Guidelines for the measurement of BCR-ABL1 transcripts in chronic myeloid leukaemia

Molecular testing for the BCR-ABL1 fusion gene by real time quantitative polymerase chain reaction (RT-qPCR) is the most sensitive routine approach for monitoring the response to therapy of patients with chronic myeloid leukaemia. In the context of tyrosine kinase inhibitor (TKI) therapy, the technique is most appropriate for patients who have achieved complete cytogenetic remission and can be used to define specific therapeutic milestones. To achieve this effectively, standardization of the laboratory procedures and the interpretation of results are essential. We present here consensus best practice guidelines for RT-qPCR testing, data interpretation and reporting that have been drawn up and agreed by a consortium of 21 testing laboratories in the United Kingdom and Ireland in accordance with the procedures of the UK Clinical Molecular Genetics Society.

A point prevalence survey of antibiotic prescriptions: benchmarking and patterns of use

center dot Inappropriate antimicrobial use has been associated with increased morbidity and hospital costs.

Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

Background: Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P = 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).

Contextualism as an important facet of individualism-collectivism: personhood beliefs across 37 national groups

Beliefs about personhood are understood to be a defining feature of individualism-collectivism (I-C), but they have been insufficiently explored, given the emphasis of research on values and self-construals. We propose the construct of contextualism, referring to beliefs about the importance of context in understanding people, as a facet of cultural collectivism. A brief measure was developed and refined across 19 nations (Study 1: N = 5,241), showing good psychometric properties for cross-cultural use and correlating well at the nation level with other supposed facets and indicators of I-C. In Study 2 (N = 7,623), nation-level contextualism predicted ingroup favoritism, corruption and differential trust of ingroup and outgroup members, while controlling for other facets of I-C, across 34 nations. We conclude that contextualism is an important part of cultural collectivism. This highlights the importance of beliefs alongside values and self-representations, and contributes to a wider understanding of cultural processes.

A 7000 yr perspective on volcanic ash clouds affecting northern Europe

The ash cloud resulting from the 2010 eruption of Eyjafjöll caused severe disruption to air travel across Europe but as a geological event, it is not unprecedented. Analysis of peat and lake sediments from northern Europe has revealed the presence of microscopic layers of Icelandic volcanic ash (tephra). These sedimentary records, together with historical records of Holocene ash falls, demonstrate that Icelandic volcanoes have generated substantial ash clouds that reached northern Europe many times. Here we present the first comprehensive compilation of sedimentary and historical records of ash-fall events in northern Europe, spanning the last 7000 years. Within this period ten tephra layers have been identified in the Faroe Islands, 14 in Great Britain, 11 in Germany, 38 in Scandinavia and 33 in Ireland. Seven ash fall events have been historically documented prior to the Eyjafjöll 2010 event. Ash fall events appear to be more frequent in the last 1500 years, but it is unclear whether this reflects a true increase in eruption frequency or dispersal, or is an artefact of the records themselves or the way they have been generated. In the last 1,000 years, volcanic ash clouds reached Northern Europe with a mean return interval of 53 ± 8 years (the range of return intervals is between 6 and 112 years). Modelling using the ash records for the last millennium indicates that for any 10 year period there is a 17% probability of tephra fallout event in Northern Europe. These values must be considered as conservative estimates due to the nature of tephra capture and preservation in the sedimentary record.

Recruitment bias and clinical characterstics of participants with severe cerebral palsy in a cross-sectional survey

Aim.  This article is a report of recruitment bias in a sample of 5–25-year-old patients with severe cerebral palsy.

Background.  The way in which study participants are recruited into research can be a source of bias.

Method.  A cross-sectional survey of 5–25-year-old patients with severe cerebral palsy using standardized questionnaires with parents/carers was undertaken in 2007/2008. A case register was used as the sampling frame, and 260 families were approached: 178/260 (68%) responded and 82/260 families never replied (non-respondents). Among responders: 127/178 (71%) opted in to the study, but only 123/127 were assessed, and 82/178 were opted out (or refused). Multivariable logistic regression giving odds ratios was used to study the association between participant characteristics and study outcomes (responders vs. non-responders; opting in vs. opting out; assessed vs. eligible, but not assessed).

Results.  Responders (compared with non-responders) were significantly more likely to have a family member with cerebral palsy who was male and resident in more affluent areas. Families who opted in (compared with those opting out and refusing) were more likely to have a family member with cerebral palsy and intellectual impairment and to reside in certain geographical areas. Families who were actually assessed (compared with all eligible, but not assessed) were more likely to have a family member with cerebral palsy and intellectual impairment.

Conclusion.  Several sources of bias were identified during recruitment for this study. This has implications for the interpretation and conclusions of surveys of people with disabilities and complex needs.

The impact of intellectual impairment on the quality of life of children with cerebral palsy

Cerebral palsy is the most common cause of physical disability in childhood and half of these children will have an intellectual impairment. This article reports on the quality of life of children with cerebral palsy and explores the impact of intellectual impairment. Learning disability nurses have a critical role to play in improving the quality of life for this patient group, particularly in relation to their physical health and creating opportunities to promote social skill development and social inclusion.

Oromotor dysfunction and communication impairments in children with cerebral palsy: a Register study

Aim  To report the prevalence, clinical associations, and trends over time of oromotor dysfunction and communication impairments in children with cerebral palsy (CP).

Method  Multiple sources of ascertainment were used and children followed up with a standardized assessment including motor speech problems, swallowing/chewing difficulties, excessive drooling, and communication impairments at age 5 years.

Results  A total of 1357 children born between 1980 and 2001 were studied (781 males, 576 females; median age 5y 11mo, interquartile range 3–9y; unilateral spastic CP, n=447; bilateral spastic CP, n=496; other, n=112; Gross Motor Function Classification System [GMFCS] level: I, 181; II, 563; III, 123; IV, 82; IV, 276). Of those with ‘early-onset’ CP (n=1268), 36% had motor speech problems, 21% had swallowing/chewing difficulties, 22% had excessive drooling, and 42% had communication impairments (excluding articulation defects). All impairments were significantly related to poorer gross motor function and intellectual impairment. In addition, motor speech problems were related to clinical subtype; swallowing/chewing problems and communication impairments to early mortality; and communication impairments to the presence of seizures. Of those with CP in GMFCS levels IV to V, a significant proportion showed a decline in the rate of motor speech impairment (p=0.008) and excessive drooling (p=0.009) over time.

Interpretation  These impairments are common in children with CP and are associated with poorer gross motor function and intellectual impairment.