Effect of peri-implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures: Consensus report of group 2 of the SEPA/DGI/OF workshop

OBJECTIVES: The aim of this study was to comprehensively assess the literature in terms of the effect of peri‐implant mucosal thickness on esthetic outcomes and the efficacy of soft tissue augmentation procedures to increase the mucosal thickness with autogenous grafts or soft tissue substitutes. MATERIAL AND METHODS: Two systematic reviews (SR) were performed prior to the consensus meeting to assess the following questions. Review 1, focused question: In systemically healthy patients with an implant‐supported fixed prosthesis, what is the influence of thin as compared to thick peri‐implant mucosa on esthetic outcomes? Review 2, focused question 1: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of connective tissue graft (CTG), as compared to absence of a soft tissue grafting procedure, in terms of gain in peri‐implant soft tissue thickness (STT) reported by randomized controlled clinical trials (RCTs) or controlled clinical trials (CCTs)? Review 2, focused question 2: In systemically healthy humans with at least one dental implant (immediate or staged implant), what is the efficacy of CTG, as compared to soft tissue substitutes, in terms of gain in peri‐implant STT reported by RCTs or CCTs? The outcomes of the two SRs, the consensus statements, the clinical implications, and the research recommendations were discussed and subsequently approved at the consensus meeting during the group and plenary sessions. CONCLUSIONS: There was a tendency of superior esthetic outcomes in the presence of a thick mucosa. The connective tissue graft remains the standard of care in terms of increasing mucosa thickness

Nothing Ventured — Nothing Gained? Empirical Evidence on Venture Capital Financing in Switzerland

This paper analyses the Determinants of Venture Capital Staging and Syndication in Switzerland. I find that among the different affiliations of VC investors in Switzerland especially independent investors make more extensive use of staged capital infusions. Moreover, the results suggest that staging is employed as a tool for mitigating risks in VC financing. In addition, I find that Syndication can serve as an entrance strategy for foreign VC providers. Furthermore, I find evidence that firms, which realize the benefit of staging, do also become conscious of the value added in financing Start Ups by involving partners. Consequently, VC firms that make use of staging are also more open to syndication. With respect to the value-added of Co-Investment behavior, I show that syndication positively impacts the success rate of a VC provider, whereas VC firms that are more locally embedded do exhibit lower success rates for their investment portfolio

Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis

CCAAT/enhancer binding protein alpha (CEBPA) mutations in AML are associated with favourable prognosis and are divided into N- and C-terminal mutations. The majority of AML patients have both types of mutations. We assessed the prognostic significance of single (n=7) and double (n=12) CEBPA mutations among 224 AML patients. Double CEBPA mutations conferred a decisively favourable overall (P=0.006) and disease-free survival (P=0.013). However, clinical outcome of patients with single CEBPA mutations was not different from CEBPA wild-type patients. In a multivariable analysis, only double – but not single – CEBPA mutations were identified as independent prognostic factors. These findings indicate heterogeneity within AML patients with CEBPA mutations

Mitigation of Moral Hazard and Adverse Selection in Venture Capital Financing: The Influence of the Country’s Institutional Setting

A venture capitalist (VC) needs to trade off benefits and costs when attempting to mitigate agency problems in their investor-investee relationship. We argue that signals of ventures complement the VC’s capacity to screen and conduct a due diligence during the pre-investment phase, but its attractiveness may diminish in institutional settings supporting greater transparency. Similarly, whereas a VC may opt for contractual covenants to curb potential opportunism by ventures in the post-investment phase, this may only be effective in settings supportive of shareholder rights enforcement. Using an international sample of VC contracts, our study finds broad support for these conjectures. It delineates theoretical and practical implications for how investors can best deploy their capital in different institutional settings whilst nurturing their relationships with entrepreneurs

A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication

Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes. In poliovirus-infected cells, ER and Golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral RNA synthesis. Virus replication is inhibited by brefeldin A (BFA), implicating some components(s) of the cellular secretory pathway in virus growth. Formation of characteristic vesicles induced by expression of viral proteins was not inhibited by BFA, but they were functionally deficient. GBF1, a guanine nucleotide exchange factor for the small cellular GTPases, Arf, is responsible for the sensitivity of virus infection to BFA, and is required for virus replication. Knockdown of GBF1 expression inhibited virus replication, which was rescued by catalytically active protein with an intact N-terminal sequence. We identified a mutation in GBF1 that allows growth of poliovirus in the presence of BFA. Interaction between GBF1 and viral protein 3A determined the outcome of infection in the presence of BFA

A Search for Jet Handedness in Hadronic Z0Z^0 Decays

We have searched for signatures of polarization in hadronic jets from $Z^0 \to q \bar{q}$ decays using the ``jet handedness'' method. The polar angle asymmetry induced by the high SLC electron-beam polarization was used to separate quark jets from antiquark jets, expected to be left- and right-polarized, respectively. We find no evidence for jet handedness in our global sample or in a sample of light quark jets and we set upper limits at the 95% C.L. of 0.063 and 0.099 respectively on the magnitude of the analyzing power of the method proposed by Efremov {\it et al.}Comment: Revtex, 8 pages, 2 figure

Ibrutinib for Relapsed / Refractory CLL: A UK and Ireland Analysis of Outcomes in 315 patients

In 2014, ibrutinib was made available for relapsed/refractory chronic lymphocytic leukaemia (CLL) patients. The UK CLL Forum collected data from UK/Ireland patients with a minimum of 1 year follow-up with pre-planned primary endpoints; the number of patients still on therapy at 1 year (Discontinuation Free Survival; DFS) and 1 year overall survival (OS). With a median 16 months follow-up, data on 315 patients demonstrated 1 year DFS of 73.7% and 1 year OS of 83.8%. Patients with better pre-treatment performance status (PS 0/1 vs 2+) had superior DFS (77.5% vs 61.3%;p14 days and had OS of 89.7%, while 26% of patients had dose reductions and 13% had temporary treatment breaks >14 days. We could not demonstrate a detrimental effect of dose reductions alone (1 year OS: 91.7%), but patients who had first year treatment breaks > 14 days, particularly permanent cessation of ibrutinib had both reduced 1 year OS (68.5%) and also a statistically significant excess mortality rate beyond one year. Although outcomes appear inferior to the RESONATE trial (1 year OS;90%: PFS;84%), this may partly reflect the inclusion of PS 2+ patients and that 17.5% of patients permanently discontinued ibrutinib due to an event other than disease progression

Diagnosis of acute myeloid leukemia according to the WHO classification in the Japan Adult Leukemia Study Group AML-97 protocol

We reviewed and categorized 638 of 809 patients who were registered in the Japan Adult Leukemia Study Group acute myeloid leukemia (AML)-97 protocol using morphological means. Patients with the M3 subtype were excluded from the study group. According to the WHO classification, 171 patients (26.8%) had AML with recurrent genetic abnormalities, 133 (20.8%) had AML with multilineage dysplasia (MLD), 331 (51.9%) had AML not otherwise categorized, and 3 (0.5%) had acute leukemia of ambiguous lineage. The platelet count was higher and the rate of myeloperoxidase (MPO)-positive blasts was lower in AML with MLD than in the other WHO categories. The outcome was significantly better in patients with high (≥50%) than with low (<50%) ratios of MPO-positive blasts (P < 0.01). The 5-year survival rates for patients with favorable, intermediate, and adverse karyotypes were 63.4, 39.1, and 0.0%, respectively, and 35.5% for those with 11q23 abnormalities (P < 0.0001). Overall survival (OS) did not significantly differ between nine patients with t(9;11) and 23 with other 11q23 abnormalities (P = 0.22). Our results confirmed that the cytogenetic profile, MLD phenotype, and MPO-positivity of blasts are associated with survival in patients with AML, and showed that each category had the characteristics of the WHO classification such as incidence, clinical features, and OS

Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion

Amassments of heterochromatin in somatic cells occur in close contact with the nuclear envelope (NE) but are gapped by channel- and cone-like zones that appear largely free of heterochromatin and associated with the nuclear pore complexes (NPCs). To identify proteins involved in forming such heterochromatin exclusion zones (HEZs), we used a cell culture model in which chromatin condensation induced by poliovirus (PV) infection revealed HEZs resembling those in normal tissue cells. HEZ occurrence depended on the NPC-associated protein Tpr and its large coiled coil-forming domain. RNAi-mediated loss of Tpr allowed condensing chromatin to occur all along the NE's nuclear surface, resulting in HEZs no longer being established and NPCs covered by heterochromatin. These results assign a central function to Tpr as a determinant of perinuclear organization, with a direct role in forming a morphologically distinct nuclear sub-compartment and delimiting heterochromatin distribution

SARS-Coronavirus Replication Is Supported by a Reticulovesicular Network of Modified Endoplasmic Reticulum

Positive-strand RNA viruses, a large group including human pathogens such as SARS-coronavirus (SARS-CoV), replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified host cell membranes. Membrane structures supporting viral RNA synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. Generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to be defined. Poorly characterized double-membrane vesicles (DMVs) were previously implicated in SARS-CoV RNA synthesis. We have now applied electron tomography of cryofixed infected cells for the three-dimensional imaging of coronavirus-induced membrane alterations at high resolution. Our analysis defines a unique reticulovesicular network of modified endoplasmic reticulum that integrates convoluted membranes, numerous interconnected DMVs (diameter 200–300 nm), and “vesicle packets” apparently arising from DMV merger. The convoluted membranes were most abundantly immunolabeled for viral replicase subunits. However, double-stranded RNA, presumably revealing the site of viral RNA synthesis, mainly localized to the DMV interior. Since we could not discern a connection between DMV interior and cytosol, our analysis raises several questions about the mechanism of DMV formation and the actual site of SARS-CoV RNA synthesis. Our data document the extensive virus-induced reorganization of host cell membranes into a network that is used to organize viral replication and possibly hide replicating RNA from antiviral defense mechanisms. Together with biochemical studies of the viral enzyme complex, our ultrastructural description of this “replication network” will aid to further dissect the early stages of the coronavirus life cycle and its virus-host interactions