Clinical-haematological changes and predictors of severity in acute food protein-induced enterocolitis syndrome reactions at oral food challenge: a multicentre observational study.

BACKGROUND: Oral food challenge (OFC) is the gold standard for diagnosis of acute Food Protein-Induced Enterocolitis Syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated. OBJECTIVE: To assess clinical-haematological changes and predictors of severity of FPIES reactions at OFC. METHODS: Observational multicentre prospective study. Children aged 0-18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centres in Spain and Italy. OFC Outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed based on published '2017 FPIES Consensus' criteria. Clinical characteristics were recorded, and full blood count was done at baseline, reaction onset and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC. RESULTS: 81 children had positive OFC (mild in 11% (9/81), moderate in 61% (49/81), severe in 28% (23/81)). Increase in neutrophils and reduction in eosinophils, basophils and lymphocytes was observed (P-value<0.05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not gender, age, culprit food, cumulative dose and previous reaction severity) was associated with reduced odds of severe reaction compared to giving multiple doses in a single day. CONCLUSION: Distinct haematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may associate a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.

Local allergic rhinitis in children: Clinical characteristics and role of basophil activation test as a diagnostic tool.

BACKGROUND: Local allergic rhinitis (LAR) is a condition involving a localized nasal allergic response in absence of systemic atopy. Most studies on LAR have been performed in adults. We aimed to describe clinical characteristics of LAR pediatric patients, its clinical evolution over a 7-year follow-up period and to study the role of basophil activation test (BAT), for its diagnosis. METHODS: Forty-four children with non-allergic rhinitis (NAR) were included (24 males, 20 females, aged under 15 years). Nasal allergen provocation test (NAPT) and BAT were performed with Dermatophagoides pteronyssinus and Phleum pratense. RESULTS: Seven patients (16%) were diagnosed of LAR. Six reacted to D pteronyssinus and one to P pratense. All LAR and 86% of NAR patients presented perennial symptoms. Fifty-seven percent of NAR and LAR patients referred persistent symptoms. Around half of NAR and LAR patients reported mild-moderate clinical manifestations. Three LAR patients associated conjunctival symptoms, proportionally more than NAR patients (19%, 7 out of 37). NAR patients presented bronchial asthma (n = 10) more frequently than LAR children (n = 1). More than half of LAR and NAR patients presented family history of atopy. BAT was negative in all LAR patients. On follow-up, 3 LAR patients and 10 of the 25 NAR patients who agreed to be retested, presented systemic sensitization. Dust mites were the most frequent allergen involved. CONCLUSIONS: LAR should be ruled out in children with NAR. Almost half of children with LAR develop systemic sensitization over time. BAT shows low sensitivity for the diagnosis of LAR in children.

SEA 2022 Standards for Global Control of Cardiovascular Risk. / Estándares SEA 2022 para el control global del riesgo cardiovascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to better knowledge of vascular disease, its prevention and treatment. It is well known that cardiovascular diseases are the leading cause of death in our country and entail a high degree of disability and health care costs. Arteriosclerosis is a multifactorial disease and therefore its prevention requires a global approach that takes into account the different risk factors with which it is associated. Therefore, this document summarizes the current level of knowledge and includes recommendations and procedures to be followed in patients with established cardiovascular disease or at high vascular risk. Specifically, this document reviews the main symptoms and signs to be evaluated during the clinical visit, the laboratory and imaging procedures to be routinely requested or requested for those in special situations. It also includes vascular risk estimation, the diagnostic criteria of the different entities that are cardiovascular risk factors, and makes general and specific recommendations for the treatment of the different cardiovascular risk factors and their final objectives. Finally, the document includes aspects that are not usually referenced in the literature, such as the organization of a vascular risk consultation.

Onset of Nut Allergy in a Pediatric Cohort: Clinical and Molecular Patterns in the AFRUSEN Study.

BACKGROUND AND OBJECTIVE: Nut allergy is a growing problem, yet little is known about its onset in children. Objective: To characterize the onset of nut allergy in children in southern Europe. METHODS: The study population comprised consecutive patients up to 14 years of age who visited allergy departments with an initial allergic reaction to peanut, tree nut, or seed. The allergy work-up included a clinical history, food challenge, skin prick testing, determination of whole-extract sIgE, and ImmunoCAP ISAC-112 assay. RESULTS: Of the 271 children included, 260 were first diagnosed with nut allergy at a mean age of 6.5 years and at a mean (SD) of 11.8 (21.2) months after the index reaction. The most common culprit nuts at onset were walnut (36.5%), peanut (28.5%), cashew (10.4%), hazelnut (8.5%), pistachio (5.4%), and almond (5%). Onset of peanut allergy was more frequent in children ≤6 years and walnut in those aged >6 years (P=.032). In 65% of cases, the allergic reaction occurred the first time the patient consumed the nut, and 35% of reactions were anaphylactic. Overall, polysensitization to nuts was detected by skin prick testing in 64.9% of patients, although this rate was lower among walnut-allergic children (54.7%) and peanut-allergic children (54.1%) (P<.0001). Sensitization to 2S albumins was predominant (75%), especially Jug r 1 (52.8%), whereas sensitization to lipid transfer proteins was less relevant (37%). CONCLUSION: In the population we assessed, the onset of nut allergy occurred around 6 years of age, slightly later than that reported in English-speaking countries. Walnut was the main trigger, followed by peanut. 2S albumin storage proteins, especially Jug r 1, were the most relevant allergens. This study will help guide management and may contribute to preventive strategies in pediatric nut allergy.

Spintronic memristors for neuromorphic circuits based on the angular variation of tunnel magnetoresistance.

In this study, a new type of compact magnetic memristor is demonstrated. It is based on the variation of the conductivity of a nano-sized magnetic tunnel junction as a function of the angle between the in-plane reference layer magnetization and a free layer exhibiting an isotropic in-plane coercivity. The free layer magnetization is rotated by two spin transfer torque contributions: one originating from the in-plane magnetized reference layer and the other one from an additional perpendicular polarizer integrated in the stack. Thanks to a proper tuning of the relative influence of these two torques, the magnetization of the free layer can be rotated step by step clockwise or anticlockwise in a range of angle between 0° (parallel configuration) and 180° (anti-parallel configuration) by sending pulses of current through the stack, of one or opposite polarity. The amplitude of the rotation steps and therefore of the conductance variations depends on the pulse amplitude and duration. In this way, we achieve monotonous variations of the resistance with the voltage polarity through the application of pulses in the ns range. We also retrieve the analytical expression of critical current density which is found to be in good agreement with the experimental results. The thermal stability of the intermediate resistance levels and the role of Joule heating are also discussed.

Measurement of the Spin Absorption Anisotropy in Lateral Spin Valves.

The spin absorption process in a ferromagnetic material depends on the spin orientation relative to the magnetization. Using a ferromagnet to absorb the pure spin current created within a lateral spin valve, we evidence and quantify a sizable orientation dependence of the spin absorption in Co, CoFe, and NiFe. These experiments allow us to determine the spin-mixing conductance, an elusive but fundamental parameter of the spin-dependent transport. We show that the obtained values cannot be understood within a model considering only the Larmor, transverse decoherence, and spin diffusion lengths, and rather suggest that the spin-mixing conductance is actually limited by the Sharvin conductance.

An electron holography study of perpendicular magnetic tunnel junctions nanostructured by deposition on pre-patterned conducting pillars.

The fabrication of multi-gigabit magnetic random access memory (MRAM) chips requires the patterning of magnetic tunnel junctions at very small dimensions (sub-30 nm) and a very dense pitch. This remains a challenge due to the difficulty in etching magnetic tunnel junction stacks. We previously proposed a strategy to circumvent this problem by depositing the magnetic tunnel junction material on prepatterned metallic pillars, resulting in the junction being naturally shaped during deposition. Upon electrical contact, the deposit on top of the pillars constitutes the magnetic storage element of the memory cell. However, in this process, the magnetic material is also deposited in the trenches between the pillars that might affect the memory cell behaviour. Here we study the magnetic interactions between the deposit on top of the pillars and in the trenches by electron holography, at room temperature and up to 325 °C. Supported by models, we show that the additional material in the trenches is not perturbing the working principle of the memory chip and can even play the role of a flux absorber which reduces the crosstalk between neighboring dots. Besides, in the studied sample, the magnetization of the 1.4 nm thick storage layer of the dots is found to switch from out-of-plane to an in-plane configuration above 125 °C, but gradually decreases with temperature. Electron holography is shown to constitute a very efficient tool for characterizing the micromagnetic configuration of the storage layer in MRAM cells.

Indium Tin Oxide optical access for magnetic tunnel junctions in hybrid spintronic-photonic circuits.

The all-optical magnetization reversal of magnetic layers, by picosecond optical pulses, is of particular interest as it shows the potential for energy-efficient and fast magnetic tunnel junction (MTJ) elements. This approach requires memory elements that are optically and electronically accessible, for optical writing and electronic read-out. In this paper, we propose the integration of indium tin oxide (ITO) as a transparent conducting electrode for magnetic tunnel junctions in integrated spintronic-photonic circuits. To provide light with sufficient energy to the MTJ free layer and allow electrical read-out of the MTJ state, we successfully integrated indium tin oxide as a top transparent electrode. The study shows that ITO film deposition by physical vapor deposition with conditions such as high source power and low O2 flow achieves smooth and conductive thin films. Increase in grain size was associated with low resistivity. Deposition of 150 nm ITO at 300 W, O2 flow of 1 sccm and 8.10-3 mbar vacuum pressure results in 4.8 × 10-4 Ω.cm resistivity and up to 80% transmittance at 800 nm wavelength. The patterning of ITO using CH4/H2 chemistry in a reactive ion etch process was investigated showing almost vertical sidewalls for diameters down to 50 nm. The ITO based process flow was compared to a standard magnetic tunnel junctions fabrication process flow based on Ta hard mask. Electrical measurements validate that the proposed process based on ITO results in properties equivalent to the standard process. We also show electrical results of magnetic tunnel junctions having all-optical switching top electrode fabricated with ITO for optical access. The developed ITO process flow shows very promising initial results and provides a way to fabricate these new devices to integrate all-optical switching magnetic tunnel junctions with electronic and photonic elements.

Thermal robustness of magnetic tunnel junctions with perpendicular shape anisotropy.

The concept of Perpendicular Shape Anisotropy STT-MRAM (PSA-STT-MRAM) has been recently proposed as a solution to enable the downsize scalability of STT-MRAM devices beyond the sub-20 nm technology node. For conventional p-STT-MRAM devices with sub-20 nm diameters, the perpendicular anisotropy arising from the MgO/CoFeB interface becomes too weak to ensure thermal stability of the storage layer. In addition, this interfacial anisotropy rapidly decreases with increasing temperature which constitutes a drawback in applications with a large range of operating temperatures. Here, we show that by using a PSA based storage layer, the source of anisotropy is much more robust against thermal fluctuations than the interfacial anisotropy, which allows considerable reduction of the temperature dependence of the coercivity. From a practical point of view, this is very interesting for applications having to operate on a wide range of temperatures (e.g. automotive -40 °C/+150 °C).

A systematic review of pharmacological therapies and their effectiveness on health-related quality of life outcomes in patients with juvenile-onset systemic lupus erythematosus.

Juvenile-onset systemic lupus erythematosus (JSLE) presents with an aggressive course and high morbidity associated with disease and treatment. JSLE patients have a poorer health-related quality of life (HRQoL) when compared with age-matched patients with other rheumatologic disorders. We aim to summarize the impact of current pharmacological therapies on the HRQoL of JSLE patients. Search strategies were developed across seven databases. Randomized clinical trials (RCTs) and cohort studies comparing interventions to standard therapy, placebo or pre-post cohort comparisons for more than 4 weeks were included. The outcome included self-reported scales compared at baseline and a therapeutic time point. Risk of bias was evaluated by using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment scale. A total of 2812 articles were narrowed down to 309 for full-text screening. Four RCTs and one prospective cohort study, with a total of 634 JSLE patients, met the inclusion criteria. Four of the studies had a controlled intervention plus standard therapy compared with standard therapy alone or placebo. Multiple indices were used to evaluate HRQoL. These included the Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters tool, Kids Fatigue Severity Scale and Child Depression Inventory. A single study reported a significant improvement while remaining studies reported no difference or failed to report the statistical analysis. Although HRQoL is significantly impaired in JSLE, evidence regarding its improvement is limited due to the small number of eligible studies, heterogeneity in scales, and HRQoL domains. A universal HRQoL questionnaire for JSLE needs to be established and used in both the research and clinical setting. All studies should adhere to reporting guidelines.

[Acceptance Of Death And Its Dehospitalisation]. / Aceptación de la muerte y su deshospitalización.

INTRODUCTION: Death is part of life. The awareness that death is inevitable could be the cause of mental disorders. OBJECTIVE: To determine the level of death anxiety in old people as regards age, gender, social aspects, physical and leisure activities, self-esteem, religion or advanced disease, as well as their preferences on the place where they want to die. MATERIAL AND METHOD: Cross-sectional observational study. Face-to-face interviews and Death Anxiety Scale (DAS) of Templer on 300 patients over 75years-old without a diagnosis of dementia, selected randomly in four health centres. RESULTS: A total of 288 surveys were completed. The mean age was 84.8 (15.2) years, and 147 (51.0%) were older than 85years. The score of medium-high anxiety observed in the DAS was higher in women (50%-39.6%; P=.030), in those who did not perform physical activity (68%-26.4%; P<.001), in those who did not take part in leisure activities (63.5%-41.7%; P=.007), in patients with depressed mood (60.4%-41.6%; P<.008), and in patients without advanced disease (48.3%-3 5.8%; P=.036). The fear of having a painful death was present in 255 (88.5%). Physical activity reduced the risk of medium-high anxiety by 5.3 times (OR=.188, P<.001), and screening positive for depression increased it by 2.9 times (OR=2.943, P=.014). As regards the place where they would prefer to die, 177 (61.5%) answered «at home¼, and 28 (9.7%) «in the hospital.¼ CONCLUSIONS: Older people do fear a painful death, but they are not really afraid of dying. Male gender and performing physical or leisure activities is related to low levels of death anxiety. Advanced disease leads to greater acceptance of the end of life. The desire to die at home, and to «dehospitalise¼ the death prevails.

Remission and low disease activity state (LDAS) are protective of intermediate and long-term outcomes in SLE patients. Results from LUMINA (LXXVIII), a multiethnic, multicenter US cohort.

OBJECTIVE: The objective of this report is to determine the impact of remission and low disease activity state (LDAS) on damage accrual and mortality in systemic lupus erythematosus (SLE) patients. PATIENTS AND METHODS: Visits from the Lupus in Minority populations: Nature vs. Nurture (LUMINA) cohort were categorized into remission (Systemic Lupus Activity Measure (SLAM) score = 0 and prednisone ≤ 5 mg/day and no immunosuppressants), LDAS ((not on remission), SLAM score ≤ 3, prednisone ≤ 7.5 mg/day, no immunosuppressants), or neither: active. Remission and LDAS visits were combined because of the relatively small number of remission visits. Their impact on damage accrual and mortality were examined by Poisson and logistic multivariable regressions adjusting for variables known to affect these outcomes. RESULTS: A total of 3879 visits for 558 patients (28% Caucasian, 37% African descent, 35% Hispanic) were studied. These visits corresponded to 71 in remission, 585 in LDAS, and 3223 active. The longer the percentage of time the patients were in remission/LDAS, the less damage accrual observed (rate ratio 0.1773 (95% confidence interval (CI) 0.1216 to 0.2584) p < 0.0001). A trend was observed in terms of mortality although statistical significance was not reached (odds ratio 0.303 (95% CI 0.063 to 1.456), p = 0.1360). CONCLUSIONS: The longer the patient's state on Remission/LDAS, the less damage accrual that occurs. The protective effect on mortality was not statistically significant.

DNA barcoding of large oak-living cerambycids: diagnostic tool, phylogenetic insights and natural hybridization between Cerambyx cerdo and Cerambyx welensii (Coleoptera: Cerambycidae).

Three large saproxylic cerambycids with different pest/legal status co-occur in the Iberian oak woodlands, Cerambyx welensii (Cw), Cerambyx cerdo (Cc) and Prinobius myardi (Pm): Cw is an emerging pest, Cc is a protected but sometimes harmful species and Pm is a secondary/minor pest. A precise taxonomic diagnosis is necessary for research, management or protection purposes, but may be problematic mainly because Cw and Cc larvae are morphologically indistinguishable. To resolve this constraint, we genotyped adults, larvae and eggs collected over a wide geographical range using the mitochondrial barcoding of the cytochrome c oxidase subunit I (COI). A Neighbour-Joining tree phylogram revealed three distinct clusters corresponding to Cw, Cc and Pm. We further first sequenced for Cw and Cc two mitochondrial (12S rRNA and 16S rRNA) and one nuclear (28S rRNA) gene fragments. For the first two genes, interspecific divergence was lower than in COI, and for the 28S (lower mutation rate), the two species shared identical haplotypes. Two approaches for species delimitation (General Mixed Yule Coalescent (GMYC), Barcode Index Number (BIN)) confirmed the species distinctiveness of Cc and Cw. The Bayesian COI gene tree showed a remarkable genetic divergence between Cc populations from Iberia and the rest of Europe. Such divergence has relevant taxonomic connotations and stresses the importance of a wide geographical scale sampling for accurate DNA barcoding species identification. Incongruities between morphology/lineage and COI barcodes in some individuals revealed natural hybridization between Cw and Cc. Natural hybridization is important from a phylogenetic/evolutionary perspective in these cerambycids, but the prevalence of (and the behavioural/ecological factors involved in) interspecific cross-breeding remain to be investigated.

A highly thermally stable sub-20 nm magnetic random-access memory based on perpendicular shape anisotropy.

A new approach to increase the downsize scalability of perpendicular STT-MRAM is presented. It consists of significantly increasing the thickness of the storage layer in out-of-plane magnetized tunnel junctions (pMTJ) as compared to conventional pMTJ in order to induce a perpendicular shape anisotropy (PSA) in this layer. This PSA is obtained by depositing a thick ferromagnetic (FM) layer on top of an MgO/FeCoB based magnetic tunnel junction (MTJ) so that the thickness of the storage layer is of the order of or larger than the diameter of the MTJ pillar. In contrast to conventional spin transfer torque magnetic random access memory (STT-MRAM) wherein the demagnetizing energy opposes the interfacial perpendicular magnetic anisotropy (iPMA), in these novel memory cells, both PSA and iPMA contributions favor the out-of-plane orientation of the storage layer magnetization. Using thicker storage layers in these PSA-STT-MRAMs has several advantages. Due to the PSA, very high and easily tunable thermal stability factors can be achieved, even down to sub-10 nm diameters. Moreover, a low damping material can be used for the thick FM material thus leading to a reduction of the write current. The paper describes this new PSA-STT-MRAM concept, practical realization of such memory arrays, magnetic characterization demonstrating thermal stability factor above 200 for MTJs as small as 8 nm in diameter and possibility to maintain the thermal stability factor above 60 down to 4 nm diameter.

Highly Efficient Spin-to-Charge Current Conversion in Strained HgTe Surface States Protected by a HgCdTe Layer.

We report the observation of spin-to-charge current conversion in strained mercury telluride at room temperature, using spin pumping experiments. We show that a HgCdTe barrier can be used to protect the HgTe from direct contact with the ferromagnet, leading to very high conversion rates, with inverse Edelstein lengths up to 2.0±0.5 nm. The influence of the HgTe layer thickness on the conversion efficiency is found to differ strongly from what is expected in spin Hall effect systems. These measurements, associated with the temperature dependence of the resistivity, suggest that these high conversion rates are due to the spin momentum locking property of HgTe surface states.

[Air pollution, cardiovascular risk and hypertension]. / Contaminación atmosférica, riesgo cardiovascular e hipertensión arterial.

Air pollution is a worrying factor and has an impact on public health. Multiple studies relate exposure to air pollutants with an increase in cardiovascular events, cardiovascular mortality and mortality for all causes. A relationship has also been demonstrated between increased pollution and high blood pressure, as well as a higher prevalence of hypertension. Pollutants that play a more relevant role in this association are particulate matters, nitrogen dioxide and sulphur dioxide. The objective of this review is to understand the mechanisms involved in this increase and to find the most recent publications that relate pollution, cardiovascular risk and hypertension.