The role of EPID in vivo dosimetry in the risk management of stereotactic lung treatments.

BACKGROUND AND OBJECTIVE: In this work we report our experience with the use of in vivo dosimetry (IVD) in the risk management of stereotactic lung treatments. METHODS: A commercial software based on the electronic portal imaging device (EPID) signal was used to reconstruct the actual planning target volume (PTV) dose of stereotactic lung treatments. The study was designed in two phases: i) in the observational phase, the IVD results of 41 consecutive patients were reviewed and out-of-tolerance cases were studied for root cause analysis; ii) in the active phase, the IVD results of 52 patients were analyzed and corrective actions were taken when needed. Moreover, proactive preventions were further introduced to reduce the risk of future failures. The error occurrence rate was analyzed to evaluate the effectiveness of proactive actions. RESULTS: A total of 330 fractions were analyzed. In the first phase, 13 errors were identified. In the active phase, 12 errors were detected, 5 of which needed corrective actions; in 4 patients the actions taken corrected the error. Several preventions and barriers were introduced to reduce the risk of future failures: the planning checklist was updated, the procedure for vacuum pillows was improved, and use of the respiratory compression belt was optimized. A decrease in the failure rate was observed, showing the effectiveness of procedural adjustment. CONCLUSION: The use of IVD allowed the quality of lung stereotactic body radiation therapy (SBRT) treatments to be improved. Patient-specific and procedural corrective actions were successfully taken as part of risk management, leading to an overall improvement in the dosimetric accuracy.

Development of an MIP based electrochemical sensor for TGF-ß1 detection and its application in liquid biopsy.

Oral cancer is one of the most common types of cancer in Europe and its large diffusion requires, together with prevention, the development of low-cost and reliable portable platforms for its diagnosis, with features of high selectivity and sensitivity. In this study, the development and characterization of a molecularly imprinted polymer (MIP)-based electrochemical sensor for TGF-ß1 detection are reported. The optimized biosensor is a potential tool for the early screening of oral cancer. A biomimetic surface has been obtained by electropolymerization of o-phenylenediamine (o-PD) on platinum electrodes, in the presence of TGF-ß1 as a template molecule. MIP synthesis, template removal and TGF-ß1 rebinding have been monitored by Differential Pulse Voltammetry (DPV). Atomic Force Microscopy (AFM) has been performed to investigate and characterize the surface morphology and the influence of the washing step on MIP and NIP (non-imprinted polymer as the control) while the thickness of the polymer layer has been measured by Scanning Transmission Electron Microscopy (STEM) analysis. The MIP sensor performance has been tested in both buffer solution and saliva samples with TGF-ß1, showing a linear response in the considered range (from 20 ng ml-1 down to 0.5 ng ml-1), an outstanding LOD of 0.09 ng mL-1 and affinity and selectivity to TGF-ß1 also in the presence of interfering molecules. The sensor was used also for the detection of target molecules in spiked saliva samples with good recovery results suggesting the possibility of the use of the proposed system for large scale fast screening in oral cancer diagnosis.

Hybrid Shell-Beam Inverse Finite Element Method for the Shape Sensing of Stiffened Thin-Walled Structures: Formulation and Experimental Validation on a Composite Wing-Shaped Panel.

This work presents a novel methodology for the accurate and efficient elastic deformation reconstruction of thin-walled and stiffened structures from discrete strains. It builds on the inverse finite element method (iFEM), a variationally-based shape-sensing approach that reconstructs structural displacements by matching a set of analytical and experimental strains in a least-squares sense. As iFEM employs the finite element framework to discretize the structural domain and as the displacements and strains are approximated using element shape functions, the kind of element used influences the accuracy and efficiency of the iFEM analysis. This problem is addressed in the present work through a novel discretization scheme that combines beam and shell inverse elements to develop an iFEM model of the structure. Such a hybrid discretization paradigm paves the way for more accurate shape-sensing of geometrically complex structures using fewer sensor measurements and lower computational effort than traditional approaches. The hybrid iFEM is experimentally demonstrated in this work for the shape sensing of bending and torsional deformations of a composite stiffened wing panel instrumented with strain rosettes and fiber-optic sensors. The experimental results are accurate, robust, and computationally efficient, demonstrating the potential of this hybrid scheme for developing an efficient digital twin for online structural monitoring and control.

Design and Implementation of a Framework for Smart Home Automation Based on Cellular IoT, MQTT, and Serverless Functions.

Smart objects and home automation tools are becoming increasingly popular, and the number of smart devices that each dedicated application has to manage is increasing accordingly. The emergence of technologies such as serverless computing and dedicated machine-to-machine communication protocols represents a valuable opportunity to facilitate management of smart objects and replicability of new solutions. The aim of this paper is to propose a framework for home automation applications that can be applied to control and monitor any appliance or object in a smart home environment. The proposed framework makes use of a dedicated messages-exchange protocol based on MQTT and cloud-deployed serverless functions. Furthermore, a vocal command interface is implemented to let users control the smart object with vocal interactions, greatly increasing the accessibility and intuitiveness of the proposed solution. A smart object, namely a smart kitchen fan extractor system, was developed, prototyped, and tested to illustrate the viability of the proposed solution. The smart object is equipped with a narrowband IoT (NB-IoT) module to send and receive commands to and from the cloud. In order to evaluate the performance of the proposed solution, the suitability of NB-IoT for the transmission of MQTT messages was evaluated. The results show how NB-IoT has an acceptable latency performance despite some minimal packet loss.

A Cloud-IoT Architecture for Latency-Aware Localization in Earthquake Early Warning.

An effective earthquake early warning system requires rapid and reliable earthquake source detection. Despite the numerous proposed epicenter localization solutions in recent years, their utilization within the Internet of Things (IoT) framework and integration with IoT-oriented cloud platforms remain underexplored. This paper proposes a complete IoT architecture for earthquake detection, localization, and event notification. The architecture, which has been designed, deployed, and tested on a standard cloud platform, introduces an innovative approach by implementing P-wave "picking" directly on IoT devices, deviating from traditional regional earthquake early warning (EEW) approaches. Pick association, source localization, event declaration, and user notification functionalities are also deployed on the cloud. The cloud integration simplifies the integration of other services in the architecture, such as data storage and device management. Moreover, a localization algorithm based on the hyperbola method is proposed, but here, the time difference of arrival multilateration is applied that is often used in wireless sensor network applications. The results show that the proposed end-to-end architecture is able to provide a quick estimate of the earthquake epicenter location with acceptable errors for an EEW system scenario. Rigorous testing against the standard of reference in Italy for regional EEW showed an overall 3.39 s gain in the system localization speed, thus offering a tangible metric of the efficiency and potential proposed system as an EEW solution.

Responsiveness to left-prefrontal tDCS varies according to arousal levels.

Over the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted structural and state-dependent functional factors. On these grounds, we aimed at verifying whether the behavioural effects induced by a common tDCS montage (F3-rSOA) were influenced by the participants' arousal levels, as part of a broader mechanism of state-dependency. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects were evaluated as a function of subjective and physiological arousal predictors (STAI-Y State scores and pre-stimulus pupil size, respectively). We showed that prefrontal tDCS hindered task learning effects on response speed such that performance improvement occurred during sham, but not real stimulation. Moreover, both subjective and physiological arousal predictors significantly explained performance during real tDCS, with interaction effects showing performance improvement only with moderate arousal levels; likewise, pupil response was affected by real tDCS according to the ongoing levels of arousal, with reduced dilation during higher arousal trials. These findings highlight the potential role of arousal in shaping the neuromodulatory outcome, thus emphasizing a more careful interpretation of null or negative results while also encouraging more individually tailored tDCS applications based on arousal levels, especially in clinical populations.

Experimental Shape Sensing and Load Identification on a Stiffened Panel: A Comparative Study.

The monitoring of loads and displacements during service life is proving to be crucial for developing a modern Structural Health Monitoring framework. The continuous monitoring of these physical quantities can provide fundamental information on the actual health status of the structure and can accurately guide pro-active condition-based maintenance operations, thus reducing the maintenance costs and extending the service life of the monitored structures. Pushed by these needs and by the simultaneous development in the field of strain sensing technologies, several displacement reconstruction and load identification methods have been developed that are based on discrete strain measurements. Among the different formulations, the inverse Finite Element Method (iFEM), the Modal Method (MM) and the 2-step method, the latter being the only one able to also compute the loads together with the displacements, have emerged as the most accurate and reliable ones. In this paper, the formulation of the three methods is summarized in order to set the numerical framework for a comparative study. The three methods are tested on the reconstruction of the external load and of the displacement field of a stiffened aluminium plate starting from experimentally measured strains. A fibre optic sensing system has been used to measure surface strains and an optimization procedure has been performed to provide the best fibre pattern, based on five lines running along the stiffeners' direction and with a back-to-back measuring scheme. Additional sensors are used to measure the applied force and the plate's deflection in some locations. The comparison of the results obtained by each method proves the extreme accuracy and reliability of the iFEM in the reconstruction of the deformed shape of the panel. On the other hand, the Modal Method leads to a good reconstruction of the displacements, but also exhibits a sensitivity to the choice of the modes considered for the specific application. Finally, the 2-step approach is able to correctly identify the loads and to reconstruct the displacements with an accuracy that depends on the modeling of the experimental setup.

Recent Advances in Internet of Things Solutions for Early Warning Systems: A Review.

Natural disasters cause enormous damage and losses every year, both economic and in terms of human lives. It is essential to develop systems to predict disasters and to generate and disseminate timely warnings. Recently, technologies such as the Internet of Things solutions have been integrated into alert systems to provide an effective method to gather environmental data and produce alerts. This work reviews the literature regarding Internet of Things solutions in the field of Early Warning for different natural disasters: floods, earthquakes, tsunamis, and landslides. The aim of the paper is to describe the adopted IoT architectures, define the constraints and the requirements of an Early Warning system, and systematically determine which are the most used solutions in the four use cases examined. This review also highlights the main gaps in literature and provides suggestions to satisfy the requirements for each use case based on the articles and solutions reviewed, particularly stressing the advantages of integrating a Fog/Edge layer in the developed IoT architectures.

Femtomolar Biodetection by a Compact Core-Shell 3D Chiral Metamaterial.

Advanced sensing tools, detecting extremely low concentrations of circulating biomarkers, can open unexplored routes toward early diagnostics and diseases progression monitoring. Here, we demonstrate the sensing capabilities of a chip-based metamaterial, combining 3D chiral geometry with a functional core-shell nanoarchitecture. The chiral metamaterial provides a circular polarization-dependent optical response, allowing analysis in a complex environment without significant background interferences. The functional nanoarchitecture, based on the conformal coating with a polymer shell, modifies the chiral metamaterial near- and far-field optical response because of the energy transfer between dielectric shell polarization charges and plasmonic core free electrons, leading to efficient interaction with biomolecules. The system sensitivity slope is 27 nm/pM, in the detection of TAR DNA-binding protein 43, clinically relevant for neurodegenerative diseases. Measurements were performed in spiked solution and in human serum with concentrations from 1 pM down to 10 fM, which is a range not accessible with common immunological assays, opening new perspectives for next-generation biomedical systems.

Near-field enhancement in oxidized close gap aluminum dimers.

Aluminum bowtie nanoantennas represent a possibility to confine and enhance electromagnetic (EM) field at optical frequencies in subwavelength regions by using an abundant and inexpensive metal. The native oxidation process of this metal is often viewed as a limitation for its application in plasmonics. Here, we show that in close gap configurations, the high refractive index of the native aluminum oxide helps in squeezing the plasmonic mode in extremely reduced size volumes, providing a higher EM near-field confinement and enhancement in the bowtie antenna gaps than achieved in the pure aluminum counterpart. Hence, the study provides new perspectives in the use of such a plasmonic antenna geometry within this aluminum system, which can be useful for improving plasmonics-enabled effects such as surface-enhanced Raman scattering- and light-matter interaction in strong coupling regime.

Interventions for replacing missing teeth: alveolar ridge preservation techniques for dental implant site development.

BACKGROUND: Alveolar bone changes following tooth extraction can compromise prosthodontic rehabilitation. Alveolar ridge preservation (ARP) has been proposed to limit these changes and improve prosthodontic and aesthetic outcomes when implants are used. This is an update of the Cochrane Review first published in 2015. OBJECTIVES: To assess the clinical effects of various materials and techniques for ARP after tooth extraction compared with extraction alone or other methods of ARP, or both, in patients requiring dental implant placement following healing of extraction sockets. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 19 March 2021), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2021, Issue 2), MEDLINE Ovid (1946 to 19 March 2021), Embase Ovid (1980 to 19 March 2021), Latin American and Caribbean Health Science Information database (1982 to 19 March 2021), Web of Science Conference Proceedings (1990 to 19 March 2021), Scopus (1966 to 19 March 2021), ProQuest Dissertations and Theses (1861 to 19 March 2021), and OpenGrey (to 19 March 2021). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. A number of journals were also handsearched. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) on the use of ARP techniques with at least six months of follow-up. Outcome measures were: changes in the bucco-lingual/palatal width of alveolar ridge, changes in the vertical height of the alveolar ridge, complications, the need for additional augmentation prior to implant placement, aesthetic outcomes, implant failure rates, peri-implant marginal bone level changes, changes in probing depths and clinical attachment levels at teeth adjacent to the extraction site, and complications of future prosthodontic rehabilitation. DATA COLLECTION AND ANALYSIS: We selected trials, extracted data, and assessed risk of bias in duplicate. Corresponding authors were contacted to obtain missing information. We estimated mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes, with 95% confidence intervals (95% CI). We constructed 'Summary of findings' tables to present the main findings and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 16 RCTs conducted worldwide involving a total of 524 extraction sites in 426 adult participants. We assessed four trials as at overall high risk of bias and the remaining trials at unclear risk of bias. Nine new trials were included in this update with six new trials in the category of comparing ARP to extraction alone and three new trials in the category of comparing different grafting materials. ARP versus extraction: from the seven trials comparing xenografts with extraction alone, there is very low-certainty evidence of a reduction in loss of alveolar ridge width (MD -1.18 mm, 95% CI -1.82 to -0.54; P = 0.0003; 6 studies, 184 participants, 201 extraction sites), and height (MD -1.35 mm, 95% CI -2.00 to -0.70; P < 0.0001; 6 studies, 184 participants, 201 extraction sites) in favour of xenografts, but we found no evidence of a significant difference for the need for additional augmentation (RR 0.68, 95% CI 0.29 to 1.62; P = 0.39; 4 studies, 154 participants, 156 extraction sites; very low-certainty evidence) or in implant failure rate (RR 1.00, 95% CI 0.07 to 14.90; 2 studies, 70 participants/extraction sites; very low-certainty evidence). From the one trial comparing alloplasts versus extraction, there is very low-certainty evidence of a reduction in loss of alveolar ridge height (MD -3.73 mm; 95% CI -4.05 to -3.41; 1 study, 15 participants, 60 extraction sites) in favour of alloplasts. This single trial did not report any other outcomes. Different grafting materials for ARP: three trials (87 participants/extraction sites) compared allograft versus xenograft, two trials (37 participants, 55 extraction sites) compared alloplast versus xenograft, one trial (20 participants/extraction sites) compared alloplast with and without membrane, one trial (18 participants, 36 extraction sites) compared allograft with and without synthetic cell-binding peptide P-15, and one trial (30 participants/extraction sites) compared alloplast with different particle sizes. The evidence was of very low certainty for most comparisons and insufficient to determine whether there are clinically significant differences between different ARP techniques based on changes in alveolar ridge width and height, the need for additional augmentation prior to implant placement, or implant failure. We found no trials which evaluated parameters relating to clinical attachment levels, specific aesthetic or prosthodontic outcomes for any of the comparisons. No serious adverse events were reported with most trials indicating that the procedure was uneventful. Among the complications reported were delayed healing with partial exposure of the buccal plate at suture removal, postoperative pain and swelling, moderate glazing, redness and oedema, membrane exposure and partial loss of grafting material, and fibrous adhesions at the cervical part of previously preserved sockets, for the comparisons xenografts versus extraction, allografts versus xenografts, alloplasts versus xenografts, and alloplasts with and without membrane. AUTHORS' CONCLUSIONS: ARP techniques may minimise the overall changes in residual ridge height and width six months after extraction but the evidence is very uncertain. There is lack of evidence of any differences in the need for additional augmentation at the time of implant placement, implant failure, aesthetic outcomes, or any other clinical parameters due to lack of information or long-term data. There is no evidence of any clinically significant difference between different grafting materials and barriers used for ARP. Further long-term RCTs that follow CONSORT guidelines (www.consort-statement.org) are necessary.

Cancer potencies and margin of exposure used for comparative risk assessment of heated tobacco products and electronic cigarettes aerosols with cigarette smoke.

Health risk associated with the use of combustible cigarettes is well characterized and numerous epidemiological studies have been published for many years. Since more than a decade, innovative non-combusted tobacco products have emerged like heated tobacco products (HTP) or electronic cigarettes (EC). Long-term effects of these new products on health remain, however, unknown and there is a need to characterize associated potential health risks. The time dedicated to epidemiological data generation (at least 20 to 40 years for cancer endpoint), though, is not compatible with innovative development. Surrogates need, therefore, to be developed. In this work, non-cancer and cancer risks were estimated in a range of HTP and commercial combustible cigarettes based upon their harmful and potentially harmful constituent yields in aerosols and smoke, respectively. It appears that mean lifetime cancer risk values were decreased by more than one order of magnitude when comparing HTPs and commercial cigarettes, and significantly higher margin of exposure for non-cancer risk was observed for HTPs when compared to commercial cigarettes. The same approach was applied to two commercial ECs. Similar results were also found for this category of products. Despite uncertainties related to the factors used for the calculations and methodological limitations, this approach is valuable to estimate health risks associated to the use of innovative products. Moreover, it acts as predictive tool in absence of long-term epidemiological data. Furthermore, both cancer and non-cancer risks estimated for HTPs and ECs highlight the potential of reduced risk for non-combusted products when compared to cigarette smoking.

Selected Harmful and Potentially Harmful Constituents Levels in Commercial e-Cigarettes.

A broad range of commercially available electronic cigarette (e-cigarette) systems were tested for levels of emissions of harmful and potentially harmful constituents (HPHC), with a particular focus on the carbonyls: acetaldehyde, acrolein, and formaldehyde. The tobacco-specific nitrosamines N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-bipyridyl)-1-butanone; the elements arsenic, cadmium, chromium, lead, and nickel; benzene; 1,3-butadiene; and benzo(a)pyrene were also quantified. The results show that except for the levels of carbonyls, all types of e-cigarettes performed in a similar manner, and emission levels for HPHCs were generally not quantifiable. However, levels of carbonyls, especially formaldehyde, were highly variable. Overall, the lowest levels of formaldehyde were observed in cartridge systems, which generally achieved substantial reductions in yields in comparison with cigarette smoke. Formaldehyde levels in open tank systems were variable; however, the median formaldehyde levels across different brands were substantially lower than the formaldehyde levels in cigarette smoke. The results for variable-power devices operated at the highest voltage confirmed existing literature data regardless of orientation and differences in puffing regimes. Furthermore, our results show that many products deliver consistent HPHC yields over a broad range of testing conditions (with minimal variability from one device to another, under a range of puffing conditions). However, some products exhibit high variability in emissions of HPHCs. The use of air blanks is further highlighted to assess nonproduct-related contributions to HPHC levels to avoid misrepresentation of the data. Overall, our results highlight that some but not all electronic cigarettes deliver low levels of carbonyls consistently across the full e-liquid depletion cycle under different test conditions. The need for further research and standardization work on assessment of variable-voltage electronic cigarettes is emphasized.

Precision cut lung slices: a novel versatile tool to examine host-pathogen interaction in the chicken lung.

The avian respiratory tract is a common entry route for many pathogens and an important delivery route for vaccination in the poultry industry. Immune responses in the avian lung have mostly been studied in vivo due to the lack of robust, relevant in vitro and ex vivo models mimicking the microenvironment. Precision-cut lung slices (PCLS) have the major advantages of maintaining the 3-dimensional architecture of the lung and includes heterogeneous cell populations. PCLS have been obtained from a number of mammalian species and from chicken embryos. However, as the embryonic lung is physiologically undifferentiated and immunologically immature, it is less suitable to examine complex host-pathogen interactions including antimicrobial responses. Here we prepared PCLS from immunologically mature chicken lungs, tested different culture conditions, and found that serum supplementation has a detrimental effect on the quality of PCLS. Viable cells in PCLS remained present for ≥ 40 days, as determined by viability assays and sustained motility of fluorescent mononuclear phagocytic cells. The PCLS were responsive to lipopolysaccharide stimulation, which induced the release of nitric oxide, IL-1ß, type I interferons and IL-10. Mononuclear phagocytes within the tissue maintained phagocytic activity, with live cell imaging capturing interactions with latex beads and an avian pathogenic Escherichia coli strain. Finally, the PCLS were also shown to be permissive to infection with low pathogenic avian influenza viruses. Taken together, immunologically mature chicken PCLS provide a suitable model to simulate live organ responsiveness and cell dynamics, which can be readily exploited to examine host-pathogen interactions and inflammatory responses.

Symmetry Breaking in Oligomer Surface Plasmon Lattice Resonances.

We describe a novel plasmonic-mode engineering, enabled by the structural symmetry of a plasmonic crystal with a metallic oligomer as unit cell. We show how the oligomer symmetry can tailor the scattering directions to spatially overlap with the diffractive orders directions of a plasmonic array. Applied to the color generation field, the presented approach enables the challenging achievement of a broad spectrum of angle-dependent colors since smooth and continuous generation of transmitted vibrant colors, covering both the cyan-magenta-yellow and the red-green-blue color spaces, is demonstrated by scattering angle- and polarization-dependent optical response. The addition of a symmetry driven level of control multiplies the possibility of optical information storage, being of potential interest for secured optical information encoding but also for nanophotonic applications, from demultiplexers or signal processing devices to on-chip optical nanocircuitry.

SBRT planning for spinal metastasis: indications from a large multicentric study.

BACKGROUND: The dosimetric variability in spine stereotactic body radiation therapy (SBRT) planning was investigated in a large number of centres to identify crowd knowledge-based solutions. METHODS: Two spinal cases were planned by 48 planners (38 centres). The required prescription dose (PD) was 3â€¯× 10 Gy and the planning target volume (PTV) coverage request was: VPD > 90% (minimum request: VPD > 80%). The dose constraints were: planning risk volume (PRV) spinal cord: V18Gy < 0.35 cm3, V21.9 Gy < 0.03 cm3; oesophagus: V17.7 Gy < 5 cm3, V25.2 Gy < 0.03 cm3. Planners who did not fulfil the protocol requirements were asked to re-optimize the plans, using the results of planners with the same technology. Statistical analysis was performed to assess correlations between dosimetric results and planning parameters. A quality index (QI) was defined for scoring plans. RESULTS: In all, 12.5% of plans did not meet the protocol requirements. After re-optimization, 98% of plans fulfilled the constraints, showing the positive impact of knowledge sharing. Statistical analysis showed a significant correlation (p < 0.05) between the homogeneity index (HI) and PTV coverage for both cases, while the correlation between HI and spinal cord sparing was significant only for the single dorsal PTV case. Moreover, the multileaf collimator leaf thickness correlated with the spinal cord sparing. Planners using comparable delivery/planning system techniques produced different QI, highlighting the impact of the planner's skills in the optimization process. CONCLUSION: Both the technology and the planner's skills are fundamentally important in spine SBRT planning optimization. Knowledge sharing helped to follow the plan objectives.

WITHDRAWN: Interventions for replacing missing teeth: different types of dental implants.

BACKGROUND: Dental implants are available in different materials, shapes and with different surface characteristics. In particular, numerous implant designs and surface modifications have been developed for improving clinical outcome. This is an update of a Cochrane review first published in 2002, and previously updated in 2003, 2005 and 2007. OBJECTIVES: Primary: to compare the clinical effects of different root-formed osseointegrated dental implant types for replacing missing teeth for the following specific comparisons: implants with different surface preparations, but having similar shape and material; implants with different shapes, but having similar surface preparation and material; implants made of different materials, but having similar surface preparation and shape; different implant types differing in surface preparation, shape, material or a combination of these.Secondary: to compare turned and roughened dental implants for occurrence of early implant failure (before prosthetic loading) and occurrence of peri-implantitis. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 17 January 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 12), MEDLINE via OVID (1946 to 17 January 2014) and EMBASE via OVID (1980 to 17 January 2014). We placed no restrictions on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included any randomised controlled trial (RCT) comparing osseointegrated dental implants of different materials, shapes and surface properties having a follow-up in function of at least one year. Outcome measures were success of the implants, radiographic peri-implant marginal bone levels changes and incidence of peri-implantitis. DATA COLLECTION AND ANALYSIS: At least two review authors independently conducted screening, risk of bias assessment and data extraction of eligible trials in duplicate. We expressed results using fixed-effect models (if up to three studies were present in a meta-analysis) or random-effects models (when there were more than three studies) using mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). We reported the following endpoints: one, three, five and 10 years after functional loading. MAIN RESULTS: We identified 81 different RCTs. We included 27 of these RCTs, reporting results from 1512 participants and 3230 implants in the review. We compared 38 different implant types with a follow-up ranging from one to 10 years. All implants were made of commercially pure titanium or its alloys, and had different shapes and surface preparations. We judged two trials to be at low risk of bias, 10 to be at unclear risk of bias and 15 to be at high risk of bias. On a 'per participant' rather than 'per implant' basis, we found no significant differences between various implant types for implant failures. The only observed statistically significant difference for the primary objective regarded more peri-implant bone loss at Nobel Speedy Groovy implants when compared with NobelActive implants (MD -0.59 mm; 95% CI -0.74 to -0.44, different implant shapes). The only observed statistically significant difference for the secondary objective was that implants with turned (smoother) surfaces had a 20% reduction in risk to be affected by peri-implantitis than implants with rough surfaces three years after loading (RR 0.80; 95% CI 0.67 to 0.96). There was a tendency for implants with turned surfaces to fail early more often than implants with roughened surfaces. AUTHORS' CONCLUSIONS: Based on the results of the included RCTs, we found no evidence showing that any particular type of dental implant had superior long-term success. There was limited evidence showing that implants with relatively smooth (turned) surfaces were less prone to lose bone due to chronic infection (peri-implantitis) than implants with much rougher surfaces (titanium-plasma-sprayed). These findings were based on several RCTs, often at high risk of bias, with few participants and relatively short follow-up periods.

Assessment of priority tobacco additives per the requirements in the EU Tobacco Products Directive (2014/40/EU): Part 2: Smoke chemistry and in vitro toxicology.

This publication is part of a series of three publications and describes the non-clinical assessment performed to fulfill the regulatory requirement per Art. 6 (2) of the EU Tobacco Products Directive 2014/40/EU under which Member States shall require manufacturers and importers of cigarettes and Roll Your Own tobacco containing an additive that is included in the priority list established by Commission Implementing Decision (EU) 2016/787 to carry out comprehensive studies (European Comission, 2016). This publication contains the results of a literature search, comprehensive smoke chemistry, additive transfer, and in vitro toxicity studies for the 13 priority additives (carob bean extract, cocoa powder, fenugreek extract, fig juice concentrate, geraniol, glycerol, guaiacol, guar gum, liquorice extract powder, maltol, l-menthol (synthetic), propylene glycol, and sorbitol) commissioned by the members of the Priority Additives Tobacco Consortium to independent Contract Research Organizations. Comparisons of the 39 World Health Organisation smoke emissions in smoke from cigarettes with and without priority additives identified some differences that, with few exceptions, were minor and well within the inherent variability of the analytical method observed for the 3R4F monitor cigarette. Most differences were not statistically significant and did not show consistent additive-related increases or decreases. However, test cigarettes with guar gum showed a statistically significant, additive-related increase in formaldehyde and cadmium; test cigarettes with sorbitol showed a statistically significant, additive-related increase in formaldehyde and acrolein; test cigarettes with glycerol showed a statistically significant, additive-related decrease in phenols, benzo[a]pyrene and N-nitrosoanabasine; and test cigarettes with propylene glycol showed a statistically significant, additive-related decrease in phenol and m + p-cresols. These changes were not observed when the additives were tested as a mixture. None of the increases or decreases in smoke chemistry translated into changes in the in vitro toxicity. Comparisons of the in vitro toxicity of smoke from cigarettes with and without priority additives gave some differences that were minor, well within the inherent variability of the assays, not statistically significant, and did not show consistent additive-related increases or decreases. Thus, it can be concluded that the addition of priority additives had no effect on the in vitro toxicity of the cigarette smoke. The results obtained in our studies are consistent with those in scientific literature.

Assessment of priority tobacco additives per the requirements of the EU Tobacco Products Directive (2014/40/EU): Part 1: Background, approach, and summary of findings.

This paper is part of a series of 3 publications and describes the non-clinical and clinical assessment performed to fulfill the regulatory requirement per Art. 6 (2) of the EU Tobacco Products Directive 2014/40/EU; under which Member States shall require manufacturers and importers of cigarettes and roll-your-own tobacco containing an additive that is included in the priority list established by Commission Implementing Decision (EU) 2016/787 to carry out comprehensive studies. The Directive requires manufacturers and importers of cigarettes and Roll Your Own tobacco to examine for each additive whether it; contributes to and increases the toxicity or addictiveness of tobacco products to a significant or measurable degree; if it leads to a characterizing flavor of the product; if it facilitates inhalation or nicotine uptake, and if it results in the formation of CMR (carcinogenic, mutagenic and reprotoxic) constituents and if these substances increase the CMR properties of the respective tobacco product to a significant or measurable degree. This publication gives an overview on comprehensive smoke chemistry, in vitro toxicity, and human clinical studies commissioned by the members of the Priority Additives Tobacco Consortium to independent Contract Research Organizations (CROs) where the emissions of test cigarettes containing priority additives were compared to emissions emerging from an additive-free reference cigarette. Whilst minor changes in smoke chemistry parameters were observed when comparing emissions from test cigarettes with emissions from additive-free reference cigarettes, only two of the additives (sorbitol and guar gum) tested led to significant increases in a limited number of smoke constituents. These changes were not observed when sorbitol or guar gum were tested in a mixture with other priority additives. None of the priority additives resulted in increases in in vitro toxicity (Ames, Micronucleus, Neutral Red Uptake) or led to changes in smoking behavior or absorption (rate or amount) of nicotine measured during the human clinical study as compared to the additive-free reference cigarette.