Making an accurate diagnosis of anterior mediastinal lesions: a proposal for a new diagnostic algorithm from the BTOG Thymic Malignancies Special Interest Group.

Due to the rising demand in cross-sectional thoracic imaging, anterior mediastinal lesions are being identified with increasing frequency. Following iterative and multidisciplinary discussions, the BTOG Thymic Malignancies Special Interest Group have developed an algorithm to standardise the diagnostic approach for these relatively uncommon but important conditions which span from benign (thymic remnant, thymic hyperplasia and thymic cysts) to suspected localised thymomas to suspected more aggressive malignancy (thymic carcinoma, lymphoma and germ cell tumours). For each condition, we provide a brief description, an overview of the key radiological findings and a description of the proposed algorithm including the rationale behind the recommendations. We also highlight the role of magnetic resonance (MR) imaging for the characterisation of anterior mediastinal masses in specific indications when the necessary local resources and expertise exist. In addition, we hope this provides the rationale for service development in MR of the anterior mediastinum where current resource and expertise requires development. Through this standardised pathway, we hope to drive improvements in patient care by rationalising surveillance schedules, avoiding unnecessary resections of benign entities with their associated morbidity and optimising the diagnostic work-up prior to the appropriate treatment of anterior mediastinal malignancies.

Incidental findings in low dose CT lung cancer screening of high-risk smokers: Results from the Manchester lung Health Check pilot.

Here we report the prevalence of incidental findings (IF) in the Manchester Lung Health Check pilot, which delivered mobile low-dose CT targeted lung cancer screening. 187 IFs were reported in 158 participants (11.2 % of individuals screened; n = 1,409). 101 IFs in 90 participants (6.4 %) were concerning for extra-pulmonary malignancy. IFs resulted in 118 imaging studies, 20 invasive investigations, and 106 new diagnoses, including 5 malignancies (0.35 %). Clinical management of IFs required 84 specialist reviews (6.0 %), 34 medication changes (2.4 %) and 10 interventional treatments (0.71 %). Lung cancer screening detects clinically relevant IFs but further research is needed to better understand the potential benefits and harms of such findings to participants.

Targeted lung cancer screening selects individuals at high risk of cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in populations eligible for lung cancer screening. The aim of this study was to determine whether a brief CV risk assessment, delivered as part of a targeted community-based lung cancer screening programme, was effective in identifying individuals at high risk who might benefit from primary prevention. METHODS: The Manchester Lung Screening Pilot consisted of annual low dose CT (LDCT) over 2 screening rounds, targeted at individuals in deprived areas at high risk of lung cancer (age 55-74 and 6-year risk ≥1.51%, using PLCOM2012 risk model). All participants of the second screening round were eligible to take part in the study. Ten-year CV risk was estimated using QRISK2 in participants without CVD and compared to age (±5 years) and sex matched Health Survey for England (HSE) controls; high risk was defined as QRISK2 score ≥10%. Coronary artery calcification (CAC) was assessed on LDCT scans and compared to QRISK2 score. RESULTS: Seventy-seven percent (n=920/1,194) of screening attendees were included in the analysis; mean age 65.6 ± 5.4 and 50.4% female. QRISK2 and lung cancer risk (PLCOM2012) scores were correlated (r = 0.26, p < 0.001). Median QRISK2 score was 21.1% (IQR 14.9-29.6) in those without established CVD (77.6%, n = 714/920), double that of HSE controls (10.3%, IQR 6.6-16.2; n = 714) (p < 0.001). QRISK2 score was significantly higher in those with CAC (p < 0.001). Screening attendees were 10-fold more likely to be classified high risk (OR 10.2 [95% CI 7.3-14.0]). One third (33.7%, n = 310/920) of all study participants were high risk but not receiving statin therapy for primary CVD prevention. DISCUSSION: Opportunistic CVD risk assessment within a targeted lung cancer screening programme is feasible and is likely to identify a very large number of individuals suitable for primary prevention.

MRI of small bowel Crohn's disease: determining the reproducibility of bowel wall gadolinium enhancement measurements.

This study aims to determine inter- and intra-observer variation in MRI measurements of relative bowel wall signal intensity (SI) in Crohn's disease. Twenty-one small bowel MRI examinations (11 male, mean age 40), including T1-weighted acquisitions acquired 30 to 120s post-gadolinium, were analysed. Maximal bowel wall SI (most avid, conspicuous contrast enhancement) in designated diseased segments was measured by two radiologists and two trainees using self-positioned "free" regions of interest (ROIs) followed by "fixed" ROIs chosen by one radiologist, and this procedure was repeated 1 month later. Relative enhancement (post-contrast SI minus pre-contrast SI/pre-contrast SI) was calculated. Data were analysed using Bland-Altman limits of agreement and intra-class correlation. Inter-observer agreement for relative enhancement was poor (spanning over 120%) using a free ROI-95% limits of agreement -0.69, 0.70 and -0.47, 0.74 for radiologists and trainees, respectively, only marginally improved by use of a fixed ROI -0.60, 0.67 and -0.59, 0.49. Intra-class correlation ranged from 0.46 to 0.72. Intra-observer agreement was slightly better and optimised using a fixed ROI-95% limits of agreement -0.52, 0.50 and -0.34, 0.28 for radiologists and trainees, respectively. Intra-class correlation ranged from 0.49 to 0.86. Relative bowel wall signal intensity measurements demonstrate wide limits of observer agreement, unrelated to reader experience but improved using fixed ROIs.

Thermoenergetics of pre-moulting and moulting kookaburras (Dacelo novaeguineae): they're laughing.

We examined the effect of temperature on resting metabolic rate in seven field-captured laughing kookaburras (Dacelo novaeguineae) during late winter and early spring. Basal metabolic rate averaged 201+/-3.4 ml O(2) h(-1) (0.603 ml O(2) g(-1) h(-1)). Overall thermal conductance (K(o)) declined with ambient temperature ( T(a)) and averaged 0.026 ml O(2) g(-1) h(-1) degrees C(-1) at T(a)s<10 degrees C. Day-night differences in body temperatures (2.6 degrees C) and in alpha-phase versus rho-phase minimum metabolic rates were much greater (33%) than predicted for 340-g nonpasserine birds and suggest that these animals operate as low-metabolic intensity animals in their rest phase, but normal-metabolic intensity animals during their active phase. Metabolic rate was measured in four of the same birds undergoing moult. Thermal conductance increased to 60% above pre-moult values about 6 weeks after moult began. Basal metabolic rate of moulting birds showing peak thermal conductance readings averaged 17 ml O(2) h(-1) higher than pre-moult measurements. Although this increase was not statistically significant, we believe the moult costs of kookaburras are too low to overcome the inherent variability of BMR determination. We suggest that moult costs of kookaburras are only somewhat higher than the measured costs of protein synthesis of other endotherms.

A method to estimate urinary electrolyte excretion in patients at risk for developing cerebral salt wasting.

OBJECT: Two major criteria are necessary to diagnose cerebral salt wasting (CSW): a cerebral lesion and a large urinary excretion of Na+ and Cl- at a time when the extracellular fluid (ECF) volume is contracted. Nevertheless, it is difficult for the physician to confirm from bedside observation that a patient has a contracted ECF volume. Hyponatremia, although frequently present, should not be a criterion for a diagnosis of salt wasting. A contracted ECF volume is unlikely if there are positive balances of Na+ and Cl-. The goal of this study was to assess the accuracy of calculating balances for Na+ plus K+ and of Cl- over 1 to 10 days in an intensive care unit (ICU) setting. METHODS: A prospective comparison of measured and estimated quantities of Na+ plus K+ and of Cl- excreted over 1 to 10 days in 10 children and 12 adults who had recently received a traumatic brain injury or undergone recent neurosurgery. Plasma concentrations of electrolytes were recorded at the beginning and end of the study period. The total volumes infused and excreted and the concentrations of Na+, K+, and Cl- in the infusate were obtained from each patient's ICU chart. The electrolytes in the patients' urine were measured and calculated. Correlations between measured and calculated values for excretions of Cl- and of Na+ plus K+ were excellent. CONCLUSIONS: Mass balances for Na+ plus K+ and for Cl- can be accurately estimated. These data provide information to support or refute a clinical diagnosis of CSW. The danger of relying on balances for these electrolytes measured within a single day to diagnose CSW is illustrated.

Electrokinetic movement and biodegradation of 2,4-dichlorophenoxyacetic acid in silt soil.

The coupling of electrokinetic movement of an organic contaminant, 2,4-dichlorophenoxyacetic acid (2,4-D), through soil and its biodegradation in situ has been demonstrated. In a first experiment, the direction and rate of movement of 2,4-D were determined using homogeneously contaminated soil (864 mg 2,4-D/kg dry weight soil) compacted into six individual compartments, 6 cm long, 3 cm wide, and 4 cm deep. Each compartment was bordered by a carbon felt anode and a stainless steel cathode. The application of a current density of 3.72 A/m(2) led to migration of 2,4-D towards the anode at a rate of approximately 4 cm/day. In a second experiment, electrokinetic movement and biodegradation were combined in situ. Sterilized silt soil contaminated with ring-labeled 14C-2,4-D (811 mg 2,4-D/kg dry weight soil) was compacted into a single soil compartment, 22 cm long, 7 cm wide, and 4 cm deep, in a 4.5 cm region adjacent to the cathode. The remainder of the compartment was filled with sterilized soil (to a total weight of 1,015 g). Burkholderia spp. RASC c2 (1.88 x 10(11) cells), a tetracycline-resistant bacterium with chromosomally encoded degradative genes for 2,4-D, was inoculated into the soil at a position 14-16 cm from the cathode. The reactor was placed within a sealed perspex box, with a constant air flow connected to sodium hydroxide traps. Under an applied current density of 0.89 A/m(2), the pollutant moved towards the bacteria. As it reached the inoculated region, its concentration decreased in the soil and 14CO2 was recovered in the traps. At the end of the experiment, 87.1% of radiolabel had been removed from the soil, 5.8% of which was recovered as 14CO2. A third, control, experiment showed a significant contrast in the absence of an electric current, where a slow rate of diffusion controlled the movement of both 2,4-D and bacteria in the soil and biodegradation occurred at the interface between the diffusing fronts.

Recombinant expression analysis of natural and synthetic bovine alpha-casein in Escherichia coli.

As a prelude to developing a yeast-based fermentation process for the production of phenylalanine-free alpha-casein as a foodstuff for patients suffering from phenylketonuria, we cloned the gene encoding bovine alpha-casein. We synthesised a modified gene sequence encoding the same, but devoid of phenylalanine codons and with a codon bias similar to that of naturally occurring highly expressed genes in Saccharomyces cerevisiae. The results show that both gene sequences are readily expressed in Escherichia coli when cloned in an E. coli bacteriophage T7 promoter-driven plasmid vector. In this host, the natural and synthetic casein proteins were produced at levels equating to 18.0% and 7.6% of the cell's soluble protein, respectively.

Endoscopic third ventriculocisternostomies In the infant: pre- & post-operative magnetic resonance imaging EvaluationElective project

PURPOSE: To determine whether it is possible to select patients with obstructive hydrocephalus, in the under 1 age group for endoscopic third ventriculocisternostomy (ETV) using pre-operative T2 weighted turbo spin echo (T2W-TSE) sagittal sequence Magnetic Resonance (MR) imaging; and to assess ventriculocisternostomy patency using post-operative T2W-TSE MR.PATIENTS AND METHODS: A retrospective review of MR examinations and clinical notes of 11 patients under 1 year of age who had ETV, was performed. The post-operative flow MR images were divided into the presence or absence of flow-related signal changes.RESULTS: In 6 of the 11 patients, ETV was successful (54.5%) i.e. no VP shunt or revision of the ETV was required. 9 patients had post-operative T2W-TSE MR examinations - 8 of these 9 MR studies correlated to the clinical situation (89%). The remaining MR examination showed a CSF flow void but the ETV failed at 3 weeks. CONCLUSION: Pre-operative MR using T2W-TSE to select suitable candidates for ETV improves the success rate from < 40% to 54.5%. Post-operatively MRI is a good predictor of whether the ETV has been successful or not.Sharman, A. (2000). Clinical Radiology55, 989. Copyright 2000 The Royal College of Radiologists.

Determinants of successful direct current cardioversion for atrial fibrillation and flutter: the importance of rapid referral.

Direct current (DC) cardioversion is an effective means of restoring sinus rhythm in patients with atrial fibrillation or flutter; however, the existing literature contains conflicting evidence on which factors are useful predictors of success. In a study of 171 patients undergoing DC cardioversion, we found that duration of arrhythmia prior to DC cardioversion was the only significant predictor of both successful cardioversion and subsequent maintenance of sinus rhythm (P < 0.001). Rapid DC cardioversion after the onset of atrial fibrillation or flutter significantly increases the likelihood of a successful outcome in both the short-term and long-term.

Crab stomach pyloric muscles display not only excitatory but inhibitory and neuromodulatory nerve terminals.

Movements of the foregut in crustaceans are produced by striated muscles that are innervated by motor neurons in the stomatogastric ganglion (STG). Firing of the STG motor neurons generates excitatory junctional potentials (EJPs) in the stomach muscles. We now provide evidence for the existence of separate inhibitory and neuromodulatory innervations of some pyloric muscles in the foregut of several crabs, Callinectes sapidus, Cancer magister, and Cancer borealis. Electron microscopic examination of several pyloric muscles revealed three distinct types of nerve terminals. Excitatory terminals were readily identified by the spherical shape of their small, clear synaptic vesicles. These terminals also housed a few large dense core vesicles. Inhibitory nerve terminals were recognized by the elliptical shape of their small, clear synaptic vesicles, and contacted the muscles at well-defined synapses equipped with dense bar active zones. Bath application of GABA reduced the amplitudes of EJPs in a pyloric muscle of C. borealis, consistent with the presence of GABAergic inhibitory innervation. Neuromodulatory terminals were characterized by their predominant population of large dense and dense core vesicles. These terminals formed synapses with presynaptic dense bars on the muscle, as well as on the excitatory and inhibitory nerve terminals. The presence of the inhibitory and neuromodulatory terminals creates a functional context for previously described reports of neuromodulatory actions on stomach muscles and suggests that the transfer function from STG motor patterns to pyloric movement may be orchestrated by a complex innervation from sources outside of the STG itself.

Some new terms for duplicated genes.

If we are to investigate the relationships between genes, which can involve complex combinations of duplication, deletion and speciation, we need precise terminology. The terms 'paralogy' and 'orthology' have proved very useful in distinguishing two different relationships between homologous genes. Some relationships, however, are not included in either of these terms. I propose three new terms, for use in situations in which one or both lineages that lead to two present-day genes involve gene duplications.

An amphioxus Msx gene expressed predominantly in the dorsal neural tube.

Genomic and cDNA clones of an Msx class homeobox gene were isolated from amphioxus (Branchiostoma floridae). The gene, AmphiMsx, is expressed in the neural plate from late gastrulation; in later embryos it is expressed in dorsal cells of the neural tube, excluding anterior and posterior regions, in an irregular reiterated pattern. There is transient expression in dorsal cells within somites, reminiscent of migrating neural crest cells of vertebrates. In larvae, mRNA is detected in two patches of anterior ectoderm proposed to be placodes. Evolutionary analyses show there is little phylogenetic information in Msx protein sequences; however, it is likely that duplication of Msx genes occurred in the vertebrate lineage.

Estimation of Hox gene cluster number in lampreys.

Hox gene clusters are linked arrays of related homeobox genes with important roles in patterning the main body axis of animal embryos. Almost all invertebrates analyzed in detail, including a cephalochordate, have a single Hox gene cluster. In contrast, mammals have four such clusters inferred to have arisen by duplication. Data from other jawed vertebrates, including teleost fish, suggest they have at least four Hox gene clusters, implying that cluster duplication dates to very early in vertebrate evolution. Lampreys descended from one of the earliest vertebrate lineages and are thus critical in dating the duplication events. Here we analyze the Hox gene complement of a freshwater lamprey, Lampetra, using degenerate PCR. By analysis of the DNA sequences, deduced protein sequences, and by comparison to previous data from the distantly related sea lamprey, we conclude that lampreys have approximately 21 Hox genes from paralogous groups 1-10, plus a group 13 Hox gene. The data support the presence of three Hox gene clusters in lampreys more strongly than they support the presence of one, two or four gene clusters. We discuss how this situation may have arisen in evolution.

An integrated microbial process for the bioremediation of soil contaminated with toxic metals.

Microbially catalyzed reactions, which occur in the natural sulfur cycle, have been integrated in a microbiological process to remove toxic metals from contaminated soils. Bioleaching using sulfuric acid produced by sulfur-oxidizing bacteria was followed by precipitation of the leachate metals as insoluble sulfides by sulfate-reducing bacteria. Metal contaminants including Cd, Co, Cr, Cu, Mn, Ni, and Zn were efficiently leached from an artificially contaminated soil. Mn, Ni, and Zn were the only target elements that were significantly leached from soil minerals. Pb leaching was slow and remained incomplete over a period of 180 days. Mineral components such as Fe, Ca and Mg were also leached but the eventual reduction in soil mass was only approximately 10%. An industrially contaminated soil was also efficiently leached and approximately 69% of the main toxic metals present, Cu, Ni, and Mn, were removed after 175 days. The leachate that resulted from the action of sulfur-oxidizing bacteria on contaminated soil was stripped of metals using an anaerobic bioreactor containing a mixed culture of sulfate-reducing bacteria which precipitated soluble metal species as solid metal sulfides. More than 98% of the metals were removed from solution with the exception of Mn, Ni, and Pb, where 80-90% were removed. The metal content of the resultant effluent liquor was low enough to meet European criteria for discharge into the environment.