The differential analytic index in Simons-Sullivan differential K-theory

We define the Simons-Sullivan differential analytic index by translating the Freed-Lott differential analytic index via explicit ring isomorphisms between Freed-Lott differential K-theory and Simons-Sullivan differential K-theory. We prove the differential Grothendieck-Riemann-Roch theorem in Simons-Sullivan differential K-theory using a theorem of Bismut.Comment: 14 pages. Comments are welcome. Final version. To appear in Annals of Global Analysis and Geometr

Topological Defects on Fluctuating Surfaces: General Properties and the Kosterlitz-Thouless Transition

We investigate the Kosterlitz-Thouless transition for hexatic order on a free fluctuating membrane and derive both a Coulomb gas and a sine-Gordon Hamiltonian to describe it. The Coulomb-gas Hamiltonian includes charge densities arising from disclinations and from Gaussian curvature. There is an interaction coupling the difference between these two densities, whose strength is determined by the hexatic rigidity, and an interaction coupling Gaussian curvature densities arising from the Liouville Hamiltonian resulting from the imposition of a covariant cutoff. In the sine-Gordon Hamiltonian, there is a linear coupling between a scalar field and the Gaussian curvature. We discuss gauge-invariant correlation function for hexatic order and the dielectric constant of the Coulomb gas. We also derive renormalization group recursion relations that predict a transition with decreasing bending rigidity $\kappa$.Comment: REVTEX, 45 pages with 11 postscript figures compressed using uufiles. Accepted for publication in Phys. Rev.

Prospective comparative study of spiral computer tomography and magnetic resonance imaging for detection of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is often detected at a relatively late stage when tumour size prohibits curative surgery. Screening to detect HCC at an early stage is performed for patients at risk. AIM: The aim of this study was to compare prospectively the diagnostic accuracy and classification for management of the two state of the art secondline imaging techniques: triphasic spiral computer tomography (CT) and super paramagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI). PATIENTS: Sixty one patients were evaluated between January 1996 and January 1998. Patients underwent CT and MRI within a mean interval of 6.75 days. METHODS: CT and MRI were evaluated blindly for the presence and number of lesions, characterisation of these lesions, and classification for management. For comparison of the data on characterisation, the CT and MRI findings were compared with histopathological studies of the surgical specimens and/or follow up imaging. Data of patients not lost to follow up were available to January 2001. RESULTS: SPIO enhanced MRI detected more lesions and overall smaller lesions than triphasic spiral CT (number of lesions 189 v 124; median diameter 1.0 v 1.8 cm; Spearman rank's correlation coefficient 0.63, p<0.001). There was no significant difference in accuracy between CT and MRI for lesion characterisation. The agreement in classification for management was very good (weighted kappa 0.91, 95% CI 0.83-0.99). CONCLUSION: SPIO enhanced MRI detects more and smaller lesions, but both techniques are comparable in terms of classification for management. SPIO enhanced MRI may be preferred as there is no exposure to ionising radiation

'Nurses' self-management support to hospitalised patients: a scoping review

Aims and Objectives: To review the current literature to map and explore the interventions that have been considered or used by nurses to support adult patients' self-management during hospitalisation. Background: Nurses can play an important role in supporting patients' self-management. Currently, however, it is unclear how nurses perform this task during a patient's stay in hospital. Traditionally, nurses take the primary role in managing patients' care during hospitalisation. Ideally, patients should have the opportunity to continue applying strategies to manage their health conditions as much as possible while in the hospital. This can increase patients' self-efficacy and decrease unnecessary readmissions. Design: Scoping review informed by the Joanna Briggs Institute methodology. Methods: A database search was undertaken using Pubmed, CINAHL, Psycinfo, Cochrane, Embase and grey literature sources. Data from the included studies were mapped and summarised in a narrative summary. To synthesise the information that was given about each intervention, we conducted a qualitative inductive content analysis. Results are reported in accordance with the guidelines for reporting Items for systematic review and meta-analyses extension for scoping review (PRISMA-ScR) (Supplementary File 1). Results: 83 documents were included in this review. Based on the information about the interventions, three themes were identified: 'self-management support activities', 'focus of self-management support' and the 'intervention procedure'. Five self-management support activities can be distinguished: 'giving education', 'counselling and coaching', 'enhancing responsibility', 'engaging family-caregivers' and 'supporting transition from hospital to home'. The interventions focused on improving disease-related knowledge and on strengthening several self-management skills. Information about the procedure, development and the theoretical underpinning of the intervention was often limited. Conclusions: Most activities within the nursing interventions to support adult patients' self-management during hospitalisation are the part of regular nursing care. However, the transfer of responsibility for care task to the patient is relatively new. Further research could focus on developing interventions addressing all aspects of self-management and that are embedded in the patient's care pathway across settings.Pathophysiology, epidemiology and therapy of agein

Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and wi

Safety of second-generation drug-eluting stents three years after randomised use in the TWENTE trial

Aims: To assess three-year clinical outcome following randomised use of the second-generation Resolute zotarolimus-eluting stent (ZES) and the XIENCE V everolimus-eluting stent (EES). For Resolute ZES and randomised use, outcome data ≥3 years are relatively scarce. Methods and results: The TWENTE trial examined 1,391 patients with stable angina or non-ST-elevation acute coronary syndromes, of whom 21.6% were diabetics, 70.1% had complex B2 or C lesions and 77.4% had “off-label” indications for DES use. Three-year follow-up data were obtained in 1,381 patients (99.3%; 10 withdrawals). Adverse clinical events were independently adjudicated. The primary endpoint target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction and clinically indicated target vessel revascularisation, was 12.1% for Resolute ZES and 13.4% for XIENCE V EES (p=0.50). Cardiac death rates were 1.9% vs. 3.5% (p=0.06); the other individual components of TVF also showed no significant between-group differences. The rates of definite-or-probable stent thrombosis (1.4% vs. 1.6%, p=0.82) and very late stent thrombosis (0.6% vs. 0.4%, p=1.0) did not differ between the groups. Conclusions: Three-year follow-up data of patients included in the randomised TWENTE trial demonstrated similar and sustained safety and efficacy of Resolute ZES and XIENCE V EE

Value of the SYNTAX score for periprocedural myocardial infarction according to WHO and the third universal definition of myocardial infarction:insights from the TWENTE trial

Aims: The SYNTAX score is a tool to quantify the complexity of coronary artery disease. We investigated the relation between the SYNTAX score and the occurrence of a periprocedural myocardial infarction (PMI) according to the historical definition of the World Health Organization (WHO) and the recently updated universal definition of MI. Methods and results: The SYNTAX score was calculated in 1,243 patients enrolled in TWENTE, a randomised trial which assessed second-generation drug-eluting stents. PMI was defined by the WHO definition and the third universal definition of MI. Patients were divided into tertiles of the SYNTAX score: ≤7 (n=430); >7 and <15 (n=390); ≥15 (n=423). PMI according to the WHO definition occurred more frequently in patients in the highest SYNTAX score tertile (7.3% vs. 3.1% vs. 1.6%, p<0.001) compared to the mid and lowest tertile. Similar findings were seen for universal PMI (9.9% vs. 7.7% vs. 3.7%, p<0.01). After multivariate analysis, SYNTAX score was a significant independent correlate of PMI for both definitions: the highest SYNTAX score tertile had an almost five times higher risk for WHO PMI, and a three times higher risk for universal PMI. Conclusions: In a broad patient population treated with second-generation DES, the SYNTAX score was able to stratify the risk of PM

Impact of previous coronary artery bypass surgery on clinical outcome after percutaneous interventions with second generation drug-eluting stents in TWENTE trial and Non-Enrolled TWENTE registry

AbstractBackgroundPatients with previous coronary artery bypass grafting (CABG) who underwent percutaneous coronary intervention (PCI) have an increased repeat revascularization rate, but data on contemporary second-generation drug-eluting stents (DES) are scarce.MethodsWe evaluated 1-year clinical outcome following secondary revascularization by PCI in patients of the TWENTE trial and non-enrolled TWENTE registry, and compared patients with previous CABG versus patients without previous CABG.ResultsOf all 1709 consecutive patients, 202 (11.8%) had previously undergone CABG (on average 11.2±8.5years ago). CABG patients were older (68.5±9.4years vs. 64.1±10.7years, P<0.001) and more often had diabetes (28.7% vs. 20.9%, P=0.01) and previous PCI (40.1% vs. 19.8%, P<0.001) compared to patients without previous CABG. Nevertheless, a higher target vessel revascularization (TVR) rate following PCI in the CABG patients (9.4% vs. 2.3%, P<0.001) was the only significant difference in clinical outcome at 1-year follow-up (available for 99.6%). Among CABG patients, the TVR rate was significantly higher in patients treated for graft lesions (n=65; 95.4% in vein grafts) than in patients treated for native coronary lesions only (n=137) (18.5% vs. 5.1%, P=0.002). Among 1638 patients with PCI of native coronary lesions only, there was only a non-significant difference in TVR between patients with previous CABG versus patients without previous CABG (5.1% vs. 2.3%, P=0.08).ConclusionsPatients with previous CABG showed a favorable safety profile after PCI with second-generation DES. Nevertheless, their TVR rate was still much higher, driven by more repeat revascularizations after PCI of degenerated vein grafts. In native coronary lesions, there was no such difference

Induction of broad multifunctional CD8+ and CD4+ T cells by hepatitis B virus antigen-based synthetic long peptides ex vivo

Introduction: Therapeutic vaccination based on synthetic long peptides (SLP®) containing both CD4+ and CD8+ T cell epitopes is a promising treatment strategy for chronic hepatitis B infection (cHBV). Methods: We designed SLPs for three HBV proteins, HBcAg and the non-secreted proteins polymerase and X, and investigated their ability to induce T cell responses ex vivo. A set of 17 SLPs was constructed based on viral protein conservation, functionality, predicted and validated binders for prevalent human leukocyte antigen (HLA) supertypes, validated HLA I epitopes, and chemical producibility. Results: All 17 SLPs were capable of inducing interferon gamma (IFNɣ) production in samples from four or more donors that had resolved an HBV infection in the past (resolver). Further analysis of the best performing SLPs demonstrated activation of both CD8+ and CD4+ multi-functional T cells in one or more resolver and patient sample(s). When investigating which SLP could activate HBV-specific T cells, the responses could be traced back to different peptides for each patient or resolver. Discussion: This indicates that a large population of subjects with different HLA types can be covered by selecting a suitable mix of SLPs for therapeutic vaccine design. In conclusion, we designed a set of SLPs capable of inducing multifunctional CD8+ and CD4+ T cells ex vivo that create important components for a novel therapeutic vaccine to cure cHBV.</p