106 research outputs found

    Epidemiology, clinical features, aetiology and course of acute infectious diarrhoea in infants

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    Forage systems for goat production in South Africa.

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    Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.Goats are found in almost every country and are an important source of protein and produce lactose-free milk. In South Africa, survival rates of goat kids are low, mainly due to malnutrition. Intensive goat production systems based on cultivated pastures were evaluated, at various stocking rates to evaluate the effects of improved nutrition on goat production. The pastures chosen to be evaluated for goat production were Pennisetum clandestinum (Kikuyu) and Secale cereale (Stooling rye). Kikuyu is one of the more important dryland summer pasture species in KwaZulu-Natal. Three stocking rates of goats on kikuyu were evaluated using ewes with kids. When analysing the period to weaning, the ewes lost weight in all stocking rate treatments and for both years. The years had a significant effect on weight loss (P<0.001; R²=95.7%) with a mean ADG of -0.0267 kg.animalˉ¹.dayˉ¹. There was a significant difference between ADGs between stocking rates, with ADGs of -0.0157, -0.026 and -0.0384 kg.animalˉ¹.dayˉ¹ at stocking rates of 30, 45 and 60 goats.haˉ¹ respectively (P<0.001; R²=95.7%). The analyses of the entire grazing period showed no significant difference in ewe ADGs between treatments, but a significant difference between the two years (P=0.03), with a mean ADG of -0.0205 kg.animalֿ¹.dayֿ¹. There was no significant difference between kid masses between treatments. There was a significant difference between kid performance between years (P<0.001; R²=21.8%). However, factors such as ewe start mass (P<0.001) and whether the kid was a singleton or a multiple (P=0.015) had an influence on kid ADG, while gender had no significant effect (P=0.446). Interpretation of the combined ewe plus kid weight revealed that the high stocking rate produced the highest total mass per hectare (P<0.001) with an overall mean of 2377 kg.haˉ¹. Kid ADG was positively correlated to ewe ADG (P=0.013; R²=5.8%) although this was not a strong relationship. Protein was negatively correlated to pasture height (P=0.036; R²=30.8%) and had a quadratic relationship with ADG (P<0.001; R²=48.4%) with maximum ADG occurring at protein levels of 26.17%. Rainfall was different between the two seasons, which affected pasture growth, with the stocking rates in the second year being too low, so the maximum stocking rate per hectare was not reached. Stooling rye is a pasture used predominantly in South Africa and is a good source of high quality winter feed. Four stocking rates were evaluated over winter, using pregnant ewes. Rainfall was not an important variable since supplementary irrigation was given and the difference in temperatures between the years was negligible. The rate of weight gain showed a similar response for both years with the level of weight gain varying significantly between years (P=0.001; R²=90.2%). The regressions for ADG on stocking rate were determined and were y=0.2340-0.00293x for 2001 (P=0.151; R²=58.0%) and y=0.1292-0.002198x for 2002 (P=0.137; R²=61.6%). Gain per hectare was determined, as were the stocking rates at which maximum gain per hectare were achieved and this was determined to be 40 goats.haֿ¹ during 2001 and 29 goats.haֿ¹ for 2002. The respective ADGs at these stocking rates were 0.1168 and 0.0633 kg.dayֿ¹ and daily gains.haֿ¹ were 4.672 and 1.898 kg.haֿ¹.dayֿ¹ respectively. Herbage analyses revealed that there were extremely high levels of protein in the pasture (33.87%) even though the pasture was not excessively fertilised. Average daily gain was negatively related to NDF levels (P=0.006; R²=38.4%). ADF levels (P<0.001; R²=48.4%) and NDF levels (P<0.001; R²=60.4%) showed a quadratic relationship with pasture age. Blood serum revealed that selenium levels in all treatments were lower than the normal range, while all other minerals were within the normal range. To maximise animal performance, the highest quality pasture should be offered to producing animals, namely growing animals. The seasonal variation between years has a large effect on the performance of goats on pastures

    Interactive Mixed-media Virtual Environment Prototyping

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    This paper details a tool for designing and simulating virtual environments in two dimensions. The system consists of computer controlled agents projected onto a whiteboard. Markings (which can be altered dynamically) on the whiteboard represent the obstructions (walls). A camera captures new images of the whiteboard constantly. The image is then processed by the image-processing component to determine where the walls are and this information is fed into the artificial intelligence component so that the agents move about realistically and do not move through walls. Natural movement throughout the environment is successfully implemented via a robust collision detection system as well as bounded path finding techniques. The AI system is efficient enough to allow for relatively large agent numbers, as well as operation at acceptable frame rate. The image processing first transforms the input images so that the projected area forms a rectangle. The image is then segmented by dividing the image into regions and calculating a threshold for each region based on an offset from the mean

    Computational validation of clonal and subclonal copy number alterations from bulk tumor sequencing using CNAqc

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    Copy number alterations (CNAs) are among the most important genetic events in cancer, but their detection from sequencing data is challenging because of unknown sample purity, tumor ploidy, and general intra-tumor heterogeneity. Here, we present CNAqc, an evolution-inspired method to perform the computational validation of clonal and subclonal CNAs detected from bulk DNA sequencing. CNAqc is validated using single-cell data and simulations, is applied to over 4000 TCGA and PCAWG samples, and is incorporated into the validation process for the clinically accredited bioinformatics pipeline at Genomics England. CNAqc is designed to support automated quality control procedures for tumor somatic data validation

    Factor VIII cross-matches to the human proteome reduce the predicted inhibitor risk in missense mutation hemophilia A.

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    Single missense mutations in the F8 gene encoding the coagulation protein factor VIII (FVIII) give rise predominantly to non-severe hemophilia A. Despite only a single amino acid sequence difference between the replacement, therapeutic FVIII (tFVIII) and the patient's endogenous FVIII, tFVIII may still be perceived as foreign by the recipient's immune system and trigger an immune response (inhibitor). Inhibitor formation is a life-long risk for non-severe hemophilia A patients treated with tFVIII, but remains difficult to predict. The aim of this study was to understand whether fortuitous, primary sequence cross-matches between tFVIII and proteins in the human proteome are the reason why certain F8 mutations are not associated with inhibitor formation. We predicted which tFVIII differences are potentially perceived as foreign by helper T cells a necessary precursor to inhibitor development and then scanned potentially immunogenic peptides against more than 100,000 proteins in the proteome. As there are hundreds of disease-causing F8 missense mutations and the Human Leucocyte Antigen gene complex governing peptide presentation to helper T cells is highly polymorphic, these calculations pose a huge combinatorial challenge that we addressed computationally. We identify that cross-matches between tFVIII and the human proteome are commonplace and have a profound impact on the predicted risk of inhibitor development. Our results emphasize the importance of knowing both the F8 missense mutation and the Human Leucocyte Antigen alleles of a patient with missense mutation hemophilia A if his underlying risk of inhibitor development is to be estimated

    Decision-making and referral processes for patients with motor neurone disease: a qualitative study of GP experiences and evaluation of a new decision-support tool

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    Background The diagnosis of motor neurone disease (MND) is known to be challenging and there may be delay in patients receiving a correct diagnosis. This study investigated the referral process for patients who had been diagnosed with MND, and whether a newly-developed tool (The Red Flags checklist) might help General Practitioners (GPs) in making referral decisions. Methods We carried out interviews with GPs who had recently referred a patient diagnosed with MND, and interviews/surveys with GPs who had not recently referred a patient with suspected MND. We collected data before the Red Flags checklist was introduced; and again one year later. We analysed the data to identify key recurring themes. Results Forty two GPs took part in the study. The presence of fasciculation was the clinical feature that most commonly led to consideration of a potential MND diagnosis. GPs perceived that their role was to make onward referrals rather than attempting to make a diagnosis, and delays in correct diagnosis tended to occur at the specialist level. A quarter of participants had some awareness of the newly-developed tool; most considered it useful, if incorporated into existing systems. Conclusions While fasciculation is the most common symptom associated with MND, other bulbar, limb or respiratory features, together with progression should be considered. There is a need for further research into how decision-support tools should be designed and provided, in order to best assist GPs with referral decisions. There is also a need for further work at the level of secondary care, in order that referrals made are re-directed appropriately

    Aflatoxin Contamination in Food and Body Fluids in Relation to Malnutrition and Cancer Status in Cameroon

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    Aflatoxins are food contaminants usually associated with hepatitis, immunodepression, impairment of fertility and cancer. The present work was to determine the presence of aflatoxins in eggs, milk, urine, and blood samples that were collected from various sources and periods; and hepatitis B virus antigen in blood samples. Aflatoxin was found in eggs (45.2%), cow raw milk (15.9%), breast milk (4.8%), urine from kwashiorkor and marasmic kwashiorkor children (45.5%), and sera from primary liver cancer patients (63.9%); HbsAg was also detected in 69.4% of the serum samples, but there was no association between both factors. Both AF and hepatitis B virus seem to be risk factors that could increase the incidence and prevalence rates of malnutrition and cancer in Cameroon

    The co-evolution of the genome and epigenome in colorectal cancer.

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    Colorectal malignancies are a leading cause of cancer-related death1 and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4-7. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,370 samples from 30 primary cancers and 8 concomitant adenomas and generated 1,207 chromatin accessibility profiles, 527 whole genomes and 297 whole transcriptomes. We found positive selection for DNA mutations in chromatin modifier genes and recurrent somatic chromatin accessibility alterations, including in regulatory regions of cancer driver genes that were otherwise devoid of genetic mutations. Genome-wide alterations in accessibility for transcription factor binding involved CTCF, downregulation of interferon and increased accessibility for SOX and HOX transcription factor families, suggesting the involvement of developmental genes during tumourigenesis. Somatic chromatin accessibility alterations were heritable and distinguished adenomas from cancers. Mutational signature analysis showed that the epigenome in turn influences the accumulation of DNA mutations. This study provides a map of genetic and epigenetic tumour heterogeneity, with fundamental implications for understanding colorectal cancer biology
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