<div>Sea turtles are integral components of many marine ecosystems. Green turtles (Chelonia mydas) are generally herbivorous, feed primarily on seagrasses, and are endangered in the Caribbean. The species utilizes extensive marine habitats for foraging and migratory routes, and because of its broad distribution, it is difficult to conduct population assessments. Here, I assessed commonly used techniques for monitoring green turtles in the wild. Specifically: (1) biopsy sampling for molecular assays and (2) unoccupied aerial vehicles (UAVs) deployment and boat-based surveys for population monitoring.</div><div><br></div><div>Skin biopsies are collected from sea turtles for a variety of molecular analyses; however, very little information exists on the natural healing rates at the site of the biopsy in the wild. In Chapter 2, I monitored the healing rates of 17 juvenile green turtles in Eleuthera, The Bahamas, for up to 488 d after taking a 6mm biopsy tissue sample. Complete tissue repair and maturation was observed after a year and a half, and there was no evidence of infection at any point during the healing process. While scarring persisted for several months, biopsy sampling had minimal long-term impact.</div><div><br></div><div>UAVs are increasingly being used to monitor marine megafauna. In Chapter 3, I evaluated the efficacy of using UAVs to detect sea turtles when compared to boat-based surveys. During UAV surveys, the UAV was flown along preprogrammed routes in four creek systems. A boat survey was conducted simultaneously on the same path. I used regression analyses for each survey type to assess the effects of environmental variables on turtle detection rates My results indicate that there were no statistically significant difference between the numbers of turtle detected via boat or UAV surveys; however, there were clear differences in the time and potential cost associated with either method.</div>

Cervical carcinoma is a major cause of morbidity and mortality among women worldwide. Histological subtype, lymphovascular space invasion and tumor grade could have a prognostic and predictive value for patients’ outcome and the knowledge of these histologic characteristics may influence clinical decision making. However, studies evaluating the diagnostic value of various biopsy techniques regarding these parameters of cervical cancer are scarce. We reviewed 318 cases of cervical carcinoma with available pathology reports from preoperative core needle biopsy (CNB) assessment and from final postoperative evaluation of the hysterectomy specimen. Setting the postoperative comprehensive pathological evaluation as reference, we analysed CNB assessment of histological tumor characteristics. In addition, we performed multivariable logistic regression to identify factors influencing the accuracy in identifying LVSI and tumor grade. CNB was highly accurate in discriminating histological subtype. Sensitivity and specificity were 98.8% and 89% for squamous cell carcinoma, 92.9% and 96.6% for adenocarcinoma, 33.3% and 100% in adenosquamous carcinoma respectively. Neuroendocrine carcinoma was always recognized correctly. The accuracy of the prediction of LVSI was 61.9% and was positively influenced by tumor size in preoperative magnetic resonance imaging and negatively influenced by strong peritumoral inflammation. High tumor grade (G3) was diagnosed accurately in 73.9% of cases and was influenced by histological tumor type. In conclusion, CNB is an accurate sampling technique for histological classification of cervical cancer and represents a reasonable alternative to other biopsy techniques.

Before major athletic events, a taper is often prescribed to facilitate recovery and enhance performance. However, it is unknown which taper model is most effective for peaking maximal strength and positively augmenting skeletal muscle. Thus, the purpose of this study was to compare performance outcomes and skeletal muscle adaptations following a step vs. an exponential taper in strength athletes. Sixteen powerlifters (24.0 ± 4.0 years, 174.4 ± 8.2 cm, 89.8 ± 21.4 kg) participated in a 6-week training program aimed at peaking maximal strength on back squat [initial 1-repetition-maximum (1RM): 174.7 ± 33.4 kg], bench press (118.5 ± 29.9 kg), and deadlift (189.9 ± 41.2 kg). Powerlifters were matched based on relative maximal strength, and randomly assigned to either (a) 1-week overreach and 1-week step taper or (b) 1-week overreach and 3-week exponential taper. Athletes were tested pre- and post-training on measures of body composition, jumping performance, isometric squat, and 1RM. Whole muscle size was assessed at the proximal, middle, and distal vastus lateralis using ultrasonography and microbiopsies at the middle vastus lateralis site. Muscle samples ( = 15) were analyzed for fiber size, fiber type [myosin-heavy chain (MHC)-I, -IIA, -IIX, hybrid-I/IIA] using whole muscle immunohistochemistry and single fiber dot blots, gene expression, and microRNA abundance. There were significant main time effects for 1RM squat ( < 0.001), bench press ( < 0.001), and deadlift, ( = 0.024), powerlifting total ( < 0.001), Wilks Score ( < 0.001), squat jump peak-power scaled to body mass ( = 0.001), body mass ( = 0.005), fat mass ( = 0.002), and fat mass index ( = 0.002). There were significant main time effects for medial whole muscle cross-sectional area (mCSA) ( = 0.006) and averaged sites ( < 0.001). There was also a significant interaction for MHC-IIA fiber cross-sectional area (fCSA) ( = 0.014) with comparisons revealing increases following the step-taper only ( = 0.002). There were significant main time effects for single-fiber MHC-I% ( = 0.015) and MHC-IIA% ( = 0.033), as well as for MyoD ( = 0.002), MyoG ( = 0.037), and miR-499a ( = 0.033). Overall, increases in whole mCSA, fCSA, MHC-IIA fCSA, and MHC transitions appeared to favor the step taper group. An overreach followed by a step taper appears to produce a myocellular environment that enhances skeletal muscle adaptations, whereas an exponential taper may favor neuromuscular performance.

<p> Volatile organic compounds (VOCs) are byproducts of metabolic processes that can be uniquely dysregulated by various medical conditions and are expressed in biological samples. Therefore, VOCs expressed in breath, urine and other sample types may be utilized for noninvasive, rapid, and accurate diagnostics in a point-of-care setting. Currently, the most common methods for VOC detection include gas chromatography-mass spectrometry (GC-MS) and electronic noses (E-noses) that integrate nanosensors. Both methods present important advantages and challenges that allow their implementation for different applications. While GC-MS can be used to directly identify VOCs in complex matrices, it is a non-portable and high-cost instrument. On the other hand, E-noses are portable and user-friendly VOC detectors, but they do not allow for direct VOC identification or quantification. Among different VOC rich sample types, breath offers the advantage of being a virtually limitless source of endogenous biomarkers that can be implemented for noninvasive VOC detection.</p> <p><br></p> <p>The presented thesis focuses on the optimization of the operating parameters (heater and sensor voltages) of a metal oxide (MOX) sensor and breath sampling techniques (sensor casing, breath fractionation, and exhalation volume) for their implementation in exhaled VOC analysis. In parallel, an in-house feature extraction algorithm was developed and implemented for the optimization of a MOX sensor composed of a tin oxide (SnO2) sensing layer. The optimized sensor parameters (heater voltage equal to 2 V and sensor voltage equal to 0.8 V) and breath sampling protocol (24 L of whole breath analyzed using the in-house sensor casing design) were tested with exhaled breath samples from distinct volunteers which could be successfully separated with 100% accuracy. The sensor response also showed a high degree of intrasubject reproducibility (RSD < 6%). Additionally, the sensor performance was further validated under ambient conditions, and sensor degradation was studied over the course of 3 months. Finally, sensor response to synthetic VOC profiles and individual VOC standards was explored. Optimized SnO2 sensors distinguished between VOC mixtures regardless of variations in relative humidity (RH) levels. Furthermore, the characteristic sensor response to VOC standards indicates that the sensors are most sensitive toward isopropanol by a factor of 1.15 in 45% RH and a factor of 3.58 in 85% RH relative to isoprene. </p> <p><br></p> <p>To translate the potential of MOX sensors to point-of-care biomedical applications, there first exists the need to establish a reference of sensor baseline signals corresponding to exhaled breath samples from healthy individuals. SnO2 sensors and breath sampling methods were implemented for the collection of individual samples from 109 relatively healthy volunteers. 10 of these volunteers provided 9 additional samples over the course of six months. In parallel, exhaled breath samples were also analyzed by GC-MS to comprehensively profile VOCs present in the samples. The results from these experiments not only aid in the identification of the healthy breath signal baseline but also allow the exploration of VOC reproducibility over time. High variation between samples from distinct volunteers was observed, but samples longitudinally collected across volunteers could not be distinguished, alluding to the existence of a universal range of sensor signals that could describe the composition of exhaled breath from healthy subjects. Finally, results were compared with relevant confounding variables to better understand how VOCs are impacted by an array of factors that are not directly correlated to disease diagnosis. Sensor signals were significantly elevated in breath samples from male volunteers compared to samples from female subjects (p-value = 0.044). Interestingly, isoprene signals resulting from the GC-MS analysis were also higher in male subjects relative to females. No other relationships were identified between sensor signals and the confounding variables of interest. </p> <p><br></p> <p>Future work would require a deeper understanding of sensor degradation and life cycle, along with sensor testing using a broader range of individual VOC standards and more complex VOC profiles. Additionally, further comparison between sensor signal and GC-MS signal of relevant VOC biomarkers present in breath would be beneficial. Nonetheless, the presented be leveraged in future investigations aiming to identify biomarkers for different medical conditions. Finally, the findings disclosed in the deposited thesis suggest the ability of a SnO2 nanosensor array to be implemented for breath analysis, providing a noninvasive, easy to use, and reliable diagnostic device in a point-of-care setting. </p>

Colonoscopy provides a minimally invasive tool for examining and treating the colon without surgery, but current endoscope designs still cause a degree of pain and injury to the colon wall. The most common colonoscopies are long tubes inserted through the rectum, with locomotion actuators, fiber optic lights, cameras, and biopsy tools on the distal end. The stiffness required to support these tools makes it difficult for the scopes to navigate the twisted path of the colon without damaging the inside wall of the colon or distorting its shape. In addition, little is known about how sharp and forceful endoscopes can be without accidentally cutting into tissue during navigation. In order to solve the requirements of stiffness (to support tools) and flexibility (to navigate turns), we expanded on a design by Zehel et al. [49], who proposed surrounding a flexible endoscope with an external exoskeleton structure, with controllable stiffness. The exoskeleton structure is comprised of rigid, articulating tubular units, which are stiffened or relaxed by four control cables. The stiffened or locked exoskeleton structure aids navigation and provides stability for the endoscope when it protrudes beyond the exoskeleton structure for examination and procedures. This research determined the design requirements of such an exoskeleton structure and simulated its behavior in a sigmoid colon model. To predict just how pointed an endoscope can be without damaging tissue under a given force, we extrapolated a strength model of the descending colon from published stress-strain curves of human colon tissue. Next we analyzed how friction, cable forces, and unit angles interact to hold the exoskeleton structure in a locked position. By creating two- and three-dimensional models of the exoskeleton structure, we optimized the dimensions of the units of an exoskeleton structure (diameter, thickness, and leg angle) and cable holders ( cable attachment location) to achieve the turns of the sigmoid colon, while still remaining lockable. Models also predicted the loss of force over the exoskeleton structure due to curving, further determining the required cable angles and friction between units. Finally we determined how the stiffness of the endoscope stem affected locking ability and wear inside the exoskeleton structure. / Ph. D.

Three-dimensional (3D) printing techniques for patient-individual medicine has found its way into veterinary neurosurgery. Because of the high accuracy of 3D printed specific neurosurgical navigation devices, it seems to be a safe and reliable option to use patient- individual constructions for sampling brain tissue. Due to the complexity and vulnerability of the brain a particularly precise and safe procedure is required. In a recent cadaver study a better accuracy for the 3D printed MRI-based patient individual stereotactic brain biopsy device for dogs is determined compared to the accuracies of other biopsy systems which are currently used in veterinary medicine. This case report describes the clinical use of this 3D printed MRI-based patient individual brain biopsy device for brain sampling in three dogs. The system was characterized by a simple handling. Furthermore, it was an effective and reliable tool to gain diagnostic brain biopsy samples in dogs with no significant side effects.

Background: Dogs with acquired chronic liver disease often have hemostatic derangements. It is currently unknown whether dogs with acquired chronic liver disease have decreased platelet function and alterations in von Willebrand factor (vWF) that may contribute to hemostatic abnormalities. Hypothesis: Dogs with chronic liver disease have prolonged platelet closure time (CT), assessed with the PFA-100®, and buccal mucosal bleeding time (BMBT), and increased vWF concentration compared to healthy dogs. Animals: Eighteen dogs with chronic acquired liver disease undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy and eighteen healthy age-matched control dogs. Methods: Prospective study. BMBT, CT using the PFA-100®, and vWF antigen were measured in dogs with chronic liver enzyme elevation undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy. After undergoing ultrasound-guided needle biopsy, dogs were monitored for hemorrhage with serial packed cell volume measurements and focused assessment with sonography. An unpaired t-test was used for normally distributed data and the Mann-Whitney test was used when non-Gaussian distribution was present. The level of significance was set at P <0.05. Results: The CT was not different between the two groups (P = 0.27). The BMBT was significantly longer in the liver disease group compared to the control group (P = 0.019). There was no difference in the mean vWF antigen of the two groups (P = 0.077). Conclusions and clinical relevance: These results demonstrate mild impairment of primary hemostasis in dogs with chronic liver disease based on prolongation of BMBT. / Master of Science / Background: Dogs with chronic liver disease often have abnormal blood clotting activity. It is currently unknown whether dogs with chronic liver disease have decreased platelet function and alterations in von Willebrand factor (vWF) that may contribute to blood clotting abnormalities. Platelet function can be assessed using the PFA-100®, which measures platelet closure time (CT), and buccal mucosal bleeding time (BMBT). The PFA-100 simulates blood in circulation to assess platelet function. BMBT is a crude but readily available test to assess platelet function in practices without sophisticated methods of assessing platelet function. Hypothesis: Dogs with chronic liver disease have prolonged CT and BMBT, which both suggest platelet dysfunction. Additionally, dogs with chronic liver disease have increased vWF concentration compared to healthy dogs. Animals: Eighteen dogs with chronic acquired liver disease undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy and eighteen healthy age-matched control dogs. Methods: Prospective study. BMBT, CT, and vWF antigen were measured in dogs with chronic liver disease undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy. After undergoing ultrasound-guided needle biopsy, dogs were monitored for hemorrhage. Results: The CT was not different between the two groups but the BMBT was significantly longer in the liver disease group compared to healthy dogs. There was no difference in the mean vWF antigen between the two groups. Conclusions and clinical relevance: These results demonstrate mild impairment of blood clotting activity in dogs with chronic liver disease based on prolongation of BMBT compared to healthy dogs. Prolongation of BMBT compared to healthy dogs is suggestive of endothelial dysfunction and/or platelet dysfunction in dogs with chronic liver disease.

<p dir="ltr">Human brain tumors present significant challenges due to their heterogeneous nature, known as intra-tumoral heterogeneity (ITH), which evolves over space and time, leading to treatment resistance and poor patient outcomes. Current diagnostic methods rely on pre-surgical imaging and single biopsy samples, providing only a partial understanding of the tumor microenvironment (TME) and often resulting in incomplete targeting of tumor mutations, leaving residual disease vulnerable to recurrence. Our hypothesis proposes a novel approach: utilizing multimodal and multiparametric <i>in vivo</i> imaging to map the cellular and molecular characteristics of the TME. By correlating imaging signatures with underlying somatic and genomic aberrations, we aim to develop a predictive model guiding personalized targeted therapies to effectively address the heterogeneity of brain tumors.</p><p dir="ltr">To achieve this goal, we designed, tested, and validated a predictive model through a pilot study using clinical MRI scans and one stereotactic biopsy sample. Subsequently, we optimized a multimodal and multiparametric imaging protocol including MRI and PET scans, to acquire comprehensive morphological, functional, and molecular data from the TME. Additionally, we established a detailed pipeline for subject recruitment, data collection, and post-processing to ensure the robustness and reliability of our model.</p><p dir="ltr">This innovative approach has the potential to overcome the limitations of current diagnostic methods by providing a comprehensive understanding of the TME using minimally-invasive imaging techniques. By correlating imaging data with ground truth pathology and genomics, this model will enhance brain tumor diagnosis and facilitate the implementation of targeted therapies, ultimately improving treatment response and patient outcomes.</p>

In the present study the cross sectional areas of individual muscle fibers were investigated with focus on statistical methodology. This thesis includes data from two studies; Resistance Study and Method Study. The Resistance Study analyzes the effect of exercise by comparing muscle fiber area before and after eight weeks of resistance training. Muscle biopsies from the vastus lateralis muscle were obtained from young male participants. The purpose of the Method Study was to examine the variation between right and left leg. Contrary to previous studies, this thesis focuses on individual data rather than on group-based data, and therefore takes a different approach than the previously published articles. This is proven to be successful since information is lost when analyzing group-wise, as the increase in small muscle fibers did not show when analyzing as a group. The results of the Resistance Study is similar to the results of the Method Study. Means and standard deviations have a wide spread both between subjects and between biopsies taken from the same subject. Inference on the 10th and 90th percentiles shows a positive pattern in the Resistance Study, in the sense that both the smallest and the largest muscle fibers have grown as a result of the resistance training. If muscle fiber area is used as a proxy for training effect, the conclusion is that many people seem to have responded well to the training.

The percutaneous biopsy is a critical intervention for diagnosis and staging in cancer therapy. Robotic systems can improve the efficiency and outcome of such procedures while alleviating stress for physicians and patients. However, the high complexity of operation and the limited possibilities for robotic integration in the operating room (OR) decrease user acceptance and the number of deployed robots. Collaborative systems and standardized device communication may provide approaches to overcome named problems. Derived from the IEEE 11073 SDC standard terminology of medical device systems, we designed and validated a medical robotic device system (MERODES) to access and control a collaborative setup of two KUKA robots for ultrasound-guided needle insertions. The system is based on a novel standard for service-oriented device connectivity and utilizes collaborative principles to enhance user experience. Implementing separated workflow applications allows for a flexible system setup and configuration. The system was validated in three separate test scenarios to measure accuracies for 1) co-registration, 2) needle target planning in a water bath and 3) in an abdominal phantom. The co-registration accuracy averaged 0.94 ± 0.42 mm. The positioning errors ranged from 0.86 ± 0.42 to 1.19 ± 0.70 mm in the water bath setup and from 1.69 ± 0.92 to 1.96 ± 0.86 mm in the phantom. The presented results serve as a proof-of-concept and add to the current state of the art to alleviate system deployment and fast configuration for percutaneous robotic interventions.