Miracle-dz/UniFAR-FTUs huggingface dataset:
Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer.

PURPOSE A phase III, multicenter, randomized study compared conventional dosing of fluorouracil (FU) plus folinic acid with pharmacokinetically guided FU dose adjustment in terms of response, tolerability, and survival. PATIENTS AND METHODS Two hundred eight patients with measurable metastatic colorectal cancer were randomly assigned to one of two arms: arm A (104 patients; 96 assessable), in which the FU dose was calculated based on body-surface area; and arm B (104 patients; 90 assessable), in which the FU dose was individually determined using pharmacokinetically guided adjustments. The initial regimen was 1,500 mg/m(2) FU plus 200 mg/m(2) folinic acid infusion during a continuous 8-hour period administered once weekly. FU doses were adjusted weekly in arm B based on a single-point measurement of FU plasma concentrations at steady state until the therapeutic range (targeted area under the curve 20-25 mg x h x L(-1)) previously established in other studies was reached. RESULTS An intent-to-treat analysis of the 208 patients showed the objective response rate was 18.3% in arm A and 33.7% in arm B (P = .004). Median overall survival was 16 months in arm A and 22 months in arm B (P = .08). The mean FU dose throughout treatment was 1,500 mg/m(2)/wk in arm A and 1,790 +/- 386 mg/m(2)/wk (range, 900 to 3,300 mg/m(2)/wk) in arm B. Toxic adverse effects were significantly more frequent and severe in arm A compared with arm B (P = .003). CONCLUSION Individual FU dose adjustment based on pharmacokinetic monitoring resulted in significantly improved objective response rate, a trend to higher survival rate, and fewer grade 3/4 toxicities. These results support the value of pharmacokinetically guided management of FU dose in the treatment of metastatic colorectal patients.
Multilevel-DFT based low-complexity hybrid precoding for millimeter wave MIMO systems

The millimeter wave (mmWave) multiple-input multiple-output is a promising technique for next-generation (5G) communication systems. The inherently high path loss in mmWave can be compensated by adopting large antenna array. However, huge cost of radio frequency (RF) chains at high frequencies, as well as large number of antennas, makes full-digital precoding in mmWave-MIMO system infeasible. Hence, hybrid analog/digital precoding techniques are proposed to reduce the hardware cost of RF components while achieving similar performance as full-digital precoder. Usually it requires iterative process and matrix inversion to split full-digital precoder into hybrid structure. In this paper, we propose a low-complexity hybrid precoding algorithm with predefined rotated multilevel-DFT codebook. It can leverage orthogonal mapping process to avoid iterative process and matrix inversion. Simulation results demonstrate that the proposed algorithm can achieve 97.6% spectrum efficiency compared with state-of-the-art low-complexity hybrid precoding algorithm while reducing 99.7% complexity in terms of complex multiplications.
Time-Indexed Formulations for Machine Scheduling Problems: Column Generation

Time-indexed formulations for machine scheduling problems have received a great deal of attention; not only do the linear programming relaxations provide strong lower bounds, but they are good guides for approximation algorithms as well. Unfortunately, time-indexed formulations have one major disadvantage--their size. Even for relatively small instances the number of constraints and the number of variables can be large. In this paper, we discuss how Dantzig-Wolfe decomposition techniques can be applied to alleviate, at least partly, the difficulties associated with the size of time-indexed formulations. In addition, we show that the application of these techniques still allows the use of cut generation techniques.
High implicit self‐esteem is not necessarily advantageous: discrepancies between explicit and implicit self‐esteem and their relationship with anger expression and psychological health

Two studies investigated how discrepancies between implicit and explicit self‐esteem are related to mental and physical health. We found that, compared to congruent self‐esteem, discrepant self‐esteem was related to more anger suppression, a more depressive attributional style, more nervousness, and more days of impaired health. The result applies not only to fragile (high explicit, low implicit) self‐esteem, but also to damaged (low explicit, high implicit) self‐esteem. These findings show that high implicit self‐esteem is not necessarily advantageous. In individuals with low explicit self‐esteem having high implicit self‐esteem was related to more health problems than having low implicit self‐esteem. Taken together the results suggest that discrepancies between implicit and explicit SE are detrimental to mental and physical health. Copyright © 2007 John Wiley & Sons, Ltd.
Frequency Dependence of Signal Power and Spatial Reach of the Local Field Potential

Despite its century-old use, the interpretation of local field potentials (LFPs), the low-frequency part of electrical signals recorded in the brain, is still debated. In cortex the LFP appears to mainly stem from transmembrane neuronal currents following synaptic input, and obvious questions regarding the ‘locality’ of the LFP are: What is the size of the signal-generating region, i.e., the spatial reach, around a recording contact? How far does the LFP signal extend outside a synaptically activated neuronal population? And how do the answers depend on the temporal frequency of the LFP signal? Experimental inquiries have given conflicting results, and we here pursue a modeling approach based on a well-established biophysical forward-modeling scheme incorporating detailed reconstructed neuronal morphologies in precise calculations of population LFPs including thousands of neurons. The two key factors determining the frequency dependence of LFP are the spatial decay of the single-neuron LFP contribution and the conversion of synaptic input correlations into correlations between single-neuron LFP contributions. Both factors are seen to give low-pass filtering of the LFP signal power. For uncorrelated input only the first factor is relevant, and here a modest reduction (<50%) in the spatial reach is observed for higher frequencies (>100 Hz) compared to the near-DC () value of about . Much larger frequency-dependent effects are seen when populations of pyramidal neurons receive correlated and spatially asymmetric inputs: the low-frequency () LFP power can here be an order of magnitude or more larger than at 60 Hz. Moreover, the low-frequency LFP components have larger spatial reach and extend further outside the active population than high-frequency components. Further, the spatial LFP profiles for such populations typically span the full vertical extent of the dendrites of neurons in the population. Our numerical findings are backed up by an intuitive simplified model for the generation of population LFP.
The experience of faculty 1 development: patterns of variation in conceptions of teaching

As research demands continue to weigh heavily on junior and non‐tenured faculty, the need to maintain and develop sound teaching is crucial. Yet few studies have systematically explored how a faculty development program (FDP) can impact the way that faculty experience or conceive of teaching. In this study, we examine how a year‐long FDP impacts the conceptions of teaching held by early‐career faculty. We interviewed 22 tenure‐track faculty participants, pre‐ and post‐program, categorizing their conceptions of teaching from the transcripts. The analysis drew on conceptual frameworks of faculty conceptions of teaching derived from phenomenographic literature increasingly used in Europe, Asia, and Australia, but not in the USA. The present study identifies and explores a range of patterns of experience that emerged over the course of an American FDP program. We discuss the broader implications of these patterns for the study and understanding of faculty development programs. Alors que les demandes reliées à la recherche pèsent lourdement sur les enseignants débutants et sans permanence, le besoin de maintenir et de développer une solide pédagogie s'avère crucial. Pourtant, peu de recherches ont systématiquement exploré quel impact peut avoir un programme de développement pour les enseignants (PDE) sur la façon selon laquelle les enseignants conçoivent ou font l'expérience de l'enseignement. Dans le cadre de cette recherche, nous examinons comment un PDE d'une durée d'un an peut avoir un impact sur les conceptions de l'enseignement entretenues par des enseignants en début de carrière. Nous avons effectué des entretiens auprès de 22 enseignants en pré‐titularisation conditionnelle (tenure‐track), avant et suite à leur participation au programme, et avons catégorisé leurs conceptions de l'enseignement à partir des transcriptions. L'analyse s'est inspirée de cadres conceptuels portant sur les conceptions de l'enseignement provenant de la littérature phénoménographique de plus en plus utilisée en Europe, en Asie et en Australie, mais pas aux Etats‐Unis. Cette étude identifie et explore un éventail de modèles d'expériences qui ont pris forme tout au long d'un programme américain de PDE. Nous présentons les implications plus vastes de ces modèles pour contribuer à l’étude et à la compréhension des programmes de développement pédagogique.
Complex Regulation of Spiral Ganglion Neuron Firing Patterns by Neurotrophin-3

Auditory information is conveyed into the CNS via the spiral ganglion neurons, cells that possess distinctive electrophysiological properties that vary according to their cochlear innervation. Neurons from the base of the cochlea fire action potentials with shorter latencies and durations with more rapid accommodation than apical neurons (Adamson et al., 2002b). Interestingly, these features are altered by exposure to brain-derived neurotrophic factor and neurotrophin-3 (NT-3), suggesting that the electrophysiological diversity is not preprogrammed into the neurons but instead results from extrinsic regulation. In support of this, gradients of neurotrophins exist in the cochlea that could account for the apex- base differences in firing. To understand the determinants of spiral ganglion function, we characterized the NT-3 concentration dependence and mode of action on spiral ganglion neurons. Whole-cell current-clamp recordings were made from mouse basal spiral ganglion neurons (postnatal day 5) exposed to different concentrations of NT-3 for 3 d in vitro. Measurements of accommodation, latency, onset time course, and action potential latency revealed a nonmonotonic dependence on NT-3 concentration, with a peak effect occurring at 10 ng/ml. Addition of NT-3 at different time points showed that neurotrophin exposure altered the firing features of existing neurons rather than supporting differential survival. These experiments establish that the electrophysiological phenotype of spiral ganglion neurons depends critically on the precise concentration of NT-3 and that the functional organization of this component of the peripheral auditory system results from a complex interplay between multiple kinds of neurotrophins and their cognate receptors.
Development of a Measure of Coping with Multiple Sclerosis Caregiving

Development of a self-report measure of coping specific to multiple sclerosis (MS) caregiving is needed to advance our understanding of the role of coping in adaptation to caring for a person with MS and to contribute to a lack of empirical data on MS caregiving. A total of 213 MS caregivers and their care recipients completed a Coping with MS Caregiving Inventory (CMSCI) and measures of adjustment (psychological distress), appraisal and illness. A subsample ( n = 64) also completed the Ways of Coping Checklist (WCC) and additional adjustment measures (depression, caregiving impact, dyadic adjustment, and relationship conflict and reciprocity). Factor analyses revealed 5 factors: Supportive Engagement, Criticism and Coercion, Practical Assistance, Avoidance, and Positive Reframing. Subscales had internal reliabilities comparable to similar scales and were empirically distinct. Preliminary construct validation data are consistent with recent MS caregiving research that links passive avoidant emotion-focused coping with poorer adjustment, and relationship-focused coping caregiving research that links greater reliance on positive relationship-focused coping and less reliance on criticism with better adjustment. Results extend this research by revealing new relations between coping and adaptation to MS caregiving. Convergent validation data suggest that although the inventory differs from the WCC, it does share certain conceptual similarities with this scale.
Verlauf unipolar depressiver, bipolar manisch-depressiver und schizo-affektiver Erkrankungen und PsychosenErgebnisse einer prospektiven Studie

Der Verlauf affektiver Erkrankungen wurde prospektiv seit 1959 bis 1975 studiert an 159 unipolaren Depressionen, 95 bipolaren manisch-depressiven Erkrankungen und 150 schizoaffektiven Psychosen. Die drei Patientengruppen unterscheiden sich nicht signifikant bezüglich Alter (ca. 60 Jahre) und Geschlechtsverteilung. Hingegen bestehen markante Unterschiede bezüglich Beobachtungsund Krankheitsdauer als Folge des unterschiedlichen Erstmanifestationsalters. Unipolare Depressionen verlaufen viel günstiger als bipolare und schizoaffektive, die letzteren beiden ähneln sieh in vielen Merkmalen. Unipolare Depressionen beginnen im Mittel mit 45 Jahren, bipolare mit 35 und schizoaffektive mit 32. Die Krankheitsdauer unipolarer Depressionen ist markant kürzer als diejenige der andern beiden Gruppen. Unipolare Depressionen heilen auch oft (in ca. 40% der Fälle) spontan ab, in dieser Gruppe finden sich aber auch am allenneisten Suizide 00% I1ir die ganze Gruppe, 13-14% bei Ersthospitalisierten). Bei einer durchschnittlichen Beobachtungsdauer seit der Ersterkrankung von 19-27 Jahren (je nach Krankheitsgruppe) wurden bei unipolaren Depressionen 4 Phasen auf 19 Jahre, bei bipolaren 9 auf 26 und bei schizoaffektiven 7 auf 27 beobachtet. Auch hier ist also der Verlauf der unipolaren Störungen relativ günstig, hingegen entsteht außer der Tatsache der Suizide auch noch durch das hohe Manifestationsalter dieser Krankheitsgruppe ein Bias zugunslen eines optimistischeren Bildes. Es wird Aufgabe einer künftigen Untersuchung sein, genauer herauszuschälen, ob früherkrankte unipolar Depressive häufiger abheilen als Späterkrankungen. Die Suizidrate ist bis jetzt in beiden Gruppen gleich. Die Phasendauer wurde in erster Linie durch Bildung intraindividueller Mittelwerte dargestellt und diese wiederum für ganze Krankheitsgruppen gemittelt. In diesem Sinne dauern unipolar depressive Phasen im Durchschnitt 5,95 Monate, bipolare 4,4 und schizoaffektive 4,65 Monate. Relativ oft wird eine Chronifizierung im Sinne einer Dauer von über 12 bzw. 24 Monaten beobachtet. Die letzte beobachtete Krankheitsphase dauerte länger als ein Jahr bei 24,5% der unipolaren, 17,9% der bipolaren und 18% der schizoaffektiven Kranken. Innerhalb dieser Untergruppen findet sich eine Dauer der lelzten Phase von über zwei Jahren bei 17% der unipolaren, 13,7% der bipolaren, 12% der Course of Unipolar Depressive, Bipolar Manic-Depressive, and Schizoaffective Disorders. Results of a Prospective Longitudinal Study
VLSI circuit partitioning by cluster-removal using iterative improvement techniques

Move-based iterative improvement partitioning methods such as the Fiduccia-Mattheyses (FM) algorithm and Krishnamurthy's Look-Ahead (LA) algorithm are widely used in VLSI CAD applications largely due to their time efficiency and ease of implementation. This class of algorithms is of the "local improvement" type. They generate relatively high quality results for small and medium size circuits. However, as VLSI circuits become larger, these algorithms are not so effective on them as direct partitioning tools. We propose new iterative-improvement methods that select cells to move with a view to moving clusters that straddle the two subsets of a partition into one of the subsets. The new algorithms significantly improve partition quality while preserving the advantage of time efficiency. Experimental results on 25 medium to large size ACM/SIGDA benchmark circuits show up to 70% improvement over FM in cutsize, with an average of per-circuit percent improvements of about 25%, and a total cut improvement of about 35%. They also outperform the recent placement-based partitioning tool Paraboli and the spectral partitioner MELO by about 17% and 23%, respectively, with less CPU time. This demonstrates the potential of iterative improvement algorithms in dealing with the increasing complexity of modern VLSI circuitry.
Enumerating Pathways of Proton Abstraction Based on a Spatial and Electrostatic Analysis of Residues in the Catalytic Site

The pathways of proton abstraction (PA), a key aspect of most catalytic reactions, is often controversial and highly debated. Ultrahigh-resolution diffraction studies, molecular dynamics, quantum mechanics and molecular mechanic simulations are often adopted to gain insights in the PA mechanisms in enzymes. These methods require expertise and effort to setup and can be computationally intensive. We present a push button methodology – Proton abstraction Simulation (PRISM) – to enumerate the possible pathways of PA in a protein with known 3D structure based on the spatial and electrostatic properties of residues in the proximity of a given nucleophilic residue. Proton movements are evaluated in the vicinity of this nucleophilic residue based on distances, potential differences, spatial channels and characteristics of the individual residues (polarity, acidic, basic, etc). Modulating these parameters eliminates their empirical nature and also might reveal pathways that originate from conformational changes. We have validated our method using serine proteases and concurred with the dichotomy in PA in Class A β-lactamases, both of which are hydrolases. The PA mechanism in a transferase has also been corroborated. The source code is made available at www.sanchak. com/prism.
The Employee Engagement Landscape and HRD

The Problem. Employee engagement strategies are widely applied in practice, yet the construct remains underdeveloped in the human resource development (HRD) literature. This underdevelopment in the HRD scholarly community, combined with high levels of interest in the HRD practitioner community, highlights the need for closing the gap in theory, scholarship, and practice. To develop and support possible engagement-related interventions, HRD researchers and practitioners must be at the forefront of the emerging engagement conversation. The Solution. This article provides a definition and framework of employee engagement within the context of HRD, specifically in the areas of theory, scholarship, and practice. In addition, this article provides an overview of articles related to the latest thinking, research, and strategy development for generating employee engagement in practice found within this special issue. The Stakeholders. The intended audience for this article includes HRD scholars, scholar-practitioners, and practitioners interested in the development and use of employee engagement as an organizational performance and workplace culture -building strategy.
Being Pursued Online

Building upon Eck and Clarke’s (2003) ideas for explaining crimes in which there is no face-to-face contact between victims and offenders, the authors developed an adapted lifestyle–routine activities theory. Traditional conceptions of place-based environments depend on the convergence of victims and offenders in time and physical space to explain opportunities for victimization. With their proposed cyberlifestyle–routine activities theory, the authors moved beyond this conceptualization to explain opportunities for victimization in cyberspace environments where traditional conceptions of time and space are less relevant. Cyberlifestyle–routine activities theory was tested using a sample of 974 college students on a particular type of cybervictimization—cyberstalking. The study’s findings provide support for the adapted theoretical perspective. Specifically, variables measuring online exposure to risk, online proximity to motivated offenders, online guardianship, online target attractiveness, and online deviance were significant predictors of cyberstalking victimization. Implications for advancing cyberlifestyle–routine activities theory are discussed.
Functionality in Electrospun Nanofibrous Membranes Based on Fiber's Size, Surface Area, and Molecular Orientation

Electrospinning is a versatile method for forming continuous thin fibers based on an electrohydrodynamic process. This method has the following advantages: (i) the ability to produce thin fibers with diameters in the micrometer and nanometer ranges; (ii) one-step forming of the two- or three-dimensional nanofiber network assemblies (nanofibrous membranes); and (iii) applicability for a broad spectrum of molecules, such as synthetic and biological polymers and polymerless sol-gel systems. Electrospun nanofibrous membranes have received significant attention in terms of their practical applications. The major advantages of nanofibers or nanofibrous membranes are the functionalities based on their nanoscaled-size, highly specific surface area, and highly molecular orientation. These functionalities of the nanofibrous membranes can be controlled by their fiber diameter, surface chemistry and topology, and internal structure of the nanofibers. This report focuses on our studies and describes fundamental aspects and applications of electrospun nanofibrous membranes.
Psychometric Analyses of the Adult Manifest Anxiety Scale–Adult Version among Young and Middle-Aged Adults

Responses of 871 adults to the Adult Manifest Anxiety Scale–Adult version (AMAS-A) were factor analyzed using the method of principal axis factoring with promax rotation. Factor analysis yielded a four-factor solution: three anxiety factors (Worry/Oversensitivity, Stress, and Physiological Anxiety) and a Lie factor. The AMAS-A’s three factor structure of anxiety is consistent with multidimensional theories of anxiety and lends support to the validity of the interpretation of the AMAS-A scores as reflecting anxiety in several dimensions. Temporal stability and convergent and discriminant validity of the AMAS-A test scores were also examined in a sample of 76 young and middleaged adults. Results indicated good to excellent test-retest reliability for the AMAS-A scores over a 2- to 3-week interval. Evidence for convergent and discriminant validity of the AMAS-Ascores as measures of various aspects of anxietywas found. Implications of the findings are discussed.