Comparative assessment of live cyprinid and salmonid movement networks in England and Wales.

Disease poses a significant threat to aquaculture. While there are a number of factors contributing to pathogen transmission risk, movement of live fish is considered the most important. Understanding live fish movement patterns for different aquaculture sectors is therefore crucial to predicting disease occurrence and necessary for the development of effective, risk-based biosecurity, surveillance and containment policies. However, despite this, our understanding of live movement patterns of key aquaculture species, namely salmonids and cyprinids, within England and Wales remains limited. In this study, networks reflecting live fish movements associated with the cyprinid and salmonid sectors in England and Wales were constructed. The structure, composition and key attributes of each network were examined and compared to provide insight into the nature of trading patterns and connectedness, as well as highlight sites at a high risk of spreading disease. Connectivity at both site and catchment level was considered to facilitate understanding at different resolutions, providing further insight into disease outbreaks, with industry wide implications. The study highlighted that connectivity through live fish movements was extensive for both industries. The salmonid and cyprinid networks comprised 2533 and 3645 nodes, with a network density of 5.81 × 10-4 and 4.2 × 10-4, respectively. The maximum network reach of 2392 in the salmonid network was higher, both in absolute terms and as a proportion of the overall network, compared to maximum network reach of 2085 in the cyprinid network. However, in contrast, the number of sites in the cyprinid network with a network reach greater than one was 513, compared to 171 in the salmonid network. Patterns of connectivity indicated potential for more frequent yet smaller scale disease outbreaks in the cyprinid industry and less frequent but larger scale outbreaks in the salmonid industry. Further, high connectivity between river catchments within both networks was shown, posing challenges for zoning at the catchment level for the purpose of disease management. In addition to providing insight into pathogen transmission and epidemic potential within the salmonid and cyprinid networks, the study highlights the utility of network analysis, and the value of accessible, accurate live fish movement data in this context. The application of outputs from this study, and network analysis methodology, to inform future disease surveillance and control policies, both within England and Wales and more broadly, is discussed.

The contact structure of Great Britain's salmon and trout aquaculture industry.

We analyse the network structure of the British salmonid aquaculture industry from the perspective of infectious disease control. We combine for the first time live fish transport (or movement) data covering England and Wales with data covering Scotland and include network layers representing potential transmission by rivers, sea water and local transmission via human or animal vectors in the immediate vicinity of each farm or fishery site. We find that 7.2% of all live fish transports cross the England-Scotland border and network analysis shows that 87% of English and Welsh nodes and 72% of Scottish nodes are reachable from cross-border connections via live fish transports alone. Consequently, from a disease-control perspective, the contact structures of England and Wales and of Scotland should not be considered in isolation. We also show that large epidemics require the live fish movement network and so control strategies targeting movements can be very effective. While there is relatively low risk of widespread epidemics on the live fish transport network alone, the potential risk is substantially amplified by the combined interaction of multiple network layers.

Marteilia refringens and Marteilia pararefringens sp. nov. are distinct parasites of bivalves and have different European distributions.

Marteilia refringens causes marteiliosis in oysters, mussels and other bivalve molluscs. This parasite previously comprised two species, M. refringens and Marteilia maurini, which were synonymized in 2007 and subsequently referred to as M. refringens 'O-type' and 'M-type'. O-type has caused mass mortalities of the flat oyster Ostrea edulis. We used high throughput sequencing and histology to intensively screen flat oysters and mussels (Mytilus edulis) from the UK, Sweden and Norway for infection by both types and to generate multi-gene datasets to clarify their genetic distinctiveness. Mussels from the UK, Norway and Sweden were more frequently polymerase chain reaction (PCR)-positive for M-type (75/849) than oysters (11/542). We did not detect O-type in any northern European samples, and no histology-confirmed Marteilia-infected oysters were found in the UK, Norway and Sweden, even where co-habiting mussels were infected by the M-type. The two genetic lineages within 'M. refringens' are robustly distinguishable at species level. We therefore formally define them as separate species: M. refringens (previously O-type) and Marteilia pararefringens sp. nov. (M-type). We designed and tested new Marteilia-specific PCR primers amplifying from the 3' end of the 18S rRNA gene through to the 5.8S gene, which specifically amplified the target region from both tissue and environmental samples.

Randomised feasibility study to compare the use of Therabite® with wooden spatulas to relieve and prevent trismus in patients with cancer of the head and neck.

Our aim was to compare the efficacy of the Therabite® jaw motion rehabilitation system (Atos Medical) with that of wooden spatulas to relieve and prevent trismus in patients who have had radiotherapy for stage three and four oral and oropharyngeal cancer. Secondary aims were to assess the feasibility and the impact of exercise on health-related quality of life (QoL), and the use of health services after treatment. We designed a randomised, open-label, controlled, three-centre feasibility study to compare the effectiveness and cost of the Therabite® and wooden spatulas. We studied compliance with exercises and health-related QoL, assessed cost using three health economics measures, and conducted semistructured interviews with patients. Patients were randomised into two groups: the Therabite® group (n=37) and the wooden spatula group (n=34). All patients had some sense of jaw tightening before the study started. Mean mouth opening after six months increased in both groups, but the difference between the groups was not significant (p=0.39). Completion rates for the three economic measures were good. There was no significant difference between the two groups in frequency of contact with care services or in QoL. Exercises during and after radiotherapy can ameliorate trismus in patients with stage three and four oral and oropharygeal cancers, but differences between groups in efficacy, compliance, QoL, or use of hospital or community health services, were not significant.

Prognostic factors for disease relapse in patients with neuroendocrine tumours who underwent curative surgery.

AIM: Surgery is the only modality of cure in patients diagnosed with neuroendocrine tumours (NETs). The aim of this study was to identify prognostic factors associated with disease relapse in patients with NETs treated by potentially-curative surgery. METHODS: Sequential patients registered in The Christie European NET Society (ENETS) Centre of Excellence, with grade (G)1 or G2 NETs who had undergone curative surgery (February 2002-June 2014) were included. Investigated prognostic factors for relapse were: age, gender, TNM stage, tumour-localisation, functionality, genetic predisposition, presence of multiple NETs, second malignancy, grade (Ki-67-based), presence of vascular and/or perineural invasion, necrosis, surgical margin (R0/R1), Eastern Cooperative Oncology Group performance status and Adult Comorbidity Evaluation co-morbidity score. RESULTS: One hundred and eighty-eight patients were identified [median age of 60 years (range 16-89)]. With a median follow-up of 2.6 years, 43 relapses occurred. The estimated median relapse-free survival (RFS) for the entire cohort was 8.0 years (95% confidence interval [CI] 5.9-10.0 years). In univariate analysis, primary NET location (p = 0.01), ENETS T-(HR-1.4; 95%-CI 1.0-2.0, p = 0.026), N-(HR-2.0, 95%-CI 1.1-3.9, p = 0.026) and M-stage (HR-2.6, 95%-CI 1.1-6.3, p = 0.052), grade (Ki-67%-based) (HR-2.5; 95%-CI 1.4-4.7; p = 0.003) and perineural invasion (HR-2.1; 95%-CI 1.1-3.9; p = 0.029) were prognostic for relapse. Factors remaining significant after multivariable analysis were tumour size (HR-1.67; 95%-CI 1.04-2.70; p = 0.03), nodal involvement (HR-2.61; 95%-CI 1.17-5.83; p = 0.013) and Ki-67 at the time of diagnosis (HR-1.93; 95%-CI 1.24-3.0; p = 0.002). CONCLUSION: Size of tumour, lymph node involvement and Ki-67 were independent prognostic factors for relapse after potentially curative surgery in NET.

Developing best-practice Bayesian Belief Networks in ecological risk assessments for freshwater and estuarine ecosystems: a quantitative review.

Bayesian Belief Networks (BBNs) are being increasingly used to develop a range of predictive models and risk assessments for ecological systems. Ecological BBNs can be applied to complex catchment and water quality issues, integrating multiple spatial and temporal variables within social, economic and environmental decision making processes. This paper reviews the essential components required for ecologists to design a best-practice predictive BBN in an ecological risk assessment (ERA) framework for aquatic ecosystems, outlining: (1) how to create a BBN for an aquatic ERA?; (2) what are the challenges for aquatic ecologists in adopting the best-practice applications of BBNs to ERAs?; and (3) how can BBNs in ERAs influence the science/management interface into the future? The aims of this paper are achieved using three approaches. The first is to demonstrate the best-practice development of BBNs in aquatic sciences using a simple nutrient model. The second is to discuss the limitations and challenges aquatic ecologists encounter when applying BBNs to ERAs. The third is to provide a framework for integrating best-practice BBNs into ERAs and the management of aquatic ecosystems. A quantitative review of the application and development of BBNs in aquatic science from 2002 to 2014 was conducted to identify areas where continued best-practice development is required. We outline a best-practice framework for the integration of BBNs into ERAs and study of complex aquatic systems.

An isotoxic planning comparison study for stage II-III non-small cell lung cancer: is intensity-modulated radiotherapy the answer?

AIMS: Recent clinical series suggest that treating patients with isotoxic twice-daily radiotherapy may be beneficial. This dosimetric planning study compared the use of intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DRT) to deliver isotoxic treatment for non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Twenty patients with stage II/III NSCLC were selected. A dose-escalated plan was produced retrospectively for each using three different methods: (i) three to five beams 3DRT; (ii) seven beams inverse-planned conformal radiotherapy; (iii) seven beams IMRT. The starting point for dose escalation was 55.8 Gy in 1.8 Gy per fraction twice-daily. The number of fractions was then increased until one or more organ at risk tolerance dose was exceeded or a maximum dose of 79.2 Gy was reached. RESULTS: The median escalated doses were 70.2, 66.6 and 64.8 Gy for IMRT, 3DRT and inverse-planned conformal radiotherapy, respectively. IMRT allowed a significant dose increase in comparison with the other two methods (P < 0.05), whereas no significant difference was found between 3DRT and inverse-planned conformal radiotherapy. IMRT was more successful at escalating dose in patients where the brachial plexus and spinal canal were close to the planning target volume. IMRT did not allow the escalation of dose beyond 70.2 Gy (82.8 Gy BED10, 69 Gy EQD2) due to the proximity of disease to the great vessels and the proximal bronchial tree. CONCLUSIONS: IMRT allows increased dose escalation compared with conformal radiotherapy. However, there is limited opportunity to escalate the prescription dose beyond 70.2 Gy twice-daily in disease close to the central mediastinal structures.

Acute dermatitis in farmed trout: an emerging disease.

A new skin condition, known as puffy skin disease (PSD), emerged in farmed rainbow trout Oncorhynchus mykiss (Walbaum) in 2002. The number of new cases increased considerably from 2006. Clinical signs include white or grey skin patches, which become raised and red with excessive mucous production and scale loss. Fish are inappetant and lose condition. Histologically, the key feature is epithelial hyperplasia. We undertook a questionnaire study of trout farmers in England and Wales to investigate prevalence and risk factors. PSD was reported on 37% (n = 49) of rainbow trout sites, located in 28 river catchments. The increase in cases from 2006 onwards was mirrored by the increase in red mark syndrome (RMS). Prevalence and severity of PSD were highest in the summer months. The presence of PSD was associated with RMS (OR = 9.7, P < 0.001). Sites receiving live rainbow trout in the previous 12 months were considerably more likely to have PSD (OR = 5.3. P < 0.01), which suggests an infectious aetiology. The size of affected fish and prevalence varied between farms, indicating that farm-level factors are important. Future research should further investigate the aetiology of PSD and practices to manage the disease.

Obstetric complications and psychological well-being: experiences of Bangladeshi women during pregnancy and childbirth.

Women in developing countries experience postnatal depression at rates that are comparable with or higher than those in developed countries. However, their personal experiences during pregnancy and childbirth have received little attention in relation to postnatal depression. In particular, the contribution of obstetric complications to their emotional well-being during the postpartum period is still not clearly understood. This study aimed to (a) describe the pregnancy and childbirth experiences among women in Bangladesh during normal childbirth or obstetric complications and (b) examine the relationship between these experiences and their psychological well-being during the postpartum period. Two groups of women--one group with obstetric complications (n=173) and the other with no obstetric complications (n=373)--were selected from a sample of women enrolled in a community-based study in Matlab, Bangladesh. The experiences during pregnancy and childbirth were assessed in terms of a five-point rating scale from 'severely uncomfortable=1' to 'not uncomfortable at all=5'. The psychological status of the women was assessed using a validated local version of the Edinburgh Postnatal Depression Scale (EPDS) at six weeks postpartum. Categorical data were analyzed using the chi-square test and continuous data by analysis of variance. Women with obstetric complications reported significantly more negative experiences during their recent childbirth [95% confidence interval (CI) 1.36-1.61, p<0.001] compared to those with normal childbirth. There was a significant main effect on emotional well-being due to experiences of pregnancy [F (4,536)=4.96, p=0.001] and experiences of childbirth [F (4,536)=3.29, p=0.01]. The EPDS mean scores for women reporting severe uncomfortable pregnancy and childbirth experiences were significantly higher than those reporting no such problems. After controlling for the background characteristics, postpartum depression was significantly associated with women reporting a negative childbirth experience. Childbirth experiences of women can provide important information on possible cases of postnatal depression.

A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker.

BACKGROUND: Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study. PATIENTS AND METHODS: Blood samples were obtained prospectively from 54 consenting patients and analysed by CellSearch and isolation by size of epithelial tumour cells (ISET). CellSearch exploits immunomagnetic capture of CTCs-expressing epithelial markers, whereas ISET is a marker independent, blood filtration device. Circulating tumour cell expression of epithelial and mesenchymal markers was assessed to explore any discrepancy in CTC number between the two platforms. RESULTS: ISET detected CTCs in more patients than CellSearch (93% vs 40%) and in higher numbers (median CTCs/7.5 ml, 9 (range 0-240) vs 0 (range 0-144)). Heterogeneity observed for epithelial cell adhesion molecule, pan-cytokeratin (CK), E-Cadherin, Vimentin and CK 7 expression in CTCs may account for discrepancy in CTC number between platforms. CONCLUSION: ISET detects more CTCs than CellSearch and offers flexible CTC characterisation with potential to investigate CTC biology and develop biomarkers for pancreatic cancer patient management.

Disturbance governs dominance of an invasive forb in a temporary wetland.

Dominance of invasive species is often assumed to be due to a superior ability to acquire resources. However, dominance in plant communities can arise through multiple interacting mechanisms, including disturbance. Inter-specific competition can be strongly affected by abiotic conditions, which can determine the outcome of competitive interactions. We evaluated competition and disturbance as mechanisms governing dominance of Phyla canescens (hereafter lippia), an invasive perennial forb from South America, in Paspalum distichum (perennial grass, hereafter water couch) meadows in floodplain wetlands of eastern Australia. Water couch meadows (in the study area) are listed under the Ramsar Convention due to their significance as habitat for migratory waterbirds. In the field, we monitored patterns of vegetation boundaries between the two species in response to flooding. Under controlled glasshouse conditions, we explored competitive interactions between the native water couch and lippia subject to different soil moisture/inundation regimes. We did this using a pairwise factorial glasshouse experiment that manipulated neighbor density (9 treatments) and soil moisture/inundation (4 treatments). In the field trial, inundation increased the cover of water couch. Under more controlled conditions, the invader had a competitive effect on the native species only under dry soil conditions, and was strongly inhibited by inundation. This suggests that dry conditions favor the growth of the invader and wetter (more historical) conditions favor the native grass. In this system, invader dominance is governed by altered disturbance regimes which give the invader a competitive advantage over the native species.

Use of multiple biological markers in radiotherapy-treated head and neck cancer.

OBJECTIVE: Management of patients with head and neck squamous cell carcinoma is often based on clinical parameters, with little appreciation of the underlying tumour biology. Single biological marker studies fail to acknowledge the complexity of these tumours. Our aim was to define a profile of biological markers associated with outcome. DESIGN: This retrospective study involved consecutive patients with oropharyngeal squamous cell carcinoma treated with primary radiotherapy between 1996 and 2001. Pre-treatment biopsies were used to study the immunohistochemical expression of nine biological markers. Markers were chosen to reflect biologically relevant pathways. RESULTS: Following analysis of nine markers, a profile of two markers was derived (carbonic anhydrase 9 and major vault protein), the co-expression of which conferred a significantly poor probability of locoregional control. The prognostic effect of these biomarkers in combination was greater than their effect individually. CONCLUSION: Biomarker profiles can be established which highlight large differences in locoregional control. Identifying tumours that express both carbonic anhydrase 9 and major vault protein may facilitate patient selection for more aggressive treatment.

Percutaneous vertebroplasty in osteoporosis, myeloma and Langerhans' cell histiocytosis.

This review aims to assess the effectiveness of percutaneous vertebroplasty as a treatment for the severe refractory pain associated with vertebral fracture, in a group of patients with fractures secondary to either osteoporotic or neoplastic disease. A retrospective review of 20 patients treated with percutaneous vertebroplasty in Cork University Hospital up until March 2007 was carried out and a questionnaire was prepared and distributed. Prior to vertebroplasty, patients had been symptomatic with severe pain for a mean of 20.9 weeks. Of those thirteen whom replied to a postal questionnaire, 12 (92.3%) reported pain relief and this improvement occurred within 7 days in 9 (81.8%). This was associated with decreased analgesic requirements, as determined on chart review. Prior to the procedure only 5 (38.4%) were independently mobile and this figure rose to 10 (76.9%) afterwards, occurring within one week in the majority. Subjective outcomes were better in the group of patients with neoplasm-induced fractures.

Dural AVM supplied by the ophthalmic artery.

Dural arteriovenous malformations in the anterior cranial fossa are rare and are especially prone to haemorrhage. These lesions are usually treated by surgical excision. We report the embolization of an anterior cranial fossa DAVM using an endovascular approach via the ophthalmic artery.

Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials.

BACKGROUND: Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial. PATIENTS AND METHODS: We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method. RESULTS: Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25). CONCLUSIONS: Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.

Impact of laparotomy and liver resection on the peritoneal concentrations of fibroblast growth factor 2, vascular endothelial growth factor and hepatocyte growth factor.

PURPOSE: Some data have suggested that major surgery is associated with the post-operative growth of residual tumour masses but the mechanism of this is unknown. This study was designed to determine the relationship between intraperitoneal (IP) cytokine levels, and laparotomy in benign and malignant settings. METHODS: Intraperitoneal fluid specimens were obtained at the start and at the end of laparotomy in patients with benign conditions (n=10) and in others undergoing resection of hepatic metastases from colorectal cancer (n=10). Using ELISA the concentration of the angiogenic cytokines, HGF, VEGF-A, VEGF-C, VEGF-D and FGF-2 was determined. RESULTS: The data show that in 16 of 20 patients there was a significant increase (P=0.006) in the IP concentration of hepatocyte growth factor (HGF) but not in the other growth factors by the end of the operation. The mean increase in HGF concentration was 821.5 pg/ml (95% CI: 11.0-6,426.0). Neither the groups (malignant and non-malignant) nor the length of operation correlated with greater or lesser increases in HGF. CONCLUSION: The observation that the increase in HGF occurred in both the cancer and non-cancer groups suggests that it is the surgery rather than the disease that is associated with the increased cytokine concentration. As HGF is a potent endothelial, epithelial and mesenchymal mitogen the data highlight HGF as a potential target for anti-cancer treatments in the peri-operative period. However, investigators should closely monitor wound healing as this may be compromised by this new class of drugs.

Garré's chronic diffuse sclerosing osteomyelitis of the sacrum: a rare condition mimicking malignancy.

Garré's chronic diffuse sclerosing osteomyelitis (DSOM) is a rare disease that occurs most commonly in the mandible. We present a case of sacral DSOM that simulated an expanding destructive sacral tumour. Treatment was conducted on the basis of the available experience with the mandibular form of the disease, with partial symptomatic relief, but progressive sclerosis of the sacral lesion. To the best of our knowledge, this is the first case initially presenting in the sacrum. As an osteolytic expanding lesion simulating malignancy, it is important to recognize this entity in the sacrum.

The pretzel sign: angiographic pattern of tortuous intra-aneurysmal blood flow in a giant serpentine aneurysm.

Giant serpentine aneurysms (GSAs) form a specific subgroup of giant cerebral aneurysms that have pathognomonic angiographic features. We report the angiographic findings of a GSA demonstrating a striking convoluted dynamic flow pattern, which we have called the 'pretzel sign'. The aneurysm was successfully treated by permanent occlusion of the parent vessel using a detachable balloon. GSAs should be identified prior to treatment in view of their particular management requirements.