Characterisation of a Novel Radiation Detector and Demonstration of a Novel Error Detection Algorithm for Application in Radiotherapy

Radiation detectors play an important role in radiology departments, particularly in relation to imaging and dosimetry. The significant advances achieved in material properties and high-quality electronic systems during previous decades has led to a continual expansion of their role and usage. In turn, this has had a concomitant impact upon the rapid progress of radiation detector technologies, specifically those utilised in medical imaging and dosimetry. This thesis aims to evaluate a radiation detector for a particular function, and to assess its suitability for said function within radiology and radiotherapy departments. Two novel radiation detectors, one for low energy imaging (kV) and another for radiotherapy (MV), are named Lassena (kV) and Lassena (MV) respectively. These detectors underwent an evaluation for the first time in order to assess their performance. Lassena (kV) was assessed in terms of image resolution and noise level to obtain the detective quantum efficiency (DQE) values representing image quality. DQE (0.5) values were 0.46-0.59 for three beam energies. Lassena (MV) was evaluated regarding its dosimetric properties, including linearity based on dose rate, reproducibility, and uniformity. Lassena (MV) has a high degree of short-term reproducibility, an acceptable pixel uniformity-response at high dose rates, and acceptable linearity with a coefficient of determination of 0.8624. Lassena (kV) displayed promising results whilst Lassena (MV) exhibited high sensitivity to radiation. A Monte Carlo system consisting of a linear accelerator and radiation detector was built and calibrated in order to assess dose verification applications within radiotherapy using a radiation detector. Anatomical changes during radiation therapy (such as parotid shrinkage and sinusitis for a nasopharyngeal case) were replicated. Analysis of computational EPID images started to warn of a risk of deviation from the planned dose at -26.3% volume loss of the parotid gland. This is most likely to happen in the third week of the treatment, however, the user must be aware of the limitations present due to anatomical overlapping and gamma analysis

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 341)

This bibliography lists 133 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during September 1990. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance

Olfaction, among the First Senses to Develop and Decline

Olfaction is one of the most conserved senses across species. It plays a crucial role in animals’ and humans’ life by influencing food intake, reproduction and social behavior. The olfactory system is composed of a peripheral neuroepithelium and a central olfactory nerve and is one of the few central nervous system (CNS) structures with direct access to the external environment without passage through the Blood Brain Barrier (BBB). This makes this nerve system of importance for understanding how exogenous stimuli may contribute to neuronal damage as well as for diagnostic and therapeutic purposes. Interestingly, olfactory activity physiologically declines with aging, but its alteration can be further impaired by various neurological conditions. For example, in progressive neurodegenerative disorders, such as Alzheimer’s disease (AD), olfaction is the first sense to be impaired before the onset of cognitive symptoms, suggesting that olfactory transmission may characterize early neural network imbalances. In this work, we will explore the main olfactory anatomical structures, the cytoarchitecture, the neurogenesis, several pathological conditions characterized by olfactory deficit and the potential use of this sense to diagnose and treat CNS pathologies

Development of laser spectroscopy for scattering media applications

Laser spectroscopy for both large and small spatial scales has been developed and used in various applications ranging from remote monitoring of atmospheric mercury in Spain to investigation of oxygen contents in wood, human sinuses, fruit, and pharmaceutical solids. Historically, the lidar group in Lund has performed many differential absorption lidar (DIAL) measurements with a mobile lidar system that was first described in 1987. During the years the lidar group has focused on fluorescence imaging and mercury measurements in the troposphere. Five lidar projects are described in this thesis: fluorescence imaging measurement outside Avignon, France, a unique lidar project at a mercury mine in Almadén, Spain, a SO2 flux measurement at a paper mill in Nymölla, Sweden, and two fluorescence imaging projects related to remote monitoring of vegetation and building facades characterization. A new method to measure wind speed remotely in combination with DIAL measurements is presented in this thesis. The wind sensor technique is called videography and is based on that images of plumes are grabbed continuously and the speed is estimated by the use of image processing. A technique that makes it possible to measure a gas in solids and turbid media, non-intrusively, is presented in this thesis. The technique is called gas in scattering media absorption spectroscopy (GASMAS) and has been used since 2001. The GASMAS concept means that a traditional spectroscopy instrument, based on tunable diode lasers, is used but the gas cell or optical path is replaced by a material that strongly scatters light. Mostly, wavelength modulation spectroscopy has been utilized. Four projects using the GASMAS technique to measure gases in fruit, wood, pharmaceutical solids, and human tissue are presented. Two applications have shown a great potential so far; to be able to diagnose the health of human sinuses and gas ventilation in sinuses, and to measure gas inside pharmaceutical solids. A performance analysis of the GASMAS technique is included. This thesis also presents a technique to suppress optical noise in fiber lasers and how to construct a compact tunable diode laser spectroscopy system based on plug-in boards for a standard computer

Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated protein CD79B

Pneumococcal interactions with the host : threats and therapeutic approaches

Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium responsible for substantial morbidity and mortality worldwide. Apart from causing severe pneumonia, septicemia or meningitis, pneumococci are also major contributors to less severe diseases like otitis media and sinusitis. Pneumococcal autolysis was thought to be the main route that S. pneumoniae utilizes in order to deliver its virulence factors. Recently a new mechanism has been proposed, the release of extracellular vesicles (EVs). Presence of adhesins and other virulence factors on EVs leads to cell responses after contact with vesicles. We observed that pneumococcal EVs are indeed a mechanism for the delivery of virulence factors to host cells, and that interactions of vesicles with dendritic cells lead to activation of cells and release of pro-inflammatory cytokines. Since EVs mimic the outside of a bacterium, they can play a role as decoys for the immune system. Tightly linked to this decoy function is the ability of EVs to promote immune evasion through binding of serum components. Indeed, we discovered that pneumococcal EVs are able to bind several components of the human complement system, leading to formation of the membrane attack complex on vesicles. Outer membrane vesicles (OMVs) released from Gram-negative bacteria have been directly used as vaccines in numerous preclinical mouse models. We isolated pneumococcal vesicles and found that they are able to confer serotype-independent protection in mice. Moreover, these vesicles stimulate the production of antibodies directed against pneumococcal antigens. These antibodies are able to increase opsonophagocytosis of pneumococci by mouse macrophages, and are required for protection, as demonstrated by the absence of protection in mice that are not able to produce B lymphocytes. Moreover, in our model the vesicles are able to protect mice against an infection with a pneumococcal strain of serotype 3, to a higher degree than what we observed for the currently available pneumococcal vaccine PCV13. The protective effect in humans of PCV13 against IPD caused by serotype 3 is debated. The structure of the pneumococcal capsule differs vastly between serotypes. We found that these differences have profound consequences in determining the disease progression in terms of pneumonia or septicemia, in mice. In particular, we observed that serotype 2 was quickly cleared from the lungs but migrated efficiently to the blood, while serotype 3 remained in the lungs, since the thick capsule made bacteria able to adhere less to cells and better avoid opsonization by the complement system. Fate of pneumococcal disease is tightly linked to the immune response against pneumococci. We found that a compound used in traditional Chinese medicine is able to potentiate the response of dendritic cells against pathogens, as well as increase the antimicrobial activities of host cells. Overall, the work in this thesis provides information on pneumococcal interactions with the host immune system and highlights the potential use of vesicles in future vaccination strategies

Combining Free Text and Structured Electronic Medical Record Entries to Detect Acute Respiratory Infections

The electronic medical record (EMR) contains a rich source of information that could be harnessed for epidemic surveillance. We asked if structured EMR data could be coupled with computerized processing of free-text clinical entries to enhance detection of acute respiratory infections (ARI).A manual review of EMR records related to 15,377 outpatient visits uncovered 280 reference cases of ARI. We used logistic regression with backward elimination to determine which among candidate structured EMR parameters (diagnostic codes, vital signs and orders for tests, imaging and medications) contributed to the detection of those reference cases. We also developed a computerized free-text search to identify clinical notes documenting at least two non-negated ARI symptoms. We then used heuristics to build case-detection algorithms that best combined the retained structured EMR parameters with the results of the text analysis.An adjusted grouping of diagnostic codes identified reference ARI patients with a sensitivity of 79%, a specificity of 96% and a positive predictive value (PPV) of 32%. Of the 21 additional structured clinical parameters considered, two contributed significantly to ARI detection: new prescriptions for cough remedies and elevations in body temperature to at least 38°C. Together with the diagnostic codes, these parameters increased detection sensitivity to 87%, but specificity and PPV declined to 95% and 25%, respectively. Adding text analysis increased sensitivity to 99%, but PPV dropped further to 14%. Algorithms that required satisfying both a query of structured EMR parameters as well as text analysis disclosed PPVs of 52-68% and retained sensitivities of 69-73%.Structured EMR parameters and free-text analyses can be combined into algorithms that can detect ARI cases with new levels of sensitivity or precision. These results highlight potential paths by which repurposed EMR information could facilitate the discovery of epidemics before they cause mass casualties

Could Proteomic Research Deliver the Next Generation of Treatments for Pneumococcal Meningitis?

Streptococcus pneumoniae is the most common bacterial cause of community-acquired meningitis worldwide. Despite optimal antibiotic therapy and supportive care, the mortality of this condition remains very high at 20–30% in the developed world and over 60% in under-resourced hospitals. In developed countries, approximately half of the survivors suffer intellectual impairment, hearing loss, or other neurological damage. There is an urgent need for more information about the mechanisms of brain damage and death in pneumococcal meningitis so that new treatments can be designed. Using proteomic techniques and bioinformatics, the protein content of cerebrospinal fluid can be examined in great detail. Animal models have added greatly to our knowledge of possible mechanisms and shown that hippocampal apoptosis and cortical necrosis are distinct mechanisms of neuronal death. The contribution of these pathways to human disease is unknown. Using proteomic techniques, neuronal death pathways could be described in CSF samples. This information could lead to the design of novel therapies to minimize brain damage and lower mortality. This minireview will summarize the known pathogenesis of meningitis, and current gaps in knowledge, that could be filled by proteomic analysis

Impact of acoustic airflow nebulization on intrasinus drug deposition of a human plastinated nasal cast: New insights into the mechanisms involved

International audienceThe impact of 100 Hz (Hertz) acoustic frequency airflow on sinus drug deposition of aerosols was investigated using a human plastinated nasal cast. The influence of drug concentration and endonasal anatomical features on the sinus deposition enhanced by the 100 Hz acoustic airflow was also examined. Plastinated models were anatomically, geometrically and aerodynamically validated (endoscopy, CT scans, acoustic rhinometry and rhinomanometry). Using the gentamicin as a marker, 286 experiments of aerosol deposition were performed. Changes of airborne particles metrology produced under different nebulization conditions (100 Hz acoustic airflow and gentamicin concentration) were also examined. Aerodynamic and geometric investigations highlighted a global behaviour of plastinated models in perfect accordance with a nasal decongested healthy subject. The results of intrasinus drug deposition clearly demonstrated that the aerosols can penetrate into the maxillary sinuses. The 100 Hz acoustic airflow led to increase the deposition of drug into the maxillary sinuses by a factor 2-3 depending on the nebulization conditions. A differential intrasinus deposition of active substance depending on maxillary ostium anatomical features and drug concentration was emphasized. The existence of a specific transport mechanism of penetration of nebulized particles delivered with acoustic airflow was proposed