Miracle-dz/UniFAR-FTUs huggingface dataset:
High-dose cyclophosphamide or melphalan with escalating doses of mitoxantrone and autologous bone marrow transplantation for refractory solid tumors.

As the dose-limiting toxicity of mitoxantrone is hematological, the drug is suitable for dose escalation and use in intensive chemotherapy followed by autologous bone marrow rescue. Adult patients with therapy-resistant solid tumors received a regimen of high-dose cyclophosphamide (7 g/m2) and escalating doses of mitoxantrone in dose steps of 30, 45, 60, and 75 mg/m2. Both drugs were given i.v. on 3 consecutive days. Despite the addition of mesnum (3.5 to 7 g/m2), hemorrhagic cystitis occurred on the second day in four of eight patients, irrespective of the mesnum or mitoxantrone dose. Therefore, the cyclophosphamide in the combination regimen was replaced by high-dose melphalan (180 mg/m2). Mucositis was dose limiting at 75 mg/m2 of mitoxantrone. Responses were seen in eight of ten evaluable patients with four complete responses. Three responders received, after the autologous bone marrow transplantation program, radiotherapy or surgery on pretreatment bulky tumor localizations. Five patients still have disease-free survival after 9 to 36 mo. Pharmacokinetic studies of mitoxantrone were performed by high-performance liquid chromatography with UV detection. The plasma disappearance of mitoxantrone fitted into a three-compartment model with a mean t1/2 alpha of 10 min, a mean t1/2 beta of 96 min, and a slow elimination phase of 172 h. The mean distribution volume was 4294 +/- 3836 liters. We conclude that the high-dose cyclophosphamide-mitoxantrone regimen led to unexpected bladder toxicity, but the combination of melphalan (180 mg/m2) and mitoxantrone (60 mg/m2) can probably be given without major extramedullary toxicity. However, more patients should be evaluated at this dose before definite conclusions can be drawn about toxicity.
The influence of social presence on enjoyment and intention to use of a robot and screen agent by elderly users

When using a robot or a screen agent, elderly users might feel more enjoyment if they experience a stronger social presence. In two experiments with a robotic agent and a screen agent (both n=30) this relationship between these two concepts could be established. Besides, both studies showed that social presence correlates with the intention to use the system, although there were some differences between the agents. This implicates that factors that influence social presence are relevant when designing assistive agents for elderly people.
Falls from Heights: A Surgical Experience of 200 Consecutive Cases

SummaryA review of 200 patients who fell from various heights is reported. The age incidence was greatest in the first three decades, the first decade being greatest. The higher the fall, the greater the mortality. Statistically, the 0–10 year and over 50 years age groups had the same mortality rate. The condition of the patient on ad-mission influenced survival. Patients who entered the hospital comatose or in shock had a greater mortality rate. Multiple injuries of long bones or visceral injuries alone did not affect survival, but these injuries associated with either pelvic or skull fractures increased mortality. Patients with vertebral fractures had minimal clinical symptoms and the association of vertebral and os calcis fractures was not frequent in these vertical deceleration injuries. Clinical management of patients with multiple injuries is discussed.
States' rights, women's obligations: Contemporary welfare reform in historical perspective

This abstract asks how the demise of the federal ‘‘entitlement’’ to welfare will affect how low-income single mothers will be governed. Historical-institutional analysis is used to predict how the states, given their regained authority, are likely to define eligibility and procedural rules for welfare. These expectations are tested by analyzing the new state plans for the administration of the Temporary Assistance to Needy Families block grant program. Indices of eligibility rules and procedural rules are created and combined in a typology that depicts the new varieties of welfare governance planned by the states. The central argument is that as historical precedents would imply, the decentralization of authority for welfare is promoting the development of forms of welfare governance that vary dramatically from state to state, and which tend, predominantly, toward restrictive and coercive forms of rule. These developments mean that the obligations of poor women are being emphasized over their access to social provision. [Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: getinfo@haworthpressinc. com <Website: http://www.haworthpressinc. com>] For helpful comments on earlier drafts of this paper, the author wishes to thank David Brian Robertson, Jodi Sandfort, Sally Selden, Jeff Stonecash, Susan Thistle, John Yinger and three anonymous reviewers for Women & Politics. Women & Politics, Vol. 21(1) 200
Key Management Determinants For Cloud Computing Adoption

Although there are a significant number of advantages associated with cloud computing, there is less clarity of what are the key management determinants for cloud computing adoption. This research aims to evaluate the significance of various factors that influence the adoption decision of cloud computing services by organisations within the United Kingdom (UK). The ‘Technology-Organisation-Environment’ (TOE) adoption framework was used to develop eight hypotheses which allowed data collection through a self-created questionnaire based survey that was completed by 257 mid-to-senior level decision making business and IT professionals from a range of UK end-user organisations. The derived hypotheses were tested using various data analysis techniques including factor analysis and logistic regression. The results show that four of the eight factors examined have a significant influence on the adoption decision of cloud computing services in the UK. Those key factors are competitive pressure, complexity, technology readiness and trading partner pressure. The latter predictor; trading partner pressure, had the highest level of significance on the adoption decision of cloud services. The findings reveal how important the environmental context surrounding both the competitive pressure and more importantly trading partner pressure is on cloud adoption. This enables end-user organisations to better evaluate the cloud and vendors the opportunity of improving their offerings.
HIV Rev Assembly on the Rev Response Element (RRE): A Structural Perspective

HIV-1 Rev is an ~13 kD accessory protein expressed during the early stage of virus replication. After translation, Rev enters the nucleus and binds the Rev response element (RRE), a ~350 nucleotide, highly structured element embedded in the env gene in unspliced and singly spliced viral RNA transcripts. Rev-RNA assemblies subsequently recruit Crm1 and other cellular proteins to form larger complexes that are exported from the nucleus. Once in the cytoplasm, the complexes dissociate and unspliced and singly-spliced viral RNAs are packaged into nascent virions or translated into viral structural proteins and enzymes, respectively. Rev binding to the RRE is a complex process, as multiple copies of the protein assemble on the RNA in a coordinated fashion via a series of Rev-Rev and Rev-RNA interactions. Our understanding of the nature of these interactions has been greatly advanced by recent studies using X-ray crystallography, small angle X-ray scattering (SAXS) and single particle electron microscopy as well as biochemical and genetic methodologies. These advances are discussed in detail in this review, along with perspectives on development of antiviral therapies targeting the HIV-1 RRE.
The Convergence of Multi-Level Methods for Solving Finite-Element Equations in the Presence of Singularities

The known convergence proofs for multi-level methods assume the quasi-uniformity of the family of domain triangulations used. Such triangulations are not suitable for problems with singularities caused by re-entrant corners and abrupt changes in the boundary condi- tions. In this paper it is shown that families of properly refined grids yield the same convergence behavior of multi-level methods for such singular problems as quasi-uniform subdivisions do for H2-regular problems. 1. The Continuous Problem, Its Discretization and the Multi-Level Method. Using multi-level techniques ((1), (3), (4), (6), (7), (8), (10)), it is possible to solve the large systems of linear equations arising in connection with finite-element methods with an amount of work roughly proportional to the number of unknowns. This property makes multi-level methods at least theoretically superior to all other solution methods, including fast solvers based on FFT-like algorithms which may be directly applied to special problems only. The convergence of multi-level methods was proved, for example, by Nicolaides (10), Bank and Dupont (4) and Hackbusch (8). All these proofs assume a certain amount of elliptic regularity of the continuous problem to be solved approximately, and quasi-uniform subdivisions of the domain in finite elements. Assuming H1+a- regularity, such quasi-uniform triangulations and a Jacobi-like smoothing procedure, Bank and Dupont (4) and Hackbusch (8) showed the following result: The rate of convergence of a full iteration step of the multi-level method behaves like O(m 0/2), uniformly in the number of levels, for a growing number m of smoothing steps per level. In the optimal case a = 1, the problem has to be H2-regular. This means, for example, that the region is not allowed to have re-entrant corners. If this condition is violated, the convergence rate of the multi-level procedure decreases, and, in addition, the approximation properties of the finite-element discretization itself change for the worse because of the presence of singularities in the solution not captured by the quasi-uniform grids. The strongly nonuniform, systematically re- fined triangulations suitable for these problems are not included in the theory so far. The aim of the present paper is to fill this gap.
The development of fears from early adolesence to young adulthood: a multivariate study

Background Common fears change over development. Genetic and environmental risk factors for fears are partly shared across fears and partly fear-specific. The nature of the changes in common and fear-specific genetic and environmental risk factors over time is unknown. Method Self-reported fears were obtained at ages 13–14, 16–17 and 19–20 from 2404 twins in the Swedish Twin Study of Child and Adolescent Development. A multivariate longitudinal twin analysis was conducted with Mx. Results Eighteen individual items formed four fear factors: animal, blood-injury, situational, and social. The best-fit model had no quantitative or qualitative sex effects or shared environmental effects, but included a strong common factor with a stable cross-time structure with highest loadings on situational and lowest loadings on social fears. New common and fear-specific genetic risk factors emerged over development. With increasing age, genetic effects declined in overall importance and became more fear-specific. Cross-time continuity in specific genetic effects was highest for animal and lowest for social fears. Social fears had a ‘burst’ of specific genetic effects in late adolescence. Individual-specific environmental factors impacted both on the general fear factor and on specific fears. Compared to genetic effects, the impact of the unique environment was more time-specific. Conclusions Genetic and environmental risk factors for individual fears are partly mediated through a common fear factor and are partly fear-specific in their effect. The developmental pattern of these risk factors is complex and dynamic with new common and specific genetic effects arising in late adolescence and early adulthood.
Work-nonwork interference: Preliminary results on the psychometric properties of a new instrument

Orientation: Recently, a new work-nonwork interference instrument was developed to measure the interference between work and nonwork roles in the South African context (Koekemoer, Mostert & Rothmann, 2010). However, no information is available on the psychometric properties of this instrument. Research purpose: The objectives of this study were to investigate the internal validity (construct, discriminant and convergent validity), reliability and external validity (relationship with theoretically relevant variables, including job characteristics, home characteristics, burnout, ill health and life satisfaction) of the instrument. Motivation for the study: Work-family interaction is a key topic receiving significant research attention. In order to facilitate comparison across work-family studies, the use of psychometrically sound instruments is of great importance. Research design, approach and method: A cross-sectional survey design was used for the target population of married employees with children working at a tertiary institution in the North West province ( n = 366). In addition to the new instrument, job characteristics, home characteristics, burnout, ill health and life satisfaction were measured. Main findings: The results provided evidence for construct, discriminant and convergent validity, reliability and significant relations with external variables. Practical/managerial implications: The new instrument can be used by researchers and managers as a test under development to investigate the interference between work and different nonwork roles (i.e. parental role, spousal role, work role, domestic role) and specific relations with antecedents (e.g. job/home characteristics) and well-being (e.g. burnout, ill health and life satisfaction). Contribution/value-add: This study provides preliminary information on the psychometric properties of a new instrument that measures the interference between work and nonwork.
Systems of Spatial Reference in Human Memory

Seven experiments examined the spatial reference systems used in memory to represent the locations of objects in the environment. Participants learned the locations of common objects in a room and then made judgments of relative direction using their memories of the layout (e.g., "Imagine you are standing at the shoe, facing the lamp; point to the clock"). The experiments manipulated the number of views that observers were allowed to experience, the presence or absence of local and global reference systems (e.g., a rectangular mat on which objects were placed and the walls of the room, respectively), and the congruence of local and global reference systems. Judgments of relative direction were more accurate for imagined headings parallel to study views than for imagined headings parallel to novel views, even with up to three study views. However, study views misaligned with salient reference systems in the environment were not strongly represented if they were experienced in the context of aligned views. Novel views aligned with a local reference system were, under certain conditions, easier to imagine than were novel views misaligned with the local reference system. We propose that learning and remembering the spatial structure of the surrounding environment involves interpreting the layout in terms of a spatial reference system. This reference system is imposed on the environment but defined by egocentric experience.
Examining preschoolers' nutrition knowledge using a meal creation and food group classification task: age and gender differences

Eating behaviours begin to develop during early childhood, but relatively little is known about preschoolers' nutrition knowledge. The current study examined age and gender differences in this knowledge using two tasks: food group classification and the creation of unhealthy, healthy and preferred meals. Sixty‐nine three‐ to six‐year‐old children were interviewed. Findings suggest that the healthy meals children created were lower in calories and fat than their preferred and unhealthy meals. Older children and girls had a larger discrepancy in the calorie/fat content of their healthy and unhealthy meals than younger children and boys, respectively. Children's created meals showed some dietary variety, but many children could not provide valid explanations for why they selected the foods they did. Children were better at classifying fruits and vegetables than foods from the grain and dairy group. This study highlights the utility of using ecologically valid measures to understand children's developing nutrition knowledge.
Predicting wear and blood metal ion levels in metal‐on‐metal hip resurfacing

Suboptimal component position and design are thought to lead to edge wear and raised blood metal ion levels in metal‐on‐metal hip resurfacing (MOM‐HR). These factors are thought to influence the “contact patch to rim distance” (CPRD), and calculation of this distance may improve prediction of wear and blood metal ion levels. We measured blood cobalt and chromium ion levels and the wear rates of the bearing surfaces in 165 MOM‐HR retrieval cases. We then determined the contribution and effect sizes of cup inclination and version angles, component size and design, and CPRD (calculated from case‐specific data) on blood metal ion levels and component wear rates. Acetabular orientation explained between 16.3% and 28.5% of the variation in wear rates and metal ion levels, whereas component size and design explained between 7.3% and 21.8% of the variability. In comparison, CPRD explained up to 67.7% of the variability, significantly greater than any other variable (all p < 0.0001). CPRD is a good predictor of wear and improves our understanding of wear performance and the mechanisms leading to edge loading. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:167–174, 2014.
Twice-Exceptional Learners

Twice-exceptionality is gaining increasing recognition in the gifted education literature but little is understood about the knowledge and awareness of this concept within the educational and psychological community, or about professionals’ experience working with this population of learners. Three-hundred and seventeen individuals completed an online Twice-Exceptional Needs Assessment, which consisted of 14 questions assessing issues pertaining to twice-exceptionality knowledge and experience, as well as knowledge of policies relevant to both gifted and special education. Results indicated that educators were more familiar with standards within their specific area of expertise (e.g., gifted or special education) and that fewer professionals were familiar with the use of Response to Intervention with twice-exceptional children. Gifted education professionals had significantly more knowledge and experience with twice-exceptionality than did professionals in other domains. We conclude with implications for educators and recommendations for expanding professional understanding of twice-exceptionality outside the field of gifted education to meet twice-exceptional students’ multifaceted needs.
The stoichiometry of protection against soman and VX toxicity in monkeys pretreated with human butyrylcholinesterase.

Bioscavengers of organophophates (OP) have been examined as potential substitutes for the currently approved drug treatment against OP toxicity. The present work was designed to assess the ability of butyrylcholinesterase, purified from human serum (HuBChE), to prevent the toxicity induced by soman and VX in rhesus monkeys. The consistency of the data across species was then evaluated as the basis for the extrapolation of the data to humans. The average mean residence time of the enzyme in the circulation of monkeys following an intravenous loading was 34 hr. High bioavailability of HuBChE in blood (>80%) was demonstrated after intramuscular injection. A molar ratio of HuBChE:OP approximately 1.2 protected against an i.v. bolus injection of 2.1 x LD50 VX, while a ratio of 0.62 was sufficient to protect monkeys against an i.v. dose of 3.3 x LD50 of soman, with no additional postexposure therapy. A remarkable protection was also seen against soman-induced behavioral deficits detected in the performance of a spatial discrimination task. The consistency of the results across several species offers a reliable prediction of both the stoichiometry of the scavenging and the extent of prophylaxis with HuBChE against nerve agent toxicity in humans.
Effect of a Single Dose of Ritonavir on the Pharmacokinetic Behavior of Elvucitabine, a Nucleoside Reverse Transcriptase Inhibitor, Administered in Healthy Volunteers

ABSTRACT The purpose of this study was to determine the effect of a single dose of 300 mg of ritonavir on the plasma pharmacokinetics (PK) of a single dose of 20 mg of elvucitabine when the two drugs were coadministered in healthy subjects. In a three-way crossover design, 30 subjects received 20 mg of elvucitabine, 300 mg of ritonavir, or 20 mg of elvucitabine coadministered with 300 mg of ritonavir. Elvucitabine concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry assay. The PK of elvucitabine was determined using both noncompartmental and compartmental analyses. Models were developed and tested using ADAPT-II, while a population analysis was performed using IT2S. Comparisons of PK parameters between groups were done with SAS. The pharmacokinetic behavior of elvucitabine was best described by a two-compartment linear model using two absorption rates and a first-order elimination rate. Ritonavir significantly impacted the PK of elvucitabine by reducing elvucitabine's bioavailability, with the most plausible explanation being an inhibition on influx transporters by ritonavir. The decrease in elvucitabine bioavailability when elvucitabine was coadministered with ritonavir may be due to ritonavir's inhibiting influx gut transporters. Continued development of elvucitabine is warranted to better characterize its PK and to determine its in vivo efficacy against human immunodeficiency virus.
In vivo actin cross-linking induced by Vibrio cholerae type VI secretion system is associated with intestinal inflammation

Type VI secretion systems (T6SSs) have recently been recognized as potential virulence determinants of many Gram-negative bacterial pathogens. Although mechanistic studies are lacking, T6SS-dependent phenotypes can be observed in various animal models of infection. Presumably translocation of T6SS effectors into target cells is involved in virulence, but few such effectors have been identified. A hallmark of T6SS function is the in vitro secretion of Hcp and VgrG proteins, which are thought to form part of an extracellular secretion apparatus. One well-characterized effector domain is the C-terminal actin cross-linking domain (ACD) of the VgrG-1 protein, constitutively secreted by the T6SS of Vibrio cholerae strain V52. Previous work indicated that translocation of VgrG-1 occurred only after endocytic uptake of bacteria into host cells. VgrG-1-induced actin cross-linking impaired phagocytic activity of host cells, eventually causing cell death. To determine whether V. cholerae T6SS is functional during animal infection, derivatives of V52 were used to infect infant mice. In this infection model a diarrheal response occurred, and actin cross-linking could be detected. These host responses were dependent on a functional T6SS and on the ACD of VgrG-1. Gene expression and histologic studies showed innate immune activation and immune cell infiltration in the intestinal lumen. The T6SS-dependent inflammatory response was also associated with increased recovery of V. cholerae from the intestine. We conclude that the T6SS of V52 induces an inflammatory diarrhea that facilitates replication of V. cholerae within the intestine.