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Biomedical subjects

David J Hill

Publications and source records attributed to David J Hill.

At least 19 recordsLinked to original sources

Cancer control policy in Australia.

Australia has an evolving national cancer control agenda. In this paper, we review the history and development of cancer control policies in Australia up to the end of 2005, and discuss the principal publications produced by both government and non-government groups which have given rise to cancer control recommendations, goals and targets. These cancer control plans have arisen in response to the impact of cancer on the Australian community and in recognition of the health gains that can be made through effective cancer control. They have been developed either in the context of a broader framework of health policy or as specific endeavours in regard to cancer. The specific recommendations and strategies proposed have focused on reducing the impact of cancer in the Australian population. Most commonly, recommendations, goals, and targets within the cancer control plans have addressed points along the continuum of care, specific cancers, and frameworks and processes. The strength of these reports is their comprehensive approach in identifying priority cancers and areas where specific developments should impact on morbidity and mortality. In the future, cancer control plans should be better supported by economic evaluations, and greater financial support for implementation and regular assessment is needed to identify progress on cancer outcomes. The more recent national and State cancer control plans include the development of frameworks to foster a coordinated and cohesive approach to the delivery of cancer care. These plans represent important reforms in cancer care in Australia, and have the potential to reduce the impact of cancer on the community and improve health outcomes.

Journal Article↗

4. Food allergy in childhood.

Food allergies in children present with a wide spectrum of clinical manifestations, including anaphylaxis, urticaria, angioedema, atopic dermatitis and gastrointestinal symptoms (such as vomiting, diarrhoea and failure to thrive). Symptoms usually begin in the first 2 years of life, often after the first known exposure to the food. Immediate reactions (occurring between several minutes and 2 hours after ingestion) are likely to be IgE-mediated and can usually be detected by skin prick testing (SPT) or measuring food-specific serum IgE antibody levels. Over 90% of IgE-mediated food allergies in childhood are caused by eight foods: cows milk, hens egg, soy, peanuts, tree nuts (and seeds), wheat, fish and shellfish. Anaphylaxis is a severe and potentially life-threatening form of IgE-mediated food allergy that requires prescription of self-injectable adrenaline. Delayed-onset reactions (occurring within several hours to days after ingestion) are often difficult to diagnose. They are usually SPT negative, and elimination or challenge protocols are required to make a definitive diagnosis. These forms of food allergy are not usually associated with anaphylaxis. The mainstay of diagnosis and management of food allergies is correct identification and avoidance of the offending antigen. Children often develop tolerance to cows milk, egg, soy and wheat by school age, whereas allergies to nuts and shellfish are more likely to be lifelong.

Breast Feeding↗

Neutral additives enhance the metal-chelate affinity adsorption of nucleic acids: role of water activity.

Immobilized metal-chelate affinity chromatography has been widely used in the purification of proteins, and we have recently found that it can also be applied to purification of nucleic acids through interactions involving exposed bases, especially purines. Here we report that the inclusion of moderate quantities of neutral solutes in the buffer substantially enhances the binding affinity of nucleic acids for immobilized metal-chelate affinity adsorbents. Addition of 20% (v/v) of solutes such as ethanol, methanol, isopropanol, n-propanol, and dimethyl sulfoxide enhances the initial affinity of binding of total yeast RNA by 4.4-, 3.8-, 3.7-, 3.0-, and 2.8-fold, respectively for Cu(II)-iminodiacetic acid (IDA) agarose adsorbent, and the weaker adsorption by Cu(II)-nitrilotriacetic acid (NTA) agarose was even more strongly enhanced. The adsorption affinities of the smaller oligodeoxynucleotide molecules A20, G20, C20 and T20 also increase with the addition of ethanol, suggesting that the effect is not significantly mediated by conformational changes. Binding enhancement generally correlates with reduction of water activity by the various solutes, as predicted by several models of solution thermodynamics, consistent with an entropic contribution by displacement of waters from the metal-chelate. Interestingly, the enhancement was not seen with the proteins bovine serum albumin and lysozyme.

Adsorption↗

Atopic disease and breast-feeding--cause or consequence?

BACKGROUND: A number of studies have observed an association between breast-feeding and increased risk of development of asthma and eczema. It has been proposed that these results might be due to early signs of atopic disease in the infant causing mothers to prolong breast-feeding. OBJECTIVE: We sought to determine whether early symptoms of atopic disease (eczema, food reaction, or asthma) or positive skin prick test responses reduce the likelihood of ceasing breast-feeding. METHODS: A prospective birth cohort of 620 infants from Melbourne, Australia, was used. Telephone interviews every 4 weeks were conducted until 64 weeks and then again at 78 and 104 weeks to determine duration of breast-feeding (both exclusive and total) and evidence of atopic disease. Because of the varying time of onset of atopic symptoms, they were modeled as time-varying covariates in Cox models. RESULTS: Only 52 (8.4%) infants did not establish breast-feeding, whereas an additional 103 (25.0%) did not establish exclusive breast-feeding. Early signs of atopic disease or sensitization were independently associated with an approximately 28% reduction in risk of ceasing exclusive breast-feeding (adjusted hazard ratio, 0.72; 95% CI, 0.53-0.97); P=.029), but there was no evidence for a relationship with risk of ceasing breast-feeding completely (adjusted hazard ratio, 1.12; 95% CI, 0.92-1.37; P=.262). CONCLUSION: Early signs of atopic disease might prolong the duration of exclusive breast-feeding. This could mask a protective effect of breast-feeding or even result in breast-feeding appearing to be a risk factor for the development of atopic diseases. Future investigation of the relationship between breast-feeding and atopic diseases should consider this possibility.

Adult↗

The diagnosis and management of egg allergy.

Egg allergy is a common food hypersensitivity in children. Atopic dermatitis represents the main clinical manifestation in infancy. On first exposure, many of these infants present with urticaria, angioedema, or anaphylaxis. The role of egg allergy in gastrointestinal conditions is less well understood. The "gold standard" for the diagnosis of egg allergy is the double-blind, placebo-controlled food challenge. Diagnostic cut-off levels have been defined for food-specific serum immunoglobulin E antibody level and skin prick test wheal diameter that predict an adverse challenge outcome. This has significantly reduced the need for formal food challenges. Atopy patch testing, in conjunction with immunoglobulin E-based tests, may further improve the accuracy of predicting a positive challenge. The treatment of egg allergy consists of dietary elimination, or a maternal elimination diet in breast-fed infants. Approximately two thirds of infants with egg allergy will become tolerant by 7 years of age.

Allergens↗

Learning from neural control.

One of the amazing successes of biological systems is their ability to "learn by doing" and so adapt to their environment. In this paper, first, a deterministic learning mechanism is presented, by which an appropriately designed adaptive neural controller is capable of learning closed-loop system dynamics during tracking control to a periodic reference orbit. Among various neural network (NN) architectures, the localized radial basis function (RBF) network is employed. A property of persistence of excitation (PE) for RBF networks is established, and a partial PE condition of closed-loop signals, i.e., the PE condition of a regression subvector constructed out of the RBFs along a periodic state trajectory, is proven to be satisfied. Accurate NN approximation for closed-loop system dynamics is achieved in a local region along the periodic state trajectory, and a learning ability is implemented during a closed-loop feedback control process. Second, based on the deterministic learning mechanism, a neural learning control scheme is proposed which can effectively recall and reuse the learned knowledge to achieve closed-loop stability and improved control performance. The significance of this paper is that the presented deterministic learning mechanism and the neural learning control scheme provide elementary components toward the development of a biologically-plausible learning and control methodology. Simulation studies are included to demonstrate the effectiveness of the approach.

Algorithms↗

Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific.

Restriction of dietary protein during gestation and lactation in the rat results in a reduction in beta cell mass, insulin content and release in the offspring, and glucose intolerance when the offspring reach adulthood. The present study was designed to identify if a particular developmental window existed during prenatal development when endocrine pancreatic development was most susceptible to nutritional insult. Pregnant rats received a low-protein (8%, LP), but isocalorific diet from conception to parturition, during the first 2 weeks of gestation (LP (1-2)), the second week only (LP (2)), or the third week (LP (3)). At other times, they received a 20% protein (C) diet, while control animals received this diet continuously. When the offspring were examined at 130 days age, animals that had received LP diet had a significantly impaired glucose tolerance compared with control-fed animals. Pancreatic morphology was examined in the offspring on postnatal days 1 and 21. The LP diet resulted in a significant decrease in the numbers of large (more than 10 000 microm(2)) and medium (between 5000 and 10 000 microm(2)) sized islets present at postnatal day 1 for all LP treatments. Consequently, mean islet area and the mean number of beta cells were reduced. The impact of LP diet was most pronounced in LP (2) for females and in LP (3) for males, and this was greater than for continuous LP exposure. Insulin and Glut-2 mRNA expression were impacted negatively by LP in early and late gestation, but increased following administration in mid-gestation. Total pancreatic insulin content was not altered by LP treatment. Pdx-1, a transcription factor associated with both beta cell development and insulin gene transcription, was decreased in female offspring following LP (1-2) and LP (3), but not in males. Pancreatic expression of nestin mRNA, and the abundance of nestin-immunoreactive cells within islets, was decreased by all LP treatments. By postnatal day 21, the mean islet area and number of beta cells had largely recovered. However, insulin and Glut-2 mRNAs were elevated in offspring exposed to LP diet, particularly in females. The studies show that LP dietary insult in early, middle, or late gestation, all result in a relative deficiency of beta cells following birth, due to a failure to develop larger islets, but that females were particularly susceptible in mid-gestation and males in late gestation.

Animal Nutritional Physiological Phenomena↗

Maternal hyperinsulinemia predisposes rat fetuses for hyperinsulinemia, and adult-onset obesity and maternal mild food restriction reverses this phenotype.

We have previously shown that artificial rearing of newborn female rat pups on a high-carbohydrate (HC) milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype) and that the maternal HC phenotype was transmitted to their progeny (2-HC rats) because of fetal development in the HC female rat. The aims of this study were to investigate 1) the fetal adaptations that predisposed the progeny for the expression of the HC phenotype in adulthood and 2) whether the transfer of the HC phenotype to the progeny could be reversed by maternal food restriction. Fetal parameters such as plasma insulin and glucose levels, mRNA level of preproinsulin gene, pancreatic insulin content, and islet insulin secretory response in vitro were determined. On gestational day 21, 2-HC fetuses were hyperinsulinemic, had increased insulin content and mRNA level of the preproinsulin gene in their pancreata and demonstrated an altered glucose-stimulated insulin secretory response by isolated islets. Modification of the intrauterine environment in HC female rats was achieved by pair feeding them to the amount of diet consumed by age-matched control rats from the time of their weaning. This mild dietary restriction reversed their HC phenotype and also prevented the development of the HC phenotype in their progeny. These findings show that mal-programming of the progeny of the hyperinsulinemic-obese HC female for the expression of the HC phenotype is initiated in utero and that normalization of the maternal environment in HC female rats by mild food restriction resulted in the normal phenotype in their progeny.

Animals↗

The US national isotope program: current status and strategy for future success.

Since their introduction in the 1940s, peaceful use of stable isotopes and radioisotopes in the United States has expanded continuously. Today, new isotopes for diagnostic and therapeutic uses are not being developed, critical isotopes for national security are in short supply, and demand for isotopes critical to homeland security exceeds supply. While commercial suppliers, both domestic and foreign, can only meet specific needs, the nation needs a consistent, reliable supply of radioactive and stable isotopes for research, medical, security, and space power applications. The national isotope infrastructure, defined as both facilities and trained staff at national laboratories and universities, is in danger of being lost due to chronic underfunding. With the specific recommendations given herein, the US Department of Energy may realign and refocus its Isotope Program to provide a framework for a successful National Isotope Program.

Government Agencies↗

Women's satisfaction with their breast prosthesis: what determines a quality prosthesis?

The aim of this study is to determine what factors constitute a quality prosthesis and ascertain which factors affect prosthesis satisfaction. Sixty-four women who received full funding for their prosthesis and 38 women who received their hospital's usual funding were recruited. Women rated the information provided about breast prostheses very highly, with 85% reporting that it was "very good" or "excellent." Satisfaction was significantly associated with how well the prosthesis fit (1 week, p = .001; 3 months, p = .01), level of comfort (3 months, p=.005), and appearance of the prosthesis when worn (6 months, p = .001). Quality was significantly associated with how well it fit (1 week, p = .001; 3 months, p = .001), how natural it felt (1 week, p = .001; 6 months, p = .01), the weight of the prosthesis (3 months, p = .003), and appearance when worn (6 months, p = .03). The results will be used to improve women's access to a quality prosthesis.

Adult↗

Effect of a low-allergen maternal diet on colic among breastfed infants: a randomized, controlled trial.

BACKGROUND: There is controversy regarding whether hypersensitivity to food proteins contributes to colic among breastfed infants. METHODS: A randomized, controlled trial of a low-allergen maternal diet was conducted among exclusively breastfed infants presenting with colic. In the active arm, mothers excluded cow's milk, eggs, peanuts, tree nuts, wheat, soy, and fish from their diet; mothers in the control group continued to consume these foods. Outcomes were assessed after 7 days, as the change in cry/fuss duration over 48 hours, with validated charts. The primary end point was a reduction in cry/fuss duration of > or =25% from baseline. Mothers also assessed the responses to diet with categorical and visual analog scales. RESULTS: Of 107 infants, 90 completed the trial (mean age: 5.7 weeks; range: 2.9-8.6 weeks; 54 male infants). Infants in both groups presented with significant distress (geometric mean: low-allergen group: 690 minutes per 48 hours; control group: 631 minutes per 48 hours). In follow-up assessments on days 8 and 9, there were significantly more responders in the low-allergen group (74% vs 37%), ie, an absolute risk reduction of 37% (95% confidence interval: 18-56%). Cry/fuss duration per 48 hours was reduced by a substantially greater amount in the low-allergen group; the adjusted geometric mean ratio was 0.79 (95% confidence interval: 0.63-0.97), ie, an average reduction of 21% (95% confidence interval: 3-37%). Mothers' subjective assessments of the responses to diet indicated little difference between the groups. CONCLUSION: Exclusion of allergenic foods from the maternal diet was associated with a reduction in distressed behavior among breastfed infants with colic presenting in the first 6 weeks of life.

Allergens↗

Adipose tissue gene expression profiling reveals distinct molecular pathways that define visceral adiposity in offspring of maternal protein-restricted rats.

There is increasing evidence that poor early growth confers an increased risk of type 2 diabetes, hypertension, and other features of the metabolic syndrome in later life. We hypothesized that this may result from poor nutrition during early life exerting permanent effects on the structure and function of key metabolic organ systems. To study the long-term impact of early-life undernutrition on susceptibility to visceral adiposity, we used a rat model of maternal protein restriction (MPR) in which dams were fed a low-protein diet (containing 8% instead of 20% protein in control diet) throughout pregnancy and lactation. MPR offspring were born smaller than controls (offspring of dams on control diet) and in adulthood developed visceral adiposity. We compared the pattern of gene expression in visceral adipose tissue (VAT) between MPR offspring and controls with Affymetrix rat expression arrays. Of the total number of genes and expressed sequence tags analyzed (15,923 probe sets), 9,790 (61.5%) were expressed in VAT. We identified 650 transcripts as differentially expressed > or =1.5-fold in the VAT of MPR offspring. Gene ontology analysis revealed a global upregulation of genes involved in carbohydrate, lipid, and protein metabolism. A number of genes involved in adipocyte differentiation, angiogenesis, and extracellular matrix remodeling were also upregulated. However, in marked contrast to other rodent models of obesity, the expression of a large number of genes associated with inflammation was reduced in this rat model. Thus visceral adiposity in this early-life programmed rat model is marked by dynamic changes in the transcriptional profile of VAT. Our data provide new insights into the molecular mechanisms that underlie the early-life programming of visceral adiposity.

Adipose Tissue↗

Single-site modifications and their effect on the folding stability of m-phenylene ethynylene oligomers.

[reaction: see text] The folded structure of a m-phenylene ethynylene oligomer is tolerant to single-site modifications to both the backbone sequence and end groups. The helical structure is reinforced by multiple noncovalent interactions, allowing the oligomer sequence to be customized without a significant change in stability in most cases. The small changes that are observed are consistent with the expected behavior of pi-stacked systems and demonstrate subtle control over folding through single-site modifications.

Journal Article↗

The diagnostic value of skin prick testing in children with food allergy.

The diagnostic accuracy of the skin prick test (SPT) in food allergy is controversial. We have developed diagnostic cut-off levels for SPT in children with allergy to cow milk, egg and peanut. Based on 555 open food challenges in 467 children (median age 3.0 yr) we defined food-specific SPT weal diameters that were '100% diagnostic' for allergy to cow milk (>or=8 mm), egg (>or=7 mm) and peanut (>or=8 mm). In children < 2 yr of age, the corresponding weal diameters were >or=6 mm, >or=5 mm and >or=4 mm, respectively. These SPT cut-off levels were prospectively validated in 90 consecutive children <or=2 yr with challenge-proven food allergy. In young infants under 6 months of age who have not previously been exposed to a particular food item, the SPT were often negative or below the diagnostic cut-off but reached the diagnostic cut-off at the time of challenge in the second year of life. We assessed the diagnostic agreement between food-specific immunoglobulin E (IgE) antibody levels and SPT in a cohort of 820 infants and children under 2 yr of age (median age 13.1 months) with suspected allergy to cow milk, egg or peanut. When applying published 95%-positive predictive CAP values, the diagnostic accuracy of SPT and IgE antibody levels was similar for cow milk, but SPT was more sensitive in diagnosing allergy to egg (p < 0.0001) and peanut (p < 0.0001). Further studies are required to define age-specific diagnostic IgE antibody and SPT cut-off levels use in infants under 2 yr of age with suspected food allergies.

Age Factors↗