Resumo: O Diabetes mellitus (DM) é uma alteração metabólica que pode comprometer a estabilidade do implante dentário devido a influência no tecido ósseo. O objetivo do estudo foi avaliar o efeito do Diabetes Mellitus e da insulinoterapia na osseointegração estabelecida ao redor de implantes instalados em tíbia de ratos. Foram utilizados 80 ratos Wistar, os quais foram divididos em 4 grupos: controle de 2 meses (C2m), controle de 4 meses (C4m), diabético (D) e insulínico (I). Os implantes de superfície lisa (2,2mmx4mm) foram instalados na tíbia do rato. Após um período de 2 meses para osseointegração, o grupo C2m foi sacrificado. A indução do DM foi realizada com dose única de estreptozotocina (40mg/Kg) pela veia peniana. Os ratos do grupo I receberam insulina subcutânea (8,5 U/dia) e os demais receberam solução salina (0,9%) pela mesma via. Os níveis da glicemia plasmática foram avaliados periodicamente pelo método enzimático da glicose-oxidase. Dois meses após a indução do DM, os grupos C4m, D e I foram sacrificados. A relação do tecido ósseo com o implante foi avaliada pelas análises: radiográfica (subtração radiográfica digital); bioquímica; histométrica e torque de remoção do implante. Os dados das análises radiográfica, bioquímica e histométrica foram comparados nos grupos pelo teste ANOVA, p>0,05. Os dados da análise do torque de remoção foram comparados nos grupos pelo teste Kruskal Wallis e Friedman, p>0,05. Os resultados mostraram que o grupo D apresentou níveis de glicemia plasmática acima de 300mg/dL e significativamente mais alto do que os grupos C4m e I após a indução do DM e esta condição sistêmica foi mantida até o final do experimento. / Abstract: The Diabetes mellitus (DM) is a metabolic disease that can impair the dental implant establishment by bone tissue influence. The aim of this study was evaluate the effect of Diabetes Mellitus (DM) and insulin therapy on osseointegration around dental implants. Eighty implants were placed in 80 tibiae of adult rats. After a healing period of two months, the animals were divided into four groups of 20 animals each and subdivided into 10 rats for removal torque analysis and 10 rats for histometric analysis. Group C2m was sacrificed at this time. DM was induced using 40mg/kg Streptozotocin in a diabetic group (group D) and an insulinic group (group I). During two months, group I received subcutaneous doses of 8.5 UI insulin twice a day. Groups C4m (control of 4months) and D received only saline. After two months, the animals of groups D, I and C4m were sacrificed. The glycemic control of the animals was monitored during the experiment. The relation of bone with implant was evaluated by 18 radiographic (digital subtraction radiography), bioquimic, histometric and removal torque analysis. Data obtained with radiographic, bioquimic and histometric analysis were analyzed and compared by ANOVA test, p>0,05. Data obtained with removal torque analysis were analyzed and compared by Kruskal Wallis and Friedman tests, p>0,05. The glycemic controls were within normal range for groups A, C and I and higher for group D and maintained during experiment. Greater significant values of ALP serum and Ca urinary were determined in group D after DM induction. There was a significant difference in gray shade values in the subtraction image between groups D (123±9) and I (136±5) (p<0.05) on bone formation around the implant while there were no significant differences between control groups A (127±13) and C (133±10) and insulinic group. / Orientador: Gulnara Scaf / Coorientador: Elcio Marcantonio Junior / Banca: Julio César Joly / Banca: Maria Lúcia Rubo Rezende / Banca: Guilherme Monteiro Tosoni / Banca: Marisa Aparecida Cabrini Gabrielli / Doutor

Cette thèse porte sur la perception visuelle, auditive et audiovisuelle des voyelles nasales [ɑ̃] (« lent »),[ɔ̃] (« long ») et [ɛ̃] (« lin ») par des adultes devenus sourds, implantés cochléaires et implantés dutronc cérébral. L’étude sur la perception visuelle des voyelles, auprès de 22 adultes devenus sourds,redéfinit les sosies labiaux des voyelles nasales et propose une mise à jour de la classification desvisèmes. Trois études sur l’identification auditive des voyelles nasales auprès de 82, 15 et 10 adultesimplantés cochléaires mettent en évidence leur difficulté à reconnaitre les trois voyelles nasales, qu’ilsperçoivent comme des voyelles orales. Les analyses acoustiques et perceptives suggèrent que lesadultes implantés cochléaires s’appuient sur les informations fréquentielles des deux premiers picsspectraux mais négligent les informations d’intensité relative de ces pics. D’après l’étude menéeauprès de 13 adultes implantés du tronc cérébral, des informations acoustiques linguistiques sonttransmises par l’implant du tronc cérébral mais la fusion entre les informations auditives et visuellespourrait être optimisée pour l’identification des voyelles. Enfin, une enquête auprès de 179orthophonistes pointe le besoin d’une information sur la définition phonétique articulatoire actualiséedes voyelles [ɑ̃] et [ɛ̃]. / This thesis focuses on the visual, auditory and auditory-visual perception of french nasal vowels [ɑ̃](« lent »), [ɔ̃] (« long ») and [ɛ̃] (« lin ») by Cochlear Implant (CI) and Auditory Brainstem Implant(ABI) adults users. The study on visual perception of vowels, with 22 deafened adults, redefines thelip configuration of french nasal vowels and provides an update of the classification of vocalic visualphonemes. Three studies on auditory identification of nasal vowels with 82, 15 and 10 CI usershighlight their difficulty in recognizing the three nasal vowels, which they perceive as oral vowels.Acoustic and perceptual analyzes suggest that adults with CI rely on frequency informations of thefirst two spectral peaks but miss the informations of relative intensity of these peaks. The study with13 ABI users show that some linguistic acoustic cues are transmitted by the ABI but the fusion ofauditory and visual features could be optimized for the identification of vowels. Finally, a survey of179 Speech Language and Hearing Therapists show the need of an update on the phonetic articulationof french nasal vowels [ɑ̃] and [ɛ̃].

Ce travail porte sur l’étude du comportement biomécanique d’un modèle cadavérique et d’un modèle in vitro de l’arthroplastie totale de hanche. Nous avons cherché à mettre en relief et à étudier des paramètres qui pouvaient nous permettre de disposer d’une méthode d’analyse objective de la stabilité de l’implant acétabulaire. La première partie décrit le contexte de l'étude. Nous avons insisté sur les différentes méthodes d’analyses qui permettent d’analyser la stabilité d’un implant osseux. En effet, malgré l’utilisation quotidienne des implants, le taux d’échec d’ostéointégration reste élevé. Ces échecs s’accompagnent d’une morbidité importante et d’un surcout notable. Parmi les causes d’échec identifiées, le descellement aseptique de la cupule acétabulaire dans l’arthroplastie de hanche peut être lié à un défaut de stabilité primaire, non obtenu lors de l’intervention chirurgicale. Il a été montré que le descellement de la cupule acétabulaire pouvait résulter d'une faible stabilité primaire entre la cupule et l'os l'entourant. Les chirurgiens qui pratiquent l’arthroplastie de hanche évaluent de manière empirique la stabilité obtenue ou non de l’implant acétabulaire en écoutant le son produit lorsqu'ils impactent la cupule ou à leur ressenti en la manipulant. Une méthode d'estimation de la stabilité primaire pourrait permettre au chirurgien orthopédique de mieux appréhender la stabilité des implants qu’il pose au bloc opératoire. L'objet principal de ce travail de thèse était ainsi d'étudier les signaux d'impacts sur le cotyle prothétique. Dans un premier temps, nous avons réalisé une étude de l'insertion de la cupule par impacts sur un modèle cadavérique (sujets anatomiques de l’école de chirurgie du fer à moulin) dans des conditions proches de celle de l'opération en clinique. Une corrélation a été trouvée entre le moment d'impact et la stabilité (R2=0.69). Cette étude expérimentale a ainsi montré le potentiel de la méthode de traitement des signaux d'impact dans la prédiction de la stabilité primaire de la cupule acétabulaire. Mais nous avons observé des modifications entre les signaux obtenus sur les différents sujets. Nous avons posé comme hypothèse que ces modifications étaient liées à la variation des tissus mous entre chaque sujet. Le troisième volet de cette thèse a donc porté sur l’analyse du comportement biomécanique de notre modèle en présence d’une quantité plus ou moins importante de muscle.Nous avons utilisé à nouveau le modèle in vitro que nous avions développé et avons ajouté dans le système d’impaction des tranches de poitrine de dinde d’épaisseur variable. Le but de cette seconde étude était d’intégrer le paramètre lié à l’existence d’une épaisseur variable de tissus mous dans l'interaction dynamique entre le marteau, l'ancillaire (et la cupule) et le tissu osseux lors de l'insertion. La valeur de la moyenne et de l’écart-type de l'indicateur Im obtenues pour tous les échantillons et toutes les configurations pour une valeur d’épaisseur des tissus mous égale à 10 mm (respectivement 30 mm) étaient égales à 0,592 ± 0,141 (respectivement 0,552 ± 0,139). L’analyse statistique a montré qu'il n'y avait pas eu d'effet significatif de la valeur de l’épaisseur des tissus mous sur les valeurs de l'indicateur Im (F = 3,16; p = 0,08). Malgré les limitations évidentes d’une étude in vitro sur un modèle partiel d’arthroplastie totale de hanche, ces résultats, ainsi que les résultats précédents obtenus sur les sujets anatomiques, montrent la faisabilité du développement d'un dispositif médical dédié à l'estimation de la stabilité de l'implant acétabulaire et qui pourrait être utilisé comme système d'aide à la décision par le chirurgien orthopédique. / Abstract:This work studies the biomechanical behavior of a cadaveric model and an in vitro model of total hip arthroplasty. We sought to highlight and study parameters that could allow us to have a method of objective analysis of the stability of the acetabular cup implant.The first part describes the context of the study. We have emphasized the different methods of analysis that make it possible to analyse the stability of a bone implant. Indeed, despite the daily use of implants, the failure rate of osseointegration remains high and failures still happen due to inadequate mechanical behavior of the prosthesis.Among the identified causes of failure, aseptic loosening of the acetabular cup after hip arthroplasty may be related to a primary defect in stability, not achieved during the surgical procedure. It has been shown that loosening of the acetabular cup may result from poor primary stability between the prosthetic cup and the surrounding bone.A method of estimating primary stability could allow the orthopaedic surgeon to better control the stability of the implants he poses in the operating room.The main purpose of this thesis work was to study the impact signals on the prosthetic acetabulum.Firstly, we carried out a study of the insertion of the cup by impacts on a cadaveric model. A correlation was found between impact time and stability (R2 = 0.69). This experimental study has thus shown the potential of the impact signal processing method in predicting the primary stability of the acetabular cup. But we observed changes between the signals obtained on the different subjects. We hypothesized that these changes were related to soft tissue variation between subjects.The third part of this thesis focused on analysing the biomechanical behavior of our model in the presence of soft tissues.We used again the in vitro model that we had developed and added in the impaction system turkey slices of varying thickness.The purpose of this second study was to integrate the parameter related to the existence of a variable thickness of soft tissues in the dynamic interaction between the hammer, the ancillary (and the cup) and the bone tissue during the insertion. The mean and standard deviation of the Im indicator obtained for all samples and configurations at a soft tissue thickness value of 10 mm (30 mm) was 0.592 ± 0.141, (respectively 0.552 ± 0.139). Statistical analysis showed that there was no significant effect of the value of soft tissue thickness on the values of the Im indicator (F = 3.16, p = 0.08). Despite the obvious limitations of an in vitro study on a partial model of total hip arthroplasty, these results, as well as the previous results obtained on anatomical subjects, show the feasibility of developing a medical device dedicated to estimating the stability of the acetabular implant and which could be used as a decision support system by the orthopaedic surgeons.

Cochlear implants (CIs) are prosthetic devices used to partially restore hearing for profound and severely deaf individuals. CIs convert sounds into electrical pulses which stimulate the auditory nerve fibers. An accurate model of auditory nerve fibers (ANFs) would help in improving the functionality of CIs. Previous studies have shown that the original Hodgkin-Huxley (1952) model (with kinetics adjusted for mammalian body temperature) may be better at describing nodes of Ranvier in ANFs than models for other mammalian axon types. However, the Hodgkin-Huxley model is still unable to explain a number of phenomena observed in auditory nerve responses to CI stimulation, such as short-term and long-term adaptation, the time-course of relative refractoriness, and stimulus-dependent random fluctuations in membrane threshold. Recent physiological investigations of spiral ganglion cells have shown the presence of a number of ion channel types not considered in the previous modelling studies, including low-threshold potassium (𝐼^KLT) channels and hyperpolarization-activated cation (𝐼^h) channels. In this thesis, inclusion of these ion channel types in a stochastic Hodgkin-Huxley model is investigated. Four versions of the model are formed and compared: that is, the standard Hodgkin-Huxley model, the standard model with /h only added, the standard model with 𝐼^KLT only added, and finally, the standard model with both h and 𝐼^KLT added. Two group of responses are explored: i) single-pulse responses and ii) pules-train responses. For the single pulse responses, a charge-balanced biphasic stimulus pulse is used. The effect of varying the pulse-width and the interphase gap is investigated for both leading phase polarities. Results are compared to responses for single monophasic stimulus pulses in some cases. Pulse-train responses are investigated for charge-balanced depolarizing-phase leading biphasic pulses at rates of 200, 800, and 2000 pulse/s. Results from single-pulse responses show an increase in spike threshold when one or both of these channel types are included. The addition of 𝐼^KLT increases random threshold fluctuations in the stochastic model, particularly for longer pulse widths. For pulse-train responses, rapid adaptation in spike rate may be resulting from 𝐼^KLT whereas 𝐼^h produces slower "short-term" adaptation. Thus, the simulation results suggest that including 𝐼^KLT and/or 𝐼^h in a Hodgkin-Huxley model improves the accuracy of the model in describing auditory nerve fiber responses during cochlear implant stimulation. / Thesis / Master of Applied Science (MASc)

Aim To assess the clinical outcomes of zirconia implants, namely survival rate and the prevalence of fracture, based on a systematic review of the literature. Material and method An electronic search was conducted in three databases (PubMed, Web of Science, Science Direct), last updated in October 2022. Inclusion criteria were clinical human studies providing information on implant failure rates in any group of patients receiving zirconia dental implants. Log-rank test was used to compare the survival distributions of implants between some groups of variables. Interval survival rate (ISR) and cumulative survival rate (CSR) were calculated. Results Thirty-seven publications were included in the review, with 2941 zirconia implants in 1766 patients, with a mean follow-up of 36.3 ± 22.7 months. There were 182 implant failures, with the great majority of them occurring within the first year after implant installation. Twenty-four implant fractures were reported, most of them in implants of narrow diameter. There was no statistically significant difference of implant failure between the anterior and posterior regions (p = 0.798), nor between maxilla and mandible (p = 0.341), nor between one- and two-piece implants (p = 0.787). The CSR after 10 years was 88.1 %. Conclusion Clinical studies assessing clinical outcomes of zirconia implants in humans have a relatively short mean follow-up time. Zirconia implants present a CSR of 88.1% after 10 years, with most failures happening within the first year after implant installation. Implants of narrow diameter present higher risk of fractures than implants of wider diameter. / Syfte Att bedöma de kliniska resultaten av zirkonia implantat, överlevnadsgrad och förekomst av frakturer, baserat på en systematisk översikt av litteraturen. Material och metod En elektronisk sökning gjordes i tre olika databaser (PubMed, Web of Science, Science Direct), senast uppdaterad i oktober 2022. Inklusions kriterier var kliniska humanstudier som gav information om frekvensen av implantatfel hos vilken grupp patienter som helst som fick zirkonia tandimplantat. Log-rank test användes för att jämföra överlevnadsfördelningen av implantat mellan vissa grupper av variabler. Intervallöverlevnadsfrekvens (ISR) och kumulativ överlevnadsfrekvens (CSR) beräknades. Resultat Trettio-sju publikationer inkluderades i granskningen, med 2941 zirkonia implantat hos 1766 patienter, med en genomsnittlig uppföljning på 36,3 ± 22,7 månader. Det förekom 182 implantatfel, varav den stora majoriteten inträffades under det första året efter implantatinstallationen. Tjugo-fyra implantatfrakturer rapporterades, de flesta i implantat med smal diameter. Det fanns ingen statistiskt signifikant skillnad av implantatfel mellan de främre och bakre områdena (p = 0,798), inte heller mellan maxilla och underkäken (p = 0,341), inte heller mellan implantat i ett och två delar (p = 0,787). CSR efter 10 år var 88,1 %. Slutsats Kliniska studier som bedömer kliniska resultat av zirkonia implantat hos människor har en relativt kort genomsnittlig uppföljningstid. Zirkonia implantat uppvisar en CSR på 88,1 % efter 10 år, med de flesta fel som inträffar inom det första året efter implantatinstallationen. Implantat med smal diameter ger högre risk för frakturer än implantat med bredare diameter.

No description available.

Published Article / Extensive work has been done in the area of manufacturing implants for medical purposes, and more recently the development of customised implants. Areas of application include cranio/maxillo-facial implants, dental drill guides, hip, knee and shoulder replacements, as well as different implants for the spine. Due to their high prevalence and complex anatomical geometry the purpose of this study is to investigate the current state of the industry regarding customised medical implants for cranio/maxillofacial and orthopaedic surgery. Implant customisation has far-reaching benefits, and a collective approach to solving current difficulties will require an in-depth study of successes already achieved. Several issues in this regard are examined, including what defines customisation, regulatory issues that govern customisation and design constraints, trends in different areas of application, suitable materials, and finally which manufacturing techniques are being employed, with a focus on the use of Layer Manufacturing technologies and their role in custom-made medical implants.

No description available.

O objetivo deste estudo foi avaliar clínica e radiograficamente implantes curtos com 5 e 6 mm de comprimento (Titamax WS Neodent/ Curitiba-Brasil) unitários instalados em região posterior de mandíbula e maxila com pouca altura óssea. Foram instalados 10 implantes em 8 pacientes devidamente selecionados a partir de critérios de inclusão pré-determinados. Os mesmos receberam carregamento protético somente após o tempo convencional de espera para a osseointegração. Seis implantes foram instalados em mandíbula e 4 implantes em maxila. Tomadas radiográficas foram realizadas para avaliação das perdas ósseas verticais e horizontais nos tempos T0 (Instalação cirúrgica), T1 (Reabertura), T2 (Instalação protética) e T3 (Acompanhamento de 6 meses). Foram avaliados parâmetros biológicos como, sangramento gengival, índice de mucosa ceratinizada, índice de placa e índice de inflamação gengival. Também foram avaliados parâmetros protéticos como proporção coroa-implante e distância mesiodistal. Apenas um implante (Titamax WS Cortical 5.0x6.0) foi perdido ainda no período de osseointegração portanto o índice de sucesso foi de 90% no período avaliado. A alteração do nível ósseo foi analisada em três períodos diferentes, da instalação cirúrgica à cirurgia de reabertura (período 1), da reabertura à instalação protética (Período 2) e da instalação protética ao controle de seis meses (Período 3). Avaliando-se a perda óssea vertical nos três períodos separadamente foram encontrados valores muito semelhantes, inclusive iguais estatisticamente (ANOVA, p<0,05). O valor de perda óssea no período 1 foi de 0,32mm; no período 2 foi de 0,22mm e no período 3 foi de 0,29mm. Isso significa que os procedimentos cirúrgicos foram igualmente causadores de perda óssea marginal mesmo tomando-se alguns cuidados na execução destas etapas. A média de perda óssea vertical e horizontal no período total de acompanhamento foi de 0,87 ±0,46 e 0,24± 0,34 respectivamente. Estes valores foram considerados dentro do intervalo de perda óssea esperado. A boa condição de saúde gengival e higiene oral descartaram a possibilidade de associação entre os índices periodontais e a perda óssea periimplantar. O teste estatístico de Regressão Linear (p<0,05) mostrou não haver relação de causa/efeito entre perda óssea e os parâmetros protéticos, apesar de elevada proporção coroa/implantes (média 1,88). Com base nos resultados encontrados neste trabalho, concluiu-se que os implantes curtos, mesmo os de comprimento 5 e 6mm, devem ser considerados como uma importante alternativa de tratamento para casos unitários. Sugere-se porém, um maior tempo clínico de acompanhamento para que seja possível traçar um perfil do comportamento destes implantes a longo prazo. / The aim of this study was to evaluate clinically and radiographically short unit implants with 5 and 6 mm in length (Titamax WS - Neodent / Curitiba, Brazil) installed in the posterior mandible and maxilla with little bone height. Ten implants were installed in eight carefully selected patients from inclusion criteria pre-determined. They received prosthetic loading only after the conventional time waiting for the osseointegration. Six implants were placed in the mandible and four implants in the maxilla. Radiographs were performed to evaluate the vertical and horizontal bone loss in T0 (surgery installation), T1 (uncovering), T2 (prosthetic installation) and T3 (follow-up of 6 months). Biological parameters were evaluated such as gingival bleeding index, keratinized mucosa amount, plaque index and gingival inflammation index. Prosthetic parameters were also evaluated as crown-implant ratio and mesiodistal distance. Only one implant (Titamax WS Cortical 5.0x6.0) was lost, it occurred during the healing fase. Therefore the success rate was 90% in the period. Bone level change was analyzed in three different periods, from surgical installation to uncovering surgery (1st period), from uncovering to prosthetic installation (2nd Period) and from prosthetic installation prosthetic to six months control (3rd Period ). Vertical bone loss values were very similar when evaluated in the three periods separately, even the same statistically (ANOVA, p <0.05). The amount of bone loss in 1st period was 0.32 mm in the 2nd period was 0.22 mm and in the 3rd period was 0.29 mm. This means that surgical procedures were also cause marginal bone loss even taking some care in implementing these steps. The average vertical and horizontal bone loss in the total period of observation was 0.87 ± 0.46 and 0.24 ± 0.34 respectively. These values were considered within the range of bone loss expected. The gingival good condition of health and oral hygiene ruled out the possibility of an association between periodontal indices and bone loss. Statistical analysis of linear regression (p <0.05) showed no cause and effect relationship between bone loss and prosthetic parameters, despite the high crown / implant ratio (average 1.88). Based on the findings of this study, it was concluded that short implants, even the 5 and 6 mm in length, should be considered as an important alternative treatment for single crows. It is suggested a longer clinical follow-up to make it possible to trace a pattern of behavior of these implants over the long term.

Hydroxyapatite (HA) is a biologically active ceramic used in surgery to replace bone. While HA promotes bone growth, it suffers from weak mechanical properties and does not possess any antibacterial property. Multi walled carbon nanotubes (MWCNTs), as one of the strongest and stiffest materials, have the potential to strengthen and toughen HA, thus expanding the range of clinical uses for the material. Furthermore, Silver nanoparticles (Ag NPs) can be decorated to sidewalls of the MWCNTs which could be released over a period of time to prevent infection following surgery. This work sought to develop and characterise Ag NPs- MWCNTs – HA composites in four main areas: 1) production and characterisation of the composite, 2) evaluation of mechanical properties, 3) investigation of antimicrobial property and 4) assessment of biological response to in vitro cell culture. Pristine (p-MWCNTs) and acid treated MWCNTs (f-MWCNTs) were decorated with Ag NPs. In the presence of 0.5 wt % Ag NPs-MWCNTs, HA was precipitated by the wet precipitation method in the presence of either poly vinyl alcohol (PVA) or Hexadecyl trimethyl ammonium bromide (HTAB) as the surfactant. Composites were characterised using various techniques and the diameteral tensile strength and compressive strength of the composites were measured. The antibacterial effect of these composites was investigated against clinically relevant microbe, Staphylococcus aureus. To determine the ability of the HOB cells to differentiate and mineralize in the presence of the composite, HOB cells were cultured on the composites for 21 days. Gene expression studies was performed along with the biochemical assays and scanning electron microscopy was used for qualitative analysis. Pure HA was used as control in all the studies. The study revealed that both the MWCNTs and surfactants play a crucial role in the nucleation and growth of the HA. XRD and FTIR characterisation revealed that HA was the primary phase in all the synthesised powders. Composites made with f-MWCNTs were found to have better dispersion and better interaction with the HA compared to composites with p-MWCNTs. Although mechanical strength was improved in all the composites, p-MWCNTs composites exhibiting maximum strength. Antibacterial studies showed 80% bacterial reduction in the treatment composites compared to pure HA. The biocompatibility study showed reduced activity of the HOB cells, however, no significant difference was observed between the control and the treatments. This systematic study of the synthesis and properties of the Ag NPs- MWCNTs-HA composites has resulted in improved understanding of the production and processing of these materials and the effect of MWCNTs and silver nanoparticles on primary human osteoblast cells. Additionally, it has yielded interesting biocompatibility result favouring the use of MWCNTs in the development of implants. There is potential to translate Ag NPs-MWCNTs-HA composites into clinically approved product.