ESTABLISHING IDENTITY OF NON-EU NATIONALS IN IRISH MIGRATION PROCESSES. ESRI RESEARCH SERIES NUMBER 69 DECEMBER 2017

Establishing the identity of non-EEA nationals1 entering the EU is often the first step in determining eligibility for visas, certain residence or visitor permissions and permissions associated with international protection statuses. Establishing identity is an EU-level policy priority as set out in both the European Agenda on Security (European Commission, 2015a) and the European Agenda on Migration (European Commission, 2015b). No legal or overarching definition of ‘identity’ in the context of migration procedures exists in the majority of Member States. For the purposes of migration, identity is generally established by documents such as birth certificates, passports or other identity papers. Biometric identification refers to physical characteristics including fingerprints and digital facial images. Any individual wishing to enter Ireland, whether visa required or not, is subject to immigration controls at ports of entry. All non-EEA (both visa required and non-visa required) nationals require permission to enter Ireland upon arrival.2 Visa required non-EEA nationals must apply for a visa to travel to Ireland. However, an Irish visa is a form of pre-entry clearance to travel to a point of entry to the State only (Quinn, 2011). In almost all cases a passport or travel document is required in order for a non-EEA national to be issued a visa, to register in the State and to access the territory at the border. Protection applicants are not required to have a passport or travel document to access the asylum procedure. This study looks at the processes in place for establishing the identities of applicants for: short- and long-stay visas; residence and visitor permissions; international protection and permission to remain; and in relation to persons subject to a deportation order who have exhausted the asylum process. This study also looks at the process of establishing applicants’ identities at the point of access to the national territory

Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity

Obesity-related insulin resistance is a highly prevalent and growing health concern, which places stress on the pancreatic islets of Langerhans by increasing insulin secretion to lower blood glucose levels. The glucose transporters GLUT1 and GLUT3 play a key role in glucose-stimulated insulin secretion in human islets, while GLUT2 is the key isoform in rodent islets. However, it is unclear whether other glucose transporters also contribute to insulin secretion by pancreatic islets. Herein, we show that SLC2A6 (GLUT6) is markedly upregulated in pancreatic islets from genetically obese leptin-mutant (ob/ob) and leptin receptor-mutant (db/db) mice, compared to lean controls. Furthermore, we observe that islet SLC2A6 expression positively correlates with body mass index in human patients with type 2 diabetes. To investigate whether GLUT6 plays a functional role in islets, we crossed GLUT6 knockout mice with C57BL/6 ob/ob mice. Pancreatic islets isolated from ob/ob mice lacking GLUT6 secreted more insulin in response to high-dose glucose, compared to ob/ob mice that were wild type for GLUT6. The loss of GLUT6 in ob/ob mice had no adverse impact on body mass, body composition, or glucose tolerance at a whole-body level. This study demonstrates that GLUT6 plays a role in pancreatic islet insulin secretion in vitro but is not a dominant glucose transporter that alters whole-body metabolic physiology in ob/ob mice

A global analysis of genetic interactions in Caenorhabditis elegans

Abstract Background Understanding gene function and genetic relationships is fundamental to our efforts to better understand biological systems. Previous studies systematically describing genetic interactions on a global scale have either focused on core biological processes in protozoans or surveyed catastrophic interactions in metazoans. Here, we describe a reliable high-throughput approach capable of revealing both weak and strong genetic interactions in the nematode Caenorhabditis elegans. Results We investigated interactions between 11 'query' mutants in conserved signal transduction pathways and hundreds of 'target' genes compromised by RNA interference (RNAi). Mutant-RNAi combinations that grew more slowly than controls were identified, and genetic interactions inferred through an unbiased global analysis of the interaction matrix. A network of 1,246 interactions was uncovered, establishing the largest metazoan genetic-interaction network to date. We refer to this approach as systematic genetic interaction analysis (SGI). To investigate how genetic interactions connect genes on a global scale, we superimposed the SGI network on existing networks of physical, genetic, phenotypic and coexpression interactions. We identified 56 putative functional modules within the superimposed network, one of which regulates fat accumulation and is coordinated by interactions with bar-1(ga80), which encodes a homolog of β-catenin. We also discovered that SGI interactions link distinct subnetworks on a global scale. Finally, we showed that the properties of genetic networks are conserved between C. elegans and Saccharomyces cerevisiae, but that the connectivity of interactions within the current networks is not. Conclusions Synthetic genetic interactions may reveal redundancy among functional modules on a global scale, which is a previously unappreciated level of organization within metazoan systems. Although the buffering between functional modules may differ between species, studying these differences may provide insight into the evolution of divergent form and function

Comparison of electrical impedance tomography and spirometry-based measures of airflow in healthy adult horses

Electrical impedance tomography (EIT) is a non-invasive diagnostic tool for evaluating lung function. The objective of this study was to compare respiratory flow variables calculated from thoracic EIT measurements with corresponding spirometry variables. Ten healthy research horses were sedated and instrumented with spirometry via facemask and a single-plane EIT electrode belt around the thorax. Horses were exposed to sequentially increasing volumes of apparatus dead space between 1,000 and 8,500 mL, in 5–7 steps, to induce carbon dioxide rebreathing, until clinical hyperpnea or a tidal volume of 150% baseline was reached. A 2-min stabilization period followed by 2 minutes of data collection occurred at each timepoint. Peak inspiratory and expiratory flow, inspiratory and expiratory time, and expiratory nadir flow, defined as the lowest expiratory flow between the deceleration of flow of the first passive phase of expiration and the acceleration of flow of the second active phase of expiration were evaluated with EIT and spirometry. Breathing pattern was assessed based on the total impedance curve. Bland-Altman analysis was used to evaluate the agreement where perfect agreement was indicated by a ratio of EIT:spirometry of 1.0. The mean ratio (bias; expressed as a percentage difference from perfect agreement) and the 95% confidence interval of the bias are reported. There was good agreement between EIT-derived and spirometry-derived peak inspiratory [−15% (−46–32)] and expiratory [10% (−32–20)] flows and inspiratory [−6% (−25–18)] and expiratory [5% (−9–20)] times. Agreement for nadir flows was poor [−22% (−87–369)]. Sedated horses intermittently exhibited Cheyne-Stokes variant respiration, and a breath pattern with incomplete expiration in between breaths (crown-like breaths). Electrical impedance tomography can quantify airflow changes over increasing tidal volumes and changing breathing pattern when compared with spirometry in standing sedated horses

Inkjet printed LED based pH chemical sensor for gas sensing

Predictable behaviour is a critical factor when developing a sensor for potential deployment within a wireless sensor network (WSN). The work presented here details the fabrication and performance of an optical chemical sensor for gaseous acetic acid analysis, which was constructed using inkjet printed deposition of a colorimetric chemical sensor. The chemical sensor comprised a pH indicator dye (bromophenol blue), phase transfer salt tetrahexylammonium bromide and polymer ethyl cellulose dissolved in 1-butanol. A paired emitter-detector diode (PEDD) optical detector was employed to monitor responses of the colorimetric chemical sensor as it exhibits good sensitivity, low power consumption, is low cost, accurate and has excellent signal to noise ratios. The chemical sensor formulation was printed directly onto the surface the emitter LED, and the resulting chemical sensors characterised with respect to their layer thickness, response time and recovery time. The fabrication reproducibility of inkjet printed chemical sensors in comparison to drop casted chemical sensors was investigated. Colorimetric chemical sensors produced by inkjet printing, exhibited an improved reproducibility for the detection of gaseous acetic acid with a relative standard deviation of 5.5 % in comparison to 68.0 % calculated for drop casted sensors (n = 10). The stability of the chemical sensor was also investigated through both intra and inter-day studies

Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Function and CT Coronary Angiogram (CorCTCA) study

Background: Microvascular and/or vasospastic anginas are relevant causes of ischemia with no obstructive coronary artery disease (INOCA) in patients after computed tomography coronary angiography (CTCA). Objectives: Our research has 2 objectives. The first is to undertake a diagnostic study, and the second is to undertake a nested, clinical trial of stratified medicine. Design: A prospective, multicenter, randomized, blinded, sham-controlled trial of stratified medicine (NCT03477890) will be performed. All-comers referred for clinically indicated CTCA for investigation of suspected coronary artery disease (CAD) will be screened in 3 regional centers. Following informed consent, eligible patients with angina symptoms are enrolled before CTCA and remain eligible if CTCA excludes obstructive CAD. Diagnostic study: Invasive coronary angiography involving an interventional diagnostic procedure (IDP) to assess for disease endotypes: (1) angina due to obstructive CAD (fractional flow reserve ≤0.80); (2) microvascular angina (coronary flow reserve <2.0 and/or index of microvascular resistance >25); (3) microvascular angina due to small vessel spasm (acetylcholine); (4) vasospastic angina due to epicardial coronary spasm (acetylcholine); and (5) noncoronary etiology (normal coronary function). The IDP involves direct invasive measurements using a diagnostic coronary guidewire followed by provocation testing with intracoronary acetylcholine. The primary outcome of the diagnostic study is the reclassification of the initial CTCA diagnosis based on the IDP. Stratified medicine trial: Participants are immediately randomized 1:1 in the catheter laboratory to therapy stratified by endotype (intervention group) or not (control group). The primary outcome of the trial is the mean within-subject change in Seattle Angina Questionnaire score at 6 months. Secondary outcomes include safety, feasibility, diagnostic utility (impact on diagnosis and certainty), and clinical utility (impact on treatment and investigations). Health status assessments include quality of life, illness perception, anxiety-depression score, treatment satisfaction, and physical activity. Participants who are not randomized will enter a follow-up registry. Health and economic outcomes in the longer term will be assessed using electronic patient record linkage. Value: CorCTCA will prospectively characterize the prevalence of disease endotypes in INOCA and determine the clinical value of stratified medicine in this population

Palliative radiotherapy after oesophageal cancer stenting (ROCS): a multicentre, open-label, phase 3 randomised controlled trial

Background: patients with advanced oesophageal cancer have a median survival of 3-6 months, and most require intervention for dysphagia. Self-expanding metal stent (SEMS) insertion is the most typical form of palliation in these patients, but dysphagia deterioration and re-intervention are common. This study examined the efficacy of adjuvant external beam radiotherapy (EBRT) compared with usual care alone in preventing dysphagia deterioration and reducing service use after SEMS insertion.Methods: this was a multicentre, open-label, phase 3 randomised controlled trial based at cancer centres and acute care hospitals in England, Scotland, and Wales. Patients (aged ≥16 years) with incurable oesophageal carcinoma receiving stent insertion for primary management of dysphagia were randomly assigned (1:1) to receive usual care alone or EBRT (20 Gy in five fractions or 30 Gy in ten fractions) plus usual care after stent insertion. Usual care was implemented according to need as identified by the local multidisciplinary team (MDT). Randomisation was via the method of minimisation stratified by treating centre, stage at diagnosis (I-III vs IV), histology (squamous or non-squamous), and MDT intent to give chemotherapy (yes vs no). The primary outcome was difference in proportions of participants with dysphagia deterioration (&gt;11 point decrease on patient-reported European Organisation for Research and Treatment of Cancer quality of life questionnaire-oesophagogastric module [QLQ-OG25], or a dysphagia-related event consistent with such a deterioration) or death by 12 weeks in a modified intention-to-treat (ITT) population, which excluded patients who did not have a stent inserted and those without a baseline QLQ-OG25 assessment. Secondary outcomes included survival, quality of life (QoL), morbidities (including time to first bleeding event or hospital admission for bleeding event and first dysphagia-related stent complications or re-intervention), and cost-effectiveness. Safety analysis was undertaken in the modified ITT population. The study is registered with the International Standard Randomised Controlled Trial registry, ISRCTN12376468, and ClinicalTrials.gov, NCT01915693, and is completed.Findings: 220 patients were randomly assigned between Dec 16, 2013, and Aug 24, 2018, from 23 UK centres. The modified ITT population (n=199) comprised 102 patients in the usual care group and 97 patients in the EBRT group. Radiotherapy did not reduce dysphagia deterioration, which was reported in 36 (49%) of 74 patients receiving usual care versus 34 (45%) of 75 receiving EBRT (adjusted odds ratio 0·82 [95% CI 0·40-1·68], p=0·59) in those with complete data for the primary endpoint. No significant difference was observed in overall survival: median overall survival was 19·7 weeks (95% CI 14·4-27·7) with usual care and 18·9 weeks (14·7-25·6) with EBRT (adjusted hazard ratio 1·06 [95% CI 0·78-1·45], p=0·70; n=199). Median time to first bleeding event or hospital admission for a bleeding event was 49·0 weeks (95% CI 33·3-not reached) with EBRT versus 65·9 weeks (52·7-not reached) with usual care (adjusted subhazard ratio 0·52 [95% CI 0·28-0·97], p=0·038; n=199). No time versus treatment interaction was observed for prespecified QoL outcomes. We found no evidence of differences between trial group in time to first stent complication or re-intervention event. The most common (grade 3-4) adverse event was fatigue, reported in 19 (19%) of 102 patients receiving usual care alone and 22 (23%) of 97 receiving EBRT. On cost-utility analysis, EBRT was more expensive and less efficacious than usual care.Interpretation: patients with advanced oesophageal cancer having SEMS insertion for the primary management of their dysphagia did not gain additional benefit from concurrent palliative radiotherapy and it should not be routinely offered. For a minority of patients clinically considered to be at high risk of tumour bleeding, concurrent palliative radiotherapy might reduce bleeding risk and the need for associated interventions.Funding: National Institute for Health Research Health Technology Assessment Programme.</p

Anointed or appointed? Father–daughter succession within the family business

With the focus on events and outcomes shaping most of the existing family business research on intra-family succession, the subtleties of the incumbent-successor relationship and the dynamic nature of succession as a process of becoming is somewhat neglected. In particular, we have limited understanding of how successor identities are constructed as legitimate between incumbent and successor during father-daughter succession. This article addresses this gap in understanding by exploring how the daughter successor engages in identity work with the father incumbent during the process of succession and the role of father-daughter gendered relations in shaping her successor identity. Using a two-stage research design strategy, we draw upon empirical evidence derived from 14 individual and joint semi-structured interviews to present a narrative analysis of five father-daughter dyads. In so doing, we unveil how the daughter’s successor identity was co-constructed as legitimate and how father-daughter gendered relations influenced this process. Although daughters rely on certain father-daughter relations (preparation, endorsement and osmotic credibility) for legitimacy, they also need to develop independently from their father in order to heighten their own visibility and establish credibility

Head-to-head comparison of BAM15, semaglutide, rosiglitazone, NEN, and calorie restriction on metabolic physiology in female <i>db/db</i> mice

Metabolic disorders such as type 2 diabetes, fatty liver disease, hyperlipidemia, and obesity commonly co-occur but clinical treatment options do not effectively target all disorders. Calorie restriction, semaglutide, rosiglitazone, and mitochondrial uncouplers have all demonstrated efficacy against one or more obesity-related metabolic disorders, but it currently remains unclear which therapeutic strategy best targets the combination of hyperglycaemia, liver fat, hypertriglyceridemia, and adiposity. Herein we performed a head-to-head comparison of 5 treatment interventions in the female db/db mouse model of severe metabolic disease. Treatments included ∼60 % calorie restriction (CR), semaglutide, rosiglitazone, BAM15, and niclosamide ethanolamine (NEN). Results showed that BAM15 and CR improved body weight and liver steatosis to levels superior to semaglutide, NEN, and rosiglitazone, while BAM15, semaglutide, and rosiglitazone improved glucose tolerance better than CR and NEN. BAM15, CR, semaglutide, and rosiglitazone all had efficacy against hypertriglyceridaemia. These data provide a comprehensive head-to-head comparison of several key treatment strategies for metabolic disease and highlight the efficacy of mitochondrial uncoupling to correct multiple facets of the metabolic disease milieu in female db/db mice.</p