The bacterial cell wall is a nearly universal structure that offers protection and gives the cell its shape. However, environmental stressors, such as cell wall-targeting antibiotics and... Show moreThe bacterial cell wall is a nearly universal structure that offers protection and gives the cell its shape. However, environmental stressors, such as cell wall-targeting antibiotics and hyperosmotic conditions, can induce bacteria to shift to a wall-deficient state. It is unknown whether the lack of this cell wall ‘barrier’ can enable DNA exchange via horizontal gene transfer (HGT), a process that facilitates the spread of antibiotic resistance amongst bacteria. The research in this thesis confirms that wall-deficiency enables HGT in the actinobacterium Kitasatospora viridifaciens. Specifically, we show that wall-deficient L-forms take up extracellular material including DNA, sugar polymers and lipid nanoparticles via an endocytosis-like mechanism, which in case of DNA uptake leads to genetic transformation. Moreover, wall-less cells exchange genomic DNA in a DNAse-resistant manner, most likely via cell-cell fusion and/or production of extracellular vesicles. We also isolated vesicle-producing actinobacteria from a wastewater treatment plant, an environment that is considered a hotspot for the spread of antibiotic resistance genes. Lastly, growth of K. viridifaciens under hyperosmotic stress conditions leads to genetic instability, which together with HGT can contribute to enhanced genome plasticity. In summary, this thesis provides important insights into the consequences of bacterial cell wall-deficiency for HGT and evolution. Show less
After standard surgery for neck hernias, about 25% of patients report low satisfaction. This thesis applied inferential statistics to clinical data and Machine Learning to medical imaging, with the... Show moreAfter standard surgery for neck hernias, about 25% of patients report low satisfaction. This thesis applied inferential statistics to clinical data and Machine Learning to medical imaging, with the goal of finding out where differences in functional outcomes after surgery come from and how artificial intelligence can improve the diagnostic and prognostic process. The initial idea that differences in functional recovery were due to surgical technique was refuted by an RCT from this dissertation. The differences in functional recovery between three different surgical groups (removal of the intervertebral disc without artificial material, placement of intervertebral disc prosthesis, and fusion of vertebrae with a cage) were found to be minimal. It was striking that not surgical technique, but patients' mental health and preoperative, radiological imaging were found to be predictive of clinical recovery after surgery. Although the intervertebral disc prosthesis did not deliver on the promise of preserving mobility and thus could not prevent degeneration at adjacent levels, using Deep Learning based solely on the preoperative MRI of the neck, researchers were able to predict, among other things, which patients would require reoperation after surgery for that adjacent degeneration. The Deep Learning model did that significantly better than an experienced neuroradiologist and neurosurgeon. Such Deep Learning models eliminate the need for time-consuming questionnaires and are thus more cost-effective and less stressful for the patient, while they can be used to identify radiological features important for predicting the postoperative course. After validation with larger radiological datasets, these models can support clinical decision-making and help physicians develop personalized treatment strategies. Challenges within image analysis research for the spine lies in integrating different models into one automated process, preferably built into the electronic health record. Show less
PurposeAdding instrumented spondylodesis to decompression in symptomatic spinal stenosis with degenerative spondylolisthesis is subject of debate. The presence of spondylolisthesis due to... Show morePurposeAdding instrumented spondylodesis to decompression in symptomatic spinal stenosis with degenerative spondylolisthesis is subject of debate. The presence of spondylolisthesis due to degeneration is an indicator of severe facet joint and intervertebral disc degeneration, and this may fit increased instability of the spine. We aim to establish the incidence of degenerative spondylolisthesis in spinal stenosis surgical candidates and to evaluate the incidence of failure of decompressive surgery without concomitant spondylodesis as initial treatment.MethodsMedical files of all operated patients for spinal stenosis between 2007 and 2013 were evaluated. Demographic characteristics, pre-operative radiological characteristics (level of stenosis, presence, and grade of spondylolisthesis), surgical technique, incidence, and indication for reoperation were summarised, as well as the type of reoperation. Patient satisfaction was classified as 'satisfied' or 'unsatisfied' after initial and secondary surgery. The follow-up was 6 to 12 years.ResultsNine hundred thirty-four patients were included, and 253 (27%) had a spondylolisthesis. Seventeen percent of the spondylolisthesis patients receiving decompression were reoperated versus 12% of the stenosis patients (p=.059). Reoperation in the spondylolisthesis group concerned instrumented spondylodesis in 38 versus 10% in the stenosis group. The satisfaction percentage was comparable in the stenosis and the spondylolisthesis group two months after surgery (80 vs. 74%). Of the 253 spondylolisthesis patients, 1% initially received instrumented spondylodesis and 6% in a second operation.ConclusionLumbar stenosis with and without (low-grade) degenerative spondylolisthesis can usually effectively be treated with mere decompression. Instrumented surgery in a second surgical procedure does not lead to less satisfaction with surgical outcomes. Show less
BACKGROUND CONTEXT: Anterior cervical discectomy with an interbody cage (ACDF) to obtain fusion is a common procedure in cervical spine surgery. Presently, polyetheretherketone (PEEK) with (auto)... Show moreBACKGROUND CONTEXT: Anterior cervical discectomy with an interbody cage (ACDF) to obtain fusion is a common procedure in cervical spine surgery. Presently, polyetheretherketone (PEEK) with (auto) graft is frequently used for interbody fusion although alternative implant tech- nology like 3-D printing titanium has been introduced recently. PURPOSE: Reporting the clinical and quantitative radiological outcome of a prospective cohort of 3-D printed porous titanium implants. STUDY DESIGN/SETTING: Prospective study of patients with single level ACDF using 3-D printed porous titanium cervical implants. These data were compared with 48 patients from the PEEK with autograft group of the previously performed CAncellous Structured Ceramic Arthrode- sis DEvice trial. PATIENT SAMPLE: Fourty-nine patients were included. OUTCOME MEASURES: Neck disability index (NDI), visual analog scale (VAS), self -reported perceived recovery, and fusion status. METHODS: The clinical outcomes and fusion rates were documented at 3, 6, and 12 months. Dynamic X-rays were analyzed to determine range of motion (ROM) of the operated level. Fusion was defined as rotation <= 4 degrees and <= 1.25 mm translation on flexion -extension films. RESULTS: The mean NDI improved from 41.2 preoperatively to 19.4 at 12 months postopera- tively. Both VAS arm and VAS neck improved significantly after surgery and 77.1% of the patients reported complete or nearly complete recovery at 12 months. The mean ROM of the affected disc level decreased from 8.7 degrees (range 2.6 -21.4) before surgery to 1.6 degrees (0.0 -4.6 degrees) after 12 months. The fusion rate at 3, 6, and 12 months was 84%, 89%, and 91% respectively, compared with 67%, 72%, and 90%, in the PEEK group. CONCLUSIONS: 3-D printed porous titanium cervical implants resulted in significant clinical improvement after surgery. The fusion rate of porous titanium compared with PEEK with autograft at 12 months was similar, although porous titanium resulted in faster consolidation. In addition, one level anterior cervical fusion can be successfully achieved without additional plating. (c) 2020 Elsevier Inc. All rights reserved. Show less
This dissertation provides a novel perspective on the interaction between quantifier scope and ellipsis. It presents a detailed investigation of the scopal interaction between English negative... Show moreThis dissertation provides a novel perspective on the interaction between quantifier scope and ellipsis. It presents a detailed investigation of the scopal interaction between English negative indefinites, modals, and quantified phrases in ellipsis. One of the crucial observations is that a negative indefinite in object position cannot scope out of a verbal ellipsis site, while Quantifier Raising (QR) of a quantificational object can escape a verbal ellipsis site. This dissertation presents a unified account of this state of affairs in the context of multidominance. It is argued that both English negative indefinites and quantificational determiners decompose into two independent elements. Their formation is the result of a morphological process, Fusion Under Adjacency. The locality/adjacency required for fusion is established under remerge (multidominance), in combination with cyclic Spell-Out/linearization. The main claim of this dissertation is that the PF-process of ellipsis can block this morphological process. It is proposed that the timing of Fusion Under Adjacency and (derivational) ellipsis plays a crucial role: Fusion Under Adjacency has to take place before the ellipsis licensor is merged. The lack of a blocking effect of ellipsis in QR is accounted for by the fact that QR always has a landing site below the ellipsis licensor. In addition to providing an account for the scopal behavior of quantificational elements under ellipsis, this dissertation also sheds new light on the syntax-to-PF mapping. It contributes to our understanding of how multidominant phrase markers are transferred to PF for (non-)pronunciation in a cyclic model of the grammar. This study is of relevance to scholars interested in the nature of ellipsis and quantifier scope, and the syntax-PF connection, as well as to a general syntactic readership. Show less
