Studying fast-ion populations using oscillations in solid-state neutral-particle analyzer signal and neutral-beam injection power.

A method for determining the fast-ion population density in magnetically confined plasmas as a function of pitch-radius, (λ, R), using a solid-state neutral-particle analyzer (ssNPA) signal and neutral-beam injection (NBI) power-output data has been developed. Oscillations in the NBI power output are replicated only in the active part of the ssNPA signal, allowing this to be separated from the passive and background signals, which usually complicate data from this diagnostic. Results obtained using this method are compared with those from standard techniques using data from the Mega-Amp Spherical Tokamak Upgrade spherical tokamak.

Analysis of headache management in Andalusia.

INTRODUCTION AND OBJECTIVE: Headache is a frequent reason for consultation between primary care physicians, emergency services physicians, and neurology specialists; however, it is not always well managed. The Andalusian Society of Neurology's Headache Study Group (SANCE) aimed to analyse headache management at different levels of care. MATERIAL AND METHODS: We conducted a descriptive cross-sectional study with data gathered through a retrospective survey in July 2019. Participants completed a series of structured questionnaires on different social and work-related variables from 4 different groups of healthcare professionals (primary care [PC], emergency departments, neurology departments, headache units). RESULTS: A total of 204 healthcare professionals completed the survey: 35 emergency department physicians, 113 PC physicians, 37 general neurologists, and 19 neurologists specialising in headache. Eighty-five percent of PC physicians reported prescribing preventive drugs, which were maintained for at least 6 months (59%), with flunarizine and amitriptyline being the most commonly used. Most patients attended at neurology consultations (65%) are referred by PC physicians, with changes in the headache pattern being the main reason for referral (74%). Healthcare professionals across all levels of care showed great interest in headache and in receiving training in headache management (97% of PC physicians, 100% of emergency services physicians, 100% of general neurologists). CONCLUSIONS: Migraine sparks great interest among healthcare professionals from different levels of care. Our results also reveal a lack of resources for headache management, which is reflected in the long waiting times. Other means of bilateral communication between different levels of care should be explored (eg, e-mail).

The factors associated with the trend in incidence of Bacteraemia and associated mortality over 30 years.

BACKGROUND: Studies have reported increased incidence of BSI over the past decades and indicate that it is necessary to investigate the causes. The aim of this study was to determine the factors affecting trends in the incidence of bacteraemias and associated mortality. METHODS: We conducted a retrospective cohort study assessing prospectively collected data of all clinically significant bacteraemias between 1991 and 2020 in a 450-bed hospital. We determined the evolution of bacteraemia-associated incidence, adjusted 30-day mortality and performed multivariable logistic regression to compare the evolution of variables associated with mortality between 5-year periods. RESULTS: 6777 episodes were included, 59.7% males, age 66.5 ± 18.2, 39.4% ≥ 75 years. The incidence total increased: 43.8/100,000/year in 1991-1995 to 205 in 2016-2020; community-acquired bacteraemia (24.9 to 139) and hospital-acquired (0.36/1000 inpatients-days to 1.09). Bacteraemia with source in vascular catheter, urinary and biliary tract increased. The 30-day mortality rate of patients was 1179/6777 (17.4%) in the whole series and population-adjusted mortality incidence increased from 11.4/100,000 in 1991-1996 to 28.4 in 2016-2020 (RR 2.49, 95% CI 2.01-3.08). Mortality was higher in men (18.2% vs 16.3%) and those over 74 years (22.2% vs 14.3%). Appropriate empirical antimicrobial treatment improved (66.5% to 73.1%), 30-day mortality of patients decreased from 26.1 to 13.9%. When comparing the evolution of the factors associated with mortality between 1991 and 1996 vs 2016-2020, the frequency of some variables associated with higher mortality increased: male sex (OR 1.38, 95% CI 1.10-1,74), age (OR 1.02, 1.01-10.3), immunosuppressive treatment (OR 3.1, 2.09-4.6), polymicrobial bacteraemia (OR 1.76, 1.12-2.79), and others decreased: severe sepsis/septic shock (OR 0.70, 0.52-0.93), spontaneous bacterial peritonitis in cirrhosis (OR 0.06, 0.02-0.23), endocarditis (OR 0.54, 0.35-0.83); on the other hand, the frequency of factors associated with lower mortality increased: urinary (OR 1.67, 95% CI 1.23-2.27) and bile tract source (OR 1.59, 1.04-2.43), and adequate empirical treatment (OR 1.42, 95% CI 1.10-1.83). CONCLUSIONS: The incidence of bacteraemia increased due to more elderly, co-morbid patients undergoing procedures and more device related bacteraemia. The percentage of mortality decreased because adequate empirical treatment improved, decreased spontaneous bacterial peritonitis in cirrhosis and endocarditis, and increased bacteraemia of urinary and biliary tract source.

The Adolescent Problem Gambling Prevalence Associated with Leisure-Time Activities and Risky Behaviors in Southern Spain.

Gambling addiction is increasing and is becoming a public health concern due to the rise of gambling-related harms affecting the youth. Previous studies suggest a strong link between problem gambling (PG) and substance use and psychosocial and familial factors. Our main objective was to analyze the association between PG and factors like sport, leisure-time activities, and risk-taking behaviors in adolescents. A survey on substance use and addictive behaviors was performed in 2019 on a representative sample of 2240 subjects (14-18 years) from the Southern Spain Region. Data variables like socio-demographic characteristics, sport, leisure and free time activities, family environment, PG (Lie-Bet Scale), compulsive internet use (CIUS Scale), and consumption of alcohol and cannabis were collected using a standardized questionnaire. Weighted PG prevalence was estimated in either sex, as well as the differences between various levels of PG using chi-square tests. Crude and adjusted weighted logistic regression models were used to identify predictors associated with PG. The prevalence of PG was associated with shopping frequency, compulsive internet use, cannabis use in the previous month, higher family economic status, and having a homemaker father which increased the likelihood of PG. On the contrary, cultural hobbies such as playing an instrument, painting, singing, and writing, and having a working mother were inversely associated with PG. Our results suggest that encouraging participation in creative activities along with supervised shopping and monitoring compulsive internet use and cannabis consumption may contribute some protection against adolescent PG. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-022-00950-7.

The role of soils in the regulation of hazards and extreme events.

The frequency and intensity of natural hazards and extreme events has increased throughout the last century, resulting in adverse socioeconomic and ecological impacts worldwide. Key factors driving this increase include climate change, the growing world population, anthropogenic activities and ecosystem degradation. One ecologically focused approach that has shown potential towards the mitigation of these hazard events is the concept of nature's contributions to people (or NCP), which focuses on enhancing the material and non-material benefits of an ecosystem to reduce hazard vulnerability and enhance overall human well-being. Soils, in particular, have been identified as a key ecosystem component that may offer critical hazard regulating functionality. Thus, this review investigates the modulating role of soils in the regulation of natural hazards and extreme events, with a focus on floods, droughts, landslides and sand/dust storms, within the context of NCP. This article is part of the theme issue 'The role of soils in delivering Nature's Contributions to People'.

Self-adaptive diagnostic of radial fast-ion loss measurements on the ASDEX Upgrade tokamak (invited).

A poloidal array of scintillator-based Fast-Ion Loss Detectors (FILDs) has been installed in the ASDEX Upgrade (AUG) tokamak. While all AUG FILD systems are mounted on reciprocating arms driven externally by servomotors, the reciprocating system of the FILD probe located just below the midplane is based on a magnetic coil that is energized in real-time by the AUG discharge control system. This novel reciprocating system allows, for the first time, real-time control of the FILD position including infrared measurements of its probe head temperature to avoid overheating. This considerably expands the diagnostic operational window, enabling unprecedented radial measurements of fast-ion losses. Fast collimator-slit sweeping (up to 0.2 mm/ms) is used to obtain radially resolved velocity-space measurements along 8 cm within the scrape-off layer. This provides a direct evaluation of the neutral beam deposition profiles via first-orbit losses. Moreover, the light-ion beam probe (LIBP) technique is used to infer radial profiles of fast-ion orbit deflection. This radial-LIBP technique is applied to trapped orbits (exploring both the plasma core and the FILD stroke near the wall), enabling radial localization of internal plasma fluctuations (neoclassical tearing modes). This is quantitatively compared against electron cyclotron emission measurements, showing excellent agreement. For the first time, radial profiles of fast-ion losses in MHD quiescent plasmas as well as in the presence of magnetic islands and edge localized modes are presented.

Implementation of synthetic fast-ion loss detector and imaging heavy ion beam probe diagnostics in the 3D hybrid kinetic-MHD code MEGA.

A synthetic fast-ion loss (FIL) detector and an imaging Heavy Ion Beam Probe (i-HIBP) have been implemented in the 3D hybrid kinetic-magnetohydrodynamic code MEGA. First synthetic measurements from these two diagnostics have been obtained for neutral beam injection-driven Alfvén Eigenmode (AE) simulated with MEGA. The synthetic FILs show a strong correlation with the AE amplitude. This correlation is observed in the phase-space, represented in coordinates (Pϕ, E), being toroidal canonical momentum and energy, respectively. FILs and the energy exchange diagrams of the confined population are connected with lines of constant E', a linear combination of E and Pϕ. First i-HIBP synthetic signals also have been computed for the simulated AE, showing displacements in the strike line of the order of ∼1 mm, above the expected resolution in the i-HIBP scintillator of ∼100 µm.

Upgrade and absolute calibration of the JET scintillator-based fast-ion loss detector.

The JET FILD is a scintillator-based Fast-ion Loss Detector optimized to measure fusion-born alpha-particle losses. This work covers its upgrade and absolute calibration in preparation for the following JET DT experiments. A fast scintillator material (TG-Green) has been installed in the JET FILD. A heater jacket is installed around the fiber bundle, responsible for transmitting the light from the scintillator plate, to anneal the fiber obscuring due to neutron damage. The JET FILD has been upgraded with a 1 Mpx camera and 2 MHz photomultiplier data acquisition hardware. Full-orbit simulations give an estimate of the shading effects on the scintillator plate of the first wall structures and provide a synthetic signal of the JET FILD. A detector instrument function enables absolute values of fast-ion losses using calibration factors. The calibration factors are made available in a shot-to-shot basis for the characterized species and energies and with corrections for the diagnostic conditions. The fast acquisition system sets the Nyquist frequency (1 MHz) above the typical mode frequencies (≈102 kHz), thus making it possible to identify MHD-induced fast-ion losses.

Impact of the COVID-19 pandemic on tuberculosis management in Spain.

BACKGROUND: The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. METHODS: Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. RESULTS: A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 (P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 (P = 0.001). CONCLUSIONS: The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.

Dataset of working mPEG-alkyne with scCO2.

This article contains data related to the research article entitled "Carbon dioxide sorption and melting behavior of mPEG-alkyne". The presented data gives information on the thermodynamics properties of the solvent and the polymer. The time saturation of mPEG-alkyne in supercritical carbon dioxide (scCO2) was evaluated in a high-pressure variable volume cell in different period of time at different pressure at the same temperature. The effects of pressure and temperature on the density of CO2 when it is above supercritical conditions are determined with Sanchez Lacombe and Bender Equation and compared with the NIST database and values of equation of Bender. The characteristic parameters of CO2 were determined with the equations proposed by Chengyong Wang et al. [1] and the sum of squared error was calculated for each parameter. Furthermore in this work the solubility data of scCO2/polymer mixture were correlated with Sanchez Lacombe Equation of State (SL EOS) and Heuristic model proposed by Irene Pasquali et al. [2]. This work describes the methodology for solving the SL EOS between the polymer and scCO2 and the procedure of determining the solubility parameter with the group contribution method necessary to apply the heuristic model is described.

Minimally Invasive Hemodynamic Assessment during Obstetric Hysterectomy for Invasive Placentation with Epidural Anesthesia.

BACKGROUND: The present study aimed to describe the evolution of hemodynamic parameters over time of patients with invasive placentation during their third trimester who were delivered via cesarean section and subsequently underwent obstetric hysterectomy under epidural anesthesia. METHODS: A prospective, descriptive, longitudinal, 11-month cohort study of 43 patients aged between 18 and 37 years who presented with invasive placentation. Minimal invasive monitoring was placed before the administration of epidural anesthesia for hemodynamic parameter tracking during the cesarean section. After delivery, the patients underwent an obstetric hysterectomy. Blood loss, hemodynamic parameters, and coagulation were managed via goal-directed therapy. Parameters were compared via repeated measures ANOVA and effect size estimation (Cohen's d). RESULTS: The mean age of the patients was 29.2 ± 3.4 years and was moderately overweight. They had minor cardiac index variance (P=NS, no significance), vascular systemic resistance index (NS), heart rate (P=NS), and median arterial pressure (P=NS). Differences were observed in the stroke volume index (P=0.015) due to moderately higher values (d = 0.3, P=0.016) in the middle of the surgery. Patients had lower cardiac index (d = -0.36, NS) and cardiac workload requirements (d = -0.29, P=0.034) toward the completion of surgery. CONCLUSION: Patients who are in their third trimester and who subsequently underwent obstetric hysterectomy under epidural anesthesia had modest surgical hemodynamic variance and reduced cardiac workload requirements toward the end of the surgery.

Neutrophil/lymphocyte ratio: Can a non-specific marker of inflammation helps to confirm the inflammatory hypothesis of the serious mental diseases? A case-control study.

BACKGROUND: The hypotheses of autoimmune, allergic or infectious etiology of severe mental illness have been reported in the scientific literature repeatedly. The main objective of this work is to study the relationship of inflammatory, autoimmunity or recent infection markers with the fact of suffering Severe Mental Disorders (SMD). METHODS: In the present case-control study, adult patients with a diagnosis of SMD were compared with controls who underwent routine health checks that included analytical control. Cases with psychosis substance-induced and controls with diagnosis of any psychiatric illness were excluded. In both groups, patients with chronic inflammatory diseases or intercurrent infectious disease were also excluded. A set of common analytical parameters, markers of infectious diseases and inflammatory markers were retrieved for both groups, as well as demographic and clinical data. RESULTS: A total of 212 subjects (81 cases and 131 controls) were recruited. From cases, 70 (86.4%) have a diagnosis of Schizophrenia Disease (SD) and 11 (13.6%) of Schizoaffective Disorder (SAD). In the multivariate model the female sex (OR 0.24, 95% CI 0.12-0.46) and the neutrophil-lymphocyte ratio (OR 3.00, 95% CI 1.91-4.70) were associated with the fact of being case. CONCLUSIONS: Patients with SMD seem to have higher inflammatory markers compared to the general population, being the neutrophil-lymphocyte ratio, the marker associated with more strength. The role of inflammatory processes in the etiology of this type of disorders, if confirmed, opens interesting and innovative therapeutic possibilities.

Biological role of excretory-secretory proteins in endemic parasites of Latin America and the Caribbean.

Neglected tropical diseases (NTDs) share certain traits: they are parasitic infections, prevailing in tropical environments and affecting marginalized sectors of the population. Six NTDs - ascariasis, cysticercosis, echinococcosis, hookworm infection, onchocerciasis and trichuriasis - all of them endemic in Latin America and the Caribbean (LAC), are analysed in this work. This review aims to discuss key information on the function of excretory/secretory (E/S) proteins from these parasites in their infectivity, pathogeny and diagnosis. The modulation of the host immune system to favour the permanence and survival of the parasite is also discussed. An updated knowledge on the function of E/S molecules in endemic parasitoses in LAC may lead to new approaches for the clinical management and diagnosis of these diseases. In turn, this could allow us to optimize their treatment and make it more affordable - a relevant goal given the economic constraints that the region is facing.

Meropenem antimicrobial stewardship program: clinical, economic, and antibiotic resistance impact.

There are few prospective studies with sufficient duration in time to evaluate clinical and antibiotic resistance impact of antibiotic stewardship programs (ASP). This is a descriptive study between January 2012 and December 2017, pre-post intervention. A meropenem ASP was initiated in January 2015; in patients who started treatment with meropenem, an infectious disease physician performed treatment recommendations to prescribers. Prospective information was collected to evaluate adequacy of meropenem prescription to local guidelines and to compare results between cases with accepted or rejected intervention. Analysis was performed to verify variables associated with intervention acceptance and with any significant change in meropenem consumption, hospital-acquired multidrug-resistant (MDR) bloodstream infections (BSIs), and 30-day all-cause crude death in MDR BSIs. Adequacy of meropenem prescription and de-escalation from meropenem treatment to narrower-spectrum antibiotic improved progressively over time, after ASP implementation (p < 0.001). Interventions on prescription were performed in 330 (38.7%) patients without meropenem justified treatment; in 269, intervention was accepted and in 61 not. Intervention acceptance was associated with shorter duration of treatment, cost, and inpatient days (p < 0.05); intervention rejection was not associated with severity of patient. During the period 2015-2017, meropenem consumption decreased compared with 2012-2014 (rate ratio [RR] 0.67; 95% CI 0.58-0.77, p < 0.001). Also decreased were hospital-acquired MDR BSI rate (RR 0.63; 95% CI 0.38-1.02, p = 0,048) and 30-day all-cause crude death in MDR BSIs (RR 0.45; 95% CI 0.14-1.24, p = 0.096), coinciding in time with ASP start-up. The decrease and better use of meropenem achieved had a sustained clinical, economic, and ecological impact, reducing costs and mortality of hospital-acquired MDR BSIs.

Correlation between Streptococcus bovis bacteremia and density of cows in Galicia, northwest of Spain.

BACKGROUND: There are few data on the epidemiology of infections caused by Streptococcus bovis (Sb). Some studies suggest that both residence in rural areas and contact with livestock could be potential risk factors. METHODS: We performed a retrospective study for the period 2005-2016 of all cases of bacteremia caused by Sb in Galicia (a region in the northwest of Spain). The association between the incidence rate of Sb bacteremia and the number of cattle by province and district was analyzed. RESULTS: 677 cases were included with a median age of 76 years, 69.3% males. The most frequent infections were endocarditis (234 cases, 34.5%), primary bacteremia (213 cases, 31.5%) and biliary infection (119 cases, 17.5%). In 252 patients, colon neoplasms were detected (37.2%). S. gallolyticus subsp. gallolyticus was the predominant species (52.3%). Mortality was 15.5% (105 cases). The annual incidence rate was 20.2 cases/106 inhabitants and was correlated with the density of cattle (p < 0.001), but not with rurality. When comparing the two provinces with a strong predominance of rural population, but with important differences in the number of cattle, such as Orense and Lugo, with 6% and 47.7% of Galician cattle, respectively, the rates were very different: 15.8 and 43.6 cases/106, respectively, with an RR of 2.7 (95% CI, 2.08-3.71). Some districts of the province of Lugo had rates higher than 100 cases/106 inhabitants. CONCLUSIONS: Our study shows a significant correlation between the rates of Sb bacteremia and cattle density, suggesting a possible transmission of Sb from cows to people.

A rotary and reciprocating scintillator based fast-ion loss detector for the MAST-U tokamak.

The design and unique feature of the first fast-ion loss detector (FILD) for the Mega Amp Spherical Tokamak - Upgrade (MAST-U) is presented here. The MAST-U FILD head is mounted on an axially and angularly actuated mechanism that makes it possible to independently adapt the orientation [0°, 90°] and radial position [1.40 m, 1.60 m] of the FILD head, i.e., its collimator, thus maximizing the detector velocity-space coverage in a broad range of plasma scenarios with different q95. The 3D geometry of the detector has been optimized to detect fast-ion losses from the neutral beam injectors. Orbit simulations are used to calculate the strike map and predict the expected signals. The results show a velocity-space range of [4 cm, 13 cm] in gyroradius and [30°, 85°] in pitch angle, covering the entire neutral beam ion energy range. The optical system will provide direct sight of the scintillator and simultaneous detection with two cameras, giving high spatial and temporal resolution. The MAST-U FILD will shed light on the dominant fast-ion transport mechanisms in one of the world's two largest spherical tokamaks through absolute measurements of fast-ion losses.

Beam-Ion Acceleration during Edge Localized Modes in the ASDEX Upgrade Tokamak.

The acceleration of beam ions during edge localized modes (ELMs) in a tokamak is observed for the first time through direct measurements of fast-ion losses in low collisionality plasmas. The accelerated beam-ion population exhibits well-localized velocity-space structures which are revealed by means of tomographic inversion of the measurement, showing energy gains of the order of tens of keV. This suggests that the ion acceleration results from a resonant interaction between the beam ions and parallel electric fields arising during the ELM. Orbit simulations are carried out to identify the mode-particle resonances responsible for the energy gain in the particle phase space. The observation motivates the incorporation of a kinetic description of fast particles in ELM models and may contribute to a better understanding of the mechanisms responsible for particle acceleration, ubiquitous in astrophysical and space plasmas.

Recycling of polyurethanes from laboratory to industry, a journey towards the sustainability.

The recycling of any kind of plastic to convert it in valuable products is one of the main challenges of today's society. Besides, if the recycling process is itself green, then it would be a great achievement. This paper reviews the way covered from the first attempts of reusing the polyurethane (PU) scraps as a filler for cushions to the last chemical routes employing green recycling agents. Polyurethane is the 6th most used polymer all over the world with a production of 18 millions tons per year, which means a daily production of PU specialties greater than 1 million of cubic meters, equivalent to the volume of the Empire State Building. The thermostable nature of the majority of the polyurethanes specialties has made that the preferred solution for their recycling are the chemical recycling processes. Among them, glycolysis is the one that receives a greater attention from an industrial point of view, so this review puts the spotlight on it. However, the existing reviews in literature do not paid a special attention on glycolysis and only give a superficial description of the process. Nevertheless, in the present review, the scientific literature relative to glycolysis is completely reviewed, updated and ordered according the type of PU specialty recycled. Additionally, the other main chemical recycling processes are also revisited in a more extended and deeper way than in the previous approaches to this topic. Moreover, it is crucial to take into account that some of these technologies, which were described in the literature as promising technologies at laboratory scale are now commercial processes running at industrial scale. For that reason, it is essential to remark that the present review comprises not only a detailed state of art of the scientific literature on the subject, also includes a detailed revision of the past and running on pilot plants and industrial facilities, including several patents, which has never been covered in the current literature. Moreover, this review also describes the most recent studies employing crude glycerol (biodiesel subproduct) as an economic, sustainable and environmental friendly cleavage agent, which should lead the way to the industrial implantation of split-phase glycolysis in a near future, providing high quality recovered products, susceptible of replacing raw ones in the synthesis of new PU specialties. What is more, this review intends that any reader could know and understand the reactions involved in the polyurethane chemistry and recycling, the main polyurethanes types and the fundamentals of the recycling strategies in order to comprehend what are the advantages and drawbacks of each recycling process as starting point for looking for new advantageous alternatives from an environmental, technical and economic point of view. Broader context. This paper reviews the main advances in the polyurethane (PU) recycling field, from laboratory and academia processes to pilot plant and industrial scale ones, including the most relevant patents in the subject. Opposite to other common used plastics, PUs are not polymerization but condensation polymers, synthesized from polyols and isocyanates. The wide diversity of polyols and isocyanates allows the synthesis of numerous different compounds covering a huge range of applications. As a direct consequence of their commercial success, an increasing quantity of PU waste is being disposed by landfilling in the last decades. Such waste comprises not only post-consumer products but also scrap from slabstock manufacturing, which can reach the 10% of the total foam production. However, the massive enforcement of the environmental laws is pointing out a new route in the polymer waste removal sector based in the polymer recycling, and this fact has placed the research in waste treatment as one of the most prolific topics nowadays. In fact, polymer recycling processes have experienced a growing attention from the research and industrial worlds as a direct result of the enforcement of the environmental legislations. Hence, it is essential to develop new environmental sustainable recycling processes with the aim of conserving the natural resources, reducing the amount of waste disposed in landfills and enhancing the sustainability for forthcoming generation.

Pembrolizumab for advanced melanoma: experience from the Spanish Expanded Access Program.

BACKGROUND: The programmed death (PD-1) inhibitor pembrolizumab has been recently approved for the treatment of advanced melanoma. We evaluated the clinical activity of pembrolizumab in melanoma patients treated under the Spanish Expanded Access Program. METHODS: Advanced melanoma patients who failed to previous treatment lines were treated with pembrolizumab 2 mg/kg every three weeks. Patients with brain metastases were not excluded if they were asymptomatic. Data were retrospectively collected from 21 centers in the Spanish Melanoma Group. RESULTS: Sixty-seven advanced melanoma patients were analyzed. Most patients were stage M1c (73.1%), had high LDH levels (55.2%) and had ECOG PS 1 or higher (59.7%). For cutaneous melanoma patients, median overall survival was 14.0 months; the 18-month overall survival rate was 47.1%. Overall response rate was 27%, including three patients with complete responses (6.5%). Median response duration was not reached, with 83.3% of responses ongoing (3.5 m+ to 20.4 m+). From ten patients included with brain metastases, four (40%) had an objective response, two (20%) of them achieved a complete response. Significant prognostic factors for overall survival were LDH level, ECOG PS and objective response. There were no serious adverse events. CONCLUSION: Although this was a heavily pretreated cohort, pembrolizumab activity at the approved dose and schedule was confirmed in the clinical setting with long-term responders, also including patients with brain metastases.

Conceptual design of the ITER fast-ion loss detector.

A conceptual design of a reciprocating fast-ion loss detector for ITER has been developed and is presented here. Fast-ion orbit simulations in a 3D magnetic equilibrium and up-to-date first wall have been carried out to revise the measurement requirements for the lost alpha monitor in ITER. In agreement with recent observations, the simulations presented here suggest that a pitch-angle resolution of ∼5° might be necessary to identify the loss mechanisms. Synthetic measurements including realistic lost alpha-particle as well as neutron and gamma fluxes predict scintillator signal-to-noise levels measurable with standard light acquisition systems with the detector aperture at ∼11 cm outside of the diagnostic first wall. At measurement position, heat load on detector head is comparable to that in present devices.