The development of a questionnaire to assess the attitudes of older people to end-of-life issues (AEOLI)

Objectives: To develop an end-of-life attitudes questionnaire for use in a large community-based sample of older people. Design: Nominal groups and standardization of questions. Participants: Eighteen older people, ten academics and five specialist palliative care health professionals were involved in nominal groups. Thirty older people took part in initial pilot work and a further 50 were involved in reliability testing. Results: A 27-item attitudes of older people to end-of-life issues (AEOLI) questionnaire. Discussion: In modern times, death and dying predominantly occurs among older people and yet we know very little about older people's attitudes to end-of-life care. The AEOLI questionnaire can be used in large scale surveys to elicit attitudes on end-of life issues considered important by older people and health care professionals

Replication and discovery of musculoskeletal QTLs in LG/J and SM/J advanced intercross lines

AR056280 awarded to DAB and AL. AIHC supported by IMS and Elphinstone Scholarship from the University of Aberdeen. GRV supported by Medical Research Scotland (Vac-929-2016).Peer reviewedPublisher PD

Controlled thermal expansion printed wiring boards based on liquid crystal polymer dielectrics

Dielectric materials based on innovative Liquid Crystal Polymers (LCP's) have been used to fabricate surface mount printed wiring boards (PWB's) with a coefficient of thermal expansion matched to leadless ceramic chip carriers. Proprietary and patented polymer processing technology has resulted in self reinforcing material with balanced in-plane mechanical properties. In addition, LCP's possess excellent electrical properties, including a low dielectric constant (less than 2.9) and very low moisture absorption (less than 0.02%). LCP-based multilayer boards processed with conventional drilling and plating processes show improved performance over other materials because they eliminate the surface flatness problems of glass or aramid reinforcements. Laser drilling of blind vias in the LCP dielectric provides a very high density for use in direct chip attach and area array packages. The material is ideally suited for MCM-L and PCMCIA applications fabricated with very thin dielectric layers of the liquid crystal polymer

Cognitive behaviour therapy (CBT) for anxiety and depression in adults with mild intellectual disabilities (ID): a pilot randomised controlled trial

Background: Several studies have showed that people with intellectual disabilities (ID) have suitable skills to undergo cognitive behavioural therapy (CBT). Case studies have reported successful use of cognitive behavioural therapy techniques (with adaptations) in people with ID. Modified cognitive behavioural therapy may be a feasible and effective approach for the treatment of depression, anxiety, and other mood disorders in ID. To date, two studies have reported group-based manaulised cognitive behavioural treatment programs for depression in people with mild ID. However, there is no individual manualised programme for anxiety or depression in people with intellectual disabilities. The aims of the study are to determine the feasibility of conducting a randomised controlled trial for CBT in people with ID. The data will inform the power calculation and other aspects of carrying out a definitive randomised controlled trial.Methods: Thirty participants with mild ID will be allocated randomly to either CBT or treatment as usual (TAU). The CBT group will receive up to 20 hourly individual CBT over a period of 4 months. TAU is the standard treatment which is available to any adult with an intellectual disability who is referred to the intellectual disability service (including care management, community support, medical, nursing or social support). Beck Youth Inventories (Beck Anxiety Inventory & Beck Depression Inventory) will be administered at baseline; end of treatment (4 months) and at six months to evaluate the changes in depression and anxiety. Client satisfaction, quality of life and the health economics will be secondary outcomes.Discussion: The broad outcome of the study will be to produce clear guidance for therapists to apply an established psychological intervention and identify how and whether it works with people with intellectual disabilities

Randomised evaluation of assertive community treatment: 3-year outcomes

The only randomised controlled trial to test high-fidelity assertive community treatment (ACT) in the UK (the Randomised Evaluation of Assertive Community Treatment (REACT) study) found no advantage over usual care from community mental health teams in reducing the need for inpatient care and in other clinical outcomes, but participants found ACT more acceptable and engaged better with it. One possible reason for the lack of efficacy of ACT might be the short period of follow-up (18 months in the REACT study). This paper reports on participants' service contact, in-patient service use and adverse events 36 months after randomisation

Identification and Diagnostic Performance of a Small RNA within the PCA3 and BMCC1 Gene Locus That Potentially Targets mRNA

Background: PCA3 is a long noncoding RNA (lncRNA) with unknown function, upregulated in prostate cancer. LncRNAs may be processed into smaller active species. We hypothesized this for PCA3. Methods: We computed feasible RNA hairpins within the BMCC1 gene (encompassing PCA3) and searched a prostate transcriptome for these. We measured expression using qRT-PCR in three cohorts of prostate cancer tissues (n = 60), exfoliated urinary cells (n = 484 with cancer and n = 166 controls), and in cell lines (n = 22). We used in silico predictions and RNA knockup to identify potential mRNA targets of short transcribed RNAs. Results: We predicted 13 hairpins, of which PCA3-shRNA2 was most abundant within the prostate transcriptome. PCA3-shRNA2 is located within intron 1 of PCA3 and appears regulated by androgens. Expression of PCA3-shRNA2 was upregulated in malignant prostatic tissues, exfoliated urinary cells from men with prostate cancer (13–273 fold change; t test P < 0.003), and closely correlated to PCA3 expression (r = 0.84–0.93; P < 0.001). Urinary PCA3-shRNA2 (C-index, 0.75–0.81) and PCA3 (C-index, 0.78) could predict the presence of cancer in most men. PCA3-shRNA2 knockup altered the expression of predicted target mRNAs, including COPS2, SOX11, WDR48, TEAD1, and Noggin. PCA3-shRNA2 expression was negatively correlated with COPS2 in patient samples (r = −0.32; P < 0.001). Conclusion: We identified a short RNA within PCA3, whose expression is correlated to PCA3, which may target mRNAs implicated in prostate biology

Exact score distribution computation for ontological similarity searches

<p>Abstract</p> <p>Background</p> <p>Semantic similarity searches in ontologies are an important component of many bioinformatic algorithms, e.g., finding functionally related proteins with the Gene Ontology or phenotypically similar diseases with the Human Phenotype Ontology (HPO). We have recently shown that the performance of semantic similarity searches can be improved by ranking results according to the probability of obtaining a given score at random rather than by the scores themselves. However, to date, there are no algorithms for computing the exact distribution of semantic similarity scores, which is necessary for computing the exact <it>P</it>-value of a given score.</p> <p>Results</p> <p>In this paper we consider the exact computation of score distributions for similarity searches in ontologies, and introduce a simple null hypothesis which can be used to compute a <it>P</it>-value for the statistical significance of similarity scores. We concentrate on measures based on Resnik's definition of ontological similarity. A new algorithm is proposed that collapses subgraphs of the ontology graph and thereby allows fast score distribution computation. The new algorithm is several orders of magnitude faster than the naive approach, as we demonstrate by computing score distributions for similarity searches in the HPO. It is shown that exact <it>P</it>-value calculation improves clinical diagnosis using the HPO compared to approaches based on sampling.</p> <p>Conclusions</p> <p>The new algorithm enables for the first time exact <it>P</it>-value calculation via exact score distribution computation for ontology similarity searches. The approach is applicable to any ontology for which the annotation-propagation rule holds and can improve any bioinformatic method that makes only use of the raw similarity scores. The algorithm was implemented in Java, supports any ontology in OBO format, and is available for non-commercial and academic usage under: <url>https://compbio.charite.de/svn/hpo/trunk/src/tools/significance/</url></p

Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing

Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one-fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content. These findings have implications for diverse areas of mammalian biology and demonstrate how genome-wide association studies can be extended via low-coverage sequencing to species with highly recombinant outbred populations

Estimating adjusted prevalence ratio in clustered cross-sectional epidemiological data

BACKGROUND: Many epidemiologic studies report the odds ratio as a measure of association for cross-sectional studies with common outcomes. In such cases, the prevalence ratios may not be inferred from the estimated odds ratios. This paper overviews the most commonly used procedures to obtain adjusted prevalence ratios and extends the discussion to the analysis of clustered cross-sectional studies. METHODS: Prevalence ratios(PR) were estimated using logistic models with random effects. Their 95% confidence intervals were obtained using delta method and clustered bootstrap. The performance of these approaches was evaluated through simulation studies. Using data from two studies with health-related outcomes in children, we discuss the interpretation of the measures of association and their implications. RESULTS: The results from data analysis highlighted major differences between estimated OR and PR. Results from simulation studies indicate an improved performance of delta method compared to bootstrap when there are small number of clusters. CONCLUSION: We recommend the use of logistic model with random effects for analysis of clustered data. The choice of method to estimate confidence intervals for PR (delta or bootstrap method) should be based on study design

The nose is the best niche for detection of experimental pneumococcal colonisation in adults of all ages, using nasal wash.

Previous studies have suggested that the pneumococcal niche changes from the nasopharynx to the oral cavity with age. We use an Experimental Human Pneumococcal Challenge model to investigate pneumococcal colonisation in different anatomical niches with age. Healthy adults (n = 112) were intranasally inoculated with Streptococcus pneumoniae serotype 6B (Spn6B) and were categorised as young 18-55 years (n = 57) or older > 55 years (n = 55). Colonisation status (frequency and density) was determined by multiplex qPCR targeting the lytA and cpsA-6A/B genes in both raw and culture-enriched nasal wash and oropharyngeal swab samples collected at 2-, 7- and 14-days post-exposure. For older adults, raw and culture-enriched saliva samples were also assessed. 64% of NW samples and 54% of OPS samples were positive for Spn6B in young adults, compared to 35% of NW samples, 24% of OPS samples and 6% of saliva samples in older adults. Many colonisation events were only detected in culture-enriched samples. Experimental colonisation was detected in 72% of young adults by NW and 63% by OPS. In older adults, this was 51% by NW, 36% by OPS and 9% by saliva. The nose, as assessed by nasal wash, is the best niche for detection of experimental pneumococcal colonisation in both young and older adults