Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin degludec in combination with bolus insulin aspart is safe and effective in children and adolescents with type 1 diabetes

Insulin degludec (IDeg) once‐daily was compared with insulin detemir (IDet) once‐ or twice‐daily, with prandial insulin aspart in a treat‐to‐target, randomized controlled trial in children 1–17 yr with type 1 diabetes, for 26 wk (n = 350), followed by a 26‐wk extension (n = 280). Participants were randomized to receive either IDeg once daily at the same time each day or IDet given once or twice daily according to local labeling. Aspart was titrated according to a sliding scale or in accordance with an insulin:carbohydrate ratio and a plasma glucose correction factor. Randomization was age‐stratified: 85 subjects 1–5 yr. (IDeg: 43), 138 6–11 yr (IDeg: 70) and 127 12–17 yr (IDeg: 61) were included. Baseline characteristics were generally similar between groups overall and within each stratification. Non‐inferiority of IDeg vs. IDet was confirmed for HbA1c at 26 wk; estimated treatment difference (ETD) 0.15% [−0.03; 0.32]95%CI. At 52 wk, HbA1c was 7.9% (IDeg) vs. 7.8% (IDet), NS; change in mean FPG was −1.29 mmol/L (IDeg) vs. +1.10 mmol/L (IDet) (ETD −1.62 mmol/L [−2.84; −0.41]95%CI, p = 0.0090) and mean basal insulin dose was 0.38 U/kg (IDeg) vs. 0.55 U/kg (IDet). The majority of IDet treated patients (64%) required twice‐daily administration to achieve glycemic targets. Hypoglycemia rates did not differ significantly between IDeg and IDet, but confirmed and severe hypoglycemia rates were numerically higher with IDeg (57.7 vs. 54.1 patient‐years of exposure (PYE) [NS] and 0.51 vs. 0.33, PYE [NS], respectively) although nocturnal hypoglycemia rates were numerically lower (6.0 vs. 7.6 PYE, NS). Rates of hyperglycemia with ketosis were significantly lower for IDeg vs. IDet [0.7 vs. 1.1 PYE, treatment ratio 0.41 (0.22; 0.78)95%CI, p = 0.0066]. Both treatments were well tolerated with comparable rates of adverse events. IDeg achieved equivalent long‐term glycemic control, as measured by HbA1c with a significant FPG reduction at a 30% lower basal insulin dose when compared with IDet. Rates of hypoglycemia did not differ significantly between the two treatment groups; however, hyperglycemia with ketosis was significantly reduced in those treated with IDeg.
‐ acetyl ‐ L ‐ cysteine reduces arsenite ‐ induced cytotoxicity through chelation in U 937 monocytes and macrophages

In the present study, in order to clarify the preventive mechanism of N-acetyl-L-cysteine (NAC) on arsenite-induced apoptosis in U937 cells, which lack functional p53, the cytotoxicity among U937 cells [monocytes and 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated macrophages] receiving NAC treatment at different times post arsenite treatment was examined. TPA-treated macrophages were more resistant to arsenite-induced apoptosis than monocytes, which may be associated with the induction of Bcl-2 expression. Pretreatment with 20 mM NAC prior to arsenite exposure suppressed apoptosis up to 75% in the monocytes and 100% in the macrophages. However, 6-h NAC pretreatment and subsequent washing out of NAC from the culture medium prior to arsenite treatment did not inhibit the arsenite-induced apoptosis. Post-treatment by NAC up to 1 h following arsenite exposure almost completely inhibited the cytotoxic effects of arsenite in U937 monocytes and macrophages. The results of the current study indicate that the preventive mechanism of NAC on arsenite-induced apoptosis in U937 monocytes and macrophages mainly involves chelation of arsenite in culture
Price Level Convergence, Relative Prices, and Inflation in Europe

If price levels are initially different across the euro area, convergence to a common level of prices would imply that inflation will be higher in countries where prices are initially low. Price level convergence thus provides a potential explanation for recent cross-country differences in European inflation, a worrisome development under the ECBs "one-size-fits-all" monetary policy. I present direct evidence on price level convergence in Europe, using a unique data set, and then investigate how much of the recent divergence of national inflation rates can be explained by price level convergence. I show that between 1990 and 1999 prices did become less dispersed in the euro area. Convergence is especially evident for traded goods, and more in the first half of the 1990s than the second half. By some measures, traded goods price dispersion across the euro area is now close to that across U.S. cities. Despite an on-going process of convergence, deviations from the law of one price are large. Finally, I find a statistically-significant and robust negative relationship between the 1999 price level and 2000 inflation rate in Europe, and that the contribution of price level convergence to explaining inflation differentials is often quite important economically. Still, factors other than price convergence explain most of the cross-country inflation differences.
Working Papers in Responsible Banking & Finance

We apply Chordia et al.’s (2008) conception of short-horizon return predictability as inverse indicator of market efficiency to the analysis of instruments on the world’s largest carbon exchange, ICE’s ECX. We find strong relationship between liquidity and market efficiency such that when spreads narrow, return predictability diminishes. This is more pronounced for the highest trading carbon futures and during periods of low liquidity. Since the start of trading in the Kyoto commitment period of the EU Emissions Trading Scheme (EU-ETS) prices continuously moved nearer to unity with random walk benchmarks, and this improves from year to year. Overall, our findings suggest trading quality in the EU-ETS has improved markedly and matures over the 2008-2011 compliance years. These findings are significant for global climate change policy. WP No 12-004
Successful Intraoperative Spinal Cord Monitoring During Scoliosis Surgery Using a Total Intravenous Anesthetic Regimen Including Dexmedetomidine

Summary: Intraoperative neurophysiological monitoring (IONM) during corrective spinal surgery is widely used. Because of the possible interference with the recording of evoked potentials by inhalational anesthetics, total intravenous anesthetic (TIVA) regimens have been advocated. TIVA regimens may be difficult to use in pediatric populations due to metabolic factors. We report on the results of multimodality IONM during 18 cases in which a TIVA regimen incorporating dexmedetomidine (Precedex, Hespira, Lake Forest, IL) was used. Monitoring techniques included sensory (SSEP) and motor evoked potentials (MEP), as well as pedicle screw stimulation. SSEPs were maintained within an acceptable range of baseline amplitude (50%) and latency (10%), and MEPs remained elicitable throughout each case. We therefore found that the anesthetic regimen did not significantly interfere with any of the monitoring modalities used and conclude that IONM in the presence of dexmedetomidine is feasible under appropriate conditions.
Re-examining Monetary and Fiscal Policy for the 21st Century

This book provides a much-needed re-examination of monetary and fiscal policies, their application in the real world and their potential for macroeconomic policy in the 21st century. It provides a detailed discussion and critique of the ‘new consensus' in macroeconomics along with the monetary and fiscal policies encapsulated within it.
Industry Effects and Appropriability Measures in the Stock Markets Valuation of R&D and Patents

This paper examines the stock market's valuation of a firm's innovative activity. We estimate the market's relative valuation of firms' tangible and intangible assets, focusing on knowledge capital in the form of accumulated "stocks" of R&D and patents. We tried to improve upon our estimates of the stock market's valuation of knowledge capital embodied in such "stocks" by bringing in measures of the appropriability environment facing a firm from the Yale Survey on Industrial Research and Development. The responses to Survey questions about the effectiveness of patents as a mechanism for protecting the returns from innovation turn out to be of some use: there is evidence of an interaction between industry level measures of the effectiveness of patents and the market's valuation of a firm's past R&D and patenting performance, as well as its current R&D moves. We find no evidence, however, that other appropriability mechanisms differ enough across industries to leave measurable traces in our data. The structure of the Yale Survey makes it possible to estimate the sampling error in the appropriability measures derived from it. This information was used by us in an errors-in-variables context, but with little success. In the absence of R&D variables, our estimates imply that a two standard deviation increase in our index of patent effectiveness would raise the value of a patent held by our average firm from $0.4 million to $1.0 million. When R&D variables are introduced into the equations, the patents variables become insignificant - R&D expenditures are a better measure of input to the innovative function of firms than patents are of its output - but we estimate that the same experiment would induce changes in q of between 10 and 27 percent for the average firm, approximately doubling the market's valuation of this kind of capital.
Lessons on Effective Teaching from Middle School ESL Students

Jaime loved to read about the Greek gods and complained of being bored a lot in class. He expressed the opinion that he was not challenged academically. Maria loved the Olsen twins (Kate and Ashley) and wanted to be a singer and an actress when she grew up. Rosa wanted to become a doctor, but confessed that she sometimes felt that she was not a good student because she did not make 100% on all her assignments. Angel was reported by his teacher to be the hardest working of all the students, and he told me that he wanted to be an engineer when he grew up. These four students were perceived to be progressing well academically by their mainstream and ESL teachers. Enrique was at risk academically. He was failing many classes and his parents were often called in for conferences. Enrique did not like school and described himself as the person who made the teachers mad because “I just do some jokes to the teachers and they get mad, . and they tell my family. Teachers get all this voice and sometimes they kick me out of class. ” Enrique did not consider himself to be a good student and preferred to earn money with his father on the weekends working on construction sites. Enrique, a seventh grader, skipped classes sometimes, especially science, without the mainstream teacher knowing. Enrique told me that by skipping science he could eat lunch with the eighth graders and be with his friend Jaime who was in the eighth grade. Lupe was also at risk academically and behaviorally. She was suspended on two occasions during the course of the six-month study. She was very precocious and used a lot of sexual terminology and inappropriate language around other students. She did not like Rosa or Maria. She expressed her love for animals and her desire to be a veterinarian when she grew up. These six students, all originally from Mexico, presented unique instructional challenges to their mainstream teacher. Children who arrive in a new country by age six or seven do better academically later in middle school and high school than older arrivals (Gibson, 1988). Of course there are exceptions, but in general, the older arrivals (middle school and Lessons on Effective Teaching From Middle School ESL Students
A comparative analysis of two land reform models, the Mashishimale farm management model and the Nkumbuleni strategic partnership model, South Africa

The Sustainable Restitution Support - South Africa (SRS-SA) program aimed at the development of a post-settlement support model that could be used to support beneficiaries of land reform in South Africa, especially those who received the land through restitution. The two land restitution claims were identified namely Mashishimale in the Limpopo Province and Nkumbuleni in KwaZulu Natal Province in South Africa. The main objective of the study is to determine the essential elements of two post-settlement support models to successfully implement and manage land reform projects in a sustainable manner namely: Mashishimale Farm Management Model (FMM) and Nkumbuleni Strategic Partnership Model (SPM). The data was collected through meetings and interviews with different stakeholders or role players. The study reveals that the following actions are essential for the successful post-settlement to restitution farms: The execution of baseline study (survey) to determine the socio-economic situation in a community (beneficiaries). The appointment of an independent project facilitator/coordinator to ensure effective and efficient communication. A well-defined management structure and the appointment of a knowledgeable, skilful and experienced farm manager(s) or strategic partner. The development of a business plan for the farm with the support of professional agriculturist. The identification of qualified professional extension advisor to provide advice and guidance to the manager(s) or strategic partner. Appointment of a mentor to guide advice and train the manager(s) or strategic partner. Financial support to manage the farm (Grants; Comprehensive Agricultural Support Program; financial institutions and specifically the Land Bank).
Circulating Sclerostin and Irisin Are Related and Interact with Gender to Influence Adiposity in Adults with Prediabetes

Objectives. Sclerostin, an osteocyte-specific protein, has been found to be related to adiposity and glucose metabolism. Irisin, a myokine, can affect browning of white fat and influence glucose and energy homeostasis. Taken together, this suggests a probable network among fat, bone, and muscle that may influence health outcomes. The aims of this study were to investigate the relationship of circulating sclerostin and irisin and their association with adiposity (assessed by body mass index (BMI)). Materials/Methods. A cross-sectional study included 98 adults with impaired fasting glucose and/or impaired glucose tolerance. 75 gm OGTT was performed in all subjects. Fasting plasma samples were obtained for glycated hemoglobin, calcium, creatinine, serum sclerostin and irisin. Results. Circulating irisin and sclerostin were highly correlated (r = −0.4; P < 0.001). After controlling for age, gender, and BMI, irisin was significantly related to sclerostin (P < 0.001). Multivariate linear regression analysis demonstrated that circulating sclerostin (β = −0.45; P < 0.05) and irisin (β = −0.46; P < 0.05) were negatively associated with BMI, independent of age in males. In females, no relationship of sclerostin or irisin to BMI was found. Conclusions. Circulating irisin and sclerostin are highly related. Interventions targeting irisin could affect sclerostin and vice versa.
Intraspecies Competition in Serratia marcescens Is Mediated by Type VI-Secreted Rhs Effectors and a Conserved Effector-Associated Accessory Protein

ABSTRACT The type VI secretion system (T6SS) is widespread in Gram-negative bacteria and can deliver toxic effector proteins into eukaryotic cells or competitor bacteria. Antibacterial T6SSs are increasingly recognized as key mediators of interbacterial competition and may contribute to the outcome of many polymicrobial infections. Multiple antibacterial effectors can be delivered by these systems, with diverse activities against target cells and distinct modes of secretion. Polymorphic toxins containing Rhs repeat domains represent a recently identified and as-yet poorly characterized class of T6SS-dependent effectors. Previous work had revealed that the potent antibacterial T6SS of the opportunistic pathogen Serratia marcescens promotes intraspecies as well as interspecies competition (S. L. Murdoch, K. Trunk, G. English, M. J. Fritsch, E. Pourkarimi, and S. J. Coulthurst, J Bacteriol 193:6057–6069, 2011, http://dx.doi.org/10.1128/JB.05671-11). In this study, two new Rhs family antibacterial effectors delivered by this T6SS have been identified. One of these was shown to act as a DNase toxin, while the other contains a novel, cytoplasmic-acting toxin domain. Importantly, using S. marcescens, it has been demonstrated for the first time that Rhs proteins, rather than other T6SS-secreted effectors, can be the primary determinant of intraspecies competition. Furthermore, a new family of accessory proteins associated with T6SS effectors has been identified, exemplified by S. marcescens EagR1, which is specifically required for deployment of its associated Rhs effector. Together, these findings provide new insight into how bacteria can use the T6SS to deploy Rhs-family effectors and mediate different types of interbacterial interactions. IMPORTANCE Infectious diseases caused by bacterial pathogens represent a continuing threat to health and economic prosperity. To counter this threat, we must understand how such organisms survive and prosper. The type VI secretion system is a weapon that many pathogens deploy to compete against rival bacterial cells by injecting multiple antibacterial toxins into them. The ability to compete is vital considering that bacteria generally live in mixed communities. We aimed to identify new toxins and understand their deployment and role in interbacterial competition. We describe two new type VI secretion system-delivered toxins of the Rhs class, demonstrate that this class can play a primary role in competition between closely related bacteria, and identify a new accessory factor needed for their delivery.
HOMOGENEITY FOR TIME-DELAY SYSTEMS

The notion of homogeneity is extended to the time-delay nonlinear systems. It is shown that under some conditions the stability of homogeneous functional systems on a sphere implies the global stability of the system. The notion of local homogeneity is introduced, the relations between stability of the locally approximating dynamics and the original time-delay system are established. An example of the proposed theory application is given.
Synergistic Antimicrobial Action of Chlorhexidine and Ozone in Endodontic Treatment

Objectives. The aim of this study was to determine whether irrigation with sodium hypochlorite, chlorhexidine, and ozone gas, alone or in combination, were effective against Enterococcus faecalis and Candida albicans; these are microorganisms frequently isolated from teeth with periapical lesions resistant to endodontic treatment. Material and Methods. 220 single root teeth, recently extracted, were inoculated with Candida albicans and Enterococcus faecalis. The formulations tested were sodium hypochlorite at 1, 3, and 5% chlorhexidine at 0.2% and 2% and ozone gas applied for different periods of time. The combination of sodium hypochlorite at 5% and chlorhexidine at 2%, with gaseous ozone, were also assessed. For the most active treatments the mechanism of action was assessed through flow cytometry. Results. Sodium hypochlorite, chlorhexidine, and gaseous ozone alone were ineffective in completely eliminating the microorganisms. The association of chlorhexidine at 2% followed by ozone gas for 24 seconds promoted the complete elimination of Candida albicans and Enterococcus faecalis. Flow cytometry shows that ozone and chlorhexidine act differently, which could explain its synergic activity. Conclusions. This new disinfection protocol, combining irrigation with chlorhexidine at 2% and ozone gas for 24 seconds, may be advantageous when treating infected root canals.
Impact of Tumor HER2/ERBB2 Expression Level on HER2-Targeted Liposomal Doxorubicin-Mediated Drug Delivery: Multiple Low-Affinity Interactions Lead to a Threshold Effect

Numerous targeted nanotherapeutics have been described for potential treatment of solid tumors. Although attention has focused on antigen selection and molecular design of these systems, there has been comparatively little study of how cellular heterogeneity influences interaction of targeted nanoparticles with tumor cells. Antigens, such as HER2/ERBB2, are heterogeneously expressed across different indications, across patients, and within individual tumors. Furthermore, antigen expression in nontarget tissues necessitates optimization of the therapeutic window. Understanding the performance of a given nanoparticle under different regimens of antigen expression has the ability to inform patient selection and clinical development decisions. In this work, HER2-targeted liposomal doxorubicin was used as a model-targeted nanoparticle to quantitatively investigate the effect of HER2 expression levels on delivery of doxorubicin to the nucleus. We find quantitatively greater nuclear doxorubicin delivery with increasing HER2 expression, exhibiting a threshold effect at approximately 2 × 105 HER2 receptors/cell. Kinetic modeling indicated that the threshold effect arises from multiple low-affinity interactions between the targeted liposome and HER2. These results support previous data showing little or no uptake into human cardiomyocytes, which express levels of HER2 below the threshold. Finally, these results suggest that HER2-targeted liposomal doxorubicin may effectively target tumors that fall below traditional definitions of HER2-positive tumors, thereby expanding the potential population of patients that might benefit from this agent. Mol Cancer Ther; 12(9); 1816–28. ©2013 AACR.
Global and Local Convergence of Line Search Filter Methods for Nonlinear Programming

Line search methods for nonlinear programming using Fletcher and Leyffer’s filter method, which replaces the traditional merit function, are proposed and their global and local convergence properties are analyzed. Previous theoretical work on filter methods has considered trust region algorithms and only the question of global convergence. The presented framework is applied to barrier interior point and active set SQP algorithms. Under mild assumptions it is shown that every limit point of the sequence of iterates generated by the algorithm is feasible, and that there exists at least one limit point that is a stationary point for the problem under consideration. Furthermore, it is shown that the proposed methods do not suffer from the Maratos effect if the search directions are improved by second order corrections, so that fast local convergence to strict local solutions is achieved. A new alternative filter approach employing the Lagrangian function instead of the objective function with identical global convergence properties is briefly discussed.
Language Recognition for Mono-and Multi-lingual Documents

In this paper we describe language recognition algorithms for monoand multi-lingual documents that are based on mixed-order n-grams, Markov chains, maximum likelihood, and dynamic programming. We compare the monolingual algorithm to those suggested by other researchers. This comparison suggests that this algorithm significantly outperforms commonly used language recognition algorithms. We then describe the multilingual algorithm, which allows for segmenting a multilingual document into single language chunks and identifying the languages of those chunks.