Turning Milestones into Quantified Objectives: Food waste

This document sets out to define food waste, investigate how best it can be measured and provides a first assessment of the impacts of setting a food waste reduction target in the EU

Pancreatic cancer intrinsic PI3Kα activity accelerates metastasis and rewires macrophage component.

Pancreatic ductal adenocarcinoma (PDAC) patients frequently suffer from undetected micro-metastatic disease. This clinical situation would greatly benefit from additional investigation. Therefore, we set out to identify key signalling events that drive metastatic evolution from the pancreas. We searched for a gene signature that discriminate localised PDAC from confirmed metastatic PDAC and devised a preclinical protocol using circulating cell-free DNA (cfDNA) as an early biomarker of micro-metastatic disease to validate the identification of key signalling events. An unbiased approach identified, amongst actionable markers of disease progression, the PI3K pathway and a distinctive PI3Kα activation signature as predictive of PDAC aggressiveness and prognosis. Pharmacological or tumour-restricted genetic PI3Kα-selective inhibition prevented macro-metastatic evolution by hindering tumoural cell migratory behaviour independently of genetic alterations. We found that PI3Kα inhibition altered the quantity and the species composition of the produced lipid second messenger PIP3 , with a selective decrease of C36:2 PI-3,4,5-P3 . Tumoural PI3Kα inactivation prevented the accumulation of pro-tumoural CD206-positive macrophages in the tumour-adjacent tissue. Tumour cell-intrinsic PI3Kα promotes pro-metastatic features that could be pharmacologically targeted to delay macro-metastatic evolution

End-stage kidney disease due to haemolytic uraemic syndrome - outcomes in 241 consecutive ANZDATA Registry cases

Extent: 11p.Background: The aim of this study was to investigate the characteristics and outcomes of patients receiving renal replacement therapy for end-stage kidney disease (ESKD) secondary to haemolytic uraemic syndrome (HUS). Methods: The study included all patients with ESKD who commenced renal replacement therapy in Australia and New Zealand between 15/5/1963 and 31/12/2010, using data from the ANZDATA Registry. HUS ESKD patients were compared with matched controls with an alternative primary renal disease using propensity scores based on age, gender and treatment era. Results: Of the 58422 patients included in the study, 241 (0.4%) had ESKD secondary to HUS. HUS ESKD was independently associated with younger age, female gender and European race. Compared with matched controls, HUS ESKD was not associated with mortality on renal replacement therapy (adjusted hazard ratio [HR] 1.14, 95% CI 0.87-1.50, p = 0.34) or dialysis (HR 1.34, 95% CI 0.93-1.93, p = 0.12), but did independently predict recovery of renal function (HR 54.01, 95% CI 1.45-11.1, p = 0.008). 130 (54%) HUS patients received 166 renal allografts. Overall renal allograft survival rates were significantly lower for patients with HUS ESKD at 1 year (73% vs 91%), 5 years (62% vs 85%) and 10 years (49% vs 73%). HUS ESKD was an independent predictor of renal allograft failure (HR 2.59, 95% CI 1.70-3.95, p < 0.001). Sixteen (12%) HUS patients experienced failure of 22 renal allografts due to recurrent HUS. HUS ESKD was not independently associated with the risk of death following renal transplantation (HR 0.92, 95% CI 0.35-2.44, p = 0.87). Conclusions: HUS is an uncommon cause of ESKD, which is associated with comparable patient survival on dialysis, an increased probability of renal function recovery, comparable patient survival post-renal transplant and a heightened risk of renal transplant graft failure compared with matched ESKD controls.Wen Tang, Janaki Mohandas, Stephen P McDonald, Carmel M Hawley, Sunil V Badve, Neil Boudville, Fiona G Brown, Philip A Clayton, Kathryn J Wiggins, Kym M Bannister, Scott B Campbell and David W Johnso

CONTRIBUTION OF TROUT YOLK-SAC FRY (SALMO TRUTTA L.) ORIGINATING FROM WILD STOCK TO FISHING IN THE MOSELOTTE RIVER, FRANCE

The Moselotte River has been severely affected by human activity and in some of its stretches this has impaired reproduction of trout, which has added to an adverse effect on the trout population arising from a high fishing pressure by local anglers. To offset this problem, the local anglers annually release about 50,000 yolk-sac fry that have been derived from wild native breeding stock. It was possible to monitor the fry released in 1999 and 2000 using a method of mass marking by immersion in a fluoromarking agent (Alizarin Red S). The trout enter the fishery at 3 years and about 90% of the trout caught are three or four years old. Fish that had been released represented 25.5% and 36.7% of the catches respectively in 2002 and 2003, two percentages that do not differ significantly. This proportion varied according to the location in the river. The age structure of the marked fish that were caught was similar to that of fish hatched in the wild

Is there a role for locoregional treatment of the primary tumor in de novo metastatic breast cancer in the era of tailored therapies? Evidences, unresolved questions and a practical algorithm

International audienceImprovements in systemic therapies have changed the face of de novo metastatic breast cancer (dnMBC), with a 5-year survival rate exceeding 25 %. Increasing evidence suggests that a subset of patients could benefit from a locoregional treatment (LRT) with prolonged survival, although the diversity of publications on the subject make it difficult to draw any conclusions. In this review, we summarize the available data on retrospective, prospective and current ongoing clinical trials. Since factors such as tumor biology, pattern of metastatic dissemination and the timing of the treatment are closely linked to the therapeutic strategy, we focus on papers which include these aspects. We discuss recent studies indicating that exclusive radiotherapy provides results comparable with those obtained by surgery. We will then discuss the biological rationale for LRT. Finally, we propose a decision-tree to select the optimal candidates for LRT in dnMBC patients

Frog diazepam-binding inhibitor: peptide sequence, cDNA cloning, and expression in the brain.

Three peptides derived from diazepam-binding inhibitor (DBI) were isolated in pure form from the brain of the frog Rana ridibunda. The primary structures of these peptides showed that they correspond to mammalian DBI-(1-39), DBI-(58-87), and DBI-(70-87). A set of degenerate primers, whose design was based on the amino acid sequence data, was used to screen a frog brain cDNA library. The cloned cDNA encodes an 87-amino acid polypeptide, which exhibits 68% similarity with porcine and bovine DBI. Frog DBI contains two paired basic amino acids (Lys-Lys) at positions 14-15 and 62-63 and a single cysteine within the biologically active region of the molecule. Northern blot analysis showed that DBI mRNA is expressed at a high level in the brain but is virtually absent in peripheral tissues. The distribution of DBI mRNA and DBI-like immunoreactivity in the frog brain was studied by in situ hybridization and immunocytochemistry. Both approaches revealed that the DBI gene is expressed in ependymal cells and circumventricular organs lining the ventricular cavity. Since amphibia diverged from mammals at least 250 million years ago, the data show that evolutionary pressure has acted to conserve the structure of DBI in the vertebrate phylum. The distribution of both DBI mRNA and DBI-like immunoreactivity indicates that DBI is selectively expressed in glial cells