Physicochemical properties and encapsulation of silicon in double emulsions for healthier food applications.

This article analyses the potential use of double emulsions as silicon delivery systems with reference to the influence of the composition of the inner aqueous phase (W1, containing NaCl and sodium caseinate or gelatin) on silicon encapsulation and physicochemical properties of food-grade W1/O/W2. Irrespective of W1, DEs initially showed a well-defined monomodal distribution, with the widest range registering in the sample with gelatin. All samples developed a bimodal distribution during storage (3 ± 2 °C). Heating increased the range of droplet size distribution. DEs exhibited high physical stability (creaming), decreasing over storage; this behaviour was generally unaffected by W1 composition, which maintained similar stability (95-96%) at the end of storage. Viscosity was generally unaffected by formulation, storage time or heating treatment. Si encapsulation efficiency (72.4 and 78.3%) was not affected by W1 composition, while Si encapsulation stability was generally unaffected by either storage or heating. These DEs can be used as potential ingredient (with lower fat content, better fatty acid profile and with the potential Si health benefits) for the development of healthier foods including meat products.

Genetic parameters for birthweight environmental variability in mice.

Data from a divergent experiment for birthweight (BrW) environmental variability were used to estimate genetic parameters for BrW trait and its environmental variability by fitting both homoscedastic (HO) and heteroscedastic (HE) models. A total of 5 475 records of BrW from animals born from inbred dams, and 7 140 pedigree records were used. The heritability of BrW using the model HO was 0.27, with the litter effect much more important, 0.43. The model HE provided a genetic correlation between the trait and its environmental variability that was very high and negative, -0.97, and a high value for the additive genetic variance for environmental variability, suggesting an artefact in the model. The residual skewness was found to be essentially null. A model considering the genetic correlation null was also fitted, and used to obtain the breeding values for the selection process. Moreover, the trait was considered as maternal resulting in similar estimates under the model HO, but more reasonable for the genetic correlation between the trait and its environmental variability of 0.48 with a value of 0.25 for the additive genetic variance regarding environmental variability under the model HE. This led to the conclusion that environmental variability of BrW in mice must be selected via dams. Estimated parameters in a reduced dataset without inbred animals did not substantially change this conclusion.

Restricting inbreeding while maintaining selection response for weight gain in Mus musculus.

An experiment with mice was designed to test the relative efficiency of three selection methods that help to minimize the rate of inbreeding during selection. A common house mice (Mus musculus) population was selected for 17 generations to increase the weight gain between 21 and 42 days. The population was split at random into three lines A, B and C where three selection methods were applied: individual selection and random mating, weighted selection with random mating and individual selection with minimum coancestry mating, respectively. There were three replicates for each line. Cumulated selection response was similar in the three lines, but there were differences in the level of inbreeding attained (in percentage): 31.24 (method A), 24.72 (method B) and 27.88 (method C). As consequence, lines B and C (weighted selection and minimum coancestry) showed a lower value of deterioration of fitness traits (the intrauterine mortality and the mortality at birth) than line A (random mating).

[Tonic pupil after COVID-19 infection]. / Pupila tónica después de la infección por COVID-19.

The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since been reported. We present the case of a patient with a bilateral tonic pupil in the postinfectious context of COVID-19. Brain magnetic resonance imaging and laboratory tests were normal, a 0.125% pilocarpine test confirmed the diagnosis.

Tonic pupil after COVID-19 infection.

The latest global health threat is the ongoing outbreak of respiratory disease, which was named COVID-19 and multiple ever-evolving neurological complications have since been reported. We present the case of a patient with a bilateral tonic pupil in the postinfectious context of COVID 19. Brain magnetic resonance imaging and laboratory tests were normal, a 0.125% pilocarpine test confirmed the diagnosis.

18F-FDG-PET in guided dose-painting with intensity modulated radiotherapy in oropharyngeal tumours: A phase I study (FiGaRO).

BACKGROUND AND PURPOSE: The FiGaRO trial assessed the feasibility and safety of using an FDG-PET-based dose-painting technique to deliver a radiotherapy (RT) boostto the FDG-avid primary tumour in patients with locally advanced high and intermediate risk oropharyngeal cancer. MATERIALS AND METHOD: Patients underwent a planning 18FDG-PET-CT scan, immobilised in the treatment position, after one cycle of induction chemotherapy. The volume of persistent FDG-avidity in the primary tumour was escalated to 71.5 Gy in30 fractions delivered using a simultaneous integrated boost Intensity Modulated RT (SIB-IMRT) technique. RT was delivered with concomitant Cisplatin following 2 cycles of induction chemotherapy. The primary outcome was the incidence of grade ≥ 3 late mucosal toxicity 12 months post-treatment, with an excess rate of >10% regarded as unacceptable. RESULTS: Twenty-nine patients were included and twenty-four were treated between 2014 and 2018, in two UK centres. Median follow-up was 36 months (range 4-56 months). Pre-defined planning target volume objectives and organ at risk dose constraints were met in all cases. There were no incidents of acute grade 4 toxicity. There were 4 cases of grade ≥ 3 mucosal toxicity at 12 months post-treatment (19.1%). There were no cases of persistent mucosal ulceration at 12 months. Overall survival at 3-years was 87.5%, 92.9% for intermediate and 70.0% for high risk patients. CONCLUSION: Late toxicity rates, although higher than anticipated, are comparable to contemporary published data for standard dose chemo-IMRT. Results suggest improved 3y survival rates for high risk patients. This approach merits further investigation. ClinicalTrials.gov Identifier: NCT02953197.

Study of out-of-field dose in photon radiotherapy: A commercial treatment planning system versus measurements and Monte Carlo simulations.

PURPOSE: An accurate assessment of out-of-field dose is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. Although treatment planning systems (TPSs) calculate dose distributions outside the treatment field, little is known about the accuracy of these calculations. The aim of this work is to thoroughly compare the out-of-field dose distributions given by two algorithms implemented in the Monaco TPS, with measurements and full Monte Carlo simulations. METHODS: Out-of-field dose distributions predicted by the collapsed cone convolution (CCC) and Monte Carlo (MCMonaco ) algorithms, built into the commercially available Monaco version 5.11 TPS, are compared with measurements carried out on an Elekta Axesse linear accelerator. For the measurements, ion chambers, thermoluminescent dosimeters, and EBT3 film are used. The BEAMnrc code, built on the EGSnrc system, is used to create a model of the Elekta Axesse with the Agility collimation system, and the space phase file generated is scored by DOSXYZnrc to generate the dose distributions (MCEGSnrc ). Three different irradiation scenarios are considered: (a) a 10 × 10 cm2 field, (b) an IMRT prostate plan, and (c) a three-field lung plan. Monaco's calculations, experimental measurements, and Monte Carlo simulations are carried out in water and/or in an ICRP110 phantom. RESULTS: For the 10 × 10 cm2 field case, CCC underestimated the dose, compared to ion chamber measurements, by 13% (differences relative to the algorithm) on average between the 5% and the ≈2% isodoses. MCMonaco underestimated the dose only from approximately the 2% isodose for this case. Qualitatively similar results were observed for the studied IMRT case when compared to film dosimetry. For the three-field lung plan, dose underestimations of up to ≈90% for MCMonaco and ≈60% for CCC, relative to MCEGSnrc simulations, were observed in mean dose to organs located beyond the 2% isodose. CONCLUSIONS: This work shows that Monaco underestimates out-of-field doses in almost all the cases considered. Thus, it does not describe dose distribution beyond the border of the field accurately. This is in agreement with previously published works reporting similar results for other TPSs. Analytical models for out-of-field dose assessment, MC simulations or experimental measurements may be an adequate alternative for this purpose.

10-MV SBRT FFF IRRADIATION TECHNIQUE IS ASSOCIATED TO THE LOWEST PERIPHERAL DOSE: THE OUTCOME OF 142 TREATMENT PLANS FOR THE 10 MOST COMMON TUMOUR LOCATIONS.

There is a growing interest in the combined use of Stereotactic Body Radiation Therapy (SBRT) with Flattening Filter Free (FFF) due to the high local control rates and reduced treatment times, compared to conventionally fractionated treatments. It has been suggested that they may also provide a better radiation protection to radiotherapy patients as a consequence of the expected decrease in peripheral doses. This work aims to determine this reduction in unattended out-of-field regions, where no CT information is available but an important percentage of second primary cancers occur. For that purpose, ten different cases suitable for SBRT were chosen. Thus, 142 different treatment plans including SBRT, as well as 3D-CRT, IMRT and VMAT (with standard fractionation) in low and high energies for Varian (FF and FFF), Siemens and Elekta machines were created. Then, photon and neutron peripheral dose in 14 organs were assessed and compared using two analytical models. For the prostate case, uncomplicated and cancer free control probability estimation was also carried out. As a general behavior, SBRT plans led to the lowest peripheral doses followed by 3D-CRT, VMAT and IMRT, in this order. Unflattened beams proved to be the most effective in reducing peripheral doses, especially for 10 MV. The obtained results suggest that FFF beams for SBRT with 10 MV represent the best compromise between dose delivery efficiency and peripheral dose reduction.

External photon radiation treatment for prostate cancer: Uncomplicated and cancer-free control probability assessment of 36 plans.

PURPOSE: To perform a systematic and thorough assessment, using the Uncomplicated and Cancer-Free Control Probability (UCFCP) function, of a broad range of photon prostate cancer RT treatments, on the same scenario (a unique pelvic CT set). UCFCP considers, together with the probabilities of local tumour control (TCP) and deterministic (late) sequelae (NTCP), the second primary cancer risk (SPCR) due to photon and neutron peripheral doses. METHODS AND MATERIALS: Thirty-six radiotherapy plans were produced for the same CT. 6, 10, 15 and 18 MV 3DCRT, IMRT and VMAT (77.4 Gy in 43 fractions) and 6 and 10 MV SBRT (36.25 Gy in 5 fractions with flattened and FFF beams) for Elekta, Siemens and Varian Linacs plans were included. DVH and peripheral organ dosimetry were used to compute TCP, NTCP, and SPCR (the competition and LNT models) for further plan ranking. RESULTS: Biological models (and parameters) used predicted an outcome which is in agreement with epidemiological findings. SBRT plans showed the lowest SPCR and a below average NTCPrectal. High energy plans did not rank worse than the low energy ones. Intensity modulated plans were ranked above the 3D conformal techniques. CONCLUSIONS: According to UCFCP, the best plans were the10 MV SBRTs. SPCR rates were low and did not show a substantial impact on plan ranking. High energy intensity-modulated plans did not increase in excess the average of SPCR. Even more, they ranked among the best, provided that MU were efficiently managed.

[25 years experience in cerebrospinal shunt. Are new systems better?]. / 25 años de experiencia en válvulas de derivación ventrículo-peritoneal. Son mejores los nuevos sistemas?

INTRODUCTION: Since the introduction of the first ventricular shunt in 1949, the cerebrospinal shunts are the most used choice for the management of hydrocephalus in children. With the technological advance, systems have been developing increasingly sophisticated. Our aim is to study the incidence of complications after the implantation of these shunts and the variables associated to it. MATERIAL AND METHODS: We perform a retrospective study between 1981 and 2006, gathering the patients between 0 and 15 years treated at our Hospital for the placement of a cerebrospinal shunt or as consequence of a problem of the device. We analyze the tipe of shunt (Hakim, Pudentz, Delta, Orbis-Sigma, Strata, Codman), etiology of hydrocephalus, age, immediate and late complications, permanence of the system, changes of the system and cerebrospinal fluid. The qualitative data were analyze by c2 test. We also estimate survival of shunts with Kaplan-Meier stimator and make a multivariant Cox regression analysis. RESULTS: A total of 75 patients. The main etiology for hydrocephalous was myelomeningocele, followed by congenital and posthemorrhagic. Most of the patients presented complications of the system in the follow-up. They were adjusted for age, sex, etiology, shunt and surgeon. The variable that had an independent effect for predicting the presence of a complication was the type of shunt, being the most ancient systems those with major survival. The most frequent complication in the immediate period (< 3 month) was the obstruction and infection of the proximal catheter or shunt. Distal catheter disconnection or break prevailed in the late one. We got few functional complications, these were not related with the type of shunt. CONCLUSIONS: In our experience, the shunts with the less short-term probability of complication (< 3 months) have been old simple systems like Hakim and Pudentz. The functional complications, that are those which presumably should be reduced by the new programmable systems, don,t seem do it, neither mean longer survival of the system.

2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary.

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.

Peripheral equivalent neutron dose model implementation for radiotherapy patients.

PURPOSE: Neutron peripheral contamination in high-energy radiotherapy implies an increase of secondary radiation-induced cancer risk. Although peripheral neutron dose (PND) has been evaluated in organs, few studies have been performed regarding patient size. This work aims to improve an existing methodology for adult patient PND estimations to generalize it to young and children, for its implementation in treatment planning systems (TPS). METHODS: As a first step, we aimed to generalize the previous model to be usable with any thermal neutron detector. Then, taking into account total neutron spectra and dose-to-point thermal neutron fluence measurements for three phantom sizes (adult, teen and child) and two common treatment locations (H&N and abdomen), the new model was proposed. It represents an upgraded parameterization and extension of the existing one, including patient anatomy. Finally, comparison between estimations and measurements, as well as validation against the original model, was carried out for 510 measured patients. RESULTS: Concordance found between experimental and theoretical estimations makes us confident about later implementation in treatment planning systems. Comparison among the previous and upgraded models shows no significant differences for the adult case. However, an important underestimation (34.1% on average) can be observed regarding child case for the original one. CONCLUSIONS: An improved generalization of an existing PND model, considering patient anatomy has been validated and used in real patients. The final methodology is easily implementable in clinical routine and TPS thanks to the ready availability of input parameters (patient height and weight, high-energy MU and facility characterization).

Neutron measurements in radiotherapy: A method to correct neutron sensitive devices for parasitic photon response.

One of the major causes of secondary malignancies after radiotherapy treatments are peripheral doses, known to increase for some newer techniques (such as IMRT or VMAT). For accelerators operating above 10MV, neutrons can represent important contribution to peripheral doses. This neutron contamination can be measured using different passive or active techniques, available in the literature. As far as active (or direct-reading) procedures are concerned, a major issue is represented by their parasitic photon sensitivity, which can significantly affect the measurement when the point of test is located near to the field-edge. This work proposes a simple method to estimate the unwanted photon contribution to these neutrons. As a relevant case study, the use of a recently neutron sensor for "in-phantom" measurements in high-energy machines was considered. The method, called "Dual Energy Photon Subtraction" (DEPS), requires pairs of measurements performed for the same treatment, in low-energy (6MV) and high energy (e.g. 15MV) fields. It assumes that the peripheral photon dose (PPD) at a fixed point in a phantom, normalized to the unit photon dose at the isocenter, does not depend on the treatment energy. Measurements with ionization chamber and Monte Carlo simulations were used to evaluate the validity of this hypothesis. DEPS method was compared to already published correction methods, such as the use of neutron absorber materials. In addition to its simplicity, an advantage of DEPs procedure is that it can be applied to any radiotherapy machine.

[Topical cyclosporine in the treatment of ocular actinic prurigo]. / Ciclosporina tópica como tratamiento del prúrigo actínico ocular.

CASE REPORT: A 14-year-old girl from Peru suffered severe limbitis and conjunctivitis. She also presented with clinical skin features diagnosed as actinic prurigo (AP). Her symptoms were successfully controlled with sustained topical therapy of 2% Cyclosporine A. DISCUSSION: AP is an idiopathic photodermatosis that affects mainly the hispanic population of Latin America. There are ocular signs of severe limbitis and conjunctivitis (like atopic keratoconjunctivitis) in 45% of cases. Literature on the subject is very limited and currently topical cyclosporine seems to be the best therapy available.

Using a Tandem Pelletron accelerator to produce a thermal neutron beam for detector testing purposes.

Active thermal neutron detectors are used in a wide range of measuring devices in medicine, industry and research. For many applications, the long-term stability of these devices is crucial, so that very well controlled neutron fields are needed to perform calibrations and repeatability tests. A way to achieve such reference neutron fields, relying on a 3 MV Tandem Pelletron accelerator available at the CNA (Seville, Spain), is reported here. This paper shows thermal neutron field production and reproducibility characteristics over few days.

Improving the neutron-to-photon discrimination capability of detectors used for neutron dosimetry in high energy photon beam radiotherapy.

The increasing interest of the medical community to radioinduced second malignancies due to photoneutrons in patients undergoing high-energy radiotherapy, has stimulated in recent years the study of peripheral doses, including the development of some dedicated active detectors. Although these devices are designed to respond to neutrons only, their parasitic photon response is usually not identically zero and anisotropic. The impact of these facts on measurement accuracy can be important, especially in points close to the photon field-edge. A simple method to estimate the photon contribution to detector readings is to cover it with a thermal neutron absorber with reduced secondary photon emission, such as a borated rubber. This technique was applied to the TNRD (Thermal Neutron Rate Detector), recently validated for thermal neutron measurements in high-energy photon radiotherapy. The positive results, together with the accessibility of the method, encourage its application to other detectors and different clinical scenarios.

[Study of renal function and compensatory changes in children with single kidney]. / Determinación de función renal y cambios compensadores en niños con riñón único.

INTRODUCTION: It has always been thought that a reduction of renal tissue in childhood sometimes causes some irreversible injury in the remnant kidney as the years go by. The aim of this paper is to look over the presence of these changes and identify the risk of nephropaty throughout several parameters. MATERIAL AND METHODS: We reviewed 38 children, 23 males and 15 females, aged between 1 and 15 years, who had lost unilateral renal mass because of congenital or adquired diseases. We made two groups of patients on the basis of having born without any unilateral renal function -group I- or having lost unilateral renal function after the second year of life. We measured: Somatometry, arterial pressure, glomerular filtration, microalbuminuria, renal volume and gammagraphic studies were also made. We also considered the presence of contralateral anomalies. RESULTS: Body weight and height were within normal percentiles. Arterial pressure increased in 5 patients. Seric creatinine was normal, creatinine clearance (Ccr) was higher than normal in all patients of both groups, and urinary excretion of protein was normal. Renal volume of remnant kidney was similar in both groups, and no relation with renal function level was found, but it increased through the years. Isotopic studies showed ectatic drainage in all urinary systems. Contralateral anomalies were seen in 7 patients, and they consisted in hydronephrosis and vesico-ureteral reflux. CONCLUSIONS: Hypertension was not related to the cause of renal absence nor the pathology of remnant kidney. Ccr was higher than normal, showing an hyperfiltration status, not confirmed by the values of isotopic filtrate. Renal volume reached by the single kidney was affected by the time after the renal loss, and apparently has been slowed down in cases with contralateral anomalies.

Commissioning the neutron production of a Linac: development of a simple tool for second cancer risk estimation.

PURPOSE: Knowing the contribution of neutron to collateral effects in treatments is both a complex and a mandatory task. This work aims to present an operative procedure for neutron estimates in any facility using a neutron digital detector. METHODS: The authors' previous work established a linear relationship between the total second cancer risk due to neutrons (TR(n)) and the number of MU of the treatment. Given that the digital detector also presents linearity with MU, its response can be used to determine the TR(n) per unit MU, denoted as m, normally associated to a generic Linac model and radiotherapy facility. Thus, from the number of MU of each patient treatment, the associated risk can be estimated. The feasibility of the procedure was tested by applying it in eight facilities; patients were evaluated as well. RESULTS: From the reading of the detector under selected irradiation conditions, m values were obtained for different machines, ranging from 0.25 × 10(-4)% per MU for an Elekta Axesse at 10 MV to 6.5 × 10(-4)% per MU for a Varian Clinac at 18 MV. Using these values, TR(n) of patients was estimated in each facility and compared to that from the individual evaluation. Differences were within the range of uncertainty of the authors' methodology of equivalent dose and risk estimations. CONCLUSIONS: The procedure presented here allows an easy estimation of the second cancer risk due to neutrons for any patient, given the number of MU of the treatment. It will enable the consideration of this information when selecting the optimal treatment for a patient by its implementation in the treatment planning system.

The delta-TCP concept: a clinically useful measure of tumor control probability.

PURPOSE: The aim of this article is to provide a quantitative tool to evaluate the influence of the different dose regions in a non-uniformly irradiated tumour upon the probability of controlling that tumor. METHODS AND MATERIALS: First, a method to generate a distribution of the probability of controlling the cells in a voxel (VCP) is explored and found not to be useful. Second, we introduce the concept of delta-TCP, which represents the gain or loss in the overall TCP as a result of each particular bin in a DVH not receiving the prescribed dose (the same concept is applicable to dose cubes or to a fraction of the bin). The delta-TCP method presented here is based on the Poisson TCP model, but any other model could also be used. Third, using this tool, with parameters appropriate to Stage C prostate tumors, the consequences of "cold" and "hot" dose regions have been explored. RESULTS: We show that TCP is affected by the minimum dose, even if it is delivered to a very small volume (20% dose deficit to 5% of the volume makes the TCP decrease by 18%), and that a hot region may be "wasted" unless the boost is to the bulk of the volume. An example of the application of the delta-TCP concept to a prostate radiotherapy plan is also given. CONCLUSION: The delta-TCP distribution adds more objective information to the original DVH by enabling the clinician or planner to directly evaluate the effects of a non-uniform dose distribution on local control.

Individualization of dose prescription based on normal-tissue dose-volume and radiosensitivity data.

PURPOSE: The aim of this paper is to illustrate the potential gain in tumor control probability (TCP) of prostate cancer patients by individualizing the prescription dose according to both normal-tissue (N-T) dose-volume and radiosensitivity data. METHODS AND MATERIALS: Two exercises have been carried out. Firstly, patients' dose prescriptions were individualised on the basis of N-T dose-volume histograms (DVHs) alone and secondly modeling potential differences in N-T sensitivity as well. In both cases, the change in tumor control that may be achieved by individualizing patients' dose was estimated assuming that after the dose adjustments, every patient had (1) the same value of normal tissue complication probability (NTCP) (5%) and (2) NTCP equal to the average NTCP before individualization (i.e., without increasing the average NTCP). The Lyman-Kutcher-Burman NTCP model was used to predict the N-T response curves with two different sets of parameters. The first exercise, based only on individual NT DVHs (i.e., assuming all patient equally radiosensitive), was over a real population of 50 prostate cancer patients. The second exercise modeled a 10,000-prostate-cancer patient population with varying NT dose-volume distributions and radiosensitivity (through allowing TD(50) to vary). RESULTS: A gain of more than 9% in TCP was predicted when doses were individualized based only on DVHs so that every patient had 5% NTCP after dose adjustments. By adding the estimate of radiosensitivity, the gain increased to more than 15%. When the individualisation was performed without increasing the mean NTCP, then the potential gain in TCP was almost 5% (for adjustment based on DVH distribution solely) increasing to 7% with the additional consideration of radiosensitivity. CONCLUSIONS: There is a potential gain (increase in local tumor control) from dose individualisation strategies based on both N-T dose-volume data and radiosensitivity (assuming that this is available). Dose prescription individualization based only on dose-volume data can be exploited provided that reliable N-T response models are available. There will be additional gains if some estimate of N-T radiosensitivity is available to allow further patient stratification, identification of patients with high radiosensitivity being particularly important.