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.

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.

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.

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.

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.

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.

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.

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.

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.

Expression of reg/PSP, a pancreatic exocrine gene: relationship to changes in islet beta-cell mass.

A cDNA termed reg was recently isolated by differential screening of a library prepared from regenerating islets isolated from pancreatic remnants of rats subjected to 90% pancreatectomy and nicotinamide treatment. This led to speculation that this gene may be involved in expansion of beta-cell mass. In the current study we have measured reg expression after implantation and resection of a solid insulinoma tumor into rats, maneuvers known, respectively, to reduce and reexpand the volume of beta-cells in the islet. Animals with an implanted insulinoma tumor became profoundly hypoglycemic. Islet beta-cells declined from the normal 75% of total islet volume to less than 30%, in concert with a marked reduction in the reg mRNA level. Removal of the tumor resulted in a sharp increase in beta-cell replication, as measured by [3H]thymidine incorporation and a return to normal beta-cell volume within 4 days of tumor resection. This was associated with a transient induction in reg expression compared to that in tumor-bearing animals, effectively returning the amount of reg mRNA to the levels found in normal animals within 48 h; at later time points after tumor removal (3-7 days) reg expression declined, but then rose toward normal. In situ hybridization analysis localized the initial induction in reg mRNA expression to the exocrine pancreas. Continuous infusion of insulin into normal rats for 4 days, a maneuver that does not significantly reduce beta-cell mass, resulted in dramatically reduced insulin mRNA in islets, but no change in the levels of reg mRNA. We conclude that the diminution in pancreatic beta-cell mass caused by subcutaneous implantation of an insulinoma is associated with reduced reg gene expression and that the increase in beta-cell replication after resection of the tumor is preceded by return of reg gene expression toward normal.

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.

Adenylate cyclase activity in neocortex and fetal zone membrane fractions of the human fetal adrenal gland.

Whether peptide hormones other than ACTH may be responsible for the difference in size or rate and pattern of steroidogenesis of the fetal zone (FZ) compared to those of the neocortex (NC) of the human fetal adrenal gland is controversial. In the present investigation, the activity of adenylate cyclase in membrane fractions of separated zones of the human fetal adrenal gland was determined. Basal adenylate cyclase activity was 2- to 3-fold greater in NC than in FZ membrane fractions. The addition of ACTH-(1-24) stimulated adenylate cyclase activity in both zones, but the activity was more sensitive to ACTH (10(-10) M) in NC fractions than in FZ fractions (10(-7) M). In addition to ACTH-(1-24), the effect of other ACTH-related peptides on the activity of adenylate cyclase in the separated zones of the adrenal gland was investigated. 16K fragments 2-36, gamma 3MSH, alpha MSH, beta-endorphin, leu-enkephalin, and met-enkephalin, as well as hCG, FSH, prostaglandin E2, prostaglandin F2 alpha, epinephrine, and norepinephrine did not stimulate adenylate cyclase activity in either zone. It is concluded that basal and ACTH-(1-24)-stimulated adenylate cyclase activities are greater in NC than in FZ membrane fractions. In addition, the results of the present investigation do not support the concept that other ACTH-related peptides or peptide or protein hormones increase steroidogenesis by stimulating adenylate cyclase activity in the human fetal adrenal gland.

Effect of intraarterial papaverine on cerebral circulation time.

PURPOSE: To measure the mean cerebral circulation time (CCT) in patients with symptomatic vasospasm stemming from subarachnoid hemorrhage and to determine any change after papaverine treatment. METHODS: We studied 27 patients who received intraarterial papaverine from November 1992 to August 1995 to determine the CCT in 59 carotid territories. CCT was measured from the first image in which contrast was seen above the supraclinoid internal carotid artery to the peak filling of parietal cortical veins. Angiograms at the time of presentation were examined in 19 of the 27 patients. A control population of 19 patients (30 carotid territories) was also studied. RESULTS: The mean CCT on presentation was 6.8 seconds +/- 1.1. The prepapaverine mean CCT was 6.1 seconds +/- 1.2. The immediate postpapaverine mean CCT was 3.8 seconds +/- 0.8. CCT decreased in 58 of 59 territories treated with papaverine; the mean change was -35.7%. In eight of these patients, CCT rose on the following day to 6.1 seconds +/- 1.1. In the control group, mean CCT was 5.9 seconds +/- 0.8. The mean CCT in patients with subarachnoid hemorrhage was slightly prolonged on presentation relative to that in control subjects. CONCLUSION: Intraarterial papaverine produces a consistent decrease in CCT in patients with vasospasm.

Intracranial pressure monitoring during intraarterial papaverine infusion for cerebral vasospasm.

PURPOSE: Intraarterial papaverine infusions are performed to reverse cerebral arterial vasospasm resulting from subarachnoid hemorrhage, but such infusions may lead to increases in intracranial pressure (ICP). This study was undertaken to determine when ICP monitoring is indicated during papaverine treatment. METHODS: Seventy-eight vessels were treated in 51 sessions in 28 patients with symptomatic vasospasm. ICP, papaverine doses, and infusion rates were recorded during treatment sessions. The procedural data, Hunt and Hess scores, Fisher grades, Glasgow Coma Scale scores, and ages for all subjects were reviewed and analyzed retrospectively. RESULTS: Baseline ICP ranged from 0 to 34 mm Hg. With typical papaverine doses of 300 mg per territory and infusion times ranging from 5 to 60 minutes per vessel, ICP increases above baseline during papaverine infusion ranged from 0 to 60 mm Hg. Significant (> or = 20 mm Hg) ICP increases during therapy were observed even in patients with low baseline ICP and with papaverine infused at the slowest rate. Patients with a baseline ICP of more than 15 mm Hg were much more likely to have significant ICP increases than were patients with a baseline ICP of 0 to 15 mm Hg. Hunt and Hess scores, Fisher grades, age, and Glasgow Coma Scale scores on admission and immediately before treatment did not correlate with ICP increases during papaverine infusion. Patients with ICP increases of more than 10 mm Hg during therapy were more likely to experience adverse clinical events than were patients with ICP increases of < or = 10 mm Hg. Reduction in the rate of papaverine infusion, or termination of infusion, resulted in reversal of drug-induced ICP elevation. CONCLUSION: ICP monitoring during intraarterial papaverine infusions for cerebral vasospasm is recommended for all patients and is particularly important for patients with elevated baseline ICP. Continuous ICP monitoring facilitates safe and time-efficient drug delivery.

Increase in diameters of vasospastic intracranial arteries by intraarterial papaverine administration.

OBJECT: This study was conducted to determine if there is a change in intracranial arterial diameters after papaverine infusion for vasospasm and to determine whether the change occurs in proximal, intermediate, and distal arteries. METHODS: The authors measured arterial diameters retrospectively in all patients who received intraarterial papaverine for treatment of vasospasm between November 1992 and August 1995. Patients who received papaverine in the same session with or following angioplasty were excluded. Measurements were made in a blinded manner with the aid of a magnification loupe at 12 predetermined sites on each angiogram before and after papaverine infusion. Eighty-one treatments in 34 patients were included. Angiograms obtained at the time of presentation with subarachnoid hemorrhage (SAH) were examined in 26 of the 34 patients. Nine carotid territories visualized by repeated angiography on the day after infusion were examined to determine the duration of the papaverine effect. CONCLUSIONS: In all treatment groups an increase was found in the average arterial diameters ranging from 2.8 to 73.9%, with a mean increase of 26.5%. Increases in diameter were observed in proximal, intermediate, and distal arteries. The timing of treatments ranged from Day 3 to Day 19 post-SAH, and there was no relationship between timing and arterial responsiveness (r = -0.06). There was a moderately good correlation between the degree of vasospasm in an artery and its responsiveness to papaverine (r = -0.54, -0.66, and -0.66, for proximal, intermediate, and distal arteries, respectively). The effect of papaverine did not persist until the following day in patients in whom repeated angiography was performed.

Ultrasonography in children of cystic abdominal masses not related to the genitourinary system.

A variety of cystic abdominal masses not related to the genitourinary tract may be encountered in the pediatric population. Ultrasound is the most informative imaging modality in the workup of these masses which include lymphangiomas, duplication cysts, enteric cysts, mesothelial cysts, pseudocysts, choledochal cysts, and gastrointestinal teratomas. The clinical and sonographic characteristics of these lesions are presented.