Do ‘passive’ medical titanium surfaces deteriorate in service in the absence of wear?

Globally, more than 1000 tonnes of titanium (Ti) is implanted into patients in the form of biomedical devices on an annual basis. Ti is perceived to be ‘biocompatible’ owing to the presence of a robust passive oxide film (approx. 4 nm thick) at the metal surface. However, surface deterioration can lead to the release of Ti ions, and particles can arise as the result of wear and/or corrosion processes. This surface deterioration can result in peri-implant inflammation, leading to the premature loss of the implanted device or the requirement for surgical revision. Soft tissues surrounding commercially pure cranial anchorage devices (bone-anchored hearing aid) were investigated using synchrotron X-ray micro-fluorescence spectroscopy and X-ray absorption near edge structure. Here, we present the first experimental evidence that minimal load-bearing Ti implants, which are not subjected to macroscopic wear processes, can release Ti debris into the surrounding soft tissue. As such debris has been shown to be pro-inflammatory, we propose that such distributions of Ti are likely to effect to the service life of the device.

Novel bioactive scaffolds incorporating nanogels as potential drug eluting devices

Big advances are being achieved in the design of new implantable devices with enhanced properties. For example, synthetic porous three-dimensional structures can mimic the architecture of the tissues, and serve as templates for cell seeding. In addition, polymeric nanoparticles are able to provide a programmable and sustained local delivery of different types of biomolecules. In this study novel alternative scaffolds with controlled bioactive properties and architectures are presented. Two complementary approaches are described. Firstly, scaffolds with nanogels as active controlled release devices incorporated inside the three-dimensional structure are obtained using the thermally induced phase separation (TIPS) method. Secondly, a novel coating method using the spraying technique to load these nanometric crosslinked hydrogels on the surface of two-dimensional (2D) and three-dimensional (3D) biodegradable scaffolds is described. The scanning electron microscopy (SEM) images show the distribution of the nanogels on the surface of different substrates and also inside the porous structure of poly-a-hydroxy ester derivative foams. Both of them are compared in terms of manufacturability, dispersion and other processing variables.

Recent advances in fibre grating devices and their sensing applications

Over the last twenty years, we have been continuously seeing R&D efforts and activities in developing optical fibre grating devices and technologies and exploring their applications for telecommunications, optical signal processing and smart sensing, and recently for medical care and biophotonics. In addition, we have also witnessed successful commercialisation of these R&Ds, especially in the area of fibre Bragg grating (FBG) based distributed sensor network systems and technologies for engineering structure monitoring in industrial sectors such as oil, energy and civil engineering. Despite countless published reports and papers and commercial realisation, we are still seeing significant and novel research activities in this area. This invited paper will give an overview on recent advances in fibre grating devices and their sensing applications with a focus on novel fibre gratings and their functions and grating structures in speciality fibres. The most recent developments in (i) femtosecond inscription for microfluidic/grating devices, (2) tilted grating based novel polarisation devices and (3) dual-peak long-period grating based DNA hybridisation sensors will be discussed.

Clinical utility of implantable neurostimulation devices as adjunctive treatment of uncontrolled seizures

About one third of patients with epilepsy are refractory to medical treatment. For these patients, alternative treatment options include implantable neurostimulation devices such as vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation systems (RNS). We conducted a systematic literature review to assess the available evidence on the clinical efficacy of these devices in patients with refractory epilepsy across their lifespan. VNS has the largest evidence base, and numerous randomized controlled trials and open-label studies support its use in the treatment of refractory epilepsy. It was approved by the US Food and Drug Administration in 1997 for treatment of partial seizures, but has also shown significant benefit in the treatment of generalized seizures. Results in adult populations have been more encouraging than in pediatric populations, where more studies are required. VNS is considered a safe and well-tolerated treatment, and serious side effects are rare. DBS is a well-established treatment for several movement disorders, and has a small evidence base for treatment of refractory epilepsy. Stimulation of the anterior nucleus of the thalamus has shown the most encouraging results, where significant decreases in seizure frequency were reported. Other potential targets include the centromedian thalamic nucleus, hippocampus, cerebellum, and basal ganglia structures. Preliminary results on RNS, new-generation implantable neurostimulation devices which stimulate brain structures only when epileptic activity is detected, are encouraging. Overall, implantable neurostimulation devices appear to be a safe and beneficial treatment option for patients in whom medical treatment has failed to adequately control their epilepsy. Further large-scale randomized controlled trials are required to provide a sufficient evidence base for the inclusion of DBS and RNS in clinical guidelines.

Assessment of biodegradable magnesium alloys for enhanced mechanical and biocompatible properties

Biomaterials have been used for more than a century in the human body to improve body functions and replace damaged tissues. Currently approved and commonly used metallic biomaterials such as, stainless steel, titanium, cobalt chromium and other alloys have been found to have adverse effects leading in some cases, to mechanical failure and rejection of the implant. The physical or chemical nature of the degradation products of some implants initiates an adverse foreign body reaction in the tissue. Some metallic implants remain as permanent fixtures, whereas others such as plates, screws and pins used to secure serious fractures are removed by a second surgical procedure after the tissue has healed sufficiently. However, repeat surgical procedures increase the cost of health care and the possibility of patient morbidity. This study focuses on the development of magnesium based biodegradable alloys/metal matrix composites (MMCs) for orthopedic and cardiovascular applications. The Mg alloys/MMCs possessed good mechanical properties and biocompatible properties. Nine different compositions of Mg alloys/MMCs were manufactured and surface treated. Their degradation behavior, ion leaching, wettability, morphology, cytotoxicity and mechanical properties were determined. Alloying with Zn, Ca, HA and Gd and surface treatment resulted in improved mechanical properties, corrosion resistance, reduced cytotoxicity, lower pH and hydrogen evolution. Anodization resulted in the formation of a distinct oxide layer (thickness 5-10 μm) as compared with that produced on mechanically polished samples (~20-50 nm) under ambient conditions. It is envisaged that the findings of this research will introduce a new class of Mg based biodegradable alloys/MMCs and the emergence of innovative cardiovascular and orthopedic implant devices.^

Systematic review of the health and societal effects of medication organisation devices

Acknowledgements The authors would like to thank, Estelle Payerne (article screening, data extraction and bias assessment); Trish Boyton (article retrieval and screening) and Laura Cawley (search terms and title screening) for their invaluable help in conducting this systematic review. Funding The research was funded by the UK National Institute for Health Research Health Technology Assessment Programme.

Piezoelectric energy harvesting using blood-flow-like excitation for implantable devices

The goal of this research is to produce a system for powering medical implants to increase the lifetime of the implanted devices and reduce the battery size. The system consists of a number of elements – the piezoelectric material for generating power, the device design, the circuit for rectification and energy storage. The piezoelectric material is analysed and a process for producing a repeatable high quality piezoelectric material is described. A full width half maximum (FWHM) of the rocking curve X-Ray diffraction (XRD) scan of between ~1.5° to ~1.7° for test wafers was achieved. This is state of the art for AlN on silicon and means devices with good piezoelectric constants can be fabricated. Finite element modelling FEM) was used to design the structures for energy harvesting. The models developed in this work were established to have an accuracy better than 5% in terms of the difference between measured and modelled results. Devices made from this material were analysed for power harvesting ability as well as the effect that they have on the flow of liquid which is an important consideration for implantable devices. The FEM results are compared to experimental results from laser Doppler vibrometry (LDV), magnetic shaker and perfusion machine tests. The rectifying circuitry for the energy harvester was also investigated. The final solution uses multiple devices to provide the power to augment the battery and so this was a key feature to be considered. Many circuits were examined and a solution based on a fully autonomous circuit was advanced. This circuit was analysed for use with multiple low power inputs similar to the results from previous investigations into the energy harvesting devices. Polymer materials were also studied for use as a substitute for the piezoelectric material as well as the substrate because silicon is more brittle.

Mobile Technologies: Expectancy, Usage, and Acceptance of Clinical Staff and Patients at a University Medical Center

BACKGROUND: Despite their increasing popularity, little is known about how users perceive mobile devices such as smartphones and tablet PCs in medical contexts. Available studies are often restricted to evaluating the success of specific interventions and do not adequately cover the users' basic attitudes, for example, their expectations or concerns toward using mobile devices in medical settings. OBJECTIVE: The objective of the study was to obtain a comprehensive picture, both from the perspective of the patients, as well as the doctors, regarding the use and acceptance of mobile devices within medical contexts in general well as the perceived challenges when introducing the technology. METHODS: Doctors working at Hannover Medical School (206/1151, response 17.90%), as well as patients being admitted to this facility (213/279, utilization 76.3%) were surveyed about their acceptance and use of mobile devices in medical settings. Regarding demographics, both samples were representative of the respective study population. GNU R (version 3.1.1) was used for statistical testing. Fisher's exact test, two-sided, alpha=.05 with Monte Carlo approximation, 2000 replicates, was applied to determine dependencies between two variables. RESULTS: The majority of participants already own mobile devices (doctors, 168/206, 81.6%; patients, 110/213, 51.6%). For doctors, use in a professional context does not depend on age (P=.66), professional experience (P=.80), or function (P=.34); gender was a factor (P=.009), and use was more common among male (61/135, 45.2%) than female doctors (17/67, 25%). A correlation between use of mobile devices and age (P=.001) as well as education (P=.002) was seen for patients. Minor differences regarding how mobile devices are perceived in sensitive medical contexts mostly relate to data security, patients are more critical of the devices being used for storing and processing patient data; every fifth patient opposed this, but nevertheless, 4.8% of doctors (10/206) use their devices for this purpose. Both groups voiced only minor concerns about the credibility of the provided content or the technical reliability of the devices. While 8.3% of the doctors (17/206) avoided use during patient contact because they thought patients might be unfamiliar with the devices, (25/213) 11.7% of patients expressed concerns about the technology being too complicated to be used in a health context. CONCLUSIONS: Differences in how patients and doctors perceive the use of mobile devices can be attributed to age and level of education; these factors are often mentioned as contributors of the problems with (mobile) technologies. To fully realize the potential of mobile technologies in a health care context, the needs of both the elderly as well as those who are educationally disadvantaged need to be carefully addressed in all strategies relating to mobile technology in a health context.

MobiMed: Framework for Rapid Application Development of Medical Mobile Apps

In the medical field images obtained from high definition cameras and other medical imaging systems are an integral part of medical diagnosis. The analysis of these images are usually performed by the physicians who sometimes need to spend long hours reviewing the images before they are able to come up with a diagnosis and then decide on the course of action. In this dissertation we present a framework for a computer-aided analysis of medical imagery via the use of an expert system. While this problem has been discussed before, we will consider a system based on mobile devices. Since the release of the iPhone on April 2003, the popularity of mobile devices has increased rapidly and our lives have become more reliant on them. This popularity and the ease of development of mobile applications has now made it possible to perform on these devices many of the image analyses that previously required a personal computer. All of this has opened the door to a whole new set of possibilities and freed the physicians from their reliance on their desktop machines. The approach proposed in this dissertation aims to capitalize on these new found opportunities by providing a framework for analysis of medical images that physicians can utilize from their mobile devices thus remove their reliance on desktop computers. We also provide an expert system to aid in the analysis and advice on the selection of medical procedure. Finally, we also allow for other mobile applications to be developed by providing a generic mobile application development framework that allows for access of other applications into the mobile domain. In this dissertation we outline our work leading towards development of the proposed methodology and the remaining work needed to find a solution to the problem. In order to make this difficult problem tractable, we divide the problem into three parts: the development user interface modeling language and tooling, the creation of a game development modeling language and tooling, and the development of a generic mobile application framework. In order to make this problem more manageable, we will narrow down the initial scope to the hair transplant, and glaucoma domains.

Proximity detection protocols for IoT devices

In recent years, we have witnessed the growth of the Internet of Things paradigm, with its increased pervasiveness in our everyday lives. The possible applications are diverse: from a smartwatch able to measure heartbeat and communicate it to the cloud, to the device that triggers an event when we approach an exhibit in a museum. Present in many of these applications is the Proximity Detection task: for instance the heartbeat could be measured only when the wearer is near to a well defined location for medical purposes or the touristic attraction must be triggered only if someone is very close to it. Indeed, the ability of an IoT device to sense the presence of other devices nearby and calculate the distance to them can be considered the cornerstone of various applications, motivating research on this fundamental topic. The energy constraints of the IoT devices are often in contrast with the needs of continuous operations to sense the environment and to achieve high accurate distance measurements from the neighbors, thus making the design of Proximity Detection protocols a challenging task.

Chemiluminescence – based bioanalytical devices for astrobiological, food safety and clinical applications

At the intersection of biology, chemistry, and engineering, biosensors are a multidisciplinary innovation that provide a cost-effective alternative to traditional laboratory techniques. Due to their advantages, biosensors are used in medical diagnostics, environmental monitoring, food safety and many other fields. The first part of the thesis is concerned with learning the state of the art of paper-based immunosensors with bioluminescent (BL) and chemiluminescent (CL) detection. The use of biospecific assays combined with CL detection and paper-based technology offers an optimal approach to creating analytical tools for on-site applications and we have focused on the specific areas that need to be considered more in order to ensure a future practical implementation of these methods in routine analyses. The subsequent part of the thesis addresses the development of an autonomous lab-on-chip platform for performing chemiluminescent-based bioassays in space environment, exploiting a CubeSat platform for astrobiological investigations. An origami-inspired microfluidic paper-based analytical device has been developed with the purpose of assesses its performance in space and to evaluate its functionality and the resilience of the (bio)molecules when exposed to a radiation-rich environment. Subsequently, we designed a paper-based assay to detect traces of ovalbumin in food samples, creating a user-friendly immunosensing platform. To this purpose, we developed an origami device that exploits a competitive immunoassay coupled with chemiluminescence detection and magnetic microbeads used to immobilize ovalbumin on paper. Finally, with the aim of exploring the use of biomimetic materials, an hydrogel-based chemiluminescence biosensor for the detection of H2O2 and glucose was developed. A guanosine hydrogel was prepared and loaded with luminol and hemin, miming a DNAzyme activity. Subsequently, the hydrogel was modified by incorporating glucose oxidase enzyme to enable glucose biosensing. The emitted photons were detected using a portable device equipped with a smartphone's CMOS (complementary metal oxide semiconductor) camera for CL emission detection.

Reasons For Brazilian Women To Switch From Different Contraceptives To Long-acting Reversible Contraceptives.

Long-acting reversible contraceptives (LARCs) include the copper-releasing intrauterine device (IUD), the levonorgestrel-releasing intrauterine system (LNG-IUS) and implants. Despite the high contraceptive efficacy of LARCs, their prevalence of use remains low in many countries. The objective of this study was to assess the main reasons for switching from contraceptive methods requiring daily or monthly compliance to LARC methods within a Brazilian cohort. Women of 18-50 years of age using different contraceptives and wishing to switch to a LARC method answered a questionnaire regarding their motivations for switching from their current contraceptive. Continuation rates were evaluated 1 year after method initiation. Sample size was calculated at 1040 women. Clinical performance was evaluated by life table analysis. The cutoff date for analysis was May 23, 2013. Overall, 1167 women were interviewed; however, after 1 year of use, the medical records of only 1154 women were available for review. The main personal reason for switching, as reported by the women, was fear of becoming pregnant while the main medical reasons were nausea and vomiting and unscheduled bleeding. No pregnancies occurred during LARC use, and the main reasons for discontinuation were expulsion (in the case of the IUD and LNG-IUS) and a decision to undergo surgical sterilization (in the case of the etonogestrel-releasing implant). Continuation rate was ~95.0/100 women/year for the three methods. Most women chose a LARC method for its safety and for practical reasons, and after 1 year of use, most women continued with the method.

Microfluidic Paper-based Devices For Bioanalytical Applications.

Paper has become increasingly recognized as a very interesting substrate for the construction of microfluidic devices, with potential application in a variety of areas, including health diagnosis, environmental monitoring, immunoassays and food safety. The aim of this review is to present a short history of analytical systems constructed from paper, summarize the main advantages and disadvantages of fabrication techniques, exploit alternative methods of detection such as colorimetric, electrochemical, photoelectrochemical, chemiluminescence and electrochemiluminescence, as well as to take a closer look at the novel achievements in the field of bioanalysis published during the last 2 years. Finally, the future trends for production of such devices are discussed.

Motivating Medical Students To Learn Basic Science Concepts Using Chronic Myeloid Leukemia As An Integration Theme.

To report on the use of chronic myeloid leukemia as a theme of basic clinical integration for first year medical students to motivate and enable in-depth understanding of the basic sciences of the future physician. During the past thirteen years we have reviewed and updated the curriculum of the medical school of the Universidade Estadual de Campinas. The main objective of the new curriculum is to teach the students how to learn to learn. Since then, a case of chronic myeloid leukemia has been introduced to first year medical students and discussed in horizontal integration with all themes taught during a molecular and cell biology course. Cell structure and components, protein, chromosomes, gene organization, proliferation, cell cycle, apoptosis, signaling and so on are all themes approached during this course. At the end of every topic approached, the students prepare in advance the corresponding topic of clinical cases chosen randomly during the class, which are then presented by them. During the final class, a paper regarding mutations in the abl gene that cause resistance to tyrosine kinase inhibitors is discussed. After each class, three tests are solved in an interactive evaluation. The course has been successful since its beginning, 13 years ago. Great motivation of those who participated in the course was observed. There were less than 20% absences in the classes. At least three (and as many as nine) students every year were interested in starting research training in the field of hematology. At the end of each class, an interactive evaluation was performed and more than 70% of the answers were correct in each evaluation. Moreover, for the final evaluation, the students summarized, in a written report, the molecular and therapeutic basis of chronic myeloid leukemia, with scores ranging from 0 to 10. Considering all 13 years, a median of 78% of the class scored above 5 (min 74%-max 85%), and a median of 67% scored above 7. Chronic myeloid leukemia is an excellent example of a disease that can be used for clinical basic integration as this disorder involves well known protein, cytogenetic and cell function abnormalities, has well-defined diagnostic strategies and a target oriented therapy.

Triboelectric Effect As A New Strategy For Sealing And Controlling The Flow In Paper-based Devices.

We reported here for the first time that triboelectric charges on PET sheets can be used to seal and control the flow rate in paper-based devices. The proposed method exhibits simplicity and low cost, provides reversible sealing and minimizes the effect of sample evaporation.