Technical Note: GATE-RTion: a GATE/Geant4 release for clinical applications in scanned ion beam therapy.

PURPOSE: GATE-RTion is a validated version of GATE for clinical use in the field of light ion beam therapy. This paper describes the GATE-RTion project and illustrates its potential through clinical applications developed in three European centers delivering scanned proton and carbon ion treatments. METHODS: GATE-RTion is a collaborative framework provided by the OpenGATE collaboration. It contains a validated GATE release based on a specific Geant4 version, a set of tools to integrate GATE into a clinical environment and a network for clinical users. RESULTS: Three applications are presented: Proton radiography at the Centre Antoine Lacassagne (Nice, France); Independent dose calculation for proton therapy at the Christie NHS Foundation Trust (Manchester, UK); Independent dose calculation for protons and carbon ions at the MedAustron Ion Therapy center (Wiener Neustadt, Austria). CONCLUSIONS: GATE-RTion builds the bridge between researchers and clinical users from the OpenGATE collaboration in the field of Light Ion Beam Therapy. The applications presented in three European facilities using three completely different machines (three different vendors, cyclotron- and synchrotron-based systems, protons, and carbon ions) demonstrate the relevance and versatility of this project.

Contemporaneous evaluation of inguinal hernia causation: a European perspective.

AIM: The aim of the study was to evaluate any social, occupational and physical factors, which may influence the occurence or cause of a primary inguinal hernia in two European countries. METHODS: A questionnaire was completed by all the respondents in the setting of an out-patient clinic prospectively at the time of initial presentation and the data were collected on a secure database. All responses for each question were explored via appropriate descriptive statistics. Statistical comparisons were made using Fisher's exact test where appropriate. RESULTS: 537 adults completed the questionnaire and had their data analysed. Comparisons between those that presented with a primary complaint of either 'bulge/swelling' or 'discomfort/pain' found no differences in occupation, age or any other demographic data. Equal proportions of patients who described a single strenuous event presented with a bulge/swelling or discomfort/pain. The reporting of a causative single strenuous event was not significantly influenced by occupation, lifestyle or amount of activity carried out nor was there any significant influence upon when a hernia presented after the suspected strenuous event, although the majority reported a lump within 1 week. CONCLUSION: This study cannot at present support the belief that a single strenuous event will be the sole cause for the development of a primary inguinal hernia.

Association between High Levels of Parathyroid Hormone and Frailty: The Nepean Osteoporosis and Frailty (NOF) Study.

BACKGROUND: Frailty is associated with poor outcomes hence identification of risks factors is pivotal. Since the independent role of parathyroid hormone (PTH) in frailty remains unexplored, we aimed to determine this in a population of older individuals with a history of falling. DESIGN: Cross-sectional study. SETTING: Falls and Fracture Clinic, Nepean Hospital (Penrith, Australia). PARTICIPANTS: 692 subjects (mean age=79, 65% women) assessed between 2009-2015. MEASUREMENTS: Assessment included clinical examination, mood, nutrition, grip strength, gait velocity, bone densitometry and posturography. Chemistry included serum PTH, calcium, vitamin D (25(OH)D3), creatinine and albumin. Normocalcemic subjects were divided into 4 groups: (1) Normal: 25(OH)D3 >50nmol/L and PTH between 1.6-6.8pmol/L; (2) PTH responsive: low 25(OH)D3 (<50nmol/L) and high PTH (>6.8pmol/L); (3) PTH unresponsive: low 25(OH)D3 and normal PTH; (4) Hyper PTH (>6.8pmol/L) with normal 25(OH)D3. Frailty was defined using Fried's criteria. Difference between the groups was assessed using one-way ANOVA and X2 analysis. Multinomial logistic regression evaluated the association between the groups and the number of Fried's criteria adjusted for age, BMI, renal function, 25(OH)D3 levels, and albumin. RESULTS: 22.6% subjects had high PTH levels (>6.8pmol/L). All subjects in the high PTH groups had significantly lower grip strength, gait velocity, limits of stability, and higher BMI. The PTH responsive group had a higher risk of pre-frailty (ß=3.8, 95% CI = 3.42 - 5.22, p≷ 0.01) and frailty (ß=8.26, 95% CI = 2.8-16.1, p<0.01). The risk of frailty was also higher in the Hyper PTH group (ß=2.3, 95% CI = 1.74-4.32, p<0.01). CONCLUSION: We have reported an independent association of high PTH levels with high number of falls and with the clinical components of physical frailty in community dwelling older persons. Our results suggest a possible role of PTH in frailty that deserves further exploration.

A beam model for focused proton pencil beams.

INTRODUCTION: We present a beam model for Monte Carlo simulations of the IBA pencil beam scanning dedicated nozzle installed at the Skandion Clinic. Within the nozzle, apart from entrance and exit windows and the two ion chambers, the beam traverses vacuum, allowing for a beam that is convergent downstream of the nozzle exit. MATERIALS AND METHODS: We model the angular, spatial and energy distributions of the beam phase space at the nozzle exit with single Gaussians, controlled by seven energy dependent parameters. The parameters were determined from measured profiles and depth dose distributions. Verification of the beam model was done by comparing measured and GATE acquired relative dose distributions, using plan specific log files from the machine to specify beam spot positions and energy. RESULTS: GATE-based simulations with the acquired beam model could accurately reproduce the measured data. The gamma index analysis comparing simulated and measured dose distributions resulted in >95% global gamma index pass rates (3%/2 mm) for all depths. CONCLUSION: The developed beam model was found to be sufficiently accurate for use with GATE e.g. for applications in quality assurance (QA) or patient motion studies with the IBA pencil beam scanning dedicated nozzles.

[A girl with abdominal pain and haematomas on the belly]. / Een meisje met buikpijn en hematomen op de buik.

A 14-year-old girl with anorexia nervosa was referred to our paediatric hospital. She had a five-day history of severe abdominal pain. On abdominal sonography and MRI a duodenal wall hematoma was seen, correlating anatomically to abdominal bruises found on physical examination. The girl admitted to self-injury related to her eating disorder.

Macroscopic and Histologic Analysis of Vessel Wall Reaction After Mechanochemical Endovenous Ablation Using the ClariVein OC Device in an Animal Model.

OBJECTIVE/BACKGROUND: Mechanochemical endovenous ablation (MOCA) has been developed as a tumescentless technique to ablate saphenous veins and to avoid heat induced complications and post-procedural pain. The mechanism of action of MOCA is poorly understood. The present experiments were conducted to determine the effect of MOCA on vein wall injury and sclerosis in an animal model. METHODS: A total of 36 lateral saphenous veins (LSVs) were treated in 18 goats according to the human protocol. Veins from nine goats were evaluated 45 min after the procedure, while in the remaining nine, the treated veins were evaluated 6 weeks later. All treated veins were divided equally over three treatment groups: (i) MOCA, (ii) mechanical ablation without the sclerosant, and (iii) liquid sclerotherapy alone. The histological effects of treatment on the vein wall were systematically evaluated. RESULTS: The average diameter of the LSV was 4.0 ± 0.5 mm. Technical success was achieved in all but one LSV (35/36; 97%), with a median procedure time of 14 min (range 9-22 min). In the acute group, histological examination showed that mechanical ablation (alone or MOCA) induced severe injury to the endothelium in 82% but no damage to other layers of the vein wall. Mechanical ablation led to vasoconstriction. After 6 weeks follow-up, four of six MOCA treated veins were occluded. The occluded segments consisted mainly of fibrotic lesions probably evolved from organised thrombus. No occlusions were observed after sclerotherapy or mechanical treatment alone. No major complications occurred during procedures or follow-up. CONCLUSION: MOCA is associated with an increased occlusion rate compared with its separated components of mechanical ablation or sclerotherapy. The occlusion consists of cellular fibrotic material likely to be evolved from organised thrombus with fibrotic alterations to the surrounding media and adventitia. This study underlines the hypothesis that the additive use of MOCA increases the effectiveness of sclerosants alone by inducing endothelial damage and probably vasoconstriction.

Searches for Sterile Neutrinos with the IceCube Detector.

The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for the oscillation signatures of light sterile neutrinos. No evidence for anomalous ν_{µ} or ν[over ¯]_{µ} disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3+1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation. The exclusion limits extend to sin^{2}2θ_{24}≤0.02 at Δm^{2}∼0.3 eV^{2} at the 90% confidence level. The allowed region from global analysis of appearance experiments, including LSND and MiniBooNE, is excluded at approximately the 99% confidence level for the global best-fit value of |U_{e4}|^{2}.

Evidence for Astrophysical Muon Neutrinos from the Northern Sky with IceCube.

Results from the IceCube Neutrino Observatory have recently provided compelling evidence for the existence of a high energy astrophysical neutrino flux utilizing a dominantly Southern Hemisphere data set consisting primarily of ν(e) and ν(τ) charged-current and neutral-current (cascade) neutrino interactions. In the analysis presented here, a data sample of approximately 35,000 muon neutrinos from the Northern sky is extracted from data taken during 659.5 days of live time recorded between May 2010 and May 2012. While this sample is composed primarily of neutrinos produced by cosmic ray interactions in Earth's atmosphere, the highest energy events are inconsistent with a hypothesis of solely terrestrial origin at 3.7σ significance. These neutrinos can, however, be explained by an astrophysical flux per neutrino flavor at a level of Φ(E(ν))=9.9(-3.4)(+3.9)×10(-19) GeV(-1) cm(-2) sr(-1) s(-1)(E(ν)/100 TeV(-2), consistent with IceCube's Southern-Hemisphere-dominated result. Additionally, a fit for an astrophysical flux with an arbitrary spectral index is performed. We find a spectral index of 2.2(-0.2)(+0.2), which is also in good agreement with the Southern Hemisphere result.

Single-port laparoscopic appendectomy in children: single center experience in 50 patients.

BACKGROUND: Recent years evolution of minimal invasive laparoscopic procedures led to new techniques, like single-port laparoscopy (SPL), resulting in nearly-scarless procedures. The purpose of this study is to evaluate that SPL appendectomy is a safe and feasible procedure using a commercially available trocar (LESS: Laparo Endoscopic Single Site trocar; Olympus TriPort+) in pediatric patients. METHODS: From July 2011 to March 2014 all patients undergoing SPL appendectomy under 18 years were included in this retrospective study. Per- en postoperative data were collected in a prospective database. RESULTS: A total of 50 children (mean age 12 years) diagnosed as acute appendicitis underwent SPL appendectomy. SPL appendectomy was feasible and safe in all cases, both in non-perforated and perforated appendicitis. In one procedure (2%) an extra trocar was placed. Seven patients (14%) were readmitted to the hospital after initial uncomplicated postoperative course. One patient (2%) needed reoperation due to a wound abscess. Three patients (6%) were readmitted due to intra-abdominal abscesses for which antibiotics were given. CONCLUSIONS: SPL appendectomy is a safe and feasible procedure in children with acute appendicitis.

Flavor Ratio of Astrophysical Neutrinos above 35 TeV in IceCube.

A diffuse flux of astrophysical neutrinos above 100 TeV has been observed at the IceCube Neutrino Observatory. Here we extend this analysis to probe the astrophysical flux down to 35 TeV and analyze its flavor composition by classifying events as showers or tracks. Taking advantage of lower atmospheric backgrounds for showerlike events, we obtain a shower-biased sample containing 129 showers and 8 tracks collected in three years from 2010 to 2013. We demonstrate consistency with the (fe:fµ:fτ)⊕≈(1:1:1)⊕ flavor ratio at Earth commonly expected from the averaged oscillations of neutrinos produced by pion decay in distant astrophysical sources. Limits are placed on nonstandard flavor compositions that cannot be produced by averaged neutrino oscillations but could arise in exotic physics scenarios. A maximally tracklike composition of (0:1:0)⊕ is excluded at 3.3σ, and a purely showerlike composition of (1:0:0)⊕ is excluded at 2.3σ.

Development of a general analysis and unfolding scheme and its application to measure the energy spectrum of atmospheric neutrinos with IceCube: IceCube Collaboration.

We present the development and application of a generic analysis scheme for the measurement of neutrino spectra with the IceCube detector. This scheme is based on regularized unfolding, preceded by an event selection which uses a Minimum Redundancy Maximum Relevance algorithm to select the relevant variables and a random forest for the classification of events. The analysis has been developed using IceCube data from the 59-string configuration of the detector. 27,771 neutrino candidates were detected in 346 days of livetime. A rejection of 99.9999 % of the atmospheric muon background is achieved. The energy spectrum of the atmospheric neutrino flux is obtained using the TRUEE unfolding program. The unfolded spectrum of atmospheric muon neutrinos covers an energy range from 100 GeV to 1 PeV. Compared to the previous measurement using the detector in the 40-string configuration, the analysis presented here, extends the upper end of the atmospheric neutrino spectrum by more than a factor of two, reaching an energy region that has not been previously accessed by spectral measurements.

Comprehensive nutritional status in sarco-osteoporotic older fallers.

OBJECTIVES: In older persons, the combination of osteoporosis and sarcopenia has been proposed as a subset of frailer individuals at higher risk of falls and fractures. However, the particular nutritional status of the sarco-osteoporotic (SOP) patients remains unknown. The goal of this study was to obtain a comprehensive picture of nutritional status in SOP patients. DESIGN: Cross-sectional study. SETTING: Falls and Fractures Clinic, Nepean Hospital (Penrith, Australia). PARTICIPANTS: 680 subjects (mean age=79, 65% female) assessed between 2008-2013. MEASUREMENTS: Assessment included medical history, mini-nutritional assessment, physical examination, bone densitometry and body composition by DXA, and blood tests for nutritional status (albumin, creatinine, hemoglobin, vitamin D, vitamin B-12, calcium, phosphate and folate). Patients were divided in 4 groups: 1) osteopenia/osteoporosis (BMD<-1.0 SD); 2) sarcopenia; 3) SOP; and 4) normal (no sarcopenia/no osteoporosis). Difference between groups was assessed with one-way ANOVA and chi square analysis. Multivariable linear regression evaluated the association between the groups and measures of nutritional parameters. RESULTS: Sarcopenia was present in 47.4% of those with osteopenia (167/352) and 62.7% in those with osteoporosis (91/145). Mean age of the SOP was 80.4±7 years. SOP patients showed significantly higher prevalence of falls and fractures. Univariate analyses showed that SOP were more likely than normal to have a BMI< 25 (OR 2.42 95%CI 1.45-4.041, p<0.001), a MNA score <12 (OR 2.0, 95%CI 1.15-3.49, p<0.05), serum folate <20 nmol/L (OR 4.0 95%CI 1.35-11.87, p<0.01) and hemoglobin <120g/L (OR 2.0 95%CI 1.28-3.30, p<0.01). Multivariate analysis showed that a MNA score <12 was independently associated with SOP compared to normal when adjusted for age and gender. Hemoglobin <120g/L, BMI <25, and GDS >6 remained independently associated with SOP after adjustment for all variables including inflammatory conditions. Hypoalbuminemia (<35 g/L) was associated with just osteopenia/osteoporosis (OR: 2.03, 95%CI 1.08-3.81, p<0.01) and just sarcopenia (OR: 1.77, 95%CI 1.0-3.0, p<0.01) compared to normal. No differences in vitamin D, glomerular filtration rate, albumin, corrected calcium, phosphate, red blood cells folate or vitamin B12 levels were found between the subgroups. CONCLUSIONS: In approaching SOP patients, early prevention protocols directed to optimize their nutritional status would be a key strategy to prevent poor outcomes such as falls and fractures in this high risk population. Therefore, nutritional assessment and early nutritional supplementation should be essential domains in this strategy.

Observation of high-energy astrophysical neutrinos in three years of IceCube data.

A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm-2 s-1 sr-1 per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7σ. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.

Evidence for high-energy extraterrestrial neutrinos at the IceCube detector.

We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4σ level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.

Measurement of atmospheric neutrino oscillations with IceCube.

We present the first statistically significant detection of neutrino oscillations in the high-energy regime (>20 GeV) from an analysis of IceCube Neutrino Observatory data collected in 2010 and 2011. This measurement is made possible by the low-energy threshold of the DeepCore detector (~20 GeV) and benefits from the use of the IceCube detector as a veto against cosmic-ray-induced muon background. The oscillation signal was detected within a low-energy muon neutrino sample (20-100 GeV) extracted from data collected by DeepCore. A high-energy muon neutrino sample (100 GeV-10 TeV) was extracted from IceCube data to constrain systematic uncertainties. The disappearance of low-energy upward-going muon neutrinos was observed, and the nonoscillation hypothesis is rejected with more than 5σ significance. In a two-neutrino flavor formalism, our data are best described by the atmospheric neutrino oscillation parameters |Δm(32)(2)|=(2.3(-0.5)(+0.6))×10(-3) eV(2) and sin(2)(2θ(23))>0.93, and maximum mixing is favored.

First observation of PeV-energy neutrinos with IceCube.

We report on the observation of two neutrino-induced events which have an estimated deposited energy in the IceCube detector of 1.04±0.16 and 1.14±0.17 PeV, respectively, the highest neutrino energies observed so far. These events are consistent with fully contained particle showers induced by neutral-current ν(e,µ,τ) (ν(e,µ,τ)) or charged-current ν(e) (ν(e)) interactions within the IceCube detector. The events were discovered in a search for ultrahigh energy neutrinos using data corresponding to 615.9 days effective live time. The expected number of atmospheric background is 0.082±0.004(stat)(-0.057)(+0.041)(syst). The probability of observing two or more candidate events under the atmospheric background-only hypothesis is 2.9×10(-3) (2.8σ) taking into account the uncertainty on the expected number of background events. These two events could be a first indication of an astrophysical neutrino flux; the moderate significance, however, does not permit a definitive conclusion at this time.

Search for dark matter annihilations in the sun with the 79-string IceCube detector.

We have performed a search for muon neutrinos from dark matter annihilation in the center of the Sun with the 79-string configuration of the IceCube neutrino telescope. For the first time, the DeepCore subarray is included in the analysis, lowering the energy threshold and extending the search to the austral summer. The 317 days of data collected between June 2010 and May 2011 are consistent with the expected background from atmospheric muons and neutrinos. Upper limits are set on the dark matter annihilation rate, with conversions to limits on spin-dependent and spin-independent scattering cross sections of weakly interacting massive particles (WIMPs) on protons, for WIMP masses in the range 20-5000 GeV/c2. These are the most stringent spin-dependent WIMP-proton cross section limits to date above 35 GeV/c2 for most WIMP models.

Mechanochemical endovenous ablation of small saphenous vein insufficiency using the ClariVein(®) device: one-year results of a prospective series.

OBJECTIVE: This study evaluated the feasibility, safety and 1-year results of mechanochemical endovenous ablation (MOCA™) of small saphenous vein (SSV) insufficiency. DESIGN: Prospective cohort study. MATERIALS AND METHODS: Fifty consecutive patients were treated for primary SSV insufficiency with MOCA™ using the ClariVein(®) device and polidocanol. Initial technical success, complications, patient satisfaction and visual analogue scale (VAS) pain score were assessed. Anatomic and clinical success was assessed at 6 weeks and at 1 year. RESULTS: Initial technical success of MOCA™ was 100%. At the 6-week assessment, all treated veins were occluded. The 1-year follow-up duplex showed anatomic success in 94% (95% confidence interval, 0.87-1). Venous clinical severity score (VCSS) decreased significantly from 3.0 (interquartile range (IQR) 2-5) before treatment to 1.0 (IQR 1-3, P < 0.001) at 6 weeks and to 1.0 (IQR 1-2, P < 0.001) at 1 year. Median procedural VAS score for pain was 2 (IQR 2-4). No major complications were observed, especially no nerve injury. CONCLUSIONS: MOCA™ is a safe, feasible and efficacious technique for treatment of SSV insufficiency. One-year follow-up shows a 94% anatomic success rate and no major complications.