Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort: The PESA (Progression of Early Subclinical Atherosclerosis) Study

Background— Data are limited on the presence, distribution, and extent of subclinical atherosclerosis in middle-aged populations. Methods and Results— The PESA (Progression of Early Subclinical Atherosclerosis) study prospectively enrolled 4184 asymptomatic participants 40 to 54 years of age (mean age, 45.8 years; 63% male) to evaluate the systemic extent of atherosclerosis in the carotid, abdominal aortic, and iliofemoral territories by 2-/3-dimensional ultrasound and coronary artery calcification by computed tomography. The extent of subclinical atherosclerosis, defined as presence of plaque or coronary artery calcification ≥1, was classified as focal (1 site affected), intermediate (2–3 sites), or generalized (4–6 sites) after exploration of each vascular site (right/left carotids, aorta, right/left iliofemorals, and coronary arteries). Subclinical atherosclerosis was present in 63% of participants (71% of men, 48% of women). Intermediate and generalized atherosclerosis was identified in 41%. Plaques were most common in the iliofemorals (44%), followed by the carotids (31%) and aorta (25%), whereas coronary artery calcification was present in 18%. Among participants with low Framingham Heart Study (FHS) 10-year risk, subclinical disease was detected in 58%, with intermediate or generalized disease in 36%. When longer-term risk was assessed (30-year FHS), 83% of participants at high risk had atherosclerosis, with 66% classified as intermediate or generalized. Conclusions— Subclinical atherosclerosis was highly prevalent in this middle-aged cohort, with nearly half of the participants classified as having intermediate or generalized disease. Most participants at high FHS risk had subclinical disease; however, extensive atherosclerosis was also present in a substantial number of low-risk individuals, suggesting added value of imaging for diagnosis and prevention. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT01410318.
Immunoglobulin switch transcript production in vivo related to the site and time of antigen-specific B cell activation

Immunoglobulin (Ig) class switch recombination is associated with the production and splicing of germline IgCH messenger RNA transcripts. Levels of gamma 1 transcripts in mouse spleen sections were assessed by semiquantitative analysis of reverse transcriptase polymerase chain reaction (PCR) products during primary and secondary antibody responses to chicken gamma globulin (CGG). This was correlated with the appearance of CGG-specific B cells and their growth and differentiation to plasma cells. After primary immunization with CGG, gamma 1 switch transcripts appeared after 4 d, peaked at a median of six times starting levels between 10 and 18 d after immunization, and returned to background levels before secondary immunization at 5 wk. By contrast, after secondary challenge with CGG, a sevenfold increase in transcripts occurs during the first d. The level again doubles by day 3, when it is six times that which is seen at the peak of the primary response. After day 4, there was a gradual decline over the next 2-3 wk. Within 12 h of secondary immunization, antigen-specific memory B cells appeared in the outer I zone and by 24 h entered S phase, presumably as a result of cognate interaction with primed T cells. Over the next few hours, they migrated to the edge of the red pulp, where they grew exponentially until the fourth day, when they synchronously differentiated to become plasma cells. The same pattern was seen for the migration, growth, and differentiation of virgin hapten-specific B cells when CGG-primed mice were challenged with hapten protein. The continued production of transcripts after day 3 indicates that switching also occurs in germinal centers, but in a relatively small proportion of their B cells. The impressive early production of switch transcripts during T cell-dependent antibody responses occurs in cells that are about to undergo massive clonal expansion. It is argued that Ig class switching at this time, which is associated with cognate T cell-B cell interaction in the T zone, has a major impact on the class and subclasses of Ig produced during the response.
Developing a medical school: Expansion of medical student capacity in new locations: AMEE Guide No. 55

Background: A concern about an impending shortage of physicians and a worry about the continued maldistribution of physicians to medically underserved areas have encouraged the expansion of medical school training places in many countries, either by the creation of new medical schools or by the creation of regional campuses. Aims: In this Guide, the authors, who have helped create new regional campuses and medical schools in Australia, Canada, UK, USA, and Thailand share their experiences, triumphs, and tribulations, both from the views of the regional campus and from the views of the main Medical School campus. While this Guide is written from the perspective of building new regional campuses of existing medical schools, many of the lessons are applicable to new medical schools in any country of the world. Many countries in all regions of the world are facing rapid expansion of medical training facilities and we hope this Guide provides ideas to all who are contemplating or engaged in expanding medical school training places, no matter where they are. Description: This Guide comprises four sections: planning; getting going; pitfalls to avoid; and maturing and sustaining beyond the first years. While the context of expanding medical schools may vary in terms of infrastructure, resources, and access to technology, many themes, such as developing local support, recruiting local and academic faculty, building relationships, and managing change and conflict in rapidly changing environments are universal themes facing every medical academic development no matter where it is geographically situated. Further information: The full AMEE Guide, printed separately, in addition contains case examples from the authors’ experiences of successes and challenges they have faced.
How to Grow a Mind: Statistics, Structure, and Abstraction

In coming to understand the world—in learning concepts, acquiring language, and grasping causal relations—our minds make inferences that appear to go far beyond the data available. How do we do it? This review describes recent approaches to reverse-engineering human learning and cognitive development and, in parallel, engineering more humanlike machine learning systems. Computational models that perform probabilistic inference over hierarchies of flexibly structured representations can address some of the deepest questions about the nature and origins of human thought: How does abstract knowledge guide learning and reasoning from sparse data? What forms does our knowledge take, across different domains and tasks? And how is that abstract knowledge itself acquired?
Comparison of Glutathione, Cysteine, and Their Redox Potentials in the Plasma of Critically Ill and Healthy Children

Background Oxidative stress is known to play a role in critical illness due to an imbalance in reactive oxygen species and reactive nitrogen species, and the body’s ability to detoxify pro-oxidants using small molecule anti-oxidants and anti-oxidant enzymes. Objective To compare the concentrations of plasma redox metabolites and redox potentials for the Cys/CySS and GSH/GSSG thiol/disulfide pairs in critically ill children with healthy control children. Methods We performed a prospective clinical observational study of children ages ≤18 years and weight ≥6 kg, who were hospitalized between January 2010 and April 2012 in a 30-bed multidisciplinary medical-surgical pediatric intensive care unit (PICU). We measured the plasma concentrations of Cys, CySS, GSH, and GSSG within the first 24 h of PICU arrival, and we calculated the redox potential for the Cys/CySS (Eh Cys/CySS) and GSH/GSSG (Eh GSH/GSSG) thiol/disulfide pairs in the plasma of 61 critically ill children and 16 healthy control children. Results Critically ill children have less Cys (p = 0.009), less CySS (p = 0.011), less Total Cys ([Cys] + 2[CySS], p = 0.01), more GSSG (p < 0.001), and more oxidized Eh GSH/GSSG (p < 0.001) compared to healthy children. Conclusion Our results demonstrate that in the presence of pediatric critical illness, the Total Cys/CySS thiol pool decreases while GSH is likely one component of the cellular redox system that reduces CySS back to Cys, thus maintaining Eh Cys/CySS. The Total Cys pool is more abundant than the Total GSH pool in the plasma of children. Further investigation is needed to elucidate the differences in redox potentials in subgroups of critically ill children, and to determine whether differences in redox metabolite concentrations and redox potentials correlate with severity of critical illness and clinical outcomes.
Chronic Nicotine Exposure Initiated in Adolescence and Unpaired to Behavioral Context Fails to Enhance Sweetened Ethanol Seeking

Nicotine use in adolescence is pervasive in the United States and, according to the Gateway Hypothesis, may lead to progression towards other addictive substances. Given the prevalence of nicotine and ethanol comorbidity, it is difficult to ascertain if nicotine is a gateway drug for ethanol. Our study investigated the relationship between adolescent exposure to nicotine and whether this exposure alters subsequent alcohol seeking behavior. We hypothesized that rats exposed to nicotine beginning in adolescence would exhibit greater alcohol seeking behavior than non-exposed siblings. To test our hypothesis, beginning at P28, female rats were initially exposed to once daily nicotine (0.4 mg/kg, SC) or saline for 5 days. Following these five initial injections, animals were trained to nose-poke for sucrose reinforcement (10%, w/v), gradually increasing to sweetened ethanol (10% sucrose; 10% ethanol, w/v) on an FR5 reinforcement schedule. Nicotine injections were administered after the behavioral sessions to minimize acute effects of nicotine on operant self-administration. We measured the effects of nicotine exposure on the following aspects of ethanol seeking: self-administration, naltrexone (NTX)-induced decreases, habit-directed behavior, motivation, extinction and reinstatement. Nicotine exposure did not alter self-administration or the effectiveness of NTX to reduce alcohol seeking. Nicotine exposure blocked habit-directed ethanol seeking. Finally, nicotine did not alter extinction learning or cue-induced reinstatement to sweetened ethanol seeking. Our findings suggest that nicotine exposure outside the behavioral context does not escalate ethanol seeking. Further, the Gateway Hypothesis likely applies to scenarios in which nicotine is either self-administered or physiologically active during the behavioral session.
Prognostic Significance of Elevated Cardiac Troponin in Acute Gastrointestinal Bleeding

Background Acute gastrointestinal bleeding (AGIB) is responsible for over 140,000 hospitalizations annually. Cardiovascular-related deaths account for 30% of the patients surviving the initial episode of AGIB. The purpose of this study was to identify the impact of elevated troponin on short-term mortality and length of stay (LOS) of these patients. Methods From July 2013 to July 2016, 290 patients admitted with a diagnosis of AGIB and who had cardiac troponin I measured within 24 h of presentation were retrospectively reviewed. Clinical variables including 30-day mortality, 30-day readmission and LOS were then compared between the groups of troponin elevation and no troponin elevation. Results The overall 30-day mortality among patients with AGIB was 6.5% (19/290). Cardiac troponin was elevated in 10% of patients (29/290). Among patients with normal troponin, 5% (13/261) died within 30 days. In patients with troponin elevation, 21% died in the same period (6/29, P = 0.001). The LOS was also higher in patients with troponin elevation (6 vs. 5 days, P = 0.02). There was no difference in 30-day readmission among the two groups. Past history of coronary artery disease, congestive heart failure, hypertension, aspirin use and elevated creatinine was more common in patients with troponin elevation. On multivariate analysis, troponin elevation on presentation is associated with increased mortality (odds: 5.50, CI: 1.73 - 17.47, P = 0.004). Conclusion In patients admitted to the inpatient service with AGIB, elevated troponin I on presentation is associated with high short-term mortality and longer hospital stay.
Somatosensory function in speech perception

Somatosensory signals from the facial skin and muscles of the vocal tract provide a rich source of sensory input in speech production. We show here that the somatosensory system is also involved in the perception of speech. We use a robotic device to create patterns of facial skin deformation that would normally accompany speech production. We find that when we stretch the facial skin while people listen to words, it alters the sounds they hear. The systematic perceptual variation we observe in conjunction with speech-like patterns of skin stretch indicates that somatosensory inputs affect the neural processing of speech sounds and shows the involvement of the somatosensory system in the perceptual processing in speech.
Prebiotics in Chronic Intestinal Inflammation

&NA; Prebiotics are nondigestible fermentable fibers that are reported to have health benefits for the host. Older as well as more recent studies show beneficial effects in experimental colitis and lately also in human inflammatory bowel diseases (IBD), such as Crohn's disease, ulcerative colitis, and chronic pouchitis. In this review we give an overview of the benefits of prebiotics in rodent IBD models and in IBD patients and discuss their possible protective mechanisms. Commensal intestinal bacteria induce and perpetuate chronic intestinal inflammation, whereas others are protective. However, most of the current medications are directed against the exaggerated proinflammatory immune response of the host, some of them toxic and costly. Feeding prebiotics changes the composition of the intestinal microflora toward more protective intestinal bacteria and alters systemic and mucosal immune responses of the host. Therapy for IBD targeting intestinal bacteria and their function is just emerging. Prebiotics have the promise to be relatively safe, inexpensive, and easy to administer. Unraveling their protective mechanisms will help to develop rational applications of prebiotics. However, the initial promising results with dietary prebiotics in preclinical trials as well as small studies in human IBD will need to be confirmed in large randomized controlled clinical trials.
A Transplantation Assay for Mouse Cells Responsive to Antigenic Stimulation by Sheep Erythrocytes.∗

Summary When cell suspensions containing normal mouse spleen or lymph node cells mixed with sheep erythrocytes are injected into heavily-irradiated mice, foci of hemolysin-producing cells are formed in the spleens of the recipients. A method is described for demonstration of these foci, and evidence is presented that they result from the proliferation of antigen-sensitive precursors of hemolysin-producing cells. The demonstration of the existence of “antigen-sensitive” cells provides strong support for the view that cell proliferation is involved in the generation of hemolysin-producing cells.
Query-specific visual semantic spaces for web image re-ranking

Image re-ranking, as an effective way to improve the results of web-based image search, has been adopted by current commercial search engines. Given a query keyword, a pool of images are first retrieved by the search engine based on textual information. By asking the user to select a query image from the pool, the remaining images are re-ranked based on their visual similarities with the query image. A major challenge is that the similarities of visual features do not well correlate with images' semantic meanings which interpret users' search intention. On the other hand, learning a universal visual semantic space to characterize highly diverse images from the web is difficult and inefficient. In this paper, we propose a novel image re-ranking framework, which automatically offline learns different visual semantic spaces for different query keywords through keyword expansions. The visual features of images are projected into their related visual semantic spaces to get semantic signatures. At the online stage, images are re-ranked by comparing their semantic signatures obtained from the visual semantic space specified by the query keyword. The new approach significantly improves both the accuracy and efficiency of image re-ranking. The original visual features of thousands of dimensions can be projected to the semantic signatures as short as 25 dimensions. Experimental results show that 20% – 35% relative improvement has been achieved on re-ranking precisions compared with the state-of-the-art methods.
Bayesian methods of analysis for cluster randomized trials with binary outcome data.

We explore the potential of Bayesian hierarchical modelling for the analysis of cluster randomized trials with binary outcome data, and apply the methods to a trial randomized by general practice. An approximate relationship is derived between the intracluster correlation coefficient (ICC) and the between-cluster variance used in a hierarchical logistic regression model. By constructing an informative prior for the ICC on the basis of available information, we are thus able implicitly to specify an informative prior for the between-cluster variance. The approach also provides us with a credible interval for the ICC for binary outcome data. Several approaches to constructing informative priors from empirical ICC values are described. We investigate the sensitivity of results to the prior specified and find that the estimate of intervention effect changes very little in this data set, while its interval estimate is more sensitive. The Bayesian approach allows us to assume distributions other than normality for the random effects used to model the clustering. This enables us to gain insight into the robustness of our parameter estimates to the classical normality assumption. In a model with a more complex variance structure, Bayesian methods can provide credible intervals for a difference between two variance components, in order for example to investigate whether the effect of intervention varies across clusters. We compare our results with those obtained from classical estimation, discuss the relative merits of the Bayesian framework, and conclude that the flexibility of the Bayesian approach offers some substantial advantages, although selection of prior distributions is not straightforward.
High Frequency of a Single Nucleotide Substitution (c.-6-180T>G) of the Canine MDR1/ABCB1 Gene Associated with Phenobarbital-Resistant Idiopathic Epilepsy in Border Collie Dogs

A single nucleotide substitution (c.-6-180T>G) associated with resistance to phenobarbital therapy has been found in the canine MDR1/ABCB1 gene in Border Collies with idiopathic epilepsy. In the present study, a PCR-restriction fragment length polymorphism assay was developed for genotyping this mutation, and a genotyping survey was carried out in a population of 472 Border Collies in Japan to determine the current allele frequency. The survey demonstrated the frequencies of the T/T wild type, T/G heterozygote, and G/G mutant homozygote to be 60.0%, 30.3%, and 9.8%, respectively, indicating that the frequency of the mutant G allele is extremely high (24.9%) in Border Collies. The results suggest that this high mutation frequency of the mutation is likely to cause a high prevalence of phenobarbital-resistant epilepsy in Border Collies.
Experimental study on the feasibility of in-beam PET for accurate monitoring of proton therapy

Positron emission tomography (PET) is currently the only feasible method for in-situ and noninvasive three-dimensional monitoring of the precision of the treatment in highly conformal ion therapy. Its positive clinical impact has been proven for fractionated carbon ion therapy of head and neck (H&N) tumors at the experimental facility at the Gesellschaft fur Schwerionenforschung (GSI), Darmstadt, Germany. Following previous promising experiments, the possible extension of the method to the monitoring of proton therapy has been investigated further in extensive in-beam measurements at GSI. Millimeter accuracy for verification of the lateral field position and for the most challenging issue of range monitoring has been demonstrated in monoenergetic and spread-out Bragg-peak (SOBP) proton irradiation of polymethyl methacrylate (PMMA) targets. The irradiation of an inhomogeneous phantom with tissue equivalent inserts in combination with further dynamic analysis has supported the extension of such millimeter precision to real clinical cases, at least in regions of interest for low perfused tissues. All the experimental investigations have been reproduced by the developed modeling rather well. This indicates the possible extraction of valuable clinical information as particle range in-vivo, irradiation field position, and even local deviations from the dose prescription on the basis of the comparison between measured and predicted activity distributions. Hence, the clinical feasibility of in-beam PET for proton therapy monitoring is strongly supported.
Pattern of discharge of respiratory neurons during systemic vasomotor waves.

CHERNIACK, NEIL S. , NORMAN H. EDELMAN, AND ALFRED P. FISHMAN. Pattern of discharge of respiratory neurons during systemic vasomotor waves. Am. J. Physiol. 217(5) : 1375-l 383. 1969.Systemic blood pressure oscillations, produced in paralyzed dogs by arresting ventilation or by hemorrhage during mechanical ventilation, were related to the phasic phrenic nerve electrical activity. Oscillations synchronous with each burst of phrenic nerve activity (“Traube-Hering” waves) occurred in hemorrhaged animals and during arrested ventilation. Oscillations unrelated to the frequency of the phrenic nerve bursts (“Mayer” waves) occurred only after hemorrhage. The integrated activity of each phrenic nerve burst was less and the bursts were more frequent during Mayer waves than during Traube-Hering waves. Neither wave pattern was abolished by carotid chemoand baroreceptor denervation. Maneuvers (vagotomy or arrested ventilation) which slowed the bursts of phrenic nerve activity and increased the electrical activity of each burst converted Mayer to Traube-Hering waves. The reverse changes in phrenic nerve activity and rate (produced by raising body temperature) changed Traube-Hering to Mayer waves. Traube-Hering waves seem to be caused by a direct influence of the phasic activity of respiratory neurons on vasomotor activity. This phasic activity can prevent Mayer waves.
Instruction set definition and instruction selection for ASIPs

Application Specific Instruction set Processors (ASIPs) are field or mask programmable processors of which the architecture and instruction set are optimised to a specific application domain. ASIPs offer a high degree of flexibility and are therefore increasingly being used in competitive markets like telecommunications. However, adequate CAD techniques for the design and programming of ASIPs are missing hitherto. An interactive approach for the definition of optimised microinstruction sets of ASIPs is presented. A second issue is a method for instruction selection when generating code for a predefined ASIP. A combined instruction set and data-path model is generated, onto which the application is mapped. <<ETX>>