Demonstration of event position reconstruction based on diffusion in the NEXT-white detector.

Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from 83mKr calibration electron captures (E∼45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias <1mm. A convolutional neural network approach is then used to quantify diffusion for longer tracks (E≥1.5 MeV), from radiogenic electrons, yielding a precision of 3 cm on the event barycenter. The precision achieved with these methods indicates the feasibility energy calibrations of better than 1% FWHM at Qßß in pure xenon, as well as the potential for event fiducialization in large future detectors using an alternate method that does not rely on primary scintillation.

Magnetic double-J stent: Evaluation of tolerance and impact on quality of life compared to traditional double-J stent.

INTRODUCTION: The placement of a ureteral stent is one of the most widely performed procedures in urology. It can have a negative impact on the patients' quality of life, requiring a cystoscopy for its removal. The objective of this study is to evaluate the symptoms and impact on quality of life derived from the use of a magnetic double-J stent (Black Star®) and compare them to those presented in patients with a traditional double-J stent (OptiMed®). MATERIAL AND METHODS: We conducted a comparative, prospective, randomized study in 46 patients who underwent ureterorenoscopy with double-J stent placement between August 2019 and June 2020. Of all patients included, 23 had a traditional double-J stent placed (group A) and 23 had a magnetic double-J stent (group B) placed. We evaluated the results of the Ureteral Stent Symptom Questionnaire (USSQ) in both groups, assessed the technical difficulty related to stent removal and the pain during the procedure using the Visual Analogue Scale (VAS). We also reviewed the need for medical attention due to problems related to the stent or after its removal. RESULTS: There were no statistically significant differences between groups regarding the answers in the USSQ and the complications related to the use of the stent. Group B showed less pain (1.52 vs. 4, VAS, p = 0.001) and less difficulty during removal (1.61 vs. 3, p < 0.001) associated with a shorter procedure duration (11.65 min vs. 22.17 min p < 0.001). CONCLUSIONS: The tolerance shown by the use of magnetic double-J is comparable to the tolerance of traditional stent, since it does not cause an increase in urinary symptoms nor worsens the quality of life of patients during its use.

Treatment for rectourethral fistulas after radical prostatectomy with biological material interposition through a perineal access.

INTRODUCTION: Rectal injury is a rare complication after extraperitoneal laparoscopic radical prostatectomy. The development of rectourethral fistulas (URF) from rectal injuries is one of the most feared and of more complex resolution in urology. MATERIAL AND METHODS: Between 2013 and 2020 we have operated on a total of 5 patients with URF after extraperitoneal endoscopic radical prostatectomy through a perineal access using the interposition of biological material. All fistulas had a diameter of less than 6 mm at endoscopy and were less than 6 cm apart from the anal margin. RESULTS: The mean age of the patients was 64 years old. All patients had a previous bowel and urinary diversion for at least 3 months. Under general anesthesia and with the patient in a forced lithotomy position, fistulorraphy and interposition of biological material of porcine origin (lyophilized porcine dermis [Permacol®]) were performed through a perineal access. Mean operative time was 174 min (140-210). Most patients were discharged on the third postoperative day. The bladder catheter was left in place for a mean of 40 days (30-60). Prior to its removal, cystography and a Gastrografin® barium enema were performed, showing resolution of the fistula in all cases. CONCLUSIONS: The interposition of biological material from porcine dermis through perineal approach is a safe alternative with good results in patients submitted to urethrorectal fistulorraphy after radical prostatectomy.

Determination of consensus k Q values for megavoltage photon beams for the update of IAEA TRS-398.

The IAEA is currently coordinating a multi-year project to update the TRS-398 Code of Practice for the dosimetry of external beam radiotherapy based on standards of absorbed dose to water. One major aspect of the project is the determination of new beam quality correction factors, k Q , for megavoltage photon beams consistent with developments in radiotherapy dosimetry and technology since the publication of TRS-398 in 2000. Specifically, all values must be based on, or consistent with, the key data of ICRU Report 90. Data sets obtained from Monte Carlo (MC) calculations by advanced users and measurements at primary standards laboratories have been compiled for 23 cylindrical ionization chamber types, consisting of 725 MC-calculated and 179 experimental data points. These have been used to derive consensus k Q values as a function of the beam quality index TPR20,10 with a combined standard uncertainty of 0.6%. Mean values of MC-derived chamber-specific [Formula: see text] factors for cylindrical and plane-parallel chamber types in 60Co beams have also been obtained with an estimated uncertainty of 0.4%.

Brachytherapy organ dose estimation using Monte Carlo simulations of realistic patient models.

Radiation Therapy Planning Systems (RTPS) currently used in hospitals contain algorithms based on deterministic simplifications that do not properly consider electrons lateral transport in the areas where there are changes of density, and as a result, erroneous dose predictions could be produced. According to this, the present work proposes the use of Monte Carlo method in brachytherapy planning systems, which could affect positively on the radiotherapy treatment planning, since it provides results that are more accurate and takes into account the in homogeneities density variations. This paper presents a Monte Carlo (MC) simulation of a brachytherapy prostate treatment with I-125 seeds, using the latest version of MCNP, v.6.1.1. To that, a 3D model of the anatomy of a real anonymized patient is created from the segmentation of Computed Tomography (CT) images. Treatment over this 3D model is simulated and the dose given to each organ is obtained. These doses are compared with those calculated by deterministic planning system used in hospital demonstrating the effectiveness of MC method in the planning of brachytherapy treatments, because of not only the results precision but also regarding the affordable computing times.

Peripheral dose around a mobile linac for intraoperative radiotherapy: radiation protection aspects.

The aim of this work is to analyse the scattered radiation produced by the mobile accelerator Mobetron 1000. To do so, detailed Monte Carlo simulations using two different codes, Penelope2008 and Geant4, were performed. Measurements were also done. To quantify the attenuation due to the internal structures, present in the accelerator head, on the scattered radiation produced, some of the main structural shielding in the Mobetron 1000 has been incorporated into the geometry simulation. Results are compared with measurements. Some discrepancies between the calculated and measured dose values were found. These differences can be traced back to the importance of the radiation component due to low energy scattered electrons. This encouraged us to perform additional calculations to separate the role played by this component. Ambient dose equivalent, H*(10), outside of the operating room (OR) has been evaluated using Geant4. H*(10) has been measured inside and outside the OR, being its values compatible with those reported in the literature once the low energy electron component is removed. With respect to the role played by neutrons, estimations of neutron H*(10) using Geant4 together with H*(10) measurements has been performed for the case of the 12 MeV electron beam. The values obtained agree with the experimental values existing in the literature, being much smaller than those registered in conventional accelerators. This study is a useful tool for the clinical user to investigate the radiation protection issues arising with the use of these accelerators in ORs without structural shielding. These results will also enable to better fix the maximum number of treatments that could be performed while insuring adequate radiological protection of workers and public in the hospital.

Correction factors for ionization chamber measurements with the 'Valencia' and 'large field Valencia' brachytherapy applicators.

Treatment of small skin lesions using HDR brachytherapy applicators is a widely used technique. The shielded applicators currently available in clinical practice are based on a tungsten-alloy cup that collimates the source-emitted radiation into a small region, hence protecting nearby tissues. The goal of this manuscript is to evaluate the correction factors required for dose measurements with a plane-parallel ionization chamber typically used in clinical brachytherapy for the 'Valencia' and 'large field Valencia' shielded applicators. Monte Carlo simulations have been performed using the PENELOPE-2014 system to determine the absorbed dose deposited in a water phantom and in the chamber active volume with a Type A uncertainty of the order of 0.1%. The average energies of the photon spectra arriving at the surface of the water phantom differ by approximately 10%, being 384 keV for the 'Valencia' and 343 keV for the 'large field Valencia'. The ionization chamber correction factors have been obtained for both applicators using three methods, their values depending on the applicator being considered. Using a depth-independent global chamber perturbation correction factor and no shift of the effective point of measurement yields depth-dose differences of up to 1% for the 'Valencia' applicator. Calculations using a depth-dependent global perturbation factor, or a shift of the effective point of measurement combined with a constant partial perturbation factor, result in differences of about 0.1% for both applicators. The results emphasize the relevance of carrying out detailed Monte Carlo studies for each shielded brachytherapy applicator and ionization chamber.

Calibration of a thermoluminescent dosimeter worn over lead aprons in fluoroscopy guided procedures.

Fluoroscopy guided interventional procedures provide remarkable benefits to patients. However, medical staff working near the scattered radiation field may be exposed to high cumulative equivalent doses, thus requiring shielding devices such as lead aprons and thyroid collars. In this situation, it remains an acceptable practice to derive equivalent doses to the eye lenses or other unprotected soft tissues with a dosimeter placed above these protective devices. Nevertheless, the radiation backscattered by the lead shield differs from that generated during dosimeter calibration with a water phantom. In this study, a passive personal thermoluminescent dosimeter (TLD) was modelled by means of the Monte Carlo (MC) code Penelope. The results obtained were validated against measurements performed in reference conditions in a secondary standard dosimetry laboratory. Next, the MC model was used to evaluate the backscatter correction factor needed for the case where the dosimeter is worn over a lead shield to estimate the personal equivalent dose H p (0.07) to unprotected soft tissues. For this purpose, the TLD was irradiated over a water slab phantom with a photon beam representative of the result of a fluoroscopy beam scattered by a patient. Incident beam angles of 0° and 60°, and lead thicknesses between the TLD and phantom of 0.25 and 0.5 mm Pb were considered. A backscatter correction factor of 1.23 (independent of lead thickness) was calculated comparing the results with those faced in reference conditions (i.e., without lead shield and with an angular incidence of 0°). The corrected dose algorithm was validated in laboratory conditions with dosimeters irradiated over a thyroid collar and angular incidences of 0°, 40° and 60°, as well as with dosimeters worn by interventional radiologists and cardiologists. The corrected dose algorithm provides a better approach to estimate the equivalent dose to unprotected soft tissues such as eye lenses. Dosimeters that are not shielded from backscatter radiation might underestimate personal equivalent doses when worn over a lead apron and, therefore, should be specifically characterized for this purpose.

'Aeromonas intestinalis' and 'Aeromonas enterica' isolated from human faeces, 'Aeromonas crassostreae' from oyster and 'Aeromonas aquatilis' isolated from lake water represent novel species.

Four Aeromonas strains from clinical and environmental samples differed from known species on the basis of rpoD gene sequence. Multilocus phylogenetic analysis and in silico DNA-DNA hybridization confirmed them as four new species even though their 16S rRNA gene sequence similarity with their closest relatives was >98.7%, as occurred for other Aeromonas spp.

VoxelMages: a general-purpose graphical interface for designing geometries and processing DICOM images for PENELOPE.

The design and construction of geometries for Monte Carlo calculations is an error-prone, time-consuming, and complex step in simulations describing particle interactions and transport in the field of medical physics. The software VoxelMages has been developed to help the user in this task. It allows to design complex geometries and to process DICOM image files for simulations with the general-purpose Monte Carlo code PENELOPE in an easy and straightforward way. VoxelMages also allows to import DICOM-RT structure contour information as delivered by a treatment planning system. Its main characteristics, usage and performance benchmarking are described in detail.

Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria.

Urinary tract infections (UTI) are common among elderly patients in residential care facilities, as well as in the hospital setting. Identifying new biochemical markers of UTI is an active line of research since UTI management is resource intensive. Paraoxonase-1 (PON1) forms part of the patient's immune system, the response-to-injury and inflammation. Our study sought to evaluate alterations in inflammation-related paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2) in patients with an indwelling catheter to assess their potential usefulness as biomarkers of infection. Patients (n = 142) who had had the urinary catheter removed and 100 healthy volunteers were recruited. In all participants we measured serum PON1 activity, PON1 concentration, CCL2, procalcitonin and C-reactive protein (CRP). Results indicated that patients had higher CCL2, CRP and procalcitonin concentrations than the control group, and lower paraoxonase activity. There were no significant differences in PON1 concentrations. When comparing the diagnostic accuracy of CRP, procalcitonin, CCL2 and the PON1-related variables in discriminating between patients with and those without UTI, we found a considerable degree of overlap between groups, i.e., a low diagnostic accuracy. However, there were significant inverse logarithmic correlations between serum paraoxonase activity and the number of days the urinary catheter had been in situ. Our results suggest that measurement of these biochemical variables may be useful in investigating complications of long-term use of these devices and help to improve the economic and clinical investment required in the management of the often-associated infection.

Technical Note: Dosimetry of Leipzig and Valencia applicators without the plastic cap.

PURPOSE: High dose rate (HDR) brachytherapy for treatment of small skin lesions using the Leipzig and Valencia applicators is a widely used technique. These applicators are equipped with an attachable plastic cap to be placed during fraction delivery to ensure electronic equilibrium and to prevent secondary electrons from reaching the skin surface. The purpose of this study is to report on the dosimetric impact of the cap being absent during HDR fraction delivery, which has not been explored previously in the literature. METHODS: geant4 Monte Carlo simulations (version 10.0) have been performed for the Leipzig and Valencia applicators with and without the plastic cap. In order to validate the Monte Carlo simulations, experimental measurements using radiochromic films have been done. RESULTS: Dose absorbed within 1 mm of the skin surface increases by a factor of 1500% for the Leipzig applicators and of 180% for the Valencia applicators. Deeper than 1 mm, the overdosage flattens up to a 10% increase. CONCLUSIONS: Differences of treating with or without the plastic cap are significant. Users must check always that the plastic cap is in place before any treatment in order to avoid overdosage of the skin. Prior to skin HDR fraction delivery, the timeout checklist should include verification of the cap placement.

Design and characterization of a new high-dose-rate brachytherapy Valencia applicator for larger skin lesions.

PURPOSE: The aims of this study were (i) to design a new high-dose-rate (HDR) brachytherapy applicator for treating surface lesions with planning target volumes larger than 3 cm in diameter and up to 5 cm in size, using the microSelectron-HDR or Flexitron afterloader (Elekta Brachytherapy) with a (192)Ir source; (ii) to calculate by means of the Monte Carlo (MC) method the dose distribution for the new applicator when it is placed against a water phantom; and (iii) to validate experimentally the dose distributions in water. METHODS: The penelope2008 MC code was used to optimize dwell positions and dwell times. Next, the dose distribution in a water phantom and the leakage dose distribution around the applicator were calculated. Finally, MC data were validated experimentally for a (192)Ir mHDR-v2 source by measuring (i) dose distributions with radiochromic EBT3 films (ISP); (ii) percentage depth-dose (PDD) curve with the parallel-plate ionization chamber Advanced Markus (PTW); and (iii) absolute dose rate with EBT3 films and the PinPoint T31016 (PTW) ionization chamber. RESULTS: The new applicator is made of tungsten alloy (Densimet) and consists of a set of interchangeable collimators. Three catheters are used to allocate the source at prefixed dwell positions with preset weights to produce a homogenous dose distribution at the typical prescription depth of 3 mm in water. The same plan is used for all available collimators. PDD, absolute dose rate per unit of air kerma strength, and off-axis profiles in a cylindrical water phantom are reported. These data can be used for treatment planning. Leakage around the applicator was also scored. The dose distributions, PDD, and absolute dose rate calculated agree within experimental uncertainties with the doses measured: differences of MC data with chamber measurements are up to 0.8% and with radiochromic films are up to 3.5%. CONCLUSIONS: The new applicator and the dosimetric data provided here will be a valuable tool in clinical practice, making treatment of large skin lesions simpler, faster, and safer. Also the dose to surrounding healthy tissues is minimal.

Cost effectiveness analysis of fesoterodine compared to mirabegron in first-line therapy setting for overactive bladder with urge urinary incontinence, from the Spanish National Health System perspective. / Análisis de coste efectividad de fesoterodina comparado con mirabegron en el marco de tratamiento de primera línea para vejiga hiperactiva con incontinencia urinaria de urgencia, desde la perspectiva del Sistema Nacional de Salud español.

OBJECTIVES: To evaluate the cost-effectiveness of first-line treatment of Overactive Bladder (OAB) with fesoterodine relative to mirabegron, from the Spanish National Health System (NHS) perspective. METHODS: A decision tree model was developed to represent a typical clinical process of 52-week of treatment for an OAB patient with urge urinary incontinence (UUI) initiating first-line therapy with fesoterodine 4mg, including optional titration to 8mg, vs.mirabegron 50mg. Efficacy data were obtained from a Bayesian indirect treatment meta-analysis. Patients with UUI of less than one episode/day were defined as treatment responder and persistence was assessed at weeks 4, 12 and 24. At week 12, non-responders discontinued treatment permanently. Quality-adjusted life years (QALYs) were calculated based on time spent in responder and non-responder states. OAB-related drug and medical care costs including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections and depression) were modeled and expressed in €2015. RESULTS: At week 52, the percentage of responders was 20.8% for patients starting on fesoterodine 4mg who optionally titrated to 8mg and 19.4% for patients treated with mirabegron. QALYs were slightly higher with fesoterodine than mirabegron (0.7703vs. 0.7668, difference=0.0035). Fesoterodine treatment also had slightly higher total costs than mirabegron (3,296€vs. 3,217, difference=79€), resulting in a cost of 22,523/QALY€ gained for fesoterodine versus mirabegron. Probabilistic sensitivity analysis confirmed the slight advantage of fesoterodine with a 61.1% probability of being cost-effective at the 30,000€ willingness-to-pay for 1QALY threshold. CONCLUSIONS: Given the relatively small 1-year cost difference between the two treatments, fesoterodine can be considered a cost-effective option relative to mirabegron for the first-line management of OAB with UUI in Spain.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

High frequencies of antibiotic resistance genes in infants' meconium and early fecal samples.

The gastrointestinal tract (GIT) microbiota has been identified as an important reservoir of antibiotic resistance genes (ARGs) that can be horizontally transferred to pathogenic species. Maternal GIT microbes can be transmitted to the offspring, and recent work indicates that such transfer starts before birth. We have used culture-independent genetic screenings to explore whether ARGs are already present in the meconium accumulated in the GIT during fetal life and in feces of 1-week-old infants. We have analyzed resistance to ß-lactam antibiotics (BLr) and tetracycline (Tcr), screening for a variety of genes conferring each. To evaluate whether ARGs could have been inherited by maternal transmission, we have screened perinatal fecal samples of the 1-week-old babies' mothers, as well as a mother-infant series including meconium, fecal samples collected through the infant's 1st year, maternal fecal samples and colostrum. Our results reveal a high prevalence of BLr and Tcr in both meconium and early fecal samples, implying that the GIT resistance reservoir starts to accumulate even before birth. We show that ARGs present in the mother may reach the meconium and colostrum and establish in the infant GIT, but also that some ARGs were likely acquired from other sources. Alarmingly, we identified in both meconium and 1-week-olds' samples a particularly elevated prevalence of mecA (>45%), six-fold higher than that detected in the mothers. The mecA gene confers BLr to methicillin-resistant Staphylococcus aureus, and although its detection does not imply the presence of this pathogen, it does implicate the young infant's GIT as a noteworthy reservoir of this gene.

Evaluation of lens absorbed dose with Cone Beam IGRT procedures.

The purpose of this work is to evaluate the absorbed dose to the eye lenses due to the cone beam computed tomography (CBCT) system used to accurately position the patient during head-and-neck image guided procedures. The on-board imaging (OBI) systems (v.1.5) of Clinac iX and TrueBeam (Varian) accelerators were used to evaluate the imparted dose to the eye lenses and some additional points of the head. All CBCT scans were acquired with the Standard-Dose Head protocol from Varian. Doses were measured using thermoluminescence dosimeters (TLDs) placed in an anthropomorphic phantom. TLDs were calibrated at the beam quality used to reduce their energy dependence. Average dose to the lens due to the OBI systems of the Clinac iX and the TrueBeam were 0.71 ± 0.07 mGy/CBCT and 0.70 ± 0.08 mGy/CBCT, respectively. The extra absorbed dose received by the eye lenses due to one CBCT acquisition with the studied protocol is far below the 500 mGy threshold established by ICRP for cataract formation (ICRP 2011 Statement on Tissue Reactions). However, the incremental effect of several CBCT acquisitions during the whole treatment should be taken into account.