Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke: Results of the MERCI Trial

Background and Purpose— The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA. Methods— We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients. Results— Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (P<0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score ≤2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Conclusions— A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.
Modeling Electrophysiological Coupling and Fusion between Human Mesenchymal Stem Cells and Cardiomyocytes

Human mesenchymal stem cell (hMSC) delivery has demonstrated promise in preclinical and clinical trials for myocardial infarction therapy; however, broad acceptance is hindered by limited understanding of hMSC-human cardiomyocyte (hCM) interactions. To better understand the electrophysiological consequences of direct heterocellular connections between hMSCs and hCMs, three original mathematical models were developed, representing an experimentally verified triad of hMSC families with distinct functional ion channel currents. The arrhythmogenic risk of such direct electrical interactions in the setting of healthy adult myocardium was predicted by coupling and fusing these hMSC models to the published ten Tusscher midcardial hCM model. Substantial variations in action potential waveform—such as decreased action potential duration (APD) and plateau height—were found when hCMs were coupled to the two hMSC models expressing functional delayed rectifier-like human ether à-go-go K+ channel 1 (hEAG1); the effects were exacerbated for fused hMSC-hCM hybrid cells. The third family of hMSCs (Type C), absent of hEAG1 activity, led to smaller single-cell action potential alterations during coupling and fusion, translating to longer tissue-level mean action potential wavelength. In a simulated 2-D monolayer of cardiac tissue, re-entry vulnerability with low (5%) hMSC insertion was approximately eight-fold lower with Type C hMSCs compared to hEAG1-functional hMSCs. A 20% decrease in APD dispersion by Type C hMSCs compared to hEAG1-active hMSCs supports the claim of reduced arrhythmogenic potential of this cell type with low hMSC insertion. However, at moderate (15%) and high (25%) hMSC insertion, the vulnerable window increased independent of hMSC type. In summary, this study provides novel electrophysiological models of hMSCs, predicts possible arrhythmogenic effects of hMSCs when directly coupled to healthy hCMs, and proposes that isolating a subset of hMSCs absent of hEAG1 activity may offer increased safety as a cell delivery cardiotherapy at low levels of hMSC-hCM coupling.
Acoustics and Articulation of Medial versus Final Coronal Stop Gemination Contrasts in Moroccan Arabic

This paper presents results of a simultaneous acoustic and articulatory investigation of word-medial and word-final geminate/singleton coronal stop contrasts in Moroccan Arabic (MA). The acoustic analysis revealed that, only for the wordmedial contrast, the two MA speakers adopted comparable strategies in contrasting geminates with singletons, mainly by significantly lengthening closure duration in geminates, relative to singletons. In word-final position, two speakerspecific contrasting patterns emerged. While one speaker also lengthened the closure duration for final geminates, the other speaker instead lengthened only the release duration for final geminates, relative to singletons. Consonant closure and preceding vowel were significantly longer for the geminate only in medial position, not in final position. These temporal differences were even more clearly delineated in the articulatory signal, captured via ultrasound, to which we applied the novel approach of using TRACTUS [Temporally Resolved Articulatory Configuration Tracking of UltraSound: 15] to index temporal properties of closure gestures for these geminate/singleton contrasts.
Predicting species establishment using absent species and functional neighborhoods

Abstract Species establishment within a community depends on their interactions with the local environment and resident community. Such environmental and biotic filtering is frequently inferred from functional trait and phylogenetic patterns within communities; these patterns may also predict which additional species can establish. However, differentiating between environmental and biotic filtering can be challenging, which may complicate establishment predictions. Creating a habitat‐specific species pool by identifying which absent species within the region can establish in the focal habitat allows us to isolate biotic filtering by modeling dissimilarity between the observed and biotically excluded species able to pass environmental filters. Similarly, modeling the dissimilarity between the habitat‐specific species pool and the environmentally excluded species within the region can isolate local environmental filters. Combined, these models identify potentially successful phenotypes and why certain phenotypes were unsuccessful. Here, we present a framework that uses the functional dissimilarity among these groups in logistic models to predict establishment of additional species. This approach can use multivariate trait distances and phylogenetic information, but is most powerful when using individual traits and their interactions. It also requires an appropriate distance‐based dissimilarity measure, yet the two most commonly used indices, nearest neighbor (one species) and mean pairwise (all species) distances, may inaccurately predict establishment. By iteratively increasing the number of species used to measure dissimilarity, a functional neighborhood can be chosen that maximizes the detection of underlying trait patterns. We tested this framework using two seed addition experiments in calcareous grasslands. Although the functional neighborhood size that best fits the community's trait structure depended on the type of filtering considered, selecting these functional neighborhood sizes allowed our framework to predict up to 50% of the variation in actual establishment from seed. These results indicate that the proposed framework may be a powerful tool for studying and predicting species establishment.
The Impact of Market Rules and Market Structure on the Price Determination Process in the England and Wales Electricity Market

This paper argues that the market rules governing the operation of the England and Wales electricity market in combination with the structure of this market presents the two major generators National Power and PowerGen with opportunities to earn revenues substantially in excess of their costs of production for short periods of time. Generators competing to serve this market have two strategic weapons at their disposal: (1) the price bid for each generation set and (2) the capacity of each generation set made available to supply the market each half-hour period during the day. We argue that because of the rules governing the price determination process in this market, by the strategic use of capacity availability declarations, when conditions exogenous to the behavior of the two major generators favor it, these two generators are able to obtain prices for their output substantially in excess of their marginal costs of generation. The paper establishes these points in the following manner. First, we provide a description of the market structure and rules governing the operation of the England and Wales electricity market, emphasizing those aspects that are important to the success of the strategy we believe the two generators use to exercise market power. We then summarize the time series properties of the price of electricity emerging from this market structure and price-setting process. By analyzing four fiscal years of actual market prices, quantities and generator bids into the market, we provide various pieces of evidence in favor of the strategic use of the market rules by the two major participants. The paper closes with a discussion of the lessons that the England and Wales experience can provide for the design of competitive power markets in the US, particularly California, and other countries.
Cefazolin, a new semisynthetic cephalosporin antibiotic. II. In vitro and in vivo antimicrobial activity.

Cefazolin is a new antibiotic derived from 7-aminocephalosporanic acid, having the structure of 7-[l-(lH)-tetrazolylacetamido]-3-[2-(5-methyl-l,3,4thiadiazolyl)-thiomethyl]-^/3-cephem-4-carboxylic acid. This substance is a broad-spectrum antibiotic, active in vitro against most of Gram-positive and Gram-negative species of bacteria except for Ps. aeruginosa, and is also active against penicillinase-producing strains of Staph. aureus. The activity of cefazolin against fresh isolates of E. coli and Kl. pneumoniae seems superior to those of other antibiotics used in this study. The in vitro activity of cefazolin is little influenced by size of inoculum, presence of rabbit serum, or kinds or properties of test medium. The activity of cefazolin is apparently bactericidal against both Gram-positive and Gram-negative bacteria at or above the MIC levels. In experiments on the development of resistance in vitro, the MICs of cefazolin against Staph. aureus strain 209P and E. coli strain NIHJ increase slowly in a stepwise over a period of 17 transfers. The rate of resistance development of cefazolin is comparable with that of cepholoridine or ampicillin. Cefazolin is relatively stable to enzymes from Staph. aureus and E. coli, which readily inactivate ampicillin and benzyl penicillin. Cefazolin is not remarkably degraded by the tissue homogenates of rat, although cephalothin is degraded quite rapidly. Cefazolin, in the single subcutaneous dose, shows excellent protecting activity against experimental infections in mice infected with both PC-sensitive and resistant strains of Staph. aureus, and is also fairly effective against infections in mice with Diplococcus pneumoniae, E. coli and Proteus mirabilis.
Control of rheumatoid arthritis by oral tolerance.

OBJECTIVE Previous randomized controlled trials for treatment of rheumatoid arthritis (RA) with acid-soluble chicken and bovine type II collagen (CII) have produced conflicting results. This randomized, double-blind, controlled trial examined the therapeutic effect of bovine CII tablets in RA. METHODS CII tablets were prepared by adsorption onto a lactose base. Patients with a duration of RA of > or = 2 years and who had failed treatment with at least 1 slow-acting drug were recruited, provided that they had active arthritis. Patients were randomly assigned to receive either 0.05 mg, 0.5 mg, or 5 mg of CII or placebo daily for 6 months. All slow-acting drugs were stopped at least 4 weeks before starting CII, although prednisolone was permitted at dosages < 10 mg/day. Clinical assessments were performed at screening and at 0, 1, 4, 8, 12, 16, 20, and 24 weeks of treatment. RESULTS Fifty-five patients were recruited. Initially, there were no significant differences in mean Disease Activity Scores between groups. At 24 weeks, there was a significant difference (P = 0.041, by Kruskal-Wallis analysis of variance); the major components of this difference were attributable to relatively large decreases in the 0.5 mg CII group (19% of initial values) and to minimal decreases in patients receiving placebo (3% of initial values). Twenty patients had American College of Rheumatology 20% responses; 11 of these were in the 0.5 mg CII group and 3 were in each of the other groups, a significant difference (chi2 = 14.6, P = 0.002). There was no significant difference in any clinical measure between the placebo, 0.05 mg CII, and 5 mg CII groups. There were no side effects associated with CII treatment. CONCLUSION Treatment with 0.5 mg/day of bovine CII is well tolerated and produces small, but significant, disease improvement in RA. However, the therapeutic window is narrow. The difference between our results and those of other trials may relate to the dose, species, and formulation of the CII.
Hepatitis B vaccine alone or with hepatitis B immunoglobulin in neonates of HBsAg+/HBeAg- mothers: a systematic review and meta-analysis.

OBJECTIVES The cost-effectiveness of augmenting immunization against hepatitis B infection with hepatitis B immunoglobulin (HBIG) remains controversial, particularly for the subpopulation of babies of HBsAg+/HBeAg- mothers that are considered as low-infective. We aimed to evaluate the effectiveness of vaccine alone compared with vaccine plus HBIG for the immunization of babies of HBsAg+/HBeAg- mothers. METHODS We searched PubMed, Scopus and Cochrane Central Register of Controlled Trials databases to identify studies comparing the effectiveness of combined immunization (vaccine plus HBIG) with vaccine alone in neonates of HBsAg+/HBeAg- mothers. A systematic review and meta-analysis of eligible studies was performed. RESULTS A total of nine eligible studies were identified (four randomized controlled trials). No difference was found regarding the primary outcome of our meta-analysis, namely occurrence of hepatitis B infection, between neonates who received vaccine only, compared with those who received both vaccine and HBIG (four studies, 3426 patients, OR=0.82, 95% CI=0.41-1.64). This finding was consistent with regards to seroprotection rate (four studies, 1323 patients, OR=1.24, 95% CI=0.97-1.58). Safety data were not reported in the included studies. CONCLUSIONS The available limited published evidence suggests that vaccine alone seems to be equally effective to the combination of HBIG and hepatitis B vaccine for neonates of HBsAg+/HBeAg- mothers in preventing infection. Further studies are needed in order to clarify the potential benefit of combined immunization to this specific subgroup of patients.
Uphill and Downhill in a Flat World: The Conceptual Topography of the Yupno House

Speakers of many languages around the world rely on body-based contrasts (e.g., left/right) for spatial communication and cognition. Speakers of Yupno, a language of Papua New Guinea's mountainous interior, rely instead on an environment-based uphill/downhill contrast. Body-based contrasts are as easy to use indoors as outdoors, but environment-based contrasts may not be. Do Yupno speakers still use uphill/downhill contrasts indoors and, if so, how? We report three studies on spatial communication within the Yupno house. Even in this flat world, uphill/downhill contrasts are pervasive. However, the terms are not used according to the slopes beyond the house's walls, as reported in other groups. Instead, the house is treated as a microworld, with a "conceptual topography" that is strikingly reminiscent of the physical topography of the Yupno valley. The phenomenon illustrates some of the distinctive properties of environment-based reference systems, as well as the universal power and plasticity of spatial contrasts.
New phase-vocoder techniques for pitch-shifting, harmonizing and other exotic effects

The phase-vocoder is usually presented as a high-quality solution for time-scale modification of signals, pitch-scale modifications usually being implemented as a combination of timescaling and sampling rate conversion. We present two new phase-vocoder-based techniques which allow direct manipulation of the signal in the frequency-domain, enabling such applications as pitch-shifting, chorusing, harmonizing, partial stretching and other exotic modifications which cannot be achieved by the standard time-scale sampling-rate conversion scheme. The new techniques are based on a very simple peak-detection stage, followed by a peak-shifting stage. The very simplest one allows for 50% overlap but restricts the precision of the modifications, while the most flexible techniques requires a more expensive 75% overlap.
Indicators of the appropriateness of long-term prescribing in general practice in the United Kingdom: consensus development, face and content validity, feasibility, and reliability.

OBJECTIVES: To develop valid, reliable indicators of the appropriateness of long-term prescribing in general practice medical records in the United Kingdom. DESIGN: A nominal group was used to identify potential indicators of appropriateness of prescribing. Their face and content validity were subsequently assessed in a two round Delphi exercise. Feasibility and reliability between raters were evaluated for the indicators for which consensus was reached and were suitable for application. PARTICIPANTS: The nominal group comprised a disciplinary mix of nine opinion leaders and prominent academics in the field of prescribing. The Delphi panel was composed of 100 general practitioners and 100 community pharmacists. RESULTS: The nominal group resulted in 20 items which were refined to produce 34 statements for the Delphi exercise. Consensus was reached on 30, from which 13 indicators suitable for application were produced. These were applied by two independent raters to the records of 49 purposively sampled patients in one general practice. Nine indicators showed acceptable reliability between raters. CONCLUSIONS: 9 indicators of prescribing appropriateness were produced suitable for application to the medical record of any patient on long term medication in United Kingdom general practice. Although the use of the medical record has limitations, this is currently the only available method to assess a patient's drug regimen in its entirety.
miR-335 promotes mesendodermal lineage segregation and shapes a transcription factor gradient in the endoderm

Transcription factors (TFs) pattern developing tissues and determine cell fates; however, how spatio-temporal TF gradients are generated is ill defined. Here we show that miR-335 fine-tunes TF gradients in the endoderm and promotes mesendodermal lineage segregation. Initially, we identified miR-335 as a regulated intronic miRNA in differentiating embryonic stem cells (ESCs). miR-335 is encoded in the mesoderm-specific transcript (Mest) and targets the 3′-UTRs of the endoderm-determining TFs Foxa2 and Sox17. Mest and miR-335 are co-expressed and highly accumulate in the mesoderm, but are transiently expressed in endoderm progenitors. Overexpression of miR-335 does not affect initial mesendoderm induction, but blocks Foxa2- and Sox17-mediated endoderm differentiation in ESCs and ESC-derived embryos. Conversely, inhibition of miR-335 activity leads to increased Foxa2 and Sox17 protein accumulation and endoderm formation. Mathematical modeling predicts that transient miR-335 expression in endoderm progenitors shapes a TF gradient in the endoderm, which we confirm by functional studies in vivo. Taken together, our results suggest that miR-335 targets endoderm TFs for spatio-temporal gradient formation in the endoderm and to stabilize lineage decisions during mesendoderm formation.
Modelling of nominal strength prediction for quasi-brittle materials : application to discrete element modelling of damage and fracture of asphalt concrete under fatigue loading

The prediction of the fatigue life and the rupture of structures made of quasi-brittle materials requires the development of new theoretical and numerical models. In this work, the modelling of the crack initiation and propagation under monotonic loading is firstly investigated. A size effect model for cracked structures and its generalized form for structures with defects more complex than a crack are developed. The predictions of the proposed model are compared with experimental results from the literature for various specimens of different materials and sizes. Samples with initial V-shaped and hole-shaped defects exemplify the formulation's capabilities. Then, the damage and cracking induced by cyclic fatigue loads is discussed. A local model using discrete elements is developed, that allows the coupling of two mechanisms (damage and fatigue cracking). The numerical results are compared to those of experimental bending fatigue tests. Finally, applications associated with the behavior of fiber glass reinforced asphalt concrete are analyzed in detail.
Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data

Background—Continued reductions in morbidity and mortality attributable to ischemic heart disease (IHD) require an understanding of the changing epidemiology of this disease. We hypothesized that we could use genetic correlations, which quantify the shared genetic architectures of phenotype pairs and extant risk factors from a historical prospective study to define the risk profile of a contemporary IHD phenotype. Methods and Results—We used 37 phenotypes measured in the ARIC study (Atherosclerosis Risk in Communities; n=7716, European ancestry subjects) and clinical diagnoses from an electronic health record (EHR) data set (n=19 093). All subjects had genome-wide single-nucleotide polymorphism genotyping. We measured pairwise genetic correlations (rG) between the ARIC and EHR phenotypes using linear mixed models. The genetic correlation estimates between the ARIC risk factors and the EHR IHD were modestly linearly correlated with hazards ratio estimates for incident IHD in ARIC (Pearson correlation [r]=0.62), indicating that the 2 IHD phenotypes had differing risk profiles. For comparison, this correlation was 0.80 when comparing EHR and ARIC type 2 diabetes mellitus phenotypes. The EHR IHD phenotype was most strongly correlated with ARIC metabolic phenotypes, including total:high-density lipoprotein cholesterol ratio (rG=−0.44, P=0.005), high-density lipoprotein (rG=−0.48, P=0.005), systolic blood pressure (rG=0.44, P=0.02), and triglycerides (rG=0.38, P=0.02). EHR phenotypes related to type 2 diabetes mellitus, atherosclerotic, and hypertensive diseases were also genetically correlated with these ARIC risk factors. Conclusions—The EHR IHD risk profile differed from ARIC and indicates that treatment and prevention efforts in this population should target hypertensive and metabolic disease.