A shared accretion instability for black holes and neutron stars.

Accretion disks around compact objects are expected to enter an unstable phase at high luminosity1. One instability may occur when the radiation pressure generated by accretion modifies the disk viscosity, resulting in the cyclic depletion and refilling of the inner disk on short timescales2. Such a scenario, however, has only been quantitatively verified for a single stellar-mass black hole3-5. Although there are hints of these cycles in a few isolated cases6-10, their apparent absence in the variable emission of most bright accreting neutron stars and black holes has been a continuing puzzle11. Here we report the presence of the same multiwavelength instability around an accreting neutron star. Moreover, we show that the variability across the electromagnetic spectrum-from radio to X-ray-of both black holes and neutron stars at high accretion rates can be explained consistently if the accretion disks are unstable, producing relativistic ejections during transitions that deplete or refill the inner disk. Such a new association allows us to identify the main physical components responsible for the fast multiwavelength variability of highly accreting compact objects.

Medicare for All: Considerations for Neuroradiologists.

The year 2019 featured extensive debates on transforming the United States multipayer health care system into a single-payer system. At a time when reimbursement structures are in flux and potential changes in government may affect health care, it is important for neuroradiologists to remain informed on how emerging policies may impact their practices. The purpose of this article is to examine potential ramifications for neuroradiologist reimbursement with the Medicare for All legislative proposals. An institution-specific analysis is presented to illustrate general Medicare for All principles in discussing issues applicable to practices nationwide.

Evaluating the impact of an insulin pump discontinuation action plan on patient or caregiver confidence and anxiety.

AIMS: Insulin pump failure and adverse events are common and therefore anticipatory education is recommended. Research in other chronic diseases shows written action plans improve confidence and adherence during an acute deterioration. However, no similar data exists for patients with type one diabetes mellitus provided with anticipatory education via an insulin pump action plan. This study evaluates whether an insulin pump action plan improves patient and caregiver confidence in managing a potential pump failure without a subsequent increase in anxiety. METHODS: Adults with type one diabetes mellitus and caregivers of children with type 1 diabetes on continuous subcutaneous insulin infusions across four New Zealand diabetes services participated. Participants completed a questionnaire examining pump-related adverse events and self-reported confidence and anxiety in managing pump failure. An insulin pump action plan and focused education by their diabetes team was provided, with a follow-up questionnaire at least 3 months later. RESULTS: 174/270 pump patients participated initially, with a follow-up response rate of 84.5% (147/174). Despite prior provision, many could not recall having an insulin pump action plan at study commencement (101/174, 58%), and of these 92% stated they would have liked one. Patients had good levels of confidence in the reliability of their pump and infusion sets/sites (Likert scores of 4.4/5 and 3.95/5) which was not undermined by the insulin pump action plan. Confidence in managing a potential pump failure showed a small but significant increase (3.66/5 to 3.95/5, p = 0.004) present in both adults and parents, with anxiety also showing a small increase (2.16/5 to 2.38/5, p = 0.012). CONCLUSION: Patient recall of prior insulin pump action plan education is poor, with the vast majority of patients interested in further written anticipatory education regarding potential pump failure. The provision of an insulin pump action plan increases self-reported confidence in managing unexpected pump failure with a small associated increase in anxiety.

A novel signalling screen demonstrates that CALR mutations activate essential MAPK signalling and facilitate megakaryocyte differentiation.

Most myeloproliferative neoplasm (MPN) patients lacking JAK2 mutations harbour somatic CALR mutations that are thought to activate cytokine signalling although the mechanism is unclear. To identify kinases important for survival of CALR-mutant cells, we developed a novel strategy (KISMET) that utilizes the full range of kinase selectivity data available from each inhibitor and thus takes advantage of off-target noise that limits conventional small-interfering RNA or inhibitor screens. KISMET successfully identified known essential kinases in haematopoietic and non-haematopoietic cell lines and identified the mitogen activated protein kinase (MAPK) pathway as required for growth of the CALR-mutated MARIMO cells. Expression of mutant CALR in murine or human haematopoietic cell lines was accompanied by myeloproliferative leukemia protein (MPL)-dependent activation of MAPK signalling, and MPN patients with CALR mutations showed increased MAPK activity in CD34 cells, platelets and megakaryocytes. Although CALR mutations resulted in protein instability and proteosomal degradation, mutant CALR was able to enhance megakaryopoiesis and pro-platelet production from human CD34+ progenitors. These data link aberrant MAPK activation to the MPN phenotype and identify it as a potential therapeutic target in CALR-mutant positive MPNs.

Identification of novel peptide motifs in the serpin maspin that affect vascular smooth muscle cell function.

Maspin is a non-inhibitory member of the serpin family that affects cell behaviours related to migration and survival. We have previously shown that peptides of the isolated G α-helix (G-helix) domain of maspin show bioactivity. Migration, invasion, adhesion and proliferation of vascular smooth muscle cells (VSMC) are important processes that contribute to the build-up of atherosclerotic plaques. Here we report the use of functional assays of these behaviours to investigate whether other maspin-derived peptides impact directly on VSMC; focusing on potential anti-atherogenic properties. We designed 18 new peptides from the structural moieties of maspin above ten amino acid residues in length and considered them beside the existing G-helix peptides. Of the novel peptides screened those with the sequences of maspin strand 4 and 5 of beta sheet B (S4B and S5B) reduced VSMC migration, invasion and proliferation, as well as increasing cell adhesion. A longer peptide combining these consecutive sequences showed a potentiation of responses, and a 7-mer contained all essential elements for functionality. This is the first time that these parts of maspin have been highlighted as having key roles affecting cell function. We present evidence for a mechanism whereby S4B and S5B act through ERK1/2 and AMP-activated protein kinase (AMPK) to influence VSMC responses.

Inpatient magnetic resonance cholangiopancreatography: does it increase the efficiency in emergency hepatopancreaticobiliary surgery services?

INTRODUCTION Magnetic resonance cholangiopancreatography (MRCP) is commonly used to evaluate the biliary tree, although indications for patients who require inpatient imaging are not fully defined. The aim of this study was to evaluate inpatient MRCP performed on surgical patients and to devise a treatment pathway for these patients. MATERIAL AND METHODS All adult inpatient MRCP examinations between January 2012 and December 2013 were reviewed. Demographic, clinical and radiological data were collated. RESULTS During the study period, 271 inpatient MRCP were requested, of which 234 examinations were included. The majority of patients were female (n=140) and the median age was 63 years (range 16-93 years). Surgical admissions accounted for 171 (73%) of cases. Indications for inpatient MRCP include gallstone-related complications (n=173; 74%), malignant process (n=17; 7%) and other indications (n=44; 19%). Overall, inpatient MRCP led to further inpatient interventions in 22% (gallstone group, n=32, 18%; patients with malignancy, n=8, 47%; other indications, n=12, 27%). The median duration of inpatient MRCP from request to examination was 2 days (range 0-15 days) and median reporting after examination was 1 day (range 0-14 days). DISCUSSION AND CONCLUSION Improved access and timely reporting of iMRCP may reduce length of hospital stay. Inpatient MRCP also led to further inpatient interventions, in particular, in patients with malignancy.

Insulin pump-associated adverse events are common, but not associated with glycemic control, socio-economic status, or pump/infusion set type.

AIMS: While there have been many outcome-focussed studies examining insulin pump therapy, only a few have looked at potential adverse events (AEs), with none examining the relationship between AEs and pump/infusion set type, ethnicity or socio-economic status. In addition, current data on the incidence and characteristics of pump-associated AEs are confined to one paediatric centre. We aimed to describe the incidence, characteristics and potential predictors of insulin pump-associated AEs in New Zealand adults and children with T1DM. METHODS: We approached adults and families of children with T1DM on insulin pumps in four main New Zealand centres. Participants completed a questionnaire examining pump-related issues they had experienced in the preceding 12 months. RESULTS: Response rate was 64 % with 174 of 270 eligible people participating in the study. 84 % of subjects reported one or more AEs, with an overall AE incidence of 3.42 per person/year (95 % CI 3.14, 3.73). An event serious enough to require a hospital presentation occurred in 9.8 %, all but one reporting high ketones or diabetic ketoacidosis (DKA). Set/site problems were the AE most commonly reported (by 53 % of respondents), followed by cutaneous complications (43 %) and pump malfunction (38 %). Few predictors of AEs (of any type) were found; however, a negative binomial regression model found that a longer duration of pumping (p = 0.018) and age <18 years (p = 0.043) were both associated with fewer AEs (all types combined). CONCLUSIONS: Insulin pump-associated AEs are very common. However, few variables are predictive of them with no relationships seen with glycaemic control, socio-economic status, pump manufacturer or infusion set type. Based on these findings, AEs should be anticipated in both adults and children, with anticipatory patient education and training recommended for their successful and safe use.

Clinical review: insulin pump-associated adverse events in adults and children.

AIMS: Insulin pumps are a vital and rapidly developing tool in the treatment of type 1 diabetes mellitus in both adults and children. Many studies have highlighted outcomes and assessed their potential advantages, but much of the data on adverse outcomes are limited and often based on outdated technology. We aimed to review and summarize the available literature on insulin pump-associated adverse events in adults and children. METHODS: A literature search was undertaken using PubMed, EMBASE, and the Cochrane library. Articles were then screened by title, followed by abstract, and full text as needed. A by-hand search of reference lists in identified papers was also utilised. All searches were limited to English language material, but no time limits were used. RESULTS: Current and past literature regarding insulin pump-associated adverse events is discussed, including potential metabolic and non-metabolic adverse events, in particular: pump malfunction; infusion set/site issues; and cutaneous problems. We show that even with modern technology, adverse events are common, occurring in over 40 % of users per year, with a minority, particularly in children, requiring hospital management. Hyperglycaemia and ketosis are now the most common consequences of adverse events and are usually associated with infusion set failure. This differs from older technology where infected infusion sites predominated. CONCLUSIONS: This timely review covers all potential insulin pump-associated adverse events, including their incidence, features, impacts, and contributory factors such as the pump user. The importance of ongoing anticipatory education and support for patients and families using this intensive insulin technology is highlighted, which if done well should improve the overall experience of pump therapy for users, and hopefully reduce the incidence and impact of severe adverse events.

Stakeholder attitudes towards the role and application of informed consent for newborn bloodspot screening: a study protocol.

INTRODUCTION: Newborn bloodspot screening (NBS) involves testing a small sample of blood taken from the heel of the newborn for a number of serious and life-limiting conditions. In Canada, newborn screening programmes fall under provincial and territorial jurisdiction with no federal coordination. To date, we know very little about the underlying beliefs around different consent practices or how terminology is interpreted by different individuals. Differences in attitudes may have important healthcare consequences. This study will provide empirical data comparing stakeholder opinions on their understanding of consent-related terminology, the perceived applicability of different consent approaches to newborn screening, and the requirements of these different approaches. METHODS AND ANALYSIS: Parents, healthcare professionals and policymakers will be recruited in the provinces of Ontario and Newfoundland and Labrador. Parents will be identified through records held by each provincial screening programme. Healthcare professionals will be purposively sampled on the basis of engagement with newborn screening. Within each province we will identify policymakers who have policy analysis or advisory responsibilities relating to NBS. Data collection will be by qualitative interviews. We will conduct 20 interviews with parents of young children, 10 interviews with key healthcare professionals across the range of appropriate specialties and 10 with policymakers at each site (40 per site, total, N=80). The examination of the transcripts will follow a thematic analysis approach. Recruitment started in June 2014 and is expected to be complete by June 2015. ETHICS AND DISSEMINATION: This study received ethics approval from the Ottawa Health Science Network Research Ethics Board, the Children's Hospital of Eastern Ontario Research Ethics Board (both Ontario), and the Health Research Ethics Authority (Newfoundland and Labrador). RESULTS: These will be reported in peer-reviewed publications and conference presentations. The results will have specific application to the development of parent education materials for newborn screening.

A national survey of attitudes to research in Scottish General Surgery Trainees.

INTRODUCTION: Given the importance placed on awareness and participation in research by Speciality and Training organisations, we sought to survey Scottish trainee attitudes to exposure to research practice during training and research in or out of programme. METHODS: An online survey was distributed to core and specialist trainees in general surgery in Scotland. RESULTS: Over a 4-month period, 108 trainees (75 ST/SPRs and 33 CTs) completed the survey. In their current post, most were aware of ongoing research projects (77%) and 55% were aware of trial recruitment. Only 47% attend regular journal clubs. Most believe that they are expected to present (89%) and publish (82%) during training. Most (59%) thought that participation in research is well supported. 57% were advised to undertake time out of programme research, mostly by consultants (48%) and training committee (36%). Of the 57 with time out of programme research experience, most did so in early training (37%) or between ST3-5 (47%). 28 out of the 36 (78%) without a national training number secured one after starting research. Most undertook research in a local academic unit (80%) funded by small grants (47%) or internally (33%). Most research (69%) was clinically orientated (13/55 clinical, 25/55 translational). 56% of those completing time out of programme research obtained an MD or PhD. About 91% thought that research was relevant to a surgical career. CONCLUSIONS: Most trainees believe that research is an important part of training. Generally, most trainees are exposed to research practices including trial recruitment. However, <50% attend regular journal clubs, a pertinent point, given the current 'exit exam' includes the assessment of critical appraisal skills.

Clinical fellowships in surgical training: analysis of a national pan-specialty workforce survey.

BACKGROUND: Fellowship posts are increasingly common and offer targeted opportunities for training and personal development. Despite international demand, there is little objective information quantifying this effect or the motivations behind undertaking such a post. The present study investigated surgical trainees' fellowship aims and intentions. METHODS: An electronic, 38-item, self-administered questionnaire survey was distributed in the United Kingdom via national and regional surgical mailing lists and websites via the Association of Surgeons in Training, Royal Surgical Colleges, and Specialty Associations. RESULTS: In all, 1,581 fully completed surveys were received, and 1,365 were included in the analysis. These represented trainees in core or higher training programs or research from all specialties and training regions: 66 % were male; the mean age was 32 years; 77.6 % intended to or had already completed a fellowship. Plastic surgery (95.2 %) and cardiothoracic (88.6 %) trainees were most likely to undertake a fellowship, with pediatrics (51.2 %), and urology (54.3 %) the least likely. Fellowship uptake increased with seniority (p < 0.01) and was positively correlated (p = 0.016, r = 0.767) with increasing belief that fellowships are necessary to the attainment of clinical competence, agreed by 73.1 %. Fellowship aims were ranked in descending order of importance as attaining competence, increasing confidence, and attaining subspecialist skills. CONCLUSIONS: Over three-quarters of trainees have or will undertake a clinical fellowship, varying with gender, specialty, and seniority. Competence, confidence, and subspecialty skills development are the main aims. The findings will influence workforce planning, and perceptions that current training does not deliver sufficient levels of competence and confidence merit further investigation.

Introduction, availability and role of simulation in surgical education and training: review of current evidence and recommendations from the Association of Surgeons in Training.

The utility of simulation in surgical training is now well-established, with proven validity and demonstrable transfer of skills to the clinical setting. Through a reduction in the technical learning curve, simulation can prepare surgeons for actual practice and in doing so it has the potential to improve both patient safety and service efficiency. More broadly, multi-disciplinary simulation of the theatre environment can aid development of non-technical skills and assist in preparing theatre teams for infrequently encountered scenarios such as surgical emergencies. The role of simulation in the formal training curriculum is less well-established, and availability of facilities for this is currently unknown. This paper reviews the contemporary evidence supporting simulation in surgical training and reports trainee access to such capabilities. Our national surgical trainee survey with 1130 complete responses indicated only 41.2% had access to skills simulator facilities. Of those with access, 16.3% had availability out-of-hours and only 54.0% had local access (i.e. current work place). These results highlight the paucity in current provision of surgical skills simulator facilities, and availability (or awareness of availability) varies widely between region, grade and specialty. Based on these findings and current best-evidence, the Association of Surgeons in Training propose 22 action-points for the introduction, availability and role of simulation in surgical training. Adoption of these should guide trainers, trainees and training bodies alike to ensure equitable provision of appropriate equipment, time and resources to allow the full integration of simulation into the surgical curriculum.

Platelet activation, coagulation activation and C-reactive protein in simultaneous samples from the vascular access and peripheral veins of haemodialysis patients.

INTRODUCTION: Most studies of haemodialysis (HD) patients compare venous blood samples from controls with samples from the vascular access (VA) of HD patients. We hypothesised that VA samples may be more prothrombotic compared with venous samples. METHODS: Samples were taken simultaneously from the VA and the contralateral antecubital vein, from 26 patients immediately before HD. Platelet function was assessed by (1) flow cytometric measurement of P-selectin expression and fibrinogen binding (±ADP) and 2) Ultegra rapid platelet function assay. Plasma soluble P-selectin, von Willebrand factor antigen, high sensitivity C-reactive Protein (hs-CRP), thrombin-antithrombin III complex and D-dimer measured by ELISA. RESULTS: Thrombin receptor activating peptide-induced platelet aggregation (P < 0.001) and hs-CRP (P < 0.001) were higher in VA compared with venous samples. Unstimulated platelet fibrinogen binding (P = 0.016) and ADP-stimulated P-selectin expression (P = 0.008) were lower in VA compared with venous samples. The significant difference in hsCRP persisted when patients taking and not taking antiplatelet therapy were analysed separately, but platelet activation remained significantly different only in the nonantiplatelet group. CONCLUSION: There are statistically significant differences between sampling sites, although samples from the VA do not appear to be more pro-thrombotic. Future studies comparing HD patients with controls should ensure uniformity of sampling sites to prevent inaccurate conclusions being drawn.

Lower urinary tract symptoms and sexual dysfunction: an audit of sexual symptoms among patients attending a nurse-led prostate clinic.

Significant numbers of men with lower urinary tract symptoms (LUTS) also report symptoms of sexual dysfunction (SD). The prevalence of SD in patients referred to a prostate assessment clinic, was assessed using a confidential questionnaire. Fifty-six percent of patients reported difficulties in maintaining an erection and 48% felt that improving their sexual function would benefit their quality of life. None of the referral letters from primary care mentioned symptoms of SD. Patients with LUTS seen in primary and secondary care should be assessed for SD and offered appropriate advice and management.

Transposed brachiobasilic fistula or PTFE arm graft - alternative or complementary?

PURPOSE: Our primary aims were (1) to examine the patency of transposed brachiobasilic (TBB) fistulae compared to arm arteriovenous graft (AVG) without prior transposition, and (2) to examine the patency of AVG with and without prior transposition. METHODS: Single institution; analysis of prospectively collected data between January 2001 and January 2007. Dedicated database and medical records were reviewed and results analyzed with SPSS. RESULTS: Ninety-one patients underwent 111 procedures (52 TBB: 39 AVG as index); 28 TBB failed with 17 (60%) being replaced with an ipsilateral AVG. TBB compared to AVG (without prior TBB) had significantly (log rank <0.05 ) better primary, primary assisted and secondary patency. Secondary patency at 2 yrs was 47% to 33%, respectively. Ipsilateral AVG after TBB to primary AVG had superior patency rates (secondary patency at 2 yrs 52 vs. 33%) but did not reach significance (log rank =0.073). Combined secondary patency of TBB and AVG after TBB was 81% at 2 yrs. CONCLUSIONS: The TBB offers an autogenous fistula in the upper arm which has superior patency rates to an arm AVG. Once a TBB has failed an ipsilateral AVG is technically feasible and may offer better patency than a primary AVG.

The accuracy of clinical data: a comparison between central and local data collection.

BACKGROUND: The recent liberalisation of public access to information, including surgical performance, emphasises the necessity for accurate data collection. The Information and Statistics Division of the Scottish Executive (ISD) collect such data for each patient episode, but there is concern about the reliability of this information compared with that collected in local surgical departmental audit. AIM: To determine if diagnostic and operative details were consistent between local audited and national non-audited data sets. METHODS: Three surgical units comprising eight consultants were studied. Epidemiological, diagnostic and operative data for each consultant were accessed from the eScrips Internet resource (ISD Data) and from the departmental database. A unique patient number and date of birth matched individual patient episodes and the correlation between datasets graded for accuracy and consistency. RESULTS: 8375 individual data entries were recorded (ISD 4642, local databases 3733). 3402 pairs, 6408 (76.5%) of the total, matched accurately. 742 (16%) of the ISD entries were duplicates, and in 21% of unpaired entries the wrong consultant was recorded. Overall a clinically acceptable match occurred in 86.9% of paired entries for diagnosis and 84.0% for operation. The highest match with ISD data for diagnosis (88.8%) and operation (91.8%) occurred in the unit which holds a weekly audit meeting to validate information. DISCUSSION: There are significant discrepancies in surgical data between the local audit databases and central data. There is significant duplication of entries and inaccurate consultant allocation in ISD data. The promulgation of inaccurate information could threaten reputation or career and clinicians should play a more active role in ensuring clinical data are correct.

Amyand's hernia presenting as neonatal testicular ischaemia.

Testicular ischaemia presenting in the neonatal period is most often attributable to neonatal torsion. We present an unusual case of a male neonate who presented with acute appendicitis within a patent processus vaginalis, causing cord compression and consequent testicular ischaemia.

Beyond the genome: turning data into knowledge.

Since the publication of the draft sequence of the human genome in April 2001 (1,2), the pressure on life scientists to annotate and gain useful knowledge from the millions of As, Gs, Cs and Ts, is ever increasing. Now that the initial hype has passed, the life sciences field demands the technologies and computer power that can produce and analyze data in a high-throughput manner for drug discovery and disease diagnosis. Cambridge Healthtech Institute's Beyond Genome 2001 conference(1) (17-22 June 2001, San Francisco, CA, USA) brought together the latest research in these technologies in a 'tri-conference' that encompassed the 10th Annual Conference of Bioinformatics and Genome Research, the 3rd Annual Conference of In Silico Biology and the 5th Annual Conference of Proteomics.

Randomized controlled trial of sheaths in diagnostic neuroangiography.

PURPOSE: To determine the value of arterial sheaths in diagnostic neuroangiography in a randomized controlled trial. MATERIALS AND METHODS: A total of 842 patients (411 men, 431 women; mean age, 59.4 years; age range, 29.5-94.3 years) undergoing diagnostic neuroangiography were randomly assigned to groups in which a sheath was introduced immediately after puncture of the femoral artery (sheath group) or in which a diagnostic catheter was introduced without a sheath (control group). Two hundred twenty-four (26.7%) of 839 patients were receiving anticoagulants immediately prior to the procedure. RESULTS: Complications (mostly small hematomas of the groin) occurred in 106 (12.6%) of 842 patients, with no difference between groups (53 [12.6%] of 421 patients in both; P >.99). Ease of catheter manipulation was greater in the sheath group than in the control group. Incidence of bleeding at the femoral puncture site during the procedure was less in the sheath group (seven [1.7%] of 421 patients) versus the control group (150 [35.6%] of 421 patients), with a P value less than.001. Because of bleeding, sheath insertion was necessary in 165 (39.2%) of 421 patients in the control group. This crossover group also had a higher rate of local complications (28 [17.0%] of 165 patients) than the sheath and control groups. Serious complications, such as stroke (one [0.12%] of 842 patients) and transient ischemic attacks (five [0.60%] of 842 patients), occurred with equal frequency in both the sheath and control groups. CONCLUSION: Use of arterial sheaths lessens the incidence of intraprocedural bleeding at the femoral puncture site and increases ease of catheter manipulation without increasing the number of groin complications.