Modelling temperature and fish biomass data to predict annual Scottish farmed salmon, Salmo salar L., losses: Development of an early warning tool.

Losses due to mortality are a serious economic drain on Scottish salmon aquaculture and are a limitation to its sustainable growth. Understanding the changes in losses, and associated drivers, are required to identify risks to sustainable aquaculture. Data on losses were obtained from two open source data sets: monthly losses of biomass 2003-2018 and losses of salmon over production cycles (numbers input minus output harvest) 2002-2016. Monthly loss rates increased, accelerating after 2010, while losses per production cycle displayed no trend. Two modelling frameworks were investigated to produce an early warning tool for managers about potential increases in losses. Both linear regression and beta regression showed that monthly losses related to biomass and minimum winter air temperatures with high precision and low bias. These relationships apply at both the national and regional levels where the beta regression best fit model explain 82 % and 69 % of variation in mortality, some regional differences apply, particularly for the Northern Isles. The lack of trend in losses per production cycle may have been due to shorter production cycles as more salmon were harvested earlier, and possibly increasing losses of larger salmon (which affects biomass but not numbers lost). In the long-term, the models predict that milder winters and increased biomass will be associated with increased mortality, which will need to be managed. In the short-term, given relatively little year-to-year variation in biomass, minimum winter temperature is a powerful early warning of the likely extent of losses in the Scottish salmon farming industry.

(ICORG 05-03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis.

BACKGROUND: The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10 Gy single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale. METHODS: A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20 Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis. FINDINGS: From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p = .002) but not between the pre-treatment and post-treatment pain scores. INTERPRETATION: Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients.

Benign Enhancing Foramen Magnum Lesions: Clinical Report of a Newly Recognized Entity.

Intradural extramedullary foramen magnum enhancing lesions may be due to meningioma, nerve sheath tumor, aneurysm, or meningeal disease. In this clinical report of 14 patients, we describe a novel imaging finding within the foramen magnum that simulates disease. The lesion is hyperintense on 3D-FLAIR and enhances on 3D gradient-echo sequences but is not seen on 2D-TSE T2WI. It occurs at a characteristic location related to the posterior aspect of the intradural vertebral artery just distal to the dural penetration. Stability of this lesion was demonstrated in those patients who underwent follow-up imaging. Recognition of this apparently benign lesion may prevent unnecessary patient anxiety and repeat imaging.

Spatial and temporal analysis of litter in the Celtic Sea from Groundfish Survey data: Lessons for monitoring.

The Marine Strategy Framework Directive requires EU Member States to sample and monitor marine litter. Criteria for sampling and detecting spatial and/or temporal variation in the amount of litter present have been developed and initiated throughout Europe. These include implementing standardised sampling and recording methods to enable cross-comparison and consistency between neighbours. Parameters of interest include; litter occurrence, composition, distribution and source. This paper highlights the litter-related initiatives occurring in Irish waters; presents an offshore benthic litter sampling series; provides a power analysis to determine trend detection thresholds; identifies areas and sources of litter; and proposes improvements to meet reporting obligations. Litter was found to be distributed throughout Irish waters with highest occurrences in the Celtic Sea. Over 50% of litter encountered was attributed to fishing activities: however only a small proportion of the variability in litter occurrence could be explained by spatial patterns in fishing effort. Issues in implementing standardised protocol were observed and addressed.

Arsenic speciation in blue mussels (Mytilus edulis) along a highly contaminated arsenic gradient.

Arsenic is naturally present in marine ecosystems, and these can become contaminated from mining activities, which may be of toxicological concern to organisms that bioaccumulate the metalloid into their tissues. The toxic properties of arsenic are dependent on the chemical form in which it is found (e.g., toxic inorganic arsenicals vs nontoxic arsenobetaine), and two analytical techniques, high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and X-ray absorption spectroscopy (XAS), were used in the present study to examine the arsenic species distribution in blue mussels (Mytilus edulis) obtained from an area where there is a strong arsenic concentration gradient as a consequence of mining impacted sediments. A strong positive correlation was observed between the concentration of inorganic arsenic species (arsenic compounds with no As-C bonds) and total arsenic concentrations present in M. edulis tissues (R(2) = 0.983), which could result in significant toxicological consequences to the mussels and higher trophic consumers. However, concentrations of organoarsenicals, dominated by arsenobetaine, remained relatively constant regardless of the increasing As concentration in M. edulis tissue (R(2) = 0.307). XANES bulk analysis and XAS two-dimensional mapping of wet M. edulis tissue revealed the presence of predominantly arsenic-sulfur compounds. The XAS mapping revealed that the As(III)-S and/or As(III) compounds were concentrated in the digestive gland. However, arsenobetaine was found in small and similar concentrations in the digestive gland as well as the surrounding tissue suggesting arsenobetaine may being used in all of the mussel's cells in a physiological function such as an intracellular osmolyte.

Whipple's procedure for an oligometastasis to the pancreas from a leiomyosarcoma of the thigh.

BACKGROUND: Pancreatic tumours are most frequently primary, with lesions secondary to metastasis uncommon. METHODS: This report describes the case of a 61-year-old man who underwent resection of a right thigh leiomyosarcoma 2 years prior to presentation with obstructive jaundice. Subsequent CT and endoscopic ultrasound (EUS) diagnosed metastatic leiomyosarcoma to the pancreatic head for which he underwent a Whipple's pancreaticoduodenectomy. CONCLUSION: Metastasis from an extremity leiomyosarcoma to the pancreas is an extremely rare entity, which can be diagnosed by EUS and treated successfully by pancreaticoduodenectomy.

First evidence of azaspiracids (AZAs): A family of lipophilic polyether marine toxins in scallops (Argopecten purpuratus) and mussels (Mytilus chilensis) collected in two regions of Chile.

Azaspiracids are a family of lipophilic polyether marine biotoxins that have caused a number of human intoxication incidents in Europe since 1995 following the consumption by consumers of intoxicated shellfish (Mytilus edulis). These azaspiracids have now been identified in mussels (Mytilus chilensis) and scallops (Argopecten purpuratus) from two Chilean locations. This is the first report of the occurrence of azaspiracid toxins in these species (Mytilus chilensis and Argopecten purpuratus) from Chile. The areas studied were Bahía Inglesa (III Region, 27 degrees SL) and Chiloé Archipelago, both important scallop and mussels farming areas. Separation of azaspiracid (AZA1), azaspiracid isomer (AZA6) and its analogues, 8-methylazaspiracid (AZA2) and 22-demethylazaspiracid (AZA3), was achieved using reversed-phase LC and toxins were identified using a turbo electrospray ionisation (ESI) source, to a triple quadrupole mass spectrometer. In mussels, AZA1 was the predominant toxin in mussel hepatopancreas with AZA2, AZA3 and AZA6 present in approximate equivalent amounts in the remaining tissues, 20-30% of the AZA1 level. AZA2 predominated in the scallop samples with the toxin almost entirely present in the hepatopancreas (digestive gland). AZA1 was only observed in some of the scallop samples and was present at 12-15% of the AZA2 levels. Whilst the levels of AZAs in Chilean samples are below the EU regulatory limit of 160mug/kg, it is significant that this toxin is present in Pacific Ocean species. Consequently measures should be taken by regulatory authorities to implement regular seafood monitoring to ensure safety of harvested product.

Taurine attenuates radiation-induced lung fibrosis in C57/Bl6 fibrosis prone mice.

INTRODUCTION: The amino acid taurine has an established role in attenuating lung fibrosis secondary to bleomycin-induced injury. This study evaluates taurine's effect on TGF-beta1 expression and the development of lung fibrosis after single-dose thoracic radiotherapy. METHODS: Four groups of C57/Bl6 mice received 14 Gy thoracic radiation. Mice were treated with taurine or saline supplementation by gavage. After 10 days and 14 weeks of treatment, TGF-beta1 levels were measured in serum and bronchoalveolar lavage fluid (BALF). Lung collagen content was determined using hydroxyproline analysis. RESULTS: Ten days post radiotherapy, serum TGF-beta1 levels were significantly lower after gavage with taurine rather than saline (P = 0.033). BALF TGF-beta1 at 10 days was also significantly lower in mice treated with taurine (P = 0.031). Hydroxyproline content was also significantly lower at 14 weeks in mice treated with taurine (P = 0.020). CONCLUSION: This study presents novel findings of taurine's role in protecting from TGF-beta1-associated development of lung fibrosis after thoracic radiation.

In vivo knockdown of p85alpha with an antisense oligonucleotide improves insulin sensitivity in Lep(ob/ob) and diet-induced obese mice.

Phosphoinositide 3-kinase is a key signaling intermediate necessary for the metabolic actions of insulin. In this study, we assessed the effects of in vivo knockdown of the p85alpha subunit of phosphoinositide 3-kinase on insulin sensitivity, using an antisense oligonucleotide, in lean mice, diet-induced obese mice, and obese leptin-deficient Lep (ob/ob) mice. Mice were injected with either p85alpha-targeted antisense oligonucleotide or saline twice weekly for 4 weeks. Fasting levels of glycemia and insulinemia and insulin and glucose tolerance tests were used to determine insulin sensitivity. Western blot analysis and real-time polyacrylamide chain reaction were used to assess p85alpha protein and mRNA expression. IN VIVO administration of antisense oligonucleotide resulted in 50 and 60% knockdown of liver p85alpha protein and mRNA, respectively, in the lean, diet-induced obese and Lep (ob/ob) mice. This was associated with increased phosphoinositide 3-kinase activity and improved insulin sensitivity in diet-induced obese and Lep (ob/ob) mice. Thus, p85alpha could be an important therapeutic target to ameliorate insulin resistance.

A simplified tumor regression grade correlates with survival in locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy.

BACKGROUND: Locally advanced rectal cancer is frequently treated with neoadjuvant chemoradiotherapy to reduce local recurrence and possibly improve survival. The tumor response to chemoradiotherapy is variable and may influence the prognosis after surgery. This study assessed tumor regression and its influence on survival in patients with rectal cancer treated with chemoradiotherapy followed by curative surgery. METHODS: One hundred twenty-six patients with locally advanced rectal cancer (T3/T4 or N1/N2) were treated with chemoradiotherapy followed by total mesorectal excision. Patients received long-course radiotherapy (50 Gy in 25 fractions) in combination with 5-flourouracil over 5 weeks. By means of a standardized approach, tumor regression was graded in the resection specimen using a 3-point system related to tumor regression grade (TRG): complete or near-complete response (TRG1), partial response (TRG2), or no response (TRG3). RESULTS: The 5-year disease-free survival was 72% (median follow-up 37 months), and 7% of patients had local recurrence. Chemoradiotherapy produced downstaging in 60% of patients; 21% of patients experienced TRG1. TRG1 correlated with a pathological T0/1 or N0 status. Five-year disease-free survival after chemoradiotherapy and surgery was significantly better in TRG1 patients (100%) compared with TRG2 (71%) and TRG3 (66%) (P = .01). CONCLUSION: Tumor regression grade measured on a 3-point system predicts outcome after chemoradiotherapy and surgery for locally advanced rectal cancer.

Interventional radiology in the treatment of intracranial vascular injuries and fistulae.

Traumatic intracranial vascular injuries are uncommon. However prompt diagnosis and management is essential because of the high morbidity and mortality associated with these conditions. The imaging evaluation and potential endovascular management of traumatic intracranial aneurysms and traumatic intracranial fistulae is discussed.

A randomized prospective study of extended tocopherol and pentoxifylline therapy, in addition to carbogen, in the treatment of radiation late effects.

PURPOSE: pentoxifylline (PTX) and tocopherol (vitamin E) are antioxidants previously shown to be useful in combination in the treatment of late radiation induced toxicity. The purpose of this study was to investigate the benefit of combination therapy with carbogen pentoxifylline and tocopherol in the mitigation of late radiation effects. As the optimal duration of PTX and tocopherol treatment has not been fully established, we studied short versus extended treatment duration. METHODS: we conducted a phase II prospective randomized study of short versus prolonged treatment with pentoxifylline (800 mg) and tocopherol (1000 IU) orally once daily in patients with grade three toxicity post-radical radiotherapy. In addition, all 18 patients received inhaled carbogen (95% O + 5% CO(2)) over 90 minutes, five days/week, for three weeks. The primary end point was improved in maximum Lent-Soma toxicity scores. RESULTS: maximum Lent-Soma scores improved in six of the 18 patients (response rate 33%). The proportion of patients responding to treatment in the prolonged treatment arm B was more than double than in the shorter arm A, but this did not reach statistical significance (p=0.321). Two patients who had prolonged treatment (arm B) had complete resolution of their symptoms, which was maintained at two and three year follow-ups. CONCLUSIONS: we recommend prolonged treatment for 12 months, with PTX and tocopherol in combination with carbogen therapy, in the management of late radiation effects.

Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

AIMS: To standardize the pathological analysis of total mesorectal excision specimens of rectal cancer following neoadjuvant chemoradiotherapy for locally advanced disease (T3/T4), including tumour regression. METHODS AND RESULTS: Standardized dissection and reporting was used for 60 patients who underwent total mesorectal excision following long-course chemoradiotherapy. Tumour regression was scored by two pathologists (K.S., D.G.) using both an established 5-point tumour regression grade (TRG), and a novel 3-point grade. Both scores were evaluated for interobserver variability. A complete or near-complete pathological response (3-point TRG 1) was found in 10 patients (17%). Using the 5-point TRG, there was good agreement between both pathologists (kappa = 0.64). Using the 3-point grade, agreement was excellent (kappa = 0.84). No disease recurrence has been reported in patients with a complete, or near complete pathological response (3-point TRG 1), after a mean follow-up of 22 months. CONCLUSION: Tumour regression grade is a useful method of scoring tumour response to chemoradiotherapy in rectal cancer. TRG 1 and 2 can be regarded as a complete pathological response (ypT0). A modified 3-point grade has the advantage of better reproducibility, with similar prognostic significance.

Improvement in efficacy of chemoradiotherapy by addition of an antiangiogenic agent in a murine tumor model.

BACKGROUND: Chemoradiotherapy improves survival for some cancer patients. Methods of enhancing treatment response would further enhance survival rates. The effect of the addition of an antiangiogenic agent to a chemoradiotherapy regime has not previously been examined. MATERIALS AND METHODS: C57B16 mice were inoculated with 1 x 10(6) Lewis lung carcinoma cells into the flank and randomized to 1 of 10 treatment groups when tumor volume approached 1000 mm(3). Animals received combinations of standard doses of intraperitoneal cisplatin, 5-fluorouracil, and the antiangiogenic agent genistein, together with 10 or 20 Gy of external beam radiotherapy. Animals were sacrificed at day 6 when tumor volume, microvessel density, and serum VEGF were determined. RESULTS: Mean (SEM) tumor volume in the chemoradiotherapy group was 762 (212) mm(3) versus 565 (79) mm(3) in the chemoradiotherapy plus genistein group (P = 0.04, unpaired t-test). The addition of genistein produced a significant reduction in tumor microvessel density (P = 0.01) as well as serum VEGF levels (P < 0.05) compared to those animals receiving chemoradiation alone. CONCLUSIONS: This study provides proof of principle that chemoradiation can be enhanced by the addition of an antiangiogenic agent to the regime and suggests that further examination of such regimes is warranted.

Radiotherapy and the potential exploitation of bystander effects.

Radiation-induced bystander effects are the subject of intense investigation in radiation protection. The effects predominate at low doses and have been discussed mainly in terms of the impact on low-dose risk assessment. Possible therapeutic implications have been alluded to, but not discussed in any detail. The purpose of this review was to consider bystander biology in areas of major importance or interest in radiotherapy. These include consideration of radiation-induced bystander effects during the cell cycle, under hypoxic conditions, when fractionated therapy modalities are used, or when combined radiochemotherapy is given. Also discussed are individual variations in toxicity of bystander factors and normal tissue "collateral" damage. The importance of considering the tumor in the context of the organ, and even the organism that supports it, is also discussed. Direct clinical radiotherapy studies that consider bystander effects are not in the public domain at the time of writing, but many in vitro studies are available that are relevant; some preliminary animal data have also been published. Because radiation-induced bystander effects appear to challenge many of the central assumptions that underlie radiotherapy practice, it is important to consider what unexplored treatment avenues might result from a consideration of these effects. The final part of this paper is devoted to this point.

Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity.

l-Deprenyl (R-(-)-deprenyl, selegiline) is an inhibitor of monoamine oxidase-B (MAO-B) that is known to protect nerve cells from a variety of chemical and physical insults. As apoptosis is a common mechanism of radiation-induced cell death, the effect of l-deprenyl on the survival of cultured cells and tissue explants was studied following exposure to gamma radiation. The results obtained were compared with the effects of the less-selective MAO-B inhibitor pargyline and the MAO-A inhibitor clorgyline. l-Deprenyl at a concentration of 10(-9) M protected the nontumorigenic cell line (HaCaT) and normal human urothelial explants from the effects of cobalt-60 gamma radiation, but did not protect tumorigenic human cell lines HaCaT-ras, HPV-transfected human keratinocytes (HPV-G cells), or PC3. Human bladder carcinoma explants were not protected. Clorgyline showed a smaller protective effect of normal cells, whereas pargyline had no effect. Radiation-induced delayed effects (genomic instability measured as delayed cell death) were prevented in normal cells by l-deprenyl but, interestingly, deprenyl appeared to increase the amount of delayed death in the tumorigenic cell lines. Studies using l-deprenyl prior to the exposure of nonmalignant cells to cisplatin showed that cell death due to this agent was also reduced. Treatment of cultures of nontumorigenic cells with l-deprenyl or clorgyline significantly increased the levels of the protein Bcl-2 following irradiation, but there was no such effect on the already-elevated levels of this protein in the tumour samples. Since the Bcl-2 has been shown to be an inhibitor of apoptosis or programmed cell death, this would imply that the protective effects of l-deprenyl and clorgyline involve activation of antiapoptotic pathways within the normal cell. This hypothesis is supported by data showing reduced levels of apoptosis in HaCAT cells and in normal bladder explant cultures following treatment with l-deprenyl.

BB-10010, an analog of macrophage inflammatory protein-1alpha, protects murine small intestine against radiation.

Irradiation of the small intestine can result in depletion of the epithelial stem cell compartment and is often the dose-limiting factor for radiotherapeutic treatment of tumors in the abdominal and pelvic region. Since mitotic cells are most sensitive to radiation, significant radioprotection can be achieved by reducing the number of cells in mitosis at the time of irradiation. We have previously shown that administration of macrophage inflammatory protein (MIP) -1alpha induces a transient 50% reduction in the number of mitotic cells in small intestinal crypts, including the stem cell region, and therefore, MIP-1alpha pretreatment before radiation exposure could result in a substantial reduction of the side effects associated with radiotherapy. Groups of adult mice were exposed to different doses of radiation (6, 8, 10, or 12 Gy), with or without prior administration of 200 microg BB-10010/kg 3 hr before irradiation and radiation damage was assessed by means of the microcolony survival assay. MIP-1alpha pretreatment resulted in significantly increased numbers of surviving crypts (10%) when compared to untreated irradiated animals. The observed radioprotective effects of MIP-1alpha in the small intestine should translate into reduced side effects in a clinically relevant radiotherapy context and could allow larger doses of radiation to be delivered to patients with tumors in the abdominal or pelvic region.

Value of a contrast agent in equivocal carotid ultrasound studies: pictorial essay.

The aim of the present study was to assess the use of an echo-enhancing agent (Levovist; Schering AG) in equivocal carotid bifurcation ultrasound studies and compare the information obtained with digital subtraction angiography (DSA). Contrast-enhanced carotid ultrasound studies were performed on 30 carotid bifurcations in 28 patients. The standard carotid ultrasound examinations were considered equivocal for two reasons: apparent acute internal carotid artery occlusions (n = 10), and possibly patent but critically stenosed internal carotid arteries with the residual flow lumen being incompletely visualized (n = 20). All patients underwent subsequent carotid digital subtraction angiography. All patients with apparent acute carotid occlusions (n = 10) were correctly characterized on contrast-enhanced ultrasound when compared with DSA. The majority were complete occlusions (n = 8) although in two cases there were critical carotid stenoses requiring surgical endarterectomy. In the 'incompletely visualized lumen' group (n = 20), the majority (n = 16) were correctly characterized on contrast enhanced ultrasound: 13 cases of critically stenotic but patent internal carotid arteries, two cases without a haemodynamically significant stenosis and one case of a carotid occlusion with patent vasa vasorum. One of the critical carotid stenoses was prospectively reported as occluded on the 'gold standard' angiography. In three cases the flow lumen was still incompletely visualized due to calcified plaque despite an echo-enhancing agent; angiography revealed no significant stenosis in all cases. There was one false negative for internal carotid occlusion. This occurred early in the series and could be considered to be a technical error. Importantly, there were no false positives for carotid occlusion. Contrast-enhanced carotid ultrasound significantly improves diagnostic confidence in equivocal carotid ultrasound studies. In appropriate clinical settings this may reduce the need for subsequent carotid angiography.