New Methods for Motion Management During Radiation Therapy

In this thesis, a number of new image-based techniques for the management of intrafractional motion during radiation therapy are presented. Intra-fractional motion describes all kinds of anatomy changes - most prominently respiration - that occur during a single treatment session. Spatially confining the radiation dose to the tumour tissue and thus sparing surrounding healthy tissue is assumed to be crucial for a successful treatment with limited side effects. Unfortunately, the delivery of dose distributions that are sharply confined to the tumour is greatly complicated by patient motion. If not accounted for, this motion will lead to a smearing out of the original dose distribution and will facilitate the redistribution of dose from tumour to healthy tissue. Possible technical solutions for this issue include the interruption of the radiation delivery if the tumour leaves a predefined spatial ‘window’, and the reshaping of the treatment field ‘on-the-fly’ to follow the tumour. Regardless of which delivery techniques is selected, the patient motion needs to be reliably detected in real-time to allow for an adaptation of the treatment delivery. First, we present experimental results for a novel x-ray imaging system that is attached to the treatment delivery device and enables us to continuously monitor the tumour motion during treatment delivery with sub-mm accuracy, a latency better than 90 ms, and a 7 Hz update rate. Second, we present a Monte Carlo simulation for an improved amorphous-silicon flat-panel detector that reduced treatment beam filtration by 60% and long-range MV-scatter by 80%. We conclude this thesis by presenting results of an experimental demonstration of a novel dose-saving actively-triggered 4d cone-beam computed tomography device

Different Outcomes of Experimental Hepatitis E Virus Infection in Diverse Mouse Strains, Wistar Rats, and Rabbits

Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing countries, but autochthonous cases of zoonotic genotype 3 (HEV-3) infection also occur in industrialized countries. In contrast to swine, rats, and rabbits, natural HEV infections in mice have not yet been demonstrated. The pig represents a well-established large animal model for HEV-3 infection, but a suitable small animal model mimicking natural HEV-3 infection is currently missing. Therefore, we experimentally inoculated C57BL/6 mice (wild-type, IFNAR−/−, CD4−/−, CD8−/−) and BALB/c nude (nu/nu) mice, Wistar rats, and European rabbits with a wild boar-derived HEV-3 strain and monitored virus replication and shedding, as well as humoral immune responses. HEV RNA and anti-HEV antibodies were detected in one and two out of eight of the rats and all rabbits inoculated, respectively, but not in any of the mouse strains tested. Remarkably, immunosuppressive dexamethasone treatment of rats did not enhance their susceptibility to HEV infection. In rabbits, immunization with recombinant HEV-3 and ratHEV capsid proteins induced protection against HEV-3 challenge. In conclusion, the rabbit model for HEV-3 infection may serve as a suitable alternative to the non-human primate and swine models, and as an appropriate basis for vaccine evaluation studies

A Medicinal Herb Scutellaria lateriflora Inhibits PrP Replication in vitro and Delays the Onset of Prion Disease in Mice

Transmissible spongiform encephalopathies (TSE) are characterized by the misfolding of the host encoded prion protein (PrPC) into a pathogenic isoform (PrPSc) which leads to the accumulation of β-sheet-rich fibrils and subsequent loss of neurons and synaptic functions. Although many compounds have been identified which inhibit accumulation or dissolve fibrils and aggregates in vitro there is no therapeutic treatment to stop these progressive neurodegenerative diseases. Here we describe the effects of the traditional medicinal herb Scutellaria lateriflora (S. lateriflora) and its natural compounds, the flavonoids baicalein and baicalin, on the development of prion disease using in vitro and in vivo models. S. lateriflora extract as well as both constituents reduced the PrPres accumulation in scrapie-infected cell cultures and cell-free conversion assays and lead to the destabilization of pre-existing PrPSc fibrils. Moreover, tea prepared from S. lateriflora, prolonged significantly the incubation time of scrapie-infected mice upon oral treatment. Therefore S. lateriflora extracts as well as the individual compounds can be considered as promising candidates for the development of new therapeutic drugs against TSEs and other neurodegenerative diseases like Alzheimer’s and Parkinson’s disease

Upper Esophageal Sphincter Response to Laryngeal Adductor Reflex Elicitation in Humans

Objective: The laryngeal adductor reflex (LAR) is an important mechanism to secure the airways from potential foreign body aspiration. An involvement of the upper esophageal sphincter (UES) in terms of a laryngo-UES contractile reflex has been identified after laryngeal mucosa stimulation. However, the LAR–UES relationship has not yet been fully explained. This study aimed to determine the magnitude, latency, and occurrence rate of the UES pressure response when the LAR is triggered in order to elucidate the functional relationship between the larynx and the UES. Methods: This prospective study included seven healthy volunteers (5 female, 2 male, age 22–34 years). Laryngeal penetration was simulated by eliciting the LAR 20 times in each individual by applying water-based microdroplets onto the laryngeal mucosa. UES pressures were measured simultaneously using high-resolution manometry. Results: Two distinct pressure phases (P1, P2) associated with the LAR were identified. P1 corresponded with a short-term UES pressure decrease in two subjects and a pressure increase in five subjects occurring 200 to 500 ms after the stimulus. In P2, all subjects experienced an increase in UES pressure with a latency time of approximately 800 to 1700 ms and an average of 40 to 90 mmHg above the UES resting tone. Conclusion: Foreign bodies penetrating the laryngeal inlet lead to a reflex contraction of the UES. Phase P1 could be a result of vocal fold activity caused by the LAR, leading to pressure changes in the UES. The constriction during P2 could strengthen the barrier function of the UES in preparation to a subsequent cough that may be triggered to clear the airways. Level of Evidence: 4 Laryngoscope, 2020. © 2020 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA)

The Association of Relationship Status and Sex-Life Satisfaction With Body Dissatisfaction and Drive for Muscularity in Male Weight-Lifters

Relationship status and sexuality are linked to body image concerns, but research on the connection to men’s drive for muscularity (DfM) is scarce. Extreme DfM can lead to a pathological preoccupation with muscularity and problematic eating/exercising behavior. This study investigated the relation of relationship status, relationship duration, and satisfaction with sex-life in weight-lifting men via an online survey (N = 270). Using cross-sectional data, we found that single weight-lifting men and those dissatisfied with their sex-life were more dissatisfied with their muscularity and showed stronger DfM than those in a relationship and satisfied men. Longer relationship duration was associated with less dissatisfaction with muscularity and less DfM while relationship satisfaction was not. Thus, being in a relationship and sexual satisfaction are related to less body dissatisfaction and DfM. Further research should use dyadic study designs to investigate both partners exercising and eating behavior in relation to each other

An actuated larynx phantom for pre-clinical evaluation of droplet-based reflex-stimulating laryngoscopes

The laryngeal adductor reflex (LAR) is an important protective function of the larynx to prevent aspiration and potentially fatal aspiration pneumonia by rapidly closing the glottis. Recently, a novel method for targeted stimulation and evaluation of the LAR has been proposed to enable non-invasive and reproducible LAR performance grading and to extend the understanding of this reflexive mechanism. The method relies on the laryngoscopically controlled application of accelerated water droplets in association with a high-speed camera system for LAR stimulation site and reflex onset latency identification. Prototype laryngoscopes destined for this method require validation prior to extensive clinical trials. Furthermore, demonstrations using a realistic phantom could increase patient compliance in future clinical settings. For these purposes, a model of the human larynx including vocal fold actuation for LAR simulation was developed in this work. The combination of image processing based on a custom algorithm and individual motorization of each vocal fold enables spatio-temporal droplet impact detection and controlled vocal fold adduction. To simulate different LAR pathologies, the current implementation allows to individually adjust the reflex onset latency of the ipsi- and contralateral vocal fold with respect to the automatically detected impact location of the droplet as well as the maximum adduction angle of each vocal fold. An experimental study of the temporal offset between desired and observed LAR onset latency due to image processing was performed for three average droplet masses based on highspeed recordings of the phantom. Median offsets of 100, 120 and 128 ms were found (n=16). This offset most likely has a multifactorial cause (image processing delay, inertia of the mechanical components, droplet motion). The observed offset increased with increasing droplet mass, as fluid oscillations after impact may have been detected as motion. In future work, alternative methods for droplet impact detection could be explored and the observed offset could be used for compensation of this undesirable delay

Evidence for West Nile Virus and Usutu Virus Infections in Wild and Resident Birds in Germany, 2017 and 2018

Wild birds play an important role as reservoir hosts and vectors for zoonotic arboviruses and foster their spread. Usutu virus (USUV) has been circulating endemically in Germany since 2011, while West Nile virus (WNV) was first diagnosed in several bird species and horses in 2018. In 2017 and 2018, we screened 1709 live wild and zoo birds with real-time polymerase chain reaction and serological assays. Moreover, organ samples from bird carcasses submitted in 2017 were investigated. Overall, 57 blood samples of the live birds (2017 and 2018), and 100 organ samples of dead birds (2017) were positive for USUV-RNA, while no WNV-RNA-positive sample was found. Phylogenetic analysis revealed the first detection of USUV lineage Europe 2 in Germany and the spread of USUV lineages Europe 3 and Africa 3 towards Northern Germany. USUV antibody prevalence rates were high in Eastern Germany in both years. On the contrary, in Northern Germany, high seroprevalence rates were first detected in 2018, with the first emergence of USUV in this region. Interestingly, high WNV-specific neutralizing antibody titers were observed in resident and short-distance migratory birds in Eastern Germany in 2018, indicating the first signs of a local WNV circulation

Collaborative Assessment and Management of Suicidality (CAMS) compared to enhanced treatment as usual (E-TAU) for suicidal patients in an inpatient setting: study protocol for a randomized controlled trial

Santel M, Beblo T, Neuner F, et al. Collaborative Assessment and Management of Suicidality (CAMS) compared to enhanced treatment as usual (E-TAU) for suicidal patients in an inpatient setting: study protocol for a randomized controlled trial. BMC Psychiatry. 2020;20(1): 183.Background The Collaborative Assessment and Management of Suicidality (CAMS) is a therapeutic framework that has been shown to reduce suicidal ideation and overall symptom distress. CAMS has not been previously evaluated in a standard acute inpatient mental health care setting with only short treatment times for suicidal patients. In this randomized controlled trial (RCT) we are investigating whether CAMS is more effective than Enhanced-Treatment as Usual (E-TAU) in reducing suicidal thoughts as primary outcome variable. We are also investigating depressive symptoms, general symptom relief, and the quality of the therapeutic alliance as secondary outcomes. Methods/Design This RCT is designed as a single-center, two-armed, parallel group observer-blinded clinical effectiveness investigation. We are recruiting and randomizing 60 participants with different diagnoses, who are admitted as inpatients because of acute suicidal thoughts or behaviors into the Clinic for Psychiatry and Psychotherapy, Ev. Hospital Bethel in Bielefeld, Germany. The duration of treatment will vary depending on patients’ needs and clinical assessments ranging between 10 and 40 days. Patients are assessed four times, at admission, discharge, 1 month, and 5 months post-discharge. The primary outcome measure is the Beck Scale for Suicide Ideation. Other outcome measures are administered as assessment timepoints including severity of psychiatric symptoms, depression, reasons for living, and therapeutic relationship. Discussion This effectiveness study is being conducted on an acute ward in a psychiatric clinic where patients have multiple problems and diagnoses. Treatment is somewhat limited, and therapists have a large caseloads. The results of this study can thus be generalizable to a typical inpatient psychiatric hospital settings

Use of waveform lidar and hyperspectral sensors to assess selected spatial and structural patterns associated with recent and repeat disturbance and the abundance of sugar maple (Acer saccharum Marsh.) in a temperate mixed hardwood and conifer forest.

Abstract Waveform lidar imagery was acquired on September 26, 1999 over the Bartlett Experimental Forest (BEF) in New Hampshire (USA) using NASA\u27s Laser Vegetation Imaging Sensor (LVIS). This flight occurred 20 months after an ice storm damaged millions of hectares of forestland in northeastern North America. Lidar measurements of the amplitude and intensity of ground energy returns appeared to readily detect areas of moderate to severe ice storm damage associated with the worst damage. Southern through eastern aspects on side slopes were particularly susceptible to higher levels of damage, in large part overlapping tracts of forest that had suffered the highest levels of wind damage from the 1938 hurricane and containing the highest levels of sugar maple basal area and biomass. The levels of sugar maple abundance were determined through analysis of the 1997 Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) high resolution spectral imagery and inventory of USFS Northern Research Station field plots. We found a relationship between field measurements of stem volume losses and the LVIS metric of mean canopy height (r2 = 0.66; root mean square errors = 5.7 m3/ha, p \u3c 0.0001) in areas that had been subjected to moderate-to-severe ice storm damage, accurately documenting the short-term outcome of a single disturbance event