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Background The putative Ergothioneine Transporter, SLC22A4/OCTN1, is expressed in the intestine and monocytes/macrophages, and its widely represented missense variant L503F (0.4 Minor Allele Frequency in Caucasians) has been found to be associated with Crohn’s disease, sporadic colorectal cancer in early age and ulcerative colitis (UC) patients. The leucine-to-phenylalanine substitution at amino acid 503 affects OCTN1 capacity to transport ergothioneine, acetylcholine and likely other substrates of endogenous or microbial origin; however, whether this defect contributes to inflammatory bowel disease (IBD) pathogenesis, and the mechanistic underpinnings, remain elusive. Methods In order to gain mechanistic insight on the role of SLC22A4 in IBD, we first analyzed primary monocytes from healthy donors and UC patients of varying OCTN1 genotypes. Then we stably knocked down or overexpressed OCTN1 and its disease-associated variant in the monocytic cell line THP-1. Finally, we compared wild-type and OCTN1 knockout C57BL/6 mice in a chemical colitis paradigm in vivo. Results Primary adherent monocytes from healthy donors homozygous for the IBD-associated allele (TT) displayed a significant enhancement of interleukin 1 beta (IL-1β) response to peptidoglycan (PGN) compared to the other genotypes. Likewise, cells from UC patients bearing the 503F variant released more IL-1β in response to live bacteria and displayed reduced expression of autophagy markers (e.g. p62, LC3), compared to patients negative for the variant. In agreement with these findings, OCTN1-deficient THP-1 macrophages secreted reduced amounts of IL-1β when challenged in vitro with PGN or live bacteria. Most relevant, THP1 cells engineered to overexpress the 503F variant of OCTN1 displayed a much stronger IL-1β response to muramyl dipeptide and PGN challenge, compared to cells transduced with the “wild type” transporter. Also consistent with a role for OCTN1 variants in inflammatory cascades relevant to IBD, in vivo studies revealed milder DSS-induced colitis in OCTN1 knockout mice compared to wild-type animals, both at the peak of disease severity and at the end of the recovery period. Conclusion Collectively our initial evidence supports the view that OCTN1 may have a causative role in IBD via deranged bacterial sensing and cytokine production, with 503F likely behaving as a gain-of-function variant. Thus, targeting OCTN1 variant may provide unprecedented opportunities for the personalized treatment of IBD patients and a better understanding of disease pathogenesis.

Aims In 2018, we published early results from a cohort of patients treated with stereotactic body radiotherapy (SBRT) after previous radiotherapy with definitive or postoperative intent. We sought to provide extended follow-up of this cohort to confirm the safety and efficacy of this approach in a real-world scenario. Materials and methods Fifty patients affected by local relapse after previous definitive or postoperative radiotherapy were treated with SBRT. Treatment provided a total dose of 30 Gy in five fractions. Data about biochemical relapse-free survival (BRFS) and metastasis-free survival (MFS), together with adverse events, were analysed. Toxicity was reported according to Common Terminology Criteria for Adverse Events (CTCAE) score v.4.03. Results After a median follow-up of 48.2 months, the median BRFS was 43 months. A Gleason score >7 and concomitant androgen deprivation therapy were shown to be predictors of the worst BRFS (hazard ratio 2.42, 95% confidence interval 1.09–5.41, P = 0.02; hazard ratio 2.83, 95% confidence interval 1.17–6.8, P = 0.02, respectively). The median MFS was not reached; concomitant androgen deprivation therapy was confirmed to be predictive of the worst MFS (hazard ratio 4.75, 95% confidence interval 1.52–14.8, P = 0.007). Late grade 1 and 2 rectal and bladder toxicity occurred in three (6%) and 13 (26%) patients, respectively. One patient experienced both grade 3 acute and chronic bladder toxicity. Conclusion Salvage SBRT re-irradiation after previous postoperative or definitive radiotherapy for local prostate cancer recurrence confirmed promising results in terms of oncological outcomes and the safety of this approach.

We report the experimental realization of a new kind of optical lattice for ultra-cold atoms where arbitrarily large separation between the sites can be achieved without renouncing to the stability of ordinary lattices. Two collinear lasers, with slightly different commensurate wavelengths and retroreflected on a mirror, generate a superlattice potential with a periodic "beat-note" profile where the regions with large amplitude modulation provide the effective potential minima for the atoms. To prove the analogy with a standard large spacing optical lattice we study Bloch oscillations of a Bose Einstein condensate with negligible interactions in the presence of a small force. The observed dynamics between sites separated by ten microns for times exceeding one second proves the high stability of the potential. This novel lattice is the ideal candidate for the coherent manipulation of atomic samples at large spatial separations and might find direct application in atom-based technologies like trapped atom interferometers and quantum simulators., Comment: 5 pages, 4 figures

We study the ultimate bounds on the sensitivity of a Bloch-oscillation atom interferometer where the external force is estimated from the measurement of the on-site atomic density. For external forces such that the energy difference between lattice sites is smaller than the tunneling energy, the atomic wave function spreads over many lattice sites, increasing the separation between the occupied modes of the lattice and naturally enhancing the sensitivity of the interferometer. To investigate the applicability of this scheme we estimate the effect of uncontrolled fluctuations of the tunneling energy and the finite resolution of the atom detection. Our analysis shows that a horizontal lattice combined with a weak external force allow for high sensitivities. Therefore, this setup is a promising solution for compact devices or for measurements with high spatial resolution.

Resume L’utilisation d’Internet et des medias sociaux est l’activite la plus frequente aujourd’hui pour les adolescents et jeunes adultes. Aujourd’hui, la question n’est plus tant le temps passe en ligne mais a partir de combien de temps est-ce pathologique ou a partir de quel âge peut-on etre en ligne sans que cela ne soit trop jeune. Une large part du developpement social et emotionnel se deroule sur Internet pour la jeune generation. Internet leur offre un portail pour leur distraction et leur communication avec des avantages mais aussi des risques. Devant l’ampleur de ce phenomene, nous avons realise une revue de la litterature afin de faire un point sur la situation actuelle de l’usage d’Internet pour les adolescents/jeunes adultes concernant la cyberdependance, en particulier celle liee aux medias sociaux et aux jeux video ainsi que ses comorbidites avec des pathologies psychiatriques et son impact psychologique. Nous avons egalement recherche la litterature concernant les enjeux de la representation du soi, ses consequences sur l’atteinte de la vie privee et la perte de l’estime de soi, le cyberharcelement et les troubles du sommeil. Les jeunes sont a risque de vivre des experiences negatives plus que les parents n’ont tendance a le realiser. Internet et les medias sociaux sont un sujet d’actualite qui presente un grand interet a etre explore en lien avec des enjeux sociologiques, psychologique et psychiatrique. Les consequences cliniques se font deja ressentir avec la presence de comorbidites et de dependances en psychiatrie mais aussi la presence de consequences physiques en pediatrie.

Background Ulcerative colitis is a chronic invalidating disease, whose therapeutic strategies include amino-salicylates, steroids, probiotics, immune-modulators, biologics, fecal microbiota transplantation and surgery. In clinical practice, there is little evidence available about elements that could predict response to each of the above-mentioned therapies. Our study suggests that OCTN1, an organic cation transporter directly involved in innate immunity, with its variants (C503L homozygous, heterozygous or T503F), could have a role in predicting individual response to biologic therapies (antiTNFa and vedolizumab). Methods In this prospective study, we enrolled a cohort of, 80 patients with active ulcerative colitis (51 in treatment with anti-TNF alpha agents and, 29 with vedolizumab), determining their OCTN1 genotype and evaluating their clinical response to therapy, calculated with clinical Mayo score, after six weeks (T1), six months (T2) and after three years (T3). Results Left colitis at diagnosis was more frequent in C503L patients (60% left colitis vs, 40% pancolitis) than patients with T503F (42.8% left colitis vs, 57.2 pancolitis). In the same way, the average age at diagnosis was sensibly lower in patients with T503F genotype (34.7 years C503L vs, 25 years T503F). We used clinical response at T2 (6 months) as a primary outcome of our study. Among patients under anti-TNF alpha therapies, patients with C503L genotype were divided into, 8 no responders and, 6 responders (43% responders vs, 57% no responders); patients with T503F genotype were divided into, 10 responders and, 2 no responder (80% responders vs, 20% no responders). On the contrary, patients under vedolizumab therapy showed different trends: patients with C503L genotype were divided into, 12 responders and, 3 no responders (83% responders vs, 17% no responders); patients with T503F genotype were, 1 responder and, 1 no responder (50% responders vs, 50% no responders). After, 3 years, patients responders to anti-TNF alpha therapies at T2, with T503F genotype, still maintain the response to the same drug. Conclusion Patients with the T503F genotype present an overall worse course of the disease, with a higher rate of pancolitis and younger age at diagnosis. Patients with the C503L genotype showed a better response to vedolizumab, whilst patients with the T503F genotype showed a better response to anti-TNF alpha. We can therefore conclude that the presence of the mutation (allele T) increases the response rate to anti-TNF alpha, especially for the homozygous mutated genotype (OR=371.82, p=0.009), but for the heterozygous genotype as well (OR=10.95, p=0.088).

We report on the dynamical formation of self-bound quantum droplets in attractive mixtures of $^{39}$K atoms. Considering the experimental observations of Semeghini et al., Phys. Rev. Lett. 120, 235301 (2018), we perform numerical simulations to understand the relevant processes involved in the formation of a metastable droplet from an out-of-equilibrium mixture. We first analyze the so-called self-evaporation mechanism, where the droplet dissipates energy by releasing atoms, and then we consider the effects of losses due to three-body recombinations and to the balancing of populations in the mixture. We discuss the importance of these three mechanisms in the observed droplet dynamics and their implications for future experiments.

Purpose High precision radiosurgery demands comprehensive delivery-quality-assurance techniques. The use of a liquid-filled ion-chamber-array for robotic-radiosurgery delivery-quality-assurance was investigated and validated using several test scenarios and routine patient plans. Methods and material Preliminary evaluation consisted of beam profile validation and analysis of source–detector-distance and beam-incidence-angle response dependence. The delivery-quality-assurance analysis is performed in four steps: (1) Array-to-plan registration, (2) Evaluation with standard Gamma-Index criteria (local-dose-difference ⩽ 2%, distance-to-agreement ⩽ 2 mm, pass-rate ⩾ 90%), (3) Dose profile alignment and dose distribution shift until maximum pass-rate is found, and (4) Final evaluation with 1 mm distance-to-agreement criterion. Test scenarios consisted of intended phantom misalignments, dose miscalibrations, and undelivered Monitor Units. Preliminary method validation was performed on 55 clinical plans in five institutions. Results The 1000SRS profile measurements showed sufficient agreement compared with a microDiamond detector for all collimator sizes. The relative response changes can be up to 2.2% per 10 cm source–detector-distance change, but remains within 1% for the clinically relevant source–detector-distance range. Planned and measured dose under different beam-incidence-angles showed deviations below 1% for angles between 0° and 80°. Small-intended errors were detected by 1 mm distance-to-agreement criterion while 2 mm criteria failed to reveal some of these deviations. All analyzed delivery-quality-assurance clinical patient plans were within our tight tolerance criteria. Conclusion We demonstrated that a high-resolution liquid-filled ion-chamber-array can be suitable for robotic radiosurgery delivery-quality-assurance and that small errors can be detected with tight distance-to-agreement criterion. Further improvement may come from beam specific correction for incidence angle and source–detector-distance response.

We report on the study of binary collisions between quantum droplets formed by an attractive mixture of ultracold atoms. We distinguish two main outcomes of the collision, i.e. merging and separation, depending on the velocity of the colliding pair. The critical velocity $v_c$ that discriminates between the two cases displays a different dependence on the atom number $N$ for small and large droplets. By comparing our experimental results with numerical simulations, we show that the non-monotonic behavior of $v_c(N)$ is due to the crossover from a compressible to an incompressible regime, where the collisional dynamics is governed by different energy scales, i.e. the droplet binding energy and the surface tension. These results also provide the first evidence of the liquid-like nature of quantum droplets in the large $N$ limit, where their behavior closely resembles that of classical liquid droplets.

Self-bound quantum droplets are a newly discovered phase in the context of ultracold atoms. In this Letter, we report their experimental realization following the original proposal by Petrov [Phys. Rev. Lett. 115, 155302 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.155302], using an attractive bosonic mixture. In this system, spherical droplets form due to the balance of competing attractive and repulsive forces, provided by the mean-field energy close to the collapse threshold and the first-order correction due to quantum fluctuations. Thanks to an optical levitating potential with negligible residual confinement, we observe self-bound droplets in free space, and we characterize the conditions for their formation as well as their size and composition. This work sets the stage for future studies on quantum droplets, from the measurement of their peculiar excitation spectrum to the exploration of their superfluid nature.

Resume Le nombre d’enfants et d’adolescents diagnostiques et traites pour une bipolarite a considerablement augmente alors que seulement quelques uns de ces enfants ont reellement un diagnostic s’apparentant a une maladie bipolaire « typique ». La controverse actuelle concerne les enfants et adolescents avec une irritabilite chronique, des crises de colere et une comorbidite elevee pour les troubles de l’hyperactivite avec deficit de l’attention et consideres jusqu’a present comme souffrant d’une forme developpementale de manie. Pour ces enfants, le DSM-5 a propose un nouveau diagnostic : le trouble severe de regulation de l’humeur (TSRH). Beaucoup d’enfants diagnostiques bipolaires ou comme ayant des troubles des conduites, souffrent en realite de TSRH. Aussi, a travers l’expose du cas clinique d’un enfant agite, nous avons illustre un tableau clinique de TSRH. Ce patient semblait souffrir de troubles de l’opposition avec provocation, associes a un risque d’evolution psychopathique et presentait finalement cette pathologie qui s’inscrit en realite dans un trouble de l’humeur. Dans une perspective integrative, l’instabilite psychomotrice associee au TSRH est analysee ici selon une evaluation clinique standardisee couplee a une investigation des aspects psychopathologiques et psychomoteurs. Notre observation a ainsi abouti a un diagnostic de TSRH associe a une instabilite psychomotrice syndromique. Les perspectives therapeutiques sont ensuite exposees a partir des connaissances actuelles sur les dimensions psychodynamique et neurophysiologique des instabilites psychomotrices et plus particulierement de celles liees a un TSRH associe a un trouble de la personnalite.

Resume L’attribution du diagnostic de bipolarite en pedopsychiatrie a particulierement augmente ces dernieres annees, en particulier aux Etats-Unis pourtant les donnees epidemiologiques ne montrent pas d’augmentation de sa prevalence. Beaucoup d’enfants en souffrance n’ont pas recu de diagnostique car ils avaient un trouble qui n’avait pas encore ete defini. Le DSM-5 a nomme ce trouble Disruptive Mood Dysregulation Disorder (DMDD). Dans la litterature francophone, on retrouve le terme de dysregulation emotionnelle et comportementale severe (DES). Les criteres fondamentaux du DES sont (1) une irritabilite chronique severe et (2) des crises de rage, celles-ci comprennent des manifestations verbales et comportementales qui sont des reactions disproportionnees en termes de duree et d’intensite par rapport a la situation qui les a provoquees. Ces enfants presentent donc un tableau clinique de troubles disruptifs qui exprime en realite une pathologie de l’humeur internalisee, marquee par une instabilite thymique associee a une dysphorie. Ces « rages » caracterisent donc un nouveau type specifique de trouble de l’humeur chez l’enfant. De plus, autant le DES n’est pas une predisposition pour un trouble bipolaire, autant il l’est pour les troubles depressifs apparaissant precocement a l’âge adulte. Ainsi, le diagnostic de DES vise a distinguer ces enfants de ceux souffrant de troubles bipolaires et a eviter d’attribuer a tort un diagnostic de troubles des conduites ce qui aurait des consequences prejudiciables d’un point de vu societal et therapeutique. En effet, les enjeux de la prise de conscience de l’existence du DES sont majeurs pour la prise en charge, notamment medicamenteuse.

Purpose Stereotactic body radiation therapy (SBRT) approach for treating early stage solid tumor and metastases is increasing worldwide. In 2013 the Italian Association of Medical Physicists (AIFM) constituted a working group in order to standardize SBRT dosimetric aspects. A survey was designed aiming to delineate the status of the technology applied in SBRT on a national level. Clinical evaluation of SBRT was out of the present study. Methods A questionnaire was designed by three medical physicists expert of SBRT using Google Forms containing questions regarding image-guidance solutions, respiratory management, delivery mode, treatment planning system (TPS) commissioning, and QA approach. A large number of medical physicists from 54 centers with heterogeneous technology was invited to participate and 45 of them completed the survey. Experts were asked to provide suggestions based on personal experience and specificity. Results After two webcall and two versions, the final questionnaire was developed. Results showed great heterogeneity in terms of technologies, image-guidance solutions, respiratory management, delivery mode, TPS commissioning and QA approach. The most available delivery system was conventional linacs with VMAT modality; the most common energies used were 6 MV and 6 MV-FFF; for the 56% of centers robotic couch was available, CBCT was the most used IGRT technique (78% of centers) and 40% of centers did not use respiratory management during treatment delivery. The smallest measured field size for lateral beam profiles was lower than 1 × 1 cm2, while only the 62% of centers used the same field size for the TPS commissioning (from 1 × 1 cm2 to 4 × 4 cm2). A large number of centers (51%) feel the necessity to upgrade their dosimetric devices dedicated to SBRT QA. Conclusions This survey on SBRT could allow to improve the QA procedure and to define minimum requirements for SBRT dosimetric verification.

Purpose Accurate and reliable patient-specific QA is required for CyberKnife (CK) MLC treatment plans. Films are the current method of choice, but filmless solutions are starting to be introduced in the routine [1] . Aim of this study is to test the sensitivity of a filmless QA technique to simulated delivery errors for CK MLC plans, and to discuss which γ -index criteria are adequate; DVH implications were also analyzed. Methods Preliminarily, routine garden fence tests were employed to assess MLC leaf positioning accuracy. Test plans were then delivered to Octavius 1000SRS array (PTW) and EBT3 (Ashland), editing leaf positions of five clinical plans (prostate/pancreas) with three error types: MLC banks opened, both of 0.3 mm (03 mm OUT)/0.5 mm (05 mm OUT), one of 1 mm (1 mm X2)), closed (both of 0.5 mm (05 mm IN)) and shifted (both of 1 mm (1 mm X1X2)). Γ-index analysis was performed comparing the measured plans to the unedited dose distributions using three criteria: 2%2 mm, 3%1 mm, 2%1 mm. For patient plans, DVH implications were also considered. Results The garden fence leaf positioning distribution mean over 11578 values is 0.07 ± 0.16 mm. The 95% percentile is 0.34 mm, with 141 values (1.2%) outside the 0.5 mm tolerance. In Fig. 1 1000SRS passing rates for the edited and the unedited plans are reported for two cases. For all plans, the highest influence on pass-rate is found for increased segments size. With both banks opened of 0.3 mm a mean passing rate decrease from 94.0% to 80.2% was observed (3%1 mm). EBT3 show analogous results. In Table 1 the simulated errors effect on DVH parameters is reported for Plan2. A 0.3 mm opening produced a total of 7 OAR constraint violations over all plans. Conclusions High sensitivity in the detection of small delivery errors, slightly affecting DVHs, is achievable for CK MLC plans delivery QA even employing filmless solutions. A 2%2 mm criteria is not always tight enough.

Purpose The CyberKnife (CK) M6 series is equipped with a MLC intended to achieve higher delivery efficiency than the circular IRIS variable collimator and to expand the feasibility of CK treatments to larger tumors. This study aimed to evaluate the CK-MLC performance for SBRT plans focusing on (i) comparison with IRIS (ii) large volume tumor treatments (iii) dosimetric delivery accuracy. Methods (i) IRIS and MLC plans in 3–5 fractions were created for 30 liver, 15 pancreas and 10 prostate cases and compared in terms of coverage, conformity (nCI), dose gradient (R50), homogeneity (HI), OAR doses, PTV gEUD, MU normalized to prescription dose (MU/PD), treatment time both estimated by TPS (tTPS) and measured (tmeas). Prostate plans MU/PD and tTPS were compared with similar published data [1] , [2] . (ii) SBRT MLC plans (30 Gy/5 fractions) were optimized for large PTVs (240 cm3 ÷ 1140 cm3, diameters 8 cm ÷ 14 cm) in one pancreas and three liver cases. Plan quality, treatment time and feasibility to meet OAR constraints were evaluated. (iii) Delivery QA was performed for 50 MLC plans using different techniques. Results (i) Compared to IRIS ( Table 1 ), MLC achieved equivalent coverage, conformity, homogeneity and EUD without compromising OAR sparing and improving (p Conclusions MLC improves dose fall-off and delivery efficiency compared to IRIS. Time reduction is partially lost when measured and is highly variable among different studies. MLC permits to extend CK SBRT treatments to larger PTVs maintaining high dosimetric accuracy.

Purpose Currently, most of the multicenter analyses on treatment planning rely on the extraction of selected data from the DVH of each plan. A grouped analysis can be biased due to different algorithms implemented in different TPSs used to generate the DVH. In this work we used a consistent method to present a preliminary analysis of multiple data coming from a national survey on stereotactic body radiotherapy (SBRT) planning. Methods A single spine case was shared among 36 radiation oncology centers. The dose prescription was 30 Gy in 3 fractions with specific constraints on target coverage and dose to nearby organs at risk. Data were collected in DICOM-RT format. A script was developed in R language using the RadOnc R-Package for recalculating the DVHs using the same algorithm. Specific DVH points (V30Gy, D90%, D2%) collected from the centers were compared with those recalculated with RadOnc. A grouped analysis of recalculated DVHs was performed therefore eliminating the bias due to different DVH calculation algorithms. Results Differences between collected and recalculated DVHs were minimal, however in some cases deviations up to 1.5% were observed. The multiple-DVH analysis showed a notable variability on target dose level (Fig. 1), up to 150% likely related to constraints on target coverage and SBRT technique. This variability was caused mainly by different planning optimization strategies, rather than by the use of a specific treatment technology. Conclusions The observed variability suggests that comparable standards in patient treatment among different centers can be obtained if a consistent high-level data sharing capability is granted. In the strive to harmonize the planning process, this analysis constitutes a first step toward the creation of a platform of crowd-knowledge-based planning guidelines. This platform could represent a high-quality benchmark for those centers that are willing to implement SBRT techniques (concept expressed in Fig. 1).

This article discusses how to reduce the barriers universities and industry face when working together on collaborative research projects. As a best practices study, the article describes lessons that should not be viewed as isolated experiments, but as practices that can create the synergy required to drive collaborative research, innovation, and digital inclusion. This is particularly critical for developing and growth market countries, but appropriate for all.

Purpose The aim of the present work was to evaluate small field size output factors (OFs) using the latest diamond detector commercially available, PTW-60019 microDiamond, over different CyberKnife systems. OFs were measured also by silicon detectors routinely used by each center, considered as reference. Methods Five Italian CyberKnife centers performed OFs measurements for field sizes ranging from 5 to 60 mm, defined by fixed circular collimators (5 centers) and by Iris ™ variable aperture collimator (4 centers). Setup conditions were: 80 cm source to detector distance, and 1.5 cm depth in water. To speed up measurements two diamond detectors were used and their equivalence was evaluated. MonteCarlo (MC) correction factors for silicon detectors were used for comparing the OF measurements. Results Considering OFs values averaged over all centers, diamond data resulted lower than uncorrected silicon diode ones. The agreement between diamond and MC corrected silicon values was within 0.6% for all fixed circular collimators. Relative differences between microDiamond and MC corrected silicon diodes data for Iris ™ collimator were lower than 1.0% for all apertures in the totality of centers. The two microDiamond detectors showed similar characteristics, in agreement with the technical specifications. Conclusions Excellent agreement between microDiamond and MC corrected silicon diode detectors OFs was obtained for both collimation systems fixed cones and Iris ™ , demonstrating the microDiamond could be a suitable detector for CyberKnife commissioning and routine checks. These results obtained in five centers suggest that for CyberKnife systems microDiamond can be used without corrections even at the smallest field size.

Robotic radiosurgery demands comprehensive delivery quality assurance (DQA), but guidelines for commissioning of the DQA method is missing. We investigated the stability and sensitivity of our film-based DQA method with various test scenarios and routine patient plans. We also investigated the applicability of tight distance-to-agreement (DTA) Gamma-Index criteria.We used radiochromic films with multichannel film dosimetry and re-calibration and our analysis was performed in four steps: 1) Film-to-plan registration, 2) Standard Gamma-Index criteria evaluation (local-pixel-dose-difference ≤2%, distance-to-agreement ≤2 mm, pass-rate ≥90%), 3) Dose distribution shift until maximum pass-rate (Maxγ) was found (shift acceptance1 mm), and 4) Final evaluation with tight DTA criteria (≤1 mm). Test scenarios consisted of purposefully introduced phantom misalignments, dose miscalibrations, and undelivered MU. Initial method evaluation was done on 30 clinical plans.Our method showed similar sensitivity compared to the standard End-2-End-Test and incorporated an estimate of global system offsets in the analysis. The simulated errors (phantom shifts, global robot misalignment, undelivered MU) were detected by our method while standard Gamma-Index criteria often did not reveal these deviations. Dose miscalibration was not detected by film alone, hence simultaneous ion-chamber measurement for film calibration is strongly recommended. 83% of the clinical patient plans were within our tight DTA tolerances.Our presented methods provide additional measurements and quality references for film-based DQA enabling more sensitive error detection. We provided various test scenarios for commissioning of robotic radiosurgery DQA and demonstrated the necessity to use tight DTA criteria.

A project dedicated to stereotactic body radiotherapy (SBRT) dosimetric aspects started in the framework of the Italian Association of Medical Physics (AIFM) SBRT working group. Its main objectives are manifold but sharing the knowledge between different clinics is the one of the most important. More than 30 centres, equipped with Varian, Elekta, Siemens or CyberKnife linac were enrolled. The project was divided in several work-packages, the first one evaluated the relative measurements with detectors routinely used by individual centers and in the following different detectors run in various centre. Each centre in the same work-package performed dose profile of field size ranging from 0.6 × 0.6 cm 2 to 5.0 × 5.0 cm 2 , and relative output factors (ROF) measurements with a diamond or silicon diode or scintillator detector. In workpackage-1 ROF values measured in the first phase were compared with the ones measured with a microdiamond showing a higher inter-center consistency with this dosimeter compared to routine detectors. In workpackage-2 a silicon diode of new generation was used also to develop a mathematical relation from multicentric experimental data, which describes and predicts the ROF as a function of effective field size for TrueBeam Varian and Elekta linacs. Workpackage-3 used a plastic scintillator for TPR20, 10 and ROF; the latter showed a greater variability. Workpackage-4 used diamond and plastic scintillator with Cyberknife beams, to evaluate if microDiamond could be a suitable alternative to silicon diodes for OF determination and to validate the feasibility of using the scintillator as a reference detector in consideration of the CerenkovLightRatio and experimental uncertainties. The results of the study for all the detectors emphasized the usefulness of a multi-center validation over a single center approach.

Adult human skeletal muscle-derived cells (HuSkMC) propagated in vitro are under investigation as a cell-based therapy for the treatment of myocardial infarction. We have characterized HuSkMC with respect to cell identity and state of differentiation as a prerequisite to their clinical use. Flow cytometric analysis of propagated HuSkMC revealed a population of cells that expressed the myoblast markers CD56 and desmin. The presence of myoblasts in these cultures was further confirmed by their capacity to form myotubes and increase creatine kinase activity when cultured in low serum conditions. The non-myoblast fraction of these propagated cells expressed TE7, a marker associated with the fibroblast phenotype. Spontaneous differentiation of myoblasts occurred during serial propagation of HuSkMC, as judged by myotube formation, thereby reducing the myoblast representative fraction with continued cell expansion. We examined transforming growth factor beta2 (TGF-beta2) for its utility in controlling this spontaneous differentiation of adult human myoblasts in vitro. Propagation of HuSkMC in the presence of 1 ng/ml TGF-beta2 for 5 days decreased desmin expression within the myoblast population and caused a parallel reduction of creatine kinase activity. CD56 expression was unaffected, indicating a differential regulation of these myoblast markers. The reduction in desmin expression and creatine kinase activity was, however, reversible upon the removal of TGF-beta. These data collectively indicate that TGF-beta2 restrained differentiation of adult human skeletal myoblasts during propagation without causing irreversible loss of the myoblast phenotype, demonstrating the potential utility of using TGF-beta2 during cultivation and expansion of HuSkMC intended for therapeutic implantation.