The expression of tumour suppressors and proto-oncogenes in tissues susceptible to their hereditary cancers.

BackgroundStudies of familial cancers have found that only a small subset of tissues are affected by inherited mutations in a given tumour suppressor gene (TSG) or proto-oncogene (POG), even though the mutation is present in all tissues. Previous tests have shown that tissue specificity is not due to the presence vs absence of gene expression, as TSGs and POGs are expressed in nearly every type of normal human tissue. Using published microarray expression data we tested the related hypothesis that tissue-specific expression of a TSG or POG is highest in tissue where it is of oncogenic importance.MethodsWe tested this hypothesis by examining whether individual TSGs and POGs had higher expression in the normal (noncancerous) tissues where they are implicated in familial cancers relative to those tissues where they are not. We examined data for 15 TSGs and 8 POGs implicated in familial cancer across 12 human tissue types.ResultsWe found a significant difference between expression levels in susceptible vs nonsusceptible tissues. It was found that 9 (60%, P<0.001) of the TSGs and 5 (63%, P<0.001) of the POGs had their highest expression level in the tissue type susceptible to their oncogenic effect.ConclusionsThis highly significant association supports the hypothesis that mutation of a specific TSG or POG is likely to be most oncogenic in the tissue where the gene has its highest level of expression. This suggests that high expression in normal tissues is a potential marker for linking cancer-related genes with their susceptible tissues

Hurlstone Park

Hurlstone Park, in the City of Canterbury, is part of the traditional land of the Wangal people. Hawkesbury sandstone outcrops form cliffs above Cooks River at the southern edge of the suburb, and two small creeks once ran down the hill from the Canterbury Road ridge, ending in wetlands along the river bank

Belmore

Belmore, in the City of Canterbury, is part of the traditional land of the Bediagal people. The area was once covered by a forest of Sydney blue gum, blackbutt, red mahogany and ironbark trees, growing on clay soils derived from Wianamatta shales. Water came from three small creeks, which flowed in a north-easterly direction into Cooks River.The earliest colonial surveyors followed an Aboriginal pathway (which became Punchbowl Road/Milperra Road) which led from Cooks River to Georges River. Before 1810, this pathway became a convenient access road from Sydney through Canterbury Farm, crossing Cooks River at the 'Punch Bowl' ford, and land grants were surveyed along the route. Once over the ford, travellers could turn south on a track, now Burwood Road at Belfield, and pass through country which is today's suburb of Belmore, south-east to King's Grove Farm and the land grants beyond. Canterbury Road was not formed as an access road into Sydney until after the 1830s, and it was not gazetted until 1856

An Improved Maize Marketing System For Zimbabwe

A research article

Temporal trend in the transfer of Sellafield-derived 14C into different size fractions of the carbonate component of NE Irish Sea sediment

From 1994 onwards, 14C discharges from the Sellafield nuclear fuel reprocessing plant have been made largely to the Northeast Irish Sea. They represent the largest contributor to UK and European populations of the collective dose commitment derived from the entire nuclear industry discharges. Consequently, it is important to understand the long-term fate of 14C in the marine environment. Research undertaken in 2000 suggested that the carbonate component of Northeast Irish Sea sediments would increase in 14C activity as mollusc shells, which have become enriched in Sellafield-derived 14C, are broken down by physical processes including wave action and incorporated into intertidal and sub-tidal sediments. The current study, undertaken in 2011, tested this hypothesis. The results demonstrate significant increases in 14C enrichments found in whole mussel shells compared to those measured in 2000. Additionally, in 2000, there was an enrichment above ambient background within only the largest size fraction (>500 μm) of the intertidal inorganic sediment at Nethertown and Flimby (north of Sellafield). In comparison, the present study has demonstrated 14C enrichments above ambient background in most size fractions at sites up to 40 km north of Sellafield, confirming the hypothesis set out more than a decade ago

A radiological study of the temporomandibular joint : factors affecting joint morphology

Thesis (Ph.D.) -- University of Adelaide, Dept. of Oral Pathology and Oral Surgery, 198

Photonic bandgap fiber with multiple hollow cores

We report the fabrication and characterization of the first photonic bandgap fiber with multiple hollow waveguiding cores. Perspectives for scaling to highly multicore designs are discussed

Phase II randomised, placebo-controlled, clinical trial of interleukin-1 receptor antagonist in intracerebral haemorrhage: BLOcking the Cytokine IL-1 in ICH (BLOC-ICH)

PURPOSE: Recombinant human interleukin-1 receptor antagonist (anakinra) is an anti-inflammatory with efficacy in animal models of stroke. We tested the effect of anakinra on perihaematomal oedema in acute intracerebral haemorrhage (ICH) and explored effects on inflammatory markers. METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled trial in patients with acute, spontaneous, supratentorial ICH between May 2019 and February 2021. Patients were randomised to 100 mg subcutaneous anakinra within 8 h of onset, followed by five, 12-hourly, 100 mg subcutaneous injections, or matched placebo. Primary outcome was oedema extension distance (OED) on a 72 h CT scan. Secondary outcomes included plasma C-reactive protein (CRP) and interleukin-6 (IL-6). FINDINGS: 25 patients (target = 80) were recruited, 14 randomised to anakinra, 11 to placebo. Mean age was 67 and 52% were male. The anakinra group had higher median baseline ICH volume (12.6 ml, interquartile range[IQR]:4.8-17.9) versus placebo (5.5 ml, IQR:2.1-10.9). Adjusting for baseline, 72 h OED was not significantly different between groups (mean difference OED anakinra vs placebo -0.05 cm, 95% confidence interval [CI]: -0.17-0.06, p = 0.336). There was no significant difference in area-under-the-curve to Day 4 for IL-6 and CRP, but a post-hoc analysis demonstrated IL-6 was 56% (95% CI: 2%-80%) lower at Day 2 with anakinra. There were 10 and 2 serious adverse events in anakinra and placebo groups, respectively, none attributed to anakinra. CONCLUSION: We describe feasibility for delivering anakinra in acute ICH and provide preliminary safety data. We lacked power to test for effects on oedema thus further trials will be required

Better value primary care is needed now more than ever

Healthcare systems globally are facing multiple challenges, with ageing populations, increasing chronic disease, rising multimorbidity, and innovative treatments and technologies all leading to rising costs. With finite resources, and an increasing recognition of the potential harms to patients of overdiagnosis and overtreatment, it is essential that resources are used optimally. We explore how the value based healthcare framework can help decisions about how to allocate resources, and the importance of good evidence not only for patient treatment but for the organisation of health service