411 research outputs found
Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea
ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK
SURGICAL NAVIGATION AND AUGMENTED REALITY FOR MARGINS CONTROL IN HEAD AND NECK CANCER
I tumori maligni del distretto testa-collo rappresentano un insieme di lesioni dalle diverse caratteristiche patologiche, epidemiologiche e prognostiche. Per una porzione considerevole di tali patologie, l’intervento chirurgico finalizzato all’asportazione completa del tumore rappresenta l’elemento chiave del trattamento, quand’anche esso includa altre modalità quali la radioterapia e la terapia sistemica.
La qualità dell’atto chirurgico ablativo è pertanto essenziale al fine di garantire le massime chance di cura al paziente. Nell’ambito della chirurgia oncologica, la qualità delle ablazioni viene misurata attraverso l’analisi dello stato dei margini di resezione. Oltre a rappresentare un surrogato della qualità della resezione chirurgica, lo stato dei margini di resezione ha notevoli implicazioni da un punto di vista clinico e prognostico. Infatti, il coinvolgimento dei margini di resezione da parte della neoplasia rappresenta invariabilmente un fattore prognostico sfavorevole, oltre che implicare la necessità di intensificare i trattamenti postchirurgici (e.g., ponendo indicazione alla chemioradioterapia adiuvante), comportando una maggiore tossicità per il paziente. La proporzione di resezioni con margini positivi (i.e., coinvolti dalla neoplasia) nel distretto testa-collo è tra le più elevate in ambito di chirurgia oncologica.
In tale contesto si pone l’obiettivo del dottorato di cui questa tesi riporta i risultati. Le due tecnologie di cui si è analizzata l’utilità in termini di ottimizzazione dello stato dei margini di resezione sono la navigazione chirurgica con rendering tridimensionale e la realtà aumentata basata sulla videoproiezione di immagini. Le sperimentazioni sono state svolte parzialmente presso l’Università degli Studi di Brescia, parzialmente presso l’Azienda Ospedale Università di Padova e parzialmente presso l’University Health Network (Toronto, Ontario, Canada).
I risultati delle sperimentazioni incluse in questo elaborato dimostrano che l'impiego della navigazione chirurgica con rendering tridimensionale nel contesto di procedure oncologiche ablative cervico-cefaliche risulta associata ad un vantaggio significativo in termini di riduzione della frequenza di margini positivi. Al contrario, le tecniche di realtà aumentata basata sulla videoproiezione, nell'ambito della sperimentazione preclinica effettuata, non sono risultate associate a vantaggi sufficienti per poter considerare tale tecnologia per la traslazione clinica.Head and neck malignancies are an heterogeneous group of tumors. Surgery represents the mainstay of treatment for the large majority of head and neck cancers, with ablation being aimed at removing completely the tumor. Radiotherapy and systemic therapy have also a substantial role in the multidisciplinary management of head and neck cancers. The quality of surgical ablation is intimately related to margin status evaluated at a microscopic level. Indeed, margin involvement has a remarkably negative effect on prognosis of patients and mandates the escalation of postoperative treatment by adding concomitant chemotherapy to radiotherapy and accordingly increasing the toxicity of overall treatment. The rate of margin involvement in the head and neck is among the highest in the entire field of surgical oncology.
In this context, the present PhD project was aimed at testing the utility of 2 technologies, namely surgical navigation with 3-dimensional rendering and pico projector-based augmented reality, in decreasing the rate of involved margins during oncologic surgical ablations in the craniofacial area. Experiments were performed in the University of Brescia, University of Padua, and University Health Network (Toronto, Ontario, Canada).
The research activities completed in the context of this PhD course demonstrated that surgical navigation with 3-dimensional rendering confers a higher quality to oncologic ablations in the head and neck, irrespective of the open or endoscopic surgical technique. The benefits deriving from this implementation come with no relevant drawbacks from a logistical and practical standpoint, nor were major adverse events observed. Thus, implementation of this technology into the standard care is the logical proposed step forward. However, the genuine presence of a prognostic advantage needs longer and larger study to be formally addressed.
On the other hand, pico projector-based augmented reality showed no sufficient advantages to encourage translation into the clinical setting. Although observing a clear practical advantage deriving from the projection of osteotomy lines onto the surgical field, no substantial benefits were measured when comparing this technology with surgical navigation with 3-dimensional rendering. Yet recognizing a potential value of this technology from an educational standpoint, the performance displayed in the preclinical setting in terms of surgical margins optimization is not in favor of a clinical translation with this specific aim
The Use of Skeletal Muscle to Amplify Action Potentials in Transected Peripheral Nerves
Upper limb amputees suffer with problems associated with control and attachment of prostheses. Skin-surface electrodes placed over the stump, which detect myoelectric signals, are traditionally used to control hand movements. However, this method is unintuitive, the electrodes lift-off, and signal selectivity can be an issue.
One solution to these limitations is to implant electrodes directly on muscles. Another approach is to implant electrodes directly into the nerves that innervate the muscles. A significant challenge with both solutions is the reliable transmission of biosignals across the skin barrier.
In this thesis, I investigated the use of implantable muscle electrodes in an ovine model using myoelectrodes in combination with a bone-anchor, acting as a conduit for signal transmission. High-quality readings were obtained which were significantly better than skin-surface electrode readings. I further investigated the effect of electrode configurations to achieve the best signal quality.
For direct recording from nerves, I tested the effect of adsorbed endoneural basement membrane proteins on nerve regeneration in vivo using microchannel neural interfaces implanted in rat sciatic nerves. Muscle and nerve signal recordings were obtained and improvements in sciatic nerve function were observed.
Direct skeletal fixation of a prosthesis to the amputation stump using a bone-anchor has been proposed as a solution to skin problems associated with traditional socket-type prostheses. However, there remains a concern about the risk of infection between the implant and skin. Achieving a durable seal at this interface is therefore crucial, which formed the final part of the thesis. Bone-anchors were optimised for surface pore size and coatings to facilitate binding of human dermal fibroblasts to optimise skin-implant seal in an ovine model. Implants silanised with Arginine-Glycine-Aspartic Acid experienced significantly increased dermal tissue infiltration. This approach may therefore improve the soft tissue seal, and thus success of bone-anchored implants.
By addressing both the way prostheses are attached to the amputation stump, by way of direct skeletal fixation, as well as providing high fidelity biosignals for high-level intuitive prosthetic control, I aim to further the field of limb loss rehabilitation
Hierarchical, informed and robust machine learning for surgical tool management
This thesis focuses on the development of a computer vision and deep learning based system for the intelligent management of surgical tools. The work accomplished included the development of a new dataset, creation of state of the art techniques to cope with volume, variety and vision problems, and designing or adapting algorithms to address specific surgical tool recognition issues. The system was trained to cope with a wide variety of tools, with very subtle differences in shapes, and was designed to work with high volumes, as well as varying illuminations and backgrounds. Methodology that was adopted in this thesis included the creation of a surgical tool image dataset and development of a surgical tool attribute matrix or knowledge-base. This was significant because there are no large scale publicly available surgical tool datasets, nor are there established annotations or datasets of textual descriptions of surgical tools that can be used for machine learning. The work resulted in the development of a new hierarchical architecture for multi-level predictions at surgical speciality, pack, set and tool level. Additional work evaluated the use of synthetic data to improve robustness of the CNN, and the infusion of knowledge to improve predictive performance
Bionic Lid Implant for Natural Closure (BLINC)
Facial nerve palsy (FNP) leads to an inability to blink. The exposed eye is at risk of developing corneal keratopathy and currently there is a lack of solution to active eye closure that is immediate and reliable. Bionic Lid Implant for Natural Closure (BLINC) proposes the use of an implantable actuator combined with the effects of an eyelid sling for dynamic eye closure. The aims of this thesis are to 1) explore the clinical need for BLINC, 2) describe the BLINC technology, and 3) present the results of its application in cadaveric and live models.
Methods
The aims of this project are addressed in three parts. In part one, the current therapies addressing key clinical end points in FNP from an ocular perspective and the setting where BLINC may first be used are explored. In part two the science behind BLINC is outlined. Finally in part three application of BLINC in cadaveric and live models are studied followed by a discussion on future steps preceding a pilot study in humans.
Results
Patients with FNP consistently identify issues related to the eye a primary concern. Current reanimation strategies offer the possibility of dynamic eye closure but the results are delayed and often unpredictable. BLINC reliably achieves active eye closure in cadaveric models by means of a wireless-powered, implantable electromagnetic actuator in conjunction with an eyelid sling. BLINC closes the eye in a similar fashion to natural closure
for a symmetrical blink in FNP. Successful application of an inactive device in its complete form is achieved in a live animal without significant morbidity.
Conclusion
BLINC offers the possibility of restoring active eye closure with use of an implantable actuator. The concept has been successfully demonstrated in cadaveric models with successful device implantation in a live model. Future live trials are needed to address the remaining biocompatibility issues in preparation for human application
Retinal erythropoietin distribution and neuroprotective effect in a nanoparticulate drug delivery system after subconjunctival and topical administration in an animal glaucoma model
Tese de Doutoramento em Ciências Veterinárias na especialidade ClínicaABSTRACT - Glaucoma is a neurodegenerative ocular disease with substantial impact in public health, as it causes retinal ganglion cells (RGC) degeneration and irreversible blindness. Neuroprotective strategies have been a focus of research in glaucoma, and the use of erythropoietin and its recombinant forms, like epoetin beta (EPOβ), have shown anti-apoptotic effects on RGC. We aimed to create a nanoformulation carrying EPOβ, adequate for topical ocular administration, that could provide neuroprotection to the retina in cases of glaucoma, with absent or residual secondary effects and the advantage of promoting patients’ compliance to the treatment. Therefore, chitosan and hyaluronic acid (CS/HA) nanoparticles for topical ocular deliver of epoetin beta (EPOβ) were developed, aiming to deliver EPOβ to the retina in a sustained profile. Firstly, in vitro and ex vivo studies of the physicochemical stability, cytotoxicity, release and permeation profiles and mucoadhesive strength of the CS/HA-EPOβ nanoparticles were performed. These nanoparticles allowed EPOβ permeation through ocular membranes in ex vivo assays, with no in vitro cytotoxicity. Afterwards, healthy Wistar Hannover rats were used for subconjunctival and topical administrations of CS/HA-EPOβ nanoparticles, to assess the formulation’s local and systemic influence, its biological tolerance and safety, its effect in retinal electrophysiology, and EPOβ’s distribution in ocular tissues. A sustained EPOβ delivery to the retina was observed using both routes of administration, with no side-effects. Finally, we explored the topical ocular delivery of CS/HA-EPOβ nanoparticles using a rat glaucoma model. We assessed retinal morphological and physiological changes in response to the nanoformulation applied through topical ocular route, using electroretinography and histological evaluation, which comprised immunofluorescence, hematoxylin and eosin staining and apoptosis assessment (cleaved caspase-3). Topical ocular administration of CS/HA EPOβ nanoparticles in glaucomatous rats allowed EPOβ permeation, including by transcorneal pathway, reaching the inner retina. Improvements in retinal electrical activity and thickness, and in apoptosis reduction occurred earlier and more significantly in the treatment group. In conclusion, EPOβ reached the retina, where its neuroprotective action was observed, thus demonstrating the feasibility of topical administration of neuroprotective agents in nanoformulations, targeting the posterior ocular segment. Results were promising and contribute to the development of new therapeutic strategies to preserve the visual acuity of patients with glaucoma or other neurodegenerative ocular diseasesRESUMO - DISTRIBUIÇÃO E EFEITO NEUROPROTETOR DA ERITROPOIETINA NA RETINA APÓS ADMINISTRAÇÃO TÓPICA E SUBCONJUNTIVAL DE UM SISTEMA DE NANOPARTÍCULAS NUM MODELO ANIMAL DE GLAUCOMA - O glaucoma é uma doença ocular neurodegenerativa com impacto substancial na saúde pública, causando degeneração das células ganglionares da retina (CGR) e cegueira irreversível. Várias estratégias neuroprotetoras têm sido estudadas no glaucoma e a epoetina beta (EPOβ), uma forma recombinante da eritropoietina, demonstrou efeitos antiapoptóticos nas CGR. Desta forma, surgiu o interesse em criar uma formulação com EPOβ para administração tópica ocular, com vista a neuroproteção da retina em casos de glaucoma, com o mínimo de efeitos secundários e com a vantagem de promover a adesão dos pacientes ao tratamento. Para tal foram desenvolvidas nanopartículas de quitosano e ácido hialurónico (CS/HA) às quais foi adicionada epoetina beta (EPOβ). Inicialmente, foram realizados estudos in vitro e ex vivo da estabilidade físico-química, citotoxicidade, perfis de libertação e permeação e mucoadesividade das nanopartículas CS/HA-EPOβ. Estas permitiram a permeação de EPOβ em membranas oculares nos ensaios ex vivo, sem citotoxicidade in vitro. Seguidamente, ratos Wistar Hannover saudáveis foram usados para administração subconjuntival e tópica das nanopartículas CS/HA-EPOβ, para avaliar o impacto local e sistémico da formulação, a tolerância biológica e segurança, o efeito na eletrofisiologia da retina e a distribuição da EPOβ nos tecidos oculares. Observou-se uma permeação sustentada de EPOβ até à retina em ambas as vias de administração, sem efeitos adversos. Finalmente, estudámos a via ocular tópica utilizando um modelo experimental de glaucoma em ratos. Avaliámos as alterações morfológicas e fisiológicas da retina em resposta à nanoformulação, através de eletrorretinografia e avaliação histológica por imunofluorescência e coloração de hematoxilina-eosina, e avaliação de apoptose (caspase-3 clivada). A administração tópica ocular de nanopartículas de CS/HA-EPOβ em ratos glaucomatosos permitiu a permeação da EPOβ, inclusive por via transcorneal, até à retina. No grupo de animais tratados ocorreram, mais cedo e de forma mais considerável, melhorias na atividade elétrica e na espessura da retina, e na redução da apoptose. Em suma, a EPOβ chegou à retina, onde foi possível constatar a sua ação neuroprotetora, demonstrando assim a viabilidade da administração tópica de agentes neuroprotetores em nanoformulações, visando o segmento posterior do olho. Os resultados foram promissores e oferecem um contributo significativo para o desenvolvimento de novas formas terapêuticas para preservar a acuidade visual de pacientes com glaucoma ou outras doenças oculares neurodegenerativasN/
Control and Estimation Methods Towards Safe Robot-assisted Eye Surgery
Vitreoretinal surgery is among the most delicate surgical tasks in which physiological hand tremor may severely diminish surgeon performance and put the eye at high risk of injury. Unerring targeting accuracy is required to perform precise operations on micro-scale tissues. Tool tip to tissue interaction forces are usually below human tactile perception, which may result in exertion of excessive forces to the retinal tissue leading to irreversible damages. Notable challenges during retinal surgery lend themselves to robotic assistance which has proven beneficial in providing a safe steady-hand manipulation. Efficient assistance from the robots heavily relies on accurate sensing and intelligent control algorithms of important surgery states and situations (e.g. instrument tip position measurements and control of interaction forces). This dissertation provides novel control and state estimation methods to improve safety during robot-assisted eye surgery.
The integration of robotics into retinal microsurgery leads to a reduction in surgeon perception of tool-to-tissue forces at sclera. This blunting of human tactile sensory input, which is due to the inflexible inertia of the robot, is a potential iatrogenic risk during robotic eye surgery. To address this issue, a sensorized surgical instrument equipped with Fiber Bragg Grating (FBG) sensors, which is capable of measuring the sclera forces and instrument insertion depth into the eye, is integrated to the Steady-Hand Eye Robot (SHER). An adaptive control scheme is then customized and implemented on the robot that is intended to autonomously mitigate the risk of unsafe scleral forces and excessive insertion of the instrument. Various preliminary and multi-user clinician studies are then conducted to evaluate the effectiveness of the control method during mock retinal surgery procedures.
In addition, due to inherent flexibility and the resulting deflection of eye surgical instruments as well as the need for targeting accuracy, we have developed a method to enhance deflected instrument tip position estimation. Using an iterative method and microscope data, we develop a calibration- and registration-independent (RI) framework to provide online estimates of the instrument stiffness (least squares and adaptive). The estimations are then combined with a state-space model for tip position evolution obtained based on the forward kinematics (FWK) of the robot and FBG sensor measurements. This is accomplished using a Kalman Filtering (KF) approach to improve the instrument tip position estimation during robotic surgery. The entire framework is independent of camera-to-robot coordinate frame registration and is evaluated during various phantom experiments to demonstrate its effectiveness
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