Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical pharmacodynamics of continuous infusion topotecan in children: systemic exposure predicts hematologic toxicity.

PURPOSE Topotecan pharmacokinetics and pharmacodynamics were studied following a 72-hour continuous infusion in 20 children with cancer (median age, 8 years; range, 3.5 to 18). METHODS Serial plasma and urine samples were collected during the infusion and for up to 6 hours following the end of infusion. Topotecan (lactone) and total (lactone plus hydroxy acid) concentrations were determined by a sensitive and specific high-performance liquid chromatography (HPLC) assay with fluorescence detection. Using maximum a posteriori-Bayesian modeling, lactone and total plasma concentrations were described separately by a two-compartment model. Hematologic toxicity was expressed as the percent decrease in absolute neutrophil count (ANC) and platelet count. The relation between systemic exposure (SE) and hematologic toxicity was modeled using a sigmoid maximum-effect model. RESULTS Systemic clearance rates for lactone and total topotecan were (mean +/- SD) 18.5 +/- 7.0 and 6.5 +/- 2.4 L/h/m2, respectively. Urinary recovery of total topotecan was (mean +/- SD) 67.5% +/- 25.2% (n = 12 patients). SE (area under the concentration-time curve from zero to infinity [AUC] or steady-state plasma concentration [Cpss]) to either topotecan lactone or total topotecan was significantly correlated to hematologic toxicity (P < .05). Overall, patients with a higher SE to topotecan experienced greater hematologic toxicity. CONCLUSION These data demonstrate a relation between systemic exposure to topotecan and clinical effect (myelosuppression). Moreover, these data provide the basis for development of individualized topotecan administration schedules.
Operating deficits and public housing: policy options for reversing the trend

A key constraint for mainstream public housing is that the net revenues after rebates at least pay for operational costs, (net of interest paid or received). If this is not the case, any addition to stock expands the additional funding requirement to pay for the deficit. In these circumstances the only option for reducing or freezing the additional funding requirement is to sell stock and therefore reduce the number of households provided with longer term assistance. The rate at which these operating deficits are growing, and the timing of when they will outstrip current real levels of grant funding is of critical policy concern. Clearly continuation of the current trends may carry with it the risk of a potential paralysis of housing assistance policy development, and a possible forced withdrawal to private rental subsidies as the only method of continuing housing assistance, with the possibility of a future fiscal blow-out. The aims of this project were therefore to: clarify the impact of public housing operating deficits on the development of comprehensive and expansive housing assistance policies; develop suitable policy options for returning public housing to operational surpluses; and by so doing; provide a context for more comprehensive and expansive housing assistance policies. The project addressed four key research questions: How should operating deficits be defined? (addressed by discussion paper, and research questions). What are the trends in operating deficits and are they or are they not restricting stock additions to public housing? (addressed by public housing accounts analysis and CEO questionnaire/interview); What are the reasons for the development of operating deficits and what are the influences of particular cost components? (addressed by public housing accounts analysis and CEO questionnaire/interview); and How can the components of operating regimes be benchmarked, what are the relevant international comparisons and what policy options can housing authorities introduce to improve outcomes? (addressed by benchmark literature review, analysis of overseas benchmarks and comparison with SHA's and Productivity Commission benchmarks).
Wave Separation, Wave Intensity, the Reservoir-Wave Concept, and the Instantaneous Wave-Free Ratio: Presumptions and Principles

Wave separation analysis and wave intensity analysis (WIA) use (aortic) pressure and flow to separate them in their forward and backward (reflected) waves. While wave separation analysis uses measured pressure and flow, WIA uses their derivatives. Because differentiation emphasizes rapid changes, WIA suppresses slow (diastolic) fluctuations of the waves and renders diastole a seemingly wave-free period. However, integration of the WIA-obtained forward and backward waves is equal to the wave separation analysis–obtained waves. Both the methods thus give similar results including backward waves spanning systole and diastole. Nevertheless, this seemingly wave-free period in diastole formed the basis of both the reservoir-wave concept and the Instantaneous wave-Free Ratio of (iFR) pressure and flow. The reservoir-wave concept introduces a reservoir pressure, Pres, (Frank Windkessel) as a wave-less phenomenon. Because this Windkessel model falls short in systole an excess pressure, Pexc, is introduced, which is assumed to have wave properties. The reservoir-wave concept, however, is internally inconsistent. The presumed wave-less Pres equals twice the backward pressure wave and travels, arriving later in the distal aorta. Hence, in contrast, Pexc is minimally affected by wave reflections. Taken together, Pres seems to behave as a wave, rather than Pexc. The iFR is also not without flaws, as easily demonstrated when applied to the aorta. The ratio of diastolic aortic pressure and flow implies division by zero giving nonsensical results. In conclusion, presumptions based on WIA have led to misconceptions that violate physical principles, and reservoir-wave concept and iFR should be abandoned.
Blockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy

AbstractSignaling through programmed death 1 (PD-1) expressed by activated T lymphocytes inhibits their function and is a major mechanism for suppressing antitumor T cell responses in the tumor microenvironment. Recent clinical trials show that blockade of the B7-H1(programmed death ligand 1 [PD-L1])/PD-1 pathway with anti–PD-1 or anti–PD-L1 is active in several malignancies and produces durable responses in a subset of patients. Clinical response to these agents may be limited by other mechanisms of T-lymphocyte suppression in the tumor microenvironment, or absence of a significant tumor-specific T cell response in the tumor. Combinations with other therapies are likely to address at least several of the major mechanisms of resistance, supported by abundant preclinical data in animal tumor model systems. The combination of anti–PD-1 with anti–CTLA-4 demonstrated promising activity in metastatic melanoma and is being tested in multiple other malignancies. Other combinations based on PD-1/PD-L1 blockade are either in early clinical development or in planning stages. Many of the combinations based on PD-1/PD-L1 blockade are expected to produce a higher incidence of autoimmune-like toxicities, but clinical experience with agents such as ipilimumab suggests that toxicities will be manageable and reversible and the overall risk-benefit ratio will be acceptable.
Fuzzy-control of a hand orthosis for restoring tip pinch, lateral pinch, and cylindrical prehensions to patients with elbow flexion intact

This study examines, through simulation, the use of fuzzy logic as a feasible control scheme for a hand orthosis that can restore fingertip pinch, lateral pinch, and cylindrical grasps to individuals suffering from C5-C7 spinal cord injuries. A simplified hand orthosis model, consisting of four fingers and a thumb, was derived for the purpose of planning appropriate grasp trajectories and for validating the fuzzy logic control architecture. For comparison a PID controller was also designed. Fuzzy logic is advantageous for this system since it eliminates solving coupled nonlinear equations of motion. For the various grips, the fuzzy controller produced better performance than the PID controller.
Technical report on a haptic interface for learning anatomy

Anatomy is an essential subject for many health related courses, hence there are various tools available. In order to find out if different types of learners may have more benefits from a different mode of learning resources, a haptic system for learning anatomy was developed and three consecutive user tests were completed over 2 years. The system has been expanded according to users' feedback at each phase in a Design Research paradigm. The Technical Acceptance Model was used to measure how well this system was accepted by current students enrolled in an institution. The technical aspects of the system are discussed in this paper.
Superior Canal Dehiscence Size: Multivariate Assessment of Clinical Impact

Objective To examine the association between dehiscence length in patients with superior semicircular canal dehiscence syndrome and their clinical findings, including objective audiometric and vestibular testing results. Study Design Retrospective study. Setting Tertiary referral center. Patients Patients included in this study were diagnosed with superior semicircular canal dehiscence syndrome and underwent surgical repair of the dehiscence through middle fossa craniotomy. The dehiscence length was measured intraoperatively in all cases. Main Outcome Measures Correlation between dehiscence length with pure-tone average (PTA), average bone-conduction threshold, maximal air-bone gap, cervical vestibular evoked myogenic potential thresholds, and presenting signs and symptoms. Results The correlation between dehiscence length and maximal air-bone gap was statistically significant on both univariate and multivariate regression analyses. The correlations between dehiscence length and PTA, average bone-conduction threshold, cervical vestibular evoked myogenic potential threshold, and presenting signs and symptoms were not statistically significant. Conclusion The dehiscence length correlated positively with the maximal air-bone gap in patients with superior semicircular canal dehiscence. The correlation was statistically significant. The dehiscence length did not correlate with the other variables examined in this study.
Telencephalic Projections of the A8 Dopamine Cell Group

The telencephalic projections of the A8 dopamine cell group of the rat were assessed using both anterograde and combined retrograde-immunohistochemical methods. The projections of the A8 neurons onto the forebrain were more extensive than hitherto realized, and encompassed striatal, limbic, and allocortical regions. The A8 neurons were shown to contribute to the dopaminergic innervation of the striatum, nucleus accumbens, olfactory tubercles, amygdala, and bed nucleus of the stria terminalis, and also innervate the pyriform and entorhinal cortices. In addition, projections within the midbrain were observed, and suggested that there may be direct interconnections between the dopaminergic neurons of the A8, A9, and A10 cell groups. These data therefore suggest that the A8 dopamine cell group is uniquely situated to modulate functional activity within both nigrostriatal and mesocorticolimbic regions, and further suggests that heterogeneities of the midbrain dopamine neurons are embedded within a larger homogeneous mesotelencephalic dopamine system.
The Determinants of Earnings in Turkey Evidence from Panel Analysis

Turkish economic growth that had been going on for more than a decade has created a strong economy that is based on high demand for energy. This paper examines the effects of debt, net assets, net sales and capital on firms’ profitability in Turkey’s energy sector between 2005 and 2015. It is concluded that total debt, capital, net sales has positive effect on earnings. This result illustrate us that companies in energy market use their resources efficiently.
Does case management for patients with heart failure based in the community reduce unplanned hospital admissions? A systematic review and meta-analysis

Objectives The aim of this systematic review of randomised controlled trials (RCTs) and controlled trials (non-RCTs, NRCTs) is to investigate the effectiveness and related costs of case management (CM) for patients with heart failure (HF) predominantly based in the community in reducing unplanned readmissions and length of stay (LOS). Setting CM initiated either while as an inpatient, or on discharge from acute care hospitals, or in the community and then continuing on in the community. Participants Adults with a diagnosis of HF and resident in Organisation for Economic Co-operation and Development countries. Intervention CM based on nurse coordinated multicomponent care which is applicable to the primary care-based health systems. Primary and secondary outcomes Primary outcomes of interest were unplanned (re)admissions, LOS and any related cost data. Secondary outcomes were primary healthcare resources. Results 22 studies were included: 17 RCTs and 5 NRCTs. 17 studies described hospital-initiated CM (n=4794) and 5 described community-initiated CM of HF (n=3832). Hospital-initiated CM reduced readmissions (rate ratio 0.74 (95% CI 0.60 to 0.92), p=0.008) and LOS (mean difference −1.28 days (95% CI −2.04 to −0.52), p=0.001) in favour of CM compared with usual care. 9 trials described cost data of which 6 reported no difference between CM and usual care. There were 4 studies of community-initiated CM versus usual care (2 RCTs and 2 NRCTs) with only the 2 NRCTs showing a reduction in admissions. Conclusions Hospital-initiated CM can be successful in reducing unplanned hospital readmissions for HF and length of hospital stay for people with HF. 9 trials described cost data; no clear difference emerged between CM and usual care. There was limited evidence for community-initiated CM which suggested it does not reduce admission.
Acute left varicocele in an adult

See also the practice article by Forster and Biyani on page [321][1] and at [www.cmaj. ca/lookup/doi/10.1503/cmaj.121445][2] A 52-year-old man with a history of hypertension was referred because varicose veins had developed in his scrotum 2 weeks earlier. During examination of his genitals, an
Assessment of Stress Level among Dental School Students: An Indian Outlook

Background: Evaluating the factors influence student perception, might allow programmatic changes designed to enhance students’ psychosocial well-being and academic performance. The purpose of this study was to investigate perceived sources of stress on dental students and the role of parents in their career choice decisions. Methods: In a cross-sectional design, a modified dental environmental stress questionnaire was administered to all dental students. The responses to the questionnaire were based on a four-point Lickert scale, not stressful to severely stressful. Means and standard deviations were determined for stress scores of individuals for each item and were used to compare the classes, genders, and choices. Student's t, one way ANOVA, and Newman Keuls multiple comparison post hoc tests were used to analysed the data at the significant level of P ≤ 0.05. Results: A total of 304 undergraduate students constituted the study population. Of the respondent, 60% were men and 40% were women. The final year students presented with higher stress scores. In gender comparison, men suffered more stress (62.9%) than women (60.1%). According to the career choice decision, students forced by parents had more perception of stress (69.0%) and the students staying in the hostel (62.7%) showed more perception of stress than day scholars (56.3%). Conclusion: The study indicates that the congenial environment needs to be created for dental education and the parents also need to be counselled against forcing their children to join an educational programme i.e. not of their choice.
Linking differential domain functions of the GS3 protein to natural variation of grain size in rice

Grain yield in many cereal crops is largely determined by grain size. Here we report the genetic and molecular characterization of GS3, a major quantitative trait locus for grain size. It functions as a negative regulator of grain size and organ size. The wild-type isoform is composed of four putative domains: a plant-specific organ size regulation (OSR) domain in the N terminus, a transmembrane domain, a tumor necrosis factor receptor/nerve growth factor receptor (TNFR/NGFR) family cysteine-rich domain, and a von Willebrand factor type C (VWFC) in the C terminus. These domains function differentially in grain size regulation. The OSR domain is both necessary and sufficient for functioning as a negative regulator. The wild-type allele corresponds to medium grain. Loss of function of OSR results in long grain. The C-terminal TNFR/NGFR and VWFC domains show an inhibitory effect on the OSR function; loss-of-function mutations of these domains produced very short grain. This study linked the functional domains of the GS3 protein to natural variation of grain size in rice.
Patient perspectives on the doctor of the future.

BACKGROUND AND OBJECTIVES Health care reform has been the subject of considerable debate, particularly among those in politics, insurance, and business. Patients, however, have largely been ignored in this discussion. As the role of the health care consumer receives increased attention, it is important to consider patient values and preferences for a future system of care. This study describes what patients want and value in a future doctor METHODS This study was conducted in 1999-2000, using focus group methodology involving 78 members of communities in seven regions of Colorado. Participants were selected to ensure a distribution of rural/urban, racial/ethnic groups and different regions of the state. All participants had visited a health care provider in the previous 10 years. Data were analyzed with a team-based editing approach. RESULTS Participants identified several primary domains and subthemes that describe what they want in a doctor of the future. The primary themes related to future doctors' medical and contextual knowledge of the patient, their personal characteristics and philosophical approach to health and health care, and desired qualities of the doctor-patient relationship. CONCLUSIONS Patients wanted their future doctors to improve their experience of care and to be patient-centered, family-oriented, and community-oriented doctors. Patient perspectives of the doctor of the future should be considered in decisions about health care policy.
Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline.

OBJECTIVE The aim was to update The Endocrine Society Clinical Practice Guideline on Evaluation and Treatment of Adult Growth Hormone Deficiency (GHD) previously published in 2006. CONSENSUS PROCESS Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. CONCLUSIONS GHD can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks associated with GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual.
3′-End processing of histone pre-mRNAs in Drosophila: U7 snRNP is associated with FLASH and polyadenylation factors

3′-End maturation of histone mRNAs in higher eukaryotes requires U7 snRNA and several factors that are essential for canonical cleavage and polyadenylation. This paper reveals some interesting differences between histone 3′-end formation in Drosophila and mammalian cells. In particular, Ars2 is not essential for Drosophila histone 3′-end processing, and the Drosophila U7 snRNP is associated with several polyadenylation factors in a stable supercomplex.
Internationalcapital movements and the global order

This introduction presents an overview of the key concepts covered in this book. The book deals with capitalism's evolution within Western Europe and its offshoots, and its spread to the rest of the world after 1848. The spread of global capitalism has two dimensions, and they can be distinguished by means of an analogy. The increased globalization across the nineteenth century was due to a combination of factors, especially the new transportation and information technologies. Late-twentieth-century growth rates by the East Asian tigers and then China have set a modern standard of 'growth miracles' hard to beat, making impressive growth spurts in the past look pretty modest. During the few decades between about 1820 and the mid nineteenth century, global migrations changed dramatically. Emigration policies changed, from restricting outflows before, to adopting laissez-faire policies thereafter. The late nineteenth century also saw a large increase in the integration of international capital markets, and in the volume of international capital flows.
Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy

It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation results from the differentiation of stem-like cells committed to the myocyte lineage. These cells express stem cell markers and telomerase. Their number increased >13-fold in aortic stenosis. The finding of cell clusters with stem cells making the transition to cardiogenic and myocyte precursors, as well as very primitive myocytes that turn into terminally differentiated myocytes, provides a link between cardiac stem cells and myocyte differentiation. Growth and differentiation of these primitive cells was markedly enhanced in hypertrophy, consistent with activation of a restricted number of stem cells that, through symmetrical cell division, generate asynchronously differentiating progeny. These clusters strongly support the existence of cardiac stem cells that amplify and commit to the myocyte lineage in response to increased workload. Their presence is consistent with the notion that myocyte hyperplasia significantly contributes to cardiac hypertrophy and accounts for the subpopulation of cycling myocytes.
Racial Differences in Financial Socialization and Financial Behaviors of U.S. College Students

This chapter focuses on the effect of race on financial socialization and financial behavior of college students. Data (N = 13,845) were collected from current college students age 18 and over via an online survey throughout the United States during spring and fall of 2008. Results from means comparisons showed significant differences on the financial socialization between Black and White college students. Logistic regression results suggest important relationship exist between race and financial behaviors. Black students were less likely to save and more likely to engage in risky credit card behavior than White students after controlling for the effects of all other variables.