The RET mutation E768D confers a late-onset Familial medullary thyroid carcinoma - only phenotype with incomplete penetrance: Implications for screening and management of carrier status

Objective: We describe a 4-generation family with familial medullary thyroid carcinoma (FMTC) - a variant of multiple endocrine neoplasia type 2 (MEN 2) without extra-thyroid features. RET mutation analysis confirmed an E768D mutation in exon 13 in 8 family members, 3 affected with medullary thyroid cancer alone while the other 5 were detected to be mutation carriers. This mutation has been described in very few families worldwide and the spectrum of disease and natural history is unclear. Results: Three affected members had medullary thyroid cancer (MTC) confirmed histologically at ages 25, 50 and 56 years, respectively. The E768D mutation appears to have a less aggressive clinical course compared to other high risk RET mutations with no evidence of clinical recurrence up to I I years after initial therapy. Of five gene carriers identified, two are asymptomatic at the age of 70 and 61, and three had raised calcitonin levels at 46, 39, and 45 years. Following total thyroidectomy, one gene carrier had a histologically normal thyroid at age 46, following a mildly elevated calcitonin, one had C-cell hyperplasia at the age of 39, and one had a frank focus of carcinoma in the left thyroid lobe at the age of 45. No members had evidence of phaeochromocytoma or parathyroid disease on screening. Conclusion: The RET E768D mutation is associated with MTC with a later age at presentation, incomplete penetrance and less aggressive course compared with other high risk RET mutations. To date in this family the E768D mutation has not been associated with either phaeochromocytoma or hyperparathyroidism. The appropriate screening strategy for and management of E768D carriers is difficult reflecting the phenotypic heterogeneity.

Breast cancer mortality in neighbouring European countries with different level of breast screening but similar access to treatment: An analysis of WHO mortality database

Objective: To compare trends in breast cancer mortality within three pairs of neighbouring European countries in relation to implementation of screening. Design: Retrospective trend analysis.
Setting: Three country pairs (Northern Ireland (United Kingdom) v Republic of Ireland, the Netherlands v Belgium and Flanders (Belgian region south of the Netherlands), and Sweden v Norway).
Data sources: WHO mortality database on cause of death and data sources on mammography screening, cancer treatment, and risk factors for breast cancer mortality.
Main outcome measures: Changes in breast cancer mortality calculated from linear regressions of log transformed, age adjusted death rates. Joinpoint analysis was used to identify the year when trends in mortality for all ages began to change.
Results: From 1989 to 2006, deaths from breast cancer decreased by 29% in Northern Ireland and by 26% in the Republic of Ireland; by 25% in the Netherlands and by 20% in Belgium and 25% in Flanders; and by 16% in Sweden and by 24% in Norway. The time trend and year of downward inflexion were similar between Northern Ireland and the Republic of Ireland and between the Netherlands and Flanders. In Sweden, mortality rates have steadily decreased since 1972, with no downward inflexion until 2006. Countries of each pair had similar healthcare services and prevalence of risk factors for breast cancer mortality but differing implementation of mammography screening, with a gap of about 10-15 years.
Conclusions: The contrast between the time differences in implementation of mammography screening and the similarity in reductions in mortality between the country pairs suggest that screening did not play a direct part in the reductions in breast cancer mortality.

The SEMAINE Database: Annotated Multimodal Records of Emotionally Colored Conversations between a Person and a Limited Agent

SEMAINE has created a large audiovisual database as a part of an iterative approach to building Sensitive Artificial Listener (SAL) agents that can engage a person in a sustained, emotionally colored conversation. Data used to build the agents came from interactions between users and an operator simulating a SAL agent, in different configurations: Solid SAL (designed so that operators displayed an appropriate nonverbal behavior) and Semi-automatic SAL (designed so that users' experience approximated interacting with a machine). We then recorded user interactions with the developed system, Automatic SAL, comparing the most communicatively competent version to versions with reduced nonverbal skills. High quality recording was provided by five high-resolution, high-framerate cameras, and four microphones, recorded synchronously. Recordings total 150 participants, for a total of 959 conversations with individual SAL characters, lasting approximately 5 minutes each. Solid SAL recordings are transcribed and extensively annotated: 6-8 raters per clip traced five affective dimensions and 27 associated categories. Other scenarios are labeled on the same pattern, but less fully. Additional information includes FACS annotation on selected extracts, identification of laughs, nods, and shakes, and measures of user engagement with the automatic system. The material is available through a web-accessible database. © 2010-2012 IEEE.

The Belfast Induced Natural Emotion Database

For many years psychological research on facial expression of emotion has relied heavily on a recognition paradigm based on posed static photographs. There is growing evidence that there may be fundamental differences between the expressions depicted in such stimuli and the emotional expressions present in everyday life. Affective computing, with its pragmatic emphasis on realism, needs examples of natural emotion. This paper describes a unique database containing recordings of mild to moderate emotionally coloured responses to a series of laboratory based emotion induction tasks. The recordings are accompanied by information on self-report of emotion and intensity, continuous trace-style ratings of valence and intensity, the sex of the participant, the sex of the experimenter, the active or passive nature of the induction task and it gives researchers the opportunity to compare expressions from people from more than one culture.

Permanent Genetic Resources added to Molecular Ecology Resources Database 1 May 2009-31 July 2009

This article documents the addition of 512 microsatellite marker loci and nine pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Alcippe morrisonia morrisonia, Bashania fangiana, Bashania fargesii, Chaetodon vagabundus, Colletes floralis, Coluber constrictor flaviventris, Coptotermes gestroi, Crotophaga major, Cyprinella lutrensis, Danaus plexippus, Fagus grandifolia, Falco tinnunculus, Fletcherimyia fletcheri, Hydrilla verticillata, Laterallus jamaicensis coturniculus, Leavenworthia alabamica, Marmosops incanus, Miichthys miiuy, Nasua nasua, Noturus exilis, Odontesthes bonariensis, Quadrula fragosa, Pinctada maxima, Pseudaletia separata, Pseudoperonospora cubensis, Podocarpus elatus, Portunus trituberculatus, Rhagoletis cerasi, Rhinella schneideri, Sarracenia alata, Skeletonema marinoi, Sminthurus viridis, Syngnathus abaster, Uroteuthis (Photololigo) chinensis, Verticillium dahliae, Wasmannia auropunctata, and Zygochlamys patagonica. These loci were cross-tested on the following species: Chaetodon baronessa, Falco columbarius, Falco eleonorae, Falco naumanni, Falco peregrinus, Falco subbuteo, Didelphis aurita, Gracilinanus microtarsus, Marmosops paulensis, Monodelphis Americana, Odontesthes hatcheri, Podocarpus grayi, Podocarpus lawrencei, Podocarpus smithii, Portunus pelagicus, Syngnathus acus, Syngnathus typhle,Uroteuthis (Photololigo) edulis, Uroteuthis (Photololigo) duvauceli and Verticillium albo-atrum. This article also documents the addition of nine sequencing primer pairs and sixteen allele specific primers or probes for Oncorhynchus mykiss and Oncorhynchus tshawytscha; these primers and assays were cross-tested in both species.

Reproductive disruption in Fasciola hepatica associated with incomplete efficacy of a new experimental formulation of triclabendazole

The objective of the present study was to analyse the reproductive viability (using histopathologic studies) of Fasciola hepatica from cattle artificially infected and treated subcutaneously with a new experimental formulation of triclabendazole (8 mg/kg b.w.). The results of the efficacy controlled test, which only takes into account the presence of live adult flukes, indicated that, whilst in the control group (n=7)533 live specimens were recovered, in the test groups (doses of 8 and 12 mg/kg b.w.) only 195 and 47 adults were recovered, respectively. These numbers indicate efficacies of 69% and 95.6%, respectively. It was observed in that dose of 8 mg/kg b.w. some specimens remained viable, but they were infertile, which severely compromises the biological cycle of the trematode. in the testis tubules of flukes treated with the low dose of TCBZ (8 mg/kg), very few cells were present and the vitelline follicles were markedly reduced in size and each follicle contained very few cells. This would have direct implications for the pathogenesis of the parasitosis since the remaining parasites would produce little clinical-productive manifestations, would stimulate the immune response and would find it difficult to establish future re-infestations/re-infections. Consequently, these observations will also prompt a review of certain methodological and interpretative aspects related to efficacy tests, where the only discriminative factor is the reduction of the adult parasite load. On one hand, histopathological studies could be complementary to the efficacy controlled test for TCBZ or other BZD formulations. (C) 2010 Elsevier B.V. All rights reserved.

The UMIST database for astrochemistry 1995

We report the release of a new version of the UMIST database for astrochemistry. The database contains the rate coefficients of 3864 gas-phase reactions important in interstellar and circumstellar chemistry and involves 395 species and 12 elements. The previous (1990) version of this database has been widely used by modellers. In addition to the rate coefficients, we also tabulate permanent electric dipole moments of the neutral species and heats of formation. A numerical model of the chemical evolution of a dark cloud is calculated and important differences to that calculated with the previous database noted.

An analysis of VUV C (IV) emission from the JET divertor giving measurements of electron temperatures

A description of the radiation emitted by impurities from within a plasma is crucial if spectral line intensities are to be used in detailed studies, such as the analysis of impurity transport. The simplest and most direct check that can be made on measurements of line intensities is to analyse their ratios with other lines from the same ion. This avoids uncertainties in determining the volume of the emitting plasma and the absolute sensitivity calibration of the spectrometer and, in some cases, the need even for accurate measurements of parameters such as electron density. Consistency is required between the measured line intensity ratios and the theoretical values. The expected consistency has not been found for radiation emitted from the JET scrape-off layer (e.g. Lawson et al 2009a JINST 4 P04013), meaning that the description of the spectral line intensities of impurity emission from the plasma edge is incomplete. In order to gain further understanding of the discrepancies, an analysis has been carried out for emission from the JET divertor plasma and this is reported in this paper. Carbon was the main low Z intrinsic impurity in JET and an analysis of spectral line intensity ratios has been made for the C (IV) radiation emitted from the JET divertor. In this case, agreement is found between the measured and theoretical ratios to a very high accuracy, namely to within the experimental uncertainty of similar to +/- 10%. This confirms that the description of the line intensities for the present observations is complete. For some elements and ionization stages, an analysis of line intensity ratios can lead to the determination of parameters such as the electron temperature of the emitting plasma region and estimates of the contribution of recombination to the electron energy level populations. This applies to C (IV) and, to show the value and possibilities of the spectral measurements, these parameters have been calculated for a database of Ohmic and additionally heated phases of a large number of pulses. The importance of dielectronic, radiative and charge-exchange recombination as well as ionization has been investigated. In addition, the development of T-e throughout two example discharges is illustrated. The presented results indicate a number of areas for further investigation.