Every contact manifold can be given a non-fillable contact structure

Recently Francisco Presas Mata constructed the first examples of closed contact manifolds of dimension larger than 3 that contain a plastikstufe, and hence are non-fillable. Using contact surgery on his examples we create on every sphere S^{2n-1}, n>1, an exotic contact structure \xi_- that also contains a plastikstufe. As a consequence, every closed contact manifold M (except S^1) can be converted into a contact manifold that is not (semi-positively) fillable by taking the connected sum of M with (S^{2n-1},\xi_-).Comment: 15 pages, 4 figure

Adoption of the Website and Mobile App of a Preventive Health Program Across Neighborhoods With Different Socioeconomic Conditions in the Netherlands:Longitudinal Study

BACKGROUND: Socioeconomic disparities in the adoption of preventive health programs represent a well-known challenge, with programs delivered via the web serving as a potential solution. The preventive health program examined in this study is a large-scale, open-access web-based platform operating in the Netherlands, which aims to improve the health behaviors and wellness of its participants. OBJECTIVE: This study aims to examine the differences in the adoption of the website and mobile app of a web-based preventive health program across socioeconomic groups. METHODS: The 83,466 participants in this longitudinal, nonexperimental study were individuals who had signed up for the health program between July 2012 and September 2019. The rate of program adoption per delivery means was estimated using the Prentice, Williams, and Peterson Gap–Time model, with the measure of neighborhood socioeconomic status (NSES) used to distinguish between population segments with different socioeconomic characteristics. Registration to the health program was voluntary and free, and not within a controlled study setting, allowing the observation of the true rate of adoption. RESULTS: The estimation results indicate that program adoption across socioeconomic groups varies depending on the program’s delivery means. For the website, higher NSES groups have a higher likelihood of program adoption compared with the lowest NSES group (hazard ratio 1.03, 95% CI 1.01-1.05). For the mobile app, the opposite holds: higher NSES groups have a lower likelihood of program adoption compared with the lowest NSES group (hazard ratio 0.94, 95% CI 0.91-0.97). CONCLUSIONS: Promoting preventive health programs using mobile apps can help to increase program adoption among the lowest socioeconomic segments. Given the increasing use of mobile phones among disadvantaged population groups, structuring future health interventions to include mobile apps as means of delivery can support the stride toward diminishing health disparities

Brieskorn manifolds as contact branched covers of spheres

We show that Brieskorn manifolds with their standard contact structures are contact branched coverings of spheres. This covering maps a contact open book decomposition of the Brieskorn manifold onto a Milnor open book of the sphere.Comment: 8 pages, 1 figur

5-dimensional contact SO(3)-manifolds and Dehn twists

In this paper the 5-dimensional contact SO(3)-manifolds are classified up to equivariant contactomorphisms. The construction of such manifolds with singular orbits requires the use of generalized Dehn twists. We show as an application that all simply connected 5-manifoldswith singular orbits are realized by a Brieskorn manifold with exponents (k,2,2,2). The standard contact structure on such a manifold gives right-handed Dehn twists, and a second contact structure defined in the article gives left-handed twists.Comment: 16 pages, 1 figure; simplification of arguments by restricting classification to coorientation preserving contactomorphism

Inequivalent contact structures on Boothby-Wang 5-manifolds

We consider contact structures on simply-connected 5-manifolds which arise as circle bundles over simply-connected symplectic 4-manifolds and show that invariants from contact homology are related to the divisibility of the canonical class of the symplectic structure. As an application we find new examples of inequivalent contact structures in the same equivalence class of almost contact structures with non-zero first Chern class.Comment: 27 pages; to appear in Math. Zeitschrif

A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.</p> <p>Methods/Design</p> <p>The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 2^1/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.</p> <p>Discussion</p> <p>If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC.</p> <p>Trial Register</p> <p>Trial registered at <url>http://www.clinicaltrials.gov</url>: NCT00355862</p> <p>(EudraCT Number: 2005-005362-36)</p

A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

Peer reviewe

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial

Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age 60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.Peer reviewe