Irish film finance rebooted: the new Section 481

In 2016, the Section 481 tax incentive, the main subsidy system underpinning film and television content in Ireland, undergoes some important changes, with potentially serious implications for Irish film workers

Potential of known and short prokaryotic protein motifs as a basis for novel peptide-based antibacterial therapeutics: a computational survey

Short linear motifs (SLiMs) are functional stretches of protein sequence that are of crucial importance for numerous biological processes by mediating protein–protein interactions. These motifs often comprise peptides of less than 10 amino acids that modulate protein–protein interactions. While well-characterized in eukaryotic intracellular signaling, their role in prokaryotic signaling is less well-understood. We surveyed the distribution of known motifs in prokaryotic extracellular and virulence proteins across a range of bacterial species and conducted searches for novel motifs in virulence proteins. Many known motifs in virulence effector proteins mimic eukaryotic motifs and enable the pathogen to control the intracellular processes of their hosts. Novel motifs were detected by finding those that had evolved independently in three or more unrelated virulence proteins. The search returned several significantly over-represented linear motifs of which some were known motifs and others are novel candidates with potential roles in bacterial pathogenesis. A putative C-terminal G[AG].$motif found in type IV secretion system proteins was among the most significant detected. A KK$ motif that has been previously identified in a plasminogen-binding protein, was demonstrated to be enriched across a number of adhesion and lipoproteins. While there is some potential to develop peptide drugs against bacterial infection based on bacterial peptides that mimic host components, this could have unwanted effects on host signaling. Thus, novel SLiMs in virulence factors that do not mimic host components but are crucial for bacterial pathogenesis, such as the type IV secretion system, may be more useful to develop as leads for anti-microbial peptides or drugs

Domain-specific introduction to machine learning terminology, pitfalls and opportunities in CRISPR-based gene editing

The use of machine learning (ML) has become prevalent in the genome engineering space, with applications ranging from predicting target site efficiency to forecasting the outcome of repair events. However, jargon and ML-specific accuracy measures have made it hard to assess the validity of individual approaches, potentially leading to misinterpretation of ML results. This review aims to close the gap by discussing ML approaches and pitfalls in the context of CRISPR gene-editing applications. Specifically, we address common considerations, such as algorithm choice, as well as problems, such as overestimating accuracy and data interoperability, by providing tangible examples from the genome-engineering domain. Equipping researchers with the knowledge to effectively use ML to better design gene-editing experiments and predict experimental outcomes will help advance the field more rapidly

Computerised interventions designed to reduce potentially inappropriate prescribing in hospitalised older adults: a systematic review and meta-analysis

Background: computerised interventions have been suggested as an effective strategy to reduce potentially inappropriate prescribing (PIP) for hospitalised older adults. This systematic review and meta-analysis examined the evidence for efficacy of computerised interventions designed to reduce PIP in this patient group. Methods: an electronic literature search was conducted using eight databases up to October 2017. Included studies were controlled trials of computerised interventions aiming to reduce PIP in hospitalised older adults (≥65 years). Risk of bias was assessed using Cochrane’s Effective Practice and Organisation of Care criteria. Results: of 653 records identified, eight studies were included—two randomised controlled trials, two interrupted time series analysis studies and four controlled before–after studies. Included studies were mostly at a low risk of bias. Overall, seven studies showed either a statistically significant reduction in the proportion of patients prescribed a potentially inappropriate medicine (PIM) (absolute risk reduction {ARR} 1.3–30.1%), or in PIMs ordered (ARR 2–5.9%). However, there is insufficient evidence thus far to suggest that these interventions can routinely improve patient-related outcomes. It was only possible to include three studies in the meta-analysis—which demonstrated that intervention patients were less likely to be prescribed a PIM (odds ratio 0.6; 95% CI 0.38, 0.93). No computerised intervention targeting potential prescribing omissions (PPOs) was identified. Conclusions: this systematic review concludes that computerised interventions are capable of statistically significantly reducing PIMs in hospitalised older adults. Future interventions should strive to target both PIMs and PPOs, ideally demonstrating both cost-effectiveness data and clinically significant improvements in patient-related outcomes

Contrasting origin of B chromosomes in two cervids (Siberian roe deer and grey brocket deer) unravelled by chromosome-specific DNA sequencing.

BACKGROUND: B chromosomes are dispensable and variable karyotypic elements found in some species of animals, plants and fungi. They often originate from duplications and translocations of host genomic regions or result from hybridization. In most species, little is known about their DNA content. Here we perform high-throughput sequencing and analysis of B chromosomes of roe deer and brocket deer, the only representatives of Cetartiodactyla known to have B chromosomes. RESULTS: In this study we developed an approach to identify genomic regions present on chromosomes by high-throughput sequencing of DNA generated from flow-sorted chromosomes using degenerate-oligonucleotide-primed PCR. Application of this method on small cattle autosomes revealed a previously described KIT gene region translocation associated with colour sidedness. Implementing this approach to B chromosomes from two cervid species, Siberian roe deer (Capreolus pygargus) and grey brocket deer (Mazama gouazoubira), revealed dramatically different genetic content: roe deer B chromosomes consisted of two duplicated genomic regions (a total of 1.42-1.98 Mbp) involving three genes, while grey brocket deer B chromosomes contained 26 duplicated regions (a total of 8.28-9.31 Mbp) with 34 complete and 21 partial genes, including KIT and RET protooncogenes, previously found on supernumerary chromosomes in canids. Sequence variation analysis of roe deer B chromosomes revealed a high frequency of mutations and increased heterozygosity due to either amplification within B chromosomes or divergence between different Bs. In contrast, grey brocket deer B chromosomes were found to be more homogeneous and resembled autosomes in patterns of sequence variation. Similar tendencies were observed in repetitive DNA composition. CONCLUSIONS: Our data demonstrate independent origins of B chromosomes in the grey brocket and roe deer. We hypothesize that the B chromosomes of these two cervid species represent different stages of B chromosome sequences evolution: probably nascent and similar to autosomal copies in brocket deer, highly derived in roe deer. Based on the presence of the same orthologous protooncogenes in canids and brocket deer Bs we argue that genomic regions involved in B chromosome formation are not random. In addition, our approach is also applicable to the characterization of other evolutionary and clinical rearrangements

Transcription of a protein-coding gene on B chromosomes of the Siberian roe deer (Capreolus pygargus)

BACKGROUND: Most eukaryotic species represent stable karyotypes with a particular diploid number. B chromosomes are additional to standard karyotypes and may vary in size, number and morphology even between cells of the same individual. For many years it was generally believed that B chromosomes found in some plant, animal and fungi species lacked active genes. Recently, molecular cytogenetic studies showed the presence of additional copies of protein-coding genes on B chromosomes. However, the transcriptional activity of these genes remained elusive. We studied karyotypes of the Siberian roe deer (Capreolus pygargus) that possess up to 14 B chromosomes to investigate the presence and expression of genes on supernumerary chromosomes. RESULTS: Here, we describe a 2 Mbp region homologous to cattle chromosome 3 and containing TNNI3K (partial), FPGT, LRRIQ3 and a large gene-sparse segment on B chromosomes of the Siberian roe deer. The presence of the copy of the autosomal region was demonstrated by B-specific cDNA analysis, PCR assisted mapping, cattle bacterial artificial chromosome (BAC) clone localization and quantitative polymerase chain reaction (qPCR). By comparative analysis of B-specific and non-B chromosomal sequences we discovered some B chromosome-specific mutations in protein-coding genes, which further enabled the detection of a FPGT-TNNI3K transcript expressed from duplicated genes located on B chromosomes in roe deer fibroblasts. CONCLUSIONS: Discovery of a large autosomal segment in all B chromosomes of the Siberian roe deer further corroborates the view of an autosomal origin for these elements. Detection of a B-derived transcript in fibroblasts implies that the protein coding sequences located on Bs are not fully inactivated. The origin, evolution and effect on host of B chromosomal genes seem to be similar to autosomal segmental duplications, which reinforces the view that supernumerary chromosomal elements might play an important role in genome evolution

Safety culture in a major accredited Irish university teaching hospital: a mixed methods study using the safety attitudes questionnaire.

Background: The measurement of safety culture, the way in which members of an organisation think about and prioritise safety, in a hospital can provide valuable insight and inform quality improvement strategies. Aims: The aim of this study is to describe the safety culture of a university teaching hospital in the Republic of Ireland. Methods: This is a mixed methods survey study using the Safety Attitudes Questionnaire (SAQ). The SAQ was distributed to all staff in the study hospital. Staff attitudes towards six domains of patient safety culture were assessed over 32 Likert-scaled items. Thematic analysis was performed on qualitative data. Results: A total of 768 staff members completed and returned a copy of the SAQ. The hospital scored above the international benchmark in five out of six domains, indicating a positive safety culture, but scored below the international benchmark in the domain 'Working Conditions'. This positive safety culture was not mirrored in the qualitative data, from which five themes emerged; three major-Staffing Issues, Patient-Focused Care and Hospital Environment-and two minor-Safe Reporting Culture and Training and Education. Conclusions: In this study, a mixed methods approach was successfully used to investigate the safety culture in a large Irish hospital. Although the SAQ results indicated a positive safety culture, the qualitative data revealed a number of issues that the hospital staff felt impacted negatively on patient safety. The results of this study will inform future work on the design of an intervention to improve patient safety in the hospital

Cost-effectiveness analysis of a physician-implemented medication screening tool in older hospitalised patients in Ireland

Background: A recent randomised controlled trial conducted in an Irish University teaching hospital that evaluated a physician-implemented medication screening tool, demonstrated positive outcomes in terms of a reduction in incident adverse drug reactions. Objective: The present study objective was to evaluate the cost effectiveness of physicians applying this screening tool to older hospitalised patients compared with usual hospital care in the context of the earlier randomised controlled trial. Method: We used a cost-effectiveness analysis alongside a conventional outcome analysis in a cluster randomised controlled trial. Patients in the intervention arm (n = 360) received a multifactorial intervention consisting of medicines reconciliation, communication with patients’ senior medical team, and generation of a pharmaceutical care plan in addition to usual medical and pharmaceutical care. Control arm patients (n = 372) received usual medical and pharmaceutical care only. Incremental cost effectiveness was examined in terms of costs to the healthcare system and an outcome measure of adverse drug reactions during inpatient hospital stay. Uncertainty in the analysis was explored using a cost-effectiveness acceptability curve. Results: On average, the intervention arm was more costly but was also more effective. Compared with usual care (control), the intervention was associated with a non-statistically significant increase of €877 (95% confidence interval − €1807, €3561) in the mean healthcare cost, and a statistically significant decrease of − 0.164 (95% confidence interval − 0.257, − 0.070) in the mean number of adverse drug reaction events per patient. The associated incremental cost-effectiveness ratio per adverse drug reaction averted was €5358. The probability of the intervention being cost effective at threshold values of €0, €5000 and €10,000 was 0.236, 0.455 and 0.680, respectively. Conclusion: Based on the evidence presented, this physician-led intervention is not likely to be cost effective compared with usual hospital care. To inform future healthcare policy decisions in this field, more economic analyses of structured medication reviews by other healthcare professionals and by computerised clinical decision support software need to be conducted