New definitions of 6 clinical signs of perceptual disorder in children with cerebral palsy: an observational study through reliability measures.

BACKGROUND: Recently authors have begun to emphasize the non-motor aspects of Cerebral Palsy and their influence on motor control and recovery prognosis. Much has been written about single clinical signs (i.e., startle reaction) but so far no definitions of the six perceptual signs presented in this study have appeared in literature. AIM: This study defines 6 signs (startle reaction, upper limbs in startle position, frequent eye blinking, posture freezing, averted eye gaze, grimacing) suggestive of perceptual disorders in children with cerebral palsy and measures agreement on sign recognition among independent observers and consistency of opinions over time. DESIGN: Observational study with both cross-sectional and prospective components. SETTING: Fifty-six videos presented to observers in random order. Videos were taken from 19 children with a bilateral form of cerebral palsy referred to the Children Rehabilitation Unit in Reggio Emilia. PARTICIPANTS: Thirty-five rehabilitation professionals from all over Italy: 9 doctors and 26 physiotherapists. METHODS: Measure of agreement among 35 independent observers was compiled from a sample of 56 videos. Interobserver reliability was determined using the K index of Fleiss and reliability intra-observer was calculated by the Spearman correlation index between ranks (rho - ρ). Percentage of agreement between observers and Gold Standard was used as criterion validity. RESULTS: Interobserver reliability was moderate for startle reaction, upper limb in startle position, adverted eye gaze and eye-blinking and fair for posture freezing and grimacing. Intraobserver reliability remained consistent over time. Criterion validity revealed very high agreement between independent observer evaluation and gold standard. CONCLUSIONS: Semiotics of perceptual disorders can be used as a specific and sensitive instrument in order to identify a new class of patients within existing heterogeneous clinical types of bilateral cerebral palsy forms and could help clinicians in identifying functional prognosis. CLINICAL REHABILITATION IMPACT: To provide clinicians with a definition of 6 clinical signs found in children with cerebral palsy in routine rehabilitation settings. Future research should explore the link between these signs and motor prognosis (i.e., time to independent walking).

A study on repainting strategies for treating moderately moving targets with proton pencil beam scanning at the new Gantry 2 at PSI.

Treating moving targets using a scanning gantry for proton therapy is a promising but very challenging, not yet clinically demonstrated treatment modality. The interference of organ motion with the sequence of the beam delivery produces uncontrolled dose inhomogeneities within the target. One promising approach to overcome this difficulty is to increase the speed of scanning in order to apply the dose repeatedly (so-called repainting). To obtain sufficiently high scanning speeds a new, technologically improved gantry-Gantry 2-has been designed and is currently under construction at PSI. As there are many possible repainting strategies, the way repainting will be implemented on Gantry 2 will depend on the result of a careful analysis of the various treatment delivery strategies available. To achieve this aim, and prior to the start of experimental work with Gantry 2, simulations of dose distribution errors due to organ motion under various beam delivery strategies were investigated. The effects of motion on the dose distribution were studied for moderate motion amplitudes (5 mm) for spherical target volumes in a homogeneous medium and with homogeneous dose. In total over 200,000 dose distributions have been simulated and analyzed and selected results are discussed. From the obtained results we are confident to be able to treat moderately moving targets on Gantry 2 using repainted pencil-beam spot scanning. Continuous line scanning seems to be the most elegant solution; it provides higher repainting rates and produces superior results but is probably more difficult to realize. For larger motion amplitudes, continuous line scanning still shows good results, but we plan anyways to use a gating system for these cases, not only to reduce the inhomogeneity within the target volume but also to reduce safety margins.

Outbreak of 2009 pandemic influenza A(H1N1), Los Lagos, Chile, April-June 2009.

On 17 May 2009, the first two cases of 2009 pandemic influenza A(H1N1) were confirmed in the Metropolitan region (Santiago, Chile). On 6 June 2009, Chile reported 500 confirmed cases, seven severe and two fatal. Because six of the severe cases and the two deaths occurred in the region of Los Lagos in southern Chile, a retrospective study was conducted using data on emergency room visits as well as laboratory viral surveillance, during the period from 1 April to 31 May, in order to establish the date of the beginning of the outbreak. From 1 to 27 June, data were collected in real time, to establish the real magnitude of the outbreak, describe its transmission, clinical severity and secondary attack rates. Confirmed cases, their household contacts and healthcare workers were interviewed. This analysis showed that the outbreak in Los Lagos started on 28 April. By 27 June, a total of 14.559 clinical cases were identified, affecting mostly 5-19 year-olds. The effective reproduction number during the initial phase (20 days) was 1.8 (1.6-2.0). Of the 190 confirmed cases with severe acute respiratory infection, 71 (37.4%) presented a risk condition or underlying illness.

Prolonged fecal shedding of Shiga toxin-producing Escherichia coli among children attending day-care centers in Argentina.

In this report we describe the detection and duration of fecal shedding of Shiga toxin-producing Escherichia coil (STEC) O157 and non-O157 in symptomatic and asymptomatic cases during four events occurred among children in day-care centers in Argentina. In each event, the cases were identified among children, family contacts and staff members of the Institution. The isolates were characterized by pheno-genotyping and subtyping methods. The STEC fecal shedding was prolonged and intermittent. Strains O157:H7 (1st event); O26:H11 (2nd event); O26:H11 (3rd event) and O145:NM (4th event) were shed during 23-30, 37, 31 and 19 days, respectively. Considering the possibility of STEC intermittent long-term shedding, symptomatic and asymptomatic individuals should be excluded from the Institution until two consecutive stool cultures obtained at least 48 h apart, test negative.

On the feasibility of water calorimetry with scanned proton radiation.

Water calorimetry is considered to be the most direct primary method to realize the physical quantity gray for absorbed dose to water. The Swiss Federal Office of Metrology and Accreditation (METAS) has routinely operated a water calorimeter as primary standard for photon radiation since 2001. Nowadays, cancer therapy with proton radiation has become increasingly important and is a well established method. In the framework of the ProScan project conducted by the Paul Scherrer Institute (PSI), the spot-scanning technique is prepared for the subsequent application in hospitals, and adjusted to the recent findings of clinical research. In the absence of primary standards for proton radiation, the metrological traceability is assured by calibrating secondary standards in 60Co radiation and correcting with calculated beam quality correction factors. It is internationally recognized that the development of primary standards for proton radiation is highly desirable. In a common project of PSI and METAS, it is investigated whether a modified version of the water calorimeter in operation at METAS is suitable as primary standard for scanned proton radiation. A feasibility study has been conducted to investigate the linear energy transfer (LET) dependence of the heat defect and the influence of the time and space structure of the scanned beam on the homogeneity and stability of the temperature field in the water calorimeter. Simulations are validated against experimental data of the existing calorimeter used with photon radiation and extended to scanned proton radiation.

[Relationship between aortic arch shape and blood pressure response after coarctation repair]. / Relation entre l'architecture de la crosse aortique et la pression artérielle après cure de coarctation.

The mechanisms of secondary hypertension after repair of coarctation of the aorta are not well understood. Abnormalities of the architecture of the aortic arch and their consequences on blood pressure have not been studied. In order to study the relationship between abnormalities or aortic arch architecture and resting blood pressure ninety-four patients without re-coarctation were followed up prospectively from 1997 to 2004 (mean age 16.9 +/- 8.1 years; mean weight 57.5 +/- 18.3 Kg; interval since surgery 16.3 +/- 5.4 years). All underwent MRI angiography of the thoracic aorta which enabled the abnormalities to be classified in 3 groups: gothic arch, crenellated arch and roman arch. Twenty-four patients (25.5%) were hypertensive and 70 (74.4%) normotensive. There were 40 gothic arches (42.5%). 14 crenellated arches (15%) and 40 roman arches (42.5%). Gothic arches were more commonly observed in the hypertensive patients (18/40, [45%, 95% CI 31-62]) than the crenellated arches (4/14, [28.5%, 95% CI 7-48]) or the roman arches (2/40, [5%, 95% CI 2-12]). Only the gothic arch was independently correlated with hypertension on multivariate analysis. The authors conclude that gothic deformation of the aortic arch is an independent predictive factor of hypertension in patients operated for coarctation with an excellent result on the isthmic region. Patients with a gothic appearance of their aortic arch should be followed up closely.

Experimental characterization and physical modelling of the dose distribution of scanned proton pencil beams.

In this paper we present the pencil beam dose model used for treatment planning at the PSI proton gantry, the only system presently applying proton therapy with a beam scanning technique. The scope of the paper is to give a general overview on the various components of the dose model, on the related measurements and on the practical parametrization of the results. The physical model estimates from first physical principles absolute dose normalized to the number of incident protons. The proton beam flux is measured in practice by plane-parallel ionization chambers (ICs) normalized to protons via Faraday-cup measurements. It is therefore possible to predict and deliver absolute dose directly from this model without other means. The dose predicted in this way agrees very well with the results obtained with ICs calibrated in a cobalt beam. Emphasis is given in this paper to the characterization of nuclear interaction effects, which play a significant role in the model and are the major source of uncertainty in the direct estimation of the absolute dose. Nuclear interactions attenuate the primary proton flux, they modify the shape of the depth-dose curve and produce a faint beam halo of secondary dose around the primary proton pencil beam in water. A very simple beam halo model has been developed and used at PSI to eliminate the systematic dependences of the dose observed as a function of the size of the target volume. We show typical results for the relative (using a CCD system) and absolute (using calibrated ICs) dosimetry, routinely applied for the verification of patient plans. With the dose model including the nuclear beam halo we can predict quite precisely the dose directly from treatment planning without renormalization measurements, independently of the dose, shape and size of the dose fields. This applies also to the complex non-homogeneous dose distributions required for the delivery of range-intensity-modulated proton therapy, a novel therapy technique developed at PSI.

Monte Carlo dose calculations for spot scanned proton therapy.

Density heterogeneities can have a profound effect on dose distributions for proton therapy. Although analytical calculations in homogeneous media are relatively straightforward, the modelling of the propagation of the beam through density heterogeneities can be more problematical. At the Paul Scherrer Institute, an in-house dedicated Monte Carlo (MC) code has been used for over a decade to assess the possible deficiencies of the analytical calculations in patient geometries. The MC code has been optimized for speed, and as such traces primary protons only through the treatment nozzle and patient's CT. Contributions from nuclear interactions are modelled analytically with no tracing of secondary particles. The MC code has been verified against measured data in water and experimental proton radiographs through a heterogeneous anthropomorphic phantom. In comparison to the analytical calculation, the MC code has been applied to both spot scanned and intensity modulated proton therapy plans, and to a number of cases containing titanium metal implants. In summary, MC-based dose calculations could provide an invaluable tool for independently verifying the calculated dose distribution within a patient geometry as part of a comprehensive quality assurance protocol for proton treatment plans.

Intensity modulated proton therapy: a clinical example.

In this paper, we report on the clinical application of fully automated three-dimensional intensity modulated proton therapy, as applied to a 34-year-old patient presenting with a thoracic chordoma. Due to the anatomically challenging position of the lesion, a three-field technique was adopted in which fields incident through the lungs and heart, as well as beams directed directly at the spinal cord, could be avoided. A homogeneous target dose and sparing of the spinal cord was achieved through field patching and computer optimization of the 3D fluence of each field. Sensitivity of the resultant plan to delivery and calculational errors was determined through both the assessment of the potential effects of range and patient setup errors, and by the application of Monte Carlo dose calculation methods. Ionization chamber profile measurements and 2D dosimetry using a scintillator/CCD camera arrangement were performed to verify the calculated fields in water. Modeling of a 10% overshoot of proton range showed that the maximum dose to the spinal cord remained unchanged, but setup error analysis showed that dose homogeneity in the target volume could be sensitive to offsets in the AP direction. No significant difference between the MC and analytic dose calculations was found and the measured dosimetry for all fields was accurate to 3% for all measured points. Over the course of the treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated that organ motion in the region of the target volume was negligible. We conclude that 3D IMPT plans can be applied clinically and safely without modification to our existing delivery system. However, analysis of the calculated intensity matrices should be performed to assess the practicality, or otherwise, of the plan.

Performance of a fluorescent screen and CCD camera as a two-dimensional dosimetry system for dynamic treatment techniques.

A two-dimensionally position sensitive dosimetry system has been tested for different dosimetric applications in a radiation therapy facility with a scanning proton beam. The system consists of a scintillating (fluorescent) screen, mounted at the beam-exit side of a phantom and it is observed by a charge coupled device (CCD) camera. The observed light distribution at the screen is equivalent to the two-dimensional (2D)-dose distribution at the screen position. It has been found that the dosimetric properties of the system, measured in a scanning proton beam, are equal to those measured in a proton beam broadened by a scattering system. Measurements of the transversal dose distribution of a single pencil beam are consistent with dose measurements as well as with dose calculations in clinically relevant fields made with multiple pencil beams. Measurements of inhomogeneous dose distributions have shown to be of sufficient accuracy to be suitable for the verification of dose calculation algorithms. The good sensitivity and sub-mm spatial resolution of the system allows for the detection of deviations of a few percent in dose from the expected (intended or calculated) dose distribution. Its dosimetric properties and the immediate availability of the data make this device a useful tool in the quality control of scanning proton beams.

Proton dosimetry intercomparison based on the ICRU report 59 protocol.

BACKGROUND AND PURPOSE: A new protocol for calibration of proton beams was established by the ICRU in report 59 on proton dosimetry. In this paper we report the results of an international proton dosimetry intercomparison, which was held at Loma Linda University Medical Center. The goals of the intercomparison were, first, to estimate the level of consistency in absorbed dose delivered to patients if proton beams at various clinics were calibrated with the new ICRU protocol, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration factors. MATERIALS AND METHODS: Eleven institutions participated in the intercomparison. Measurements were performed in a polystyrene phantom at a depth of 10.27 cm water equivalent thickness in a 6-cm modulated proton beam with an accelerator energy of 155 MeV and an incident energy of approximately 135 MeV. Most participants used ionization chambers calibrated in terms of exposure or air kerma. Four ionization chambers had 60Co-based calibration in terms of absorbed dose-to-water. Two chambers were calibrated in a 60Co beam at the NIST both in terms of air kerma and absorbed dose-to-water to provide a comparison of ionization chambers with different calibrations. RESULTS: The intercomparison showed that use of the ICRU report 59 protocol would result in absorbed doses being delivered to patients at their participating institutions to within +/-0.9% (one standard deviation). The maximum difference between doses determined by the participants was found to be 2.9%. Differences between proton doses derived from the measurements with ionization chambers with N(K)-, or N(W) - calibration type depended on chamber type. CONCLUSIONS: Using ionization chambers with 60Co calibration factors traceable to standard laboratories and the ICRU report 59 protocol, a distribution of stated proton absorbed dose is achieved with a difference less than 3%. The ICRU protocol should be adopted for clinical proton beam calibration. A comparison of proton doses derived from measurements with different chambers indicates that the difference in results cannot be explained only by differences in 60Co calibration factors.

Initial experience of using an active beam delivery technique at PSI.

At PSI a new proton therapy facility has been assembled and commissioned. The major features of the facility are the spot scanning technique and the very compact gantry. The operation of the facility was started in 1997 and the feasibility of the spot scanning technique has been demonstrated in practice with patient treatments. In this report we discuss the usual initial difficulties encountered in the commissioning of a new technology, the very positive preliminary experience with the system and the optimistic expectations for the future. The long range goal of this project is to parallel the recent developments regarding inverse planning for photons with a similar advanced technology optimized for a proton beam.

Aortic valve regurgitation as the presenting sign of Takayasu arteritis.

UNLABELLED: Takayasu arteritis is a rare chronic vasculitis primarily involving the aorta and its main branches. We report an adolescent girl with Takayasu arteritis who presented with an isolated aortic valve regurgitation as part of a systemic inflammatory process. This patient was initially misdiagnosed as having rheumatic heart disease and the correct diagnosis was made only 1 year later. CONCLUSION: Takayasu arteritis should be considered among the diagnostic possibilities in patients who present with an unexplained systemic inflammatory syndrome and a cardiac murmur.

Dose calculation models for proton treatment planning using a dynamic beam delivery system: an attempt to include density heterogeneity effects in the analytical dose calculation.

The gantry for proton radiotherapy at the Paul Scherrer Institute (PSI) is designed specifically for the spot-scanning technique. Use of this technique to its full potential requires dose calculation algorithms which are capable of precisely simulating each scanned beam individually. Different specialized analytical dose calculations have been developed, which attempt to model the effects of density heterogeneities in the patient's body on the dose. Their accuracy has been evaluated by a comparison with Monte Carlo calculated dose distributions in the case of a simple geometrical density interface parallel to the beam and typical anatomical situations. A specialized ray casting model which takes range dilution effects (broadening of the spectrum of proton ranges) into account has been found to produce results of good accuracy. This algorithm can easily be implemented in the iterative optimization procedure used for the calculation of the optimal contribution of each individual scanned pencil beam. In most cases an elemental pencil beam dose calculation has been found to be most accurate. Due to the long computing time, this model is currently used only after the optimization procedure as an alternative method of calculating the dose.

The precision of proton range calculations in proton radiotherapy treatment planning: experimental verification of the relation between CT-HU and proton stopping power.

The precision in proton radiotherapy treatment planning depends on the accuracy of the information used to calculate the stopping power properties of the tissues in the patient's body. This information is obtained from computed tomography (CT) images using a calibration curve to convert CT Hounsfield units into relative proton stopping power values. The validity of a stoichiometric method to create the calibration curve has been verified by measuring pairs of Hounsfield units and stopping power values for animal tissue samples. It was found that the agreement between measurement and calibration curve is better than 1% if beam hardening effects in the acquisition of the CT images can be neglected. The influence of beam hardening effects on the quantitative reading of the CT measurements is discussed and an estimation for the overall range precision of proton beams is given. It is expected that the range of protons in the human body can be controlled to better than +/-1.1% of the water equivalent range in soft tissue and +/-1.8% in bone, which translates into a range precision of about 1-3 mm in typical treatment situations.

A technique for calculating range spectra of charged particle beams distal to thick inhomogeneities.

A method was developed for calculating range spectra of charged particles after passing through an inhomogeneous structure whose thickness was comparable to the range of the incident particles. It was shown that the spectra are strongly affected by the influence of multiple Coulomb scattering at interfaces parallel to the beam direction of two media with different relative stopping power. The calculations are in agreement with Monte Carlo simulations. The degraded Bragg peak was calculated on the basis of the computed range spectra behind the inhomogeneity interface. The method can be included into charged particle treatment planning systems where broad pencil beams are used to predict the deteriorated Bragg peak behind inhomogeneity interfaces more precisely.

The calibration of CT Hounsfield units for radiotherapy treatment planning.

Computer tomographic (CT) scans are used to correct for tissue inhomogeneities in radiotherapy treatment planning. In order to guarantee a precise treatment, it is important to obtain the relationship between CT Hounsfield units and electron densities (or proton stopping powers for proton radiotherapy), which is the basic input for radiotherapy planning systems which consider tissue heterogeneities. A method is described to determine improved CT calibrations for biological tissue (a stoichiometric calibration) based on measurements using tissue equivalent materials. The precision of this stoichiometric calibration and the more usual tissue substitute calibration is determined by a comparison of calculated proton radiographic images based on these calibrations and measured radiographs of a biological sample. It has been found that the stoichiometric calibration is more precise than the tissue substitute calibration.

Beam optics design of compact gantry for proton therapy.

A new proton therapy facility for the treatment of deep-seated tumours is being assembled. The proton beam will be applied to the patient under computer control, using dynamic scanning of a focused proton pencil beam to produce a complete three-dimensional conformation of the dose to the target volume. The beam will be applied to the supine patient using a compact isocentric gantry for protons. By combining the scanning of the beam with the beam optics and by mounting the patient couch eccentrically on the gantry, the diameter of the rotating structure can be reduced to 4 m, which is the smallest diameter designed so far for a proton gantry. The paper describes the project especially from the point of view of the optics of the beam transport system of the gantry, including the beam line used to inject the beam into the gantry.