B mu G@Sbase - a microarray database and analysis tool

The manufacture and use of a whole-genome microarray is a complex process and it is essential that all data surrounding the process is stored, is accessible and can be easily associated with the data generated following hybridization and scanning. As part of a program funded by the Wellcome Trust, the Bacterial Microarray Group at St. George's Hospital Medical School (BμG@S) will generate whole-genome microarrays for 12 bacterial pathogens for use in collaboration with specialist research groups. BμG@S will collaborate with these groups at all levels, including the experimental design, methodology and analysis. In addition, we will provide informatic support in the form of a database system (BμG@Sbase). BμG@Sbase will provide access through a web interface to the microarray design data and will allow individual users to store their data in a searchable, secure manner. Tools developed by BμG@S in collaboration with specific research groups investigating analysis methodology will also be made available to those groups using the arrays and submitting data to BμG@Sbase

The specialist breast care nurse's role in the identification and minimisation of distress in a members' only, breast cancer focused online support community

Objectives: To show how a specialist breast care nurse (SBCN) can use the distress thermometer to determine an online community member’s distress level and then use the information in their posts and blogs to identify the cause(s) and deal with them appropriately. To highlight the use of a structured written emotional expression (SWEE) format online, as a way of minimising distress. Method: A survey of online community members together with analysis of the content of members’ posts and blogs to determine whether their distress thermometer score had decreased since the SBCN had been online to deal with member distress. Results: The survey showed that four of the survey participants who completed the survey N=30 had completed a SWEE, been personal messaged by the SBCN about their distress thermometer score and declared that the information and advice they received had been instrumental in decreasing their distress score. It was not possible to identify whether a SWEE made any difference to the Distress Score. Conclusion: The SBCN can use the Distress Thermometer tool online to screen for member distress and deal with this distress through information, advice and support or referral to another health professional. A DT scores should be repeated before and after each of the breast cancer treatment stages so that appropriate interventions can be put in place to minimise or prevent the member’s distress. Specialist nurses in other specialised nursing areas can use the distress thermometer to measure and address the problems/issues causing support community members distress. That the content of a SWEE is one way in which members can document and vent about the problems causing their distress and this information can be used by the nurse to put in place appropriate solution or provide advice and support

Contralateral manual compensation for velocity-dependent force perturbations

It is not yet clear how the temporal structure of a voluntary action is coded allowing coordinated bimanual responses. This study focuses on the adaptation to and compensation for a force profile presented to one stationary arm which is proportional to the velocity of the other moving arm. We hypothesised that subjects would exhibit predictive coordinative responses which would co-vary with the state of the moving arm. Our null hypothesis is that they develop a time-dependent template of forces appropriate to compensate for the imposed perturbation. Subjects were trained to make 500 ms duration reaching movements with their dominant right arm to a visual target. A force generated with a robotic arm that was proportional to the velocity of the moving arm and perpendicular to movement direction acted on their stationary left hand, either at the same time as the movement or delayed by 250 or 500 ms. Subjects rapidly learnt to minimise the final end-point error. In the delay conditions, the left hand moved in advance of the onset of the perturbing force. In test conditions with faster or slower movement of the right hand, the predictive actions of the left hand co-varied with movement speed. Compensation for movement-related forces appeared to be predictive but not based on an accurate force profile that was equal and opposite to the imposed perturbatio

Genetic Variation in Spatio-Temporal Confined USA300 Community-Associated MRSA Isolates: A Shift from Clonal Dispersion to Genetic Evolution?

NTRODUCTION: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasingly isolated, with USA300-0114 being the predominant clone in the USA. Comparative whole genome sequencing of USA300 isolates collected in 2002, 2003 and 2005 showed a limited number of single nucleotide polymorphisms and regions of difference. This suggests that USA300 has undergone rapid clonal expansion without great genomic diversification. However, whole genome comparison of CA-MRSA has been limited to isolates belonging to USA300. The aim of this study was to compare the genetic repertoire of different CA-MRSA clones with that of HA-MRSA from the USA and Europe through comparative genomic hybridization (CGH) to identify genetic clues that may explain the successful and rapid emergence of CA-MRSA. MATERIALS AND METHODS: Hierarchical clustering based on CGH of 48 MRSA isolates from the community and nosocomial infections from Europe and the USA revealed dispersed clustering of the 19 CA-MRSA isolates. This means that these 19 CA-MRSA isolates do not share a unique genetic make-up. Only the PVL genes were commonly present in all CA-MRSA isolates. However, 10 genes were variably present among 14 USA300 isolates. Most of these genes were present on mobile elements. CONCLUSION: The genetic variation present among the 14 USA300 isolates is remarkable considering the fact that the isolates were recovered within one month and originated from a confined geographic area, suggesting continuous evolution of this clone

B mu G@Sbase-a microbial gene expression and comparative genomic database

The reducing cost of high-throughput functional genomic technologies is creating a deluge of high volume, complex data, placing the burden on bioinformatics resources and tool development. The Bacterial Microarray Group at St George's (BμG@S) has been at the forefront of bacterial microarray design and analysis for over a decade and while serving as a hub of a global network of microbial research groups has developed BμG@Sbase, a microbial gene expression and comparative genomic database. BμG@Sbase (http://bugs.sgul.ac.uk/bugsbase/) is a web-browsable, expertly curated, MIAME-compliant database that stores comprehensive experimental annotation and multiple raw and analysed data formats. Consistent annotation is enabled through a structured set of web forms, which guide the user through the process following a set of best practices and controlled vocabulary. The database currently contains 86 expertly curated publicly available data sets (with a further 124 not yet published) and full annotation information for 59 bacterial microarray designs. The data can be browsed and queried using an explorer-like interface; integrating intuitive tree diagrams to present complex experimental details clearly and concisely. Furthermore the modular design of the database will provide a robust platform for integrating other data types beyond microarrays into a more Systems analysis based future

Learning two or more languages

Book synopsis: This volume provides an up-to-date and comprehensive coverage of second language learning. The focus throughout the book is primarily on language learning, but each chapter also discusses the implications for teaching and assessment, thus informing both understanding and practice. The book contains nine sections, which aim to organise and reflect different dimensions of the diverse and complex scope of learning English as a second or additional language. Four themes which permeate the chapters are: learning and learners; learning and language; learning and language development; learning and learning context. The 36 chapters are up-to-date and authoritative, written by experts in the field. The content is accessibly written, with questions for discussion and follow-up reading suggestions provided

Genomic variations define divergence of water/wildlife-associated Campylobacter jejuni niche specialists from common clonal complexes

Although the major food-borne pathogen Campylobacter jejuni has been isolated from diverse animal, human and environmental sources, our knowledge of genomic diversity in C. jejuni is based exclusively on human or human food-chain-associated isolates. Studies employing multilocus sequence typing have indicated that some clonal complexes are more commonly associated with particular sources. Using comparative genomic hybridization on a collection of 80 isolates representing diverse sources and clonal complexes, we identified a separate clade comprising a group of water/wildlife isolates of C. jejuni with multilocus sequence types uncharacteristic of human food-chain-associated isolates. By genome sequencing one representative of this diverse group (C. jejuni 1336), and a representative of the bank-vole niche specialist ST-3704 (C. jejuni 414), we identified deletions of genomic regions normally carried by human food-chain-associated C. jejuni. Several of the deleted regions included genes implicated in chicken colonization or in virulence. Novel genomic insertions contributing to the accessory genomes of strains 1336 and 414 were identified. Comparative analysis using PCR assays indicated that novel regions were common but not ubiquitous among the water/wildlife group of isolates, indicating further genomic diversity among this group, whereas all ST-3704 isolates carried the same novel accessory regions. While strain 1336 was able to colonize chicks, strain 414 was not, suggesting that regions specifically absent from the genome of strain 414 may play an important role in this common route of Campylobacter infection of humans. We suggest that the genomic divergence observed constitutes evidence of adaptation leading to niche specialization

Foreign language enjoyment and anxiety: The effect of teacher and learner variables

Positive psychology has boosted interest in the positive as well as the negative emotions that Foreign Language learners experience. The present study examines whether – and to what extent – foreign language enjoyment (FLE) and foreign language (FL) classroom anxiety (FLCA) are linked to a range of learner internal variables and teacher/classroom-specific variables within one specific educational context. Participants were 189 British high school students learning various FLs. Higher levels of FLE were linked to higher scores on attitudes towards the FL, the FL teacher, FL use in class, proportion of time spent on speaking, relative standing and stage of development. Lower levels FLCA were linked to higher scores on attitudes towards the FL, relative standing and stage of development. FLCA thus seems less related to teacher and teacher practices than FLE. The pedagogical implication is that teachers should strive to boost FLE rather than worry too much about students’ FLCA

A Systematic Comparison of 18F-C-SNAT to Established Radiotracer Imaging Agents for the Detection of Tumor Response to Treatment

PURPOSE: An early readout of tumor response to therapy through measurement of drug or radiation-induced cell death may provide important prognostic indications and improved patient management. It has been shown that the uptake of (18)F-C-SNAT can be used to detect early response to therapy in tumors by positron emission tomography (PET) via a mechanism of caspase-3-triggered nanoaggregation. EXPERIMENTAL DESIGN: Here, we compared the preclinical utility of (18)F-C-SNAT for the detection of drug-induced cell death to clinically evaluated radiotracers, (18)F-FDG, (99m)Tc-Annexin V, and (18)F-ML-10 in tumor cells in culture, and in tumor-bearing mice in vivo. RESULTS: In drug-treated lymphoma cells, (18)F-FDG, (99m)Tc-Annexin V, and (18)F-C-SNAT cell-associated radioactivity correlated well to levels of cell death (R(2) > 0.8; P 0.05). A similar pattern of response was observed in two human NSCLC cell lines following carboplatin treatment. EL-4 tumor uptake of (99m)Tc-Annexin V and (18)F-C-SNAT were increased 1.4- and 2.1-fold, respectively, in drug-treated versus naïve control animals (P < 0.05), although (99m)Tc-Annexin V binding did not correlate to ex vivo TUNEL staining of tissue sections. A differential response was not observed with either (18)F-FDG or (18)F-ML-10. CONCLUSIONS: We have demonstrated here that (18)F-C-SNAT can sensitively detect drug-induced cell death in murine lymphoma and human NSCLC. Despite favorable image contrast obtained with (18)F-C-SNAT, the development of next-generation derivatives, using the same novel and promising uptake mechanism, but displaying improved biodistribution profiles, are warranted for maximum clinical utility

Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. METHODS: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents. CONCLUSIONS: SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM before death