Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of peripheral blood pressure with gray matter volume in 19- to 40-year-old adults

Objective To test whether elevated blood pressure (BP) relates to gray matter (GM) volume (GMV) changes in young adults who had not previously been diagnosed with hypertension (systolic BP [SBP]/diastolic BP [DBP] ≥140/90 mm Hg). Methods We associated BP with GMV from structural 3T T1-weighted MRI of 423 healthy adults between 19 and 40 years of age (mean age 27.7 ± 5.3 years, 177 women, SBP/DBP 123.2/73.4 ± 12.2/8.5 mm Hg). Data originated from 4 previously unpublished cross-sectional studies conducted in Leipzig, Germany. We performed voxel-based morphometry on each study separately and combined results in image-based meta-analyses (IBMA) to assess cumulative effects across studies. Resting BP was assigned to 1 of 4 categories: (1) SBP <120 and DBP <80 mm Hg, (2) SBP 120–129 or DBP 80–84 mm Hg, (3) SBP 130–139 or DBP 85–89 mm Hg, (4) SBP ≥140 or DBP ≥90 mm Hg. Results IBMA yielded the following results: (1) lower regional GMV was correlated with higher peripheral BP; (2) lower GMV was found with higher BP when comparing individuals in subhypertensive categories 3 and 2, respectively, to those in category 1; (3) lower BP-related GMV was found in regions including hippocampus, amygdala, thalamus, frontal, and parietal structures (e.g., precuneus). Conclusion BP ≥120/80 mm Hg was associated with lower GMV in regions that have previously been related to GM decline in older individuals with manifest hypertension. Our study shows that BP-associated GM alterations emerge continuously across the range of BP and earlier in adulthood than previously assumed. This suggests that treating hypertension or maintaining lower BP in early adulthood might be essential for preventing the pathophysiologic cascade of asymptomatic cerebrovascular disease to symptomatic end-organ damage, such as stroke or dementia.
Robert Furchgott (1916-2009): A scientist with a mission

Robert Furchgott was first noted for research on drug–receptor theory, autonomic neuroeffector mechanisms, and vascular pharmacology/physiology. His studies on drug–receptor interactions provided important knowledge about the properties of drug receptors long before methodologies were developed to study them directly. However, Furchgott achieved an enduring legacy for recognizing the importance of endothelial cells for the relaxation of vascular smooth muscle. On the basis of his own experiments and those of others, he proposed that acetylcholine interacted with muscarinic receptors at the surface of endothelial cells to release a substance called endothelium relaxing factor. Endothelium relaxing factor was later identified as nitric oxide, a colorless, odorless gas. Furchgott’s discovery of an entirely new mechanism by which blood vessels dilate revolutionized studies on the physiology of the vascular system. His work also suggested new treatments for hypertension and heart disease, and was a key factor in the development of the anti-impotence drug sildenafil. In 1998, Robert Furchgott shared the Nobel Prize in Physiology or Medicine with Ferid Murad and Louis Ignarro.
A simplified flow cytometric method for detection of inherited platelet disorders—A comparison to the gold standard light transmission aggregometry

Background Flow cytometric platelet activation has emerged as an alternative diagnostic test for inherited platelet disorders. It is, however, labor intensive and few studies have directly compared the performance of flow cytometric platelet activation (PACT) to light transmission aggregometry (LTA). The aims of this study were 1/ to develop a simplified flow cytometric platelet activation assay using microtiter plates and 2/ to correlate the outcome to gold standard method LTA, and to clinical bleeding assessment tool scores (BAT score). Methods The PACT method was developed in microtiter plates using adenosine diphosphate (ADP), collagen-derived peptide (CRP-XL) and thrombin receptor activator for peptide 6 (TRAP-6) as agonists. Antibodies against GPIIb-IIIa activation epitope (PAC1), P-selectin (CD62P) and lysosome-associated membrane glycoprotein 3 (LAMP3; CD63) were used as platelet activation markers. Sixty-six patients referred to the coagulation unit for bleeding symptoms were included in this single-center observational study. Platelet activation was determined by PACT and LTA. The results of both methods were correlated to BAT score. Results A two-by-two analysis using Cohen’s kappa analysis gave moderate agreement between LTA and PACT (82%, kappa = 0.57), when PACT analysis with ADP and CRP-XL was compared to LTA. Using LTA as reference method, positive predictive value was 70% and negative predictive value was 87%. A substantial number of patients had high BAT score and normal LTA and PACT results. Patients with abnormal LTA or PACT results had higher BAT score than patients with normal results, but the difference was not significant. Conclusions The performance in microtiter plates simplified the PACT method and enabled analysis of more patients at the same time. Our results indicate that with modification of the current PACT assay, a higher negative predictive value can be obtained. Furthermore, with comparable result to LTA the PACT could be used as a screening assay for inherited platelet disorders.
Small molecule ISRIB suppresses the integrated stress response within a defined window of activation

Significance The integrated stress response (ISR) protects cells from a variety of harmful stressors by temporarily halting protein synthesis. However, chronic ISR activation has pathological consequences and is linked to several neurological disorders. Pharmacological inhibition of chronic ISR activity emerges as a powerful strategy to treat ISR-mediated neurodegeneration but is typically linked to adverse effects due to the ISR’s importance for normal cellular function. Paradoxically, the small-molecule ISR inhibitor ISRIB has promising therapeutic potential in vivo without overt side effects. We demonstrate here that ISRIB inhibits low-level ISR activity, but does not affect strong ISR signaling. We thereby provide a plausible mechanism of how ISRIB counteracts toxic chronic ISR activity, without disturbing the cytoprotective effects of a strong acute ISR. Activation of the integrated stress response (ISR) by a variety of stresses triggers phosphorylation of the α-subunit of translation initiation factor eIF2. P-eIF2α inhibits eIF2B, the guanine nucleotide exchange factor that recycles inactive eIF2•GDP to active eIF2•GTP. eIF2 phosphorylation thereby represses translation. Persistent activation of the ISR has been linked to the development of several neurological disorders, and modulation of the ISR promises new therapeutic strategies. Recently, a small-molecule ISR inhibitor (ISRIB) was identified that rescues translation in the presence of P-eIF2α by facilitating the assembly of more active eIF2B. ISRIB enhances cognitive memory processes and has therapeutic effects in brain-injured mice without displaying overt side effects. While using ISRIB to investigate the ISR in picornavirus-infected cells, we observed that ISRIB rescued translation early in infection when P-eIF2α levels were low, but not late in infection when P-eIF2α levels were high. By treating cells with varying concentrations of poly(I:C) or arsenite to induce the ISR, we provide additional proof that ISRIB is unable to inhibit the ISR when intracellular P-eIF2α concentrations exceed a critical threshold level. Together, our data demonstrate that the effects of pharmacological activation of eIF2B are tuned by P-eIF2α concentration. Thus, ISRIB can mitigate undesirable outcomes of low-level ISR activation that may manifest neurological disease but leaves the cytoprotective effects of acute ISR activation intact. The insensitivity of cells to ISRIB during acute ISR may explain why ISRIB does not cause overt toxic side effects in vivo.
The Effect of Accent Exposure on Children’s Sociolinguistic Evaluation of Peers

Language and accent strongly influence the formation of social groups. By five years of age, children already show strong social preferences for peers who speak their native language with a familiar accent (Kinzler, Shutts, DeJesus, & Spelke, 2009). However, little is known about the factors that modulate the strength and direction of children’s accent-based group preferences. In three experiments, we examine the development of accent-based friendship preferences in children growing up in Toronto, one of the world’s most linguistically and culturally diverse cities. We hypothesized that the speaker’s type of accent and the amount of accent exposure children experienced in their everyday lives would modulate their preferences in a friend selection task. Despite literature suggesting that exposure leads to greater acceptance (Allport, 1954), we find no evidence that routine exposure to different accents leads to greater acceptance of unfamiliarly accented speakers. Children still showed strong preferences for peers who spoke with the locally dominant accent, despite growing up in a linguistically diverse community. However, children’s preference for Canadian-accented in-group members was stronger when they were paired with non native (Korean-accented) speakers compared to when they were paired with regional (British-accented) speakers. We propose that children’s ability to perceptually distinguish between accents may have contributed to this difference. Children showed stronger preferences for in-group members when the difference between accents was easier to perceive. Overall, our findings suggest that although the strength of accent-based social preferences can be modulated by the type of accent, these preferences still persist in the face of significant diversity in children’s accent exposure.
Nutritional Status and Functional Outcomes in Older Adults Admitted to Geriatric Rehabilitations: The SAFARI Study

Abstract Objective: Evidence about the role of nutritional status (NS) on functional outcomes (FO) after rehabilitation in older adults is scarce. Our aim was to analyze the association between NS and FO in older adults admitted to geriatric rehabilitation units. Methods: The Sarcopenia And Function in Aging Rehabilitation (SAFARI) multicenter study enrolled patients aged ≥65 years admitted to geriatric rehabilitation units in Italy and Spain. FO were absolute and relative functional gain (AFG-RFG) in Barthel Index (BI) at 1 and 3 months after admission. The association between NS (Mini Nutritional Assessment–Short Form) and FO was explored using linear regression and mixed models, adjusted for potential confounders. Analyses were then stratified for diagnosis at admission. Results: We included 415 patients (mean age 81.4 years [SD: 7.7]; 67% female; 9.4% malnourished [MN], 42.7% at risk of malnutrition [RM], and 48% well nourished [WN]). Admission diagnoses were hip fracture (39.5%), elective orthopedic surgery (EOS) (29.5%), and stroke (31%). In an adjusted linear mixed model, MN and RM participants had lower BI compared to WN (MN: β: −8.47, p = 0.023; RM: β: −5.22, p = 0.031), and differences between groups remained stable over time. After stratification for admission diagnosis, only MN patients admitted after EOS had worse FO, both at 30 days (AFG: β adjusted: −13.54, p < 0.001; RFG: β: −32, p < 0.001) and 3 months (AFG: β adjusted: −17.79, p < 0.001; RFG: β: −26.77, p = 0.002). Conclusions: In our sample, poor NS is associated with worse BI in older adults admitted to geriatric rehabilitation units; in patients undergoing EOS, MN is associated with worse FO. Our results documented for the first time the importance of assessing nutritional status before EOS.
World's Knowledge Spillovers : Beyond Openness and Growth

Capital goods industries, for example, nuclear reactors, steam and vapour turbines, air or gas compressors, filtering or purifying machinery and apparatus are intrinsically heterogeneous in terms of vintages and the level of technological knowledge embodied in their products. Countries decide to import wide range of varieties from different sources, which has a bearing on their growth rates. The present paper analyses the hypothesis that the types of imported capital goods and the sources of their origin matter for growth. We construct a new index that measures the level of knowledge embodied in a country’s import basket of capital goods. Using the instrumental variable method, we find that the high initial value of this index for the year 1995, leads to high growth rate of per capita income in the subsequent years during 1995~2005, that is, 10 percent increase in the value of the index raises growth rate by 2 to 3 percentage points. This paper looks beyond the simple relationship between trade openness and growth.
DEPARTMENT OF DECISION SCIENCES AND INFORMATION MANAGEMENT (KBI)

Many service systems are characterized by time-var ying demand for service. For instance in an emergency department, patient ar rival ates are usually not constant throughout the day. This arrival process is stochas tic, but nonetheless predictable to some extent (a daily pattern can often be distinguished) . However, this feature can severely complicate the process of determining appropriate s taffing levels throughout the day. In this paper, an overview of available methods for setting staffing levels under timevarying demand for service is given, with the appli cability and appropriateness in the specific context of an emergency department as the main point of interest. An important goal of an emergency department is to strive for pa tient waiting times that are sufficiently low for all patients, independent of t he arrival time, and therefore we particularly emphasize the importance of using perf ormance measures related to waiting times.
Efficacy and safety of nivolumab monotherapy in metastatic urothelial cancer (mUC): Results from the phase I/II CheckMate 032 study.

4501Background: Minimal antitumor activity of existing therapies and the observation of immune dysfunction in bladder cancer have prompted evaluation of immunotherapy in this malignancy. Nivolumab (fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody) monotherapy has shown survival benefit in patients (pts) with melanoma, lung cancer, and renal cell carcinoma. Here, we report efficacy and safety of nivolumab monotherapy in pts with mUC after ≥1 prior line of platinum-based therapy in an open-label, multicenter phase I/II study (NCT01928394). Methods: Pts (unselected by PD-L1 expression status) with mUC received nivolumab 3 mg/kg intravenously every 2 weeks until progression or discontinuation. Primary endpoint was objective response rate (ORR; RECIST 1.1). Other endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of 78 treated pts (median age 65.5 years; range, 31–85), 65.4% had received ≥2 prior therapies. At a me.
Posibilidades de uso de la Realidad Aumentada en la educación inclusiva. Estudio de caso

espanolResumen: La introduccion de la Realidad Aumentada en la esfera educativa es mayor dia a dia debido a la potencialidad que esta herramienta presenta, sin embargo los estudios sobre sus usos en educacion inclusiva son escasos. Este trabajo presenta, a traves de un estudio ex-post-facto, los resultados alcanzados sobre la vinculacion de la realidad aumentada y la educacion inclusiva, a traves de un cuestionario creado ad hoc y empleando una escala de respuesta tipo likert, se ha recogido la opinion de una muestra de N=81 maestros en formacion. El principal resultado ha sido que salvo para discapacitados visuales, es una herramienta factible de ser empleada en la esfera inclusiva y que puede potenciar la brecha digital, ademas de ser necesarios conocimientos informaticos para emplearla EnglishAbstract:The introduction of Augmented Reality in educational sphere is greater day by day because of the potential that this tool haves. In this article we presents, through an ex-post-facto study, the results accomplished about the correlation of the Augmented Reality and inclusive education, through a questionnaire created ad hoc, and used a Likert response scale, has received the opinion of a sample of N=81 pre service teachers. The main results has been that except the visual disabilities, is a tool viable to be used in inclusive sphere and it is a feasible tools to be used in inclusive sphere and can enhance the digital divide, besides being necessary computer skill to used it.
Values of fractional exhaled nitric oxide for cough-variant asthma in children with chronic cough.

Background Chronic cough is a common symptom in children. We wished to explore the value of fractional exhaled nitric oxide (FeNO) for cough-variant asthma (CVA) in children with chronic cough. Methods This prospective cohort study was conducted in the Children's Hospital of Soochow University from January 2012 to December 2014. Children aged 6-14 years with a cough of duration >4 weeks were enrolled. They underwent FeNO measurement, sputum cytology and pulmonary function tests. Results A total of 115 patients and 25 healthy controls were evaluated. For the diagnosis of CVA, the optimal FeNO cutoff value was 25 ppb with a sensitivity of 84.0%, specificity of 97.1%, positive predictive value of 97.5%, and negative predictive of being 81.4%. The FeNO level had a significant correlation with eosinophil count in sputum (P<0.05). FeNO level in CVA was decreased significantly after treatment (P=0.001). Conclusions In children, FeNO measurement might be an excellent method for diagnosing CVA with high sensitivity and specificity.
Uses and safety profile of ciclosporin in ophthalmology

Ciclosporin is a calcineurin inhibitor that acts by primarily inhibiting the action of T cells. Clinical trials in the early 1980s demonstrated that systemic ciclosporin was a promising steroid-sparing agent and was also effective in patients who are refractory to treatment with corticosteroids. However, recent years have witnessed the emergence of safer immunosuppressive agents due to the poor side-effect profile of systemic ciclosporin. Topical ciclosporin, however, has a much improved safety profile and is still used to treat a variety of ocular surface disorders including dry eye syndrome, vernal and atopic keratoconjunctivitis, severe blepharitis and high-risk corneal graft patients. This article reviews the uses and safety profile of systemic and topical ciclosporin in ophthalmology, as well as discussing alternative therapeutic agents available.
L'univers aux grandes échelles : études de l'homogénéité cosmique et de l'énergie noire à partir des relevés de quasars BOSS et eBOSS

Ce travail de these se separe en deux volets. Le premier volet concerne l'etude de l'homogeneite de l'univers, et le second une mesure de l'echelle BAO, qui constitue une regle standard permettant de mesurer l'evolution du taux d'expansion de l'univers. Ces deux analyses reposent sur l'etude de la structuration (ou clustering) des quasars des releves BOSS et eBOSS, qui couvrent la gamme en redshift 0,9 < z < 2,8. Les mesures des observables caracterisant la structuration de l'univers aux grandes echelles sont tres sensibles aux effets systematiques, nous avons donc etudies ces effets en profondeur. Nous avons mis en evidence que les selections de cibles quasars BOSS et eBOSS ne sont pas parfaitement homogenes, et corrige cet effet. Au final, la mesure de la fonction de correlation des quasars nous a permis de mesurer le biais des quasars sur la gamme en redshift 0,9 < z < 2,8. Nous obtenons la mesure actuelle la plus precise du biais, b = 3,85 ± 0,11 dans la gamme 2,2 < z < 2,8 pour le releve BOSS, et b = 2,44 ± 0,04 dans la gamme 0,9 < z < 2,2 pour le releve eBOSS. Le Principe Cosmologique stipule que notre univers est isotrope et homogene a grande echelle. Il s'agit d'un des postulats de base de la cosmologie moderne. En etudiant la structuration a tres grande echelle des quasars, nous avons prouve l'isotropie spatiale de l'univers dans la gamme 0,9 < z < 2,8, independamment de toute hypothese et cosmologie fiducielle. L'isotropie spatiale stipule que l'univers est isotrope dans chaque couche de redshift. En la combinant au principe de Copernic, qui stipule que nous ne nous situons pas a une position particuliere dans l'univers, permet de prouver que notre univers est homogene aux grandes echelles. Nous avons effectue une mesure de la dimension de correlation fractale de l'univers, D₂(r), en utilisant un nouvel estimateur, inspire de l'estimateur de Landy-Szalay pour la fonction de correlation. En corrigeant notre estimateur du biais des quasars, nous avons mesure (3 - D₂(r)) = (6,0 ± 2,1) x 10⁻⁵ entre 250 h⁻¹ Mpc et 1200 h⁻¹ Mpc pour le releve eBOSS, dans la gamme 0,9 < z < 2,2. Pour le releve BOSS, nous obtenons (3 - D₂(r)) = (3,9 ± 2,1) x 10⁻⁵, dans la gamme 2,2 < z < 2,8. De plus, nous montrons que le modele Lambda-CDM decrit tres bien la transition d'un regime structure vers un regime homogene. D’autre part, nous avons mesure la position du pic BAO dans les fonctions de correlation des quasars BOSS et eBOSS, detecte a 2,5 sigma dans les deux releves. Si nous mesurons le parametre α, qui correspond au rapport entre la position du pic mesure et la position predite par une cosmologie fiducielle (en utilisant les parametres Planck 2013), nous mesurons α = 1,074 pour le releve BOSS, et α = 1,009 pour le releve eBOSS. Ces mesures, combinees uniquement a la mesure locale de H₀, nous permettent de contraindre l'espace des parametres de modeles au-dela du Lambda-CDM.
Guide to Blended Learning

The Guide to Blended Learning is an introduction using technology and distance education teaching strategies with traditional, face-to-face classroom activities. This Guide has been designed to assist teachers adopt blended learning strategies through a step-by-step approach taking constructivist and design-based approach and reflecting on decisions taken to provide authentic learning experience in their own contexts. It provides a general discussion of types of blended learning in reference to the level of education, the needs of the students, and the subject being taught. This discussion and associated activities also review pedagogy, materials, and technology usage. Divided into eight chapters, each of these provide an overview video that triggers learning events for the teachers to focus and work on implementing blending learning.
Visual Analogy, Visual Displays, and the Nature of Design Problems: The Effect of Expertise

Analogy is a powerful heuristic for problem solving. In design, where designers are constantly exposed to visual stimuli, visual analogies are considered to be particularly helpful. To date, however, few researchers have given enough attention to visual analogy and visual displays in design contexts. This study deals with the use of these tools by investigating the effect that expertise has on them, in ill-defined and well-defined problem solving. Novice and experienced designers solved both types of design problem with exposure to visual displays and with the requirement to use visual analogy. Results showed that when visual displays and instructions to use analogy were available no expertise differences existed in well-defined problem solving. However, with the availability of only visual displays, architects tend to perform better than students. Without guidance to use analogy, students found difficulty in spontaneous recall of visual displays as candidate analogues in well-defined problems. In ill-defined problem solving, architects performed better than novice students in the use of both analogy and visual displays. However, no differences were found between the experienced designers and the advanced students in any experimental condition in this problem context.