The Middle Pleistocene glacial evolution of northern East Anglia, UK: a dynamic tectonostratigraphic-parasequence approach

The Middle Pleistocene glacial history of northern East Anglia is a controversial topic with differing opinions surrounding chronology, provenance and the relative stratigraphic framework. Reconciling the stratigraphic framework of the region is an essential first step to developing onshore–offshore geological models and a robust event-driven chronological framework. Within this study a dynamic tectonostratigraphic–parasequence methodology is applied to deposits traditionally attributed to the Anglian Glaciation (Marine Isotope Stage 12). This approach offers an insight into ice-bed coupling during glaciation and how evolving boundary conditions influenced glacier dynamics. Six major tectonostratigraphic–parasequence assemblages (A1–A6) are recognized in northern East Anglia and correlate with successive advances into the region of North Sea or Pennine lobes of the British Ice Sheet. Individual tectonostratigraphic–parasequence assemblages are bound at their base by a sedimentary contact or, more commonly, a glacitectonic zone. The geometry and structural characteristics of these glacitectonic zones reflect temporal and spatial variations in ice-bed coupling (traction), a function of substrate rheology and, in turn, variations in lithology, porewater availability and thermo-mechanical properties. The role of permafrost may also be significant, promoting proglacial/ice-marginal thrust stacking in front of advancing ice and enhanced ice-bed decoupling during subsequent overriding and subglacial till accretio

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.</p

Utility of FDG-PET Imaging for Risk Stratification of Pancreatic Neuroendocrine Tumors in MEN1

Abstract Context: Patients with multiple endocrine neoplasia type 1 (MEN1) are at high risk of malignant pancreatic neuroendocrine tumors (pNETs). Structural imaging is typically used to screen for pNETs but is suboptimal for stratifying malignant potential. Objective: To determine the utility of fluorodeoxyglucose (18F) positron emission tomography/computed tomography (18F-FDG PET/CT) for predicting the malignant potential of pNETs in MEN1. Design: Retrospective observational study. Setting: Tertiary referral hospital. Patients: Forty-nine adult patients with MEN1 carrying a common MEN1 mutation who underwent 18F-FDG PET/CT for MEN1 surveillance between 1 January 2010 and 30 September 2016. Interventions: Structural and functional imaging (magnetic resonance imaging, CT, ultrasonography, and 18F-FDG PET/CT) and surgical histopathology. Main Outcome Measures: pNET size, behavior, and histopathology. Results: Twenty-five (51.0%) of 49 patients studied had pancreatic lesions on structural imaging. Five (25%) of these had 18F-FDG-PET–avid lesions. In addition, two had solitary FDG-avid liver lesions, and one a pancreatic focus without structural correlate. Eight patients with pNETs underwent surgery (three FDG-avid lesions and five nonavid pNETs). The Ki-67 index was ≥5% in FDG-avid pNETs and &amp;lt;2% in nonavid pNETs. Overall, six of the eight (75%) patients with FDG-avid hepatopancreatic lesions harbored aggressive or metastatic NETs compared with one of 41 patients (2.4%) without hepatopancreatic FDG avidity [P &amp;lt; 0.001; sensitivity; 85.7% (95% confidence interval [CI], 48.7% to 99.3%); specificity, 95.2% (95% CI, 84.2% to 99.2%)]. Conclusion: 18F-FDG PET/CT is an effective screening modality in MEN1 for identifying pNETs of increased malignant potential. Surgical resection is recommended for FDG-avid pNETs. </jats:sec

Rare Copy Number Variants A Point of Rarity in Genetic Risk for Bipolar Disorder and Schizophrenia

Context: Recent studies suggest that control sample using a high-density microarray.Setting: The Wellcome Trust Case Control Consortium.Participants: There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents.Main Outcome Measures: Overall load of CNVs and presence of rare CNVs.Results: The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder.Conclusions: Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder