitat coupled with a possible reduction and/or dilution of the overall chemical residues. Although the spray-on application method used in the evaluation of these formulations has many advantages to the end consumer it is not the only option available for application and alternatives such as higher volume spray-on and jetting solutions should also be considered in optimizing drug migration. The drug residue concentrations in wool were considerably higher on the backline close to application site (location A), as compared to the flank (locations B) and belly (location C). Although there was some variation of drug concentrations between groups for the same location and time points, there was a trend for the highest drug levels being closest to the application site and reducing significantly with distance from this area. Drug migration was found to be relatively poor with only one treatment group (FD 0184-sol-030) having drug movement over 1% (Concentration B/A*100) from location A to location B in a 42 day period. In all other groups the total concentration migration was less than 1%. Drug migration from location A to location C was less than 1% in all groups over 42 days however drug migration from location B to C varied markedly with migration of up to 63% (Concentration C/B*100; FD 0184-sol-032) down to 25% (FD 0184- sol-030). Although there was relatively good migration in concentration between the two locations, overall migration was poor given the relatively low levels of active being found at location B and C in relation to the drug concentrations found at the application area, i.e. location A. Residue depletion was slow (e.g. from days 28 to 42) so only limited conclusions can be drawn with regard to this parameter. Although a relatively slow drug residue depletion is desirable for persistent efficacy it could have potential environmental, and health and safety implications, which impact the Wool Harvesting Interval, Wool Rehandling Interval and potentially Export Slaughter Interval. Each parameter is assessed by the APVMA in the course of product registration. This low drug depletion rate should be a consideration in the design of future residue studies and particularly the timing of wool collections. Modelling of drug concentrations in wool and relative efficacy could assist in determining dose however, as seen in the efficacy and residue studies although there is a clear relationship between louse population and drug concentration in wool within treatment group and in comparison to the untreated controls. Yet the response effect was quite variable between treatment groups and would therefore be difficult to achieve without further in vivo evaluation; particularly extended residue depletion data beyond 42 days post-treatment. As drug concentration in wool data is only available for the first 42 days from treatment and the overall depletion is slow it is difficult to see an efficacy response over time to drug concentration within group. All formulations were found to be scourable to AS 4054 (Australian Standards, 2003) and therefore commercially viable. The colouring agent used was the same in all formulations. It could be assumed from the consistent scourability that the active ingredient and excipients used did not influence binding of the colouring agent to the wool fibre. This is an important consideration for commercial formulations and given this finding it would be prudent to use the same colouring agent in any future formulations

Factors affecting formulation and efficacy of a sheep ectoparasiticide

This research thesis, FACTORS AFFECTING FORMULATION AND EFFICACY OF A SHEEP ECTOPARASITICIDE used six experimental formulations containing a range of excipients and a novel ectoparasiticide, AHC-2013. The project was conducted at Yarrandoo R&D Centre, Novartis Animal Health Australasia Pty Limited (NAH), Kemps Creek, Australia. The project utilized resources and personnel approved by NAH management, e.g. animals, animal facilities, scientific analytical equipment and technical support. Three in vivo studies in sheep were conducted to investigate efficacy, drug migration in the fleece and around the body (from the site of deposition), and the scourability of an incorporated dye from the wool – each of these associated with potential production losses of meat from louse infestation or of wool from residues. The efficacy study found no formulation fully controlled the louse populations on the sheep for the 20 week period required for regulatory approval (Holdsworth et al., 2006). Despite this, several formulations displayed efficacy above 95%; these formulations, FD 0184-sol-31, FD 0184-sol-32, FD 0184-sol-33 should be the preferred formulations considered for optimization and evaluation at equivalent and higher doses. At the evaluated dose it was demonstrated that even at the application site with the highest chemical concentrations there were small residual populations of lice. Larger populations of lice were found as concentrations declined rapidly away from the application site along the backline. Mean louse counts within the control group were reduced by 31.8% 14 days after shearing, 52.2% 28 days from shearing and peaking at 52.5% on day 56 post-shearing. The decline in mean louse count started to stabilize by day 42 (51.5%) with further subtle declines up to day 56. This trend of population decline stopped at day 70 post-shearing when an increase in the mean louse population was observed. It is probable this reversal in trend was due to a resumption of the surviving parasite’s breeding cycle, and an increase in wool length and therefore the louse habitat coupled with a possible reduction and/or dilution of the overall chemical residues. Although the spray-on application method used in the evaluation of these formulations has many advantages to the end consumer it is not the only option available for application and alternatives such as higher volume spray-on and jetting solutions should also be considered in optimizing drug migration. The drug residue concentrations in wool were considerably higher on the backline close to application site (location A), as compared to the flank (locations B) and belly (location C). Although there was some variation of drug concentrations between groups for the same location and time points, there was a trend for the highest drug levels being closest to the application site and reducing significantly with distance from this area. Drug migration was found to be relatively poor with only one treatment group (FD 0184-sol-030) having drug movement over 1% (Concentration B/A*100) from location A to location B in a 42 day period. In all other groups the total concentration migration was less than 1%. Drug migration from location A to location C was less than 1% in all groups over 42 days however drug migration from location B to C varied markedly with migration of up to 63% (Concentration C/B*100; FD 0184-sol-032) down to 25% (FD 0184- sol-030). Although there was relatively good migration in concentration between the two locations, overall migration was poor given the relatively low levels of active being found at location B and C in relation to the drug concentrations found at the application area, i.e. location A. Residue depletion was slow (e.g. from days 28 to 42) so only limited conclusions can be drawn with regard to this parameter. Although a relatively slow drug residue depletion is desirable for persistent efficacy it could have potential environmental, and health and safety implications, which impact the Wool Harvesting Interval, Wool Rehandling Interval and potentially Export Slaughter Interval. Each parameter is assessed by the APVMA in the course of product registration. This low drug depletion rate should be a consideration in the design of future residue studies and particularly the timing of wool collections. Modelling of drug concentrations in wool and relative efficacy could assist in determining dose however, as seen in the efficacy and residue studies although there is a clear relationship between louse population and drug concentration in wool within treatment group and in comparison to the untreated controls. Yet the response effect was quite variable between treatment groups and would therefore be difficult to achieve without further in vivo evaluation; particularly extended residue depletion data beyond 42 days post-treatment. As drug concentration in wool data is only available for the first 42 days from treatment and the overall depletion is slow it is difficult to see an efficacy response over time to drug concentration within group. All formulations were found to be scourable to AS 4054 (Australian Standards, 2003) and therefore commercially viable. The colouring agent used was the same in all formulations. It could be assumed from the consistent scourability that the active ingredient and excipients used did not influence binding of the colouring agent to the wool fibre. This is an important consideration for commercial formulations and given this finding it would be prudent to use the same colouring agent in any future formulations

STAT2 deficiency and susceptibility to viral illness in humans

Severe infectious disease in children may be a manifestation of primary immunodeficiency. These genetic disorders represent important experiments of nature with the capacity to elucidate nonredundant mechanisms of human immunity. We hypothesized that a primary defect of innate antiviral immunity was responsible for unusually severe viral illness in two siblings; the proband developed disseminated vaccine strain measles following routine immunization, whereas an infant brother died after a 2-d febrile illness from an unknown viral infection. Patient fibroblasts were indeed abnormally permissive for viral replication in vitro, associated with profound failure of type I IFN signaling and absence of STAT2 protein. Sequencing of genomic DNA and RNA revealed a homozygous mutation in intron 4 of STAT2 that prevented correct splicing in patient cells. Subsequently, other family members were identified with the same genetic lesion. Despite documented infection by known viral pathogens, some of which have been more severe than normal, surviving STAT2-deficient individuals have remained generally healthy, with no obvious defects in their adaptive immunity or developmental abnormalities. These findings imply that type I IFN signaling [through interferon-stimulated gene factor 3 (ISGF3)] is surprisingly not essential for host defense against the majority of common childhood viral infections

Fetal testosterone and autistic traits

Studies of amniotic testosterone in humans suggest that fetal testosterone (fT) is related to specific (but not all) sexually dimorphic aspects of cognition and behaviour. It has also been suggested that autism may be an extreme manifestation of some male-typical traits, both in terms of cognition and neuroanatomy. In this paper, we examine the possibility of a link between autistic traits and fT levels measured in amniotic fluid during routine amniocentesis. Two instruments measuring number of autistic traits (the Childhood Autism Spectrum Test (CAST) and the Child Autism Spectrum Quotient (AQ-Child)) were completed by these women about their children (N = 235), ages 6-10 years. Intelligence Quotient (IQ) was measured in a subset of these children (N = 74). fT levels were positively associated with higher scores on the CAST and AQ-Child. This relationship was seen within sex as well as when the sexes were combined, suggesting this is an effect of fT rather than of sex per se. No relationships were found between overall IQ and the predictor variables, or between IQ and CAST or AQ-Child. These findings are consistent with the hypothesis that prenatal androgen exposure is related to children exhibiting more autistic traits. These results need to be followed up in a much larger sample to test if clinical cases of ASC have elevated fT.</p

Impact of volcanism on the sedimentary record of the Neuquén rift basin, Argentina: towards a cause and effect model

The analysis of volcano-sedimentary infill in sedimentary basins constitutes a challenge for basin analysis and hydrocarbon exploration worldwide. In order to understand the contribution of volcanism to the sedimentary record in rift basins, we study the Jurassic effusive-explosive volcanic infill of an inverted extensional depocentre at the Neuquén Basin, Argentina. A cause and effect model that evaluates the relationship between volcanism and sedimentation was devised to develop a conceptual model for the tectono-stratigraphic evolution of this volcanic rift basin. We show how the variations in the volcanism, coupled with the activity of extensional faults, determined the types of volcanic edifices (i.e., composite volcanoes, graben-calderas, and lava fields). Volcanic edifices controlled the stacking patterns of the volcanic units as well as sedimentary systems. The landform of the volcanic edifices, as well as the styles and scales of the eruptions governed the sedimentary input to the basin, setting the main variables of the sedimentary systems, such as provenance, grain size, transport and deposition and geometry. As a result, the contrasting volcaniclastic input, from higher volcaniclastic input to lower volcaniclastic input, associated with different subsidence patterns, determined the high-resolution syn-rift infill patterns of the extensional depocentre. The cause and effect model presented in this study isolates the variables of the volcanic environments that control the sedimentary scenarios. We suggest that, by adjusting the first order input parameters of the model, these cause and effect scenarios could be adapted to similar rift basins, in order to establish predictive facies models with stratigraphic controls, and the impact of volcanism on their stratigraphic records.Fil: D'Elia, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Martí, Joan. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias de la Tierra Jaume Almera; EspañaFil: Muravchik, Martin. University Of Bergen; Noruega. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bilmes, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Geología y Paleontología.; ArgentinaFil: Franzese, Juan Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; Argentin

Does a local financial incentive scheme reduce inequalities in the delivery of clinical care in a socially deprived community? A longitudinal data analysis.

BACKGROUND: Socioeconomic deprivation is associated with inequalities in health care and outcomes. Despite concerns that the Quality and Outcomes Framework pay-for-performance scheme in the UK would exacerbate inequalities in primary care delivery, gaps closed over time. Local schemes were promoted as a means of improving clinical engagement by addressing local health priorities. We evaluated equity in achievement of target indicators and practice income for one local scheme. METHODS: We undertook a longitudinal survey over four years of routinely recorded clinical data for all 83 primary care practices. Sixteen indicators were developed that covered five local clinical and public health priorities: weight management; alcohol consumption; learning disabilities; osteoporosis; and chlamydia screening. Clinical indicators were logit transformed from a percentage achievement scale and modelled allowing for clustering of repeated measures within practices. This enabled our study of target achievements over time with respect to deprivation. Practice income was also explored. RESULTS: Higher practice deprivation was associated with poorer performance for five indicators: alcohol use registration (OR 0.97; 95 % confidence interval 0.96,0.99); recorded chlamydia test result (OR 0.97; 0.94,0.99); osteoporosis registration (OR 0.98; 0.97,0.99); registration of repeat prednisolone prescription (OR 0.98; 0.96,0.99); and prednisolone registration with record of dual energy X-ray absorptiometry (DEXA) scan/referral (OR 0.92; 0.86,0.97); practices in deprived areas performed better for one indicator (registration of osteoporotic fragility fracture (OR 1.26; 1.04,1.51). The deprivation-achievement gap widened for one indicator (registered females aged 65-74 with a fracture referred for a DEXA scan; OR 0.97; 0.95,0.99). Two other indicators indicated a similar trend over two years before being withdrawn (registration of fragility fracture and over-75 s with a fragility fracture assessed and treated for osteoporosis risk). For one indicator the deprivation-achievement gap reduced over time (repeat prednisolone prescription (OR 1.01; 1.01,1.01). Larger practices and those serving more affluent areas earned more income per patient than smaller practices and those serving more deprived areas (t = -3.99; p =0.0001). CONCLUSIONS: Any gaps in achievement between practices were modest but mostly sustained or widened over the duration of the scheme. Given that financial rewards may not reflect the amount of work undertaken by practices serving more deprived patients, future pay-for-performance schemes also need to address fairness of rewards in relation to workload