Understanding the lives of separating and separated families in the UK: what evidence do we need?

This study was designed to address three broad questions: What are the evidence – and data – needs around family separation in the UK? How far are these needs met by administrative, survey and other research data that currently exist or are in the process of being developed? What additional data are required, and how would these best be collected

A streamlined approach for the seismic hazard assessment of a new nuclear power plant in the UK

This article presents a streamlined approach to seismic hazard assessment aimed at providing regulatory assurance, whilst acknowledging commercial and program constraints associated with the development of safety–critical facilities. The approach was developed based on international best practice and followed the spirit of the Senior Seismic Hazard Analysis Committee (SSHAC) Level 2 requirements, while incorporating the key features of the SSHAC Level 3 process aimed at achieving regulatory assurance, but with a more flexible implementation. It has also benefited from experience gained by others regarding the implementation of the SSHAC process in projects in the USA, Switzerland and South Africa. The approach has been successfully applied as part of the Safety Case for the new-build nuclear power plant at Hinkley Point, UK. The proposed approach can be considered as a cost-effective solution for the seismic hazard evaluation of safety-significant facilities where a high level of regulatory assurance is required

¿Qué es relevante históricamente? Pensamiento histórico a través de las narrativas de los estudiantes universitarios

Resumen El objetivo es conocer a qué acontecimientos históricos atribuyen relevancia los estudiantes del Grado de Educación Primaria y en qué términos lo hacen. Para ello se analizan los patrones de pensamiento histórico que poseen los futuros docentes. Se centra la atención en el estudio de la denominada relevancia histórica. A través de pequeñas narrativas se han analizado cuáles son las capacidades del futuro docente en relación a este concepto básico del pensamiento histórico, lo cual aporta interesantes indicios acerca de cómo el alumnado entiende la historia y bajo qué premisas la narra. Para ello se han procesado 107 pequeñas narrativas construidas grupalmente por 520 individuos, todos ellos estudiantes universitarios del grado de Educación Primaria. Los textos se recopilaron durante tres cursos académicos y se analizaron siguiendo una metodología cualitativa a partir de la categorización de sus contenidos. Los resultados demuestran que los futuros docentes cuentan con unos conocimientos históricos mínimos, la mayoría de ellos limitados a los episodios que marcan los cambios de etapa histórica. Estos acontecimientos de transición entre etapas son para ellos los más relevantes de la historia de la humanidad obviando otros. Algunas de las implicaciones para su futura labor como docentes son una gran limitación de los contenidos a enseñar o una excesiva dependencia del libro de texto, entre otras. Esto lleva al desarrollo de enseñanzas basadas en la memorización y en la ausencia de reflexión sobre la propia narración histórica obviando por tanto el análisis de la relevancia de algunos eventos históricos

Antibiotic research and development: business as usual?

This article contends that poor economic incentives are an important reason for the lack of new drugs and explains how the DRIVE-AB intends to change the landscape by harnessing the expertise, motivation and diversity of its partner

Australia\u27s health 2002 : the eighth biennial report of the Australian Institute of Health and Welfare

Australia\u27s Health 2002 is the eighth biennial health report of the Australian Institute of Health and Welfare. It is the nation\u27s authoritative source of information on patterns of health and illness, determinants of health, the supply and use of health services, and health service costs and performance. Australia\u27s Health 2002 is an essential reference and information resource for all Australians with an interest in health

Like gold dust these days’: domestic violence fact-finding hearings in child contact cases

Fact-finding hearings may be held to determine disputed allegations of domestic violence in child contact cases in England and Wales, and can play a vital role for mothers seeking protection and autonomy from violent fathers. Drawing on the author’s empirical study, this article examines the implications for the holding of fact-finding hearings of judges’ and professionals’ understandings of domestic violence and the extent to which they perceive it to be relevant to contact. While more judges and professionals are developing their understanding of domestic violence, the ambit of when and how it is considered relevant to contact has grown increasingly narrow, which suggests that many disputed allegations of domestic violence are disregarded and women and children continue to be put at risk from violent fathers. This bifurcated approach is likely to have significant implications for recent developments in this area of family law which are considered in this article

Homologous recombination DNA repair defects in PALB2- associated breast cancers

Abstract: Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy