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SummaryBrain computation depends on intricately connected yet highly distributed neural networks. Due to the absence of the requisite technologies, causally testing fundamental hypotheses on the nature of inter-areal processing have remained largely out-of-each. Here we developed the first two photon holographic mesoscope, a system capable of simultaneously reading and writing neural activity patterns with single cell resolution across large regions of the brain. We demonstrate the precise photo-activation of spatial and temporal sequences of neurons in one brain area while reading out the downstream effect in several other regions. Investigators can use this new platform to understand feed-forward and feed-back processing in distributed neural circuits with single cell precision for the first time.

The coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by a novel coronavirus (SARS-CoV-2), is emerging as a worldwide public health emergency. Several scientific contributions reported the potential relevance of human leukocyte antigen (HLA) polymorphism and susceptibility to viruses, such as SARS-CoV. In our study, we examined a population of coeliac subjects presenting the HLA haplotype DQ2 and/or DQ8. Our aim was to evaluate whether HLA DQ2 and/or DQ8 haplotype play a role in SARS-CoV-2-infection. The aim was also to evaluate the difficulty in following the gluten-free diet due to all the adversities produced by the pandemic, such as the food supply disruption, and the difficulties in managing the clinical follow-up.191 consecutive coeliac patients completed a questionnaire on their current clinical status, psychological effects, and management of the gluten-free diet experienced during the COVID-19 pandemic and questions regarding possible SARS-CoV-2 infection.Out of the 191 patients who participated in the study, 42 were full-blown coeliac and 149 were in remission. From the answers provided, 84.8% of patients declared that they no longer consider themselves vulnerable to COVID-19 as they suffer from coeliac disease; 94.2% of patients did not encounter any difficulties in managing the gluten-free diet or in acquiring specific foods and 64.9% of patients in our study underwent diagnostic testing for SARS-CoV-2. Out of this number, 31.5% did so due to contacts with subjects affected by COVID-19, 26.6% for work related reasons, 11.3% due to flu-like symptoms and 30.6% for other reasons. Only 5.8% of the enrolled patients received a diagnosis of COVID-19. Out of all the patients in our population who were diagnosed with COVID-19, 94.8% developed no symptoms and none of them needed hospitalization or intensive care.The hypothesis that the HLADQ2 and/or DQ8 haplotype plays a protective role against SARS-CoV-2 infection, as against other viral infections, is intriguingly suggestive.KEY MESSAGESCOVID-19 as a public health emergency;SARS-CoV-2 and possible complications in coeliac disease;Role of HLA DQ2 and/or DQ8 in SARS-CoV-2 infection.

Resumen del póster presentado al 10th International Symposium on Metallic Multilayers (MML), celebrado en Madrid (España) del 17 al 21 de junio de 2019., Co/Pd multilayers can exhibit perpendicular magnetic anisotropy (PMA) for ultrathin thicknesses of Co and Pd layers. The PMA magnitude depends on several parameters, as the thickness of each constituent layer, the quality of the Co-Pd interface, the crystallinity of the film, or the total number of layers. In this work we present the PMA dependence with the number of Co/Pd repetitions. Such dependence was investigated by magnetometry and synchrotron light techniques. Magnetization curves obtained by SQUID magnetometer provide macroscopic parameters, as the interfacial and effective anisotropy of the multilayers, or the net magnetization of the sample. In addition, x-ray magnetic circular dichroism (XMCD) reveal microscopic details, as the anisotropy of the atomic angular momentum, the magnitude of the Co spin moment, or the hybridization of Co-Pd orbitals at the interface. Both kinds of results are combined to show a clear picture of the PMA evolution with the number of repetitions. A correlation between macroscopic and microscopic parameters is established in the whole range of thicknesses, from 2 to 40 Co/Pd repetitions., Work supported by FIS2016-76058 (AEI/FEDER, UE), H2020-MSCA-RISE-2016-734801, and Basque Government - PIBA 2018-11.

We previously reported that nuclear grade assignment of prostate carcinomas is subject to a cognitive bias induced by the tumor architecture. Here we asked whether this bias is mediated by the non conscious selection of nuclei that "match the expectation" induced by the inadvertent glance at the tumor architecture. 20 pathologists were asked to grade nuclei in high power fields of 20 prostate carcinomas displayed on a computer screen. Unknown to the pathologists each carcinoma was shown twice once before a background of a low grade tubule rich carcinoma and once before the background of a high grade solid carcinoma. Eye tracking allowed to identify which nuclei the pathologists fixated during the 8 second projection period. For all 20 pathologists nuclear grade assignment was significantly biased by tumor architecture. Pathologists tended to fixate on bigger darker and more irregular nuclei when those were projected before kigh grade solid carcinomas than before low grade tubule rich carcinomas (and vice versa). However the morphometric differences of the selected nuclei accounted for only 11 of the architecture induced bias suggesting that it can only to a small part be explained by the unconscious fixation on nuclei that "match the expectation". In conclusion selection of « matching nuclei » represents an unconscious effort to vindicate the gravitation of nuclear grades towards the tumor architecture.

We recently reported that nuclear grading in prostate cancer is subject to a strong confirmation bias induced by the tumor architecture. We now wondered whether a similar bias governs nuclear grading in breast carcinoma. An unannounced test was performed at a pathology conference. Pathologists were asked to grade nuclei in a PowerPoint presentation. Circular high power fields of 27 invasive ductal carcinomas were shown superimposed over low power background images of either tubule rich or tubule poor carcinomas. We found (a) that diagnostic reproducibility of nuclear grades was poor to moderate (weighed kappa values between 0.07 and 0.54 27 cases 44 graders) but (b) that nuclear grades were not affected by the tumor architecture. We speculate that the categorized grading in breast cancer separating tubule formation nuclear pleomorphism and mitotic figure counts in a combined three tier score prevents the bias that architecture exerts on nuclear grades in less well controlled situations.

Introducción: La adecuación de la ingesta de calcio de la población infantil española ha sido objeto de debate y controversia, pues algunos estudios señalan que puede ser inadecuada en un porcentaje variable de escolares, mientras que algunos documentos insisten en el peligro de una ingesta excesiva en un amplio porcentaje de la población escolar. Objetivos: Valorar la ingesta de calcio y las fuentes alimentarias de este nutriente en una muestra representativa de niños españoles, analizando también la adecuación del aporte a la cobertura de las ingestas recomendadas. Métodos: Se estudiaron 903 escolares (de 7 a 11 años) de diez provincias españolas: Tarragona, Cáceres, Burgos, Guadalajara, Valencia, Salamanca, Córdoba, Vizcaya, Lugo y Madrid, que constituyen una muestra representativa de la población española de dicha edad. La ingesta de energía y nutrientes se determinó utilizando un registro del consumo de alimentos durante 3 días, incluyendo un domingo. El aporte de calcio se comparó con las Ingestas Recomendadas (IR) marcadas para dicho mineral. Los parámetros antropométricos estudiados fueron el peso y la talla, lo que permitió calcular el índice de masa corporal (IMC). Resultados: En el colectivo estudiado (55,3% de niñas y 44,7% de niños), un 30,7% presentó exceso de peso (sobrepeso-23,3% y obesidad-7,4%). La ingesta de calcio de los niños estudiados (859,9 ± 249,2 mg/día) supuso un 79,5% de lo recomendado, observándose la existencia de un 76,7% de niños con ingestas menores de las recomendadas y un 40,1 con ingestas < 67% de las IR. La relación calcio/fósforo (0,74 ± 0,21), calcio/proteínas (10,1 ± 2,8) y el índice de calidad nutricional para el calcio (0,78 ± 0,29) estuvieron por debajo de lo recomendado en el 91,6%, 99,8% y 81,1% de los niños, respectivamente. En relación con la procedencia alimentaria del calcio, un 64,7% proviene de lácteos, 7,6% de varios, 7,3% de cereales, 3,5% de verduras, 3,4% de frutas y 3,3% de precocinados, las carnes y pescados aportan un 2,8%, cada grupo y las legumbres un 2,2%, sin diferencias en función del sexo. Conclusión: La ingesta de calcio es inferior a la recomendada en un elevado porcentaje de los estudiados (76,7%) y resulta en un 40,1% claramente insuficiente (< 67%de IR). Teniendo en cuenta que en la dieta media infantil española el aporte de calcio proviene mayoritariamente de los lácteos (64,7%), aumentar el consumo de este grupo de alimentos resulta deseable, especialmente en el 37,1% de los niños que no toman el mínimo de las 2 raciones/día, recomendadas.

The influence was studied of the administration of acetylsalicylic acid and acetaminophen in doses of 450 mg/kg body weight/day, and 600 mg/kg/day respectively on the alimentary efficacy coefficient (AEC), on growth and on the hepatosomatic index in rats on a diet sufficient in all nutrients required to meet the animal's needs. The AEC was studied both for the whole experimental period and at values taken weekly. The results show that both aspirin and paracetamol significantly reduce overall alimentary efficacy (p0.05) and increase the hepatosomatic index. Partial AEC values showed that the analgesics studied significantly affect the figures (p0.05) for the intermediate periods (aspirin, 0.27 +/- 0.01, vs 0.38 +/- 0.03), and that these are more affected than those of the final treatment period (aspirin, 0.33 +/- 0.14, vs 0.36 +/- 0.07).

En principio no parece inadecuado entender la politica economica como la intervención de una voluntad politica de1 Estado) en un orden fundamentalmen- te espontáneo (la economia). Puede así pensarse que ella consiste en la prolon- gación de la politica en el terreno económico. De esta concepción se desprende una cierta metodologia. Una vez determinadas la coyuntura económica y la correlación de fuerzas, se trataría de reconstruir como a partir de esta última y de los problemas y retos que presenta la primera, surge una política económica defi- nida, con una profundidad y sentido dados. Esta visión que tiene el mérito de explicar medidas que desde el punto de vista estrictamente económico pueden ser calificadas de irracionales, es, sin embargo, incompleta. A eLla le sub- yace la idea de que cada fuerza política puede identificar con precisión los inte- reses de sus bases y elaborar un proyecto de política económica coherente con su desarrollo.

Detection of silent myocardial ischaemia must be accurate and reliable. With the new digitized Holter monitoring systems these qualities are feasible. We tested one of these devices (Monitor One, Q Med) by comparison with a digitized and averaged ECG signal provided by the Marquette Case system during exercise tests in 30 patients with angiographically documented coronary artery disease. Detection and quantitation of ST segment depression episodes by the Holter system were excellent. Furthermore, indirect ECG criteria of ischaemia as R-wave amplitude variations were easily recognized. Thus digital monitors may be used to detect ischaemic events in prospective and multicentre studies for the diagnosis and prognosis of silent myocardial ischaemia.

In 38 patients with acute lymphocytic leukemia and Hodgkin's disease 60 episodes of infection were registered showing the unquestionable increased susceptibility to infections in these cases. In 90% of the patients the infectious focus was localized and the pulmonary showed to be the most frequent. The etiology of the infection was established in 53% of the episodes and the bacterial, both gram-positive as gram-negative, showed the greatest frequency. In the second place came viral infections (measles and chicken-pox). Finally, two pathogenic agents, unusual in children without cancer were seen: Candida albicans and Pneumocystis carinii. Treatment was given according to the etiological agent. When it was not determined, methycillin-gentamicin was given and if the problem was pulmonary and response was not obtained within 4 to 6 days, trimetoprim-sulfametoxazole was chosen. Five children died as direct consequence of infection (13% of the patients), 2 of them (5%) without tumoral activity at that moment.

This report describes a 34-year-old woman with an anomalous origin of the left coronary artery from the pulmonary artery. The angiographic pattern was clearly demonstrated by magnetic resonance imaging (MRI) performed before surgery. This case suggests thst MRI could play an important role in the pre-operative assessment of coronary anomalies.

In myocardial revascularisation the aims of exercise testing are: (a) to determine a relevant indication for revascularisation; (b) to assess the results of the procedure by comparison to the pre-operative data and in an absolute manner (for example, a patient who has improved the symptom-limited heart rate between 4 and 8 min of exercise duration from 110 to 140 BPM and the ST segment depression from −4 to −1,5 mm may be considered as having an excellent result although his ability to do manual work has not been recovered); and (c) to identify sufficiently early the recurrence of ischaemia. The need for a pre-operative exercise test is therefore obvious.

There is no doubt that ventricular tachycardia (VT) and ventricular fibrillation (VF) do occur during exercise testing.

Summary Background There is no evidence that phlebotomy alone is sufficient to steadily maintain haematocrit on target level in low-risk patients with polycythaemia vera. This study aimed to compare the efficacy and safety of ropeginterferon alfa-2b on top of the standard phlebotomy regimen with phlebotomy alone. Methods In 2017, we launched the Low-PV study, a multicentre, open-label, two-arm, parallel-group, investigator-initiated, phase 2 randomised trial with a group-sequential adaptive design. The study involved 21 haematological centres across Italy. Participants were recruited in a consecutive order. Participants enrolled in the study were patients, aged 18–60 years, with a diagnosis of polycythaemia vera according to 2008–16 WHO criteria. Eligible patients were randomly allocated (1:1) to receive either phlebotomy and low-dose aspirin (standard group) or ropeginterferon alfa-2b on top of the standard treatment (experimental group). Randomisation sequence was generated using five blocks of variable sizes proportional to elements of Pascal's triangle. Allocation was stratified by age and time from diagnosis. No masking was done. Patients randomly allocated to the standard group were treated with phlebotomy (300 mL for each phlebotomy to maintain the haematocrit values of lower than 45%) and low-dose aspirin (100 mg daily), if not contraindicated. Patients randomly allocated to the experimental group received ropeginterferon alfa-2b subcutaneously every 2 weeks in a fixed dose of 100 μg on top of the phlebotomy-only regimen. The primary endpoint was treatment response, defined as maintenance of the median haematocrit values of 45% or lower without progressive disease during a 12-month period. Analyses were done by intention-to-treat principle. The study was powered assuming a higher percentage of responders in the experimental group (75%) than in the standard group (50%). Here we report results from the second planned interim analysis when 50 patients had been recruited to each group. The trial is ongoing, and registered with ClinicalTrials.gov , NCT03003325 . Findings Between Feb 2, 2017, and March 13, 2020, 146 patients were screened, and 127 patients were randomly assigned to the standard group (n=63) or the experimental group (n=64). The median follow-up period was 12·1 months (IQR 12·0–12·6). For the second pre-planned interim analysis, a higher response rate in the experimental group was seen (42 [84%] of 50 patients) than in the standard group (30 [60%] of 50 patients; absolute difference 24%, 95% CI 7–41%, p=0·0075). The observed z value (2·6001) crossed the critical bound of efficacy (2·5262), and the stagewise adjusted p value early showed superiority of experimental treatment. Thus, the data safety monitoring board decided to stop patient accrual for overwhelming efficacy and to continue the follow-up, as per protocol, for 2 years. Under the safety profile, no statistically significant difference between groups in frequency of adverse events of grade 3 or higher was observed; the most frequently reported adverse events were neutropenia (four [8%] of 50 patients) in the experimental group and skin symptoms (two [4%] of 50 patients) in the standard group. No grade 4 or 5 adverse events occurred. Interpretation Supplementing phlebotomy with ropeginterferon alfa-2b seems to be safe and effective in steadily maintaining haematocrit values on target in low-risk patients with polycythaemia vera. Findings from the current study might have implications for changing the current management of low-risk patients with polycythaemia vera. Funding AOP Orphan Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro

Auricular acupuncture at the relaxation point has been shown to be effective treatment for anxiety. We hypothesized that auricular acupressure may decrease anxiety in elderly individuals who are transported by ambulance before receiving ESWL.We enrolled 100 patients with renal calculi who were transported to the local hospital by special ambulance, accompanied by 2 paramedics. Paramedic 1 performed data collection, while paramedic 2 performed auricular acupressure in patients randomly assigned to a relaxation group and a sham treated group. Anxiety was measured using a visual analog scale score on a scale of 0 to 100 mm.Each group consisted of 50 patients with similar demographic characteristics. The relaxation group had significantly decreased anxiety scores upon arrival at the hospital and lower anticipation of pain scores (mean+/-SD 57.6+/-21.8 to 15.4+/-9.8 and 35.7+/-29.7 to 9.5+/-4.1 mm VAS) than the sham treated group (55.5+/-25.9 to 49.8+/-28.9 and 37.7+/-24.1 to 33.8+/-25.2 mm VAS, respectively, 2-way repeated measure ANOVA each p=0.001). Estimated waiting times for treatment did not differ significantly between the 2 groups (5.0+/-2.5 and 5.5+/-2.95, respectively, repeated measures ANOVA p=0.83). The Post-Intervention Anxiety visual analog scale demonstrated the significant superiority of the true treatment group (19.5+/-5.9 and 66.8+/-27.9 mm VAS, respectively, p=0.001).Elderly patients who received auricular acupressure at specific relaxation points while being transported to the hospital were less anxious, anticipated less pain and were more optimistic about the outcome of treatment that they will receive than the sham treated group. These data prove that this is an effective treatment for anxiety that improves the patient overall perception of ESWL.