Proton radiography to improve proton radiotherapy: Simulation study at different proton beam energies

To improve the quality of cancer treatment with protons, a translation of X-ray Computed Tomography (CT) images into a map of the proton stopping powers needs to be more accurate. Proton stopping powers determined from CT images have systematic uncertainties in the calculated proton range in a patient of typically 3-4\% and even up to 10\% in region containing bone~\cite{USchneider1995,USchneider1996,WSchneider2000,GCirrone2007,HPaganetti2012,TPlautz2014,GLandry2013,JSchuemann2014}. As a consequence, part of a tumor may receive no dose, or a very high dose can be delivered in healthy ti\-ssues and organs at risks~(e.g. brain stem)~\cite{ACKnopf2013}. A transmission radiograph of high-energy protons measuring proton stopping powers directly will allow to reduce these uncertainties, and thus improve the quality of treatment. The best way to obtain a sufficiently accurate radiograph is by tracking individual protons traversing the phantom (patient)~\cite{GCirrone2007,TPlautz2014,VSipala2013}. In our simulations we have used an ideal position sensitive detectors measuring a single proton before and after a phantom, while the residual energy of a proton was detected by a BaF$_{2}$ crystal. To obtain transmission radiographs, diffe\-rent phantom materials have been irradiated with a 3x3~cm$^{2}$ scattered proton beam, with various beam energies. The simulations were done using the Geant4 simulation package~\cite{SAgostinelli2003}. In this study we focus on the simulations of the energy loss radiographs for various proton beam energies that are clinically available in proton radiotherapy.Comment: 6 pages, 6 figures, Presented at Jagiellonian Symposium on Fundamental and Applied Subatomic Physics, 7-12 June, 2015, Krak\'ow, Polan

<em>Mangrovimonas cancribranchiae</em> sp. nov., a novel bacterial species associated with the gills of the fiddler crab <em>Cranuca inversa</em> (Brachyura, Ocypodidae) from Red Sea mangroves

\ua9 2024 The Authors. Two bacteria, UG2_1T and UG2_2, were isolated from the gill tissues of the mangrove fiddler crab Cranuca inversa collected on the east coast of the Red Sea (Thuwal, Saudi Arabia). The cells are Gram-negative, rod-shaped, orange-pigmented, motile by gliding with no flagella, strictly aerobic, and grow at 20–37 \ub0C (optimum, 28–35 \ub0C), at pH 5.0–9.0 (optimum, pH 6.0–7.0), and with 1–11 % (w/v) NaCl (optimum, 2–4 %). They were positive for oxidase and catalase activity. Phylogenetic analysis based on 16S rRNA gene sequences indicated that isolates UG2_1T and UG2_2 belong to the genus Mangrovimonas, showing the highest similarity to Mangrovimonas spongiae HN-E26T (99.4 %). Phylogenomic analysis based on the whole genomes, independently using 49 and 120 concatenated genes, showed that strains UG2_1T and UG2_2 formed a monophyletic lineage in a different cluster from other type strain species within the genus Mangrovimonas. The genome sizes were 3.08 and 3.07 Mbp for UG2_1T and UG2_2, respectively, with a G+C content of 33.8 mol% for both strains. Values of average nucleotide identity and digital DNA–DNA hybridization between the strains and closely related species were 91.0 and 43.5 %, respectively. Chemotaxonomic analysis indicated that both strains had iso-C15: 0 and iso-C15: 1 G as dominant fatty acids, and the primary respiratory quinone was identified as MK-6. The major polar lipids comprised phosphatidylethanolamine, one unidentified glycolipid, one unidentified phospholipid, two unidentified aminolipids, and four unidentified lipids. Based on phylogenetic, phylogenomic, genome relatedness, phenotypic, and chemotaxonomical data, the two isolates represent a novel species within the genus Mangrovimonas, with the proposed name Mangrovimonas cancribranchiae sp. nov., and the type strain UG2_1T (=KCTC 102158T=DSM 117025T)

Validation of a Patient Global Assessment for extent, severity and impact to define the severity strata for the Self Assessment Vitiligo Extent Score (SA-VES)

Background: The Self Assessment Vitiligo Extent Score (SA‐VES) is a validated, patient‐reported outcome measure to assess the body surface area affected with vitiligo. Information on how to translate the obtained score into extent, severity and impact strata (mild–moderate–severe) is still lacking. Stratification is helpful to define inclusion criteria for trials, enables comparison and pooling of trial results and can be used for epidemiological research. Objectives: The aim was to develop extent, severity and impact strata for the SA‐VES based on validated anchor‐based questions. Methods: In total, 315 patients with vitiligo (non‐segmental; age ≥ 16) recruited at the Ghent University Hospital (Belgium) completed a questionnaire that was conducted in cooperation with the Dutch Society for vitiligo patients to ensure content validity. First three anchor questions included in the questionnaire [Patient Global Assessment (PtGA) for vitiligo extent, severity and impact] were assessed for content validity, construct validity and intrarater reliability. Subsequently, the PtGAs were used to stratify the SA‐VES based on ROC analysis. Results: For all PtGAs (PtGA extent, PtGA severity, PtGA impact), at least 75% of hypotheses evaluated for construct validity were confirmed. Intrarater reliability of all PtGAs was good to excellent (ICCs PtGA extent: 0.623; PtGA severity: 0.828; PtGA impact: 0.851). The optimal cut‐off values of the SA‐VES between the three global categories (mild/limited – moderate – severe/extensive) were 1.05% and 6.45% based on PtGA extent, 2.07% and 4.8% based on PtGA severity and 2% and 3.35% based on PtGA impact. Conclusion: This study provides the first guide for the interpretation of the numerical output obtained by the SA‐VES (vitiligo extent) and enables the translation into a global vitiligo grading for extent, severity and impact. As patients’ interpretation of vitiligo extent, severity and impact may vary amongst patients worldwide, future international studies will be required

POLG1 p.R722H mutation associated with multiple mtDNA deletions and a neurological phenotype

<p>Abstract</p> <p>Background</p> <p>The c.2447G>A (p.R722H) mutation in the gene <it>POLG1 </it>of the catalytic subunit of human mitochondrial polymerase gamma has been previously found in a few occasions but its pathogenicity has remained uncertain. We set out to ascertain its contribution to neuromuscular disease.</p> <p>Methods</p> <p>Probands from two families with probable mitochondrial disease were examined clinically, muscle and buccal epithelial DNA were analyzed for mtDNA deletions, and the <it>POLG1, POLG2, ANT1 </it>and <it>Twinkle </it>genes were sequenced.</p> <p>Results</p> <p>An adult proband presented with progressive external ophthalmoplegia, sensorineural hearing impairment, diabetes mellitus, dysphagia, a limb myopathy and dementia. Brain MRI showed central and cortical atrophy, and ¹⁸F-deoxyglucose PET revealed reduced glucose uptake. Histochemical analysis of muscle disclosed ragged red fibers and cytochrome c oxidase-negative fibers. Electron microscopy showed subsarcolemmal aggregates of morphologically normal mitochondria. Multiple mtDNA deletions were found in the muscle, and sequencing of the <it>POLG1 </it>gene revealed a homozygous c.2447G>A (p.R722H) mutation. His two siblings were also homozygous with respect to the p.R722H mutation and presented with dementia and sensorineural hearing impairment. In another family the p.R722H mutation was found as compound heterozygosity with the common p.W748S mutation in two siblings with mental retardation, ptosis, epilepsy and psychiatric symptoms. The estimated carrier frequency of the p.R722H mutation was 1:135 in the Finnish population. No mutations in <it>POLG2</it>, <it>ANT1 </it>and <it>Twinkle </it>genes were found. Analysis of the POLG1 sequence by homology modeling supported the notion that the p.R722H mutation is pathogenic.</p> <p>Conclusions</p> <p>The recessive c.2447G>A (p.R722H) mutation in the linker region of the <it>POLG1 </it>gene is pathogenic for multiple mtDNA deletions in muscle and is associated with a late-onset neurological phenotype as a homozygous state. The onset of the disease can be earlier in compound heterozygotes.</p

Corrigendum: Short-lived positron emitters in beam-on PET imaging during proton therapy (2015 Phys. Med. Biol. 60 8923)

Because of strong indications of multiple counting by the multi-channel scaler (MCS) during most of the experiments described in Dendooven et al (2015 Phys. Med. Biol. 60 8923–47), the production of short-lived positron emitters in the stopping of 55 MeV protons in water, carbon, phosphorus and calcium was remeasured. The new results are reported here. With proper single counting of the MCS, the new production rates are 1.1 to 2.9 times smaller than reported in Dendooven et al (2015 Phys. Med. Biol. 60 8923–47). The omission of the conversion from MCS time bin to time unit in the previous data analysis was corrected, leading to an increase of the production rate by a factor of 2.5 or 10 for some nuclides. The most copiously produced short-lived nuclides and their production rates relative to the relevant long-lived nuclides are: 12N (T 1/2  =  11 ms) on carbon (5.3% of 11C), 29P (T 1/2  =  4.1 s) on phosphorus (23% of 30P) and 38mK (T 1/2  =  0.92 s) on calcium (173% of 38gK). The number of decays integrated from the start of an irradiation as a function of time during the irradiation of PMMA and 4 tissue materials has been determined. For (carbon-rich) adipose tissue, 12N dominates up to 70 s. On bone tissue, 38mK dominates the beam-on PET counts from 0.2–0.7 s until about 80–110 s. Considering nuclides created on phosphorus and calcium, the short-lived ones provide 8 times more decays than the long-lived ones during a 70 s irradiation. Bone tissue will thus be much better visible in beam-on PET compared to PET imaging after an irradiation. From the estimated number of 12N PET counts, we conclude that, for any tissue, except carbon-poor ones, 12N PET imaging potentially provides equal quality proton range information as prompt gamma imaging with an optimized knife-edge slit camera