Artificial intelligence solution to accelerate the acquisition of MRI images: Impact on the therapeutic care in oncology in radiology and radiotherapy departments.

PURPOSE: MRI is essential in the management of brain tumours. However, long waiting times reduce patient accessibility. Reducing acquisition time could improve access but at the cost of spatial resolution and diagnostic quality. A commercially available artificial intelligence (AI) solution, SubtleMR™, can increase the resolution of acquired images. The objective of this prospective study was to evaluate the impact of this algorithm that halves the acquisition time on the detectability of brain lesions in radiology and radiotherapy. MATERIAL AND METHODS: The T1/T2 MRI of 33 patients with brain metastases or meningiomas were analysed. Images acquired quickly have a matrix divided by two which halves the acquisition time. The visual quality and lesion detectability of the AI images were evaluated by radiologists and radiation oncologist as well as pixel intensity and lesions size. RESULTS: The subjective quality of the image is lower for the AI images compared to the reference images. However, the analysis of lesion detectability shows a specificity of 1 and a sensitivity of 0.92 and 0.77 for radiology and radiotherapy respectively. Undetected lesions on the IA image are lesions with a diameter less than 4mm and statistically low average gadolinium-enhancement contrast. CONCLUSION: It is possible to reduce MRI acquisition times by half using the commercial algorithm to restore the characteristics of the image and obtain good specificity and sensitivity for lesions with a diameter greater than 4mm.

RBE of kV CBCT radiation determined by Monte Carlo DNA damage simulations.

Due to the higher LET of kilovoltage (kV) radiation, there is potential for an increase in relative biological effectiveness (RBE) of absorbed doses of radiation from kV cone beam computed tomography (CBCT) sources in reference to megavoltage or Co-60 doses. This work develops a method for accurately coupling a Monte Carlo (MC) radiation transport code (PENELOPE) with the damage simulation (MCDS) to predict relative numbers of DNA double strand breaks (DSBs). The MCDS accounts for slowing down of electrons and delta ray production within the cell nucleus; however, determining the spectrum of electrons incident on the cell nucleus from photons interacting in a larger region of tissue is not trivial. PENELOPE simulations were conducted with a novel tally algorithm invoked where electrons incident on a detection material were tracked and both the incident energy and the final deposited dose were recorded. The DSB yield predicted by a set of MCDS runs of monoenergetic electrons was then looked up in a table and weighted by the specific energy of the incident electron. Our results indicate that the RBE for DSB induction is 1.1 for diagnostic x-rays with energies from 80 to 125 kVp. We found no significant change in RBE with depth or filtration. The predicted absolute DSB yields are about three times lower for cells irradiated under anoxic conditions than the yield in cells irradiated under normoxic (5%) or fully aerobic (100%) conditions. However, oxygen concentration has a negligible (± 0.02) effect on the RBE of kV CBCT x-rays.

Sci-Fri PM: Delivery - 08: Characterizing the spatially varying fluence and spectra of a kV imaging source for dose calculations.

Kilovoltage (kV) daily image-guided radiotherapy (IGRT) procedures accumulate radiation dose within the patient that is currently not routinely incorporated in the treatment plan. As part of the process of developing a patient-specific kV dose computation tool, the kV x-ray source must be characterized. We propose a simple, clinically feasible experimental characterization method using in-air dose measurements along the transverse axis. We determine half-value layer (HVL) along the transverse axis, from which we derive the HVL-specific mass-absorption coefficient, which is used to determine beam fluence. These values are interpolated over the entire field. The spectrum at each interpolation point in the field is found from HVL and accelerating potential (kVp) using third-party software Spektr. We use this method to characterize the spatially varying fluence and spectra of a Varian® On-Board Imaging® source for energies 80, 100 and 125 kVp. This characterization is used to compute dose within a heterogeneous phantom, using our previously validated in-house dose computation software, which we compare with relative dose measurements. We show that for a 10×10 cm2 field size using no added filtration, the agreement for all three energies is within 2% for the central depth-dose profile and within 2.6% for the transverse profiles. This clinically feasible experimental characterization method for kV imaging sources represents a crucial step in the development of a patient-specific dose computation tool.

Sci-Sat AM: Brachy - 06: Monte carlo DNA damage simulations of kV cbct radiation.

When performed daily, cone beam CT (CBCT) images can accumulate radiation dose to non-negligible levels. Because kV x-rays have a larger relative biological effectiveness (RBE) than its MV x-rays, the accumulated absorbed dose needs to be multiplied by an appropriate RBE to better evaluate the impact of CBCT dose in a treatment planning context. We investigated this question using PENLEOPE simulations to look in detail at the electron energy spectra produced by kV x-rays and Co-60 γ-rays in biologically motivated geometries. The electron spectra were input into the published Monte Carlo Damage Simulation (MCDS) and used to estimate the average number of double strand breaks (DSBs) per Gy per cell. Our results suggest an approximately 10% increase in the RBE for DSB induction. For the majority of treatment planning scenarios where imaging dose is only a small fraction of the total delivered dose to target volumes and organs at risk, the increase in RBE is not critical to be factored in, however for it may play a significant role in predicting the induction of secondary cancers.

[To know, understand and combating medication errors related to computerized physician order entry]. / Connaître, comprendre et lutter contre les erreurs médicamenteuses induites par l'informatisation du circuit du médicament.

INTRODUCTION: The aim of the study is to identify medication errors related to computerized physician order entry in our hospital. METHODS: At the end of this 1-year study (2008 to 2009), 378 beds were computerized by a business software. Medication errors were identified from notifications sent to the publisher of the software, feedback of health professionals and the analysis of Pharmacists' interventions formulate following prescription errors due to computerization. They were qualified according to the medication error's French dictionary of the French Society of Clinical Pharmacy. RESULTS: Thirty-five categories of medication errors were found. Most of them appear during prescription. Dosage and concentration errors, dose errors, omission errors and drug errors are the most frequent. DISCUSSION-CONCLUSION: Three main causes were found: human factor, closely related to the software settings and the quality of user training; communication problems, related to the ergonomics; conception problems, related to intuitiveness and intricacy of the software. These results confirm the existence of medication errors induced by computerized physician order entry systems. They highlight the need to involve initial and ongoing training of users, relevance and scalability of the setup and use of mature and certified software to minimized them.

[Use of antibiotics in emergency units: qualitative and quantitative assessment]. / L'antibiothérapie aux urgences, évaluation par une approche qualitative et quantitative.

INTRODUCTION: Most antibiotic therapies are initiated in the emergency unit (EU). To better understand the antibiotic consumption survey in this unit, we compared our results to two neighbor hospitals. This quantitative data was then compared to a quality assessment of antibiotic prescription (audit). METHODS: The quantitative measure of antibiotic consumption (three markers: ceftriaxone, amoxicillin-clavulanate, and fluoroquinolones) based on the ratio DDD:1000 patient admitted in the EU was compared between one teaching hospital and the two neighbor hospitals. Qualitative measure: a retrospective clinical targeted audit of antibiotic prescriptions was performed. The compliance to guidelines for infection diagnosis and antibiotic treatment were assessed. RESULTS: Antibiotic consumption: the survey showed a higher consumption of the three antibiotics in the teaching hospital, especially for amoxicillin-clavulanate (3.7-5.5 higher). Audit: 93 files of EU patients were reviewed; their mean age was 71 years (18-96). Diagnosis was conform to the expert opinion in 70% of cases. No antibiotic was really necessary in 20% of cases, and delay between hospitalization and antibiotic prescription was relevant only for 56% of patients. The most frequently prescribed antibiotics were betalactams (penicillins 43%, third generation cephalosporin 21%, and fluoroquinolones 22%). The choice was conform to local and national guidelines in 78% of justified prescribed antibiotherapy. CONCLUSION: The qualitative assessment cannot explain the higher antibiotic consumption trend. The number of unjustified antibiotic prescriptions does not explain the variable antibiotic consumption.

Amphetamine-like stimulant cessation in an abusing patient treated with bupropion.

OBJECTIVE: Bupropion sustained release is considered to be a weak inhibitor of dopamine and serotonin reuptake. METHOD: We report the case of an amphetamine-abusing patient who self-administered bupropion. RESULTS: Since 30 years, a 52-year-old women used amphetamine derivates. She explained her need for amphetamine use in order to perform daily activities. Recently, she decided to experiment with bupropion. She abruptly stopped taking clobenzorex and simultaneously started taking bupropion (150 mg/day). The seventh day she reported a concomitant intake of clobenzorex; this induced adverse effects. Whilst taking bupropion, she described experiencing an euthymic state without any compulsion to take amphetamine drugs and was able to perform daily activities. After stopping it, no symptoms of withdrawal were reported by the patient. CONCLUSION: This observation supports an another report suggesting that bupropion may be of help in weaning from amphetamine users and should be confirmed by clinical trials.

Synthesis of polyhydroxyalkanoate in the peroxisome of Saccharomyces cerevisiae by using intermediates of fatty acid beta-oxidation.

Medium-chain-length polyhydroxyalkanoates (PHAs) are polyesters having properties of biodegradable thermoplastics and elastomers that are naturally produced by a variety of pseudomonads. Saccharomyces cerevisiae was transformed with the Pseudomonas aeruginosa PHAC1 synthase modified for peroxisome targeting by the addition of the carboxyl 34 amino acids from the Brassica napus isocitrate lyase. The PHAC1 gene was put under the control of the promoter of the catalase A gene. PHA synthase expression and PHA accumulation were found in recombinant S. cerevisiae growing in media containing fatty acids. PHA containing even-chain monomers from 6 to 14 carbons was found in recombinant yeast grown on oleic acid, while odd-chain monomers from 5 to 15 carbons were found in PHA from yeast grown on heptadecenoic acid. The maximum amount of PHA accumulated was 0.45% of the dry weight. Transmission electron microscopy of recombinant yeast grown on oleic acid revealed the presence of numerous PHA inclusions found within membrane-bound organelles. Together, these data show that S. cerevisiae expressing a peroxisomal PHA synthase produces PHA in the peroxisome using the 3-hydroxyacyl coenzyme A intermediates of the beta-oxidation of fatty acids present in the media. S. cerevisiae can thus be used as a powerful model system to learn how fatty acid metabolism can be modified in order to synthesize high amounts of PHA in eukaryotes, including plants.

Production of polyesters in transgenic plants.

Polyhydroxyalkanoates (PHAs) are bacterial polyesters having the properties of biodegradable thermoplastics and elastomers. Synthesis of PHAs has been demonstrated in transgenic plants. Both polyhydroxybutyrate and the co-polymer poly(hydroxybutyrate-co-hydroxyvalerate) have been synthesized in the plastids of Arabidopsis thaliana and Brassica napus. Furthermore, a range of medium-chain-length PHAs has also been produced in plant peroxisomes. Development of agricultural crops to produce PHA on a large scale and at low cost will be a challenging task requiring a coordinated and stable expression of several genes. Novel extraction methods designed to maximize the use of harvested plants for PHA, oil, carbohydrate, and feed production will be needed. In addition to their use as plastics, PHAs can also be used to modify fiber properties in plants such as cotton. Furthermore, PHA can be exploited as a novel tool to study the carbon flux through various metabolic pathways, such as the fatty acid beta-oxidation cycle.

Analysis of the alternative pathways for the beta-oxidation of unsaturated fatty acids using transgenic plants synthesizing polyhydroxyalkanoates in peroxisomes.

Degradation of fatty acids having cis-double bonds on even-numbered carbons requires the presence of auxiliary enzymes in addition to the enzymes of the core beta-oxidation cycle. Two alternative pathways have been described to degrade these fatty acids. One pathway involves the participation of the enzymes 2, 4-dienoyl-coenzyme A (CoA) reductase and Delta(3)-Delta(2)-enoyl-CoA isomerase, whereas the second involves the epimerization of R-3-hydroxyacyl-CoA via a 3-hydroxyacyl-CoA epimerase or the action of two stereo-specific enoyl-CoA hydratases. Although degradation of these fatty acids in bacteria and mammalian peroxisomes was shown to involve mainly the reductase-isomerase pathway, previous analysis of the relative activity of the enoyl-CoA hydratase II (also called R-3-hydroxyacyl-CoA hydro-lyase) and 2,4-dienoyl-CoA reductase in plants indicated that degradation occurred mainly through the epimerase pathway. We have examined the implication of both pathways in transgenic Arabidopsis expressing the polyhydroxyalkanoate synthase from Pseudomonas aeruginosa in peroxisomes and producing polyhydroxyalkanoate from the 3-hydroxyacyl-CoA intermediates of the beta-oxidation cycle. Analysis of the polyhydroxyalkanoate synthesized in plants grown in media containing cis-10-heptadecenoic or cis-10-pentadecenoic acids revealed a significant contribution of both the reductase-isomerase and epimerase pathways to the degradation of these fatty acids.

Importance of sequences adjacent to the terminal tripeptide in the import of a peroxisomal Candida tropicalis protein in plant peroxisomes.

The peroxisome targeting signal (PTS) required for import of the rat acyl-CoA oxidase (AOX; EC 1.3.3.6) and the Candida tropicalis multifunctional protein (MFP) in plant peroxisomes was assessed in transgenic Arabidopsis thaliana (L.) Heynh. The native rat AOX accumulated in peroxisomes in A. thaliana cotyledons and targeting was dependent on the presence of the C-terminal tripeptide S-K-L. In contrast, the native C. tropicalis MFP, containing the consensus PTS sequence A-K-I was not targeted to plant peroxisomes. Modification of the carboxy terminus to the S-K-L tripeptide also failed to deliver the MFP to peroxisomes while addition of the last 34 amino acids of the Brassica napus isocitrate lyase, containing the terminal tripeptide S-R-M, enabled import of the fusion protein into peroxisomes. These results underline the influence of the amino acids adjacent to the terminal tripeptide of the C. tropicalis MFP on peroxisomal targeting, even in the context of a protein having a consensus PTS sequence S-K-L.

Transgenic Arabidopsis plants can accumulate polyhydroxybutyrate to up to 4% of their fresh weight.

Transgenic Arabidopsis thaliana (L.) Heynh. plants expressing the three enzymes encoding the biosynthetic route to polyhydroxybutyrate (PHB) are described. These plants accumulated more than 4% of their fresh weight (approximately 40% of their dry weight) in the form of PHB in leaf chloroplasts. These very high producers were obtained and identified following a novel strategy consisting of a rapid GC-MS analysis of a large number of transgenic Arabidopsis plants generated using a triple construct, thus allowing the parallel transfer of all three genes necessary for PHB synthesis in a single transformation event. The level of PHB produced was 4-fold greater than previously published values, thus demonstrating the large potential of plants to produce this renewable resource. However, the high levels of the polymer produced had severe effects on both plant development and metabolism. Stunted growth and a loss of fertility were observed in the high-producing lines. Analysis of the metabolite composition of these lines using a GC-MS method that we have newly developed showed that the accumulation of high levels of PHB was not accompanied by an appreciable change in either the composition or the amount of fatty acids. Substantial changes were, however, observed in the levels of various organic acids, amino acids, sugars and sugar alcohols.

Increased flow of fatty acids toward beta-oxidation in developing seeds of Arabidopsis deficient in diacylglycerol acyltransferase activity or synthesizing medium-chain-length fatty acids.

Synthesis of polyhydroxyalkanoates (PHAs) from intermediates of fatty acid beta-oxidation was used as a tool to study fatty acid degradation in developing seeds of Arabidopsis. Transgenic plants expressing a peroxisomal PHA synthase under the control of a napin promoter accumulated PHA in developing seeds to a final level of 0. 06 mg g(-1) dry weight. In plants co-expressing a plastidial acyl-acyl carrier protein thioesterase from Cuphea lanceolata and a peroxisomal PHA synthase, approximately 18-fold more PHA accumulated in developing seeds. The proportion of 3-hydroxydecanoic acid monomer in the PHA was strongly increased, indicating a large flow of capric acid toward beta-oxidation. Furthermore, expression of the peroxisomal PHA synthase in an Arabidopsis mutant deficient in the enzyme diacylglycerol acyltransferase resulted in a 10-fold increase in PHA accumulation in developing seeds. These data indicate that plants can respond to the inadequate incorporation of fatty acids into triacylglycerides by recycling the fatty acids via beta-oxidation and that a considerable flow toward beta-oxidation can occur even in a plant tissue primarily devoted to the accumulation of storage lipids.

Polyhydroxyalkanoate synthesis in transgenic plants as a new tool to study carbon flow through beta-oxidation.

Transgenic plants producing peroxisomal polyhydroxy- alkanoate (PHA) from intermediates of fatty acid degradation were used to study carbon flow through the beta-oxidation cycle. Growth of transgenic plants in media containing fatty acids conjugated to Tween detergents resulted in an increased accumulation of PHA and incorporation into the polyester of monomers derived from the beta-oxidation of these fatty acids. Tween-laurate was a stronger inducer of beta-oxidation, as measured by acyl-CoA oxidase activity, and a more potent modulator of PHA quantity and monomer composition than Tween-oleate. Plants co-expressing a peroxisomal PHA synthase with a capryl-acyl carrier protein thioesterase from Cuphea lanceolata produced eightfold more PHA compared to plants expressing only the PHA synthase. PHA produced in double transgenic plants contained mainly saturated monomers ranging from 6 to 10 carbons, indicating an enhanced flow of capric acid towards beta-oxidation. Together, these results support the hypothesis that plant cells have mechanisms which sense levels of free or esterified unusual fatty acids, resulting in changes in the activity of the beta-oxidation cycle as well as removal and degradation of these unusual fatty acids through beta-oxidation. Such enhanced flow of fatty acids through beta-oxidation can be utilized to modulate the amount and composition of PHA produced in transgenic plants. Furthermore, synthesis of PHAs in plants can be used as a new tool to study the quality and relative quantity of the carbon flow through beta-oxidation as well as to analyse the degradation pathway of unusual fatty acids.

Production of new polymeric compounds in plants.

Plant metabolic engineering has recently enabled the synthesis of a range of polyhydroxyalkanoates as well as a protein-based polymer. These novel compounds can be harvested from plants as a renewable source of environmentally friendly polymers or can be used to change the physical properties of plant products, such as fibres.

Synthesis of medium-chain-length polyhydroxyalkanoates in arabidopsis thaliana using intermediates of peroxisomal fatty acid beta-oxidation.

Polyhydroxyalkanoate (PHA) is a family of polymers composed primarily of R-3-hydroxyalkanoic acids. These polymers have properties of biodegradable thermoplastics and elastomers. Medium-chain-length PHAs (MCL-PHAs) are synthesized in bacteria by using intermediates of the beta-oxidation of alkanoic acids. To assess the feasibility of producing MCL-PHAs in plants, Arabidopsis thaliana was transformed with the PhaC1 synthase from Pseudomonas aeruginosa modified for peroxisome targeting by addition of the carboxyl 34 amino acids from the Brassica napus isocitrate lyase. Immunocytochemistry demonstrated that the modified PHA synthase was appropriately targeted to leaf-type peroxisomes in light-grown plants and glyoxysomes in dark-grown plants. Plants expressing the PHA synthase accumulated electron-lucent inclusions in the glyoxysomes and leaf-type peroxisomes, as well as in the vacuole. These inclusions were similar to bacterial PHA inclusions. Analysis of plant extracts by GC and mass spectrometry demonstrated the presence of MCL-PHA in transgenic plants to approximately 4 mg per g of dry weight. The plant PHA contained saturated and unsaturated 3-hydroxyalkanoic acids ranging from six to 16 carbons with 41% of the monomers being 3-hydroxyoctanoic acid and 3-hydroxyoctenoic acid. These results indicate that the beta-oxidation of plant fatty acids can generate a broad range of R-3-hydroxyacyl-CoA intermediates that can be used to synthesize MCL-PHAs.

Synthesis of high-molecular-weight poly([R]-(-)-3-hydroxybutyrate) in transgenic Arabidopsis thaliana plant cells.

High-molecular-weight poly([R]-(-)-3-hydroxybutyrate) (PHB), a biodegradable thermoplastic, was produced from a suspension culture of transgenic Arabidopsis thaliana plant cells expressing two genes from the bacterium Alcaligenes eutrophus involved in the synthesis of PHB. The molecular structure of the plant-produced polymer was analysed by gas chromatography, mass spectrometry, proton nuclear magnetic resonance spectroscopy, infra-red spectroscopy, spectropolarimetry, differential scanning calorimetry, X-ray diffraction and size exclusion chromatography. The results indicate that the polymer from transgenic plants appears to have a chemical structure identical to that of PHB produced by bacteria. However, the molecular weight distribution of the plant-produced PHB was much broader than that of typical bacterial PHB.

Production of polyhydroxyalkanoates, a family of biodegradable plastics and elastomers, in bacteria and plants.

In response to problems associated with plastic waste and its effect on the environment, there has been considerable interest in the development and production of biodegradable plastics. Polyhydroxyalkanoates (PHAs) are polyesters that accumulate as inclusions in a wide variety of bacteria. These bacterial polymers have properties ranging from stiff and brittle plastics to rubber-like materials. Because of their inherent biodegradability, PHAs are regarded as an attractive source of nonpolluting plastics and elastomers that can be used for specialty and commodity products. The possibility of producing PHAs in large scale and at a cost comparable to synthetic plastics has arisen from the demonstration of PHA accumulation in transgenic Arabidopsis plants expressing the bacterial PHA biosynthetic genes. Synergism between knowledge of the enzymes and genes contributing to PHA synthesis in bacteria and engineering of plant metabolic pathways will be necessary for the development of crop plants that produce biodegradable plastics.