New Perspectives on European Citizenship: Roma and Minority Rights

Roma are actively engaged in a process of identity formation and transnational contentious collective action, using (and utilising) EU and European institutions to remedy longstanding grievances and a litany of state-sponsored abuses (inc. coercive sterilization, segregated schooling and social marginalization). Empowered by their newly acquired European Union citizenship, and improved political station at the international, European and local level, Roma activists are working to ensure their citizenship is never again usurped (as has been the case historically). Judicial victories at the European level have helped both to strengthen Roma identity and legitimise their national character. This begs the question: Can a polycentric polity, in this case the EU, accommodate opposing conceptions of citizenship and nationality without undermining its intergovernmental foundation/character

A new specimen of Dicynodon traquairi (Newton) (Synapsida: Anomodontia) from the Late Permian (Tartarian) of northern Scotland

A recently discovered natural mould of a complete, almost undistorted, skull and lower jaw of a dicynodont (c. 237mmoverall length), in a block of Upper Permian sandstone (= Dicynodon Assemblage Zone: Hopeman Sandstone Formation) from Clashach Quarry, Hopeman, Morayshire, is described using novel techniques, including Computed Tomography scanning (CT), Magnetic Resonance Imaging (MRI) and rapid-prototype modelling. It is assigned to the taxon Dicynodon traquairi (Newton, 1893). When compared with Dicynodon lacerticeps Owen, 1845, it is distinguished principally by having the pineal opening sunk deeply between the diverging parietals, subparallel pterygoid rami narrowly separated, with no transverse flanges, and in addition, a deeply grooved lower jaw symphysis. The southern African fauna lived on river flats in a higher (southern) palaeolatitude than the possibly desert-dwelling Scottish species. The Hopeman Sandstone Formation is of the same age as the better-known Cutties Hillock Sandstone Formation, whose fauna is briefly discussed and reviewed

Clinical application of capsule sponge testing in symptomatic reflux disease:a national prospective cohort study

Background Capsule sponge testing, using an oesophageal cell collection device with biomarkers, was implemented nationally across Scotland in 2020 for symptomatic reflux patients referred to secondary care for non-urgent endoscopy. The aim was to use capsule sponge testing as a triage tool to reduce pressures on the endoscopy service during COVID-19, focus endoscopy resources on those most likely to have pathology and streamline the patient pathway. This prospective cohort study presents the first real-world results and evaluates the clinical application of capsule sponge testing in symptomatic reflux disease based on endoscopic biopsy results. Methods Over a 32-month period, all patients undergoing capsule sponge testing for investigation of reflux symptoms across 11 Scottish health boards were identified from prospectively maintained databases. Individual patient records were interrogated to collect baseline demographics, capsule sponge test result (TFF3/atypia/p53) and ongoing clinical management. Further analysis was performed on patients who subsequently underwent upper gastrointestinal (UGI) endoscopy. Results 1385 tests were performed for reflux symptoms in 1305 patients. The median follow-up time was 20 months (IQR 12–27). 1103/1385 tests (79.6%) were negative for biomarkers. 913/1305 (70.0%) patients were discharged with no additional investigation required. 355/1305 patients (27.2%) underwent UGI endoscopy due to a positive or insufficient result or ongoing symptoms. With insufficient tests excluded, 52/314 patients (16.6%) had intestinal metaplasia (IM) on endoscopic biopsies, which strongly correlated with positive biomarkers (88.5% vs. 11.5%; p &lt; 0.001), including 1 case of dysplasia. 10/1103 sponge negative patients (0.9%) had biopsies demonstrating IM (n = 6) or malignancy (n = 4): 1 patient was diagnosed with oesophageal adenocarcinoma 27 months later and 3 patients had gastric malignancy, which relies on symptom assessment to direct to endoscopy since the capsule sponge is an oesophageal test. Conclusions Capsule sponge testing is effectively at identifying the 30% of symptomatic reflux patients requiring further investigation with UGI endoscopy and aiding the diagnosis of Barrett’s oesophagus in clinical practice. Judicious follow-up of the discharged group will be critical to validate the ongoing use of capsule sponge testing long-term.</p

Oesophageal cell collection device and biomarker testing to identify high-risk Barrett’s patients requiring endoscopic investigation

The authors thank Professor Rebecca Fitzgerald for her expertise and advice in improving this manuscript. This work is presented on behalf of all members of the CytoSCOT group, including nursing and administrative staff, without whom this work would not have been possible.Peer reviewe

Yield of colorectal cancer at colonoscopy according to faecal haemoglobin concentration in symptomatic patients referred from primary care

Background: Lower gastrointestinal (GI) symptoms are poor predictors of colorectal cancer (CRC). This study examined the diagnostic yield of colonoscopy by faecal haemoglobin concentration (f‐Hb) in symptomatic patients assessed in primary care by faecal immunochemical testing (FIT). Methods: In three Scottish NHS Boards, FIT kits (HM‐JACKarc, Hitachi Chemical Diagnostics Systems Co., Ltd, Tokyo, Japan) were used by GPs to guide referrals for patients with lower GI symptoms (lab data studied for 12 months from December 2015 onward in Tayside, 18 months from June 2018 onward in Fife, and 5 months from September 2018 onward in Greater Glasgow and Clyde). CRC cases diagnosed at colonoscopy were ascertained from colonoscopy and pathology records. Results: 4841 symptomatic patients who underwent colonoscopy after FIT submission were included. Of 2166 patients (44.7%) with f‐Hb &lt;10 µg Hb/g faeces (µg/g), 14 (0.6%) were diagnosed with CRC, with a number needed to scope (NNS) of 155. Of 2675 patients (55.3%) with f‐Hb ≥10 µg/g, 252 were diagnosed with CRC (9.4%) with a NNS of 11. Of 705 patients with f‐Hb ≥400 µg/g, 158 (22.4%) were diagnosed with CRC with a NNS of 5. Over half of those diagnosed with CRC with f‐Hb &lt;10 µg/g had co‐existing anaemia. Conclusions: Symptomatic patients with f‐Hb ≥10 µg/g should undergo further investigation for CRC, while higher f‐Hb could be used to triage its urgency during the COVID‐19 recovery phase. Patients with f‐Hb &lt;10 µg/g, without anaemia, are very unlikely to be diagnosed with CRC and the majority need no further investigation

Improving the Quality of Care in Care Homes Using the Quality Improvement Collaborative Approach: Lessons Learnt from Six Projects Conducted in the UK and The Netherlands.

The Breakthrough Series Quality Improvement Collaborative (QIC) initiative is a well-developed and widely used approach, but most of what we know about it has come from healthcare settings. In this article, those leading QICs to improve care in care homes provide detailed accounts of six QICs and share their learning of applying the QIC approach in the care home sector. Overall, five care home-specific lessons were learnt: (i) plan for the resources needed to support collaborative teams with collecting, processing, and interpreting data; (ii) create encouraging and safe working environments to help collaborative team members feel valued; (iii) recruit collaborative teams, QIC leads, and facilitators who have established relationships with care homes; (iv) regularly check project ideas are aligned with team members' job roles, responsibilities, and priorities; and (v) work flexibly and accept that planned activities may need adapting as the project progresses. These insights are targeted at teams delivering QICs in care homes. These insights demonstrate the need to consider the care home context when applying improvement tools and techniques in this setting

Structural Analysis of Papain-Like NlpC/P60 Superfamily Enzymes with a Circularly Permuted Topology Reveals Potential Lipid Binding Sites

NlpC/P60 superfamily papain-like enzymes play important roles in all kingdoms of life. Two members of this superfamily, LRAT-like and YaeF/YiiX-like families, were predicted to contain a catalytic domain that is circularly permuted such that the catalytic cysteine is located near the C-terminus, instead of at the N-terminus. These permuted enzymes are widespread in virus, pathogenic bacteria, and eukaryotes. We determined the crystal structure of a member of the YaeF/YiiX-like family from Bacillus cereus in complex with lysine. The structure, which adopts a ligand-induced, “closed” conformation, confirms the circular permutation of catalytic residues. A comparative analysis of other related protein structures within the NlpC/P60 superfamily is presented. Permutated NlpC/P60 enzymes contain a similar conserved core and arrangement of catalytic residues, including a Cys/His-containing triad and an additional conserved tyrosine. More surprisingly, permuted enzymes have a hydrophobic S1 binding pocket that is distinct from previously characterized enzymes in the family, indicative of novel substrate specificity. Further analysis of a structural homolog, YiiX (PDB 2if6) identified a fatty acid in the conserved hydrophobic pocket, thus providing additional insights into possible function of these novel enzymes

Multigene Molecular Systematics Confirm Species Status of Morphologically Convergent Pagurus Hermit Crabs

Introduction: In spite of contemporary morphological taxonomy appraisals, apparent high morphological similarity raises uncertainty about the species status of certain Pagurus hermit crabs. This is exemplified between two European species, Pagurus excavatus (Herbst, 1791) and Pagurus alatus (Fabricius 1775), whose species status is still difficult to resolve using morphological criteria alone. Methodology/Principal Findings: To address such ambiguities, we used combinations of Maximum Likelihood (ML) and Bayesian Inference (BI) methods to delineate species boundaries of P. alatus and P. excavatus and formulate an intermediate Pagurus phylogenetic hypothesis, based upon single and concatenated mitochondrial (cytochrome oxidase I [COI]) and nuclear (16S and 28s ribosomal RNA) gene partitions. The molecular data supported the species status of P. excavatus and P. alatus and also clearly resolved two divergent clades within hermit crabs from the Northeast Atlantic Ocean and the Mediterranean Sea. Conclusions/Significance: Despite the abundance and prominent ecological role of hermit crabs, Pagurus, in North East Atlantic Ocean and Mediterranean Sea ecosystems, many important aspects of their taxonomy, biology, systematics and evolution remain poorly explored. The topologies presented here should be regarded as hypotheses that can be incorporated into the robust and integrated understanding of the systematic relationships within and between species of the genus Pagurus inhabiting the Northeast Atlantic Ocean and the Mediterranean Sea

Radical surgery versus organ preservation via short-course radiotherapy followed by transanal endoscopic microsurgery for early-stage rectal cancer (TREC): a randomised, open-label feasibility study

Background: Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. Methods: TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. Findings: Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. Interpretation: Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. Funding: Cancer Research UK