Postoperativ motion påskyndar läkeprocessen och därför uppmuntras patienter på Tema Cancer, Urologen, på Karolinska Universitetssjukhuset (KS) att motionera med hjälp av dagliga mål. För att följa upp träningen används en whiteboard som visar mål och framsteg, men verktygets otymplighet gör att de önskar en mer flexibel digital lösning. Målet med detta projekt var att åt KS utveckla en digital träningstavla som uppfyller samma funktion som whiteboarden men som är mer lätthanterlig. Mjukvara för att schemalägga övningar och registrera framsteg skrevs i Java och JavaFX för att köras på en Raspberry Pi 3 Model B kopplad till en pekskärm. En patient fick prova lösningen under ett par dygn i en kvalitativ studie. Både patienten och den ansvarige fysioterapeuten intervjuades och var nöjda med lösningen. / Postoperative exercise facilitates a faster rehabilitation process, therefore patients at Tema Cancer, Urologen, at Karolinska Universitetssjukhuset (KS) are encouraged to exercise using daily exercise routines. Currently, a whiteboard is used to track the goals and progress of a patient's daily exercises, but its unwieldiness makes KS yearn for a more flexible, digital solution. The aim of this project was to develop a digital exercise board for KS, which fulfills the same function as the whiteboard but will be easier to interact with. An exercise tracking software was developed in Java and JavaFX to run on a Raspberry Pi Model 3 B connected to a touchscreen. In a qualitative study, a patient used the digital solution for a couple of days. Both the patient who tried the solution, and the physiotherapist in charge of the patient, was interviewed and were satisfied with the solution.

Barn gastro- och nutritionsmottagningen på Astrid Lindgrens barnsjukhus använder i sitt dagliga arbete ett symtomformulär som besvaras av patienter och läkare vid varje läkarbesök. Då arbetet i samband med symtomformuläret idag är tidskrävande finns ett behov av en digital lösning i form av en applikation. För att eliminera det tidskrävande arbetet är det viktigt att applikationen är kopplad till journalsystemet TakeCare. I projektet har en applikation med tillhörande databas och server utvecklats. TakeCare har kontaktats för att svara på vilka möjligheter och krav som finns gällande att koppla applikationen till deras journalsystem. Det har även utförts en kartläggning av behovsbilden kring liknande lösningar på andra mottagningar. Resultatet visar att den framtagna applikationen måste vara CE-märkt, följa GDPR och patientdatalagen samt vara godkänd av TakeCare-förvaltningen för att få kopplas till journalsystemet. TakeCare kräver även information om hur applikationen ska förvaltas och finansieras. Genom framtida arbete kan fler krav komma att visa sig viktiga för att genomföra en sammankoppling. Kartläggningen visar att det finns ett större behov av liknande digitala lösningar inom vården vilket innebär att applikationen i framtiden kan komma att eliminera en tidskrävande process på fler mottagningar än barn gastro- och nutritionsmottagningen.

Owing to computer simulations, healthcare managers-and decision makers are more capable than ever to understand and evaluate the consequences of their decisions. In 2016, the Swedish government put forward ”Vision eHealth 2025”, emphasizing the importance of digitization within the healthcare system. This thesis aimed at studying the current demands regarding eHealth in Sweden, and what simulation architecture is capable of accurately simulating a digitized Swedish healthcare system. An extensive literature study was conducted, followed by an implementation phase, and finally a validation procedure. It was first concluded that the following three areas of eHealth applications would greatly benefit Swedish healthcare: a fully integrated journal system, systems for care consultations over the internet, and systems for tele-monitoring of chronics and the elderly. The fidelity of a provided first version of a simulation architecture was then examined, and potential areas for improvement were identified. The implementation phase subsequently included changes to the following aspects of the provided simulation platform: level of generality, the patient agent class (pHome), healthcare resources, illness dynamics & levels of care, workflow chart logic, optimization criteria, user-interface, and output variables. The validation procedure consisted of four interviews with professionals knowledgeable about the Swedish healthcare system, for which the developed simulation architecture was demonstrated. It was concluded that, while the level of detail required for a simulation platform to accurately model the consequences of decision making in a digitized Swedish healthcare system is not known, the developed simulation platform is currently not satisfactory. Above all, it lacks specificity in the output variables. / Tack vare datorsimuleringar kan beslutsfattare inom sjukv˚arden b¨attre ¨an n˚agonsin f¨orst˚a och utv¨ardera konsekvenserna av sina beslut. ˚Ar 2016 publicerade den svenska regeringen ”Vision eH¨alsa 2025”. Dokumentet betonade vikten av digitalisering inom sjukv˚arden. Det h¨ar examensarbetet syftar p˚a att studera de aktuella krav som finns inom eH¨alsa i Sverige, och ¨aven simuleringsarkitekturen n¨odv¨andig f¨or att sanningsenligt simulera ett digitaliserat svenskt sjukv˚ardssystem. En omfattande litteraturstudie genomf¨ordes, f¨oljt av en implementationsfas, och till sist en valideringsprocess. F¨orst drogs slutsatsen att f¨oljande tre omr˚aden av eH¨alsa skulle bidra med stor nytta till svensk sjukv˚ard: ett fullst¨andigt integrerat journalsystem, system f¨or v˚ardkonsultationer ¨over internet, och system f¨or tele¨overvakning av kroniker och ¨aldre patienter. Sedan unders¨oktes trov¨ardigheten av en f¨orsedd f¨orsta version av en simuleringsarkitektur, och dess potentiella omr˚aden f¨or f¨orb¨attringar identifierades. Den p˚af¨oljande implementationsfasen inkluderade modifieringar till f¨oljande aspekter av den f¨orsedda simuleringsplattformen: generalitetsniv˚a, patientagentklassen (pHome), sjukv˚ardsresurser, sjukdomsdynamik & olika niv˚aer av v˚ardleverans, logiken bakom arbetsfl¨odesdiagrammen, optimiseringskriterier, anv¨andargr¨anssnittet, och outputvariabler. Valideringsprocessen bestod av fyra intervjuer med professionela yrkesm¨an kunniga om det svenska sjukv˚ardssystemet. Simuleringsplattformen demonstrerades under alla fyra intervjuer. Slutsatsen drogs att detaljniv˚an hos den utvecklade simuleringsplattformen inte ¨ar tillr¨acklig i nul¨aget f¨or att utf¨ora korrekta simuleringar. Framf¨or allt saknar outputvariablerna specificitet. Det ¨ar fortfarande inte k¨ant vilken detaljniv˚a som skulle vara tillr¨acklig i det h¨ar avseendet.

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I dagens samhälle har spårbarhet av medicintekniska hjälpmedel fått en allt viktigare innebörd inom sjukvården. En anledning till det är att de flesta hjälpmedel klassas som medicintekniska produkter vilka enligt Socialstyrelsens föreskrifter måste kunna spåras. Därför märks många hjälpmedel med streckkoder eller liknande markörer. På Karolinska Universitetssjukhuset i Solna önskar man förbättra spårbarheten av rullstolar och få en bättre översikt över vilka som är utlånade och förskrivna. En metod för att lösa detta problem är genom att digitalisera flödesprocessen för rullstolar. I det här arbetet har ett digitalt program utvecklats för att ersätta ett antal steg i flödesprocessen som i nuläget hanteras manuellt med penna och papper. Genom att digitalisera delar av processen och se över möjligheter att implementera scanners kan informationen kvalitetssäkras och arbetet effektiviseras. Resultatet visar att ett sådant program som det som utvecklades skulle vara gynnsamt för sjukhuset och skulle bidra till en bättre kontroll över rullstolsflödet. I och med arbetet har en god grund lagts för att digitalisera hanteringen av hjälpmedel och utveckla processerna.

This licentiate thesis presents ubiquitous systems for human communication and awareness from the perspectives of improving our everyday life experiences and relieving our scarcest resource, ourselves. The thesis also presents different methods of designing such systems with the user needs in focus. The goal of this work is to construct systems which support the user with context-based information and functionality that simplifies the user's tasks. The applied nature of this thesis is indicated by the three prototypes, which has been developed and evaluated. The first prototype provided spectators of sport-events with added information about the contestants and hence improved the experience of the event. The second prototype supported nurses in elderly care with their tasks by making organization and information gathering less time consuming and thus leaving more time for talking to the patients. Finally, the third prototype realized a system for ubiquitous human communication. The third prototype utilizes an algorithm for selecting and using media resources in the environment. This algorithm decouples several difficult problems and can be used to combine leading research in different areas of awareness together to create accurate resource selection. The motivation for creating prototypes has been to get experience from using systems which empower users and to find methods for satisfying user needs. Involving users early in the design process can help satisfy user needs. Hence, it is important to find methods and strategies for involving users, especially as not everyone can see the opportunities a new technology has to offer. In this thesis four methods and strategies are described and tested. These are paper prototypes, wizard of oz studies, questionnaires and real prototypes which were developed and then evaluated. These methods are compared and some of the findings are being discussed in this thesis. The evaluation of the prototypes and the user-studies show that it is possible to improve everyday life experiences using a combination of ubiquitous, pervasive, wearable and context-aware computing. A majority of all the users who answered the questionnaire for the first prototype answered that the system improved their experience of the sport event. The nurses who used the second prototype were positively surprised over how the technology could save both time and create a better group awareness. Most of the users who participated in the user-study for the third prototype were positive to using a mix of media resources to get richer communication, they were also in favour of using resources in the environment to save money and improve quality. The main results in this thesis are valuable insights into user opinions of ubiquitous systems, methods for involving users in the design process, and several design rules which can serve as a guideline for designing future ubiquitous systems. / Godkänd; 2006; 20070109 (haneit)

Prostate cancer (PCa) is the most common male cancer in Europe and the US, and only lung and colorectal cancer have a higher mortality among European men. In Sweden, PCa is the most common cause of cancer-related death for men.The overall aim of this licentiate work was to explore the need for new and complementary methods for PCa detection and to take the first step towards a novel approach: combining Raman spectroscopy and resonance sensor technology. Firstly, the main methods for PCa detection were reviewed. Secondly, to establish a robust protocol for Raman experiments in vitro, the effects of snap-freezing and laser illumination on porcine prostate tissue were studied using Raman spectroscopy and multivariate statistics. Thirdly, measurements on pork belly tissue using both a resonance sensor and a Raman fiberoptic probe were evaluated regarding correlation of the data.It was concluded that the gold standard for PCa detection and diagnosis, the prostate specific antigen test and systematic biopsy, have low sensitivity and specificity. Indolent and aggressive tumors cannot be reliably differentiated, and many men are therefore treated either unnecessarily or too late. Clinical benefits of the state-of-the-art in PCa imaging - advanced ultrasound and MR techniques - have still not been convincingly shown. There is a need for complementary and cost-effective detection methods. Raman spectroscopy and resonance sensor technology are promising alternative techniques, but hitherto their potential for PCa detection have only been investigated in vitro.No evidence of tissue degradation due to 830 nm laser illumination at an irradiance of 3 1010 W/m2 were found. Snap-freezing and subsequent storage at -80◦C gave rise to subtle but significant changes in Raman spectra, most likely related to alterations in the protein structure. The major changes in cancerous prostate tissue do not seem to be related to the protein structure, hence snap-freezing may be applied.The combined measurements on pork belly tissue showed that Raman spectroscopy provided additional discriminatory power to the resonance sensor. The Raman data explained 67% of the variability of the stiffness parameter. The differentiation of tissue types using the resonance sensor was relatively poor, likely due to its large sample volume compared to the Raman sensor. A smaller resonance sensor tip may improve the results.In summary, this work indicates that an instrument combining Raman spectroscopy and resonance sensor technology is a promising complementary method for PCa detection. Snap-freezing of samples may be used in future Raman studies of PCa. A combined instrument could potentially be used to guide prostate biopsies towards lesions suspicious for cancer, and for tumor-border demarcation during surgery. All of this should provide a more secure diagnosis and consequently more efficient treatment of the patient.

A stroke is caused by interruption of the blood supply to the brain. Yearly 15 million people around the globe endure a stroke and the costs and suffering for the people involved and the society are immense. The aim of this thesis was to investigate the response to oxygen deprivation in neurons from the medial preoptic nucleus (MPN) that have a high abundance of neuroglobin. The long term goal is to investigate the neuroprotective role of the protein in relation to stroke. Initially, the electrophysiological response of neurons to hypoxic exposure in an open system was assessed with a conventional patch-clamp setup. The first aim was to see how well the conventional system worked and if it needed improvement. Secondly, the MPN had never been investigated regarding oxygen, deprivation; hence the electrophysiological response under hypoxia needed to be investigated. The conventional patch-clamp system only allowed a reduction of the oxygen content to a level of 3-6% but not total control of the cell environment. The medial preoptic neurons showed mainly an increase of their resting membrane potential at hypoxia. The voltage activated Ca2+ and K+ currents displayed a clear attenuation when cells were subjected to hypoxia. Non-L-type Ca2+ channels were affected by hypoxic exposure and one cell indicated participation of Ca2+ activated K+ channels. However, a response could only be seen in approximately fifty percent of the neurons in the open system. This may have been due to the fact that full control of the oxygen around the neurons at hypoxia could not be achieved. A new system with full control of the ambient oxygen had to be developed in order to investigate this. After the conclusions of the first experiments, a system was developed were a labon- a-chip system was combined with the patch-clamp technique. A microfluidic system with a patch-clamp micropipette integrated was combined with optical tweezers for 3D maneuvering of the neurons. The development of patch-clamp in combination with a microfluidic system and optical tweezers allowed for full oxygen control. The experiments showed that the electrophysiological measurements were not affected by the laser when an infrared laser was used. The microfluidic system allowed very good oxygen control reaching levels of 0.5-1.5 % compared to 3-6 % in the open system. In summary, this work suggests that high voltage activated Ca2+ channels, and K+ channels are involved in the hypoxic depolarization of medial preoptic neurons. Full control of ambient oxygen in cell vicinity could be achieved by the combination of microfluidics, patch-clamp and optical tweezers. The results can be used in future studies to better understand the reaction of the brain to oxygen deprivation caused by stroke.

Prostate cancer (PCa) is the most common cancer type among men in Sweden. The most prevalent curative treatment for PCa is radical prostatectomy (RP), i.e., complete surgical removal of the prostate. Unfortunately, cancer cells are found near the resection surface in 35 % of the RP patients. This indicates an increased risk of PCa reccurence.Our main objective is to develop a novel medical instrument for detecting PCa. The idea is to combine the techniques of Raman spectroscopy (RS) and the tactile resonance method (TRM) into one integrated instrument. The TRM would provide a swift and gentle survey of the region of interest, while the RS adds detailed information of the molecular content where malignancy is suspected. The dual mode instrument could be well suited for detecting and locating tumour cells in the surgical margin during RP. The studies included in this thesis are important steps towards this objective.Paper A investigated how the two data sets from each of the technologies could be compared and combined for tissue characterisation. The data set of RS was a spectrum with peaks characteristic to the sample's molecular content. The TRM output variable was a scalar value related to the sample stiness. The data sets could be compared and combined by applying principal component analysis (PCA) to the RS spectra followed by an hierarchical cluster analysis (HCA). A linear regression analysis showed that the PCs explained 67% of the stiffness variations. HCA was used to classify each RS measurement into groups consisting of similar measurements. The TRM's sensitivity and specificity of classifying these groups were evaluated by ROC curves and the area under the curve (AUC). The harder group could successfully be discriminated from the softer groups (AUC = 0.99).Paper B used support vector machines (SVM) as a method to classify and differentiate porcine and human prostate tissue types using the combined data sets. Prostate tissue is highly inhomogenous, with streaks of small anatomical structures. The analysis was evaluated within areas of three levels of homogenity, to avoid mismatching the measured tissue. The tissue homogenity was evaluated within the RS measurement area and the tissue type was set to the main histological content. Areas in which no single tissue type surpassed the threshold level were excluded from the analysis. The cross-validation accuracy for determining the tissues types within homogenous (main tissue type > 83%) porcine samples was 82% using TRM data alone. It increased to 87% while using the combined data sets of TRM and RS. For discerning healthy and cancerous human prostate tissue, the cross-validation accuracy was 67% and 77% for TRM alone versus TRM and RS combined.Paper C covered a number of design considerations which have to be addressed during the combination of TRM and RS. The effects of attaching an RS probe into a tubular TRM element were investigated. We investigated the temperature increase caused by the laser illumination from the RS and its eect on the TRM measurement parameter Δf. We also investigated if and how RS could be performed under ambient light. A thin RS probe and a small amount of rubber latex was preferable for attaching the RS probe inside the TRM sensor. The temperature rise of the TRM sensor due to a fibreoptic NIR-RS at 270 mWduring 20 s was less than 2ºC. The variation of Δf during a 5ºC temperature change was approximately 20 Hz. This is small compared to previous in vitro TRM studies. Fibre-optic NIR-RS was feasible in a dimmed bright environment using a small light shield and automatic subtraction of a pre-recorded contaminant spectrum. The results of these studies indicate how the hardware and and software could be combined into one integrated probe for prostate cancer detection.

Stroke affects around 20 million people around the world every year. Clinically, stroke is a result of brain damage due to the shortage of oxygen delivered to the nerve cells. To minimize suffering and costs related to the disease, extensive research is performed on different levels. The focus of our research is to achieve fundamental understanding on how the lack of oxygen in brain tissue activates intrinsic biomolecular defense mechanisms that may reduce brain damage. More knowledge may hopefully lead to new therapeutic and preventive strategies on the molecular level for individuals in the risk zone for stroke or those who have just suffered a stroke. The area of study is based on the discovery of a hemoprotein called neuroglobin (Ngb), which is found in various regions in the brain, in the islets of Langerhans, and in the retina. Several studies have shown that Ngb seems to have a protective function against hypoxia-related damage. However, until now, it has not been understood how Ngb affects the nerve system and protects neurons from damage. The well-established patch-clamp technique is routinely used to measure and analyze the electrophysiological activity of individual biological cells. To perform accurate patchclamp experiments, it is important to create well-controlled physiological conditions, i.e. different oxygen levels and fast changes of nutrients and other biochemical substances. A promising approach is to apply lab-on-a-chip technologies combined with optical manipulation techniques. These give optimal control over fast changing environmental conditions and enable multiple readouts. The conventional open patch-clamp configuration cannot provide adequate control of the oxygen content. Therefore, it was substituted by a gas-tight multifunctional microfluidic system, a lab-on-a-chip, with an integrated patch-clamp micropipette. The system was combined with optical tweezers and optical spectroscopy. Laser tweezers were used to optically guide and steer single cells towards the fixed micropipette. Optical spectroscopy was used to investigate the biochemical composition of the sample. The designed, closed lab-on-a-chip acted as a multifunctional system for simultaneous electrophysiological and spectroscopic experiments with good control over the oxygen content in the liquid perifusing the cells. The system was tested in a series of experiments: optically trapped human red blood cells were steered to the fixed patch-clamp pipette within the microfluidic system. The oxygen content within the microfluidic channels was measured to 1 % compared to the usual 4-7 %. The trapping dynamics were monitored in real-time while the spectroscopic measurements were performed simultaneously to acquire absorption spectra of the trapped cell under varying environments. To measure the effect of the optical tweezers on the sample, neurons from rats in a Petri dish were optically trapped and steered towards the patch-clamp micropipette where electrophysiological investigations were performed. The optical tweezers had no effect on the electrophysiological measurements. Similar investigations within a closed microfluidic system were initiated and showed promising results for further developments of a complete lab-on-a-chip multifunctional system for reliable patch-clamp measurements. The future aim is to perform complete protocols of patch-clamp electrophysiological investigations while simultaneously monitoring the biochemical composition of the sample by optical spectroscopy. The straightforwardness and stability of the microfluidic chip have shown excellent potential to enable high volume production of scalable microchips for various biomedical applications. The subsequent ambition is to use this system as a mini laboratory that has benefits in cell sorting, patch-clamp, and fertilization experiments where the gaseous and the biochemical content is of importance. The long-term goal is to study the response of individual neurons and defense mechanisms under hypoxic conditions that may establish new ways to understand cell behavior related to Ngb for various diseases such as stroke, Alzheimer’s and Parkinson’s.