Classification and incidence of cancers in adolescents and young adults in England 1979–1997

Cancer patients aged 15–24 years have distinct special needs. High quality cancer statistics are required for service planning. Data presented by primary site are inappropriate for this age group. We have developed a morphology-based classification and applied it to national cancer registration data for England 1979–1997. The study included 25 000 cancers and 134 million person–years at risk. Rates for each diagnostic group by age, sex and time period (1979–83, 1984–87, 1988–92, 1993–1997) were calculated. Overall rates in 15–19 and 20–24-year-olds were 144 and 226 per million person–years respectively. Lymphomas showed the highest rates in both age groups. Rates for leukaemias and bone tumours were lower in 20–24 year olds. Higher rates for carcinomas, central nervous system tumours, germ-cell tumours, soft tissue sarcomas and melanoma were seen in the older group. Poisson regression showed incidence increased over the study period by an average of 1.5% per annum (P<0.0001). Significant increases were seen in non-Hodgkins lymphoma (2.3%), astrocytoma (2.3%), germ-cell tumours (2.3%), melanoma (5.1%) and carcinoma of the thyroid (3.5%) and ovary (3.0%). Cancers common in the elderly are uncommon in adolescents and young adults. The incidence of certain cancers in the latter is increasing. Future studies should be directed towards aetiology

Constructing a logistics space: perspectives form the Gulf Cooperation Council

Development plans across the Gulf Cooperation Council emphasise logistical infrastructure as a driver of economic diversification. Investments in maritime ports, roads, rail, airports and logistics cities are transforming the economic geography of the region. This study aims to make visible this neglected aspect of the physical transformation of the Gulf Cooperation Council with a focus on the understudied maritime container ports in Oman and Qatar. Shifting the analysis to emergent maritime logistical infrastructure at a regional level gives insight into the uneven developments within the Gulf Cooperation Council’s integration project. Three key features emerge: (a) a large degree of duplication in maritime port infrastructure across Gulf Cooperation Council states; (b) a regional hierarchy among Gulf Cooperation Council states that are resource rich and those dependent on public–private partnerships and (c) increasing competition among internationally dominant port operators looking to gain access to the Gulf Cooperation Council maritime port market. These features both reflect and reinforce competitive tensions within the regional integration project

Childhood solid tumours in relation to population mixing around the time of birth

In a retrospective cohort study of 673 787 live births in the Northern Region of England, 1975 - 1994, we investigated whether a higher level of population mixing around birth was a risk factor for solid tumours, by diagnostic group (Hodgkin's disease, brain and spinal tumours, neuroblastoma, other solid tumours), diagnosed during 1975-2001 under age 15 years. Logistic regression was used to relate risk to population mixing, based on (i) all movers and (ii) incomers from outside the region. Both ward and county district level analyses were performed. There was a decreased risk of brain and spinal tumours with increasing population mixing based on incomers from outside the region (OR for trend across three categories = 0.79, 95% CI: 0.66-0.95, P = 0.01 in the ward level analysis). Although this may be because of chance, it is consistent with a role of exposure to infection and immunological response in the aetiology of these tumours. For other tumour groups, there was no consistent evidence of an association between risk and population mixing

Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981–2002

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0–14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981–2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27–2.99) for osteosarcoma, 1.90 (1.58–2.21) for Ewing sarcoma and 0.21 (0.11–0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6–5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981–2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91–0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98–1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered

Epithelial-to-mesenchymal transition supports ovarian carcinosarcoma tumorigenesis and confers sensitivity to microtubule-targeting with eribulin

Ovarian carcinosarcoma (OCS) is an aggressive and rare tumour type with limited treatment options. OCS is hypothesised to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analysed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumours. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts (PDX). Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a down-regulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate EMT plays a key role in OCS tumourigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes

Efficient, non‐toxic anion transport by synthetic carriers in cells and epithelia

Transmembrane anion transporters (anionophores) have potential for new modes of biological activity, including therapeutic applications. In particular they might replace the activity of defective anion channels in conditions such as cystic fibrosis. However, data on the biological effects of anionophores are scarce, and it remains uncertain whether such molecules are fundamentally toxic. Here, we report a biological study of an extensive series of powerful anion carriers. Fifteen anionophores were assayed in single cells by monitoring anion transport in real time through fluorescence emission from halide-sensitive yellow fluorescent protein. A bis-(p-nitrophenyl)ureidodecalin shows especially promising activity, including deliverability, potency and persistence. Electrophysiological tests show strong effects in epithelia, close to those of natural anion channels. Toxicity assays yield negative results in three cell lines, suggesting that promotion of anion transport may not be deleterious to cells. We therefore conclude that synthetic anion carriers are realistic candidates for further investigation as treatments for cystic fibrosis.info:eu-repo/semantics/publishe

Simvastatin ameliorates established pulmonary hypertension through a heme oxygenase-1 dependent pathway in rats

<p>Abstract</p> <p>Background</p> <p>Simvastatin has been shown to ameliorate pulmonary hypertension by several mechanisms in experimental animal models. In this study, we hypothesized that the major benefits of simvastatin in pulmonary hypertension occur via the heme oxygenase-1 pathway.</p> <p>Methods</p> <p>Simvastatin (10 mg/kgw/day) was tested in two rat models of pulmonary hypertension (PH): monocrotaline administration and chronic hypoxia. The hemodynamic changes, right heart hypertrophy, HO-1 protein expression, and heme oxygenase (HO) activity in lungs were measured in both models with and without simvastatin treatment. Tin-protoporphyrin (SnPP, 20 μmol/kg w/day), a potent inhibitor of HO activity, was used to confirm the role of HO-1.</p> <p>Results</p> <p>Simvastatin significantly ameliorated pulmonary arterial hypertension from 38.0 ± 2.2 mm Hg to 22.1 ± 1.9 mm Hg in monocrotaline-induced PH (MCT-PH) and from 33.3 ± 0.8 mm Hg to 17.5 ± 2.9 mm Hg in chronic hypoxia-induced PH (CH-PH) rats. The severity of right ventricular hypertrophy was significantly reduced by simvastatin in MCT-PH and CH-PH rats. Co-administration with SnPP abolished the benefits of simvastatin. Simvastatin significantly increased HO-1 protein expression and HO activity in the lungs of rats with PH; however co-administration of SnPP reduced HO-1 activity only. These observations indicate that the simvastatin-induced amelioration of pulmonary hypertension was directly related to the activity of HO-1, rather than its expression.</p> <p>Conclusion</p> <p>This study demonstrated that simvastatin treatment ameliorates established pulmonary hypertension primarily through an HO-1-dependent pathway.</p

Strategies to reduce medication errors with reference to older adults

Background  In Australia, around 59% of the general population uses prescription medication with this number increasing to about 86% in those aged 65 and over and 83% of the population over 85 using two or more medications simultaneously. A recent report suggests that between 2% and 3% of all hospital admissions in Australia may be medication related with older Australians at higher risk because of higher levels of medicine intake and increased likelihood of being admitted to hospital. The most common medication errors encountered in hospitals in Australia are prescription/medication ordering errors, dispensing, administration and medication recording errors. Contributing factors to these errors have largely not been reported in the hospital environment. In the community, inappropriate drugs, prescribing errors, administration errors, and inappropriate dose errors are most common. Objectives  To present the best available evidence for strategies to prevent or reduce the incidence of medication errors associated with the prescribing, dispensing and administration of medicines in the older persons in the acute, subacute and residential care settings, with specific attention to persons aged 65 years and over. Search strategy  Bibliographic databases PubMed, Embase, Current contents, The Cochrane Library and others were searched from 1986 to present along with existing health technology websites. The reference lists of included studies and reviews were searched for any additional literature. Selection criteria  Systematic reviews, randomised controlled trials and other research methods such as non-randomised controlled trials, longitudinal studies, cohort or case-control studies, or descriptive studies that evaluate strategies to identify and manage medication incidents. Those people who are involved in the prescribing, dispensing or administering of medication to the older persons (aged 65 years and older) in the acute, subacute or residential care settings were included. Where these studies were limited, evidence available on the general patient population was used. Data collection and analysis  Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data where possible. All other data were presented in a narrative summary. Results  Strategies that have some evidence for reducing medication incidents are: •  computerised physician ordering entry systems combined with clinical decision support systems; •  individual medication supply systems when compared with other dispensing systems such as ward stock approaches; •  use of clinical pharmacists in the inpatient setting; •  checking of medication orders by two nurses before dispensing medication; •  a Medication Administration Review and Safety committee; and •  providing bedside glucose monitors and educating nurses on importance of timely insulin administration. In general, the evidence for the effectiveness of intervention strategies to reduce the incidence of medication errors is weak and high-quality controlled trials are needed in all areas of medication prescription and delivery