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Resumen Introduccion El sindrome de piernas inquietas (SPI) es un trastorno caracterizado por la necesidad imperiosa de mover las piernas, estando a menudo acompanado de sensaciones desagradables. Su frecuencia es superior en pacientes con esclerosis multiple (EM) que en la poblacion general. Objetivos Evaluar la prevalencia del SPI, segun el cumplimiento de los 4 requisitos esenciales incluidos en los criterios diagnosticos propuestos por la International Restless leg syndrome study group (IRLSSG, 2003), en una cohorte de pacientes con EM e identificar posibles factores de riesgo y repercusion clinica. Resultados Se incluyeron 120 pacientes con EM, con una edad media de inicio de 40 anos y un tiempo medio de evolucion de 46 meses. La prevalencia de SPI, segun el cumplimiento de criterios diagnosticos de la IRLSSG, fue del 23,3%. El tiempo de evolucion de EM, desde la aparicion de los primeros sintomas, fue significativamente menor en pacientes con SPI (p=0,001). La presencia de un brote reciente, asi como de sintomas de ansiedad, depresion y dolor neuropatico se asociaron de forma significativa con el riesgo de SPI (p=0,001, p Conclusiones El SPI debe ser considerado en la evaluacion neurologica de pacientes con EM, cuyo diagnostico y tratamiento precoz mejoraria la calidad de vida de estos sujetos.

CD19-directed chimeric antigen receptor (CAR) T cells have yielded impressive response rates in refractory/relapse B cell acute lymphoblastic leukemia (B-ALL); however, most patients ultimately relapse due to poor CAR T cell persistence or resistance of either CD19(+) or CD19(-) B-ALL clones. CD22 is a pan-B marker whose expression is maintained in both CD19(+) and CD19(-) relapses. CD22-CAR T cells have been clinically used in B-ALL patients, although relapse also occurs. T cells engineered with a tandem CAR (Tan-CAR) containing in a single construct both CD19 and CD22 scFvs may be advantageous in achieving higher remission rates and/or preventing antigen loss. We have generated and functionally validated using cutting-edge assays a 4-1BB-based CD22/CD19 Tan-CAR using in-house-developed novel CD19 and CD22 scFvs. Tan-CAR-expressing T cells showed similar in vitro expansion to CD19-CAR T cells with no increase in tonic signaling. CRISPR-Cas9-edited B-ALL cells confirmed the bispecificity of the Tan-CAR. Tan-CAR was as efficient as CD19-CAR in vitro and in vivo using B-ALL cell lines, patient samples, and patient-derived xenografts (PDXs). Strikingly, the robust antileukemic activity of the Tan-CAR was slightly more effective in controlling the disease in long-term follow-up PDX models. This Tan-CAR construct warrants a clinical appraisal to test whether simultaneous targeting of CD19 and CD22 enhances leukemia eradication and reduces/delays relapse rates and antigen loss.

Syndrome of the trephined (SoT) is the neurological deterioration that occurs after the performance of decompressive craniectomy in which bone is not replaced. The incidence of SoT varies, but this entity seems to be underdiagnosed. It is characterized by symptom reversal after bone replacement, which is the only definitive treatment. We report the case of a patient assessed by the Rehabilitation Service in the Critical Care Unit after a stroke, who had altered level of consciousness and abrupt motor impairment. The patient was diagnosed with SoT. Rehabilitation, with early postural changes, helped to ameliorate the symptoms until the provision of definitive treatment.

Slender footbridges with long spans and light materials may lead to serviceability problems in lateral vibrations due to walking pedestrians. The phenomenon, known as the “lock-in effect” occurs when the number of pedestrians on the footbridge reaches the “critical number”. Considering the mode of vibration in which the instability is more likely to develop, the footbridge response depends on the structural natural frequency and modal damping ratio. These parameters may not have a fixed value during the footbridge overall life cycle due to environmental and operational changes. Therefore, lateral vibration serviceability procedures should include the uncertainty in the footbridge modal parameters in the most simple and applicable way, as the dynamic response of slender footbridges is very sensitive to these uncertainties. Hence, this paper proposes a simple approach, useful for practical engineering applications, to assess the lateral vibration serviceability of slender footbridges, considering the uncertainties in natural frequency and modal damping ratio. The uncertainty is considered by two approaches: probability theory and possibility theory (fuzzy sets). As a result, the study allows checking the vibration serviceability criteria over a range of levels of uncertainty, suggesting that the external factors that affect the modal parameters are more significant when the crowd density exceeds the critical number. The study also shows the simplicity and effectiveness of the possibility theory to deal with the uncertainty in modal parameters, although for similar level of uncertainty, the dynamic response is slightly higher than using the probability theory. Finally, the proposal is applied in two real footbridges, showing a good agreement with the experimental data.

Background Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) and is associated with changes in calcium and phosphate. These related changes have been associated with increased cardiovascular mortality and CKD progression. It is not clear whether negative outcomes linked to SHPT are confounded by such factors. The present study was designed to assess the possible independent effects of SHPT [defined as patients with excessive parathyroid hormone (PTH) levels or on treatment with PTH-reducing agents] on the risk of CKD progression and cardiovascular event (CVE) incidence in CKD patients, as well as whether hypercalcaemia and/or hyperphosphataemia act as effect modifiers. Methods The study enrolled 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology (NEFRONA) cohort (Stage 3, 950; Stage 4, 612; Stage 5, 195; on dialysis, 688). Multivariate logistic and Fine and Gray regression analysis were used to determine the risk of patients suffering CKD progression or a CVE. Results The prevalence of SHPT in the cohort was 65.6% (CKD Stage 3, 54.7%; CKD Stage 4, 74.7%; CKD Stage 5, 71.4%; on dialysis, 68.6%). After 2 years, 301 patients presented CKD progression. During 4 years of follow-up, 203 CVEs were registered. Patients with SHPT showed a higher adjusted risk for CKD progression and CVE. Furthermore, hyperphosphataemia was shown to be an independent risk factor in both outcomes and did not modify SHPT effect. No significant interactions were detected between the presence of SHPT and hypercalcaemia or hyperphosphataemia. Conclusions We conclude that SHPT and hyperphosphataemia are independently associated with CKD progression and the incidence of CVE in CKD patients.

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

This work studies the influence of a vibration isolator on the response of a flexible base structure. Two strategies are compared: passive and active vibration isolation (PVI, AVI). Although the multiple advantages of AVI over PVI techniques are well known, their effect in the base structure has not to date been compared. This interaction has an important role in the performance of the general control system, especially when the vibration isolation system is not the only system on the base structure or when there are multiple isolators working simultaneously on it. In addition, the structural serviceability of the base structure can also be affected. The analysis of the vibration isolation problem is made from a wide perspective, including the effect that isolator has on the base structure. Hence assuming the base structure is a non-rigid system. The effect of the isolation system on the base response is studied for an extensive range of base structures, thus showing different possible scenarios. The influence is quantified by comparing the peak magnitude response of the base when both passive and active vibration isolation techniques are used. The theoretical results have been corroborated by undertaking experimental tests on a full-scale laboratory structure.

We present a case of a woman with idiopathic macular telangiectasia type 1, characterized by the presence of a capillary macroanaeurysm associated with macular edema with a macular star pattern. Several differential diagnoses were proposed, in which the study with a multimodal image was key to clarify the diagnosis. In addition, the various treatments used and their effectiveness are discussed.

Individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, that may be particularly prominent, already at illness onset, in those more likely to have poorer symptom remission following treatment with the first antipsychotic. The identification of strong neuroanatomical markers of symptom remission could thus facilitate stratification and individualized treatment of patients with schizophrenia. We used magnetic resonance imaging at baseline to examine brain regional and network correlates of subsequent symptomatic remission in 167 medication-naïve or minimally treated patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder entering a three-phase trial, at seven sites. Patients in remission at the end of each phase were randomized to treatment as usual, with or without an adjunctive psycho-social intervention for medication adherence. The final follow-up visit was at 74 weeks. A total of 108 patients (70%) were in remission at Week 4, 85 (55%) at Week 22, and 97 (63%) at Week 74. We found no baseline regional differences in volumes, cortical thickness, surface area, or local gyrification between patients who did or did not achieved remission at any time point. However, patients not in remission at Week 74, at baseline showed reduced structural connectivity across frontal, anterior cingulate, and insular cortices. A similar pattern was evident in patients not in remission at Week 4 and Week 22, although not significantly. Lack of symptom remission in first-episode psychosis is not associated with regional brain alterations at illness onset. Instead, when the illness becomes a stable entity, its association with the altered organization of cortical gyrification becomes more defined.

Schizophrenia is a biologically complex disorder with multiple regional deficits in cortical brain morphology. In addition, interindividual heterogeneity of cortical morphological metrics is larger in patients with schizophrenia when compared to healthy controls. Exploiting interindividual differences in the severity of cortical morphological deficits in patients instead of focusing on group averages may aid in detecting biologically informed homogeneous subgroups. The person-based similarity index (PBSI) of brain morphology indexes an individual’s morphometric similarity across numerous cortical regions amongst a sample of healthy subjects. We extended the PBSI such that it indexes the morphometric similarity of an independent individual (eg, a patient) with respect to healthy control subjects. By employing a normative modeling approach on longitudinal data, we determined an individual’s degree of morphometric dissimilarity to the norm. We calculated the PBSI for sulcal width (PBSI-SW) in patients with schizophrenia and healthy control subjects (164 patients and 164 healthy controls; 656 magnetic resonance imaging scans) and associated it with cognitive performance and cortical sulcation index. A subgroup of patients with markedly deviant PBSI-SW showed extreme deficits in cognitive performance and cortical sulcation. Progressive reduction of PBSI-SW in the schizophrenia group relative to healthy controls was driven by these deviating individuals. By explicitly leveraging interindividual differences in the severity of PBSI-SW deficits, neuroimaging-driven subgrouping of patients is feasible. As such, our results pave the way for future applications of morphometric similarity indices for subtyping of clinical populations.

Background Palbociclib and ribociclib are novel oral agents in hormone receptor-positive metastatic breast cancer. Neutropenia is a common adverse event associated with these treatments and its clinical management often requires regimen changes, such as cycle delays and dose adjustments. Objective To provide a real-world experience of the effectiveness and toxicities associated with these drugs and to evaluate the impact of regimen changes in disease progression. Setting This study was performed at Hospital Universitario La Paz, in Spain. Methods Observational, retrospective study which included hormone receptor-positive metastatic breast cancer patients who initiated treatment with palbociclib or ribociclib between March 1st, 2018 and March 1st, 2019. Main outcome measure The primary effectiveness variable was progression-free survival. Safety evaluation was performed to determine neutropenia-incidence and severity, as well as its clinical management, including dose adjustments and treatment interruptions. Correlations between these regimen changes and effectiveness were also evaluated. Results Sixty-one patients were included, 33 treated with palbociclib and 28 with ribociclib. Palbociclib was mainly used as second line of treatment in the metastatic setting (81.8%) and ribociclib as first line (67.9%). The median progression-free survival was 12.76 months (95% CI 7.5 to not estimable) in palbociclib and not reached in ribociclib. After 12 months, the progression-free survival rate was 51.5% (95% CI 34–69) in palbociclib and 78.6% (95% CI 63–94.1) in ribociclib. Neutropenia was the most common adverse event with an incidence rate of 87.9% in palbociclib and 82.1% in ribociclib. Cycle delays were needed in more than half of the patients treated with palbociclib and ribociclib (63.6% and 64.3%). Dose adjustments were seen in 42.4% and 53.6% of the patients receiving palbociclib and ribociclib, respectively. Regimen changes did not involve statistically significant differences in 12-month PFS rates in the cohort investigated. Conclusion Palbociclib and ribociclib outcomes are comparable to those reached in the phase III trials, PALOMA-3 and MONALEESA-2, respectively, and cannot be compared as they were used in different treatment settings. The toxicity profile is favourable, being neutropenia the most common adverse event, easily managed with regimen changes. Further studies are needed to confirm the observed tendency of no detrimental impact on effectiveness of these regimen changes.

SummaryBackgroundSocial and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear.AimsWe studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed.MethodThis is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model.ResultsA total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = −0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure.ConclusionsOur results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.

For the commercial culture of the three‐spot cichlid (Amphilophus trimaculatus), it is important to have available a set of protein and lipid ingredients suitable for feed manufacturing, which allow to optimize the culture at affordable costs. The in vitro digestibility was evaluated with pH‐stat technique, using stomach and intestine multi‐enzymatic extracts from A. trimaculatus juveniles. The digestion of protein ingredients was taken place both in acid and in alkaline conditions, quantifying the total of free amino acids at the end of the hydrolysis, whereas the digestion of lipid ingredients was taken place only in alkaline conditions. The digestive enzymes of this species showed a better affinity to raw materials of animal origin such as beef meal, fish meal and premium chicken meal, which presented better digestibility. The best lipid ingredient that could be used is the fish oil. However, it is possible to use ingredients from the plant sources, such as soy or cereals, and vegetable oils such as olive, corn or soy oil. It is necessary to complement this study in vitro with the digestibility analysis in vivo, in order to determine the inclusion percentages in feeds and costs and therefore to develop an efficient feed formulation for the aquaculture of A. trimaculatus.

Negative symptoms are associated with poor clinical and psychosocial outcome in schizophrenia. Their prevalence and identification in first-episode patients remains controversial. In a large cohort of patients in the early stage of schizophrenia, schizophreniform or schizoaffective disorder, we investigated, over the different phases of the OPTiMiSE trial (baseline, 4, 10 and 22 weeks of treatment), the prevalence of negative symptoms of moderate severity, unconfounded by depression and extrapyramidal symptoms at baseline. Moreover, we assessed symptomatic remission, attrition rate and psychosocial functioning in subjects with short-term (4 weeks) persistent unconfounded negative symptoms (PNS) and in those with negative symptoms that did not persist at follow-up and/or were confounded at baseline (N-PNS). Negative symptoms of moderate severity were observed in 59% of subjects at baseline. They were associated with worse psychosocial functioning and longer duration of psychosis at intake in the study. Eleven percent of subjects had PNS unconfounded at baseline and 7.9% had PNS unconfounded at both baseline and end of 4-week treatment. Psychosocial functioning was comparable in PNS and N-PNS subjects at baseline but it was significantly worse in the former group after 4-weeks. PNS subjects showed lower remission and higher attrition rates at the end of all treatment phases. Fifty-six percent of subjects completing phase 3 (clozapine treatment) had PNS, and 60% of them were non-remitters at the end of this phase. The presence of short-term PNS during the first phases of psychosis was associated with poor clinical outcome and resistance to antipsychotic treatment, including clozapine.

Methanol poisoning is often described in the literature, but not transdermal or inhalational poisoning. It usually involves variable multi-organ damage, among which visual, neurological, and gastrointestinal involvement, as well as the metabolic and electrolyte changes that can lead to death. Contact with toluene by occupational or intentional inhalation may also cause neurological abnormalities. This article describes the case of a female patient who was seen in the Emergency Department due to bilateral visual loss secondary to accidental poisoning (inhalation-transdermal) with a solvent containing methanol and toluene. She had a favorable outcome during admission after treatment with ethanol in perfusion and corticosteroids.

Resumen La manometria y la pH-metria esofagicas son tecnicas diagnosticas esenciales en la seccion de pruebas funcionales de los servicios de aparato digestivo. Permiten documentar alteraciones de naturaleza funcional en el tracto digestivo superior, bien en la motilidad esofagica y de la union esofagogastrica o bien en la exposicion al acido de la mucosa del esofago. La impedanciometria combinada con la ph-metria es necesaria para el estudio de pacientes con sintomas de enfermedad por reflujo refractarios al tratamiento. Una correcta ejecucion e interpretacion de estos procedimientos es imprescindible para tratar adecuadamente varias enfermedades funcionales esofagicas y esofagogastricas, siempre con apoyo de otras tecnicas diagnosticas como las endoscopicas y radiologicas.

This paper presents two simple numerical models to analyze the behavior of two different fluidization technologies with concentrated solar energy on the top of the bed. A bubbling fluidized bed, which operates with low particle size (Geldart A-B particles with d p = 0.1 - 0.5 mm) and a spouted bed, which uses particles with larger sizes (Geldart D with d p ≳ 1 mm). Two cases were studied with the same mass of particles (150 kg), considering the same incident solar radiation concentrated on the top of the bed (50 kW). The results obtained indicate that the airflow rate in the bubbling fluidized bed has a notable effect on the maximum temperature reached in the bed. Increasing the airflow rate (from 1.5 to 2.5 times the minimum fluidization velocity), the maximum temperature reached in the bed is reduced from 950 to 750 K. In the spouted bed, higher temperatures are reached (over 1000 K), although it takes almost 4 times longer for the temperature to be reached than in the bubbling bed. Consequently, the charging efficiency, defined as the energy stored in the particles divided by the solar energy concentrated on the bed, are similar for both cases.

Aims: Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with second-generation APs, is strongly linked to weight gain, which increases patients’ risk of developing obesity and other metabolic diseases. There is an important genetic risk component that can contribute to the appearance of these disturbances. The aim of the present study was to evaluate the effect of polymorphisms in selected candidate genes on obesity and other anthropometric and metabolic traits in 320 AP-treated FEP patients over the course of a 2-year follow-up. Methods: These patients were recruited in the multicentre PEPs study (Phenotype−genotype and environmental interaction; Application of a predictive model in first psychotic episodes). A total of 127 validated single nucleotide polymorphisms (SNPs) in 18 candidate genes were included in the genetic analysis. Results: After Bonferroni correction, SNPs in ADRA2A, FTO, CNR1, DRD2, DRD3, LEPR and BDNF were associated with obesity, abdominal circumference, triglycerides, HDL cholesterol, and/or percentage of glycated haemoglobin. Conclusions: Although our results should be interpreted as exploratory, they support previous evidence of the impact of these candidate genes on obesity and metabolic status. Further research is required to gain a better knowledge of the genetic variants that can be considered relevant metabolic risk factors. The ability to identify FEP patients at higher risk for these metabolic disturbances would enable clinicians to better select and control their AP treatment.

Chronic kidney disease (CKD) is associated with a wide number of abnormalities in mineral metabolism. Often, these alterations are the leading players in the development of comorbidities associated with CKD, which are risk factors of mortality. In this context, mineral and bone disorder associated with CKD (CKD-MBD) are highlighted, connecting bone, renal, and cardiovascular disorders. Many studies have been led to propose strategies to avoid, reduce, or slow down CKD-MBD progression using different compositions of metallic elements-based P binders such as aluminum, magnesium, or calcium. Magnesium, the aim of this review, has been used by nephrologists to treat CKD-MBD with a variable acceptation due mainly to different results on bone homeostasis. Nowadays, we have new evidence about the efficacy of magnesium supplementation on vascular calcification, renal function, and bone disorders, suggesting potential beneficial effects of Magnesium in the management of CKD-MBD.

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta‐Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1‐weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed‐effects models and mega‐analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = −0.20), cornu ammonis (CA)1 (d = −0.18), CA2/3 (d = −0.11), CA4 (d = −0.19), molecular layer (d = −0.21), granule cell layer of dentate gyrus (d = −0.21), hippocampal tail (d = −0.10), subiculum (d = −0.15), presubiculum (d = −0.18), and hippocampal amygdala transition area (d = −0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non‐users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD., The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder.In the largest study of hippocampal subfields in bipolar disorder to date, from 23 sites worldwide, we report widespread reductions in nine of 12 subfields.The lack of differences between lithium users and healthy controls supports a possible protective role of lithium in bipolar disorder.

Despite the substantial increase in the access of people with disabilities to higher education, university institutions continue to be an exclusive environment for people with intellectual disabilities. This paper aims to present a training programme for the employment and university inclusion of young people with intellectual disabilities at the Pablo de Olavide University in Seville, Spain, under the title “Training for the employment and autonomous life of people with intellectual disabilities”, which was launched in the academic year 2017–2018 and has already completed four editions. The programme includes a hybrid training system with specific university training oriented towards employment and autonomy together with inclusive training in subjects of various university degrees. The training is provided by interdisciplinary university lecturers together with support staff specialised in intervention with people with intellectual disabilities who come from experienced community associations. Other components of the experience include internships in companies, individualised academic tutoring of students, family accompaniment, and community inclusion with the use of the university residence as accommodation. Cognitive accessibility and new technologies are not lacking as supports in the process. This work shows the assessment of the fundamental actors of this experience during the four years of its development, and as a conclusion, it shows a high overall satisfaction with the programme and the radical change observed in the lives of people with intellectual disabilities after their time at the university.

Objective Currently, mammography and ultrasonography are the most used imaging techniques for breast cancer screening. However, these examinations report many indeterminate studies with a low probability of being malignant, i.e., BIRADS 3 and 4A. This prospective study aims to evaluate the value of breast magnetic resonance imaging (MRI) to clarify the BIRADS categorization of indeterminate mammography or ultrasonography studies. Methods MRI studies acquired prospectively from 105 patients previously classified as BIRADS 3 or 4A were analyzed independently by four radiologists with different experience levels. Interobserver agreement was determined by the first-order agreement coefficient (AC1), and divergent results were re-analyzed for consensus. The possible correlation between the MRI and the mammography/ultrasound findings was evaluated, and each study was independently classified in one of the five BIRADS categories (BIRADS 1 to 5). In lesions categorized as BIRADS 4 or 5 at MRI, histopathological diagnosis was established by image-guided biopsy; while short-term follow-up was performed in lesions rated as BIRADS 3. Results Breast MRI was useful in diagnosing three invasive ductal carcinomas, upgraded from BIRADS 4A to BIRADS 5. It also allowed excluding malignancy in 86 patients (81.9%), avoiding 22 unnecessary biopsies and 64 short-term follow-ups. The MRI showed good diagnostic performance with the area under roc curve, sensitivity, specificity, PPV, and NPV of 0.995, 100%, 83.5%, 10.5%, and 100%, respectively. Conclusions MRI showed to be useful as a problem-solving tool to clarify indeterminate findings in breast cancer screening and avoiding unnecessary short-follow-ups and percutaneous biopsies.

Public knowledge of both the mission and the powers of the National Intelligence Centre (CNI) are studied in this paper through a survey of 2888 students from 30 universities in Spain. The results confirmed that university students were unaware of the CNI’s mission and powers and that their vision of the CNI was of a Law Enforcement Agency with mainly counter-terrorism functions. Their knowledge differed according to their sociodemographic background and political variables. Both the implications for further scientific debate and the policies of intelligence agencies toward openness are discussed.

Introduction/Background* CHEK2 gene is located on chromosome 22 and participates in the maintenance of the genome and control of the cell cycle and apoptosis. Mutations in this gene are considered to increase the risk of breast cancer. An accumulated risk throughout life is estimated at 28-37% in these patients. Methodology Retrospective observational study Review of patients followed in the inherited cancer unit in a single tertiary centre between 1st January 2012 until 28th February 2021. The statistical analysis was carried out using SPSS 22.0. Result(s)* During the indicated period, we followed 401 patients with confirmed genetic mutations that predispose to developing gynaecological cancer. Of the total, 2.49% (10/401) were carriers of a CHEK2 mutation. Within the cohort of patients carrying a CHEK2 mutation, 7/10 (70%) had a family history of breast cancer and 1/10 (10%) a gastric cancer. 6/10 patients were diagnosed with breast cancer at 23, 37, 37, 38, 44 and 52 years old. One of them had a second contralateral breast cancer at age 47. The histology of the breast cancer was either ductal carcinoma in situ or invasive ductal carcinoma. Tumor stage was 0 in one case, I in one case, IIA in two cases and IIIA in two cases. Surgery treatment was: unilateral mastectomy with homolateral axillary lymphadenectomy in 3 patients, conservative surgery in 1 patient, conservative surgery with selective sentinel lymph node biopsy in 1 patient and conservative surgery with homolateral axillary lymphadenectomy in 1 patient. Adjuvant treatment was: chemotherapy and hormone therapy in one case, radiation therapy and chemotherapy in one case, radiation therapy and hormone therapy in one case and radiation therapy, chemotherapy and hormone therapy in the other two. Characteristics of these patients are summarized in table 1. Discussion There are several recommendations in the literature regarding the follow-up of patients carrying a CHEK2 mutation. In general, it is recommended that all female carriers should be offered intensified surveillance programs for breast cancer including annual breast radiological testing. Conclusion* Patients carrying CHEK2 mutations have a moderate risk of developing breast cancer and should be followed in specialized hereditary cancer units.

Objective: To study the differences in early-life characteristics between patients with an early onset of psychotic disorders (EOP, aged < 18 years) versus adult onset of psychotic disorders (AOP, aged >= 18 years) and to identify predictors of earlier onset. Methods: 278 patients with a first episode of psychosis between the ages of 7 and 35 years were recruited as part of a multicenter prospective longitudinal study conducted in Spain between January 1, 2009, and December 31, 2011, with diagnoses made for AOP using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and for EOP using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS). Early-stage factors such as prenatal, perinatal, and other premorbid factors were registered and compared between EOP and AOP patients. To analyze the association between baseline variables and outcome, univariate and multivariate logistic regression models were used, and the association or odds ratios (ORs) for significant risk factors were calculated. Results: 224 patients with AOP (mean +/- SD age = 25.6 +/- 5.0 years; 65.6% male) and 54 patients with EOP (16.1 +/- 1.7 years; 68.5% male) were included. Univariate analysis revealed significant differences between the groups. Specifically, compared to AOP subjects, EOP patients had more frequent obstetric complications (OCs) (P

This study is part of a coordinated-multicentre Project, funded by the Ministerio deEconomia y Competitividad (PI08/0208; PI11/00325; PI14/00612), Instituto de Salud Car-los III–Fondo Europeo de Desarrollo Regional, Union Europea, Una manera de hacer Eu-ropa, Centro de Investigacion Biomedica en Red de salud Mental, CIBERSAM, by theCERCA Programme/Generalitat de Catalunya and Secretaria d’Universitats i Recerca delDepartament d’Economia I Coneixement (2017SGR1355), Departament de Salut de laGeneralitat de Catalunya, en la convocatoria corresponent a l’any 2017 de concessio desubvencions del Pla Estrategic de Recerca i Innovacio en Salut (PERIS) 2016-2020,modalitat Projectes de recerca orientats a l’atencio primaria, amb el codi d’expedientSLT006/17/00345

Introduction Although vaccination has proven to be one of the most effective public health interventions for disease prevention, a small section of the population presents the so-called ‘vaccine hesitancy’ or vaccination doubts. It would be interesting to know the possible factors related to rejection of vaccination. Material and methods Study of cases and controls in which data have been collected from children registered in the REVA programme in the province of Valladolid with explicit rejection of parents (cases), paired with children of the same age, sex and basic health area that do have been vaccinated (controls). Telephone interview was conducted to obtain sociodemographic factors and opinion on vaccination. Results and discussion A total of 82 children were selected, of whom 30 parents agreed to take to the survey. 55% of them mention the doctor as the main source of vaccination information, which contrasts with the distrust of the detected system. Statistically significant differences in the perception of vaccination side effects between cases and controls and in the different items were observed. Statistically significant association was observed between the use of homeopathy the risk of being a case (OR = 5.75, 95% CI = 1.9 to 17.34). Conclusions Although the number of children not vaccinated by explicit rejection by their parents in Valladolid is very low, it is important to know the reasons for this decision and to make an approach guided by the approach of postures rather than the judgment of values towards these families.

BackgroundPositive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.MethodTo study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.ResultsThe result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.ConclusionThese findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

This study explored the potential association between chronic exposure to pesticide mixtures including paraquat and respiratory outcomes among Colombian farmers. Sociodemographic and occupational data, respiratory symptoms and spirometric data were collected. Paraquat in spot urine samples were quantified with solid-phase extraction high-performance liquid chromatography. Multiple Poisson regressions with robust variance were used to determine factors associated with respiratory outcomes. Profiles of pesticide mixtures used were identified among 217 farmwork-ers, but profenofos and methamidophos-based mixtures were more frequent. Chronic paraquat exposure was slightly associated with self-reported asthma (PR: 1.06; 95% CI 1.00 to 1.13). Different pesticide mixtures were associated with flu, thoracic pain, allergic rhinitis, and obstructive pattern in spirometry. Although acute exposure to paraquat is low among Colombian farmers participating in the study, associations between respiratory outcomes and chronic pesticide mixtures exposure including profenofos, methamidophos or glyphosate require further specific studies. © 2020 National Institute of Occupational Safety and Health.

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47–67.00, ROC-AUC = 71.49%, 95% CI = 69.39–73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70–60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen’s Kappa = 0.83, 95% CI = 0.829–0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.

This review summarizes different solar thermal energy storage techniques from a particle technology perspective, including sensible, latent and thermochemical techniques for low- and high-temperature applications that use particles as the storage medium in the thermal energy storage system. The focus is on applications, experimental results, modeling and future trends. This review describes two different particle technologies used to store thermal energy: packed and fluidized beds. The advantages and disadvantages of both technologies are reviewed throughout different studies found in the literature for various thermal energy storage systems. Packed beds have the main advantage of thermal stratification, which increases the efficiency of solar collectors in low-temperature sensible energy storage systems and augments the exergy content in the bed. Moreover, they have been proven to be suitable as dual-media thermocline storage systems for CSP plants. In contrast, the high mixing rates of fluidized beds makes them suitable for the rapid distribution of concentrated solar energy in particle receiver CSP systems. In addition, their high heat and mass transfer rates, compared with those of packed beds, make them the preferred particle technology for thermochemical energy storage applications. This review also notes that it is important to find new materials with an appropriate size and density that can be properly used in a fluidized bed. Additionally, more specific research efforts are necessary to improve the understanding of the behavior of these materials during the fluidization process and over a high number of charging/discharging cycles.

Resumen La presencia de infiltrados pulmonares es un hallazgo frecuente que incluye un amplio diagnóstico diferencial basado en muchas ocasiones en la historia clínica. Entre ellas, la neumonía lipoidea exógena representa una entidad poco frecuente y es preciso un elevado índice de sospecha para alcanzar su diagnóstico y evitar su progresión. En estos casos, un contexto clínico adecuado y una TC con opacidades y áreas de baja densidad pueden ser altamente sugestivos de la enfermedad. Se presenta un caso de neumonía lipoidea exógena secundaria a la utilización continuada de sustancias oleosas intranasal, que debido a los antecedentes del paciente y a las posibilidades diagnósticas tras los hallazgos de la TC, precisó confirmación histológica.

Introduction Breast cancer is one of the most prevalent cancers in the world. Traditionally, early breast cancer treatment is based on surgery and, after surgery, hormone treatment or chemotherapy. However, the neoadjuvant treatment is increasingly used. Metabolomics is the most recent “omics” which allows quantify metabolites into blood patient samples. Coupled with computational analyses it could be possible to study differential metabolomics patterns and associate them with neoadjuvant response. Material and methods Blood plasma samples from patients with breast cancer treated with neoadjuvant chemotherapy were used to perform metabolomics experiments. One sample before the treatment (basal) and one sample after the chemotherapy (post-treatment) were analyzed and clinical data regarding response (complete response or partial response) was also collected. Metabolomics experiments were performed using liquid chromatography coupled with mass-spectrometry. Bayesian network and class comparison analyses were used to establish differential metabolic patterns between conditions. Additionally, a response prediction model based on logistic regression was build using metabolomics data from basal samples. Results and discussion A network showing the relationships between metabolites was build. Comparing metabolite measurements between complete response and partial response tumors in basal samples, 19 metabolites showed a differential quantification between both types of responses. Moreover, one of these metabolites is linoleic acid, previously described as a biomarker of complete response in neoadjuvant treatment in breast cancer. Using these 19 differential metabolites, a response predictive model was build. According to this model, it is possible to predict response to neoadjuvant treatment based on the amount of one metabolite, still only identified by its mass and charge. On the other hand, comparing basal and post-treatment samples, the network showed differential metabolomics patterns. These differential metabolites could be used as predictive biomarkers of response. Conclusion This study is a proof of concept that using a new “omics” technique such as metabolomics in blood samples, coupled with computational analyses, it is possible to identify differential metabolomics patterns between complete and partial response or basal and post-treatment samples and design predictive models of response These results could facilitate in the future the implementation of blood-based tests into the clinical routine. Citation Format: Zamora P, Trilla-Fuertes L, Zapater-Moros A, Gámez-Pozo A, Prado-Vázquez G, Ferrer-Gómez M, Díaz- Almirón M, López Vacas R, Espinosa E, Fresno Vara JA. A pilot study of metabolomics biomarkers in breast cancer tumors treated with neoadjuvant therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-14.

A technique has been developed for fabrication of ultrahydrophobic Ti-6Al-4V surface by vacuum process. This report has the data related to the article “Hybrid laser and vacuum process for rapid ultrahydrophobic Ti-6Al-4 V surface formation” on the fabrication of ultrahydrophobic Ti-6Al-4V by Vacuum process (Jagdheesh et al., 2019). The present data consist of X-ray photo electron spectroscopy spectrums recorded for the laser patterned ultrahydrophobic samples, droplet image and surface chemical composition of laser patterned Ti-6Al-4V samples before vacuum process(b. v. p.) and after vacuum process (a. v. p.) for 120 min. The presented data give a clear idea about the chemical modification evolved during the vacuum process.

Due to the high strength-to-weight ratio of fibre reinforced polymers (FRPs), human-induced vibration problematic remains as a subject to be fully comprehended in order to extend the use of composites in Bridge Engineering. Thus, this paper studies an ultra-lightweight FRP footbridge, which presents excessive vertical vibrations when the fourth harmonic of a walking pedestrian is synchronised with the structure’s fundamental frequency. Focusing on the vertical bending mode, at 7.66 Hz, the bridge dynamic behaviour was assessed under the action of a single pedestrian crossing the facility at a step frequency of 1.9 Hz. As an over prediction of the footbridge response was computed using a moving force (MF) model available in a design guideline, a mass-spring-damper-actuator (MSDA) system was adopted to depict a walker. Hence, Human-Structure Interaction (HSI) phenomenon was considered. Employing the experimental results, parameters of the MSDA system were identified, leading to a HSI model that considers the first fourth harmonics of a walking human. Additionally, a parametric analysis was carried out, determining that the damping ratio of the human body and the load factor associated to the fourth harmonic are the most relevant parameters on the estimation of the response. The identified HSI model may be used as a first approximation to accurately predict the dynamic response of ultra-lightweight composite structures and should be extended to account for crowd-induced loads.

Objective: The identification of predictors of psychosis remission could guide early clinical decision-making for treatment of first-episode schizophrenia (FES).Methods: We analyzed two non-independent subsamples of patients with FES ages 18-40 years from the OPTiMiSE study dataset to investigate the demographic and clinical factors that might help to differentiate "late" re-mitters (i.e., not in remission at week 2 or 4, but achieving remission within a 10-week follow-up period) from non-remitters within the same period.Results: Subsample 1 included 216 individuals (55 females, mean age 25.9 years) treated with amisulpride in an open-label design who were not in remission at week 2. Early symptomatic response between baseline and week 2 (odds ratio (OR)- 4.186, 95% confidence interval (CI)- 2.082-8.416, p < 0.001) and older age (OR- 1.081, 95% = CI 1.026-1.138, p- 0.003) were the only variables significantly associated with a higher probability of psychosis remission at week 4. Subsample 2 was composed of the 72 participants (19 females, mean age 25.1 years) who were not in remission at week 4 and completed a 6-week double-blind randomized trial comparing continuation of amisulpride with switch to olanzapine. Depression at baseline (as measured with the Calgary Depression Scale for Schizophrenia) was significantly associated with a nearly 3-fold lower likelihood of psychosis remission during the 10-week follow-up (hazard ratio = 2.865, 95% CI = 1.187-6.916, p = 0.019).Conclusion: Our results reinforce the importance of assessing depressive symptoms in people with FES and support the relevance of an early response (as early as 2 weeks) as a predictor of clinical outcome in this population. (C) 2021 Elsevier B.V. All rights reserved.

Introduction:Bullying is a major preventable risk factor for mental disorders. Available evidence suggests school-based interventions reduce bullying prevalence rates. This study aims to test the efficacy of a web-enabled, school-based, multicomponent anti-bullying intervention to prevent school bullying and to assess its effects on mental health and quality of life.Methods and analysis:Cluster randomized controlled trial conducted in 20 publicly funded primary and secondary schools in Madrid, Spain. Schools are randomly allocated to either the intervention arm (n= 10) or conventional practices arm (n= 10). The web-enabled intervention (LINKlusive) lasts ~12 weeks and consists of three main components: (i) an online training program for teachers and parents, (ii) a web-guided educational program for students, focusing on promoting respect for diversity, empathy, and social skill development, and (iii) a web-guided, teacher-delivered, targeted intervention program for bullying situations identified based on peer-support strategies and individual intervention for those involved (i.e., bullying victims and perpetrators). The primary objective is to compare differences between peer-reported bullying victimization in the intervention and control arms at the end of the intervention. Secondary outcome measures are additional measures of bullying victimization and perpetration, mental health symptoms, self-esteem, and quality of life. A follow-up assessment is conducted 1 year after the end of the intervention. Treatment effects will be tested using multilevel mixed models, adjusting for school-, classroom-, and student-related covariates. Considering the increased bullying rates in children with special educational needs, a specific subgroup analysis will test the efficacy of the intervention on bullying prevalence, mental health, and quality of life in this particularly vulnerable population.Ethics and Dissemination:The Deontology Commission of the School of Psychology, Universidad Complutense in Madrid, Spain reviewed the study protocol and granted ethical approval on 21st January 2019. The results of the trial will be disseminated in relevant peer-reviewed journals and at conferences in the field.Trial Registration Number:ISRCTN15719015.

Background and importance The use of proton pump inhibitors (PPIs) has increased considerably in recent years, probably due to their prescription in unjustified clinical situations or their prolonged maintenance without prescription revision, which can expose the patient to adverse effects. Aim and objectives To determine the prevalence of PPI prescriptions without a clear indication in elderly patients institutionalised in a geriatric healthcare centre (GHC) that would require their deprescription assessment, as well as to quantify the prevalence of fractures in these patients. Material and methods An observational, descriptive, cross sectional study was conducted in all institutionalised patients in a GHC associated with a tertiary hospital in May 2020. The variables collected were: sex, age, PPI prescription, indication, duration of PPI treatment, number of drugs prescribed, concomitant prescription of a gastrolesive drug and bisphosphonates, history of upper gastrointestinal bleeding or gastroduodenal ulcer, and history of fracture. Suitable indications for a PPI were those included on the label. Results GHC is a 120 bed residence with 95 patients. 73.7% were women and mean age was 82.3±8.3 years. At the date of the study, 78 patients (82.1%) were being treated with a PPI, of which a clear indication according to label was found in 51.3%. The prescribed PPIs were: omeprazole 20 mg in 96.2%, lansoprazole 15 mg in 1.3% and lansoprazole 30 mg in 2.6%. At least 41% of the patients had been treated with PPIs for more than a year; for the rest of the patients, no prescription data were available prior to joining the pharmacy service. The mean number of drugs prescribed per patient was 8.3±5, 1.2% were being treated with an NSAID, 42.3% were taking acetylsalicylic acid concomitantly at antiplatelet doses and 3.8% were given bisphosphonates. The prevalence of patients being treated with a PPI and with a history of fracture was 48.7%. Conclusion and relevance There was a high prevalence of patients without a clear indication for the prescription of PPIs in the GHC. This makes it necessary to review the treatments to assess possible deprescription of these drugs. In addition, their administration could be related to an increased risk of fractures due to its high prevalence. References and/or acknowledgements Conflict of interest No conflict of interest