Peptide-based probes for cancer imaging

Receptors for regulatory peptides are overexpressed in a variety of human cancers. They represent the molecular basis for in vivo imaging with radiolabeled peptide probes. Somatostatin-derived tracers, designed to image the sst2-overexpressing neuroendocrine tumors, have enjoyed almost 2 decades of successful development and extensive clinical applications. More recent developments include second- and third-generation somatostatin analogs, with a broader receptor subtype profile or with antagonistic properties. Emerging tracers for other peptide receptors, including cholecystokinin/gastrin and GLP-1 analogs for neuroendocrine tumors, bombesin and neuropeptide-Y analogs for prostate or breast cancers, or Arg-Gly-Asp peptides for neoangiogenesis labeling, are also in current development. Application fields include both SPECT/CT and PET/CT.

Susceptibility of Escherichia coli strains isolated from outpatient children with community-acquired urinary tract infection in southern Switzerland

BACKGROUND: Based on antimicrobial resistance patterns found in Swiss university hospitals, treatment with a third-generation cephalosporin is currently advised for Swiss children with urinary tract infection. OBJECTIVE: The aim of this study was to prospectively assess the susceptibility of Escherichia coli strains isolated from children with symptomatic community-acquired urinary tract infection. METHODS: The antimicrobial susceptibility of E coli strains causing symptomatic community-acquired urinary tract infections was assessed in outpatient children attending the emergency management unit at the Department of Pediatrics, Mendrisio and Bellinzona Hospitals, Switzerland. Strains from children receiving antimicrobial prophylaxis or prescribed antimicrobials in the previous 4 weeks were excluded. Clinical and Laboratory Standards Institute methods were used for culture and identification of pathogens. E coli susceptibility testing was performed using the disk diffusion technique. RESULTS: Strains from 100 consecutive outpatient children (73 girls, 27 boys; aged 5 weeks-17 years [median, 33 months]; 100% white) were assessed. High rates of ampicillin and cotrimoxazole resistance (39 and 21 strains, respectively) and low rates of nitrofurantoin resistance (4 strains) were identified. No resistance was identified for coamoxiclav or third-generation cephalosporins. CONCLUSIONS: In these Swiss outpatient children with symptomatic community-acquired urinary tract infection, without antimicrobial prophylaxis or recent prescription of antimicrobials, uropathogenic E coli strains resistant in vitro to ampicillin and cotrimoxazole were common. However, in vitro resistance to nitrofurantoin, coamoxiclav, and third-generation cephalosporins was uncommon.

SYNTHESIS OF GRAPHENE AND ITS APPLICATIONS FOR DYE-SENSITIZED SOLAR CELLS

Graphene, which is a two-dimensional carbon material, exhibits unique properties that promise its potential applications in photovoltaic devices. Dye-sensitized solar cell (DSSC) is a representative of the third generation photovoltaic devices. Therefore, it is important to synthesize graphene with special structures, which possess excellent properties for dye-sensitized solar cells. This dissertation research was focused on (1) the effect of oxygen content on the structure of graphite oxide, (2) the stability of graphene oxide solution, (3) the application of graphene precipitate from graphene oxide solution as counter electrode for DSSCs, (4) the development of a novel synthesis method for the three-dimensional graphene with honeycomb-like structure, and (5) the exploration of honeycomb structured graphene (HSG) as counter electrodes for DSSCs. Graphite oxide is a crucial precursor to synthesize graphene sheets via chemical exfoliation method. The relationship between the oxygen content and the structures of graphite oxides was still not explored. In this research, the oxygen content of graphite oxide is tuned by changing the oxidation time and the effect of oxygen content on the structure of graphite oxide was evaluated. It has been found that the saturated ratio of oxygen to carbon is 0.47. The types of functional groups in graphite oxides, which are epoxy, hydroxyl, and carboxylgroups, are independent of oxygen content. However, the interplanar space and BET surface area of graphite oxide linearly increases with increasing O/C ratio. Graphene oxide (GO) can easily dissolve in water to form a stable homogeneous solution, which can be used to fabricate graphene films and graphene based composites. This work is the first research to evaluate the stability of graphene oxide solution. It has been found that the introduction of strong electrolytes (HCl, LiOH, LiCl) into GO solution can cause GO precipitation. This indicates that the electrostatic repulsion plays a critical role in stabilizing aqueous GO solution. Furthermore, the HCl-induced GO precipitation is a feasible approach to deposit GO sheets on a substrate as a Pt-free counter electrode for a dye-sensitized solar cell (DSSC), which exhibited 1.65% of power conversion efficiency. To explore broad and practical applications, large-scale synthesis with controllable integration of individual graphene sheets is essential. A novel strategy for the synthesis of graphene sheets with three-dimensional (3D) Honeycomb-like structure has been invented in this project based on a simple and novel chemical reaction (Li2O and CO to graphene and Li2CO3). The simultaneous formation of Li2CO3 with graphene not only can isolate graphene sheets from each other to prevent graphite formation during the process, but also determine the locally curved shape of graphene sheets. After removing Li2CO3, 3D graphene sheets with a honeycomb-like structure were obtained. This would be the first approach to synthesize 3D graphene sheets with a controllable shape. Furthermore, it has been demonstrated that the 3D Honeycomb-Structured Graphene (HSG) possesses excellent electrical conductivity and high catalytic activity. As a result, DSSCs with HSG counter electrodes exhibit energy conversion efficiency as high as 7.8%, which is comparable to that of an expensive noble Pt electrode.

Re-conceptualizing the Global Digital Divide

The article seeks a re-conceptualization of the global digital divide debate. It critically explores the predominant notion, its evolution and measurement, as well as the policies that have been advanced to bridge the digital divide. Acknowledging the complexity of this inequality, the article aims at analyzing the disparities beyond the connectivity and skills barriers. Without understating the first two digital divides, it is argued that as the Internet becomes more sophisticated and more integrated into economic, social, and cultural processes, a “third” generation of divides becomes critical. These divides are drawn not at the entry to the net but within the net itself, and limit access to content. The increasing barriers to content, though of a diverse nature, all relate to some governance characteristics inherent in cyberspace, such as global spillover of local decisions, regulation through code, and proliferation of self- and co-regulatory models. It is maintained that as the practice of intervention intensifies in cyberspace, multiple and far-reaching points of control outside formal legal institutions are created, threatening the availabil- ity of public goods and making the pursuit of public objectives difficult. This is an aspect that is rarely ad- dressed in the global digital divide discussions, even in comprehensive analyses and political initiatives such as the World Summit on the Information Society. Yet, the conceptualization of the digital divide as impeded access to content may be key in terms of ensuring real participation and catering for the longterm implications of digital technologies.

Light curing through glass ceramics: effect of curing mode on micromechanical properties of dual-curing resin cements

OBJECTIVES The aim of this study was to investigate micromechanical properties of five dual-curing resin cements after different curing modes including light curing through glass ceramic materials. MATERIALS AND METHODS Vickers hardness (VH) and indentation modulus (Y HU) of Panavia F2.0, RelyX Unicem 2 Automix, SpeedCEM, BisCem, and BeautiCem SA were measured after 1 week of storage (37 °C, 100 % humidity). The resin cements were tested following self-curing or light curing with the second-generation light-emitting diode (LED) curing unit Elipar FreeLight 2 in Standard Mode (1,545 mW/cm(2)) or with the third-generation LED curing unit VALO in High Power Mode (1,869 mW/cm(2)) or in XtraPower Mode (3,505 mW/cm(2)). Light curing was performed directly or through glass ceramic discs of 1.5 or 3 mm thickness of IPS Empress CAD or IPS e.max CAD. VH and Y HU were analysed with Kruskal-Wallis tests followed by pairwise Wilcoxon rank sum tests (α = 0.05). RESULTS RelyX Unicem 2 Automix resulted in the highest VH and Y HU followed by BeautiCem SA, BisCem, SpeedCEM, and finally Panavia F2.0. Self-curing of RelyX Unicem 2 Automix and SpeedCEM lowered VH and Y HU compared to light curing whereas self-curing of Panavia F2.0, BisCem, and BeautiCem SA led to similar or significantly higher VH and Y HU compared to light curing. Generally, direct light curing resulted in similar or lower VH and Y HU compared to light curing through 1.5-mm-thick ceramic discs. Light curing through 3-mm-thick discs of IPS e.max CAD generally reduced VH and Y HU for all resin cements except SpeedCEM, which was the least affected by light curing through ceramic discs. CONCLUSIONS The resin cements responded heterogeneously to changes in curing mode. The applied irradiances and light curing times adequately cured the resin cements even through 1.5-mm-thick ceramic discs. CLINICAL RELEVANCE When light curing resin cements through thick glass ceramic restorations, clinicians should consider to prolong the light curing times even with LED curing units providing high irradiances.

Flavor-phenomenology of two-Higgs-doublet models with generic Yukawa structure

In this article, we perform an extensive study of flavor observables in a two-Higgs-doublet model with generic Yukawa structure (of type III). This model is interesting not only because it is the decoupling limit of the minimal supersymmetric standard model but also because of its rich flavor phenomenology which also allows for sizable effects not only in flavor-changing neutral-current (FCNC) processes but also in tauonic B decays. We examine the possible effects in flavor physics and constrain the model both from tree-level processes and from loop observables. The free parameters of the model are the heavy Higgs mass, tanβ (the ratio of vacuum expectation values) and the “nonholomorphic” Yukawa couplings ϵfij(f=u,d,ℓ). In our analysis we constrain the elements ϵfij in various ways: In a first step we give order of magnitude constraints on ϵfij from ’t Hooft’s naturalness criterion, finding that all ϵfij must be rather small unless the third generation is involved. In a second step, we constrain the Yukawa structure of the type-III two-Higgs-doublet model from tree-level FCNC processes (Bs,d→μ+μ−, KL→μ+μ−, D¯¯¯0→μ+μ−, ΔF=2 processes, τ−→μ−μ+μ−, τ−→e−μ+μ− and μ−→e−e+e−) and observe that all flavor off-diagonal elements of these couplings, except ϵu32,31 and ϵu23,13, must be very small in order to satisfy the current experimental bounds. In a third step, we consider Higgs mediated loop contributions to FCNC processes [b→s(d)γ, Bs,d mixing, K−K¯¯¯ mixing and μ→eγ] finding that also ϵu13 and ϵu23 must be very small, while the bounds on ϵu31 and ϵu32 are especially weak. Furthermore, considering the constraints from electric dipole moments we obtain constrains on some parameters ϵu,ℓij. Taking into account the constraints from FCNC processes we study the size of possible effects in the tauonic B decays (B→τν, B→Dτν and B→D∗τν) as well as in D(s)→τν, D(s)→μν, K(π)→eν, K(π)→μν and τ→K(π)ν which are all sensitive to tree-level charged Higgs exchange. Interestingly, the unconstrained ϵu32,31 are just the elements which directly enter the branching ratios for B→τν, B→Dτν and B→D∗τν. We show that they can explain the deviations from the SM predictions in these processes without fine-tuning. Furthermore, B→τν, B→Dτν and B→D∗τν can even be explained simultaneously. Finally, we give upper limits on the branching ratios of the lepton flavor-violating neutral B meson decays (Bs,d→μe, Bs,d→τe and Bs,d→τμ) and correlate the radiative lepton decays (τ→μγ, τ→eγ and μ→eγ) to the corresponding neutral current lepton decays (τ−→μ−μ+μ−, τ−→e−μ+μ− and μ−→e−e+e−). A detailed Appendix contains all relevant information for the considered processes for general scalar-fermion-fermion couplings.

Oral contraceptives and the risk of thrombosis and atherosclerosis.

Oral contraceptives containing synthetic oestrogens have been used successfully as birth control for > 40 years and are currently prescribed to > 100 million women worldwide. Several new progestins have been introduced and the third generation of progestins has now been available for two decades. Oral contraceptives are prescribed over a prolonged period of time and therefore substantially impact on hormonal, metabolic and plasmatic functions. Oral contraceptives increase the risk for venous thrombosis and pulmonary embolism, particularly if associated with confounding factors, such as genetic predisposition, smoking, hypertension or obesity. The risk of developing coronary artery disease is also increased in users with cardiovascular risk factors. This article discusses mechanistic and clinical issues and reviews the need for novel approaches targeting the considerable side effects in order to reduce cardiovascular morbidity in women using oral contraceptives.

Creatine supports propagation and promotes neuronal differentiation of inner ear progenitor cells

Long-term propagation of inner ear-derived progenitor/stem cells beyond the third generation and differentiation into inner ear cell types has been shown to be feasible, but challenging. We investigated whether the known neuroprotective guanidine compound creatine (Cr) promotes propagation of inner ear progenitor/stem cells as mitogen-expanded neurosphere cultures judged from the formation of spheres over passages. In addition, we studied whether Cr alone or in combination with brain-derived neurotrophic factor (BDNF) promotes neuronal differentiation of inner ear progenitors. For this purpose, early postnatal rat spiral ganglia, utricle, and organ of Corti-derived progenitors were grown as floating spheres in the absence (controls) or presence of Cr (5 mM) from passage 3 onward. Similarly, dissociated sphere-derived cultures were differentiated for 14 days in the presence or absence of Cr (5 mM) and spiral ganglia sphere-derived cultures in a combination of Cr with the neurotrophin BDNF (50 ng/ml). We found that the cumulative total number of spheres over all passages was significantly higher after Cr supplementation as compared with controls in all the three inner ear cultures. In contrast, sphere sizes were not affected by the administration of Cr. Administration of Cr during differentiation of spiral ganglia cells resulted in a significantly higher density of β-III-tubulin-positive cells compared with controls, whereas densities of myosin VIIa-positive cells in cultures of utricle and organ of Corti were not affected by the treatment. Importantly, a combination of Cr with the neurotrophin BDNF resulted in further significantly increased densities of β-III-tubulin-positive cells in cultures of spiral ganglia cells as compared with single treatments. In sum, Cr promoted continuing propagation of rat inner ear-derived progenitor cells and supported specifically in combination with BDNF the differentiation of neuronal cell types from spiral ganglion-derived spheres.

Evidence for the involvement of proximal chromosome 3P loci in the progression of Von Hippel-Lindau related tumors

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by the development of retinal and central nervous system hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma and pancreatic islet cell tumors (PICT). The VHL gene maps to chromosome 3p25 and has been shown to be mutated in 57% of sporadic cases of RCC, implicating VHL in the genesis of RCC. We report a multigeneration VHL kindred in which four affected female siblings developed PICT at early ages. Analysis of the three coding exons of the VHL gene in this family revealed a single, missense mutation in codon 238. Inheritance of the 238 mutation has been reported to correlate with a 62% risk of pheochromocytoma development. In this kindred, all affected individuals carried the mutation as well as one additional sibling who showed no evidence of disease. Clinical screening of this individual indicated small ($<$1 cm) pancreatic and kidney tumors. Results suggest that inheritance of the codon 238 mutation does not correlate with early onset pheochromocytoma. Rather, the only individual in the pedigree with pheochromocytoma was the proband's mother who developed bilateral pheochromocytoma at the age of 62. Thus, the VHL codon 238 mutation may predispose to late onset pheochromocytoma in this family; however, it does not explain the preponderance of PICT in the third generation since this mutation has not been reported to increase the risk of developing pancreatic lesions. This suggests that inheritance of the codon 238 mutation and subsequent somatic inactivation of the wild type allele of the VHL gene may not be sufficient to explain the initiation and subsequent progression to malignancy in VHL-associated neoplasms. Since the two tumor types that most frequently progress to malignancy are RCC and PICT, we asked whether loss of heterozygosity (LOH) could be detected proximal to the VHL gene on chromosome 3 in distinct regions of 3p previously implicated by LOH and cytogenetic studies to contain tumor suppressor loci for RCC. LOH was performed on high molecular weight DNA isolated from peripheral blood and frozen tumor tissue of family members using microsatellite markers spanning 3p. Results indicated LOH for all informative 3p loci in tumor tissue from affected individuals with PICT. LOH was detected along the entire length of the chromosome arm and included the proximal region of 3p13-14.2 implicated in the hereditary form of renal cell carcinoma.^ If 3p LOH were a critical event in pancreatic islet cell tumorigenesis, then it should be expected that LOH in sporadic islet cell tumors would also be observed. We expanded LOH studies to include sporadic cases of PICT. Consistent LOH was observed on 3p with a highest frequency LOH in the region 3p21.2. This is the first evidence for an association between chromosome 3 loci and pancreatic islet cell tumorigenesis. (Abstract shortened by UMI.) ^

The Global Digital Divide as Impeded Access to Content

The paper seeks a re-conceptualization of the global digital divide debate. It critically explores the predominant notion, its evolution and measurement, as well as the policies that have been advanced to bridge the digital divide. Acknowledging the complexity of this inequality, the paper aims at analyzing the disparities beyond the connectivity and the skills barriers. Without understating the first two digital divides, it is argued that as the Internet becomes more sophisticated and more integrated into economic, social and cultural processes, a ‘third’ generation of divides becomes critical. These divides are drawn not at the entry to the net but within the net itself, and limit access to content. The increasing barriers to content, although of diverse nature, all relate to some governance characteristics inherent in cyberspace, such as global spillover of local decisions, regulation through code or proliferation of self- and co-regulatory models. It is maintained that as the practice of intervention intensifies in cyberspace, multiple and far-reaching points of control outside formal legal institutions are created, which threaten the availability of public goods and make the pursuit of public objectives difficult. This is an aspect that is rarely addressed in the global digital divide discussions, even in comprehensive analysis and political initiatives such as the World Summit on the Information Society. Yet, the conceptualization of the digital divide as impeded access to content may be key in terms of ensuring real participation and catering for the long-term implications of digital technologies.

Re-Conceptualizing the Global Digital Divide

The article seeks a re-conceptualization of the global digital divide debate. It critically explores the predominant notion, its evolution and measurement, as well as the policies that have been advanced to bridge the digital divide. Acknowledging the complexity of this inequality, the article aims at analyzing the disparities beyond the connectivity and skills barriers. Without understating the first two digital divides, it is argued that as the Internet becomes more sophisticated and more integrated into economic, social, and cultural processes, a “third” generation of divides becomes critical. These divides are drawn not at the entry to the net but within the net itself, and limit access to content. The increasing barriers to content, though of a diverse nature, all relate to some governance characteristics inherent in cyberspace, such as global spillover of local decisions, regulation through code, and proliferation of self- and co-regulatory models. It is maintained that as the practice of intervention intensifies in cyberspace, multiple and far-reaching points of control outside formal legal institutions are created, threatening the availability of public goods and making the pursuit of public objectives difficult. This is an aspect that is rarely addressed in the global digital divide discussions, even in comprehensive analyses and political initiatives such as the World Summit on the Information Society. Yet, the conceptualization of the digital divide as impeded access to content may be key in terms of ensuring real participation and catering for the long-term implications of digital technologies.

Long-Term Comparison of Everolimus-Eluting and Biolimus-Eluting Stents in All-Comer Patients

AIMS: Second-generation everolimus-eluting stents (EES) are safer and more efficient than first-generation paclitaxel-eluting stents (PES). Third-generation biolimus-eluting stents (BES) have been found to be non-inferior to PES. To date, there is no available comparative study between EES and BES. We aimed to investigate the safety and efficacy of BES with biodegradable polymer compared to EES with durable polymer at a follow-up of two years in an unselected population of consecutively enrolled patients. METHODS AND RESULTS: A group of 814 consecutive patients undergoing percutaneous coronary intervention (PCI) was enrolled between 2007 and 2010, of which 527 were treated with EES and 287 with BES implantation. Clinical outcome was compared in 200 pairs using propensity score matching. The primary endpoint was a composite of death, myocardial infarction (MI) and target vessel revascularisation (TVR) at two-year follow-up. Median follow-up was 22 months. The primary outcome occurred in 11.5% of EES and 10.5% of BES patients (HR 1.11, 95% CI: 0.61-2.00, p=0.74). At two years, there was no significant difference with regard to death (HR 0.49, 95% CI: 0.18-1.34, p=0.17), cardiac death (HR 0.14, 95% CI: 0.02-1.14, p=0.66) or MI (HR 6.10, 95% CI: 0.73-50.9, p=0.10). Stent thrombosis (ST) incidence was evenly distributed between EES (n=2) and BES (n=2) (p-value=1.0). CONCLUSIONS: This first clinical study failed to demonstrate any significant difference regarding safety or efficacy between these two types and generations of drug-eluting stents (DES).

Comparison of everolimus- and biolimus-eluting stents with everolimus-eluting bioresorbable vascular scaffold stents: study protocol of the randomized controlled EVERBIO II

BACKGROUND: Second-generation everolimus-eluting stents (EES) and third generation biolimus-eluting stents (BES) have been shown to be superior to first-generation paclitaxel-eluting stents (PES) and second-generation sirolimus-eluting stents (SES). However, neointimal proliferation and very late stent thrombosis is still an unresolved issue of drug-eluting stent (DES) implantation overall. The Absorb™ (Abbott Vascular, Abbott Park, IL, USA) is the first CE approved DES with a bioresorbable vascular scaffold (BVS) thought to reduce long-term complication rates. The EVERBIO II trial was set up to compare the BVS safety and efficacy with both EES and BES in all patients viable for inclusion. METHODS/DESIGN: The EVERBIO II trial is a single-center, assessor-blinded, randomized trial. The study population consists of all patients aged≥18 years old undergoing percutaneous coronary intervention. Exclusion criterion is where the lesion cannot be treated with BVS (reference vessel diameter>4.0 mm). A total of 240 patients will be enrolled and randomly assigned into 3 groups of 80 with either BVS, EES or BES implantation. All patients will undergo a follow-up angiography study at 9 months. Clinical follow-up for up to 5 years will be conducted by telephone. The primary endpoint is in-segment late lumen loss at 9 months measured by quantitative coronary angiography. Secondary endpoints are patient-oriented major adverse cardiac event (MACE) (death, myocardial infarction and target-vessel revascularization), device-oriented MACE (cardiac death, myocardial infarction and target-lesion revascularization), stent thrombosis according to ARC and binary restenosis at follow-up 12 months angiography. DISCUSSION: EVERBIO II is an independent, randomized study, aiming to compare the clinical efficacy, angiographic outcomes and safety of BVS, EES and BES in all comer patients. TRIAL REGISTRATION: The trial listed in clinicaltrials.gov as NCT01711931.

High colonization rates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in Swiss Travellers to South Asia- a prospective observational multicentre cohort study looking at epidemiology, microbiology and risk factors.

BACKGROUND International travel contributes to the worldwide spread of multidrug resistant Gram-negative bacteria. Rates of travel-related faecal colonization with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae vary for different destinations. Especially travellers returning from the Indian subcontinent show high colonization rates. So far, nothing is known about region-specific risk factors for becoming colonized. METHODS An observational prospective multicentre cohort study investigated travellers to South Asia. Before and after travelling, rectal swabs were screened for third-generation cephalosporin- and carbapenem-resistant Enterobacteriaceae. Participants completed questionnaires to identify risk factors for becoming colonized. Covariates were assessed univariately, followed by a multivariate regression. RESULTS Hundred and seventy persons were enrolled, the largest data set on travellers to the Indian subcontinent so far. The acquired colonization rate with ESBL-producing Escherichia coli overall was 69.4% (95% CI 62.1-75.9%), being highest in travellers returning from India (86.8%; 95% CI 78.5-95.0%) and lowest in travellers returning from Sri Lanka (34.7%; 95% CI 22.9-48.7%). Associated risk factors were travel destination, length of stay, visiting friends and relatives, and eating ice cream and pastry. CONCLUSIONS High colonization rates with ESBL-producing Enterobacteriaceae were found in travellers returning from South Asia. Though risk factors were identified, a more common source, i.e. environmental, appears to better explain the high colonization rates.

Pitfalls and premature failure of the Freedom SOLO stentless valve.

OBJECTIVES This study reports a series of pitfalls, premature failures and explantations of the third-generation Freedom SOLO (FS) bovine pericardial stentless valve. METHODS A total of 149 patients underwent aortic valve replacement using the FS. Follow-up was 100% complete with an average observation time of 5.5 ± 2.3 years (maximum 8.7 years) and a total of 825 patient-years. Following intraoperative documentation, all explanted valve prostheses underwent histological examination. RESULTS Freedom from structural valve deterioration (SVD) at 5, 6, 7, 8 and 9 years was 92, 88, 80, 70 and 62%, respectively. Fourteen prostheses required explantation due to valve-independent dysfunction (n = 5; i.e. thrombus formation, oversizing, aortic dilatation, endocarditis and suture dehiscence) or valve-dependent failure (acute leaflet tears, n = 4 and severe stenosis, n = 5). Thus, freedom from explantation at 5, 6, 7, 8 and 9 years was 95, 94, 91, 81 and 72%, respectively. An acute vertical tear along the non-coronary/right coronary commissure to the base occurred at a mean of 6.0 years (range 4.3-7.3 years) and affected size 25 and 27 prostheses exclusively. Four FS required explantation after a mean of 7.5 years (range 7.0-8.3 years) due to severe functional stenosis and gross calcification that included the entire aortic root. CONCLUSIONS The FS stentless valve is safe to implant and shows satisfying mid-term results in our single institution experience. Freedom from SVD and explantation decreased markedly after only 6-7 years, so that patients with FS require close observation and follow-up. Exact sizing, symmetric positioning and observing patient limitations are crucial for optimal outcome.