Dictionary-based software for proton dose reconstruction and submilimetric range verification.

Objective.This paper presents a new method for fast reconstruction (compatible with in-beam use) of deposited dose during proton therapy using data acquired from a PET scanner. The most innovative feature of this novel method is the production of noiseless reconstructed dose distributions from which proton range can be derived with high precision.Approach.A new MLEM & simulated annealing (MSA) algorithm, developed especially in this work, reconstructs the deposited dose distribution from a realistic pre-calculated activity-dose dictionary. This dictionary contains the contribution of each beam in the plan to the 3D activity and dose maps, as calculated by a Monte Carlo simulation. The MSA algorithm, usinga prioriinformation of the treatment plan, seeks for the linear combination of activities of the precomputed beams that best fits the observed PET data, obtaining at the same time the deposited dose.Main results.the method has been tested using simulated data to determine its performance under 4 different test cases: (1) dependency of range detection accuracy with delivered dose, (2) in-beam versus offline verification, (3) ability to detect anatomical changes and (4) reconstruction of a realistic spread-out Bragg peak. The results show the ability of the method to accurately reconstruct doses from PET data corresponding to 1 Gy irradiations, both in intra-fraction and inter-fraction verification scenarios. For this dose level (1 Gy) the method was able to spot range variations as small as 0.6 mm.Significance.out method is able to reconstruct dose maps with remarkable accuracy from clinically relevant dose levels down to 1 Gy. Furthermore, due to the noiseless nature of reconstructed dose maps, an accuracy better than one millimeter was obtained in proton range estimates. These features make of this method a realistic option for range verification in proton therapy.

Impact of an enhanced screening program on the detection of non-AIDS neoplasias in patients with human immunodeficiency virus infection.

BACKGROUND: The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH. METHODS: We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS). DISCUSSION: The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented. TRIAL REGISTRATION: ClinicalTrials.gov NCT04735445. Registered on 25 June 2019.

Finding answers in lipid profile in COVID-19 patients.

INTRODUCTION: A small percentage of patients will develop a severe form of COVID-19 caused by SARS-CoV-2 infection. Thus, it is important to predict the potential outcomes identifying early markers of poor prognosis. In this context, we evaluated the association of SARS-CoV-2 infection with lipid abnormalities and their role in prognosis. METHODS: Single-center, retrospective, observational study of COVID-19 patients admitted from March to October 2020. Clinical and laboratory data, comorbidities, and treatments for COVID-19 were evaluated. Main outcomes including intensive care unit (ICU) admission and mortality were analyzed with a multivariable Cox proportional hazards regression model. RESULTS: We selected 1489 from a total of 2038 consecutive patients with confirmed COVID-19, who had a complete lipid profile before ICU admission. During the follow-up performed in 1109 patients, we observed a decrease in T-c, HDL-c, and LDL-c in 28.6%, 42.9%, and 30.4% of patients, respectively, and an increase in TG in 76.8%. The decrease of both T-c and HDL- c was correlated with a decrease in albumin levels (r = 0.39 and r = 0.37, respectively). Kaplan-Meier survival curves found an increased ICU admission in patients with lower T-c (HR 0.55, CI 0.36-0.86), HDL-c (HR 0.61, CI 0.45-0.84), and LDL-c (HR 0.85, CI 0.74-0.97). Higher values of T-c (HR 0.45, CI 0.36-0.57), HDL-c (HR 0.66, CI 0.54-0.81), and LDL-c (HR 0.86, CI 0.78-0.94) showed a protective effect on mortality. CONCLUSIONS: Abnormalities in lipid profile are a frequent complication of SARS-CoV-2 infection and might be related to morbidity and mortality. FUNDING: Proyectos de Investigación en Salud (FIS) and cofinanced by FEDER.

Angular momentum generation in nuclear fission.

When a heavy atomic nucleus splits (fission), the resulting fragments are observed to emerge spinning1; this phenomenon has been a mystery in nuclear physics for over 40 years2,3. The internal generation of typically six or seven units of angular momentum in each fragment is particularly puzzling for systems that start with zero, or almost zero, spin. There are currently no experimental observations that enable decisive discrimination between the many competing theories for the mechanism that generates the angular momentum4-12. Nevertheless, the consensus is that excitation of collective vibrational modes generates the intrinsic spin before the nucleus splits (pre-scission). Here we show that there is no significant correlation between the spins of the fragment partners, which leads us to conclude that angular momentum in fission is actually generated after the nucleus splits (post-scission). We present comprehensive data showing that the average spin is strongly mass-dependent, varying in saw-tooth distributions. We observe no notable dependence of fragment spin on the mass or charge of the partner nucleus, confirming the uncorrelated post-scission nature of the spin mechanism. To explain these observations, we propose that the collective motion of nucleons in the ruptured neck of the fissioning system generates two independent torques, analogous to the snapping of an elastic band. A parameterization based on occupation of angular momentum states according to statistical theory describes the full range of experimental data well. This insight into the role of spin in nuclear fission is not only important for the fundamental understanding and theoretical description of fission, but also has consequences for the γ-ray heating problem in nuclear reactors13,14, for the study of the structure of neutron-rich isotopes15,16, and for the synthesis and stability of super-heavy elements17,18.

Competition between Allowed and First-Forbidden ß Decay: The Case of

The ß decay of ^{208}Hg into the one-proton hole, one neutron-particle _{81}^{208}Tl_{127} nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z<82 quadrant of neutron-rich nuclei. While both negative and positive parity states with spin 0 and 1 are expected within the Q_{ß} window, only three negative parity states are populated directly in the ß decay. The data provide a unique test of the competition between allowed Gamow-Teller and Fermi, and first-forbidden ß decays, essential for the understanding of the nucleosynthesis of heavy nuclei in the rapid neutron capture process. Furthermore, the observation of the parity changing 0^{+}→0^{-}ß decay where the daughter state is core excited is unique, and can provide information on mesonic corrections of effective operators.

A probabilistic Poisson-based model to detect PRRSV recirculation using sow production records.

Porcine reproductive and respiratory syndrome (PRRS) is a viral disease associated with a decrease in the number of born alive piglets (NBA) and an increase in the number of lost piglets (NLP) per farrowing. Under practical conditions, it is critical to assess whether a farm is suffering PRRSV recirculation in the sow herd as soon as possible. The aim of this research work was to develop a new method to detect potential PRRSV recirculation in sow production farms. Sow reproductive performance records from one farm (farm T) were used to set up the method and records from ten additional farms (farms V1 to V10) were used for validation. A conditional Poisson model of NLP on NBA was proposed to fit the data. A three-step procedure was implemented to detect potential PRRSV recirculation: (i) computation of the maximum-likelihood estimates of the expected values of NBA and NLP in a PRRSV non-recirculating scenario; (ii) calculation, for each farrowing, of the p-value associated with the probability of jointly observing deviations towards decreased NBA and increased NLP. The detection of a potential PRRSV recirculation was based on (iii) the combined p-value resulting from weighing the p-values of the last N farrowings by the chi-square-inverse method. In order to gain specificity, a displacement on the expected non-recirculating NBA and NLP values was used for tuning purposes. With this approach, two PRRSV circulating periods were detected in farm T, which were confirmed with standard laboratorial diagnostic techniques. The method was subsequently validated in farms V1 to V10, where ten PRRSV-recirculating time episodes had been diagnosed. The method proposed here was able to detect the ten PRRSV recirculations using a relatively small set of contiguous farrowings, with only two mismatched weeks, one as a false negative, in farm V1, and one as a false positive, in farm V4. It is concluded that a conditional Poisson-based model of NLP on NBA can be a useful tool for routinely detecting PRRSV recirculation in sow herds.

Effect of Porcine circovirus 2 (PCV-2) maternally derived antibodies on performance and PCV-2 viremia in vaccinated piglets under field conditions.

BACKGROUND: Nowadays, the most common presentation of PCV-2 is the subclinical infection in piglets after weaning. The success of PCV-2 vaccination is associated with the control of the clinical disease as well as the improvement of production parameters. In consequence, the objective of the present study was to analyse the effect of PCV-2 maternally derived antibody (MDA) levels on vaccine efficacy in piglets vaccinated at three weeks of age with a commercial PCV-2 subunit vaccine. The study was performed analysing a database with 6112 wean-to-slaughter piglets from 4 different European regions. RESULTS: Results showed that the use of the vaccine was able to decrease the PCV-2 viremia calculated as area under the curve (AUC = 60.29 ± 3.73), increase average daily weight gain (ADWG = 0.65 ± 0.01 kg/day) and reduce mortality (7%) in vaccinated piglets compared to non-vaccinated ones (AUC of 198.27 ± 6.14, 0.62 ± 0.01 kg/day and 11% respectively). The overall difference of ADWG between both groups was close to 30 g per day (p < 0.05), also when they were split for low and high levels of MDA titres. Moreover, the animals with the highest ADWG were observed in the group of piglets vaccinated with high or extremely high antibody titres (0.66 and 0.65 kg/day respectively). Considering only animals with extremely high antibody titres, both study groups performed similar, however there was a numerical difference of 10 g/day in favour of vaccinated piglets. Likewise, lack of correlation between ADWG and MDA was observed suggesting that no maternal antibody interference was present with the tested vaccine because the vaccinated animals grew faster compared to unvaccinated control animals, regardless of the level of maternal antibodies present at the time of vaccination. CONCLUSIONS: The results of the present study demonstrated that the MDA against PCV-2 transferred through the colostrum intake has a protective effect against this viral infection. The vaccine used in the present study (Ingelvac CircoFLEX®) was effective when applied at three weeks of age and was not affected by the level of MDA at the time of vaccination.

Outcomes by sex following treatment initiation with darunavir/cobicistat in a large Spanish cohort of the CODAR study (GeSIDA 9316).

BACKGROUND: Few women have been included in darunavir/cobicistat clinical development studies, and hardly any of them were antiretroviral experienced or treated with anything other than triple-based therapies. OBJECTIVES: Our aim was to increase our knowledge about women living with HIV undergoing darunavir/cobicistat-based regimens. METHODS: A multicentre (21 hospitals), retrospective study including a centrally selected random sample of HIV-1 patients starting a darunavir/cobicistat-based regimen from June 2014 to March 2017 was planned. Baseline characteristics, 24 and 48 week viral load response (<50 copies/mL), CD4+ lymphocyte count increase, time to change darunavir/cobicistat and adverse event occurrence were all compared by sex. The study was approved by each of the 21 ethics committees, and patients signed informed consent. RESULTS: Out of 761 participants, 193 were women. Similar characteristics were found for both sexes, except that the women had a longer duration of HIV infection (P = 0.001), and were less frequently pre-treated with darunavir/cobicistat in their previous regimen (P = 0.02). The main reason for using a darunavir/cobicistat-based regimen was simplification, without differences by sex, while monotherapy seems to be more frequently prescribed in women than in men (P = 0.067). The main outcomes, HIV viral load response, CD4+ lymphocyte count increase at 24 or 48 weeks, occurrence of adverse events, main reasons for changing and time to the modify darunavir/cobicistat regimen, did not show differences between the sexes. CONCLUSIONS: No sex disparities were found in the main study outcomes. These results support the use of a darunavir/cobicistat-based regimen in long-term pre-treated women. Clinical Trial.gov No. NCT03042390.

Large Impact of the Decay of Niobium Isomers on the Reactor ν[over ¯]_{e} Summation Calculations.

Even mass neutron-rich niobium isotopes are among the principal contributors to the reactor antineutrino energy spectrum. They are also among the most challenging to measure due to the refractory nature of niobium, and because they exhibit isomeric states lying very close in energy. The ß-intensity distributions of ^{100gs,100m}Nb and ^{102gs,102m}Nb ß decays have been determined using the total absorption γ-ray spectroscopy technique. The measurements were performed at the upgraded Ion Guide Isotope Separator On-Line facility at the University of Jyväskylä. Here, the double Penning trap system JYFLTRAP was employed to disentangle the ß decay of the isomeric states. The new data obtained in this challenging measurement have a large impact in antineutrino summation calculations. For the first time the discrepancy between the summation model and the reactor antineutrino measurements in the region of the shape distortion has been reduced.

First Accurate Normalization of the ß-delayed α Decay of

The ^{12}C(α,γ)^{16}O reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced α width, γ_{11}, of the bound 1^{-} level in ^{16}O is particularly important to determine the cross section. The magnitude of γ_{11} is determined via sub-Coulomb α-transfer reactions or the ß-delayed α decay of ^{16}N, but the latter approach is presently hampered by the lack of sufficiently precise data on the ß-decay branching ratios. Here we report improved branching ratios for the bound 1^{-} level [b_{ß,11}=(5.02±0.10)×10^{-2}] and for ß-delayed α emission [b_{ßα}=(1.59±0.06)×10^{-5}]. Our value for b_{ßα} is 33% larger than previously held, leading to a substantial increase in γ_{11}. Our revised value for γ_{11} is in good agreement with the value obtained in α-transfer studies and the weighted average of the two gives a robust and precise determination of γ_{11}, which provides significantly improved constraints on the ^{12}C(α,γ) cross section in the energy range relevant to hydrostatic He burning.

Strong Neutron Pairing in core+4n Nuclei.

The emission of neutron pairs from the neutron-rich N=12 isotones ^{18}C and ^{20}O has been studied by high-energy nucleon knockout from ^{19}N and ^{21}O secondary beams, populating unbound states of the two isotones up to 15 MeV above their two-neutron emission thresholds. The analysis of triple fragment-n-n correlations shows that the decay ^{19}N(-1p)^{18}C^{*}→^{16}C+n+n is clearly dominated by direct pair emission. The two-neutron correlation strength, the largest ever observed, suggests the predominance of a ^{14}C core surrounded by four valence neutrons arranged in strongly correlated pairs. On the other hand, a significant competition of a sequential branch is found in the decay ^{21}O(-1n)^{20}O^{*}→^{18}O+n+n, attributed to its formation through the knockout of a deeply bound neutron that breaks the ^{16}O core and reduces the number of pairs.

Quasifree (p, 2p) Reactions on Oxygen Isotopes: Observation of Isospin Independence of the Reduced Single-Particle Strength.

Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R^{3}B/LAND setup with incident beam energies in the range of 300-450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type ^{A}O(p,2p)^{A-1}N have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.

Continued propagation of the CRF19_cpx variant among HIV-positive MSM patients in Spain.

Objectives: The HIV-1 CRF19_cpx genetic form has been recently associated with greater pathogenicity. We used CoRIS, a national cohort of 31 reference hospitals in Spain, to investigate the current epidemiological situation of this variant in Spain. Patients and methods: We analysed 4734 naive HIV-1-positive patients diagnosed during the 2007-15 period with an available pol gene sequence in the CoRIS resistance database. HIV-1 CRF19_cpx was ascribed through REGA3.0 and confirmed by a phylogenetic analysis. We analysed the presence of the transmission clusters of HIV-1 CRF19_cpx by maximum likelihood [with the randomized accelerated maximum likelihood (RAxML) program] and the time to the most recent common ancestor using Bayesian inference (BEAST, v. 1.7.5). Results: Nineteen patients were infected with CRF19_cpx: all were male, they had a mean age of 42.9 years (95% CI: 36.4-52.5 years), the majority were MSM [n = 18 (95%)] and of Spanish nationality [n = 16 (84.2%)] and they had high CD4+ T cell counts (∼415 cells/mm3). Fifteen patients were grouped into four different transmission clusters: two clusters (two patients each) grouped the patients from Valencia and another cluster grouped one patient from Madrid and another from Seville. We found a larger cluster that grouped nine patients from southern Spain (Malaga and Seville), of which six presented mutation G190A. We estimated the origin of all the transmission clusters to take place between 2009 and 2010. Conclusions: We demonstrate that this variant has spread in Spain in recent years among young HIV-positive MSM and we note a recent expansion in southern Spain in patients who carry mutation G190A. We alert healthcare managers to enhance preventive measures to prevent the continuous spread of HIV-1 CRF19_cpx.

Carotenoid intake and SCD genotype exert complementary effects over fat content and fatty acid composition in Duroc pigs.

Nutritional and genetic strategies are needed to enhance intramuscular fat (IMF) and MUFA content without altering carcass leanness. Dietary vitamin A restriction has been suggested to specifically promote IMF, whereas a polymorphism of the () gene has shown to specifically increase MUFA. The purpose of this study was to investigate the combined effects of provitamin A (PVA) carotenoid intake and genotype (>) on hepatic retinoid content and on the liver, muscle (LM and gluteus medius [GM]), and subcutaneous fat (SF) content and fatty acid composition. Following a split-plot design, 32 castrated Duroc pigs, half of each of the 2 homozygous genotypes (CC and TT), were subjected from 165 to 195 d of age to 2 finishing diets differing in the PVA carotenoid content (an enriched-carotene diet [C+] and a control diet [C-]). Both diets were identical except for the corn line used in the feed. The C+ was formulated with 20% of a carotenoid-fortified corn (M37W-Ph3) whereas the C- instead used 20% of its near isogenic M37W line, which did not contain PVA carotenoids. No vitamin A was added to the diets. The C- was estimated to provide, at most, 1,300 IU of vitamin A/kg and the C+ to supply an extra amount of at least 800 IU vitamin A/kg. Compared with the pigs fed the C-, pigs fed with C+ had 3-fold more retinoic acid ( < 0.01) and 4-fold more gene expression in the liver ( = 0.06). The diet did not affect performance traits and backfat thickness, but pigs fed the C+ had less fat (4.0 vs. 5.0%; = 0.07) and MUFA (18.3 vs. 22.5%; = 0.01) in the liver, less IMF (5.4 vs. 8.3%; = 0.04) in the GM, and more fat content (90.4 vs. 87.9%; = 0.09) and MUFA (48.0 vs. 46.6%; = 0.04) in SF. The TT genotype at the gene increased MUFA ( < 0.05) in all tissues (21.4 vs. 19.5% in the liver, 55.0 vs. 53.1% in the LM, 53.9 vs. 51.7% in the GM, and 48.0 vs. 46.7% in SF for TT and CC genotypes, respectively). Liver fat and MUFA content nonlinearly declined with liver all- retinoic acid, indicating a saturation point at relatively low all- retinoic acid content. The results obtained provide evidence for a complementary role between dietary PVA and genotype, in the sense that the TT pigs fed with a low-PVA diet are expected to show higher and more monounsaturated IMF without increasing total fat content.

223Ra-dichloride spectrometric characterization: Searching for the presence of long-lived isotopes with radiological protection implications.

223Ra-dichloride was approved with the commercial name of Xofigo in 2014 for treatment of metastatic castration-resistant prostate cancer. 223Ra is obtained by neutron irradiation of 226Ra yielding 227Ac, which decays to 227Th and 223Fr, both decaying to 223Ra. Since 223Ra is predominantly (95.3%) an alpha emitter with a 11.42days long half-life, the radiopharmaceutical, its remnants, the patient, and waste material can be managed and disposed with low radiation protection requirements. 227Ac is a long-lived (T1/2=21.77years) beta emitter that demands strong radiation protection measures. In particular waste disposal has to follow the International Atomic Energy Agency (IAEA) and European Commission (EC) regulations. Since 227Ac is involved in the production of 223Ra, an impurity analysis of each batch is required after production. Due to time restrictions, the manufacturer's detection limit (<0.001%) exceeds the one required to assure that 227Ac concentrations are below direct disposal levels. To improve the detection limit, long-term accurate spectroscopy is required. Alpha and gamma spectroscopy measurements were carried out at the Complutense University Nuclear Physics Laboratory. After twelve months follow up of a sample, 227Ac concentration was found to be smaller than 10-9. This allows for direct waste disposal and no additional radiation protection restrictions than those required for 223Ra. The presence of contamination by other radioisotopes was also ruled out by this experiment. Specifically 226Ra, involved in 223Ra production as the original parent and with a very long-lived (T1/2=1577years) alpha emitter, was also below the experimental detection limit.

Efficiency measurement and Monte Carlo simulations of a CeBr3 scintillator.

CeBr3 crystals meet many of the demands of high performance scintillators, due to their excellent timing properties, good effective Z and high photon yield. It is important to characterize their efficiency and to verify whether modern Monte Carlo codes are reliable enough to reproduced the observed values. We report here on the measurement of both total and photopeak efficiency of a 1" diameter×1" height CeBr3 crystal for gamma-ray energies up to 1.4MeV at several distances, using a variety of low energy gamma rays sources. The measured experimental efficiencies are compared with simulations developed in the framework of PENELOPE and GEANT4.