14 results on '"Michele Leone"'
Search Results
2. Accurate and highly interpretable prediction of gene expression from histone modifications
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Fabrizio Frasca, Matteo Matteucci, Michele Leone, Marco J. Morelli, and Marco Masseroli
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Gene expression regulation ,Histone modifications ,Epigenetics ,Interpretability ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Histone Mark Modifications (HMs) are crucial actors in gene regulation, as they actively remodel chromatin to modulate transcriptional activity: aberrant combinatorial patterns of HMs have been connected with several diseases, including cancer. HMs are, however, reversible modifications: understanding their role in disease would allow the design of ‘epigenetic drugs’ for specific, non-invasive treatments. Standard statistical techniques were not entirely successful in extracting representative features from raw HM signals over gene locations. On the other hand, deep learning approaches allow for effective automatic feature extraction, but at the expense of model interpretation. Results Here, we propose ShallowChrome, a novel computational pipeline to model transcriptional regulation via HMs in both an accurate and interpretable way. We attain state-of-the-art results on the binary classification of gene transcriptional states over 56 cell-types from the REMC database, largely outperforming recent deep learning approaches. We interpret our models by extracting insightful gene-specific regulative patterns, and we analyse them for the specific case of the PAX5 gene over three differentiated blood cell lines. Finally, we compare the patterns we obtained with the characteristic emission patterns of ChromHMM, and show that ShallowChrome is able to coherently rank groups of chromatin states w.r.t. their transcriptional activity. Conclusions In this work we demonstrate that it is possible to model HM-modulated gene expression regulation in a highly accurate, yet interpretable way. Our feature extraction algorithm leverages on data downstream the identification of enriched regions to retrieve gene-wise, statistically significant and dynamically located features for each HM. These features are highly predictive of gene transcriptional state, and allow for accurate modeling by computationally efficient logistic regression models. These models allow a direct inspection and a rigorous interpretation, helping to formulate quantifiable hypotheses.
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- 2022
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3. Large‐Scale Transdisciplinary Collaboration for Adaptation Research: Challenges and Insights
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Georgina Cundill, Blane Harvey, Mark Tebboth, Logan Cochrane, Bruce Currie‐Alder, Katharine Vincent, Jon Lawn, Robert. J. Nicholls, Lucia Scodanibbio, Anjal Prakash, Mark New, Philippus Wester, Michele Leone, Daniel Morchain, Eva Ludi, Jesse DeMaria‐Kinney, Ahmed Khan, and Marie‐Eve Landry
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climate change ,collaboration ,transdisciplinarity ,Technology ,Environmental sciences ,GE1-350 - Abstract
Abstract An increasing number of research programs seek to support adaptation to climate change through the engagement of large‐scale transdisciplinary networks that span countries and continents. While transdisciplinary research processes have been a topic of reflection, practice, and refinement for some time, these trends now mean that the global change research community needs to reflect and learn how to pursue collaborative research on a large scale. This paper shares insights from a seven‐year climate change adaptation research program that supports collaboration between more than 450 researchers and practitioners across four consortia and 17 countries. The experience confirms the importance of attention to careful design for transdisciplinary collaboration, but also highlights that this alone is not enough. The success of well‐designed transdisciplinary research processes is also strongly influenced by relational and systemic features of collaborative relationships. Relational features include interpersonal trust, mutual respect, and leadership styles, while systemic features include legal partnership agreements, power asymmetries between partners, and institutional values and cultures. In the new arena of large‐scale collaborative science efforts, enablers of transdisciplinary collaboration include dedicated project coordinators, leaders at multiple levels, and the availability of small amounts of flexible funds to enable nimble responses to opportunities and unexpected collaborations.
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- 2019
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4. GeMI: interactive interface for transformer-based Genomic Metadata Integration
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Giuseppe Serna Garcia, Michele Leone, Anna Bernasconi, and Mark J Carman
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Machine Learning ,Metadata ,Data Mining ,Genomics ,General Agricultural and Biological Sciences ,General Biochemistry, Genetics and Molecular Biology ,Software ,Information Systems - Abstract
The Gene Expression Omnibus (GEO) is a public archive containing >4 million digital samples from functional genomics experiments collected over almost two decades. The accompanying metadata describing the experiments suffer from redundancy, inconsistency and incompleteness due to the prevalence of free text and the lack of well-defined data formats and their validation. To remedy this situation, we created Genomic Metadata Integration (GeMI; http://gmql.eu/gemi/), a web application that learns to automatically extract structured metadata (in the form of key-value pairs) from the plain text descriptions of GEO experiments. The extracted information can then be indexed for structured search and used for various downstream data mining activities. GeMI works in continuous interaction with its users. The natural language processing transformer-based model at the core of our system is a fine-tuned version of the Generative Pre-trained Transformer 2 (GPT2) model that is able to learn continuously from the feedback of the users thanks to an active learning framework designed for the purpose. As a part of such a framework, a machine learning interpretation mechanism (that exploits saliency maps) allows the users to understand easily and quickly whether the predictions of the model are correct and improves the overall usability. GeMI’s ability to extract attributes not explicitly mentioned (such as sex, tissue type, cell type, ethnicity and disease) allows researchers to perform specific queries and classification of experiments, which was previously possible only after spending time and resources with tedious manual annotation. The usefulness of GeMI is demonstrated on practical research use cases. Database URL http://gmql.eu/gemi/
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- 2022
5. The future is collaborative
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Georgina Cundill, Michele Leone, and Bruce Currie-Alder
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Climate change ,Business ,Environmental Science (miscellaneous) ,Environmental planning ,Social Sciences (miscellaneous) - Abstract
The way in which climate change research funds are managed is shifting dramatically toward investments in large collaborative research networks. This poses significant challenges for researchers, and requires changes from the institutions and funders that support them.
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- 2019
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6. A reflection on collaborative adaptation research in Africa and Asia
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Evans Kituyi, K. S. Murali, Michele Leone, Philippus Wester, Eva Ludi, Bernard Cantin, Georgina Cundill, Logan Cochrane, Mark New, Robert J. Nicholls, and Marie-Eve Landry
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Global and Planetary Change ,010504 meteorology & atmospheric sciences ,business.industry ,Corporate governance ,Global warming ,Environmental resource management ,Climate change ,010501 environmental sciences ,01 natural sciences ,Nature Conservation ,Political science ,Climate change adaptation ,business ,0105 earth and related environmental sciences - Abstract
The reality of global climate change demands novel approaches to science that are reflective of the scales at which changes are likely to occur, and of the new forms of knowledge required to positively influence policy to support vulnerable populations. We examine some of the opportunities and challenges presented by a collaborative, transdisciplinary research project on climate change adaptation in Africa and Asia that utilised a hotspot approach. A large scale effort to develop appropriate baselines was a key challenge at the outset of the program, as was the need to develop innovative methodologies to enable researchers to work at appropriate spatial scales. Efforts to match research to the biophysical scales at which change occurs need to be aware of the mismatch that can develop between these regional scales and the governance scales at which decisions are made.
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- 2017
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7. Immediate loading of two (fixed-on-2) versus three (fixed-on-3) implants placed flapless supporting cross-arch fixed prostheses: One-year results from a randomised controlled trial
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Gioacchino, Cannizzaro, Ignazio, Loi, Paolo, Viola, Vittorio, Ferri, Michele, Leone, Anna, Trullenque-Eriksson, and Marco, Esposito
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Adult ,Dental Implants ,Male ,Titanium ,Immediate Dental Implant Loading ,Denture, Complete ,Alveolar Bone Loss ,Dental Implant-Abutment Design ,Middle Aged ,Surgical Flaps ,Dental Materials ,Postoperative Complications ,Treatment Outcome ,Bone Density ,Alveolar Process ,Humans ,Jaw, Edentulous ,Female ,Dental Prosthesis, Implant-Supported ,Dental Restoration Failure ,Denture Design ,Radiography, Bitewing ,Aged ,Follow-Up Studies - Abstract
To evaluate the outcome of two (fixed-on-2 = FO2) versus three (fixed-on-3 = FO3) implants placed flapless in fully edentulous jaws and immediately restored with metal-resin screw-retained crossarch prostheses.Forty edentulous or to be rendered edentulous patients (20 in the maxilla and 20 in the mandible) were randomised to the FO2 group (20 patients: 10 in the maxilla and 10 in the mandible) and to the FO3 group (20 patients: 10 in the maxilla and 10 in the mandible) according to a parallel group design. To be immediately loaded, implants had to be inserted with a minimum torque of 60 Ncm. Outcome measures were prosthesis and implant failures, complications and periimplant marginal bone level changes evaluated up to 1-year post-loading.Flaps were raised in four patients and two prostheses were loaded early at 8 weeks in the FO2 group. One year after loading no dropout or implant failure occurred, however one FO2 maxillary prosthesis had to be remade because of repeated screw-loosening (risk difference = 0.05; 95% CI: -0.05 to 0.15; Fisher's exact test P = 1.000). Three FO2 patients were affected by complications versus five FO3 patients (risk difference = -0.1; 95% CI: -0.35 to 0.15; Fisher's exact test; P = 0.695). There were no statistically significant differences for prosthetic failures and complications between groups. There were no statistically significant differences for marginal peri-implant bone levels between the two groups (estimate of the difference = 0.031 mm; 95% Cl: -0.22 to 0.28; P (ancova) = 0.803), with both groups losing marginal bone in a statistically significant way (0.27 mm for FO2 patients and 0.24 mm for FO3 patients).These preliminary results suggest that immediately loaded cross-arch prostheses can be supported by only two or three dental implants at least up to 1-year post-loading. Longer follow-ups are needed to properly evaluate both these therapeutic options.
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- 2016
8. Clustering by soft-constraint affinity propagation: applications to gene-expression data
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Martin Weigt, Michele Leone, and Sumedha
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Statistics and Probability ,Similarity (geometry) ,Proteome ,Computer science ,FOS: Physical sciences ,computer.software_genre ,Quantitative Biology - Quantitative Methods ,Models, Biological ,Biochemistry ,Pattern Recognition, Automated ,Artificial Intelligence ,Robustness (computer science) ,Protein Interaction Mapping ,Cluster Analysis ,Computer Simulation ,Databases, Protein ,Cluster analysis ,Molecular Biology ,Quantitative Methods (q-bio.QM) ,Condensed Matter - Statistical Mechanics ,Statistical Mechanics (cond-mat.stat-mech) ,Gene Expression Profiling ,Computer Science Applications ,Hierarchical clustering ,Constraint (information theory) ,Data set ,Computational Mathematics ,Computational Theory and Mathematics ,FOS: Biological sciences ,Physics - Data Analysis, Statistics and Probability ,Affinity propagation ,Data mining ,Algorithm ,computer ,Data Analysis, Statistics and Probability (physics.data-an) ,Algorithms ,Signal Transduction - Abstract
Motivation: Similarity-measure based clustering is a crucial problem appearing throughout scientific data analysis. Recently, a powerful new algorithm called Affinity Propagation (AP) based on message-passing techniques was proposed by Frey and Dueck \cite{Frey07}. In AP, each cluster is identified by a common exemplar all other data points of the same cluster refer to, and exemplars have to refer to themselves. Albeit its proved power, AP in its present form suffers from a number of drawbacks. The hard constraint of having exactly one exemplar per cluster restricts AP to classes of regularly shaped clusters, and leads to suboptimal performance, {\it e.g.}, in analyzing gene expression data. Results: This limitation can be overcome by relaxing the AP hard constraints. A new parameter controls the importance of the constraints compared to the aim of maximizing the overall similarity, and allows to interpolate between the simple case where each data point selects its closest neighbor as an exemplar and the original AP. The resulting soft-constraint affinity propagation (SCAP) becomes more informative, accurate and leads to more stable clustering. Even though a new {\it a priori} free-parameter is introduced, the overall dependence of the algorithm on external tuning is reduced, as robustness is increased and an optimal strategy for parameter selection emerges more naturally. SCAP is tested on biological benchmark data, including in particular microarray data related to various cancer types. We show that the algorithm efficiently unveils the hierarchical cluster structure present in the data sets. Further on, it allows to extract sparse gene expression signatures for each cluster., 11 pages, supplementary material: http://isiosf.isi.it/~weigt/scap_supplement.pdf
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- 2007
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9. Replica bounds for diluted non-Poissonian spin systems
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Michele Leone, Fabio Lucio Toninelli, and Silvio Franz
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Physics ,Cavity method ,Statistical Mechanics (cond-mat.stat-mech) ,Relation (database) ,Replica ,FOS: Physical sciences ,General Physics and Astronomy ,Statistical and Nonlinear Physics ,Disordered Systems and Neural Networks (cond-mat.dis-nn) ,Condensed Matter - Disordered Systems and Neural Networks ,Degree distribution ,Condensed Matter::Disordered Systems and Neural Networks ,Subadditivity ,Statistical physics ,Mathematical Physics ,Energy (signal processing) ,Condensed Matter - Statistical Mechanics ,Spin-½ ,Interpolation - Abstract
In this paper we extend replica bounds and free energy subadditivity arguments to diluted spin-glass models on graphs with arbitrary, non-Poissonian degree distribution. The new difficulties specific of this case are overcome introducing an interpolation procedure that stresses the relation between interpolation methods and the cavity method. As a byproduct we obtain self-averaging identities that generalize the Ghirlanda-Guerra ones to the multi-overlap case., Latex file, 15 pages, 2 eps figures; Weak point revised and corrected; Misprints corrected
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- 2003
10. [Untitled]
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Silvio Franz and Michele Leone
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Optimization problem ,Cavity method ,Replica ,Statistical and Nonlinear Physics ,Condensed Matter::Disordered Systems and Neural Networks ,Satisfiability ,Combinatorics ,Range (mathematics) ,Combinatorial optimization ,Applied mathematics ,Ground state ,Mathematical Physics ,Spin-½ ,Mathematics - Abstract
In this paper we generalize to the case of diluted spin models and random combinatorial optimization problems a technique recently introduced by Guerra (cond-mat/0205123) to prove that the replica method generates variational bounds for disordered systems. We analyze a family of models that includes the Viana–Bray model, the diluted p-spin model or random XOR-SAT problem, and the random K-SAT problem, showing that the replica/cavity method, at the various levels of approximation, provides systematic schemes to obtain lower bounds of the free-energy at all temperatures and of the ground state energy. In the case of K-SAT and XOR-SAT it thus gives upper bounds of the satisfiability threshold. Our analysis underlines deep connections with the cavity method which are not evident in the long range case.
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- 2003
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11. Immediate loading of fixed cross-arch prostheses supported by flapless-placed supershort or long implants: 1-year results from a randomised controlled trial
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Gioacchino, Cannizzaro, Pietro, Felice, Jacopo, Buti, Michele, Leone, Vittorio, Ferri, and Marco, Esposito
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Adult ,Aged, 80 and over ,Dental Implants ,Male ,Immediate Dental Implant Loading ,Dental Implantation, Endosseous ,Alveolar Bone Loss ,Mandible ,Middle Aged ,Denture Retention ,Treatment Outcome ,Torque ,Bone Density ,Osseointegration ,Maxilla ,Humans ,Jaw, Edentulous ,Female ,Dental Prosthesis, Implant-Supported ,Dental Restoration Failure ,Denture Design ,Radiography, Bitewing ,Aged ,Follow-Up Studies - Abstract
To compare the outcome of cross-arch prostheses supported either by supershort (5 mm) or long (11.5 mm) implants, placed flapless and immediately restored with metal-resin screw-retained cross-arch prostheses.Thirty patients with edentulous (or to be rendered edentulous) mandibles and 30 with edentulous maxillas, who had sufficient bone to allow the placement of four and six implants respectively, which were at least 11.5 mm-long, were randomised according to a parallel group design into 2 equal groups, where they received either 5 mm or 11.5 mm-long implants at one centre. Implants with a diameter of 5 mm, were to be placed flapless with an insertion torque of at least 50 Ncm. Mandibles received four implants between the mental foramina. Implants were to be immediately loaded with metal-resin-definitive prostheses on the same day of implant placement. Patients were followed up to 1 year after loading and the outcome measures were: prosthesis and implant failures, complications, and peri-implant marginal bone level changes.No patients dropped-out. Two prostheses were remade, one on short maxillary implants and one on long mandibular implants. Two 5 mm maxillary implants which did not achieve 50 Ncm torque in soft bone of one patient, but were immediately loaded anyway, failed after 3 weeks compared to one mandibular 11.5 mm-long implant that failed after 60 days. Two complications occurred in each group. There were no statistically significant differences for prosthesis failures, implant failures and complications. Patients with mandibular short implants lost on average 0.08 mm of peri-implant bone at 1 year and patients with long mandibular implants lost 0.51 mm. Patients with short maxillary implants lost on average 0.15 mm of peri-implant bone at 1 year and patients with long maxillary implants lost 0.62 mm. Short implants showed less bone loss when compared to long implants and the differences up to 1 year were statistically significant both in maxillae (mean difference = 0.48 mm, 95% CI 0.22 to 0.73, P = 0.0011) and in mandibles (mean difference = 0.44 mm, 95% CI 0.21 to 0.66, P = 0.0009).Flapless-placed 5 mm-long implants achieved similar results as 11.5 mm-long implants when supporting immediately loaded cross-arch prostheses both in maxillae and mandibles up to 1 year after loading. These preliminary results must be confirmed by other trials, and 5- to 10-year post-loading data is necessary before making reliable recommendations.
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- 2015
12. Immediate loading of 2 (all-on-2) flapless-placed mandibular implants supporting cross-arch fixed prostheses: interim data from a 1-year follow-up prospective single cohort study
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Gioacchino, Cannizzaro, Pietro, Felice, Angelo, Giorgi, Matteo, Lazzarini, Vittorio, Ferri, Michele, Leone, and Marco, Esposito
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Adult ,Male ,Immediate Dental Implant Loading ,Alveolar Bone Loss ,Denture, Complete, Lower ,Mandible ,Cohort Studies ,Dental Prosthesis Retention ,Postoperative Complications ,Osseointegration ,Humans ,Jaw, Edentulous ,Dental Restoration Failure ,Prospective Studies ,Denture Design ,Aged ,Aged, 80 and over ,Dental Implants ,Middle Aged ,Denture Retention ,Treatment Outcome ,Torque ,Patient Satisfaction ,Female ,Dental Prosthesis, Implant-Supported ,Follow-Up Studies - Abstract
To evaluate the clinical outcome of 2 implants placed flapless in fully edentulous mandibles and immediately restored with a metal-resin screw-retained cross-arch prosthesis 1 year after loading.Eighty consecutive patients were recruited. To be immediately loaded, implants had to be inserted with a minimum torque of 80 Ncm. Outcome measures, evaluated by two independent assessors, were prosthesis and implant failures, complications, marginal bone level changes, implant stability quotient (ISQ) values and patient satisfaction.Flaps were raised in 7 patients. Twelve implants in 7 patients did not reach the planned insertion torque. Four implants in 3 patients were immediately replaced by larger diameter implants and achieved the desired torque, whereas the remaining implants were immediately loaded anyway. Two implants failed early in 2 patients, but were successfully replaced and their prostheses remade. One month after loading, 72 (90%) patients declared to be completely satisfied with the therapy, 7 (9%) partially satisfied and 1 (1%) unsatisfied. One year after loading, all prostheses were in function, though one patient did not attend the 1-year control. Eight (10%) complications occurred, all successfully treated. After 1 year, the mean marginal bone loss was 0.3 mm and mean ISQ values decreased from 75.4 to 72.4.These short-term results at 1 year after loading suggest that immediately loaded mandibular cross-arch fixed prostheses can be supported by only 2 dental implants. Longer follow-ups (around 10 years) are needed to know the prognosis of this treatment modality.
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- 2012
13. Immediate functional loading of implants placed with flapless surgery in the edentulous maxilla: 1-year follow-up of a single cohort study
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Gioacchino, Cannizzaro, Michele, Leone, and Marco, Esposito
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Adult ,Dental Implants ,Male ,Pain, Postoperative ,Wound Healing ,Dental Implantation, Endosseous ,Denture, Complete, Upper ,Middle Aged ,Denture, Overlay ,Cohort Studies ,Postoperative Complications ,Treatment Outcome ,Osseointegration ,Maxilla ,Edema ,Humans ,Jaw, Edentulous ,Female ,Dental Prosthesis, Implant-Supported ,Dental Restoration Failure ,Prospective Studies ,Tooth Socket ,Periodontitis ,Aged ,Follow-Up Studies - Abstract
To evaluate success rates and complications of implants placed with a flapless technique and immediately loaded in fully edentulous maxillae.Implants were placed in fully edentulous maxillae with a minimum insertion torque of 45 Ncm in underprepared sites to allow maximum stability at insertion using a flapless technique. Implants were immediately loaded. Outcome measures were prosthesis and implant success, biologic and prosthetic complications, pain, and edema evaluation. Stability of individual implants was assessed both manually and with Osstell at baseline and after 12 months of loading. A single sample t test was used with a significance level of .05.Thirty-three consecutively treated edentulous patients received 202 implants in the maxilla. In 10 patients, 53 implants were immediately inserted in fresh extraction sockets. At implant insertion, a flap had to be elevated to control the direction of the drill in 5 patients. Three implants in 2 patients did not reach sufficient stability and were left to heal for 45 to 90 days. All restorations (21 fixed prostheses and 12 overdentures) were delivered the same day of the surgery. Twenty-six patients experienced no or slight postoperative pain; 7 experienced moderate to severe pain. No or slight edema was recorded for 19 patients and moderate to severe edema for 14 patients. Two implants failed in 2 patients but were successfully replaced the same day they were removed. No major complications occurred. Five patients experienced biologic complications, eg, peri-implantitis; 10 experienced prosthetic complications. No prosthesis failed; however, 1 patient was unsatisfied with his overdenture and requested a fixed alternative. There was a highly significant difference (P.001) between the stability at implant insertion and after 12 months.Implants placed in the edentulous maxilla with a flapless procedure can be successfully loaded the same day of surgery.
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- 2007
14. Restoration of partially edentulous patients using dental implants with a microtextured surface: a prospective comparison of delayed and immediate full occlusal loading
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Gioacchino, Cannizzaro and Michele, Leone
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Adult ,Dental Implants ,Male ,Time Factors ,Adolescent ,Crowns ,Surface Properties ,Jaw, Edentulous, Partially ,Middle Aged ,Weight-Bearing ,Treatment Outcome ,Dental Prosthesis Design ,Humans ,Female ,Dental Prosthesis, Implant-Supported ,Prospective Studies ,Periodontal Index ,Radiography, Bitewing ,Aged ,Follow-Up Studies - Abstract
The aim of this study was to determine the clinical effectiveness of placing dental implants with microtextured surfaces into full occlusal loading at the time of placement in partially edentulous patients.Two demographically similar groups of 14 patients each were treated with a total of 92 Spline Twist Implants (Centerpulse Dental, Carlsbad, CA). Test implants were placed into immediate full occlusal loading, and control implants were restored using a conventional delayed loading procedure. Otherwise, both groups of patients received similar therapy from the same treatment team. Radiographs, periodontal indices, and Periotest values were recorded every 6 months during routine clinical follow-up appointments. The mean loading time for all prostheses was 24 months at the time of this report.No implants failed in the test group, and 1 implant failed before loading in the control group. Cumulative implant success was 98.9% for all implants placed (test group = 100%; control group = 92.9%). Periodontal measurements indicated no significant clinical differences between implants placed into immediate full occlusal loading and those loaded via a conventional delayed protocol.Immediate full occlusal loading of partial prostheses supported by microtextured implants in partially edentulous patients demonstrated excellent clinical results, with no adverse periodontal effects after 24 months of function. Additional follow-up will provide invaluable information on the long-term effects of this technique.Immediate full occlusal loading of partial prostheses supported by microtextured implants can be successfully achieved for 24 months in highly motivated patients with excellent oral hygiene.
- Published
- 2003
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