Measuring the temperature and heating rate of a single ion by imaging

We present a technique based on high resolution imaging to measure the absolute temperature and the heating rate of a single ion trapped at the focus of a deep parabolic mirror. We collect the fluorescence light scattered by the ion during laser cooling and image it onto a camera. Accounting for the size of the point-spread function and the magnification of the imaging system, we determine the spatial extent of the ion, from which we infer the mean phonon occupation number in the trap. Repeating such measurements and varying the power or the detuning of the cooling laser, we determine the anomalous heating rate. In contrast to other established schemes for measuring the heating rate, one does not have to switch off the cooling but the ion is always maintained in a state of thermal equilibrium at temperatures close to the Doppler limit

Multi-modality functional image guided dose escalation in the presence of uncertainties

AbstractBackground and purposeIn order to increase local tumour control by radiotherapy without increasing toxicity, it appears promising to harness functional imaging (FI) to guide dose to sub-volumes of the target with a high tumour load and perhaps de-escalate dose to low risk volumes, in order to maximise the efficiency of the deposited radiation dose.Methods and materialsA number of problems have to be solved to make focal dose escalation (FDE) efficient and safe: (1) how to combine ambiguous information from multiple imaging modalities; (2) how to take into account uncertainties of FI based tissue classification; (3) how to account for geometric uncertainties in treatment delivery; (4) how to add complementary FI modalities to an existing scheme. A generic optimisation concept addresses these points and is explicitly designed for clinical efficacy and for lowering the implementation threshold to FI-guided FDE. It combines classic tumour control probability modelling with a multi-variate logistic regression model of FI accuracy and an uncomplicated robust optimisation method.ResultsIts key elements are (1) that dose is deposited optimally when it achieves equivalent expected effect everywhere in the target volume and (2) that one needs to cap the certainty about the absence of tumour anywhere in the target region. For illustration, an example of a PET/MR-guided FDE in prostate cancer is given.ConclusionsFDE can be safeguarded against FI uncertainties, at the price of a limit on the sensible dose escalation

On the visualization of universal degeneracy in the IMRT problem

BACKGROUND: In general, the IMRT optimisation problem possesses many equivalent solutions. This makes it difficult to decide whether a result produced by an IMRT planning algorithm can be further improved, e.g. by adding more beams, or whether it is close to the globally best solution. RESULTS: It is conjectured that the curvature properties of the objective function around any globally optimum dose distribution are universal. This allows an assessment of optimality of dose distributions that are generated by different beam arrangements in a complementary manner to the objective function value alone. A tool to visualize the curvature structure of the objective function is devised. CONCLUSION: In an example case, it is demonstrated how the assessment of the curvature space can indicate the equivalence of rival beam configurations and their proximity to the global optimum

Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis

Cryptococcus neoformans is an opportunistic fungal pathogen preferentially causing disease in immunocompromised individuals such as organ-transplant-recipients, patients receiving immunosuppressive medications or, in particular, individuals suffering from HIV infection. Numerous studies clearly indicated that the control of C. neoformans infections is strongly dependent on a prototypic type 1 immune response and classical macrophage activation, whereas type 2-biased immunity and alternative activation of macrophages has been rather implicated in disease progression and detrimental outcomes. However, little is known about regulatory pathways modulating and balancing immune responses during early phases of pulmonary cryptococcosis. Here, we analyzed the role of group 2 innate lymphoid cells (ILC2s) for the control of C. neoformans infection. Using an intranasal infection model with a highly virulent C. neoformans strain, we found that ILC2 numbers were strongly increased in C. neoformans-infected lungs along with induction of a type 2 response. Mice lacking ILC2s due to conditional deficiency of the transcription factor RAR-related orphan receptor alpha (Rora) displayed a massive downregulation of features of type 2 immunity as reflected by reduced levels of the type 2 signature cytokines IL-4, IL-5, and IL-13 at 14 days post-infection. Moreover, ILC2 deficiency was accompanied with increased type 1 immunity and classical macrophage activation, while the pulmonary numbers of eosinophils and alternatively activated macrophages were reduced in these mice. Importantly, this shift in pulmonary macrophage polarization in ILC2-deficient mice correlated with improved fungal control and prolonged survival of infected mice. Conversely, adoptive transfer of ILC2s was associated with a type 2 bias associated with less efficient anti-fungal immunity in lungs of recipient mice. Collectively, our date indicate a non-redundant role of ILC2 in orchestrating myeloid anti-cryptococcal immune responses toward a disease exacerbating phenotype

Impact of MLC properties and IMRT technique in meningioma and head-and-neck treatments

Purpose: The impact of multileaf collimator (MLC) design and IMRT technique on plan quality and delivery improvements for head-and-neck and meningioma patients is compared in a planning study. Material and methods: Ten previously treated patients (5 head-and-neck, 5 meningioma) were re-planned for step-and-shoot IMRT (ssIMRT),sliding window IMRT (dMLC) and VMAT using the MLCi2 without (-) and with (+) interdigitation and the Agility-MLC attached to an Elekta 6MV linac. This results in nine plans per patient. Consistent patient individual optimization parameters are used. Plans are generated using the research tool Hyperion V2.4 (equivalent to Elekta Monaco 3.2) with hard constraints for critical structures and objectives for target structures. For VMAT plans, the improved segment shape optimization is used. Critical structures are evaluated based on QUANTEC criteria. PTV coverage is compared by EUD, D-mean, homogeneity and conformity. Additionally, MU/plan, treatment times and number of segments are evaluated. Results: As constrained optimization is used, all plans fulfill the hard constraints. Doses to critical structures do not differ more than 1Gy between the nine generated plans for each patient. Only larynx, parotids and eyes differ up to 1.5Gy (D-mean or D-max) or 7 % (volume-constraint) due to (1) increased scatter,(2) not avoiding structures when using the full range of gantry rotation and (3) improved leaf sequencing with advanced segment shape optimization for VMAT plans. EUD, Dmean, homogeneity and conformity are improved using the Agility-MLC. However, PTV coverage is more affected by technique. MU increase with the use of dMLC and VMAT, while the MU are reduced by using the Agility-MLC. Fastest treatments are always achieved using Agility-MLC, especially in combination with VMAT. Conclusion: Fastest treatments with the best PTV coverage are found for VMAT plans with Agility-MLC, achieving the same sparing of healthy tissue compared to the other combinations of ssIMRT, dMLC and VMAT with either MLCi2(-/+) or Agility

Anforderungen an die grafische Oberfläche eines FE-Systems aus Sicht des Ingenieurs

Aus der Einleitung: "In der Produktentwicklung hat sich die numerische Simulation mittels Finite Elemente Analyse als Standardverfahren etabliert. Die Wandlung von einem Spezialistenwerkzeug zu einem generellen Ingenieurtool bringt mit sich, dass theoretisches Wissen zur FEA beim Benutzer nicht vorausgesetzt werden kann und demzufolge im Programm geeignet implementiert sein muss. Ingenieure sind im Umgang mit CAE-Tools (FEM, CFD, CAD) und theoretischen Methoden (VDI 2221, DSM, DfX) im Produktentstehungsprozess vertraut. In diesem Zusammenhang ist die aktuelle Herausforderung eine Verbindung beider etablierten Werkzeugklassen zu schaffen, die bisher nicht erfolgt ist. Es fehlt die benutzerspezifische Anpassung von computergestützten Werkzeugen an die Denkweise von Ingenieuren und deren Nutzungskontext. Methodische Wissensbasen, Retrieval-Möglichkeiten und Suchroutinen für abgeschlossene Projekte sind in CAE-Programmen nicht integriert. Ergänzt werden diese Nachteile durch die hohen Anschaffungskosten von Software in Kombination mit schlechter Usability.

Influence of organ motion on conformal vs. intensity-modulated pelvic radiotherapy for prostate cancer

publishedVersio

Hippocampal sparing radiotherapy for glioblastoma patients: a planning study using volumetric modulated arc therapy

Background: The purpose of this study is to investigate the potential to reduce exposure of the contralateral hippocampus in radiotherapy for glioblastoma using volumetric modulated arc therapy (VMAT). Methods: Datasets of 27 patients who had received 3D conformal radiotherapy (3D-CRT) for glioblastoma with a prescribed dose of 60Gy in fractions of 2Gy were included in this planning study. VMAT plans were optimized with the aim to reduce the dose to the contralateral hippocampus as much as possible without compromising other parameters. Hippocampal dose and treatment parameters were compared to the 3D-CRT plans using the Wilcoxon signed-rank test. The influence of tumour location and PTV size on the hippocampal dose was investigated with the Mann-Whitney-U-test and Spearman's rank correlation coefficient. Results: The median reduction of the contralateral hippocampus generalized equivalent uniform dose (gEUD) with VMAT was 36 % compared to the original 3D-CRT plans (p < 0.05). Other dose parameters were maintained or improved. The median V30Gy brain could be reduced by 17.9 % (p < 0.05). For VMAT, a parietal and a non-temporal tumour localisation as well as a larger PTV size were predictors for a higher hippocampal dose (p < 0.05). Conclusions: Using VMAT, a substantial reduction of the radiotherapy dose to the contralateral hippocampus for patients with glioblastoma is feasible without compromising other treatment parameters. For larger PTV sizes, less sparing can be achieved. Whether this approach is able to preserve the neurocognitive status without compromising the oncological outcome needs to be investigated in the setting of prospective clinical trials

Treatment of Infantile Spasm Syndrome: Update from the Interdisciplinary Guideline Committee Coordinated by the German-Speaking Society of Neuropediatrics

OBJECTIVES The manuscript serves as an update on the current management practices for infantile spasm syndrome (ISS). It includes a detailed summary of the level of current evidence of different treatment options for ISS and gives recommendations for the treatment and care of patients with ISS. METHODS A literature search was performed using the Cochrane and Medline Databases (2014 to July 2020). All studies were objectively rated using the Scottish Intercollegiate Guidelines Network. For recommendations, the evidence from these studies was combined with the evidence from studies used in the 2014 guideline. RECOMMENDATIONS If ISS is suspected, electroencephalography (EEG) should be performed within a few days and, if confirmed, treatment should be initiated immediately. Response to first-line treatment should be evaluated clinically and electroencephalographically after 14 days. The preferred first-line treatment for ISS consists of either hormone-based monotherapy (AdrenoCorticoTropic Hormone [ACTH] or prednisolone) or a combination of hormone and vigabatrin. Children with tuberous sclerosis complex and those with contraindications against hormone treatment should be treated with vigabatrin. If first-line drugs are ineffective, second-line treatment options such as ketogenic dietary therapies, sulthiame, topiramate, valproate, zonisamide, or benzodiazepines should be considered. Children refractory to drug therapy should be evaluated early for epilepsy surgery, especially if focal brain lesions are present. Parents should be informed about the disease, the efficacy and adverse effects of the medication, and support options for the family. Regular follow-up controls are recommended