It would be of great value to have a precise and non-damaging neuromodulation technique in the field of basic neuroscience research and for clinical treatment of neurological diseases. Infrared neural modulation (INM) is a new modulation modality developed in the last decade, which uses pulsed or continues infrared (IR) light with a wavelength of 1200 to 2200 nm to directly alter neural signals. INM includes both infrared neural stimulation (INS) and infrared neural inhibition (INI). INM is widely investigated for use on peripheral nerves, cochlear nerve fibers, cardiac cells, and the central nervous system. This technique holds the advantages of contact-free and high spatiotemporal precision compared to the traditional electrical stimulation. It does not depend on genetic modification and exogenous absorbers as other optical techniques, such as the optogenetic technique and the enhanced near-infrared neural stimulation (e-NIR). These advantages make INM a viable technique for research and clinical applications. The primary mechanism of the INM is believed to be a photothermal effect, where the IR laser energy absorbed by water leads to a rapid local temperature change. However, so far the details of the mechanism of action potential (AP) generation and inhibition remain elusive. Another issueis that the cells may be endangeredbythe heat exposure, consequently triggering a physiologicalmalfunction or even permanent damage.These concernshave hindered the transfer of the INM technique to the clinical therapy.Therefore, the general aim of this study was to improve the understanding of the details of how INM affects the cells. Laser parameters for safe and efficient stimulation were investigated on the basis of being useful for clinical applications. A tailored heating model and in vitro INM experiments on cortex neurons were used to reach this goal.The first paper was a feasibility study. A 1550nm laser with a beam spot diameter of around 6 mm was used to irradiate the rat cortex neurons, which were seeded on multi-electrode arrays (MEA) and formed well-connected networks. A heating model based on an estimated laser beam (standard Gaussian distribution) was used to simulate temperaturechanges. The damage signal ratio (DSR),based on the temperature,was calculated to predict the heat damage. The average spike rate of all the working electrodes from two MEAs was used to evaluate the degree of theinhibition of the neural networks. Results IVshowed that it is possible to use the 1550 nm laser to safely inhibit the neural network activity and that the degree of the INI is dependent on the power of the laser.The second paper wasan application and mechanism study. The aim of this study was to investigate the safety, efficiency, and cellular mechanism of INI. The same laser as in paper Iwas used in this study. A 20 X objective was used to decrease the beam spot diameteraround 240 μm. The measured laser profile (high order Gaussian beam) was used in the heating model to predict the temperature. The model was verified by local temperature measurements viamicropipette. The action potential rates, measured by the MEA electrodes, were quantified for different temperatures. Bicuculline was added to the cortex neuron cultures to induce hyperexcitation of the neural network. The results showed that the INI is temperature dependent and that the temperature needs to be less than 46 °C at 30 s laser irradiation for safe inhibition. The IR laser couldalso be used to inhibit the hyperexcitedactivity. The degree of inhibition, for the assessed subpopulation of neurons, was better correlated with the action potential amplitude than the width of it and INIcan be accomplished without inhibitory synapses / <p>QC 20180920</p><p></p>

The department of Radiation Sciences at Umeå University has obtained an old linear accelerator, intended for educational purposes. The goal of this thesis was to find proper reinforced radiation protection in an intended bunker (a room with thick concrete walls), to ensure that the radiation outside the bunker falls within acceptable levels. The main method was with the use of Monte Carlo-simulations. To properly simulate the accelerator, knowledge of the energy distribution of emitted radiation was needed. For this, a novel method for spectra determination, using several depth dose measurements including off-axis, was developed. A method that shows promising results in finding the spectra when measurements outside the primary beam are included. The found energy spectrum was then used to simulate the accelerator in the intended bunker. The resulting dose distribution was visualized together with 3D CAD-images of the bunker, to easily see in which locations outside the bunker where the dose was high. An important finding was that some changes are required to ensure that the public does not receive too high doses of radiation on a public outdoor-area that is located above the bunker. Otherwise, the accelerator is only allowed to be run 1.8 hours per year. A workaround to this problem could be to just plant a thorn bush, covering the dangerous area of radius 3m. After such a measure has been taken, which is assumed in the following results, the focus moves to the radiation that leaks into the accelerator’s intended control room, which is located right outside the bunker’s entrance door. The results show that the accelerator is only allowed to be run for a maximum of 6.1 or 3.3 hours per year (depending on the placement of the accelerator in the room), without a specific extra reinforced radiation protection consisting mainly of lead bricks. With the specific extra protection added, the accelerator is allowed to be run 44 or 54 hours per year instead, showing a distinct improvement. However, the dose rate to the control room was still quite high, 13.7 μGy/h or 11.2 μGy/h, compared to the average dose received by someone living in Sweden, which is 0.27 μGy/h. Therefore, further measures are recommended. This is however a worst case scenario, since the leakage spectrum from the accelerator itself was simulated as having the same energy spectrum as the primarybeam at 0.1 % of the intensity, which is the maximum leakage dose according to the specifications for the accelerator. This is probably an overestimation of the intensity. Also, the energy spectra of the leakage is probably of lower energy than the primary beam in at least some directions. Implementing more knowledge of the leak spectra in future work, should therefore result in more allowed run hours for the accelerator.

Within the field of radiotherapy treatments of tumour diseases, the hunt for more accurate and effective treatment methods is a continuous process. For some years ion-beam based radiotherapy, especially the proton-beam based applications, has increased in popularity and availability. The main reason behind this is the fact that ion-beam based applications make it possible to modulate the dose after the planning target volume (PTV) defined by the radiation oncologist. This means that it becomes possible to spare tissue in another way, which might result in more effective treatments, especially in the vicinity of radio sensitive organs. Ion-beam based treatments are however more sensitive to uncertainties in PTV position and beam range as ion-beams have a fixed range depending on target media and initial energy, as opposed to the conventional x-ray beams that do not really have a defined range. Instead their intensity decreases exponentially at a rate dependent of the initial energy and target media. Therefore density heterogeneities result in uncertainties in the planned treatments. As the plans normally are created using a CT-images, for which metallic implants can yield increased heterogeneities both from the implants themselves and so called metal artifacts (distortions in the images caused by different processes as the X-rays used in image acquisition goes through metals). Metallic implants affects the accuracy of a treatment, and therefore also the related risks, so it is important to have an idea of the magnitude of the impact. Therefore the aim of this study is to estimate the impact on a proton-beam based treatment plan for six cranial implants. These were one Ti-mesh implant, one temporal plate implant, one burr-hole cover implant and three craniofix implants of different sizes, which all are commonly seen at the Skandion clinic. Also the ability of the treatment planning system (TPS), used at the clinic, to simulate the effects on the plans caused by the implants is to be studied. From this result it should be estimated if the margins and practices in place at the clinic, for when it is required to aim the beam through the implant, are sufficient or if they should be changed. This study consisted of one test on the range shift effects and one test on the lateral dose distribution changes, with one preparational test in the form of a calibration of Gafchromic EBT3 films. The range shift test was performed on three of the implants, excluding the three craniofix implants using a water phantom and a treatment plan created to represent a standard treatment in the cranial area. The lateral dose distribution change test was performed as a solid phantom study using radiochromic film, for two treatment plans (one where the PTV was located \SI{2}{\centi\metre} below surface, for all implants, and one where it was located at the surface, only for the Ti-mesh and the temporal plate). The results of both tests were compared to simulations performed in the Eclipse treatment planing system (TPS) available at Skandion. The result of the range shift test showed a maximum range shift of \SI{-1.03 +- 0.01}{\milli\metre}, for the burr-hole cover implant, and as the related Eclipse simulations showed a maximal shift of \SI{-0.17 +- 0.01}{\milli\metre} there was a clear problem with the simulation. However, this might not be because of the TPS but due to errors in the CT-image reconstruction, such as, for example, geometrical errors in the representation of the implants. As the margin applied for a similar situation at the Skandion clinic (in order to correct for several uncertainty factors) is \SI{4.2}{\milli\metre} there might be a need to increase this margin depending on the situation. For the lateral distribution effects no definite results were found as the change varied in magnitude, even if it tended to manifest as a decreasing dose for the first plan and a increasing dose for the second. It was therefore concluded that further studies are needed before anything clear can be said.

Sjukvården visar intresse för användning av Artificiell Intelligens (AI) och inom behandling för psykisk ohälsa finns behov för stöd. Intelligenta beslutsstöd kan bidra till minskad belastning för vårdpersonal och bättre behandling för patienter, men sjukvårdens känsliga natur och de konsekvenser som kan uppstå vid försummelse medför etiska utmaningar. Behandling av psykisk ohälsa är komplext och behöver utforskas för att identifiera de potentiella etiska utmaningar som kan uppstå. Genom en kvalitativ intervjustudie med åtta deltagare har området utforskats både bland AI-forskare och vårdpersonal, där insikter från båda kontexter har analyserats för att identifiera och utforska återkommande etiska utmaningar. Genom insamlad empiri och litteraturstudie har fem etiska utmaningar identifierats och utforskats: hantera felaktiga rekommendationer, hantera moraliska dilemman, uppnå patientautonomi, ansvarsdilemmat, och skapa förtroende. / Health care has taken interest in the use of AI (Artificial Intelligence) and mental health services are in need of support. Intelligent decision support systems can contribute to reduced workload for health care professionals and better treatment for patients, but the sensitive nature of health care and the possible consequences in the event of neglect or malpractice pose ethical challenges. Treatment of mental illness is complex and needs to be explored in order to identify the potential ethical challenges that can arise. Through an interview study consisting of eight participants, the problem area has been explored amongst both AI researchers and health care professionals, where insights from both contexts have been analysed in order to identify and explore recurring ethical challenges. Through empirical data and a literature study, five ethical challenges have been identified and explored: handle incorrect recommendations, handle moral dilemmas, achieve patient autonomy, the liability dilemma, and generate trust.

Background Cancer is one of the leading causes of death in Sweden. In order to develop better treatments against cancer we need to better understand it. One area of special interest is cancer metabolism and the metabolic fluxes. As these fluxes cannot be directly measured, modeling is required to determine them. Due to the complexity of cell metabolism, some limitations in the metabolism model are required. As the TCA-cycle (TriCarboxylic Acid cycle) is one of the most important parts of cell metabolism, it was chosen as a starting point. The primary goal of this project has been to evaluate the previously constructed TCA-cycle model. The first step of the evaluation was to determine the CI (Confidence Interval) of the model parameters, to determine the parameters’ identifiability. The second step was to validate the model to see if the model could predict data for which the model had not been trained for. The last step of the evaluation was to determine the uncertainty of the model simulation. Method The TCA-cycle model was created using Isotopicaly labeled data and EMUs (ElementaryMetabolic Units) in OpenFlux, an open source toolbox. The CIs of the TCA-cycle model parameters were determined using both OpenFlux’s inbuilt functionality for it as well as using amethod called PL (Profile Likelihood). The model validation was done using a leave one out method. In conjunction with using the leave on out method, a method called PPL (Prediction Profile Likelihood) was used to determine the CIs of the TCA-cycle model simulation. Results and Discussion Using PL to determine CIs had mixed success. The failures of PL are most likely caused by poor choice of settings. However, in the cases in which PL succeeded it gave comparable results to those of OpenFLux. However, the settings in OpenFlux are important, and the wrong settings can severely underestimate the confidence intervals. The confidence intervals from OpenFlux suggests that approximately 30% of the model parameters are identifiable. Results from the validation says that the model is able to predict certain parts of the data for which it has not been trained. The results from the PPL yields a small confidence interval of the simulation. These two results regarding the model simulation suggests that even though the identifiability of the parameters could be better, that the model structure as a whole is sound. Conclusion The majority of the model parameters in the TCA-cycle model are not identifiable, which is something future studies needs to address. However, the model is able to to predict data for which it has not been trained and the model has low simulation uncertainty.

The current regulation for Medical Devices (MDR) entered into force on 26 May 2021, which has entailed major changes to relevant legislation for in-house production of medical devices in healthcare. The relevance for updating existing, or the development of new standards is currently not well documented and determined and the aim of this report is to make recommendations for how the development of standards may be improved and how departments of medical technology (DMT) in practice apply standards at in-house production of medical devices. The sub-areas that are dealt with in in-house production are reprocessing of single use devices, 3D printing and medical technology software. How standards are used to support departments of medical technology in manufacturing in these areas is described and analyzed in this report. Information for the study was collected through semi-structural interviews with several DMTs and relevant authorities. The information was analyzed, discussed, and compared with previous research. The use of standards varied between DMTs, but all interviewees used standards to some extent. The study concluded that there was an interest from DMTs and a potential need to update existing standards and the production of new standards to meet DMT’s needs. / Nuvarande förordning för medicintekniska produkter (MDR) trädde i kraft den 26 maj 2021, vilket har inneburit stora förändringar på relevant lagstiftning för egentillverkning av medicintekniska produkter inom sjukvården. Relevansen för uppdatering av existerande, alternativt utveckling av nya standarder är i nuläget ej väl dokumenterat och klarlagt och målet med denna rapport är att komma med rekommendationer för hur utveckling av standarder kan förbättras samt hur medicintekniska avdelningar (MTA) i praktiken applicerar sig av standarder vid egentillverkning av medicintekniska produkter. De delområden som behandlas inom egentillverkning är reprocessing av engångsartiklar, 3D-printing och medicinteknisk mjukvara. Hur standarder används som stöd av MTA vid tillverkning inom dessa områden beskrivs och analyseras i denna rapport. Information för studien insamlades genom semi-strukturella intervjuer med flera MT-avdelningar och relevanta myndigheter.Informationen analyserades, diskuterades och jämfördes med tidigare forskning. Användandet av standarder varierade mellan MTA, men alla intervjuade använde standarder i någon utsträckning. Det framkom i studien både ett intresse för uppdatering av existerande standarder och framställning av nya standarder för att bemöta MTAs behov.

Using technology to evaluate performance is a field that previously has been limited to laboratories and high budgets. Today, the evolving of sensor technology and "internet of things" can help us provide more accessible, affordable and perhaps even more reliable feedback about performance. Still, developing such systems is not trivial and often require advanced processing methods to ensure reliability of the feedback. One such process is synchronizing data from multiple sensors.  If the sensors time is asynchronous, the presented feedback could be erroneous and give the wrong information. However, if the data is synchronized correctly it could possibly provide new insights about performance during training and rehabilitation. During this thesis a web application has been developed and used to collect data from multiple sensors during flywheel training. The data has been processed, synchronized and displayed as feedback in a user interface.The user interface displayed fatigue and bilateral asymmetry feedback from a training protocol of 15 squats at maximum intensity. 16 participants with varying background have used the interface, and evaluated it using a well known usability test. The synchronized data correlates as expected during training, but its accuracy has not yet been evaluated.The usability test resulted in an average usability score of 75, well above the tests' defined limits for "good" usability.Being able to obtain such feedback during rehabilitation in particular is deemed valuable and could be very useful in determining athletes readiness more consistently. This type of feedback is previously not available outside of a laboratory environment, but would need further development and research before it can be used and validated. It could possibly help reduce the massive spending on healthcare, and increase the longevity of athletes careers. / Att använda teknik för att utvärdera prestanda är ett område som tidigare har varit begränsat till laboratorier och höga budgetar. I dag kan utvecklingen av sensorteknik och "sakernas internet" hjälpa oss att ge mer lättillgänglig, prisvärd och kanske till och med mer tillförlitlig feedback om prestanda. Det är dock inte helt enkelt att utveckla sådana system, och ofta krävs det avancerade bearbetningsmetoder för att säkerställa att återkopplingen är tillförlitlig. En sådan process är att synkronisera data från flera sensorer.  Om sensorernas tid är asynkron kan den presenterade återkopplingen vara felaktig och ge fel information. Om uppgifterna däremot synkroniseras korrekt kan de eventuellt ge nya insikter om prestationen under träning och rehabilitering. Under denna avhandling har en webbapplikation utvecklats och använts för att samla in data från flera sensorer under svänghjulsträning. Uppgifterna har bearbetats, synkroniserats och visats som feedback i ett användargränssnitt.Användargränssnittet visade feedback om trötthet och bilateral asymmetri från ett träningsprotokoll med 15 knäböjningar vid maximal intensitet. 16 deltagare med varierande bakgrund har använt gränssnittet och utvärderat det med hjälp av ett välkänt användbarhetstest. De synkroniserade uppgifterna korrelerar som förväntat under träningen, men dess noggrannhet har ännu inte utvärderats.Användbarhetstestet resulterade i ett genomsnittligt användbarhetsbetyg på 75, vilket ligger långt över testets definierade gränser för "god" användbarhet.Att kunna få sådan återkoppling särskilt under rehabilitering bedöms som värdefullt och skulle kunna vara mycket användbart för att bestämma idrottsutövarnas beredskap på ett mer konsekvent sätt. Denna typ av feedback finns tidigare inte tillgänglig utanför en laboratoriemiljö, men skulle behöva ytterligare utveckling och forskning innan den kan användas och valideras. Den skulle eventuellt kunna bidra till att minska de enorma utgifterna för hälso- och sjukvård samt öka idrottsutövarnas livslängd.

When blood sampling is performed, problems and complications occasionally occur. Sometimes the blood sampling fails. Statistically, blood sampling fails at the first attempt in 28 percent of all cases for adults. For children, the corresponding rate is 44 percent. The project was based on the need for aids to perform blood sampling. The need was identified and recognised by the taskmasters Frida Svensson and Lisa Eliasson during their degree project in 2021. The project group’s aim was to continue the taskmasters work developing a medical technology product that facilitates blood sampling and to bring the product one step closer to the market. Text removed due to confidentiality. The text mentions the functionality of the product. The product's effect is to increase the chance of succeeding with the blood sampling at the first try. This not only increases the patient’s comfort, but also is timesaving and decreases the need of disposable materials. In the long run this contributes to large financial savings for the healthcare department. The result of the project was a prototype that embodies the product Blood Simpling II.  The product’s functions reduce the risk of complications when blood sampling is performed. At the same time, the product increases the chance of succeeding with the blood sampling at the first attempt. The project group’s successful result resulted in its purpose of bringing the product one step closer to the market. Text removed due to confidentiality. The text mentions the functionality of the product. / Vid blodprovstagning förekommer det att problem och komplikationer uppstår. Det händer att blodprovstagningen helt misslyckas. Statistiskt sett misslyckas blodprovstagningen på första försöket för vuxna i 28 procent av fallen och för barn är motsvarande siffra 44 procent. Projektet utgick från det behov av hjälpmedel att utföra blodprovstagning som uppdragsgivarna Frida Svensson och Lisa Eliasson identifierade under sitt examensarbete från 2021. Syftet var att fortsatta deras arbete att utveckla en medicinteknisk produkt som underlättar vid blodprovstagning och föra den närmare marknaden. I syfte att föra produkten närmare marknaden var det projektgruppens mål att vidareutveckla produkten. Projektgruppen skulle färdigställa komponenterna var för sig och sedan sätta samman dem till en produkt. Produktens effekt är att den ökar chansen att lyckas med blodprovtagningen redan på första försöket. Det gör att det inte bara blir behagligare för patienten utan det sparar även på värdefull tid och engångsmaterial, vilket i längden leder till stora finansiella besparingar för vården. Resultatet av projektet blev en prototyp som gestaltar produkten Blood Simpling II vars funktioner gör att risken att komplikationer uppstår vid venös blodprovstagning minskar och samtidigt ökar produkten chansen att blodprovstagningen lyckas på första försöket. Genom det resultat som projektgruppen lyckades med uppfyllde de sitt syfte att föra produkten ett steg närmare marknaden. Text borttagen på grund av sekretess. Texten nämner produktens funktionalitet vars nyhetsvärde skyddas för att bevara patenteringsmöjligheten.

The topic of this thesis is on how text mining could be used on patient-reported symptom descriptions, and how it could be used to aid doctors in their diagnostic process. Healthcare delivery today is struggling to provide care to remote settings, and costs are increasing together with the aging population. The aid provided to doctors from text mining on patient descriptions is unknown.Investigating if text mining can aid doctors by presenting additional information, based on what patients who write similar things to what their current patient is writing about, could be relevant to many settings in healthcare. It has the potential to improve the quality of care to remote settings and increase the number of patients treated on the limited resources available. In this work, patient texts were represented using the Bag-of-Words model and clustered using the k-means algorithm. The final clustering model used 41 clusters, and the ten most important words for the cluster centroids were used as representative words for the cluster. An experiment was then performed to gauge how the doctors were aided in their diagnostic process when patient texts were paired with these additional words. The results were that the words aided doctors in cases where the patient case was difficult and that the clustering algorithm can be used to provide the current patient with specific follow-up questions. / Ämnet för detta examensarbete är hur text mining kan användas på patientrapporterade symptombeskrivningar, och hur det kan användas för att hjälpa läkare att utföra den diagnostiska processen. Sjukvården har idag svårigheter med att leverera vård till avlägsna orter, och vårdkostnader ökar i och med en åldrande population. Idag är det okänt hur text mining skulle kunna hjälpa doktorer i sitt arbete. Att undersöka om läkare blir hjälpta av att presenteras med mer information, baserat på vad patienter som skriver liknande saker som deras nuvarande patient gör, kan vara relevant för flera olika områden av sjukvården. Text mining har potential att förbättra vårdkvaliten för patienter med låg tillgänglighet till vård, till exempel på grund av avstånd. I detta arbete representerades patienttexter med en Bag-of-Words modell, och klustrades med en k-means algoritm. Den slutgiltiga klustringsmodellen använde sig av 41 kluster, och de tio viktigaste orden för klustercentroider användes för att representera respektive kluster. Därefter genomfördes ett experiment för att se om och hur läkare blev behjälpta i sin diagnostiska process, om patienters texter presenterades med de tio orden från de kluster som texterna hörde till. Resultaten från experimentet var att orden hjälpte läkarna i de mer komplicerade patientfallen, och att klustringsalgoritmen skulle kunna användas för att ställa specifika följdfrågor till patienter.

In November 2016 a brand new and highly technological hospital called New Karolinska Solna opened in Stockholm. In connection with the planning of the hospital, new medical devices were procured, including a new infusion system that is now in use. Previously, each ward at the hospital had their own pumps and was responsible for updates and maintenance. Now, the hospital will instead have a floating pump system, which means that the hospital will own the pumps. The infusion pumps will be floating between the wards without being linked to a specific ward or department. The updates that were previously done when the need arose at the ward will now be a common process for the entire hospital. The aim of the project was to develop new guidelines for how the update process should be done on New Karolinska Solna's new infusion pump system. Through interviews with key personnel during the procurement process, the medical technicians department and caseworkers, new guidelines have been written, given the already existing technical conditions. During the course of the project it has been found that there are major shortcomings of information and communication within the hospital. The guidelines presented in the result are an important part to ensure that information related to the update comes to the caregivers at New Karolinska Solna, thus simplifying and streamlining the update of the infusion pumps.