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In a neoclassical intertemporal framework real investment is determined by Tobin's marginal-Q. We develop this approach to include both agency costs of debt and regime changes, where in some periods the firm may be demand constrained. This leads to a 'wedge' between marginal and average-Q and in addition to the latter variable, investment depends on capital gearing and output. The model is used to explain UK fixed investment in the manufacturing sector 1968-1990 using an error-correction model and cointegration techniques. The statistical performance of the model, including parameter stability is satisfactory. Keywords: Investment; Tobin's Q; Output; Debt; Cointegration; Error-correction-model

Background: Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma.Methods: The HER2 status was assessed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in 72 secondary lesions of gastric adenocarcinoma and in the corresponding primary tumours.Results: Concordance of FISH results, evaluable in 68 primary and matched metastatic sites, was 98.5%. Concordance of IHC results, available in 39 of the 72 paired cases, was 94.9%. Only one case showed discordance between primary tumour and metastasis, being negative by both IHC and FISH in the primary and showing HER2 overexpression and amplification in the corresponding pancreatic lymph node metastasis.Conclusion: The high concordance observed between HER2 results obtained by both IHC and FISH on primary tumours and corresponding metastases suggests that in gastric cancer HER2 status is maintained in most cases unchanged during the metastatic process. [ABSTRACT FROM AUTHOR]

Exercise enhances insulin-stimulated glucose transport in skeletal muscle through changes in signal transduction and gene expression. The aim of this study was to assess the impact of acute and short-term exercise training on whole-body insulin-mediated glucose disposal and signal transduction along the canonical insulin signalling cascade. A euglycaemic–hyperinsulinaemic clamp, with vastus lateralis skeletal muscle biopsies, was performed at baseline and 16 h after an acute bout of exercise and short-term exercise training (7 days) in obese non-diabetic ( n=7) and obese type 2 diabetic ( n=8) subjects. Insulin-mediated glucose disposal was unchanged following acute exercise in both groups. Short-term exercise training increased insulin-mediated glucose disposal in obese type 2 diabetic ( p<0.05), but not in obese non-diabetic subjects. Insulin activation of (1) IRS1, (2) IRS2, (3) phosphotyrosine-associated phosphatidylinositol-3 kinase activity and (4) the substrate of phosphorylated Akt, AS160, a functional Rab GTPase activating protein important for GLUT4 (now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) translocation, was unchanged after acute or chronic exercise in either group. GLUT4 protein content was increased in obese type 2 diabetic subjects ( p<0.05), but not in obese non-diabetic subjects following chronic exercise. Exercise training increased whole-body insulin-mediated glucose disposal in obese type 2 diabetic patients. These changes were independent of functional alterations in the insulin-signalling cascade and related to increased GLUT4 protein content. [ABSTRACT FROM AUTHOR]

Exercise-mediated enhancement of insulin sensitivity is important for the treatment of T2DM. A single bout of exercise accounts for much of the overall improvement, therefore regular exercise is important to maintain the insulin sensitising effects. [ABSTRACT FROM AUTHOR]

Acanthosis nigricans in Irish subjects is associated with severe obesity and insulin resistance. The analysis highlights that subjects with acanthosis nigricans should be screened for insulin resistance and its complications. [ABSTRACT FROM AUTHOR]