Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of Drug Clearance in Children: Impact of Allometric Exponents, Body Weight, and Age

In recent years, with the advent of pediatric exclusivity and requirements for conducting clinical studies involving children, emphasis has been placed on finding safe and efficacious doses of drugs for children. It has been suggested that one can predict the clearance (CL) of a drug in children according to this equation: CL in the child = Adult CL * (Weight of the child/70)0.75. In light of the controversy surrounding the exponent of 0.75 for the prediction of clearance, the objectives of the study were as follows: (1) to develop allometric equations based on body weight or age to predict clearance of a drug in children; (2) to determine if the fixed exponent of 0.75 is a suitable exponent for the prediction of clearance in children from adult data, as compared with the allometric exponent generated for individual drugs; (3) to determine if the allometric equation generated on the basis of age predicts clearance in children better or worse than the allometric equation generated on the basis of body weight; and (4) to propose a new approach based on the findings of the current evaluation. Five methods were used to predict drug clearance in children. Six drugs were used in the evaluation, and drug clearance in each child was predicted for a given drug. Besides evaluating the exponent of 0.75, allometric equations were developed using double log plots of clearance versus body weight or age. The exponents of the allometric equations were then used to predict drug clearance by replacement of 0.75 in the aforementioned equation. The results of the study indicate that 0.75 is not the best exponent for prediction of drug clearance in children, and a more suitable approach is to develop an allometric relationship for a given drug in children. For all 6 drugs, there were 77 children in whom the clearance was predicted. There were 48 observations for which error in the predicted clearance was 50% or more with use of the exponent 0.75, whereas there were only 13 observations with prediction error ≥50% when 0.75 was replaced by an allometric exponent developed for a given drug. In order to predict drug clearance in children with reasonable accuracy, an allometric equation should be developed for every drug and the exponent 0.75 should be replaced by the exponent of the allometric equation developed for that drug.
Entrepreneurship and regional dynamics: the case of Chile

ABSTRACT During the last 20 years, social and political consensus has afforded the successful gradual implementation of entrepreneurship policy in Chile, transforming the country into one of the world’s most productive entrepreneurship ecosystems. However, the excessive political and economic centralization that has characterized Chile raises the question of whether spatial dependence influences entrepreneurship and what factors have led to this condition. By applying spatial econometric tools to data from 320 districts in Chile during the period 2013–2014, we conclude that there is spatial dependence among districts in Chile in relation to the creation of new businesses and that the immigrant population, the presence of different categories of universities and local patenting capacity are the variables with the greatest positive effect on this dependence.
Short-Term Pain for Long-Term Gain: The Logic of Legislative Party Switching in the Contemporary American South

One of the most important career decisions for a legislator is the decision to switch parties, and it raises a theoretical puzzle: it carries significant risk, yet sometimes legislators do change partisan affiliation. We elucidate this puzzle with the first-ever systematic comparison of the entire careers of state legislative switchers and non-switchers in the American South, where the high prevalence of party switching coincided with rapid realignment toward the Republican Party. Our analysis is the first to evaluate all post-switch career decisions (retiring, running for reelection, running for higher office) simultaneously, and it is the broadest in its scope with two full decades of career data. We demonstrate that converts to the Grand Old Party (GOP) pay a reelection cost. However, they are less likely to retire than Democratic non-switchers and more likely to seek higher office. This latter finding is especially strong during the earlier part of our study—when the Republican bench in the South was not as deep and competition for the party label was not as intense. Our findings suggest that political ambition motivates legislators to trade short-term electoral costs for a more promising long-term electoral career with the ascendant party.
Permeability shapes bacterial communities in sublittoral surface sediments

The first interaction of water column-derived organic matter with benthic microbial communities takes place in surface sediments which are acting as biological filters catalyzing central steps of elemental cycling. Here we analyzed the bacterial diversity and community structure of sediment top layers at seven sites in the North Sea where sediment properties ranged from coarse-grained and highly permeable to fine-grained and impermeable. Bacterial communities in surface sediments were richer, more even and significantly different from communities in bottom waters as revealed by Illumina tag sequencing of 16S rRNA genes. Sediment permeability had a clear influence on community composition which was confirmed by CARD-FISH. Sulfate-reducing Desulfobacteraceae (2-5% of total cells), Flavobacteriaceae (3-5%) were more abundant in impermeable than in highly permeable sediments where acidobacterial Sva0725 dominated (11-15%). Myxobacterial Sandaracinaceae were most abundant in medium permeable sediments (3-7%). Woeseiaceae/JTB255 and Planctomycetes were major groups in all sediments (4-6%, 8-22%). Planctomycetes were highly diverse and branched throughout the phylum. We propose Planctomycetes as key bacteria for degradation of high molecular weight compounds and recalcitrant material entering surface sediments from the water column. Benthic Flavobacteriaceae likely have restricted capabilities for macromolecule degradation and might profit with Sandaracinaceae and Acidobacteria from low molecular weight compounds.
Reawakening Retrocyclins: Ancestral Human Defensins Active Against HIV-1

Human alpha and beta defensins contribute substantially to innate immune defenses against microbial and viral infections. Certain nonhuman primates also produce theta-defensins—18 residue cyclic peptides that act as HIV-1 entry inhibitors. Multiple human theta-defensin genes exist, but they harbor a premature termination codon that blocks translation. Consequently, the theta-defensins (retrocyclins) encoded within the human genome are not expressed as peptides. In vivo production of theta-defensins in rhesus macaques involves the post-translational ligation of two nonapeptides, each derived from a 12-residue “demidefensin” precursor. Neither the mechanism of this unique process nor its existence in human cells is known. To ascertain if human cells retained the ability to process demidefensins, we transfected human promyelocytic cells with plasmids containing repaired retrocyclin-like genes. The expected peptides were isolated, their sequences were verified by mass spectrometric analyses, and their anti-HIV-1 activity was confirmed in vitro. Our study reveals for the first time, to our knowledge, that human cells have the ability to make cyclic theta-defensins. Given this evidence that human cells could make theta-defensins, we attempted to restore endogenous expression of retrocyclin peptides. Since human theta-defensin genes are transcribed, we used aminoglycosides to read-through the premature termination codon found in the mRNA transcripts. This treatment induced the production of intact, bioactive retrocyclin-1 peptide by human epithelial cells and cervicovaginal tissues. The ability to reawaken retrocyclin genes from their 7 million years of slumber using aminoglycosides could provide a novel way to secure enhanced resistance to HIV-1 infection.
Middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke

Variability in the effects of the intraluminal suture method of middle cerebral artery occlusion (MCAO) in the rat has been a common and disadvantageous finding. Therefore, we systematically investigated the effects of suture type and rat strain on outcome. First, the clinical and neuropathological effects of permanent MCAO with either an uncoated or a silicone‐coated nylon suture were studied over 7 days in Sprague–Dawley rats (n=36 for each type of suture). Outcome was less severe with the uncoated compared with the silicone‐coated suture (e.g. total cerebral infarct volume at 24 h before any fatalities was 119.9±79.8 mm3 , cf. 183.0±36.5 mm3 , n=12 for each, P<0.05; and overall mortality rate was 12.5% cf. 33%, respectively), but much more variable (coefficient of variation was 66.6% cf. 19.9%, respectively). Second, being more consistent in its effects, the silicone‐coated suture was further studied in Wistar and Fischer‐344 rats (n=12 for each). Seventy‐five per cent of the Wistar’s died prematurely from gross hemispheric oedema. Motor deficit and extent of infarction in the Fischer‐344 rats were both significantly greater compared with Sprague‐Dawley rats (e.g. total cerebral infarct volume at 24 h in the former was 253.6±25.4 mm3 , n=11, P<0.05), and more consistent (coefficient of variation was only 10.0%). It was concluded that the silicone‐coated suture and the Fischer‐344 rats strain produced the most consistent results and their novel combination provides a reliable acute stroke model.
Changes to the cytokine microenvironment in the genital tract mucosa of HIV+ women

As previous studies have indicated that genital tract mucosal T cell function may be impaired in HIV infection, we investigated the T cell cytokine mRNA in the genital tract mucosa of HIV‐infected women to determine if there are alterations in the cytokine profile which may explain the T cell impairment. The in situ hybridization technique was used to investigate the T helper‐1 (Th1: IL‐2, interferon‐gamma (IFN‐γ)) and Th2 cytokine (IL‐4, IL‐5, IL‐10) mRNA profile in cervical biopsies from 10 HIV+ and 10 HIV− subjects. Cervical intraepithelial neoplasia (CIN) and genital infection had previously been excluded and the distribution of immunocompetent cells within the cervical mucosa was known for each subject. Non‐parametric tests were used to compare the optical density (OD) of cytokine mRNA in the HIV+ and HIV− groups. Comparisons were also made between peripheral CD4 lymphocyte counts, cervical CD4/CD8 T lymphocyte ratios and cytokine mRNA OD in HIV+ subjects. The HIV+ women had significantly higher mRNA OD for the Th2 cytokines IL‐4, IL‐5 and IL‐10 than HIV− women. There was also significantly lower IL‐2 mRNA OD in the former group. HIV+ women had lower IFN‐γ mRNA than HIV− women, but the difference was not statistically significant. There was no correlation between cytokine mRNA OD and peripheral CD4 count or cervical CD4/CD8 ratio. The predominance of Th2 cytokines, which are immuno‐inhibitory, in the cervical mucosa of HIV+ women may underlie the impaired cytotoxic potential observed in the CD8+ T lymphocytes and may contribute to the susceptibility of HIV‐infected women to recurrent genital tract infections and cervical neoplasia.
Outcome Expectancies and Ecstasy Use in Visitors of Rave Parties in the Netherlands

The aim of this study was to examine the associations between outcome expectancies and ecstasy use in a sample of visitors of raves. The type of expectancies that people endorse were explored, as well as the differences between users and nonusers in expected outcomes of ecstasy use, and the associations between expectancies and quantity of ecstasy use within the group of users. Questionnaires were administered to 844 young visitors of 7 parties in the Netherlands, of which 543 reported to be users. Drug use on these parties was high: 65% reporting ecstasy use. Factor analyses showed 7 factors: negative consequences, enhancement, euphoria, sexiness, dancing, communication and self-insight. These factors strongly discriminated between users and nonusers. In particular those who scored high on self-insight and low on negative effects were most likely to use ecstasy. The expected outcomes of ecstasy are related to ecstasy use and patterns of use providing information for health education directed on long-term negative and positive effects of ecstasy use. Longitudinal research on random samples of visitors of raves is warranted.
Firm and industry informational content from REIT FFO announcements

ABSTRACT Conveyance of information associated with REIT FFO announcements is investigated by decomposing stock returns into three components: firm-specific, industry-level and market-wide. The relative importance of firm-specific and industry information is evaluated around and following FFO announcements. The initial market reaction to REIT FFO announcements is primarily driven by the firm-specific return component. The underreaction to firm-specific information appears in drift after the announcement, especially for negative FFO surprises. FFO surprises explain the firm-specific return component, but not the industry-level return component which further suggests that FFO announcements only convey firm-specific information.
Cell proliferation studies in primary synovial chondromatosis

Primary synovial chondromatosis (PSC) is thought to be a cartilaginous metaplasia, but it may recur locally and malignant change has been reported. Histologically, the cartilage is usually cellular, with binucleate forms. These findings suggest that the disease is not simply a metaplasia but imply a proliferative component. In this study, immunohistochemical detection of Ki‐67 protein using an antigen retrieval microwave heating technique and DNA image cytometry (VIDAS image analysis system) has been used to assess the proliferative activity in 20 cases of PSC and the results have been compared with those obtained in other cartilage tissues: ten enchondromas, ten chondrosarcomas, and ten samples of normal articular cartilage. There was no detectable staining for Ki‐67 protein in cases of PSC or in benign tissues, but there was a significant association between Ki‐67 labelling index and grade in the chondrosarcomas (P<0·01). The absence of mitotic figures and the lack of Ki‐67 protein in PSC are consistent with a metaplasia. All enchondromas gave diploid DNA histograms but non‐diploid histograms were obtained in eight cases (40 per cent) of PSC, with significant populations of hyperdiploid and DNA aneuploid cells. The mean DNA content, the percentage of hyperdiploid cells, the percentage of DNA aneuploid cells, and the 2c deviation index were all significantly higher in PSC than in enchondromas (P<0·01). These findings with image cytometry suggest a proliferative process in the development of at least some cases of PSC. In terms of cell proliferative activity, PSC appears to occupy a position which is intermediate between benign enchondromas and malignant chondrosarcomas, which may explain the aggressive clinical behaviour occasionally seen in this condition. © 1998 John Wiley & Sons, Ltd.
A Study of F1 Correlation with F0 in a Tone Language: Case of Thai

This is an empirical study of vowels of Thai language as spoken in Bangkok in terms of two parameters, namely - tones, levels and contours as reflected in F0 variations, and lower formant, F1 which is high for open/ low vowels and low for close/ high vowels. We examine each one of the nine long vowels with all the five phonemic tones to find out the correlation between the pitch of voice, a laryngeal phenomenon and the first formant which is part of the resonance phenomenon. The results give us some interesting hypotheses to be explored further with data from different tonal and non-tonal languages. F1-F0 correlations, if established will have significant implications for TTS studies, for comparison across speakers for speaker characterization and forensic applications.
MPC and PID control based on Multi-Objective Optimization

The design of sophisticated control systems have led in the past ten years to the necessity of satisfying more than one design criterion. Thus, it is natural to think that those criteria can be met in an optimal manner. If several criteria have simultaneously to be optimized, one is in presence of a multi-objective optimization problem. In this paper, many efforts to design the most popular control strategies, i.e. PID and MPC, by using multi-objective optimization techniques are reviewed. Both control strategies have dissimilar optimization characteristics and therefore, they can be considered as representative of two different multi-objective optimization problems, which are described including definitions, possible solutions, algorithms and available software implementations.
The value of colposcopy in screening cervical carcinoma.

The value of colposcopy and cytology in screening CIN was analyzed in a retrospective study of 1,504 patients treated at the Department of Gynecologic Oncology, National Institute of Oncology, Budapest from 1980 to 1991. The majority (1,451) of the patients were admitted for histological confirmation of atypical colposcopic and/or cytologic findings, and 53 women were treated for cervical repair. All women underwent either cervical excision or conization. Cytologic and colposcopic findings were compared with the histological results. Sensitivity and specificity rates of cytology were 47% and 77%, respectively. The corresponding figures for colposcopy were 87% and 15% and for cytology and colposcopy together, 96% and 14%. The low sensitivity of cytology suggests that as many as 50% of CIN lesions may be overlooked if cytology alone is used for screening, i.e. in 50% of CIN associated with abnormal colposcopy the cytology was negative. We found 194 asymptomatic patients with carcinoma in situ, 40 with microinvasive and 8 with frank invasive carcinoma. This finding emphasizes the importance of cervical cancer screening. Our data suggest that, with colposcopy as a screening tool, the rate of false-negative cytology can be significantly reduced. Clinical implications of the "cytology-negative abnormal colposcopy and cytology-negative CIN" have yet to be determined. The major drawback of primary colposcopy is its low specificity with the consequence of high false-positive rate and over-treatment in a substantial number of cases. To overcome the problem of low specificity, further studies are required to identify those atypical colposcopic changes that most likely represent CIN--and high-grade CIN in particular.
Antiphospholipid antibodies and platelet activation as risk factors for thrombosis in thrombocythaemia

Abstract Introduction: Risk factors for thrombosis (TB) in thrombocythaemia (TC) associated with myeloproliferative disorder (MPD) are not well defined. Methods: We measured antiphospholipid antibodies (APLA) in 35 patients with TC associated with MPD. Fourteen had TB and 21 did not. We assayed IgG and IgM APLA by ELISA for 6 antigens: β2GP1, cardiolipin (CL), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and FVII/VIIa, together with markers of activation of platelets (CD62P) and endothelium [endothelial microparticles (EMP)]. Results: At least one positive APLA was detected in 66% of TC patients overall. The incidence was significantly higher in the TB subgroup (92.8%) than non-TB (47.6%, p < 0.05). Multiple APLA (positive for more than one antigen) were also more frequent in TB, for both IgG and IgM, for all 6 antigens tested (p < 0.05). However, IgM APLA predominated, being about 2-fold more frequently positive than IgG for all 6 antigens. Platelet CD62P was significantly higher in the TB group (p < 0.05). EMP did not differ between TB and non-TB. The most frequent thrombotic complication was recurring ischemic cerebral vascular accidents (ICVA), leading to progressive cognitive impairment. Venous TB often developed at unusual sites. Recurring and reversible TB were common features in TC. Summary: This study suggests that APLA and platelet activation are risk factors for TB in TC. APLA are prevalent in TC, and IgM APLA predominated over IgG. Activation of platelets but not of endothelium may be consistent with the reversible and recurrent features of TB in TC.
On Three Standard Results in the Theory of Insurance Demand

Abstract This article re-examines three standard results in the theory of insurance demand: (i) full coverage with a fair premium and partial coverage with an unfair premium; (ii) insurance is an inferior good under decreasing absolute risk aversion (DARA) and (iii) insurance may be a Giffen good under DARA. It has been shown recently that (i) holds for the class of insurance policies in which maximum coverage fully covers the potential loss. We show that whether (i) holds beyond this class of policies is indeterminate. In addition, we employ a unified framework to investigate the effects of changes in initial wealth and price. In particular, we show that both (ii) and (iii) hold for a certain class of insurance policies which include all commonly-used types of policies. The result also provides a unified treatment of several results in the extant literature.
Emerging Market Contagion Under Geopolitical Uncertainty

ABSTRACT We find that 10 emerging stock markets have high risk of contagion on the regional level but lower spillover with respect to the global markets, implying a potential for diversification benefits between emerging and global markets. Regional market integration seems to have been caused by trade integration, which has a policy implication for trade agreements’ systemic risk effects. We find that the geopolitical risk has no impact on either the return, or volatility spillovers. However, the general stock market risk (VIX) is connected to individual market volatilities, while the oil market is largely receiving the spillovers from the other markets.
Effect of Pre‐Exhaustion Exercise on Lower‐Extremity Muscle Activation During a Leg Press Exercise

The purpose of this study was to investigate the effect of preexhaustion exercise on lower-extremity muscle activation during a leg press exercise. Pre-exhaustion exercise, a technique frequently used by weight trainers, involves combining a single-joint exercise immediately followed by a related multijoint exercise (e.g., a knee extension exercise followed by a leg press exercise). Seventeen healthy male subjects performed 1 set of a leg press exercise with and without pre-exhaustion exercise, which consisted of 1 set of a knee extension exercise. Both exercises were performed at a load of 10 repetitions maximum (10RM). Electromyography (EMG) was recorded from the rectus femoris, vastus lateralis, and gluteus maximus muscles simultaneously during the leg press exercise. The number of repetitions of the leg press exercise performed by subjects with and without pre-ex-haustion exercise was also documented. The activation of the rectus femoris and the vastus lateralis muscles during the leg press exercise was significantly less when subjects were pre-exhausted (p < 0.05). No significant EMG change was observed for the gluteus maximus muscle. When in a pre-exhausted state, subjects performed significantly (p < 0.001) less repetitions of the leg press exercise. Our findings do not support the popular belief of weight trainers that performing pre-exhaustion exercise is more effective in order to enhance muscle activity compared with regular weight training. Conversely, pre-exhaustion exercise may have disadvantageous effects on performance, such as decreased muscle activity and reduction in strength, during multijoint exercise.