The ‘Unforgivable’?: Irish Republican Army (IRA) informers and dealing with Northern Ireland conflict legacy, 1969-2021

The case of Northern Ireland and ex-IRA informers demonstrates the difficulty of dealing with the informer legacy post-conflict. We explain why Sinn Féin and the UK state have dealt with some conflict legacy cases involving informers but not with others. Contemporary political and reputational reasons are an important explanation, but there are also legal considerations and communal pressures at play. Divisions amongst alleged and self-confessed informers further facilitate this unstructured approach to legacy. These difficulties with informers’ legacy are not unique to Northern Ireland. Similar challenges in reconciling former state agents with paramilitaries are evident across other conflicts

Birley Place: A virtual community for the delivery of health and social care education

Virtual simulation can provide high quality learning experiences through innovative and engaging activities, whilst also overcoming some of the constraints associated with physical simulation. We developed a virtual community, called Birley Place, to facilitate simulation-based learning activities. Adopting a novel approach, we modelled the virtual community on the large metropolitan city in which our institution is based. Publicly-available health and population data was used to ensure that the homes, businesses and services in the community were representative of distinct socio-economic areas of our city. The residents of the virtual community were also matched with the real-world areas based on health and lifestyle data. Our virtual community is used to facilitate learning activities across our health and social care degree programmes. In this article, we summarise how we developed Birley Place, before providing one example of how it is used to facilitate the delivery of a large-scale interprofessional education project. Birley Place is an innovative tool for delivering online and virtual simulation. The use of this virtual community facilitates learners’ understanding of the connection between settings and health status

Sources of skill in lake temperature, discharge and ice-off seasonal forecasting tools

Despite high potential benefits, the development of seasonal forecasting tools in the water sector has been slower than in other sectors. Here we assess the skill of seasonal forecasting tools for lakes and reservoirs set up at four sites in Australia and Europe. These tools consist of coupled hydrological catchment and lake models forced with seasonal meteorological forecast ensembles to provide probabilistic predictions of seasonal anomalies in water discharge, temperature and ice-off. Successful implementation requires a rigorous assessment of the tools' predictive skill and an apportionment of the predictability between legacy effects and input forcing data. To this end, models were forced with two meteorological datasets from the European Centre for Medium-Range Weather Forecasts (ECMWF), the seasonal forecasting system, SEAS5, with 3-month lead times and the ERA5 reanalysis. Historical skill was assessed by comparing both model outputs, i.e. seasonal lake hindcasts (forced with SEAS5), and pseudo-observations (forced with ERA5). The skill of the seasonal lake hindcasts was generally low although higher than the reference hindcasts, i.e. pseudo-observations, at some sites for certain combinations of season and variable. The SEAS5 meteorological predictions showed less skill than the lake hindcasts. In fact, skilful lake hindcasts identified for selected seasons and variables were not always synchronous with skilful SEAS5 meteorological hindcasts, raising questions on the source of the predictability. A set of sensitivity analyses showed that most of the forecasting skill originates from legacy effects, although during winter and spring in Norway some skill was coming from SEAS5 over the 3-month target season. When SEAS5 hindcasts were skilful, additional predictive skill originates from the interaction between legacy and SEAS5 skill. We conclude that lake forecasts forced with an ensemble of boundary conditions resampled from historical meteorology are currently likely to yield higher-quality forecasts in most cases.publishedVersio

Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms

<p>Abstract</p> <p>Background</p> <p>Suicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested.</p> <p>Methods</p> <p>DNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (<it>COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1</it>) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions.</p> <p>Results</p> <p>Our analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the <it>NTRK2 </it>locus may moderate the risk associated with history of childhood abuse.</p> <p>Conclusion</p> <p>Preliminary findings suggest that allelic variability in <it>SLC1A2/3, 5-HTR1B </it>and <it>NTRK2 </it>may be relevant to the underlying diathesis for suicidal acts.</p

Whole blood methylome-derived features to discriminate endocrine hypertension

Background: Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches. Results: Unsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods—Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine—predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL. Conclusions: The blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder

Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease

BACKGROUND: Azathioprine is a commonly prescribed therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). Combination therapy that included azathioprine was recently shown to increase the risk of death and hospitalization in patients with idiopathic pulmonary fibrosis. Whether azathioprine increases the risk of adverse outcomes in patients with fibrotic CTD-ILD, including those with CTD-associated usual interstitial pneumonia (UIP), remains unknown. METHODS: A retrospective cohort analysis was performed to determine the combined incidence rate of death, transplant and respiratory hospitalization associated with azathioprine exposure. A fibrotic CTD-ILD cohort treated with mycophenolate mofetil served as a comparator group. Incidence rates were compared with an incidence rate ratio (IRR) generated by negative binomial regression. Longitudinal pulmonary function response was then assessed using mixed effects linear regression models. RESULTS: Fifty-four patients were treated with azathioprine and forty-three with mycophenolate. Medication discontinuation due to non-respiratory side effects occurred in 27% and 5% of the azathioprine and mycophenolate cohorts, respectively. The combined incidence rate of adverse outcomes was 0.013 and 0.015 for azathioprine and mycophenolate, respectively (IRR 1.23; 95% CI 0.49-3.12; p=0.66). Similar incidence rates were observed among those with CTD-UIP (IRR 0.83; 95% CI 0.21-3.31; p=0.79). Both groups demonstrated pulmonary function stability over time, with the azathioprine group demonstrating a marginal improvement. CONCLUSIONS: A significant minority of patients could not tolerate azathioprine due to non-respiratory side effects. Of those who did tolerate azathioprine, a similar incidence of adverse outcomes was observed as those treated with mycophenolate. Both therapies were associated with stability in pulmonary function

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data