RAS testing of colorectal carcinoma—a guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Group

Analysis of colorectal carcinoma (CRC) tissue for KRAS codon 12 or 13 mutations to guide use of anti-epidermal growth factor receptor (EGFR) therapy is now considered mandatory in the UK. The scope of this practice has been recently extended because of data indicating that NRAS mutations and additional KRAS mutations also predict for poor response to anti-EGFR therapy. The following document provides guidance on RAS (i.e., KRAS and NRAS) testing of CRC tissue in the setting of personalised medicine within the UK and particularly within the NHS. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such RAS testing.

The NOTCH signaling pathway in normal and malignant blood cell production

The NOTCH pathway is an evolutionarily conserved signalling network, which is fundamental in regulating developmental processes in invertebrates and vertebrates (Gazave et al. in BMC Evol Biol 9:249, 2009). It regulates self-renewal (Butler et al. in Cell Stem Cell 6:251–264, 2010), differentiation (Auderset et al. in Curr Top Microbiol Immunol 360:115–134, 2012), proliferation (VanDussen et al. in Development 139:488–497, 2012) and apoptosis (Cao et al. in APMIS 120:441–450, 2012) of diverse cell types at various stages of their development. NOTCH signalling governs cell-cell interactions and the outcome of such responses is highly context specific. This makes it impossible to generalize about NOTCH functions as it stimulates survival and differentiation of certain cell types, whereas inhibiting these processes in others (Meier-Stiegen et al. in PLoS One 5:e11481, 2010). NOTCH was first identified in 1914 in Drosophila and was named after the indentations (notches) present in the wings of the mutant flies (Bigas et al. in Int J Dev Biol 54:1175–1188, 2010). Homologs of NOTCH in vertebrates were initially identified in Xenopus (Coffman et al. in Science 249:1438–1441, 1990) and in humans NOTCH was first identified in T-Acute Lymphoblastic Leukaemia (T-ALL) (Ellisen et al. in Cell 66:649–61, 1991). NOTCH signalling is integral in neurogenesis (Mead and Yutzey in Dev Dyn 241:376–389, 2012), myogenesis (Schuster-Gossler et al. in Proc Natl Acad Sci U S A 104:537–542, 2007), haematopoiesis (Bigas et al. in Int J Dev Biol 54:1175–1188, 2010), oogenesis (Xu and Gridley in Genet Res Int 2012:648207, 2012), differentiation of intestinal cells (Okamoto et al. in Am J Physiol Gastrointest Liver Physiol 296:G23–35, 2009) and pancreatic cells (Apelqvist et al. in Nature 400:877–881, 1999). The current review will focus on NOTCH signalling in normal and malignant blood cell production or haematopoiesis.

Low Noise Amplifier With Integrated Balanced Antenna for 60 GHz Wireless Communications

The implementation of a dipole antenna co-designed and monolithically integrated with a low noise amplifier (LNA) on low resistivity Si substrate (20 Omega . cm) manufactured in 0.35 mu m commercial SiGe HBT process with f(T)/f(max) of 170 GHz and 250 GHz is investigated theoretically and experimentally. An air gap is introduced between the chip and a reflective ground plane, leading to substantial improvements in efficiency and gain. Moreover, conjugate matching conditions between the antenna and the LNA are exploited, enhancing power transfer between without any additional matching circuit. A prototype is fabricated and tested to validate the performance. The measured 10-dB gain of the standalone LNA is centered at 58 GHz with a die size of 0.7 mm x 0.6 mm including all pads. The simulated results showed antenna directivity of 5.1 dBi with efficiency higher than 70%. After optimization, the co-designed LNA-Antenna chip with a die size of 3 mm x 2.8 mm was characterized in anechoic chamber environment. A maximum gain of higher than 12 dB was obtained.

Application of Asymmetric Marcus-Hush Theory to Voltammetry in Room-Temperature Ionic Liquids

Asymmetric MarcusHush (AMH) theory is applied for the first time in ionic solvents to model the voltammetric reduction of oxygen in 1-butyl-1-methylpyrrolidinium bis-(trifluoromethylsulfonyl)-imide and of 2-nitrotoluene (2-NT), nitrocyclopentane (NCP), and 1-nitro-butane (BuN) in trihexyltetradecylphosphonium tris(pentafluoroethyl)trifluorophosphate on a gold microdisc electrode. An asymmetry parameter, gamma, was estimated for all systems as -0.4 for the reduction of oxygen and -0.05, 0.25, and 0 +/- 0.05 for the reductions of 2-NT, NCP, and BuN, respectively, which suggests equal force constants of reactants and products in the case of 2-NT and BuN and unequal force constants for oxygen and NCP where the force constants of the oxidized species are greater than the reduced species in the case of oxygen and less than the reduced species in the case of NCP. Previously measured values for a, the Butler-Volmer transfer coefficient, reflect this in each case. Where appreciable asymmetry occurs, AMH theory was seen to parametrize the experimental data better than either Butler-Volmer or symmetric Marcus-Hush theory, allowing additionally the extraction of reorganization energy. This is the first study to provide key physical insights into electrochemical systems in room-temperature ionic liquids using AMH theory, allowing elucidation of the reorganization energies and the relative force constants of the reactants and products in each reaction.

The Routledge Handbook of Irish Criminology

The Routledge Handbook of Irish Criminology is the first edited collection of its kind to bring together the work of leading Irish criminologists in a single volume. While Irish criminology can be characterised as a nascent but dynamic discipline, it has much to offer the Irish and international reader due to the unique historical, cultural, political, social and economic arrangements that exist on the island of Ireland.

Community Sanctions and Measures

This chapter explores the use of community sanctions in the Republic of Ireland and in Northern Ireland. It locates this discussion within a wider international landscape, where the numbers of people subject to supervision in the community has risen markedly. It explores some of the reasons for this growth alongside the rationalities that are deployed to promote the use of community sanctions over time. The differing trajectories of the two jurisdictions in respect of the evolution and use of community sanctions are explored, as are some of the factors that explain areas of divergence and commonality. The chapter concludes by critically considering penal reductionism as a point of policy convergence in the two jurisdictions.

Young Men and Domestic Abuse

Surveys reveal that domestic abuse is more commonplace among teenagers and young adults than older populations, yet surprisingly little is written about young men’s involvement in it. Reporting on a three-year study based in the UK, this book explores young men’s involvement in domestic abuse, whether as victims, perpetrators or witnesses to violent behaviors between adults. Original survey data, focus group material and in-depth biographical interviews are used to make the case for a more thoroughgoing engagement with the meanings young men come to attribute to violent behavior, include the tendency among many to configure violence within families as "fights" that call for acts of male heroism. The book also highlights the dearth of services interventions for young men prone to domestic abuse, and the challenges of developing responsive practice in this area. Each section of the book highlights further online resources that those looking to conduct research in this area or apply its insights in practice can draw upon.

This is Abuse… Or is it? Domestic abuse perpetrators’ responses to anti-domestic violence publicity

Social marketing has become a key component of policy initiatives aimed at reducing the incidence of domestic abuse. However, its efficacy remains debated, with most measures of effectiveness being somewhat crude. More subtle effects of social marketing, such as the boomerang effect whereby the message engenders the opposite effect to that intended, have been detected, suggesting a need for modes of analysis sensitive to the multiple ways in which viewers react to social opprobrium. This article attempts to deliver just this. It begins with a short history and critique of the concept of social marketing. It then proceeds to explore the utility of the more complex notion that viewers often identify with the subject positions thrown open by social marketing on a quite temporary basis, before reconfiguring them. Using the responses of domestic abuse perpetrators exposed to the UK Government’s This is Abuse campaign film, the article shows how contradictory identifications with both anti-violence messages and victim-blaming discourses are negotiated by those young men prone to perpetrating domestic abuse. The article concludes by exploring how effectiveness might be better conceptualised and assessed with regard to the impact of anti-violence social marketing that speaks to domestic abuse perpetrators.

Young teenagers' experiences of domestic abuse

This article reports on the first findings from the Boys to Men Research Project. In total, 1143 pupils aged 13–14 years completed a questionnaire to assess their experiences of domestic abuse as victims, witnesses and perpetrators. Overall, 45% of pupils who had been in a dating relationship reported having been victimised, 25% having perpetrated it, with the only difference in rates of victimisation and perpetration between boys and girls being in relation to sexual victimisation. Of the whole sample, 34% reported having witnessed it in their own family. There was a relationship between victimisation and perpetration with the vast majority of perpetrators (92%) also reporting experiencing abuse from a boyfriend/girlfriend. There was also a relationship between experiencing abuse and help seeking from adults, with those who have been victimised less likely to say they would seek help if they were hit by a partner than those who had yet to experience any abuse. The relationship between help seeking and experiences of abuse is further complicated by gender, with girls twice as likely to seek help than boys, but with girls who have previously hit a partner among the most reticent group. The paper concludes with highlighting the implications of these findings for those undertaking preventative work in schools.

From Boys to Men Phase One Key Findings

The From Boys to Men Project was funded by the Economic and Social Research
Council to explore why some boys become domestic abuse perpetrators when
others do not. In so doing, it sought to establish what more could be done to
reduce the number of young men who become perpetrators. The study
involved three phases of data collection including: Phase 1 - a survey of school
children aged 13-14, Phase 2 - focus groups with 69 young people aged 13-19,
and Phase 3 - life history interviews with 30 young men, aged 16-21, who had experienced domestic violence as victims, perpetrators or witnesses.

From Boys to Men Phase Two Key Findings

The From Boys to Men Project was funded by the Economic and Social Research
Council to explore why some boys become domestic abuse perpetrators when
others do not. In so doing, it sought to establish what more could be done to
reduce the number of young men who become perpetrators. The study
involved three phases of data collection including: Phase 1 - a survey of school
children aged 13-14, Phase 2 - focus groups with 69 young people aged 13-19,
and Phase 3 - life history interviews with 30 young men, aged 16-21, who had experienced domestic violence as victims, perpetrators or witnesses.

From Boys to Men Phase Three Key Findings

The From Boys to Men Project was funded by the Economic and Social Research
Council to explore why some boys become domestic abuse perpetrators when
others do not. In so doing, it sought to establish what more could be done to
reduce the number of young men who become perpetrators. The study
involved three phases of data collection including: Phase 1 - a survey of school
children aged 13-14, Phase 2 - focus groups with 69 young people aged 13-19,
and Phase 3 - life history interviews with 30 young men, aged 16-21, who
had experienced domestic violence as victims, perpetrators or witnesses.