Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of mycophenolate mofetil in children with lupus and clinical findings in favour of therapeutic drug monitoring.

AIMS The use of mycophenolate mofetil (MMF) in children with systemic lupus erythematosus (SLE) is increasing. However, the clinical benefit of its monitoring has been scarcely studied, and little is known about its pharmacokinetics in this context. The objectives of the present study were: (i) to describe mycophenolic acid (MPA, the active moiety of MMF) pharmacokinetics, (ii) to develop a Bayesian estimator (BE) allowing the determination AUC (area under the curve) from a limited number of blood samples and (iii) to explore the relationships between exposure indices to MPA and the clinical status in children with SLE. METHODS This was a retrospective study including 36 children with SLE, extracted from the expert system ISBA, for whom full- pharmacokinetic profiles of MPA were collected together with clinical data. A pharmacokinetic model and a BE were developed using an iterative two stage Bayesian approach. ROC curve analyses and logistic regressions were used to investigate the association of exposure and active disease. RESULTS A pharmacokinetic model and a BE were developed that allowed good AUC estimation performance (bias ± SD = -0.02 ± 0.15). ROC curve analyses showed that AUC/dose <0.06 and AUC <4 mg l(-1) h were associated with a good sensitivity and specificity for active disease (78%/94% and 94%/56%, respectively). When introduced in a logistic regression model, AUC <44 mg l(-1) h and AUC/dose <0.06 were associated with an increased risk of active disease (OR = 21.2, 95% CI 2.3, 196.1, P = 0.007 and OR = 59.5, 95% CI 5.9, 588.2, P = 0.0005 respectively]. CONCLUSIONS The developed pharmacokinetic BE could be used to test prospectively the interest of MPA monitoring for limiting relapse of the disease or its progression.
A step-wise approach to integrating phylogeographic and phylogenetic biogeographic perspectives on the history of a core North American warm deserts biota

In this paper, we develop a five-step approach for analysis of historical relationships among areas of endemism using a set of 22 clades (9 mammal, 7 bird, 4 reptile, 1 amphibian, and 1 cactus) drawn from the warm deserts biota of western North America. As has been suggested in previous studies of portions of this biota, our results suggest a complex biogeographic history, but with substantial support for the influence of several major vicariant events in the diversification and assembly of the aridlands biota. We discuss and demonstrate the reciprocal strengths (and weaknesses) of phylogeography and phylogenetic biogeography for defining areas of endemism, analysing vicariance and dispersal, and dealing with temporal and spatial pseudo-congruence. r 2006 Elsevier Ltd. All rights reserved.
Intrapartum Evidence of Early-Onset Group B Streptococcus

OBJECTIVE: To estimate if neonates with early-onset group B streptococcus (GBS) sepsis have clinical evidence of fetal infection during labor or at delivery. METHODS: Retrospective cohort study of all neonates diagnosed with GBS sepsis by culture and clinical findings within the first 72 hours of life from January 1, 2000, through December 31, 2008, at Parkland Health and Hospital System. Medical records were reviewed and maternal, neonatal, and delivery data were ascertained. These neonates then were compared with all neonates delivered during the same time period. RESULTS: During the study period, 143,384 live-born neonates were delivered at our institution; 94 were diagnosed with early-onset GBS sepsis. The majority of these neonates (n=93) were diagnosed with early-onset GBS within the first hour of life. Neonates with early-onset GBS sepsis had a significant increase in preterm delivery, cesarean delivery (total and for fetal distress), 1- and 5-minute Apgar scores of 3 or lower, umbilical cord pH less than 7.0, and a base deficit of 12 mmol/L or higher. In addition, nulliparity differed between those with early-onset GBS and those without (74% compared with 33%, P<.001) as did chorioamnionitis rates (62% compared with 8%, P<.001). CONCLUSION: We believe that these findings are compelling evidence that fetuses with early-onset GBS may have signs of sepsis peripartum. We hypothesize that these data support the concept that early-onset GBS represents a spectrum of infection that often precedes birth. LEVEL OF EVIDENCE: II
Delayed-type hypersensitivity activity of the Brucella L7/L12 ribosomal protein depends on posttranslational modification

The ribosomal protein L7/L12 isolated from Brucella melitensis induces a delayed-type hypersensitivity (DTH) reaction in brucella-sensitized guinea pigs. Surprisingly, the recombinant brucella L7/L12 protein expressed in Escherichia coli as a fusion protein with a six-histidine tag cannot elicit such a reaction. The six histidines tagged to the recombinant L7/L12 protein were removed enzymatically, but the resulting protein did not induce a DTH reaction in sensitized animals. Incubation of the recombinant L7/L12 fusion protein in a B. melitensis lysate endowed the recombinant protein with a DTH activity, suggesting that the recombinant protein was modified by this treatment. Glycosylation or phosphorylation of the recombinant L7/L12 protein could not be detected. On the other hand, radiolabeled palmitic acid was found to be incorporated to the recombinant protein during its incubation in the brucella lysate. This incorporation was specific for the brucella L7/L12 protein and was inhibited when the brucella lysate was frozen and thawed before the incubation. The data reported here indicate that posttranslational modification of L7/L12 protein comprising at least an acylation step is required for the brucella L7/L12 DTH activity.
Corneal curvature gradient map: a new corneal topography map to predict the corneal healing process.

PURPOSE To evaluate a new curvature gradient topography map to predict postoperative corneal remodeling. METHODS In this retrospective study, 32 eyes of 16 patients with myopia underwent excimer ablation surgery with a postoperative high curvature gradient. The new curvature gradient map (acquired immediately postoperatively) shows the difference between the curvatures of two points over the distance between them; it was compared to the tangential curvature difference map between 1 and 12 months postoperatively to determine their relationship. Corneas were divided into 12 regions for analysis: four 90°-wide sectors centered on 0°, 90°, 180°, and 270°. There were three subdivisions in each sector: central (radius: 0 to 2.75 mm), paracentral (radius: 2.75 to 3.25 mm), and peripheral (radius: 3.25 to 4.5 mm). Linear regression analysis was performed by region. RESULTS The following regions had significant relationships between the initial curvature gradient and curvature difference between 1 and 12 months postoperatively: the paracentral zone of the 90° sector (P = .0145; R(2) = 0.1832) and both the central (P = .0034; R(2) = 0.2522) and paracentral (P = .0452; R(2) = 0.1271) zones of the 270° sector. The greatest average initial tangential curvature was in the 270° sector. CONCLUSIONS The initial curvature gradient after surgery predicted change in tangential curvature over the subsequent 12 months in areas where initial tangential curvature was greatest. When the curvature gradient was high, the surface curvature modification remained in progress months after surgery.
Effective discipline and contingency management systems in an urban junior high/middle school with an emphasis on developmental needs of young adolescents.

This study of discipline in an urban middle school focused on the nature and patterns of problems that existed in that setting in order to suggest possible systemic improvements. The study considered nine questions: (1) What constitutes a creative learning environment for poor, urban, middle school children? (2) What developmental characteristics should be considered in their discipline? (3) What kinds of discipline problems occur most frequently? (4) Are some students referred more frequently than others? (5) Do some teachers refer students more often than others? (6) Are there some days or periods during which more referrals are made?
Mind the price gap: How optimal emission pricing relates to the EU CO2 reduction targets

Abstract From the transport economic literature, it is known that optimal pricing of (environmental) externalities improves the urban system. In contrast to theory-based optimal pricing strategies, real-world policy setting often follows so-called “backcasting” approaches where certain targets are set, and policy measures are implemented in order to reach those targets. An example for the latter approach is the EU goal to reduce global greenhouse gas emissions in the transport sector by 20% until 2020 with respect to 1990 levels. This article aims to (i) compare optimal pricing and backcasting approaches for a specific case study in a simulation environment by identifying the contribution of each approach in EU’s 2020 emission reduction target, and (ii) to determine the costs required to reach the desired targets. For this purpose, an optimal emission pricing strategy is applied to a real-world scenario of the Munich metropolitan area in Germany. The highly differentiated tolls relate to individual exhaust emissions, i.e. they are calculated using damage cost estimates from the literature and vary over time of day, with traffic situation, and with vehicle type. The results indicate that the desired reduction in CO2 emissions is not reached for optimal pricing approach, and that the initial damage costs estimates need to be multiplied by a factor of 5 in order to reach the target, yielding a price of 350 CO2. When aiming at a decrease of the overall emission costs by 20% (CO2 and local pollutants), the initial cost estimates need to be multiplied by a factor of 10. Furthermore, it is shown that the major contribution to the overall emission reduction stems from behavioral changes of commuters and reverse commuters rather than from urban travelers; under some circumstances, urban travelers even increase their CO2 emission levels. Hence, the study rises awareness that conflicting trends for different types of pollutants and different types of individuals are very likely: an increase in non-methane hydrocarbon levels for urban travelers and freight depicts that pricing emissions does not necessarily result in a reduction of all pollutants or of the emissions levels of all travelers. It is shown how agent-based simulations can be used to provide valuable insights and decision support in such possibly counter-intuitive situations.
Dépenses publiques et mortalité infantile : les effets de la décentralisation

On s'interesse au lien entre la decentralisation et la sante. Tout d'abord, on met en evidence l'implication des gouvernements locaux en faveur des depenses sociales a partir d'analyses statistiques sur les taux de decentralisation, la structure des budgets locaux et la nature des depenses prises en charge. Ensuite, on formule des hypotheses sur les canaux de transmission possibles de la decentralisation sur l'etat de sante. Enfin, on montre, a partir d'une analyse en donnees de panel (echantillon de 21 pays en developpement sur la periode 1974-1994) la sensibilite du taux de mortalite infantile aux depenses publiques locales. Quatre resultats principaux emergent : (i) la presence d'un effet direct sur le TMI a la fois de la variable de depenses publiques en pourcentage du pib et des indicateurs de decentralisation ; (ii) un impact differencie des deux echelons territoriaux, au profit des gouvernements locaux : (iii) un impact d'autant plus eleve que les taux de decentralisation sont intermediaires ; et iv) une sensibilite du TMI d'autant plus forte que la decentralisation se traduit par une reorganisation de l'action publique et non une substitution d'un agent public a un autre.
Capacity of Space Time Block Codes with Adaptive Transmission in Correlated Rayleigh Fading Channels

In this paper, we study the capacity of space time block codes (STBCs) over correlated Rayleigh flat-fading MIMO channels combined with adaptive transmitting techniques. We study three adaptive schemes known as optimal power and rate allocation (opra), optimal rate allocation (ora), total channel inversion with fixed rate policy (cifr) and its truncated variant (tifr). We obtain closed form capacity expressions of STBCs combined with these adaptive schemes, taking into account the effect of channel correlation, hence avoiding numerical integrations or Monte-Carlo simulations
La burocratización del poder político: notas sobre sus consecuencias en las democracias parlamentarias

espanolEste trabajo aborda algunos de los efectos mas destacados de la progresiva burocratizacion de las democracias parlamentarias y su impacto en el poder politico. Adopta una perspectiva de analisis que trata de conjugar la inspiracion de Max Weber y otras figuras del pensamiento de la primera mitad del siglo XX con el analisis de un problema actual sobre el ejercicio del poder politico democratico. Sobre la experiencia de que la extension de la democracia ha ido acompanada de un crecimiento de las administraciones publicas y, junto a eso, de una burocratizacion creciente. El trabajo defiende la hipotesis de que esto se traduce en el desplazamiento del poder politico hacia las instancias burocraticas, cuyo peso en el proceso de toma de decisiones tiende a ocupar el espacio de la representacion politica. Se examinaran, en primer lugar, las caracteristicas distintivas de los aparatos burocraticos y su relacion con el poder politico, para despues indagar en los cambios experimentados por las instituciones democraticas en el marco de los procesos de burocratizacion EnglishThis paper addresses some outstanding effects of the gradual bureaucratization undergone by parliamentary democracies and their impact on political power. The analytical perspective adopted aims to combine the inspiration of Max Weber and other leading thinkers from the first half of the twentieth century with the analysis of a current problem on the exercise of democratic political power. Upon the experience that the spread of democracy has proceeded along with the growth of public administration to the rise of bureaucratization, the paper argues that this implies a displacement of political power towards bureaucratic agencies whose weight in decision-making tends to accupy the space of political representation. The paper examines, firstly, the distinctive features of bureaucratic units in their relation to political power. Then, it outlines some of the changes in democratic institutions produced by bureaucratization.
GAD‐Reactive T Cells Were Mainly Detected in Autoimmune‐Related Type 1 Diabetic Patients with HLA DR9

Abstract: Type 1 diabetes mellitus (T1DM) is considered to be a T cell‐mediated disease, and many reports suggest that some HLA types, especially HLA DR4 and DR9, convey susceptibility to T1DM in Japanese. We investigated the association between T cell reactivity against GAD and HLA types in “islet‐associated autoantibody‐positive” T1DM in Japanese. Blood samples were obtained from 36 “autoantibody‐positive” type 1 diabetic patients with HLA DR4 or DR9 and 23 type 2 diabetic patients with HLA DR4 or DR9 as controls. They were divided into three groups, DR4/9, DR4/X, and DR9/X groups. In each HLA type group, GAD‐reactive IFN‐γ‐producing CD4+ cells were assessed by means of intracellular cytokine staining for flow cytometry. Type 1 diabetic patients with HLA DR9/X had significantly higher numbers of GAD‐reactive IFN‐γ‐producing CD4+ cells as compared to type 1 diabetic patients with DR4/X or DR4/9 (P < 0.05) and all type 2 diabetic patients. There was no significant difference in the number of GAD‐reactive IFN‐γ‐producing CD4+ cells between type 1 diabetic and type 2 diabetic patients belonging to the DR4/X and DR4/9 groups. There was an association between T cell reactivity against GAD and HLA DR9 in Japanese type 1 diabetes.
The development of Chinese accounting and bookkeeping before 1850: insights from the Tŏng Tài Shēng business account books (1798–1850)

Claims have repeatedly been made for the importance of double-entry bookkeeping (‘DEB’) for capitalism’s development in the West, so it is valuable to explore the bookkeeping and accounting practices of economically successful organisations elsewhere. Our paper reports our exploration into the original account books contained in the archive of Tŏng Tài Shēng (‘TTS’), a substantial Chinese ‘grocery/merchant-banking’ business whose surviving books span a period from the late eighteenth century to the middle of the nineteenth century. The TTS archive is the most complete and integrated surviving merchant archive from before China’s forced opening to the West in the mid-nineteenth century. Our findings about its accounting processes and records (of which we give illustrations) shed critical light on the nature of indigenous Chinese bookkeeping and business organisation and on the larger questions about Chinese commercial culture and the path of its development, for comparison with those about the West. We find no evidence in the surviving account books of TTS to support previous arguments in the literature that at this period Chinese accounting practice for successful businesses (must have) had its own ‘Chinese DEB’ comparable to Western DEB.
SEPSIS SYNDROMES: UNDERSTANDING THE ROLE OF INNATE AND ACQUIRED IMMUNITY

ABSTRACT— An intact innate and acquired immune response are essential for defeating systemic microbial infections. Recognition molecules, inflammatory cells, and the cytokines they produce are the principal means for host tissues to recognize invading microbes and to initiate intercellular communication between the innate and acquired immune systems. However, activation of host innate immunity may also occur in the absence of microbial recognition, through expression of internal “danger” signals produced by tissue ischemia and necrosis. When activation of the innate immune system is severe enough, the host response itself can propel the patient into a systemic inflammatory response syndrome (SIRS), or even multiple system organ failure (MSOF) and shock. Although most patients survive the initial SIRS insult, these patients remain at increased risk of developing secondary or opportunistic infections because of the frequent onset of a compensatory anti‐inflammatory response syndrome (CARS). The initial activation of the innate immune response often leads to macrophage deactivation, T‐cell anergy, and the rapid apoptotic loss of lymphoid tissues, which all contribute to the development of this CARS syndrome and its associated morbidity and mortality. Initial efforts to treat the septic patient with anticytokine therapies directed at the SIRS response have been disappointing, and therapeutic efforts to modify the immune response during sepsis syndromes will require a more thorough understanding of the innate and acquired immune responses and the increased apoptosis in the lymphoid tissue.
Results of preoperative ultrasound guided fine needle aspiration biopsy of solitary thyroid nodules as compared with the histology

Summary Aim: The goal of this study was to assess the accuracy and limitations of ultrasound guided fine-needle aspiration biopsy (ug-FNAB) of solitary thyroid nodules. Methods: The ug-FNAB results of 538 patients with solitary thyroid nodules, who afterwards underwent thyroid surgery, were compared retrospectively with the histology. Patients with multinodular goiter were excluded from the study. Ug-FNAB was performed on growing and/or hypoechoic and/or hypofunctional nodules. The ug-FNAB results were grouped as follows: group 1: malignant (n = 44); group 2: malignancy cannot be ruled out (n = 173); group 3: non-malignant (n = 296), group 4: inadequate (n = 25). Results: When the cytological results of group 1 and group 2 were interpreted os being malignant and those of group 3 as being benign, sensitivity, specificity and accuracy of ug-FNAB were 96.7%, 65.8% and 69.5% respectively. The 62 thyroid carcinomas (TO biopsied presented in 59 cases a suspicious or malignant cytology (95.2%). The smallest TC diagnosed by ug-FNAB had a diameter of 0.5cm and 36.4% of all papillary TC ≤ 1 cm displayed stage pT4. The histology verified a TC in 18 cases out of the 173 ug-FNABs in group 2. Non-malignant ug-FNABs were confirmed by histology in 294 patients (99.3%) in group 3. In 4.65% of the ug-FNABs inadequate material was aspirated. Conclusion: Nodules with non-suspicious ug-FNAB results can be safely followed-up by sonography, as the cytological diagnoses were verified in more than 99% by histology. Papillary TC can be diagnosed with ug-FNAB very accurately. As stage pT4 was present in more than one third of patients with papillary TC ≤ T cm, ug-FNAB is also recommended for thyroid nodules 0.5-1 cm in diameter located adjacent to the thyroid capsule. However, microfollicular proliferations remain the limitation of ug-FNAB, as the cytology cannot distinguish between benign adenoma and follicular TC.
An electoral calculus? Dual incentives and committee assignment in the UK’s mixed-member legislatures

ABSTRACT Although mixed-member electoral systems offer an apparent opportunity to observe how different rules shape politicians’ behaviour, ‘contamination’ between the SMD and PR-list tiers has frequently confounded academic work. Investigating Scotland and Wales’ mixed-member legislatures by exploiting their different chamber sizes and an unusual dual candidacy prohibition in Wales, modelling of committee assignments uncovers a split finding. Controlling for membership of the lead governing party, list members have a higher committee workload than their constituency colleagues, and members with previous employment experience in justice and health are more likely to be assigned to the corresponding subject committee once elected. Elsewhere, expectations that members might seek assignments that best suit theorized re-election interests are not found. The hypothesized influence of electoral rules is strongly conditioned by the small size of the legislature in Wales.
Long‐Term Carcinogenicity Bioassays on Acrylonitrile Administered by Inhalation and by Ingestion to Sprague‐Dawley Rats a

Sprague-Dawley rats were exposed to acrylonitrile by inhalation at 40, 20, 10, 5 and 0 ppm, 4 hours daily, 5 days weekly, for 52 weeks and at 60 ppm, 4-7 hours daily, 5 days weekly. The latter treatment was started on 13-week-old breeders, and male and female offspring (12-day-embryos). The breeders and part of the offspring were exposed for 104 weeks; the other part of the offspring was exposed for 15 weeks only. Sprague-Dawley rats were also exposed to acrylonitrile by ingestion (stomach tube), in olive oil, at 5 mg/kg b.w. , once daily 3 times weekly for 52 weeks. Under the tested experimental conditions, acrylonitrile was shown to be carcinogenic in Sprague-Dawley rats when given by inhalation and did not produce any carcinogenic effect when given by ingestion. In the inhalation experiment, acrylonitrile caused an increase in different types of tumors and the most noticeable acrylonitrile-related tumor was encephalic glioma.