The Continuous Orbifold of N=2 Minimal Model Holography

For the N=2 Kazama-Suzuki models that appear in the duality with a higher spin theory on AdS_3 it is shown that the large level limit can be interpreted as a continuous orbifold of 2N free bosons and fermions by the group U(N). In particular, we show that the subset of coset representations that correspond to the perturbative higher spin degrees of freedom are precisely described by the untwisted sector of this U(N) orbifold. We furthermore identify the twisted sector ground states of the orbifold with specific coset representations, and give various pieces of evidence in favour of this identification.Comment: 24 pages, v2: minor correction

The symmetric orbifold of N=2 minimal models

The large level limit of the N=2 minimal models that appear in the duality with the N=2 supersymmetric higher spin theory on AdS_3 is shown to be a natural subsector of a certain symmetric orbifold theory. We study the relevant decompositions in both the untwisted and the twisted sector, and analyse the structure of the higher spin representations in the twisted sector in some detail. These results should help to identify the string background of which the higher spin theory is expected to describe the leading Regge trajectory in the tensionless limit.Comment: 32 page

Even spin minimal model holography

The even spin W^e_\infty algebra that is generated by the stress energy tensor together with one Virasoro primary field for every even spin s \geq 4 is analysed systematically by studying the constraints coming from the Jacobi identities. It is found that the algebra is characterised, in addition to the central charge, by one free parameter that can be identified with the self-coupling constant of the spin 4 field. We show that W^e_\infty can be thought of as the quantisation of the asymptotic symmetry algebra of the even higher spin theory on AdS_3. On the other hand, W^e_\infty is also quantum equivalent to the so(N) coset algebras, and thus our result establishes an important aspect of the even spin minimal model holography conjecture. The quantum equivalence holds actually at finite central charge, and hence opens the way towards understanding the duality beyond the leading 't Hooft limit.Comment: 32 pages, v2: reference added, minor changes in tex

Balloon dilatation and stenting for aortic coarctation: a systematic review and meta-analysis

Background—There is no systematic assessment of available evidence on effectiveness and comparative effectiveness of balloon dilatation and stenting for aortic coarctation. Methods and Results—We systematically searched 4 online databases to identify and select relevant studies of balloon dilatation and stenting for aortic coarctation based on a priori criteria (PROSPERO 2014:CRD42014014418). We quantitatively synthesized results for each intervention from single-arm studies and obtained pooled estimates for relative effectiveness from pairwise and network meta-analysis of comparative studies. Our primary analysis included 15 stenting (423 participants) and 12 balloon dilatation studies (361 participants), including patients ≥10 years of age. Post-treatment blood pressure gradient reduction to ≤20 and ≤10 mm Hg was achieved in 89.5% (95% confidence interval, 83.7–95.3) and 66.5% (44.1–88.9%) of patients undergoing balloon dilatation, and in 99.5% (97.5–100.0%) and 93.8% (88.5–99.1%) of patients undergoing stenting, respectively. Odds of achieving ≤20 mm Hg were lower with balloon dilatation as compared with stenting (odds ratio, 0.105 [0.010–0.886]). Thirty-day survival rates were comparable. Numerically more patients undergoing balloon dilatation experienced severe complications during admission (6.4% [2.6–10.2%]) compared with stenting (2.6% [0.5–4.7%]). This was supported by meta-analysis of head-to-head studies (odds ratio, 9.617 [2.654–34.845]) and network meta-analysis (odds ratio, 16.23, 95% credible interval: 4.27–62.77) in a secondary analysis in patients ≥1 month of age, including 57 stenting (3397 participants) and 62 balloon dilatation studies (4331 participants). Conclusions—Despite the limitations of the evidence base consisting predominantly of single-arm studies, our review indicates that stenting achieves superior immediate relief of a relevant pressure gradient compared with balloon dilatation

Tissue-engineered vascular graft remodeling in a growing lamb model: expression of matrix metalloproteinases

OBJECTIVES We have previously demonstrated the functionality and growth of autologous, living, tissue-engineered vascular grafts (TEVGs) in long-term animal studies. These grafts showed substantial in vivo tissue remodeling and approximation to native arterial wall characteristics. Based on this, in vitro and in vivo matrix metalloproteinase (MMP) activity of TEVGs is investigated as a key marker of matrix remodeling. METHODS TEVGs fabricated from biodegradable scaffolds (polyglycolic-acid/poly-4-hydroxybutyrate, PGA/P4HB) seeded with autologous vascular cells were cultured in static and dynamic in vitro conditions. Thereafter, TEVGs were implanted as pulmonary artery replacements in lambs and followed up for 2 years. Gelatin gel zymography to detect MMP-2 and -9 was performed and collagen content quantified (n=5). Latent (pro) and active MMP-2 and -9 were detected. RESULTS Comparable levels of active MMP-9 and pro-MMP-2 were detected in static and dynamic culture. Higher levels of active MMP-2 were detected in dynamic cultures. Expression of MMP-2 and -9 was minimal in native grafts but was increased in implanted TEVG. Pro-MMP-9 was expressed 20 weeks post implantation and persisted up to 80 weeks post implantation. Collagen content in vitro was increased in dynamically conditioned TEVG as compared with static constructs and was increased in vivo compared with the corresponding native pulmonary artery. CONCLUSIONS MMPs are up-regulated in vitro by dynamic culture conditions and could contribute to increased matrix remodeling, native analogous tissue formation and functional growth of TEVGs in vivo. Monitoring of MMP activity, for example, by molecular imaging techniques, may enable the non-invasive assessment of functional tissue quality in future clinical tissue-engineering application

Hemodynamic changes during physiological and pharmacological stress testing in patients with heart failure: a systematic review and meta-analysis

Although disease etiologies differ, heart failure patients with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively) both present with clinical symptoms when under stress and impaired exercise capacity. The extent to which the adaptation of heart rate (HR), stroke volume (SV), and cardiac output (CO) under stress conditions is altered can be quantified by stress testing in conjunction with imaging methods and may help to detect the diminishment in a patient’s condition early. The aim of this meta-analysis was to quantify hemodynamic changes during physiological and pharmacological stress testing in patients with HF. A systematic literature search (PROSPERO 2020:CRD42020161212) in MEDLINE was conducted to assess hemodynamic changes under dynamic and pharmacological stress testing at different stress intensities in HFpEF and HFrEF patients. Pooled mean changes were estimated using a random effects model. Altogether, 140 study arms with 7,248 exercise tests were analyzed. High-intensity dynamic stress testing represented 73% of these data (70 study arms with 5,318 exercise tests), where: HR increased by 45.69 bpm (95% CI 44.51–46.88; I2 = 98.4%), SV by 13.49 ml (95% CI 6.87–20.10; I2 = 68.5%), and CO by 3.41 L/min (95% CI 2.86–3.95; I2 = 86.3%). No significant differences between HFrEF and HFpEF groups were found. Despite the limited availability of comparative studies, these reference values can help to estimate the expected hemodynamic responses in patients with HF. No differences in chronotropic reactions, changes in SV, or CO were found between HFrEF and HFpEF. When compared to healthy individuals, exercise tolerance, as well as associated HR and CO changes under moderate-high dynamic stress, was substantially impaired in both HF groups. This may contribute to a better disease understanding, future study planning, and patient-specific predictive models. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020161212]

Comprehensive Meta-Analysis of Safety and Efficacy of Bivalirudin Versus Heparin With or Without Routine Glycoprotein IIb/IIIa Inhibitors in Patients With Acute Coronary Syndrome

AbstractObjectivesThe aim of this meta-analysis was to compare the 30-day safety and efficacy of bivalirudin with those of heparin with or without routine administration of a glycoprotein IIb/IIIa inhibitor (GPI) in patients with acute coronary syndrome (ACS).BackgroundBivalirudin has been a mainstay of anticoagulation in patients with ACS compared with heparin. The extent to which trial results have been affected by the coadministration of heparin with a GPI, however, remains unclear.MethodsA total of 13 randomized, controlled trials involving 24,605 patients were included.ResultsThere was no significant difference in 30-day mortality or myocardial infarction rate with bivalirudin compared with heparin with or without routine GPI administration. A reduction of 30-day major bleeding was observed with bivalirudin compared with heparin that was significant when GPI was routinely administered (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.45 to 0.60), p < 0.001) but not with provisionally administered GPI (OR: 0.66, 95% CI: 0.33 to 1.32; p = 0.24). The occurrence of stent thrombosis (ST) at 30 days was significantly increased with bivalirudin compared with heparin plus routinely administered GPI (OR: 1.67, 95% CI: 1.13 to 2.45, p = 0.02), but not compared with heparin plus provisionally administered GPI (OR: 2.08, 95% CI: 0.35 to 12.32, p = 0.42). The rate of acute ST (≤24 h), however, was almost 4.5-fold higher with bivalirudin compared with heparin with or without GPI, whereas the rate of subacute ST (24 h to 30 days) did not differ significantly.ConclusionsOverall, bivalirudin in ACS patients is associated with a significant reduction of major bleeding compared with heparin plus routinely administered GPI, but with a marked increase in ST rates compared with heparin with or without GPI

Hemodynamic changes during physiological and pharmacological stress testing in healthy subjects, aortic stenosis and aortic coarctation patients: a systematic review and meta-analysis

Introduction: Exercise testing has become a diagnostic standard in the evaluation and management of heart disease. While different methods of exercise and pharmacological stress testing exist, only little is known about their comparability. We aimed to assess hemodynamic changes during dynamic exercise, isometric exercise, and dobutamine stress testing at different stress intensities in healthy subjects and patients with aortic stenosis (AS) and aortic coarctation (CoA). Methods: A systematic literature search (PROSPERO 2017:CRD42017078608) in MEDLINE of interventional trials was conducted to identify eligible studies providing evidence of changes in hemodynamic parameters under different stress conditions acquired by MRI or echocardiography. A random effects model was used to estimate pooled mean changes in hemodynamics. Results: One hundred and twenty-eight study arms with a total of 3,139 stress-examinations were included. In healthy subjects/(where available) in AS, pooled mean changes (95% CIs) during light dynamic stress were 31.78 (27.82–35.74) bpm in heart rate (HR) and 6.59 (2.58–10.61) ml in stroke volume (SV). Changes during light pharmacological stress were 13.71 (7.87–19.56)/14.0 (9.82–18.18) bpm in HR, and 5.47 (0.3–10.63)/8.0 (3.82–12.18) ml in SV. Changes during light isometric stress were 18.44 (10.74–26.14)/5.0 (−1.17–11.17) bpm in HR and −4.17 (−14.37–6.03)/−4.0 (−16.43–8.43) ml in SV. Changes during moderate dynamic stress were 49.57 (40.03–59.1)/46.45 (42.63–50.27) bpm in HR and 11.64 (5.87–17.42) ml in SV. During moderate pharmacological stress, changes in HR were 42.83 (36.94–48.72)/18.66 (2.38–34.93) bpm and in SV 6.29 (−2.0–14.58)/13.11 (7.99–18.23) ml. During high intensity dynamic stress changes in HR were 89.31 (81.46–97.17)/55.32 (47.31–63.33) bpm and in SV 21.31 (13.42–29.21)/−0.96 (−5.27–3.35) ml. During high pharmacological stress, changes in HR were 53.58 (36.53–70.64)/42.52 (32.77–52.28) bpm, and in SV 0.98 (−9.32–11.27)/14.06 (−1.62–29.74) ml. HR increase and age were inversely correlated at high stress intensities. In CoA, evidence was limited to single studies. Conclusion: This systematic review and meta-analysis presents pooled hemodynamic changes under light, moderate and high intensity exercise and pharmacological stress, while considering the potential influence of age. Despite limited availability of comparative studies, the reference values presented in this review allow estimation of the expected individual range of a circulatory response in healthy individuals and patients with AS and may contribute to future study planning and patient-specific models even when stress testing is contraindicated