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Fragile X syndrome, the most common inherited form of human mental retardation, is caused by mutations of the Fmr1 gene that encodes the fragile X mental retardation protein (FMRP). Biochemical evidence indicates that FMRP binds a subset of mRNAs and acts as a regulator of translation. However, the consequences of FMRP loss on neuronal function in mammals remain unknown. Here we show that a form of protein synthesis-dependent synaptic plasticity, long-term depression triggered by activation of metabotropic glutamate receptors, is selectively enhanced in the hippocampus of mutant mice lacking FMRP. This finding indicates that FMRP plays an important functional role in regulating activity-dependent synaptic plasticity in the brain and suggests new therapeutic approaches for fragile X syndrome.

National guidelines recommend 'early' coronary angiography within 96 h of presentation for patients with non-ST elevation acute coronary syndromes (NSTE-ACS). Most patients with NSTE-ACS present to their district general hospital (DGH), and await transfer to the regional cardiac centre for angiography. This care model has inherent time delays, and delivery of timely angiography is problematic. The objective of this study was to assess a novel clinical care pathway for the management of NSTE-ACS, known locally as the Heart Attack Centre-Extension or HAC-X, designed to rapidly identify patients with NSTE-ACS while in DGH emergency departments (ED) and facilitate transfer to the regional interventional centre for 'early' coronary angiography. This was an observational study of 702 patients divided into two groups; 391 patients treated before the instigation of the HAC-X pathway (Pre-HAC-X), and 311 patients treated via the novel pathway (Post-HAC-X). Our primary study end point was time from ED admission to coronary angiography. We also assessed the length of hospital stay. Median time from ED admission to coronary angiography was 7.2 (IQR 5.1-10.2) days pre-HAC-X compared to 1.0 (IQR 0.7-2.0) day post-HAC-X (p<0.001). Median length of hospital stay was 3.0 (IQR 2.0-6.0) days post-HAC-X v 9.0 (IQR 6.0-14.0) days pre-HAC-X (p<0.0005). This equates to a reduction of six hospital bed days per NSTE-ACS admission. The introduction of this novel care pathway was associated with significant reductions in time to angiography and in total hospital bed occupancy for patients with NSTE-ACS.

Analysis of the North/South Ireland Food Consumption Survey database found that 33% of overweight and obese adults reported modifying their eating habits in the past year because of weight concerns (i.e. 514 620 adults). Assuming 10% of those modifying their diets to lose weight use a VLCD (i.e. 'widespread use') the following side effects were projected: 5146 dieters with hair loss; 124 with acute gout; thirty-one with diabetic ketoacidosis; forty-seven hospitalizations as a result of cardiac arrhythmias.

Cancer is a major cause of death in children worldwide, and the recorded incidence tends to increase with time. Internationally comparable data on childhood cancer incidence in the past two decades are scarce. This study aimed to provide internationally comparable local data on the incidence of childhood cancer to promote research of causes and implementation of childhood cancer control. This population-based registry study, devised by the International Agency for Research on Cancer in collaboration with the International Association of Cancer Registries, collected data on all malignancies and non-malignant neoplasms of the CNS diagnosed before age 20 years in populations covered by high-quality cancer registries with complete data for 2001–10. Incidence rates per million person-years for the 0–14 years and 0–19 years age groups were age-adjusted using the world standard population to provide age-standardised incidence rates (WSRs), using the age-specific incidence rates (ASR) for individual age groups (0–4 years, 5–9 years, 10–14 years, and 15–19 years). All rates were reported for 19 geographical areas or ethnicities by sex, age group, and cancer type. The regional WSRs for children aged 0–14 years were compared with comparable data obtained in the 1980s. Of 532 invited cancer registries, 153 registries from 62 countries, departments, and territories met quality standards, and contributed data for the entire decade of 2001–10. 385 509 incident cases in children aged 0–19 years occurring in 2·64 billion person-years were included. The overall WSR was 140·6 per million person-years in children aged 0–14 years (based on 284 649 cases), and the most common cancers were leukaemia (WSR 46·4), followed by CNS tumours (WSR 28·2), and lymphomas (WSR 15·2). In children aged 15–19 years (based on 100 860 cases), the ASR was 185·3 per million person-years, the most common being lymphomas (ASR 41·8) and the group of epithelial tumours and melanoma (ASR 39·5). Incidence varied considerably between and within the described regions, and by cancer type, sex, age, and racial and ethnic group. Since the 1980s, the global WSR of registered cancers in children aged 0–14 years has increased from 124·0 (95% CI 123·3–124·7) to 140·6 (140·1–141·1) per million person-years. This unique global source of childhood cancer incidence will be used for aetiological research and to inform public health policy, potentially contributing towards attaining several targets of the Sustainable Development Goals. The observed geographical, racial and ethnic, age, sex, and temporal variations require constant monitoring and research. International Agency for Research on Cancer and the Union for International Cancer Control.

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease (CKD). Remote ischemic preconditioning (RIPC) may mitigate the renal ischemia–reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI. We undertook a randomized controlled trial of RIPC to prevent AKI in 86 patients with CKD (estimated glomerular filtration rate under 60ml/min per 1.73m2) undergoing coronary artery bypass graft (CABG) surgery. Forty-three patients each were randomized to receive standard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion. The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3mg/dl within 48h of surgery. Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C, neutrophil gelatinase–associated lipocalin (NGAL), and interleukin-18 (IL-18), and urinary biomarkers including NGAL, IL-18, and kidney injury molecule-1 measured at 6, 12, and 24h after CABG, and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury. Clinical and operative characteristics were similar between the preconditioned and control groups. AKI developed in 12 patients in both groups within 48h of CABG. There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG. Thus, RIPC induced by forearm ischemia–reperfusion had no effect on the frequency of AKI after CABG in patients with CKD.

Models of integrated, multidisciplinary care are optimal in the setting of complex, chronic diseases and in the overlap of medical and mental health disease, both of which apply to alcohol-related liver disease (ALD). Alcohol use disorder (AUD) drives nearly all cases of ALD, and coexisting mental health disease is common. ALD is a complex condition with severe clinical manifestations and high mortality that can occasionally lead to liver transplantation. As a result, integrated care for ALD is an attractive proposition. The aim of this narrative review was to: (1) review the overlapping and concerning trends in the epidemiology of AUD and ALD; (2) use a theoretical framework for integrated care known as the “five-component model” as a basis to highlight the need for integrated care and the overlapping clinical manifestations and management of the 2 conditions; and (3) review the existing applications of integrated care in this area. We performed a narrative review of epidemiology, clinical manifestations, and management strategies in AUD and ALD, with a particular focus on areas of overlap that are pertinent to clinicians who manage each disease. Previously published models were reviewed for integrating care in AUD and ALD, both in the general ALD population and in the setting of liver transplantation. The incidences of AUD and ALD are rising, with a pronounced acceleration driven by the Coronavirus Disease 2019 pandemic. Hepatologists are underprepared to diagnose and treat AUD despite its high prevalence in patients with liver disease. A patient who presents with overlapping clinical manifestations of both AUD and ALD may not fit neatly into typical treatment paradigms for each individual disease but rather will require new management strategies that are appropriately adapted. As a result, the dimensions of integrated care, including collective ownership of shared goals, interdependence among providers, flexibility of roles, and newly created professional activities, are highly pertinent to the holistic management of both diseases. Integrated care models have proliferated as recognition grows of the dual pathology of AUD and ALD. Ongoing coordination across disciplines and research in the fields of hepatology and addiction medicine are needed to further elucidate optimal mechanisms for collaboration and improved quality of care.

Background Primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-segment elevation myocardial infarction (STEMI) provided PPCI is performed in a timely manner. There is conflicting data regarding the outcomes of patients treated in-hours versus out of-hours, we sought to determine whether in-hospital and long-term outcomes are different among in-hours versus out of hours PPCI patients. Table 1 In hours Out of hours (n=1299) (n=2048) p Value Gender (Male) 74.2% 77.1% 0.051 Age (years) 64.02±14.2 63.16±14.3 0.126 Hypertension 39.2% 38.3% 0.344 Diabetes mellitus 17.3% 17.7% 0.424 Hypercholestrolaemia 30.9% 29.7% 0.253 Smoking history 55.6% 58.0% 0.116 Previous MI 13.2% 11.8% 0.156 Previous CABG 2.6% 2.6% 0.539 Previous PCI 9.9% 9.6% 0.449 Cardiogenic shock 5.3% 6.4% 0.113 Ethnicity (Caucasian) 66.6% 64.4% 0.226 LVEF 43.70±7.5 43.69±7.5 0.985 CRF (eGFR <60) 18.5% 17.9% 0.227 Methods This was an observational study of 3347 STEMI patients treated with PPCI between 2004 and 2012 at a single centre with follow-up for a median of 3.3 years (IQR range 1.2–4.6 years). The primary end-point was long-term major adverse cardiac events (MACE) with all cause mortality a secondary endpoint. Of these, 1299 patients (38.8%) underwent PPCI during a weekday between 08:00 and 18:00 (routine-hours group) and 2048 (61.2%) underwent PPCI on a weekday between 18:00 and 08:00 or a weekend (out-of-hours group). Results There were no differences in baseline characteristics between the two groups with comparable door to balloon times (IHs 67.8 min vs OOHs 69.6 min, p=0.709) and procedural success (table 1). In hospital mortality rates were comparable between the two groups (IHs 3.6% vs OFHs 3.2%) with timing of presentation not predictive of outcome (HR 1.25 (95% CI 0.74 to 2.11). Over the follow-up period there were no significant differences in rates of mortality (IHs 7.4% vs OFHs 7.2%, p=0.44) or MACE (IHs 15.4% vs OFHs 14.1%, p=0.28) (figure 1) between the two groups. After adjustment for confounding variables using multivariate analysis, timing of presentation was not an independent predictor of mortality (HR 1.04 95% CI 0.78 to 1.39). Figure 1 Conclusions This large registry study demonstrates that in a large volume, well-staffed centre, PPCI outside routine-working hours is safe with no difference in outcome compared with PPCI during routine-working hours.

This research explores the learning practices of graduate humanities students in South Korea as evidenced through mobile technology. Fieldwork was carried out with 25 graduate students across several universities in Seoul involving interviews, mobile artifacts, and reflective prompts. The study asked how graduate students use mobile technology to support their learning, what learning practices are presented in this mobile technology use, and whether this combination of mobile technology use and learning practice suggest a learner trajectory (Wenger, 1998) in respect to the disciplinary community. Analysis presents the trajectories being evidenced by these graduate students, leading to a discussion on how graduate students are shaping their learning practices and participation in the humanities through mobile technology. Findings suggest the trajectories that graduate students exhibit in relation to their disciplinary communities are structured by mobile technology itself, informal and formal practices consistent with community participation, and South Korean sociocultural practice. Trajectories presented were complex aggregations of adherence, subversion, and intent, suggesting that participation in the disciplinary community was shaped by multimemberships and elements of individualized practice. The findings suggest that more robust methodologies are needed to account for the complexity of learning trajectories in sociocultural contexts. The contributions of this thesis are a more sophisticated definition of mobile learning, methodological models that allow for this definition to be evidenced, an analytical framework that coheres the disparate data points being evidenced through mobile technology, and a more holistic presentation of mobile learning than has been presented in research on South Korean higher education.

BackgroundPrevious studies have demonstrated similar outcomes over the short to mid term in patients treated with paclitaxel-eluting stents (PESs) or sirolimus-eluting stents (SESs). However there is limited “real-world” data investigating long term outcomes. This study compared outcomes at 5 years following revascularisation in these two patient groups.Methods4252 consecutive patients underwent PCI with either paclitaxel-eluting (PES) or sirolimus-eluting stents (SES) at a single centre (October 2003–January 2011). Indications for PCI included stable and unstable angina. Left main and vein graft lesions were excluded. Demographic and procedural data were collected at the time of intervention. All cause mortality data were obtained from the Office of National Statistics via the BCIS/CCAD national audit out to a median of 4.0 years (95% CI 2.4 to 5.6 years). Primary end point was major adverse cardiac events (MACE) a composite of all cause mortality, myocardial infarction and target vessel revascularisation (TVR).ResultsThere were 1592 (37%) patients treated with SES and 2660 (63%) patients treated with PES. Baseline demographic, angiographic, and procedural characteristics were similar between patients treated with PES and those treated with SES. At 5 years, there were no statistical differences in MACE between the stent types (SES 15.9% 95% CI 12.7 to 19.4 vs PES: 16.5% 95% CI 12.6 to 20.3, p=0.9). This consisted of similar rates of all-cause mortality (10.1% vs 9.3%, p=0.4), TVR (5.3% vs 6.4%, p=0.4), and stent thrombosis (2% vs 1.8%, p=0.5). In diabetic patients (n=1172 (28%)), there was a trend towards lower MACE favouring PES but this did not reach statistical significance (19% vs 24%, p=0.16). On univariate and subsequent multivariate analysis there was no benefit from either stent type.ConclusionThis “real-world” observational analysis of DES-treated patients, PES and SES demonstrates similar overall safety and efficacy over a 5-year follow-up period with low rates of TVR.Abstract 036 Figure 1MACE events over 5-year follow-up period.Abstract 036 Figure 2MACE events in DM patients over 5-year follow-up period.