Determining appropriate imaging parameters for kilovoltage intrafraction monitoring: an experimental phantom study.

Kilovoltage intrafraction monitoring (KIM) utilises the kV imager during treatment for real-time tracking of prostate fiducial markers. However, its effectiveness relies on sufficient image quality for the fiducial tracking task. To guide the performance characterisation of KIM under different clinically relevant conditions, the effect of different kV parameters and patient size on image quality, and quantification of MV scatter from the patient to the kV detector panel were investigated in this study. Image quality was determined for a range of kV acquisition frame rates, kV exposure, MV dose rates and patient sizes. Two methods were used to determine image quality; the ratio of kV signal through the patient to the MV scatter from the patient incident on the kilovoltage detector, and the signal-to-noise ratio (SNR). The effect of patient size and frame rate on MV scatter was evaluated in a homogeneous CIRS pelvis phantom and marker segmentation was determined utilising the Rando phantom with embedded markers. MV scatter incident on the detector was shown to be dependent on patient thickness and frame rate. The segmentation code was shown to be successful for all frame rates above 3 Hz for the Rando phantom corresponding to a kV to MV ratio of 0.16 and an SNR of 1.67. For a maximum patient dimension less than 36.4 cm the conservative kV parameters of 5 Hz at 1 mAs can be used to reduce dose while retaining image quality, where the current baseline kV parameters of 10 Hz at 1 mAs is shown to be adequate for marker segmentation up to a patient dimension of 40 cm. In conclusion, the MV scatter component of image quality noise for KIM has been quantified. For most prostate patients, use of KIM with 10 Hz imaging at 1 mAs is adequate however image quality can be maintained and imaging dose reduced by altering existing acquisition parameters

Determining appropriate imaging parameters for kilovoltage intrafraction monitoring: an experimental phantom study.

Kilovoltage intrafraction monitoring (KIM) utilises the kV imager during treatment for real-time tracking of prostate fiducial markers. However, its effectiveness relies on sufficient image quality for the fiducial tracking task. To guide the performance characterisation of KIM under different clinically relevant conditions, the effect of different kV parameters and patient size on image quality, and quantification of MV scatter from the patient to the kV detector panel were investigated in this study. Image quality was determined for a range of kV acquisition frame rates, kV exposure, MV dose rates and patient sizes. Two methods were used to determine image quality; the ratio of kV signal through the patient to the MV scatter from the patient incident on the kilovoltage detector, and the signal-to-noise ratio (SNR). The effect of patient size and frame rate on MV scatter was evaluated in a homogeneous CIRS pelvis phantom and marker segmentation was determined utilising the Rando phantom with embedded markers. MV scatter incident on the detector was shown to be dependent on patient thickness and frame rate. The segmentation code was shown to be successful for all frame rates above 3 Hz for the Rando phantom corresponding to a kV to MV ratio of 0.16 and an SNR of 1.67. For a maximum patient dimension less than 36.4 cm the conservative kV parameters of 5 Hz at 1 mAs can be used to reduce dose while retaining image quality, where the current baseline kV parameters of 10 Hz at 1 mAs is shown to be adequate for marker segmentation up to a patient dimension of 40 cm. In conclusion, the MV scatter component of image quality noise for KIM has been quantified. For most prostate patients, use of KIM with 10 Hz imaging at 1 mAs is adequate however image quality can be maintained and imaging dose reduced by altering existing acquisition parameters

Quantification of intrafraction prostate motion and its dosimetric effect on VMAT.

Intrafraction prostate motion degrades the accuracy of radiation therapy (RT) delivery. Whilst a number of metrics in the literature have been used to quantify intrafraction prostate motion, it has not been established whether these metrics reflect the effect of motion on the RT dose delivered to the patients. In this study, prostate motion during volumetric modulated arc therapy (VMAT) treatment of 18 patients and a total of 294 fractions was quantified through novel metrics as well as those available in the literature. The impact of the motion on VMAT dosimetry was evaluated using these metrics and dose reconstructions based on a previously validated and published method. The dosimetric impact of the motion on planning target volume (PTV) and clinical target volume (CTV) coverage and organs at risk (OARs) was correlated with the motion metrics, using the coefficient of determination (R 2 ), to evaluate their utility. Action level threshold for the prostate motion metric that best described the dosimetric impact on the PTV D95% was investigated through iterative regression analysis. The average (range) of the mean motion for the patient cohort was 1.5 mm (0.3-9.9 mm). A number of motion metrics were found to be strongly correlated with PTV D95%, the range of R 2 was 0.43-0.81. For all the motion measures, correlations with CTV D99% (range of R 2 was 0.12-0.62), rectum V65% (range of R 2 was 0.33-0.58) and bladder V65% (range of R 2 was 0.51-0.69) were not as strong as for PTV D95%. The mean of the highest 50% of motion metric was one of the best indicator of dosimetric impact on PTV D95%. Action level threshold value for this metric was found to be 3.0 mm. For an individual fraction, when the metric value was greater than 3.0 mm then the PTV D95% was reduced on average by 6.2%. This study demonstrated that several motion metrics are well correlated with the dosimetric impact (PTV D95%) of individual fraction prostate motion on VMAT delivery and could be used for treatment course adaptation

Clinical relevance of biomarkers of oxidative stress

SIGNIFICANCE Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 00, 000-000

Real-Time 3D Image Guidance Using a Standard LINAC: Measured Motion, Accuracy, and Precision of the First Prospective Clinical Trial of Kilovoltage Intrafraction Monitoring-Guided Gating for Prostate Cancer Radiation Therapy.

PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a new real-time 3-dimensional image guidance method. Unlike previous real-time image guidance methods, KIM uses a standard linear accelerator without any additional equipment needed. The first prospective clinical trial of KIM is underway for prostate cancer radiation therapy. In this paper we report on the measured motion accuracy and precision using real-time KIM-guided gating. METHODS AND MATERIALS: Imaging and motion information from the first 200 fractions from 6 patient prostate cancer radiation therapy volumetric modulated arc therapy treatments were analyzed. A 3-mm/5-second action threshold was used to trigger a gating event where the beam is paused and the couch position adjusted to realign the prostate to the treatment isocenter. To quantify the in vivo accuracy and precision, KIM was compared with simultaneously acquired kV/MV triangulation for 187 fractions. RESULTS: KIM was successfully used in 197 of 200 fractions. Gating events occurred in 29 fractions (14.5%). In these 29 fractions, the percentage of beam-on time, the prostate displacement was >3 mm from the isocenter position, reduced from 73% without KIM to 24% with KIM-guided gating. Displacements >5 mm were reduced from 16% without KIM to 0% with KIM. The KIM accuracy was measured at <0.3 mm in all 3 dimensions. The KIM precision was <0.6 mm in all 3 dimensions. CONCLUSIONS: Clinical implementation of real-time KIM image guidance combined with gating for prostate cancer eliminates large prostate displacements during treatment delivery. Both in vivo KIM accuracy and precision are well below 1 mm

The distribution of burden of dental caries in schoolchildren: a critique of the high-risk caries prevention strategy for populations

BACKGROUND: The 'high-risk approach' is a commonly adopted strategy recommended for the prevention of dental caries in populations. The scientific basis for the strategy has been questioned. The objective of this study is to assess the contribution that children identified at 'high-risk' made towards the total of new caries lesions over a 4-year period, by analysing the distribution of new lesions per 100 children. METHODS: Data are from the National Preventive Dentistry Demonstration Programme (NPDDP) in the United States. The analyses identified the distribution of new carious lesions over a 4-year period in four groups of 7 year-old children who received differing preventive regimes. RESULTS: The majority of new lesions occurred in those children classified at lowest caries risk at baseline. Irrespective of the preventive regime adopted and the initial caries levels, children classified as 'highest risk' contributed less than 6% of the total number of new lesions developing over 4 years. CONCLUSION: These findings challenge the basis for the adoption of a high-risk strategy

Reusable Components of Semantic Specifications

Semantic specifications of programming languages typically have poor modularity. This hinders reuse of parts of the semantics of one language when specifying a different language – even when the two languages have many constructs in common – and evolution of a language may require major reformulation of its semantics. Such drawbacks have discouraged language developers from using formal semantics to document their designs. In the PLanCompS project, we have developed a component-based approach to semantics. Here, we explain its modularity aspects, and present an illustrative case study: a component-based semantics for Caml Light. We have tested the correctness of the semantics by running programs on an interpreter generated from the semantics, comparing the output with that produced on the standard implementation of the language. Our approach provides good modularity, facilitates reuse, and should support co-evolution of languages and their formal semantics. It could be particularly useful in connection with domain-specific languages and language-driven software development

Advances in prevention and therapy of neonatal dairy calf diarrhoea : a systematical review with emphasis on colostrum management and fluid therapy

Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota-and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy

Antagonistic Bacterial Interactions Help Shape Host-Symbiont Dynamics within the Fungus-Growing Ant-Microbe Mutualism

Conflict within mutually beneficial associations is predicted to destabilize relationships, and theoretical and empirical work exploring this has provided significant insight into the dynamics of cooperative interactions. Within mutualistic associations, the expression and regulation of conflict is likely more complex than in intraspecific cooperative relationship, because of the potential presence of: i) multiple genotypes of microbial species associated with individual hosts, ii) multiple species of symbiotic lineages forming cooperative partner pairings, and iii) additional symbiont lineages. Here we explore complexity of conflict expression within the ancient and coevolved mutualistic association between attine ants, their fungal cultivar, and actinomycetous bacteria (Pseudonocardia). Specifically, we examine conflict between the ants and their Pseudonocardia symbionts maintained to derive antibiotics against parasitic microfungi (Escovopsis) infecting the ants' fungus garden. Symbiont assays pairing isolates of Pseudonocardia spp. associated with fungus-growing ants spanning the phylogenetic diversity of the mutualism revealed that antagonism between strains is common. In contrast, antagonism was substantially less common between more closely related bacteria associated with Acromyrmex leaf-cutting ants. In both experiments, the observed variation in antagonism across pairings was primarily due to the inhibitory capabilities and susceptibility of individual strains, but also the phylogenetic relationships between the ant host of the symbionts, as well as the pair-wise genetic distances between strains. The presence of antagonism throughout the phylogenetic diversity of Pseudonocardia symbionts indicates that these reactions likely have shaped the symbiosis from its origin. Antagonism is expected to prevent novel strains from invading colonies, enforcing single-strain rearing within individual ant colonies. While this may align ant-actinomycete interests in the bipartite association, the presence of single strains of Pseudonocardia within colonies may not be in the best interest of the ants, because increasing the diversity of bacteria, and thereby antibiotic diversity, would help the ant-fungus mutualism deal with the specialized parasites