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1.
Osteoporos Int ; 33(3): 685-694, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34648040

ABSTRACT

Osteoporotic vertebral fractures signify an increased risk of future fractures and mortality and can manifest the diagnosis of osteoporosis. We investigated the prevalence of vertebral fractures in routine CT of patients with long-term hospital records. Three out of ten patients showed osteoporotic vertebral fractures (VFs) corresponding to the highest rates reported in European population-based studies. INTRODUCTION: VFs are a common manifestation of osteoporosis, which influences future fracture risk. Their epidemiology has been investigated in population-based studies. However, few studies report the prevalence of osteoporotic VF in patients seen in clinical routine and include all common fracture levels of the thoracolumbar spine. The purpose of this study was to investigate the prevalence of osteoporotic VF in patients with CT scans and long-term hospital records and identify clinical factors associated with prevalent VFs. METHODS: All patients aged 45 years and older with a CT scan and prior hospital record of at least 5 years that were seen in the study period between September 2008 and May 2017 were reviewed. Imaging requirements were a CT scan with sagittal reformations including at least T6-L4. Patients with multiple myeloma were excluded. Fracture reading was performed using the Genant semi-quantitative method. Medical notes were reviewed for established diagnoses of osteoporosis and clinical information. Clinical factors (e.g. drug intake, chemotherapy, and mobility level) associated with prevalent VF were identified in logistic regression. RESULTS: The study population consisted of 718 patients (228 women and 490 men; mean age 69.3 ± 10.1 years) with mainly cancer staging and angiography CT imaging. The overall prevalence of VFs was 30.5%, with non-significantly more men showing a fracture (32.5%) compared to women (26.3%; p > 0.05). Intake of metamizole for ≥ 3 months was significantly associated with a prevalent VF. Medical records did not include information about bone health in 90% of all patients. CT reports did mention a VF in only 24.7% of patients with a prevalent VF on CT review. CONCLUSION: Approximately 30% of elderly patients with CT imaging and long-term hospital records showed VFs. Only one-quarter of these patients had VFs mentioned in CT reports. Osteoporosis management could be improved by consequent reporting of VFs in CT, opportunistic bone density measurements, and early involvement of fracture liaison services.


Subject(s)
Osteoporotic Fractures , Spinal Fractures , Aged , Bone Density , Female , Hospital Records , Humans , Male , Middle Aged , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/etiology , Spinal Fractures/diagnostic imaging , Spinal Fractures/epidemiology , Spinal Fractures/etiology , Spine , Tomography, X-Ray Computed
2.
Eur J Nucl Med Mol Imaging ; 48(13): 4445-4455, 2021 12.
Article in English | MEDLINE | ID: mdl-34173008

ABSTRACT

PURPOSE: To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma. MATERIAL AND METHODS: At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier's performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments. RESULTS: In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77-0.93 (sensitivity 0.91, 95% CI 0.81-0.97; specificity 0.71, 95% CI 0.44-0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72-0.9), 0.81 for [18F]-FET-PET (95% CI 0.7-0.89), and 0.81 for expert consensus (95% CI 0.7-0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities. CONCLUSION: Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas.


Subject(s)
Brain Neoplasms , Glioma , Multiparametric Magnetic Resonance Imaging , Amides , Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Humans , Magnetic Resonance Imaging , Perfusion , Positron-Emission Tomography , Protons , Retrospective Studies , Tyrosine
3.
Anim Genet ; 52(2): 155-170, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33544919

ABSTRACT

ROHs are long stretches of DNA homozygous at each polymorphic position. The proportion of genome covered by ROHs and their length are indicators of the level and origin of inbreeding. Frequent common ROHs within the same population define ROH islands and indicate hotspots of selection. In this work, we investigated ROHs in a total of 1131 pigs from 20 European local pig breeds and in three cosmopolitan breeds, genotyped with the GGP Porcine HD Genomic Profiler. plink software was used to identify ROHs. Size classes and genomic inbreeding parameters were evaluated. ROH islands were defined by evaluating different thresholds of homozygous SNP frequency. A functional overview of breed-specific ROH islands was obtained via over-representation analyses of GO biological processes. Mora Romagnola and Turopolje breeds had the largest proportions of genome covered with ROH (~1003 and ~955 Mb respectively), whereas Nero Siciliano and Sarda breeds had the lowest proportions (~207 and 247 Mb respectively). The highest proportion of long ROH (>16 Mb) was in Apulo-Calabrese, Mora Romagnola and Casertana. The largest number of ROH islands was identified in the Italian Landrace (n = 32), Cinta Senese (n = 26) and Lithuanian White Old Type (n = 22) breeds. Several ROH islands were in regions encompassing genes known to affect morphological traits. Comparative ROH structure analysis among breeds indicated the similar genetic structure of local breeds across Europe. This study contributed to understanding of the genetic history of the investigated pig breeds and provided information to manage these pig genetic resources.


Subject(s)
Inbreeding , Sus scrofa/genetics , Animals , Europe , Genome , Genotype , Homozygote , Polymorphism, Single Nucleotide , Population Density
4.
Eur J Nucl Med Mol Imaging ; 47(6): 1468-1475, 2020 06.
Article in English | MEDLINE | ID: mdl-31953672

ABSTRACT

PURPOSE: Imaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer-weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas. METHODS: Preoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging. RESULTS: In glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw-HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET. CONCLUSIONS: We found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.


Subject(s)
Brain Neoplasms , Glioma , Amides , Amino Acids , Biology , Brain Neoplasms/diagnostic imaging , Glioma/diagnostic imaging , Humans , Magnetic Resonance Imaging , Perfusion , Positron-Emission Tomography , Protons , Tyrosine
5.
Eur J Neurol ; 27(11): 2217-2224, 2020 11.
Article in English | MEDLINE | ID: mdl-32589804

ABSTRACT

BACKGROUND AND PURPOSE: Individuals with radiologically isolated syndrome (RIS) are at increased risk of converting to multiple sclerosis (MS). Early identification of later converters is crucial for optimal treatment decisions. The purpose of this study was to assess the predictive potential of optical coherence tomography (OCT) measures in individuals with RIS regarding conversion to MS. METHODS: This prospective observational cohort study included 36 individuals with RIS and 36 healthy controls recruited from two German MS centers. All individuals received baseline OCT and clinical examination and were longitudinally followed over up to 6 years. The primary outcome measure was the conversion to MS. RESULTS: During clinical follow-up of 46 (26-58) months (median, 25%-75% interquartile range), eight individuals with RIS converted to MS. Individuals converting to MS showed a thinning of the peripapillary retinal nerve fiber layer (pRNFL) and the common ganglion cell and inner plexiform layer (GCIP) at baseline and during follow-up. Individuals with a pRNFL of 99 µm or lower or a GCIP of 1.99 mm3 or lower were at a 7.5- and 8.0-fold risk for MS conversion, respectively, compared to individuals with higher measures. After correction for other known risk factors, Cox proportional hazards regression revealed a hazard ratio of 1.08 for conversion to MS for each 1 µm decline in pRNFL. CONCLUSIONS: Reduction of the pRNFL might be a novel and independent risk factor for conversion to MS in individuals with RIS. OCT might be useful for risk stratification and therapeutic decision-making in individuals with RIS.


Subject(s)
Demyelinating Diseases , Multiple Sclerosis , Demyelinating Diseases/diagnostic imaging , Humans , Multiple Sclerosis/diagnostic imaging , Prospective Studies , Retina/diagnostic imaging , Tomography, Optical Coherence
6.
Anim Genet ; 51(4): 541-556, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32510676

ABSTRACT

In this study, we identified copy number variants (CNVs) in 19 European autochthonous pig breeds and in two commercial breeds (Italian Large White and Italian Duroc) that represent important genetic resources for this species. The genome of 725 pigs was sequenced using a breed-specific DNA pooling approach (30-35 animals per pool) obtaining an average depth per pool of 42×. This approach maximised CNV discovery as well as the related copy number states characterising, on average, the analysed breeds. By mining more than 17.5 billion reads, we identified a total of 9592 CNVs (~683 CNVs per breed) and 3710 CNV regions (CNVRs; 1.15% of the reference pig genome), with an average of 77 CNVRs per breed that were considered as private. A few CNVRs were analysed in more detail, together with other information derived from sequencing data. For example, the CNVR encompassing the KIT gene was associated with coat colour phenotypes in the analysed breeds, confirming the role of the multiple copies in determining breed-specific coat colours. The CNVR covering the MSRB3 gene was associated with ear size in most breeds. The CNVRs affecting the ELOVL6 and ZNF622 genes were private features observed in the Lithuanian Indigenous Wattle and in the Turopolje pig breeds respectively. Overall, the genome variability unravelled here can explain part of the genetic diversity among breeds and might contribute to explain their origin, history and adaptation to a variety of production systems.


Subject(s)
DNA Copy Number Variations , DNA/genetics , Sus scrofa/genetics , Animals , Breeding , Female , Italy , Male , Phenotype , Species Specificity , Whole Genome Sequencing/veterinary
7.
Osteoporos Int ; 30(6): 1275-1285, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30830261

ABSTRACT

Our study proposed an automatic pipeline for opportunistic osteoporosis screening using 3D texture features and regional vBMD using multi-detector CT images. A combination of different local and global texture features outperformed the global vBMD and showed high discriminative power to identify patients with vertebral fractures. INTRODUCTION: Many patients at risk for osteoporosis undergo computed tomography (CT) scans, usable for opportunistic (non-dedicated) screening. We compared the performance of global volumetric bone mineral density (vBMD) with a random forest classifier based on regional vBMD and 3D texture features to separate patients with and without osteoporotic fractures. METHODS: In total, 154 patients (mean age 64 ± 8.5, male; n = 103) were included in this retrospective single-center analysis, who underwent contrast-enhanced CT for other reasons than osteoporosis screening. Patients were dichotomized regarding prevalent vertebral osteoporotic fractures (noFX, n = 101; FX, n = 53). Vertebral bodies were automatically segmented, and trabecular vBMD was calculated with a dedicated phantom. For 3D texture analysis, we extracted gray-level co-occurrence matrix Haralick features (HAR), histogram of gradients (HoG), local binary patterns (LBP), and wavelets (WL). Fractured vertebrae were excluded for texture-feature and vBMD data extraction. The performance to identify patients with prevalent osteoporotic vertebral fractures was evaluated in a fourfold cross-validation. RESULTS: The random forest classifier showed a high discriminatory power (AUC = 0.88). Parameters of all vertebral levels significantly contributed to this classification. Importantly, the AUC of the proposed algorithm was significantly higher than that of volumetric global BMD alone (AUC = 0.64). CONCLUSION: The presented classifier combining 3D texture features and regional vBMD including the complete thoracolumbar spine showed high discriminatory power to identify patients with vertebral fractures and had a better diagnostic performance than vBMD alone.


Subject(s)
Osteoporosis/diagnostic imaging , Osteoporotic Fractures/diagnostic imaging , Spinal Fractures/diagnostic imaging , Aged , Algorithms , Bone Density/physiology , Feasibility Studies , Female , Humans , Imaging, Three-Dimensional/methods , Incidental Findings , Male , Mass Screening/methods , Middle Aged , Osteoporosis/physiopathology , Osteoporotic Fractures/physiopathology , Radiographic Image Interpretation, Computer-Assisted/methods , Retrospective Studies , Spinal Fractures/physiopathology , Tomography, X-Ray Computed/methods
8.
Osteoporos Int ; 30(6): 1265-1274, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30903208

ABSTRACT

This feasibility study investigated the spatial heterogeneity of the lumbar vertebral bone marrow using chemical shift encoding-based water-fat MRI. Acquired texture features like contrast and dissimilarity allowed for differentiation of pre- and postmenopausal women and may serve as imaging biomarkers in the future. INTRODUCTION: While the vertebral bone marrow fat using chemical shift encoding water-fat magnetic resonance imaging (MRI) has been extensively studied, its spatial heterogeneity has not been analyzed yet. Therefore, this feasibility study investigated the spatial heterogeneity of the lumbar vertebral bone marrow by using texture analysis in proton density fat fraction (PDFF) maps. METHODS: Forty-one healthy pre- and postmenopausal women were recruited for this study (premenopausal (n = 15) 30 ± 7 years, postmenopausal (n = 26) 65 ± 7 years). An eight-echo 3D spoiled gradient echo sequence was used for chemical shift encoding-based water-fat separation at the lumbar spine. Vertebral bodies L1 to L5 were manually segmented. Mean PDFF values and texture features were extracted at each vertebral level, namely variance, skewness, and kurtosis, using statistical moments and second-order features (energy, contrast, correlation, homogeneity, dissimilarity, entropy, variance, and sum average). Parameters were compared between pre- and postmenopausal women and vertebral levels. RESULTS: PDFF was significantly higher in post- than in premenopausal women (49.37 ± 8.14% versus 27.76 ± 7.30%, p < 0.05). Furthermore, PDFF increased from L1 to L5 (L1 37.93 ± 12.85%, L2 38.81 ± 12.77%, L3 40.23 ± 12.72%, L4 42.80 ± 13.27%, L5 45.21 ± 14.55%, p < 0.05). Bone marrow heterogeneity based on texture analysis was significantly (p < 0.05) increased in postmenopausal women. Contrast and dissimilarity performed best in differentiating pre- and postmenopausal women (AUC = 0.97 and 0.96, respectively), not significantly different compared with PDFF (AUC = 0.97). CONCLUSION: Conclusively, an increased bone marrow heterogeneity could be observed in postmenopausal women. In the future, texture parameters might provide additional information to detect and monitor vertebral bone marrow alterations due to aging or hormonal changes beyond conventional anatomic imaging.


Subject(s)
Bone Marrow/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Adipose Tissue/diagnostic imaging , Adult , Aged , Body Water/diagnostic imaging , Feasibility Studies , Female , Humans , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Middle Aged , Osteoporosis, Postmenopausal/diagnostic imaging , Postmenopause , Premenopause
9.
Osteoporos Int ; 29(12): 2685-2692, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30143850

ABSTRACT

This study investigates the impact of tube current reduction and sparse sampling on femoral bone mineral density (BMD) measurements derived from multi-detector computed tomography (MDCT). The application of sparse sampling led to robust and clinically acceptable BMD measurements. In contrast, BMD measurements derived from MDCT with virtually reduced tube currents showed a considerable increase when compared to original data. INTRODUCTION: The study aims to evaluate the effects of radiation dose reduction by using virtual reduction of tube current or sparse sampling combined with standard filtered back projection (FBP) and statistical iterative reconstruction (SIR) on femoral bone mineral density (BMD) measurements derived from multi-detector computed tomography (MDCT). METHODS: In routine MDCT scans of 41 subjects (65.9% men; age 69.3 ± 10.1 years), reduced radiation doses were simulated by lowering tube currents and applying sparse sampling (50, 25, and 10% of the original tube current and projections, respectively). Images were reconstructed using FBP and SIR. BMD values were assessed in the femoral neck and compared between the different dose levels, numbers of projections, and image reconstruction approaches. RESULTS: Compared to full-dose MDCT, virtual lowering of the tube current by applying our simulation algorithm resulted in increases in BMD values for both FBP (up to a relative change of 32.5%) and SIR (up to a relative change of 32.3%). In contrast, the application of sparse sampling with a reduction down to 10% of projections showed robust BMD values, with clinically acceptable relative changes of up to 0.5% (FBP) and 0.7% (SIR). CONCLUSIONS: Our simulations, which still require clinical validation, indicate that reductions down to ultra-low tube currents have a significant impact on MDCT-based femoral BMD measurements. In contrast, the application of sparse-sampled MDCT seems a promising future clinical option that may enable a significant reduction of the radiation dose without considerable changes of BMD values.


Subject(s)
Bone Density/physiology , Femur Neck/diagnostic imaging , Femur Neck/physiopathology , Tomography, X-Ray Computed/methods , Aged , Aged, 80 and over , Algorithms , Electricity , Female , Follow-Up Studies , Humans , Male , Middle Aged , Radiation Dosage , Radiographic Image Interpretation, Computer-Assisted/methods , Reproducibility of Results , Retrospective Studies
10.
Insect Mol Biol ; 26(2): 152-163, 2017 04.
Article in English | MEDLINE | ID: mdl-27869336

ABSTRACT

The development of insecticide resistance in insect pests of crops is a growing threat to sustainable food production, and strategies that slow the development of resistance are therefore urgently required. The insecticide synergist piperonyl butoxide (PBO) inhibits certain insect detoxification systems and so may delay the evolution of metabolic resistance. In the current study we characterized resistance development in the silverleaf whitefly, Bemisia tabaci, after selection with either a neonicotinoid (thiacloprid) or pyrethroid (alpha-cypermethrin) insecticide alone or in combination with PBO. Resistance development was significantly suppressed (> 60%) in the line selected with alpha-cypermethrin + PBO compared to the line selected with alpha-cypermethrin alone. RNA sequencing (RNAseq) analyses revealed an increase in frequency of a knock-down resistance mutation but no differentially expressed genes were identified that could explain the sensitivity shift. No significant difference was observed in the level of resistance between the thiacloprid and thiacloprid + PBO selected lines, and RNA sequencing (RNAseq) analyses revealed that the cytochrome P450 monooxygenase CYP6CM1, known to metabolize neonicotinoids, was significantly upregulated (>10-fold) in both lines. The findings of this study demonstrate that PBO used in combination with certain insecticides can suppress the development of resistance in a laboratory setting; however, the mechanism by which PBO supresses resistance development remains unclear.


Subject(s)
Hemiptera/drug effects , Insecticides , Pesticide Synergists/pharmacology , Piperonyl Butoxide/pharmacology , Pyrethrins , Animals , Evolution, Molecular , Gene Expression Profiling , Genotyping Techniques , Hemiptera/genetics , Hemiptera/metabolism , Insecticide Resistance/drug effects , Selection, Genetic , Transcriptome
11.
Psychol Med ; 47(6): 1053-1061, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27938423

ABSTRACT

BACKGROUND: Previous studies hypothesized that neurodevelopmental risk factors may play a role in the pathogenesis of obsessive-compulsive disorder (OCD). Cortical folding has been shown to be a reliable indicator for normal and altered neurodevelopment, but in OCD it has barely been investigated up to now. The present study investigates whether alterations in gyrification are detectable in OCD and, if so, how these are associated with clinical characteristics. METHOD: We compared the local Gyrification Index (lGI) between 75 OCD patients and 75 matched healthy subjects across the whole brain. In addition, for those regions exhibiting an altered lGI in patients we explored a potential relationship to symptom severity, age of onset, and influence of medication. RESULTS: OCD patients had a significantly decreased lGI in right parietal, precentral but also insula, temporal, pars triangularis and rostral middle frontal regions compared to healthy subjects. A positive association with age of onset was found but no association with symptom severity. There was no effect of co-morbidity or medication. CONCLUSIONS: The reduced gyrification found in OCD confirms previous findings in other psychiatric disorders and suggests that alterations may already occur during early stages of brain development. Our findings support the idea that altered cortical folding might represent a trait characteristic of the disorder although longitudinal studies are needed to clarify the trajectory of this morphological measure in OCD.


Subject(s)
Cerebral Cortex/pathology , Magnetic Resonance Imaging/methods , Obsessive-Compulsive Disorder/pathology , Adolescent , Adult , Cerebral Cortex/diagnostic imaging , Female , Humans , Male , Middle Aged , Obsessive-Compulsive Disorder/diagnostic imaging , Young Adult
12.
Genet Mol Res ; 16(1)2017 Mar 30.
Article in English | MEDLINE | ID: mdl-28363010

ABSTRACT

Multiflorous spikelets are found in several grass species of agricultural and economic interest. In oat, this morphological characteristic is associated with the production of naked grains. Although many genetic studies have been performed over the past century, the inheritance of the multiflorous spikelet trait is not fully understood in oat. The objectives of this study were to evaluate environmental effects on the multiflorous spikelet trait, to estimate the number of genes controlling the trait, and to clone and characterize sequences of the AP2 gene in oat. Two genetic populations of recombinant inbreed lines were screened for the multiflorous spikelet trait from different years and sowing dates under field experiments. Normal, multiflorous, and mosaic spikelets were analyzed in the whole panicle for both years and sowing dates. Specific primer pairs for the AP2 gene was utilized to amplify and clone oat sequences. The results demonstrate that under higher temperature and day-length conditions, the variable expressivity of the multiflorous spikelet trait was less pronounced in both populations. Genetic analyses indicated the action of one major gene and two or three modifying genes controlling the expression of the multiflorous spikelet trait in oat, depending on the genetic background. Sequences with similarity to the AP2 gene were isolated from the oat lines UFRGS 017004-2 and URS Taura, and genetic polymorphisms were identified, which are valuable to confirm the action of AP2 on the multiflorous spikelet trait. Our results provide information to assist in the development of future studies of the multiflorous spikelet trait in oat.


Subject(s)
Avena/genetics , Avena/growth & development , Chromosomes, Plant , Flowers/genetics , Flowers/growth & development , Homeodomain Proteins/genetics , Mutation , Nuclear Proteins/genetics , Phenotype , Plant Proteins/genetics
13.
Phys Rev Lett ; 117(22): 223001, 2016 Nov 25.
Article in English | MEDLINE | ID: mdl-27925746

ABSTRACT

We report on the realization of a free-space single-photon absorber, which deterministically absorbs exactly one photon from an input pulse. Our scheme is based on the saturation of an optically thick medium by a single photon due to Rydberg blockade. By converting one absorbed input photon into a stationary Rydberg excitation, decoupled from the light field through fast engineered dephasing, we blockade the full atomic cloud and change our optical medium from opaque to transparent. We show that this results in the subtraction of one photon from the input pulse over a wide range of input photon numbers. We investigate the change of the pulse shape and temporal photon statistics of the transmitted light pulses for different input photon numbers and compare the results to simulations. Based on the experimental results, we discuss the applicability of our single-photon absorber for number resolved photon detection schemes or quantum gate operations.

14.
Mol Genet Metab ; 111(2): 133-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24125893

ABSTRACT

In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients. Alterations such as inversion/disruption and partial/total deletions of the IDS gene were found in 20/103 (19%) patients. Small insertions/deletions/indels (<22 bp) and point mutations were identified in 83/103 (88%) patients, including 30 novel mutations; except for a higher frequency of small duplications in relation to small deletions, the frequencies of major and minor alterations found in our sample are in accordance with those described in the literature.


Subject(s)
Exons , Iduronate Sulfatase/genetics , Mucopolysaccharidosis II/genetics , Mutation , Adult , Female , Genetic Association Studies , Genotyping Techniques , Humans , Mucopolysaccharidosis II/diagnosis , Mucopolysaccharidosis II/pathology , Sequence Analysis, DNA , Severity of Illness Index , South America
15.
Insect Mol Biol ; 23(4): 511-26, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24707894

ABSTRACT

The pollen beetle Meligethes aeneus is the most important coleopteran pest in European oilseed rape cultivation, annually infesting millions of hectares and responsible for substantial yield losses if not kept under economic damage thresholds. This species is primarily controlled with insecticides but has recently developed high levels of resistance to the pyrethroid class. The aim of the present study was to provide a transcriptomic resource to investigate mechanisms of resistance. cDNA was sequenced on both Roche (Indianapolis, IN, USA) and Illumina (LGC Genomics, Berlin, Germany) platforms, resulting in a total of ∼53 m reads which assembled into 43 396 expressed sequence tags (ESTs). Manual annotation revealed good coverage of genes encoding insecticide target sites and detoxification enzymes. A total of 77 nonredundant cytochrome P450 genes were identified. Mapping of Illumina RNAseq sequences (from susceptible and pyrethroid-resistant strains) against the reference transcriptome identified a cytochrome P450 (CYP6BQ23) as highly overexpressed in pyrethroid resistance strains. Single-nucleotide polymorphism analysis confirmed the presence of a target-site resistance mutation (L1014F) in the voltage-gated sodium channel of one resistant strain. Our results provide new insights into the important genes associated with pyrethroid resistance in M. aeneus. Furthermore, a comprehensive EST resource is provided for future studies on insecticide modes of action and resistance mechanisms in pollen beetle.


Subject(s)
Coleoptera/drug effects , Coleoptera/genetics , Cytochrome P-450 Enzyme System/genetics , Enzyme Induction/drug effects , Insecticide Resistance/physiology , Insecticides/pharmacology , Pyrethrins/pharmacology , Animals , Base Sequence , Coleoptera/enzymology , Expressed Sequence Tags , Insecticide Resistance/genetics , Molecular Sequence Data , Mutation , Transcriptome , Voltage-Gated Sodium Channels/genetics
17.
Integr Org Biol ; 6(1): obae004, 2024.
Article in English | MEDLINE | ID: mdl-38516554

ABSTRACT

Epigenetic mechanisms are increasingly understood to have major impacts across ecology. However, one molecular epigenetic mechanism, DNA methylation, currently dominates the literature. A second mechanism, histone modification, is likely important to ecologically relevant phenotypes and thus warrants investigation, especially because molecular interplay between methylation and histone acetylation can strongly affect gene expression. There are a limited number of histone acetylation studies on non-model organisms, yet those that exist show that it can impact gene expression and phenotypic plasticity. Wild birds provide an excellent system to investigate histone acetylation, as free-living individuals must rapidly adjust to environmental change. Here, we screen histone acetylation in the house sparrow (Passer domesticus); we studied this species because DNA methylation was important in the spread of this bird globally. This species has one of the broadest geographic distributions in the world, and part of this success is related to the way that it uses methylation to regulate its gene expression. Here, we verify that a commercially available assay that was developed for mammals can be used in house sparrows. We detected high variance in histone acetylation among individuals in both liver and spleen tissue. Further, house sparrows with higher epigenetic potential in the Toll Like Receptor-4 (TLR-4) promoter (i.e., CpG content) had higher histone acetylation in liver. Also, there was a negative correlation between histone acetylation in spleen and TLR-4 expression. In addition to validating a method for measuring histone acetylation in wild songbirds, this study also shows that histone acetylation is related to epigenetic potential and gene expression, adding a new study option for ecological epigenetics.

18.
J Clin Anesth ; 94: 111403, 2024 06.
Article in English | MEDLINE | ID: mdl-38368798

ABSTRACT

STUDY OBJECTIVE: To assess the efficacy of an ECG-based method called thoracic impedance pneumography to reduce hypoxic events in endoscopy. DESIGN: This was a single center, 1:1 randomized controlled trial. SETTING: The trial was conducted during the placement of percutaneous endoscopic gastrostomy (PEG). PATIENTS: 173 patients who underwent PEG placement were enrolled in the present trial. Indication was oncological in most patients (89%). 58% of patients were ASA class II and 42% of patients ASA class III. INTERVENTIONS: Patients were randomized in the standard monitoring group (SM) with pulse oximetry and automatic blood pressure measurement or in the intervention group with additional thoracic impedance pneumography (TIM). Sedation was performed with propofol by gastroenterologists or trained nurses. MEASUREMENTS: Hypoxic episodes defined as SpO2 < 90% for >15 s were the primary endpoint. Secondary endpoints were minimal SpO2, apnea >10s/>30s and incurred costs. MAIN RESULTS: Additional use of thoracic impedance pneumography reduced hypoxic episodes (TIM: 31% vs SM: 49%; p = 0.016; OR 0.47; NNT 5.6) and elevated minimal SpO2 per procedure (TIM: 90.0% ± 8.9; SM: 84.0% ± 17.6; p = 0.007) significantly. Apnea events >10s and > 30s were significantly more often detected in TIM (43%; 7%) compared to SM (1%; 0%; p < 0.001; p = 0.014) resulting in a time advantage of 17 s before the occurrence of hypoxic events. As a result, adjustments of oxygen flow were significantly more often necessary in SM than in TIM (p = 0.034) and assisted ventilation was less often needed in TIM (2%) compared with SM (9%; p = 0.053). Calculated costs for the additional use of thoracic impedance pneumography were 0.13$ (0.12 €/0.11 £) per procedure. CONCLUSIONS: Additional thoracic impedance pneumography reduced the quantity and extent of hypoxic events with less need of assisted ventilation. Supplemental costs per procedure were negligible. KEY WORDS: thoracic impedance pneumography, capnography, sedation, monitoring, gastrointestinal endoscopy, percutaneous endoscopic gastrostomy.


Subject(s)
Propofol , Humans , Propofol/adverse effects , Apnea , Prospective Studies , Gastrostomy/adverse effects , Electric Impedance , Endoscopy, Gastrointestinal/adverse effects , Hypoxia/etiology , Hypoxia/prevention & control
19.
AJNR Am J Neuroradiol ; 44(3): 283-290, 2023 03.
Article in English | MEDLINE | ID: mdl-36797033

ABSTRACT

BACKGROUND AND PURPOSE: Tractography of the corticospinal tract is paramount to presurgical planning and guidance of intraoperative resection in patients with motor-eloquent gliomas. It is well-known that DTI-based tractography as the most frequently used technique has relevant shortcomings, particularly for resolving complex fiber architecture. The purpose of this study was to evaluate multilevel fiber tractography combined with functional motor cortex mapping in comparison with conventional deterministic tractography algorithms. MATERIALS AND METHODS: Thirty-one patients (mean age, 61.5 [SD, 12.2] years) with motor-eloquent high-grade gliomas underwent MR imaging with DWI (TR/TE = 5000/78 ms, voxel size = 2 × 2 × 2 mm3, 1 volume at b = 0 s/mm2, 32 volumes at b = 1000 s/mm2). DTI, constrained spherical deconvolution, and multilevel fiber tractography-based reconstruction of the corticospinal tract within the tumor-affected hemispheres were performed. The functional motor cortex was enclosed by navigated transcranial magnetic stimulation motor mapping before tumor resection and used for seeding. A range of angular deviation and fractional anisotropy thresholds (for DTI) was tested. RESULTS: For all investigated thresholds, multilevel fiber tractography achieved the highest mean coverage of the motor maps (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold = 71.8%, 22.6%, and 11.7%) and the most extensive corticospinal tract reconstructions (eg, angular threshold = 60°; multilevel/constrained spherical deconvolution/DTI, 25% anisotropy threshold = 26,485 mm3, 6308 mm3, and 4270 mm3). CONCLUSIONS: Multilevel fiber tractography may improve the coverage of the motor cortex by corticospinal tract fibers compared with conventional deterministic algorithms. Thus, it could provide a more detailed and complete visualization of corticospinal tract architecture, particularly by visualizing fiber trajectories with acute angles that might be of high relevance in patients with gliomas and distorted anatomy.


Subject(s)
Brain Neoplasms , Glioma , Motor Cortex , Humans , Middle Aged , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Diffusion Tensor Imaging/methods , Motor Cortex/pathology , Glioma/diagnostic imaging , Glioma/surgery , Glioma/pathology
20.
Cerebrovasc Dis ; 34(1): 70-7, 2012.
Article in English | MEDLINE | ID: mdl-22759754

ABSTRACT

BACKGROUND AND PURPOSE: Stent retrievers are currently displacing 'classical' thrombectomy devices for recanalization in acute ischaemic stroke. The aim of our study was to show the procedural efficacy and safety of the Solitaire stent retriever as part of our multimodality endovascular approach in the treatment of ischaemic stroke. METHODS: Between March 2008 and December 2009, 104 patients [53 females (51%), 51 males (49%), mean age 67.3 years (range 31-96)] with 108 territorial occlusions were treated with the Solitaire stent alone or in conjunction with other endovascular stroke devices. All patients were referred to our service after clinical evaluation by a team of stroke neurologists as part of our standard treatment algorithm with 0.9 mg/kg i.v. recombinant tissue-type plasminogen activator and endovascular continuation of treatment in CT angiography-proven main branch occlusion. The time of angiography was defined as the moment of groin puncture. Final reperfusion success was rated according to the Thrombolysis in Cerebral Infarction (TICI) scale; the first persistent Thrombolysis in Myocardial Infarction (TIMI) 2/3 reperfusion was used for time-to-reperfusion measures. RESULTS: Fifty-eight patients were treated in conjunction with intravenous lysis, 32/104 received intra-arterial lytics. Twenty-five territories were treated with the Solitaire alone; the remaining 83 were treated with a combination of mechanical thrombectomy devices or aspiration thrombectomy followed by or in conjunction with the Solitaire. The most frequent combination was a proximal aspiration/distal access catheter and Solitaire (62/108). In 15/108 procedures, temporary stenting without thrombectomy was performed. Eighty-three successful thrombectomy attempts were performed in the remaining 93 territories. The mean number of Solitaire passes was 2.46 (median 2, max. 12). The mean time from onset to reperfusion was 265 min (range 56-1,031), median 230 min; the mean angio-to-reperfusion time was 47 min (5-186), median 38.5 min. A subanalysis showed a significant reduction of the angio-to-reperfusion time when the Solitaire was used (48.7 vs. 68 min). The rate of final TICI 2b/3 reperfusion was 79% for the anterior and 77.9% for the posterior circulation (TIMI 2/3 for both: 92.5%). During or after the first deployment of the Solitaire, 72.8% showed TIMI 2/3 reperfusion. The mean National Institute of Health Stroke Scale score on admission was 15.3 and decreased by 7.8 points at clinical discharge. The overall mortality at discharge was 16% in the anterior and 47.8% in the posterior circulation group. There were 2 cases of periprocedural intracranial haemorrhage, unrelated to the Solitaire, 6 patients had evidence of subarachnoid haemorrhage, 2 potentially related to the Solitaire deployment. In 4/108 territories, thrombus migration to previously unaffected territories was noted. Vasospasm was seen in 13% of the target vessels. One device was inadvertently detached during retrieval. All these complications had no clinical consequence. CONCLUSIONS: Our single-centre experience proves the technical feasibility and safety of the Solitaire for the treatment of acute intracranial vessel occlusion and approves previous reports with smaller patient numbers. Further multicentre studies with a randomized and prospective design will be necessary to verify the results.


Subject(s)
Arterial Occlusive Diseases/therapy , Brain Ischemia/therapy , Stents , Stroke/therapy , Thrombectomy/methods , Acute Disease/therapy , Adult , Aged , Aged, 80 and over , Cerebral Angiography/methods , Female , Humans , Male , Middle Aged , Treatment Outcome
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