| 1. |
- Mohammad, Salahuddin
(författare)
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Investigating mental health disorders in relation to job and living related factors
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Job satisfaction plays an important role for life quality and health of working individuals. While studies have shown that self-reported mental health conditions such as stress, anxiety and depression are associated with job satisfaction, a large population-based study exploring and comparing self-reported physician posed diagnosed conditions and their association with job satisfaction and job tenure is missing. First study addresses the gap along with exploring the impact of the neurotic personality trait and other possible contributing factors.Individuals with autism spectrum disorder (ASD) experience lower well-being as demonstrated epidemiologically mostly for children and adolescents. Further etiological investigation of inclusive wellbeing, in terms of five wellbeing spectrum (5-WBS) traits including neuroticism, depression, loneliness, life satisfaction and positive affect, among adults with ASD may deepen the understanding. Seond study aims to investigate if a genetic predisposition for ASD is associated with 5-WBS traits using polygenic risk score (PRS) analysis.In the first study, sixteen mental health disorders diagnosed by physicians, categorized into four major groups were investigated in relation to employment status (108,711 participants) and in relation to job satisfaction and job tenure (34,808 participants). Analyses were performed using linear regression adjusted for age, sex, TDI, BMI, education, physical activity, work hours and neuroticism. In the second study, PRS for ASD were constructed in the UK Biobank (N = 337,423), based on the GWAS conducted by Psychiatric Genetics Consortium (18,381 cases, 27,969 comparisons) using PRSice-2. First study showed Neurotic & Stress Disorders, Eating Disorders and Other Mental Health Disorders were strongly associated with lower job satisfaction and shorter job tenure in both unadjusted and adjusted analyses. Neuroticism was strongly linked to job satisfaction but was not associated with job tenure. Second study showed, ASD PRS significantly predicted associations with all 5-WBS traits, showing a positive association with the negative WBS traits, neuroticism (max R2 = 0.04%, P < 1x10-4, AUC 0.51), depression (max R2 = 0.06%, P < 1x10-4, AUC 0.51), loneliness (max R2 = 0.04%, P < 1x10-4, AUC 0.51) and a negative association with the positive WBS traits, life satisfaction (max R2 = 0.08%, P < 1x10-4, AUC 0.56), positive affect (max R2 = 0.10%, P < 1x10-4, AUC 0.53).Findings of first study clarify the complex relationship of mental health with job satisfaction and job tenure which is very important to understand in designing measures to improve working life participation of individuals with mental health issues. The findings of second study suggest that adults carrying a high load of susceptible SNPs for ASD are more likely to show a decreased well-being.
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| 2. |
- Vumma, Ravi
(författare)
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Functional Characterization of Tyrosine Transporters in fibroblast from Healthy Controls and Schizophrenic Patients
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cultured human fibroblasts offer an advantageous system to investigate the amino acid transport properties without confounding the affects of disease state and its treatment in many systemic psychiatric disorders. In previous studies, fibroblast cells have been used to investigate the tyrosine transport across plasma membranes in patients with schizophrenia and autism with out characterizing the particular amino acid transporters.The importance of the major tyrosine transporters (system-L and system-A) was investigated in this study. Systemic functional characterization of tyrosine transport in fibroblasts from healthy controls and patients with schizophrenia, with respect to the system-L isoforms (LAT1, LAT2, LAT3, and LAT4) was performed.Ten (n=10) fibroblast cell lines from healthy controls and ten (n=10) from patients with schizophrenia were included in this study. Transport and uptake of [14-C] L-tyrosine in fibroblasts was measured using the cluster tray method in the absence and presence of different specific inhibitors. The maximal transport capacity, Vmax and the affinity constant of the tyrosine-binding site, Km, of LAT1 isoform were determined.The results of this study showed that tyrosine transport in fibroblasts is facilitated mainly by the system-L and LAT1 isoform is involved in 90% of total tyrosine uptake. LAT2 isoform seems to be functionally weak in uptake of tyrosine, as not more than 3% could be contributed by it. LAT3 and LAT4 contributed around 7%. System-A (ATA2 isoform) contributed around 10%. Alanine consequently inhibited the tyrosine transport by up to 60%. Tyrosine uptake and kinetics did not differ between patients and controls at the LAT1 isoform. Moreover, the affinity of LAT1 isoform for tyrosine was higher when compared to system-L. LAT1 is also involved in around 51% of uptake of alanine.In conclusion, the present thesis, confirms the presence of system-L with its isoform LAT1 as a main transporter of tyrosine in human fibroblast cells. The competition between tyrosine and alanine to get transported is shown to probably exist mainly at LAT1 isoform. Aberrant tyrosine transport observed in previous studies in patients with schizophrenia is probably not linked to the LAT1 isoform. This study gave further importance and established fibroblast cells as a suitable experimental model for studying amino acid transport properties in humans.Key words: Fibroblasts, Tyrosine and alanine transport, System-L, LAT1, LAT2, LAT3, LAT4, Schizophrenia, Precursor of Dopamine.
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| 3. |
- Deyhle Jr, Richard
(författare)
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Cross-modal Imaging in Lung Research: From µCT dosimetry to synchrotron phase contrast microtomography biomechanical insights in preclinical lung injury models
- 2024
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lung diseases continue to present a large burden to public health, especially in industrialized countries. For abetter understanding of the underlying patho-mechanisms in lung related diseases as well as for testing theefficacy of novel therapies, preclinical studies in animal models are indispensable. The significance of preclinical X-ray based micro-computed tomography (µCT) research lies in its ability to provide high-resolution, non-invasive lung imaging of small animals as the air inside the lung acts as a natural contrast and to image the lung parenchyma longitudinally to assess functional and morphological alterations and test efficacy of therapeutic interventions. This often requires requires imaging protocols that balance between sufficient image quality and clinically relevant radiation absorbed doses. A reproducible method for evaluation of absorbed radiation absorbed doses is desirable. Absorbed radiation absorbed doses were measured in a polymethyl methacrylate (PMMA) phantom using standard TLD and a novel type of OSLD made form household salt. Four imaging protocols from MILabs “xUHR-µCT” scanner were tested. A large discrepancy was observed from results compared to vendor-provided values. The results indicate a need for thorough empirical dose measurements prior to performing longitudinal studies. Four-dimensional imaging, allows for investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. It is of significant interest to have direct visualization and quantification of interstitial lung diseases at spatial resolutions beyond the capabilities of clinical and conventional absorption-based only CT. Thus far, the high intensity of synchrotron X-ray light sources offer a tool to investigate dynamic morphological and mechanistic features, enabling dynamic in-vivo microscopy. This investigation elucidates the direct effects of interventions targeting the pathophysiology of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI) on the terminal airways and alveolar microstructure within intact lungs. In such conditions, the relationship between microscopic strain within the mechanics of the alveolar structure and the broader mechanical characteristics and viscoelastic properties of the lungs remains poorly understood. A time-resolved synchrotron phase-contrast micro-computed tomography imaging acquisition protocol based on the synchronization between the mechanical ventilation and the cardiac activity was used to resolve the lung parenchyma motion with an effective isotropic voxel size of 6 µm. Quantitative maps of microscopic local lung tissue strain within aerated lung alveolar tissue under protective mechanical ventilation in anesthetized rats were obtained. This approach was used to assess the effect of alterations in lung tissue biomechanics induced by lung injury at 7 days after single-dose, intratracheal bleomycin instillation in combination with short-term high-tidal volume (VT) mechanical ventilation. Overall, this work address the aspects of radiation exposure to in experimental imaging of small animals and lays a foundation for a more nuanced understanding of lung injury and mechanical ventilation. In the future, it may result in a more effective and less injurious respiratory support for patients with acute lung injury or chronic lung diseases.
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| 4. |
- Lendaro, Eva, 1989
(författare)
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On the use of Phantom Motor Execution for the treatment of Phantom Limb Pain
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Phantom limb pain (PLP) is a common complaint among amputees and despite having been studied for centuries, it remains a mysterious object of debate among researcher. To date, a vast number of ways to treat PLP has been proposed in the literature, however none of them has proven to be universally effective, thus creating uncertainty on how to operate clinically. The uncertainty is largely attributable to the scarcity of well conducted randomized controlled trials (RCTs) to prove the efficacy of PLP treatments. Phantom Motor Execution (PME) -exertion of voluntary phantom limb movements – aims at restoring the control over the phantom limb and the exercise of such control has been hypothesized to reverse neural changes implicated in PLP. Preliminary evidence supporting this hypothesis has been provided by clinical investigations on upper limb amputees. The main purpose of this Licentiate thesis was to enable a RCT on the use of PME for the treatment of PLP in order to provide robust and unbiased evidence for clinical practice. However, the implementation and kick-off of this clinical investigation required to complete few preparatory steps. For example, most amputees and PLP patients have lower limb amputation, thus PME needed to be adapted and validated for this population. Further, the RCT protocol needed to be carefully planned and made openly accessible, as per guidelines for conducting and publishing clinical RCT. Finally, a secondary aim of this thesis emerged with the need of providing long term relief from PLP to patient. Preliminary evidence seemed to indicate that in order to maintain pain relief, periodic rehearsal of the phantom motor skills acquired through PME is necessary. This raised the question of whether it is beneficial and possible to translate the technology from clinic to home use, question that was explored employing both quantitative and qualitative methods from engineering, medical anthropology, and user interface design. The work conducted within this thesis resulted in the extension of PME to lower limb patients by proposal and validation of a new and more user-friendly recording configuration to record EMG signals. The use of PME was then shown to be efficacious in relieving PLP with a case study on a patient. The protocol for the RCT was then designed and published. These two first steps permitted the establishment of the RCT, which is currently ongoing and expected to close in March 2021. With regard to the secondary aim of this thesis, the work conducted enabled PME to be used by the patients in the comfort of their home, while it also allowed investigate the benefits and challenges generally faced (not only by PME) in the transition from the clinic to home and its effects on treatment adherence. The work conducted is presented in the three appended publications. Future work includes the presentation of the results of the RCT. Further, having a way to modulate PLP is an incredibly useful tool to study the neural basis of PLP. By capitalizing on this tool, we are currently conducting brain imaging studies using fMRI and electroencephalography that are the main focus of the work that lies ahead.
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| 5. |
- Flyborg, Johan
(författare)
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The use of the intelligent powered toothbrush in health technology
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundApplied health technology is a research field that ties together several disciplines to improve and preserve the health and quality of life of individuals and society. Helping especially elderly to meet the above goals is an important and necessary task and assistive technology and collection of health data are part of this work.AimsPaper I aims to investigate whether the use of a powered toothbrush could maintain oral health in a group of individuals with MCI and if changes in oral health affect various aspects of quality of life. Paper II and III aims to examine the capacity of a powered toothbrush as a carrier and mediator of health-related data.MethodsFor papers I and II, the participants were recruited from the Swedish site of the multicenter project Support Monitoring And Reminder Technology for Mild Dementia and for paper III from the Department of Health at Blekinge Institute of Technology. In all three papers, a powered toothbrush has been used as a tool, sensor carrier and transmitter of data. For Quality-of-life assessment two instruments are used, The QoL-AD and OHIP 14.ResultsBy introducing an intelligent powered toothbrush in the group of older individuals with mild cognitive impairment we have showed that they, regardless of cognitive level,improved their scores for plaque index, bleeding index and deepened periodontal pockets ≥ 4mm, over 12 months. The quality-of-life instrument related to oral health improved in parallel with the improvement in oral health. Furthermore, it is possible to use the intelligent powered toothbrush both as a carrier for healt related sensors and to transfer user data via Bluetooth technology to a single-core processor that stores or forwards the data via Wifi to an external computer for processing, analysis and storage. A fesibility study regarding temperature sensor for measuring body temperature during toothbrushing have been evaluated and found to be comparable to traditional oral temperature measurement. ConclusionsAn intelligent powered toothbrush is a well-functioning tool for maintaining oral health in older people with mild cognitive impairment as well as for collecting and transferring brush and health data to external units for storage and analysis.
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| 6. |
- Wang, Chunliang, 1980-
(författare)
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Computer Assisted Coronary CT Angiography Analysis : Disease-centered Software Development
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The substantial advances of coronary CTA have resulted in a boost of use of this new technique in the last several years, which brings a big challenge to radiologists by the increasing number of exams and the large amount of data for each patient. The main goal of this study was to develop a computer tool to facilitate coronary CTA analysis by combining knowledge of medicine and image processing.Firstly, a competing fuzzy connectedness tree algorithm was developed to segment the coronary arteries and extract centerlines for each branch. The new algorithm, which is an extension of the “virtual contrast injection” method, preserves the low density soft tissue around the coronary, which reduces the possibility of introducing false positive stenoses during segmentation.Secondly, this algorithm was implemented in open source software in which multiple visualization techniques were integrated into an intuitive user interface to facilitate user interaction and provide good over¬views of the processing results. Considerable efforts were put on optimizing the computa¬tional speed of the algorithm to meet the clinical requirements.Thirdly, an automatic seeding method, that can automatically remove rib cage and recognize the aortic root, was introduced into the interactive segmentation workflow to further minimize the requirement of user interactivity during post-processing. The automatic procedure is carried out right after the images are received, which saves users time after they open the data. Vessel enhance¬ment and quantitative 2D vessel contour analysis are also included in this new version of the software. In our preliminary experience, visually accurate segmentation results of major branches have been achieved in 74 cases (42 cases reported in paper II and 32 cases in paper III) using our software with limited user interaction. On 128 branches of 32 patients, the average overlap between the centerline created in our software and the manually created reference standard was 96.0%. The average distance between them was 0.38 mm, lower than the mean voxel size. The automatic procedure ran for 3-5 min as a single-thread application in the background. Interactive processing took 3 min in average with the latest version of software. In conclusion, the presented software provides fast and automatic coron¬ary artery segmentation and visualization. The accuracy of the centerline tracking was found to be acceptable when compared to manually created centerlines.
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| 7. |
- de Lazzari, Mattia, 1996
(författare)
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Practical Implementation of Quality Assurance Guidelines for Hyperthermia Therapy
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hyperthermia therapy (HT) has been proven to be a potent enhancer of chemotherapy and radiotherapy in numerous clinical trials. The effectiveness of HT is strictly dependent on the administered thermal dose, which, in turn, is dependent on the quality of the therapeutic heat applied to the patient. Quality Assurance (QA) protocols in HT exist to ensure that heating devices can consistently deliver controlled, reproducible, and high-quality treatments. The physical characterization of HT devices requires specific procedures and instrumentation as well as adequate tissue-mimicking phantoms to perform QA experimental procedures. However, the implementation of QA guidelines is hampered due to the unavailability of suitable phantom materials and limited equipment for the QA experimental evaluation. This work addresses these gaps by (i) proposing the design of tissue-mimicking materials for routine use in HT QA procedures and (ii) demonstrating the practical implementation of the latest QA guidelines for both superficial and deep HT. A novel fat-mimicking material was developed to mimic superficial fatty tissue. This fat phantom is based on an ethylcellulose stabilized glycerol in oil emulsion and is intended to be used in superficial HT QA procedures. Measured dielectric and thermal properties were consistent with fatty tissue properties, with an acceptable variability in most of the frequency range used in HT. This fat-mimicking material was then used in the experimental implementation of HT guidelines. The physical characterization of a superficial HT device (Lucite Cone Applicator, LCA) was conducted by assessing the quality metrics defined in the HT guidelines, demonstrating acceptable performance. These findings were further validated through computational studies. For deep HT, a comparative study engaged six HT centers across Europe to assess the performance of commonly used deep regional heating devices. Preliminary results in experimental phantoms showed a good performance in terms of device heating capability and steerability. This study provided practical insights into implementing QA guidelines involving phantom properties, experimental setup, temperature acquisition, and time constraints. We are positive this research will benefit the routine implementation of deep HT guidelines in a clinical setting.
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| 8. |
- Adjeiwaah, Mary, 1980-
(författare)
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Quality assurance for magnetic resonance imaging (MRI) in radiotherapy
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic resonance imaging (MRI) utilizes the magnetic properties of tissues to generate image-forming signals. MRI has exquisite soft-tissue contrast and since tumors are mainly soft-tissues, it offers improved delineation of the target volume and nearby organs at risk. The proposed Magnetic Resonance-only Radiotherapy (MR-only RT) work flow allows for the use of MRI as the sole imaging modality in the radiotherapy (RT) treatment planning of cancer. There are, however, issues with geometric distortions inherent with MR image acquisition processes. These distortions result from imperfections in the main magnetic field, nonlinear gradients, as well as field disturbances introduced by the imaged object. In this thesis, we quantified the effect of system related and patient-induced susceptibility geometric distortions on dose distributions for prostate as well as head and neck cancers. Methods to mitigate these distortions were also studied.In Study I, mean worst system related residual distortions of 3.19, 2.52 and 2.08 mm at bandwidths (BW) of 122, 244 and 488 Hz/pixel up to a radial distance of 25 cm from a 3T PET/MR scanner was measured with a large field of view (FoV) phantom. Subsequently, we estimated maximum shifts of 5.8, 2.9 and 1.5 mm due to patient-induced susceptibility distortions. VMAT-optimized treatment plans initially performed on distorted CT (dCT) images and recalculated on real CT datasets resulted in a dose difference of less than 0.5%. The magnetic susceptibility differences at tissue-metallic,-air and -bone interfaces result in local B0 magnetic field inhomogeneities. The distortion shifts caused by these field inhomogeneities can be reduced by shimming. Study II aimed to investigate the use of shimming to improve the homogeneity of local B0 magnetic field which will be beneficial for radiotherapy applications. A shimming simulation based on spherical harmonics modeling was developed. The spinal cord, an organ at risk is surrounded by bone and in close proximity to the lungs may have high susceptibility differences. In this region, mean pixel shifts caused by local B0 field inhomogeneities were reduced from 3.47±1.22 mm to 1.35±0.44 mm and 0.99±0.30 mm using first and second order shimming respectively. This was for a bandwidth of 122 Hz/pixel and an in-plane voxel size of 1×1 mm2. Also examined in Study II as in Study I was the dosimetric effect of geometric distortions on 21 Head and Neck cancer treatment plans. The dose difference in D50 at the PTV between distorted CT and real CT plans was less than 1.0%.In conclusion, the effect of MR geometric distortions on dose plans was small. Generally, we found patient-induced susceptibility distortions were larger compared with residual system distortions at all delineated structures except the external contour. This information will be relevant when setting margins for treatment volumes and organs at risk. The current practice of characterizing MR geometric distortions utilizing spatial accuracy phantoms alone may not be enough for an MR-only radiotherapy workflow. Therefore, measures to mitigate patient-induced susceptibility effects in clinical practice such as patient-specific correction algorithms are needed to complement existing distortion reduction methods such as high acquisition bandwidth and shimming.
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| 9. |
- Rigato, Cristina, 1989
(författare)
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Direct Drive Bone Conduction Stimulation: Experimental Studies on Functionality and Transmission with Focus on the Bone Conduction Implant
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sound is conducted to the inner ear in two ways: by air and by bone. Air conduction (AC) hearing consists of sound waves entering the ear canal and reaching the cochlea, the main hearing organ, via the middle ear. In bone conduction (BC) hearing, instead, the transmission is through soft tissues and bone. These two pathways coexist and complement each other, although innormal hearing subjects the AC part is prevalent over the BC part in most of the ordinary hearing situations.BC hearing can represent an effective way to rehabilitate hearing impaired patients who would not benet from conventional AC hearing aids. This is the case when the hearing impairment is located in the outer or middle ear, or if the patients have chronic infections or malformations preventing them from wearing earmolds. The key idea in bone conduction devices (BCDs) isto generate vibrations with a transducer and transmit them via the skull bone to the inner ear.At present, the most common BCD is probably the bone anchored hearing aid (BAHA), consisting of a single-unit device attached to a skin penetrating screw in the parietal bone. To overcome the issues related to the skin penetration, the development of BCDs is recently focusing on so-called active transcutaneous devices, whose main feature is to have the bone transducer implanted under intact skin.In this thesis, the novel active transcutaneous bone conduction implant (BCI), currently in advanced clinical trial phase, was compared to BAHAs in terms of audiological tests and perceived rehabilitation effect. The outcomes showed that the BCI can be a valid alternative to BAHAs for indicated patients. Preliminary investigations were also performed on how the transmission of vibrations is affected by different ways of attaching the transducer to the skull bone. It was found that the relation varies substantially with frequency, with a general trend of improved transmission when the contact area between transducer and bone is limited.Finally, a new verication method of the implant functionality was evaluated intra- and post- operatively. The method, consisting in the measurement of the sound pressure in the nostril, seems promising and the implant to bone transmission was found stable over time.
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| 10. |
- Nie, Yali
(författare)
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Automatic Melanoma Diagnosis in Dermoscopic Imaging Base on Deep Learning System
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Melanoma is one of the deadliest forms of cancer. Unfortunately, its incidence rates have been increasing all over the world. One of the techniques used by dermatologists to diagnose melanomas is an imaging modality called dermoscopy. The skin lesion is inspected using a magnification device and a light source. This technique makes it possible for the dermatologist to observe subcutaneous structures that would be invisible otherwise. However, the use of dermoscopy is not straightforward, requiring years of practice. Moreover, the diagnosis is many times subjective and challenging to reproduce. Therefore, it is necessary to develop automatic methods that will help dermatologists provide more reliable diagnoses. Since this cancer is visible on the skin, it is potentially detectable at a very early stage when it is curable. Recent developments have converged to make fully automatic early melanoma detection a real possibility. First, the advent of dermoscopy has enabled a dramatic boost in the clinical diagnostic ability to the point that it can detect melanoma in the clinic at the earliest stages. This technology’s global adoption has allowed the accumulation of extensive collections of dermoscopy images. The development of advanced technologies in image processing and machine learning has given us the ability to distinguish malignant melanoma from the many benign mimics that require no biopsy. These new technologies should allow earlier detection of melanoma and reduce a large number of unnecessary and costly biopsy procedures. Although some of the new systems reported for these technologies have shown promise in preliminary trials, a widespread implementation must await further technical progress in accuracy and reproducibility. This thesis provides an overview of our deep learning (DL) based methods used in the diagnosis of melanoma in dermoscopy images. First, we introduce the background. Then, this paper gives a brief overview of the state-of-art article on melanoma interpret. After that, a review is provided on the deep learning models for melanoma image analysis and the main popular techniques to improve the diagnose performance. We also made a summary of our research results. Finally, we discuss the challenges and opportunities for automating melanocytic skin lesions’ diagnostic procedures. We end with an overview of a conclusion and directions for the following research plan.
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