Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of high altitude exposure on the pharmacokinetics of furosemide in healthy volunteers.

INTRODUCTION A cascade of pathophysiological events occurs with the ascension to high altitude (H). We have performed studies on the effects of exposure to H on the pharmacokinetics of drugs. The hypothesis behind these studies has been that the exposure to H, which produces marked physiological changes in the body, may alter pharmacokinetics, and consequently, pharmacodynamics. Our previous studies suggest that drugs highly bound to plasma proteins are most likely to exhibit altered disposition. OBJECTIVE In continuation of our research, we selected furosemide which is about 98% bound to plasma proteins, renally excreted and has low binding to red blood cells. SUBJECTS, MATERIALS AND METHODS Furosemide (40 mg) was administered orally to 3 groups of young healthy volunteers. One group who had been residing at sea level (group L), the same group after 15 hours of exposure to high altitude (3,600 m, group HA) and a group of volunteers living at H for at least 6 months (group HC). RESULTS Our results are in accordance with the most recent pharmacokinetic studies on furosemide in which a terminal half-life of approximately 20-30 h was reported. Total proteins were 9.3% and 12.7% higher in groups HA and HC, respectively, than in group L. Albumin in group HC was 8.2% higher than group L. Bilirubin increased 17.7% and 41.2% in groups HA and HC, respectively, in comparison with group L. A rapid disposition rate constant in groups HA and HC was the only pharmacokinetic parameter that was significantly different from those in group L. Concentration of furosemide in plasma water increased significantly after H exposure, thus, the binding diminished from 97.2% in group L to 95.1% and 91.1% in groups HA and HC, respectively. CONCLUSION Exposure to H produces an increase in the free fraction of furosemide in humans, which could be of therapeutic importance.
Choice of Resolution by Functional Trait or Taxonomy Affects Allometric Scaling in Soil Food Webs

Belowground organisms often display a shift in their mass-abundance scaling relationships due to environmental factors such as soil chemistry and atmospheric deposition. Here we present new empirical data that show strong differences in allometric scaling according to whether the resolution at the local scale is based on a taxonomic or a functional classification, while only slight differences arise according to soil environmental conditions. For the first time, isometry (an inverse 1∶1 proportion) is recognized in mass-abundance relationships, providing a functional signal for constant biomass distribution in soil biota regardless of discrete trophic levels. Our findings are in contrast to those from aquatic ecosystems, in that higher trophic levels in soil biota are not a direct function of increasing body mass.
Optimization of codon usage of plasmid DNA vaccine is required for the effective MHC class I-restricted T cell responses against an intracellular bacterium.

In an attempt to study codon usage effects of DNA vaccines on the induction of MHC class I-restricted T cell responses against an intracellular bacterium, Listeria monocytogenes, we designed two plasmid DNA vaccines encoding an H-2Kd-restricted epitope of listeriolysin O (LLO) of L. monocytogenes, LLO 91-99. One DNA vaccine, p91wt, carries the wild-type DNA sequence encoding LLO 91-99, and the other one, p91mam, possesses the altered DNA sequence in which the codon usage was optimized for murine system. Our read-through analyses with LLO 91-99/luciferase fusion genes confirmed that the optimized 91mam DNA sequence showed extremely higher translation efficiency than the wild-type sequence in murine cells. Consistent with this, i.m. injections of p91mam, but not of p91wt, into BALB/c mice were capable of inducing specific CTL- and IFN-gamma-producing CD8+ T cells able to confer partial protection against listerial challenge. Taken together, these observations suggest that optimization of codon should be taken into consideration in the construction of DNA vaccines against nonviral pathogens.
Heparan Sulfate Proteoglycans as Regulators of Fibroblast Growth Factor-2 Signaling in Brain Endothelial Cells

Fibroblast growth factor-2 (FGF2) is a potent angiogenic factor in gliomas. Heparan sulfate promotes ligand binding to receptor tyrosine kinase and regulates signaling. The goal of this study was to examine the contribution of heparan sulfate proteoglycans (HSPGs) to glioma angiogenesis. Here we show that all brain endothelial cell HSPGs carry heparan sulfate chains similarly capable of forming a ternary complex with FGF2 and fibroblast growth factor receptor-1c and of promoting a mitogenic signal. Immunohistochemical analysis revealed that glypican-1 was overexpressed in glioma vessel endothelial cells, whereas this cell-surface HSPG was consistently undetectable in normal brain vessels. To determine the effect of increased glypican-1 expression on FGF2 signaling, we transfected normal brain endothelial cells, which express low base-line levels of glypican-1, with this proteoglycan. Glypican-1 expression enhanced growth of brain endothelial cells and sensitized them to FGF2-induced mitogenesis despite the fact that glypican-1 remained a minor proteoglycan. In contrast, overexpression of syndecan-1 had no effect on growth or FGF2 sensitivity. We conclude that the glypican-1 core protein has a specific role in FGF2 signaling. Glypican-1 overexpression may contribute to angiogenesis and the radiation resistance characteristic of this malignancy.
Population Genetic Structure of the Cotton Bollworm Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) in India as Inferred from EPIC-PCR DNA Markers

Helicoverpa armigera is an important pest of cotton and other agricultural crops in the Old World. Its wide host range, high mobility and fecundity, and the ability to adapt and develop resistance against all common groups of insecticides used for its management have exacerbated its pest status. An understanding of the population genetic structure in H. armigera under Indian agricultural conditions will help ascertain gene flow patterns across different agricultural zones. This study inferred the population genetic structure of Indian H. armigera using five Exon-Primed Intron-Crossing (EPIC)-PCR markers. Nested alternative EPIC markers detected moderate null allele frequencies (4.3% to 9.4%) in loci used to infer population genetic structure but the apparently genome-wide heterozygote deficit suggests in-breeding or a Wahlund effect rather than a null allele effect. Population genetic analysis of the 26 populations suggested significant genetic differentiation within India but especially in cotton-feeding populations in the 2006–07 cropping season. In contrast, overall pair-wise F ST estimates from populations feeding on food crops indicated no significant population substructure irrespective of cropping seasons. A Baysian cluster analysis was used to assign the genetic make-up of individuals to likely membership of population clusters. Some evidence was found for four major clusters with individuals in two populations from cotton in one year (from two populations in northern India) showing especially high homogeneity. Taken as a whole, this study found evidence of population substructure at host crop, temporal and spatial levels in Indian H. armigera, without, however, a clear biological rationale for these structures being evident.
The vestibular system: balancing more than just the body.

PURPOSE OF REVIEW The review presents a selection of recent studies in the field of vestibular neuroscience, including how vestibular stimulation modulates space and body perception. RECENT FINDINGS Recent neuroimaging studies identified the operculo-insular/retroinsular cortex as the core vestibular cortex and showed how it is reorganized after vestibular dysfunctions. Subliminal galvanic vestibular stimulation (GVS) induces long-term reduction of hemispatial neglect and improves vertical perception in stroke patients, but the underlying mechanisms remain to be identified. Healthy volunteer research suggests that GVS and caloric vestibular stimulation (CVS) modulate visual and somatosensory processing and that beneficial effects of GVS/CVS in stroke patients are not limited to merely rebalancing brain hemispheric activity. Another mechanism would be that GVS/CVS anchors the self to the body, thus promoting an egocentric frame of reference. SUMMARY In addition to 'balancing the body', the vestibular cortical network contributes to modulate space, body and self-awareness. Emerging evidence suggests that the vestibular network expands into dimensions of emotion processing, mental health, and social cognition. Here, the importance of connecting vestibular physiology, affective neuroscience, and social neuroscience to better understand the psychological aspects of vertigo in otoneurology is discussed.
Teacher communication, student identity and classroom participation

This paper draws on research in progress with early school leavers and non-completers of schooling to argue that mathematics classrooms can be usefully considered as communities of practice. In these communities of practice, social relationships are negotiated and identities are formed which can be critical for these students’ long term success or failure in learning mathematics. In such social settings, processes of participation and non-participation are crucial to the construction of group and individual identities, and the social skills of the teacher and her ability to communicate and engage effectively with such students can be as important as her knowledge of content.
Structures of Bordered Pits Potentially Contributing to Isolation of a Refilled Vessel from Negative Xylem Pressure in Stems of Morus australis Poir.: Testing of the Pit Membrane Osmosis and Pit Valve Hypotheses

Two hypotheses have been proposed to explain the mechanism preventing the refilling vessel water from being drained to the neighboring functional vessels under negative pressure. The pit membrane osmosis hypothesis proposes that the xylem parenchyma cells release polysaccharides that are impermeable to the intervessel pit membranes into the refilling vessel; this osmotically counteracts the negative pressure, thereby allowing the vessel to refill. The pit valve hypothesis proposes that gas trapped within intervessel bordered pits isolates the refilling vessel water from the surrounding functional vessels. Here, using the single-vessel method, we assessed these hypotheses in shoots of mulberry (Morus australis Poir.). First, we confirmed the occurrence of xylem refilling under negative pressure in the potted mulberry saplings. To examine the pit membrane osmosis hypothesis, we estimated the semi-permeability of pit membranes for molecules of various sizes and found that the pit membranes were not semi-permeable to polyethylene glycol of molecular mass <20,000. For the pit valve hypothesis, we formed pit valves in the intervessel pits in the short stem segments and measured the maximum liquid pressure up to which gases in bordered pits were retained. The threshold pressure ranged from 0.025 to 0.10 MPa. These values matched the theoretical value calculated from the geometry of the pit chamber (0.0692-0.101 MPa). Our results suggest that gas in the pits is retained by surface tension, even under substantial positive pressure to resolve gases in the refilling vessel, whereas the molecule size required for the pit membrane osmosis mechanism in mulberry would be unrealistically large.
An algorithm with nearly optimal pseudo-regret for both stochastic and adversarial bandits

We present an algorithm that achieves almost optimal pseudo-regret bounds against adversarial and stochastic bandits. Against adversarial bandits the pseudo-regret is $O(K\sqrt{n \log n})$ and against stochastic bandits the pseudo-regret is $O(\sum_i (\log n)/\Delta_i)$. We also show that no algorithm with $O(\log n)$ pseudo-regret against stochastic bandits can achieve $\tilde{O}(\sqrt{n})$ expected regret against adaptive adversarial bandits. This complements previous results of Bubeck and Slivkins (2012) that show $\tilde{O}(\sqrt{n})$ expected adversarial regret with $O((\log n)^2)$ stochastic pseudo-regret.
Tendon or joint disorders in children after treatment with fluoroquinolones or azithromycin

Background. Fluoroquinolones (FQs) have been infrequently used in children, largely because of concern that these agents can cause lesions of the cartilage in juvenile animals. However, the relevance of this laboratory observation to children treated with FQs is unknown. A retrospective, observational study was conducted to assess the incidence and relative risk of tendon or joint disorders (TJDs) that occur after use of selected FQs compared with azithromycin (AZ), a drug with no known effect on cartilage or tendons in humans or animals. Methods. An automated database was searched to identify patients younger than 19 years who had been prescribed ofloxacin (OFX), levofloxacin, ciprofloxacin (CPX), or AZ. Potential cases of TJD occurring within 60 days of a prescription of one of the study drugs were identified based on assignment of a claims diagnosis consistent with a TJD within this period. Verified cases were identified by a blinded review of abstracts of medical records from subjects identified as potential cases. Results. The incidence of verified TJD was 0.82% for OFX (13 of 1593) and CPX (37 of 4531) and was 0.78% for AZ (118 of 15 073). The relative risk of TJD for OFX and CPX compared with AZ was 1.04 (95% confidence interval, 0.55 to 1.84) and 1.04 (95% confidence interval, 0.72 to 1.51), respectively. The distributions of claims diagnoses and time to onset of TJD were comparable for all groups. The most frequently reported category of TJD involved the joint followed by tendon, cartilage and gait disorder. Conclusions. In this observational study involving more than 6000 FQ-treated children, the incidence of TJD associated with selected FQ use in children was <1% and was comparable with that of the reference group, children treated with AZ.
What are conservatoires for? : discourses of purpose in the contemporary conservatoire

ABSTRACT This thesis is a study of a modern day UK conservatoire. In the context of recent debates on the purpose of higher education, I look at how discourses of purpose are constructed, confirmed and contested in the contemporary conservatoire. The analytical strategies I use to construct my research account follow a Foucauldian conception of discourse, an approach which allows me to combine historical and contemporary material to develop categories of discourse. By historical account, I show how the conservatoire model founded at the start of the nineteenth century embodies an institutionalisation of the discourse of classical music. Using interview texts and institutional literature gathered from my empirical setting, I identify continuities with the discourse of classical music in the contemporary conservatoire, concluding that the student is produced as a performer and interpreter of canonical works. I find the discourse of classical music challenged by more recent discourses on higher education, particularly that of higher education for employability and higher education for personal development. I argue that an over-reliance on these discourses produces a limiting approach to music in higher education by promoting technical and transferable skills over a critical and creative engagement with music. I advocate a return to practices which support discourses of new music and antispecialism, which challenge the performer as reverent interpreter and allow for engagement with a greater range of repertoire, new interpretative pathways, improvisation and composition. In doing so, the conservatoire could better fulfil its claim to being part of an education which is both musical and 'higher'. I locate my research within the field of higher education studies, and my research forms an original contribution to the sociology of music in higher education, a lesserused disciplinary approach to a newly burgeoning field.
Face Processing Strategies in Children with Autism Spectrum Disorder

The primary aim of this thesis was to investigate the face processing strategies of children with high-functioning autism. Based on the assumptions that face processing relies on holistic, configural and featural information processing of faces, and on previous findings that individuals with autism show atypicalities in configural and/or holistic face processing, experiments in the current thesis were designed in order to further investigate configural and holistic processing of faces in ASD. Experiment 1 investigated configural processing with the use of the ‘Jane Task’ (Mondloch, et al., 2002). Experiment 2 investigated holistic processing by replicating the part-whole paradigm (Joseph & Tanaka, 2003). Experiments 3 and 4 aimed to clarify the relationship between configural and holistic processing and their operationalisation, by applying the face distinctiveness effect paradigm (Johnston & Ellis, 1995). Experiment 5 aimed to further investigate the face inversion effect and its implications on configural processing. Overall, our participants with ASD showed typical holistic and configural face processing when faces were upright. However, when face stimuli were presented in inverted conditions, participants with ASD showed atypicalities and differences compared to a typically developing comparison group of children. It was concluded that children with ASD develop compensatory strategies for processing faces which are effective for upright faces, however when faces are upside down these strategies fail to support recognition and so impairments become apparent. Implications of the current findings are discussed in relation to the broader theories of autism as well as the face processing literature and the current paradigms used to investigate the different types of face processing
Romantic Relationships at Work: Why Love Can Hurt

The academic community, practitioner literature and newspapers have all taken an interest in workplace romance. This paper aims to review the literature on workplace romance and to argue that the issue of power is key to understanding the negative consequences for individuals and organizations, linking workplace romance with theories or explanatory models of power. The paper first examines definitions of workplace romance, presents evidence of its prevalence, distinguishes between different types of workplace romance, and then looks at the main issues that managers and organizations face when considering the issue. The approaches taken by research in management, law, psychology and sociology are contrasted. The motivations for romance and the place of culture are described. Secrecy, gender differences and the negative and positive outcomes for men and women are discussed. The link between romance and harassment is explored. The paper looks at what organizations have done to manage romance. The research methods that have been used are reviewed, as are the gaps and weaknesses in order to make recommendations for future research. The review synthesizes accumulated knowledge in both research and practice, ending by identifying recommendations for managers.
Cholesterol and Late-Life Cognitive Decline

High cholesterol levels are a major risk factor for cardiovascular disease, but their role in dementia and cognitive decline is less clear. This review highlights current knowledge on the role of cholesterol in late-life cognitive function, cognitive decline, and dementia. When measured in midlife, high cholesterol levels associate with an increased risk of late-life dementia and cognitive decline. However, when measured in late-life, high cholesterol levels show no association with cognitive function, or even show an inverse relation. Although statin treatment has been shown to associate with a lower risk of dementia and cognitive decline in observational studies, randomized controlled trials show no beneficial effect of statin treatment on late-life cognitive function. Lowering cholesterol levels may impair brain function, since cholesterol is essential for synapse formation and maturation and plays an important role in the regulation of signal transduction through its function as a component of the cell membrane. However, membrane cholesterol also plays a role in the formation and aggregation of amyloid-β. Factors that influence cholesterol metabolism, such as dietary intake, are shown to play a role in late-life cognitive function and the risk of dementia. In conclusion, cholesterol associates with late-life cognitive function, but the association is strongly age-dependent. There is no evidence that treatment with statins in late-life has a beneficial effect on cognitive function.
Inferring driver's turning direction through detection of error related brain activity

This work presents EEG-based Brain-computer interface (BCI) that uses error related brain activity to improve the prediction of driver's intended turning direction. In experiments while subjects drive in a realistic car simulator, we show a directional cue before reaching intersection, and analyze error related EEG potential to infer if the presented direction coincides with the driver's intention. In this protocol, the directional cue provides an initial estimation of the driving direction (based on EEG, environmental or previous driving habits), and we focus on the recognition of error-potentials it may elicit. Experiments with 7 healthy human subjects yield an average classification 0.69±0.16, which confirms the feasibility of decoding these signals to help estimating driver's turning direction. This study can be further exploited by intelligent cars to tune their driving assistant systems to improve their performance and enhance the driving experience.
Holding Children for Clinical Procedures: Perseverance in Spite of or Persevering to be Child-Centered.

Children in acute care often need procedures and interventions, and they are frequently held, often against their wishes, to enable these procedures to be completed. This report is from a qualitative investigation in which we sought to explore what happens when children undergo clinical procedures within an acute hospital, with a focus on the use of holding for procedures. Qualitative data were generated through non-participant observation of clinical procedures (n = 31) and semi-structured interviews with health professionals (n = 22), parents (n = 21), and children (n = 4) to explore the event from the participants' perspective. Data were analyzed using constant comparison. Through the central theoretical concept of perseverance, we examined the actions, inactions and interactions of health professionals, parents and children during a clinical procedure. Two broad trajectories were noted: "perseverance in spite of," when the procedure was completed despite a child's upset and lack of co-operation; and "perseverance to be child-centered," which was characterized by a purposeful plan of action focused on a child who had been prepared and informed, and which was facilitated by a "window of opportunity" at the start of the procedure when the child was calm and engaged. Our findings highlight that professionals need to be clear about their boundaries when starting or continuing with a procedure when a child is distressed, and support preparation and engagement activities with children and parents before, during, and after clinical procedures.