cssi/SciSciGPT-SciSciNet huggingface dataset:
FDA Guidance on Off-Label Promotion and the State of the Literature From Sponsors

ALTHOUGH THE US FOOD AND DRUG ADMINISTRAtion (FDA) reviews and approves drugs for specific indications, the approval does not usually limit the use of those drugs in clinical practice. Indeed, prescribing for indications not reviewed by the FDA (“off-label”) is common. In a recent study of 160 frequently prescribed drugs, off-label use represented 21% of drug mentions, and 73% of these off-label uses had little or no scientific support. Off-label use has long been controversial because large numbers of patients may receive drugs that have had only limited testing for efficacy and safety, and some off-label uses may eventually be shown to have an unfavorable risk-benefit profile. High-profile examples include the use of the combination of fenfluramine and phentermine by millions of persons for weight loss and the widespread use of hormone therapy by postmenopausal women to prevent coronary artery disease. Although the FDA does not restrict physician prescribing for off-label indications, it does regulate the manufacturer’s promotion for such use. The FDA Modernization Act of 1997 permitted sponsors to disseminate peer-reviewed studies from scientific journals about off-label uses that had been or would form part of a supplementary New Drug Application (sNDA). These provisions expired in September 2006 with the result that current law prohibits any promotion of a drug for unapproved uses. Recently, the FDA proposed new guidelines that enable sponsors to distribute publications about unapproved uses of approved drugs and devices. For drugs, for example, an sNDA is no longer required. The journal that published the article to be distributed must have both an editorial board that uses independent reviewers and a policy of full disclosure of conflict of interest; the article must be peer-reviewed; and the article should not be in a supplement funded by the sponsor. The information should address adequate and well-controlled clinical investigations and not be false, misleading, or pose a significant threat to health. Distribution is to include the product label, a relevant bibliography, and a representative publication, if it exists, that reaches a different conclusion about the unapproved use. Are these proposed changes consistent with the FDA’s mission of protecting the public health by ensuring the efficacy and safety of medications? Although peer-reviewed literature serves as the gold standard for evidence-based medicine, there are major limitations in relying on sponsordistributed literature to regulate off-label use, including the selective publication of studies, the systematic manipulation of the literature, the absence from the literature of critical data necessary for evaluating off-label use, and the potential for undermining the NDA review process.
Phase shifting of the circadian clock by induction of the Drosophila period protein

Virtually all organisms manifest circadian (24-hour) rhythms, governed by an ill-defined endogenous pacemaker or clock. Several lines of evidence suggest that the Drosophila melanogaster period gene product PER is a clock component. If PER were central to the time-keeping mechanism, a transient increase in its concentration would cause a stable shift in the phase of the clock. Therefore, transgenic flies bearing a heat-inducible copy of PER were subjected to temperature pulses. This treatment caused long-lasting phase shifts in the locomotor activity circadian rhythm, a result that supports the contention that PER is a bona fide clock component.
Low-power and low-offset comparator using latch load

A low-power and low-offset latched comparator using dynamic offset cancellation and a latch load is proposed. A latch load at the first stage provides the second stage with a large conversion gain and large trigger voltage. It reduces the power consumption and offset voltage of the comparator. The effectiveness of the proposed structure was verified by SPECTRE simulations.
4737 Outcome of direct percutaneous endoscopic jejunostomy tube placement for nutritional support in critically-ill, mechanically ventilated patients.

Background: Gastrointestinal function is adversely affected in critically-ill, mechanically ventilated patients. The most common abnormality is delayed gastric emptying. This may lead to intolerance of gastric enteral feedings despite the presence of a functioning small bowel, and may predispose to aspiration pneumonia. Placement of a direct percutaneous endoscopic jejunostomy tube (PEJ) provides direct access to the small bowel and may therefore be the preferred route of access in critically-ill, mechanically ventilated patients who require enteral nutrition support. Methods:A review of the records of all patients who underwent direct PEJ tube placement while mechanically ventilated in the ICU was undertaken. For each patient the following factors were identified: age, indication for ICU admission and PEJ placement, nutritional support prior to and after PEJ placement, calories received, complications (aspiration, diarrhea, infection, bleeding, abdominal pain, leakage, or any procedural complications), and outcome. Results: 17 patients were studied. All had successful placement of direct PEJ tubes. The mean age was 64 years with a range of 25-83 years. Indications for PEJ placement included: aspiration pneumonia =9, intolerance of gastric enteral feedings =4, anastomotic leak after esophagectomy/gastric pull-up =3, duodenal obstruction =1. There was a single complication (colonic perforation). 15/17 patients tolerated jejunal feedings within 24 hours of PEJ placement. The mean daily caloric intake through the PEJ tube was 1994 cal (range 1440-2700) and all were able to progress to their established nutritional goals. There were no cases of aspiration of PEJ feeds. 13 patients required total parenteral nutrition (TPN) prior to PEJ placement. In all these patients TPN was not required once PEJ tubes were placed. 12 patients were discharged to home or a rehabilitation facility with jejunal feeds, 3 expired in the ICU, 1 was able to resume oral intake, and 1 remains hospitalized with continued enteral feedings. Conclusions: Direct PEJ is a safe and effective method to provide enteral nutrition support to critically-ill, mechanically ventilated patients who may not tolerate gastric enteral feeds and who might otherwise require TPN.
Serrated polyps with "intermediate features" of sessile serrated polyp and microvesicular hyperplastic polyp: a practical approach to the classification of nondysplastic serrated polyps.

Sessile serrated polyps (SSPs) have been implicated in the pathogenesis of proximal colonic carcinomas, but they lack well-defined diagnostic criteria and their features overlap considerably with those of microvesicular hyperplastic polyps (MVHPs). We have noted that morphologic features of SSPs are often present in small, distally located MVHPs, suggesting that these polyps represent points on a continuum, rather than distinct entities. We evaluated the molecular features of diminutive ( or = 1 cm), proximally located polyps with a presumed biologic risk, until prospective data regarding the natural history of small, distal lesions are available.
Kinetics of the dissolution of alumina in acidic solution in a flow system

The kinetics of dissolution of alumina in aqueous solutions of H2SO4 was studied at ambient temperature under continuous-flow conditions. The results are consistent with a model involving rapid hydration of the surface, adsorption-desorption of H+ to form precursor sites, and rate-determining parallel reactions of the precursor sites to form dissolved aluminum and an insoluble surface species. The model also involves renewal of a precursor site after each dissolution step. The adsorption-desorption of H+ was represented by a Langmuir isotherm. The dissolution data were correlated by a kinetic equation that was developed by assuming the dissolution step is first order in precursor concentration, and the deactivation step is second order in precursor concentration.
Further studies on the thermally induced aging of Drosophila melanogaster.

It was found that exposing Drosophila to ionizing radiation actually extends life expectancy, rather than shortens it. A comparison was made of the survivorship of flies reared and housed under sterile conditions with those living in cultures containing the yeasts which normaliy accompany Drosophila and which are one of their immediate food sources. The effect of irradiation on the mortality rate, such as to produce an extension of life, was largely lost or absent when the flies were reared under absolutely aseptic conditions. It was also shown that the reguiar replenishment of the housing and food of individuaiiy housed Drosophila produces a considerable extension of the life span. Thermal shock exposures at 38.5 deg C for periods ranging from 1/2 to 3 hr (in fractionated dosages) resulted in a significant increase in the age-specific mortality rate of the flies surviving beyond 7 days after the exposure. The results suggest that denaturative processes may mimic the effects of time on the aging of Drosophila as reflected in mortality rates. (H.H.D.) time on the aging of Drosophila as reflected in mortality rates. (H.H.D.)
Viral hepatitis in the Arctic

Objectives. Summarize research on viral hepatitis in indigenous populations in the Arctic. Study Design. Literature review. Methods. Medline search from 1966-2003. Results. High prevalence rates of total hepatitis A antibody of > 50% and of hepatitis B of between 22% in Alaska and 42% in Greenland for total infection and between 3% in Canada and 12% in Siberia for chronic infection have been reported. Universal childhood vaccination with hepatitis A vaccine beginning at age 2 have stopped epidemics of HAV in Alaska and newborn hepatitis B immunization programs in Alaska and Canada have reduced new infections. However, in all Arctic countries several thousand persons chronically infected with HBV remain at risk for the development of cirrhosis and hepatocellular carcinoma. Prevalence rates of hepatitis C (HCV) reported are <1.4% in the Arctic. Hepatitis D virus, which co-infects with HBV, has been found in 40% of persons with HBV in Greenland. Conclusions. High rates of viral hepatitis A, B, C, and D are found in the Arctic. Effective vaccines against HAV, HBV and HDV can prevent transmission of these viruses. In addition, new antiviral therapies for HBV and HCV can be used effectively to treat many chronically infected patients. Keywords: Viral Hepatitis, Arctic, Indigenous Peoples
Improvement of ultrathin gate oxide by a novel rapid thermal oxidation process with in-situ steam generation

This paper reports for the first time the growth of ultra- thin gate oxide by rapid thermal oxidation using in-situ generated steam (Wet RTO). Compared to conventional gate oxide grown by wet furnace and dry RTO, excellent oxide integrity of Wet RTO is demonstrated. Furthermore, the Wet RTO oxides nitrided by in-situ NO rapid thermal anneal also exhibits improved device transconductance, current drivability, and hot carrier reliability.
Life Span Changes in Electrophysiological Measures of Inhibition

Three electrophysiological findings which provide suggestive evidence of weakened inhibition in children and the elderly are reviewed. First, compared to young adults, electrophysiological recordings from old adults show a greater incidence of EEG alpha in anterior cortical areas and of somatosensory evoked potentials in occipital areas, and a reduction in heterogeneity of EEG and ERP activity across recording sites. These findings suggest a relative weakening of central inhibition in old age and a loss of functional independence of cortical centers. Second, visually evoked potentials from children and the elderly demonstrate a relative lack of differentiation between patterned and unpatterned stimuli. Inhibition is known to be important within the visual system for the detection of lines and contours. Finally, children and the elderly do not dampen (inhibit) their electrophysiological responses to sensory stimuli as effectively as subjects of an intermediate age. These age-related differences in electrophysiological responsivity appear to parallel age changes in behavioral measures which are also believed to reflect weakened inhibition. The electrophysiological measures, which reflect maturity and health of CNS structural and chemical systems, indicate that inhibition plays an increasing role in the shaping of behavior as children approach late adolescence but a diminishing role as adults live beyond the fifth decade. Recent research, however, suggests that the magnitude of inhibitory loss in old age may be related to cardiovascular health. Older men who frequently participated in vigorous physical activity showed significantly less inhibitory loss than age-matched peers who seldom exercised.
The Roots of Public Attitudes Toward State Accommodation of European Muslims' Religious Practices Before and After September 11

More than nine million Muslims currently live in Western Europe, which makes them the largest religious minority in the region. There has been significant political controversy in various European states over how best to recognize Muslims' religious rights. These questions have become even more significant and contentious in the aftermath of the September 11 attacks by Islamic extremists. Using privately commissioned polls on attitudes toward Muslim religious rights taken before and after September 11 in Britain, France, and Germany, this article determines the extent of popular opposition to state accommodation of Muslim practices and tests several leading theories of attitudes toward Muslims. We conclude that the most important determinants of attitudes toward Muslims are education and religious practice.
Gene Set Analysis with Covariates

In microarray experiments, expression profiles are obtained for thousands of genes under several treatments. Traditionally, most of the statistical techniques employed are concentrated around univariate methods. They ignore the inter-gene dependence and do not use any prior biological knowledge. Gene set analysis addresses both these concerns by analyzing together a group of correlated genes, for example genes that share a common biological function, chromosomal location, or regulation. In this paper we propose a multivariate analysis of covariance model (MANCOVA) for gene set analysis with covariates. Principal component analysis (PCA) is used to address the dimensionality problem. The two testing procedures presented are shown to perform well using simulations.
Regional (14C) 2-deoxyglucose uptake during forelimb movements evoked by rat motor cortex stimulation: pons, cerebellum, medulla, spinal cord, muscle.

Electrical stimulation of the right forelimb motor (MI) sensory (SI) cortex in normal, adult rats produced repetitive left forelimb movements. Regions of increased (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically during these movements. MI stimulation activated the ipsilateral reticular tegmental pontine nucleus (RTF) and the middle (rostral-caudal) third of the pontine nuclei including pyramidal (P), medial (POM), ventral (POV), and lateral (POL) pontine nuclei. The ipsilateral inferior olivary complex was activated including dorsal accessory olive (DAO), principal olive (PO), and medial accessory olive (MAO). The contralateral lateral reticular (LR) nucleus and nucleus cuneatus (CU) were activated. Lateral vermal, paravermal, and hemispheric portions of the contralateral cerebellum were also activated. Parts of vermian lobules IV, V, VI, VII, and VIII, and lobulus simplex, crus I, crus II, paramedian lobule, and copula pyramidis were activated. Granule cell layers were activated much more than molecular layers. Discrete microzones of high granule cell 2DG uptake alternated with zones of low uptake in left paramedian lobule and copula pyramidis and may correlate with the fractured cerebellar somatotopy described physiologically by Welker and his associates. Portions of the left lateral and interpositus nuclei were metabolically activated. Medial portions of laminae I-VI were activated in the dorsal horn of cervical spinal cord. The 2DG uptake was either unchanged or decreased in the ventral horn. Thoracic and lumbar spinal cord were not activated. Monsynaptic MI and SI connections to P, POM, POV, POL, RTF, DAO, PO, MAO, LR, CU, and spinal cord could account for activation of those structures. However, there are no direct MI or SI connections to the deep cerebellar nuclei, the cerebellar hemisphere, or the muscles. Activation of these structures must be due to activation of polysynaptic pathways, sensory feedback from the moving forelimb, or both. The present experiments cannot distinguish these possibilities. Comparison of the regions activated during forelimb MI stimulation (FLMIS) to those activated during vibrissae MI stimulation (VMIS) suggests that the pontine nuclei, cerebellar hemisphere, and possibly the deep cerebellar nuclei are somatotopically organized. RTP, LR, CU, and spinal cord were activated during FLMIS but were not activated during VMIS. The failure to activate the ventral horn of cervical spinal cord may be due to known inhibition of alpha-motor neurons during motor cortex stimulation.
Characterization of two tomato AP2/ERF genes, SlCRF1 and SlCRF2 in hormone and stress responses

SlCRF1 and SlCRF2 are expressed throughout the plant, prominently in vascular tissue. Each SlCRF has a distinct pattern of cytokinin induction and regulation by abiotic stresses in different organs. Cytokinin is an essential plant hormone involved in the regulation of many growth and developmental processes. While many cytokinin signaling pathway components have been well characterized, the cytokinin response factors (CRFs) that form a branch of this pathway are less well understood. This study examines the tomato (Solanum lycopersicum (L.)) CRF genes, SlCRF1 and SlCRF2 presenting a detailed and novel characterization of their developmental expression patterns, transcriptional regulation by hormones particularly cytokinin, and response to abiotic stresses. Both SlCRF1 and SlCRF2 were predominantly expressed in vasculature in tissues throughout the plant, with an overall trend for greater SlCRF2 expression in younger organs. Hormone regulation of SlCRF1 and SlCRF2 transcripts is primarily by cytokinin, which induced both SlCRFs in different organs over a range of developmental stages. The strongest cytokinin induction was found in leaves, with SlCRF2 induced to a higher level than SlCRF1. Examination of SlCRF transcripts during abiotic stress responses revealed that SlCRF1 and SlCRF2 have distinct patterns of regulation from each other and between leaves and roots. Novel connections between SlCRFs and stresses were found in particular including a strong induction of SlCRF1 by cold stress and a strong induction of SlCRF2 by oxidative stress in roots and unique patterns of induction/repression linking both SlCRFs to drought stress and response during recovery. Overall, this study provides a clear picture of SlCRF1 and SlCRF2 expression patterns across tissues during development and in response to cytokinin and specific stresses, indicating their importance in plant growth and environmental responses.
Rational and experiential decision-making preferences of third-year student pharmacists.

Objective. To examine the rational (systematic and rule-based) and experiential (fast and intuitive) decision-making preferences of student pharmacists, and to compare these preferences to the preferences of other health professionals and student populations.Methods. The Rational-Experiential Inventory (REI-40), a validated psychometric tool, was administered electronically to 114 third-year (P3) student pharmacists. Student demographics and preadmission data were collected. The REI-40 results were compared with student demographics and admissions data to identify possible correlations between these factors.Results. Mean REI-40 rational scores were higher than experiential scores. Rational scores for younger students were significantly higher than students aged 30 years and older (p<0.05). No significant differences were found based on gender, race, or the presence of a prior degree. All correlations between REI-40 scores and incoming grade point average (GPA) and Pharmacy College Admission Test (PCAT) sc...
Development of a Directly Patterned Low-Surface-Energy Polymer Brush in Supercritical Carbon Dioxide

Carbon dioxide (CO2) is a sustainable solvent because it is nonflammable, exhibits a relatively low toxicity, and is naturally abundant. As a selective, nonpolar solvent, supercritical CO2 (scCO2) is an ideal fit for the development of low-surface-energy polymers. The development of directly patterned poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) brushes in scCO2 was investigated. PTFEMA, in particular, was selected over other fluorinated polymers because of its very high electron-beam (e-beam) sensitivity. PTFEMA brushes were grown on silicon substrates via controlled surface-initiated atom-transfer radical polymerization of TFEMA. Surface analysis techniques including ellipsometry, contact-angle goniometry, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy were used to characterize the thickness, hydrophilicity, roughness, and chemical composition of the polymer brushes. PTFEMA brushes were directly patterned in a single step using e-beam lithography and were processed in an environ...
The Shock of the New: On Migrant Imaginaries and Critical Transitions

Abstract This essay is based on recent fieldwork (2005–2006) among Sierra Leonean migrants, both legal and illegal, living in southeast London. Its focus is the lifeworld of a young Sierra Leonean man struggling to find his feet in a city that is both perplexing and perilous. It attempts to show how his struggle for legitimacy, security, income, and an ongoing sense ofconnectedness with his homeland is played out not only in his everyday survival strategies but in his active imagination.
Dilation efficacy: is 1% cyclopentolate enough?

Abstract Background Pediatric eye examinations include cycloplegia and dilation. Most clinicians use 2 or 3 different medications in drop or spray form to ease instillation. We studied whether a single drop of a cycloplegic agent would provide effective dilation as well. Methods Children between the ages of 1 and 7 years, who presented for a routine eye examination, were recruited to participate. Each child received 1% cyclopentolate in the right eye (group A), and either tetracaine with cyclopentolate (group B) or tetracaine with cyclopentolate with phenylephrine (group C) in the left eye. At the completion of the examination, a digital picture was taken of the patient’s pupils. A separate observer measured the pupil diameter and classified iris color. Results The mean pupil size for all subjects was: 6.19 mm ± 1.33 mm, for group A, 6.56 mm ± 1.25 for group B; and 6.47 mm ± 1.12 for group C. Light-colored iris patients had greater dilation as a group and darker iris patients had less dilation as a group. Evaluation of the paired eyes pupil diameter found no statistical difference. Conclusions One drop of 1% cyclopentolate provides cycloplegia and effective pupil dilation for completion of a pediatric eye examination. One drop is easier to instill than multiple drops and should be considered for use in a pediatric eye examination.
Adaptation to Peripheral Flicker

Abstract With strict fixation, a flickering disk presented in the peripheral retina rapidly appeared to lose contrast and stop flickering, owing to adaptation. Subjects measured this adaptation by continually adjusting the flicker amplitude of a peripherally viewed disk to hold it just at threshold. Results: (1) The contrast threshold for flicker increased logarithmically over time. (2) The slope of the temporal decay function increased with eccentricity (1–16 deg) and with decreasing disk size (8 deg–3.6 min arc). (3) M-scaling the stimulus size could abolish the dependence upon eccentricity for small disks, but not completely for large disks. (4) The temporal decay rate increased with flicker rate (3–15 Hz), as though each cycle of flicker elevated contrast threshold equally. Copyright © 1996 Elsevier Science Ltd.
3D multiwavelet packets on low bit-rate color video compression

In this paper, the frequency characteristic of individual basis functions in five types of multiwavelet packets and their influence on 3D packet-based color video compression are examined. The operations of switching packets and shuffling coefficients have been separately tested to evaluate their effects on the low bit-rate color video compression using spatio-temporal 3D multiwavelet packets.
Anion recognition using dimetallic coordination complexes

This article describes advances made over the past 3 years in anion recognition using coordination complexes, with a specific focus on dimetallic architectures that utilize a bridging mechanism. The formation of coordination complexes is a relatively straightforward method of constructing fluorescent and colorimetric chemosensors and imaging agents, and a particularly effective way to develop indicator displacement assays that operate in water. These assays are likely to find increased application in various aspects of analytical and environmental chemistry, as well as biomedical imaging and drug discovery. Significant progress in phosphoesterase mimics has been made, and concomitant with the increased mechanistic insight, is the discovery of a catalyst that cleaves phosphodiesters with poor O-alkyl leaving groups. Also discussed is a macrocyclic coordination complex whose shape and supramolecular function is pH-dependent.
The Effect of Different Levels of Productive Energy, Protein and Methionine upon the Growth of Broad Breasted Bronze Turkey Poults

Abstract METHIONINE supplements to the diet of turkey poults have been found to improve growth and feed efficiency by Bird et al. (1948), Atkinson et al. (1953), Pepper and Slinger (1955), Donovan et al. (1955), Lockhart and Thayer (1955), Ferguson et al. (1956a), and many others. Johnson (1950) and Saxena and McGinnis (1952) reported an improvement in feed efficiency with turkey poults due to methionine supplements. The relationship of energy, fiber, protein, and the physical form of the diet to the growth of turkeys has been reported by Scott et al. (1948), Blaylock et al. (1954), Dymsza et al. (1955), Lockhart and Thayer (1955), and Ferguson et al. (1956a, b). The purpose of the present experiment was to determine the relationship between productive energy and methionine supplementation to the diet of turkey poults fed different levels of protein. EXPERIMENTAL PROCEDURE Straight run Broad Breasted Bronze turkey poults were fed diets containing …
Performance Measurement in State Budgeting: Advancement and Backsliding from 1990 to 1995

Performance measurement has been one of the dominant themes of budget reform in the 1990s and has been prevalent in the mainstream of budgeting since the 1950s. Given the attention that performance measurement has had nationally, states might be expected to have made major strides in this arena in recent years. The article considers the current status of performance measurement practices, and identifies both advancement and backsliding made by states between 1990 and 1995. The discussion is based on data obtained from surveys of state budget offices in those two years. Indexes of performance measurement were constructed, and these became the bases of regression analyses using independent variables pertaining to state characteristics. Generally, these analyses were unsuccessful in explaining the variations among the states. The findings underscore the diversity among the states in their budgetary practices and the fact that budget reform, in the sense of increased use of performance measurement, is not necessarily achieved in a straight line of progression. The article considers possible explanations for the changes.
AD SKEPTICISM: The Consequences of Disbelief

Three studies investigated the effects of consumer skepticism toward advertising on responses to ads. Consumer skepticism, defined as the tendency toward disbelief of advertising claims (Obermiller and Spangenberg 1998), is measured in each study and then related to various measures of advertising response, including brand beliefs, ad attitudes, responses to informational and emotional appeals, efforts to avoid advertising, attention to ads, and reliance on ads versus other information sources. The results generally support the hypotheses that more skeptical consumers like advertising less, rely on it less, attend to it less, and respond more positively to emotional appeals than to informational appeals.
Retrograde lysis of coronary artery thrombus by coronary venous streptokinase administration

This study examined whether an occlusive thrombus within a coronary artery can be lysed by streptokinase retro-perfusion into the associated regional coronary vein. Experimental coronary artery thrombosis was induced in 15 closed chest dogs by placing a small copper coil at a proximal site of the left anterior descending coronary artery. Total thrombotic obstruction of this artery was verified within 10 to 60 minutes (38.0 ± 15.8, mean ± standard deviation) and streptokinase was administered within 94.0 ± 17.4 minutes from coil insertion at an average rate of 42 IU/kg per minute by one of three modes: 1) intermittent 10 minute direct coronary venous retroinfusion (five dogs); 2) continuous infusion into the pumping circuit of synchronized phased retroperfusion of the great cardiac vein with arterial blood (five dogs); and 3) for comparison, streptokinase administered intravenously (five dogs). The intracoronary thrombus was fully lysed and anterograde reperfusion established within 51.0 ± 18.7 minutes by intermittent streptokinase retroinfusion, and in 50.0 ±6.1 minutes by streptokinase supplemented synchronized retroperfusion (50.5 ± 13.2 minutes for pooled retrograde coronary venous delivery). Lysis was also induced by systemic streptokinase, but the time to lysis was significantly longer and more variable (131.6 ± 60.6 minutes) than with retrograde administration (p The retroperfusion modality appears the preferable technique because it provides early thrombolysis and, at the same time, improves cardiac function and maintains myocardial viability of the jeopardized ischemic zone pending achievement of full reflow. Thus, streptokinase retroperfusion, if promptly instituted, may be a useful complemental nonsurgical treatment of evolving acute myocardial infarction after thrombotic coronary artery occlusion.
Dimensions of interactive software requirements: synergistic opportunity

Structured analysis and design (SAD), object-oriented analysis and design (OOAD), and interface design (ID) define formal methods for discovering requirements and designing interactive software systems. Structured and object-oriented methods, collectively known as software engineering (SE) methods, specify methodologies that employ a unique set of interrelated models. Interface design methods employ user-centered techniques to understand users, their work environment and goals. Each specialized approach relies on the knowledge worker as a source of requirements where success hinges on effective coordination of activities in heterogeneous software development environments (K. Holtzblatt, Interactions, pp. 17-20, 1994). The software creation process may employ each of these methods independent of the other, in conjunction with the other, or not at all. SAD, OOAD, and ID methods yield independent views of requirements yet many of their activities, or dimensions of requirements, overlap within the context of a software development project. This paper investigates dimensions of requirements common to those methods that suggest collaborative opportunity, reduced knowledge worker burden, and improved software quality are possible. A current state analysis of requirements methods defined in the literature, and identification of interrelated and overlapping characteristics are discussed.
A model for hydraulic redistribution incorporating coupled soil-root moisture transport

Abstract. One of the adaptive strategies of vegetation, particularly in water limited ecosystems, is the development of deep roots and the use of hydraulic redistribution which enables them to make optimal use of resources available throughout the soil column. Hydraulic redistribution refers to roots acting as a preferential pathway for the movement of water from wet to dry soil layers driven by the moisture gradient – be it from the shallow to deep layers or vice versa. This occurs during the nighttime while during the daytime moisture movement is driven to fulfill the transpiration demand at the canopy. In this study, we develop a model to investigate the effect of hydraulic redistribution by deep roots on the terrestrial climatology. Sierra Nevada eco-region is chosen as the study site which has wet winters and dry summers. Hydraulic redistribution enables the movement of moisture from the upper soil layers to deeper zones during the wet months and this moisture is then available to meet the transpiration demand during the late dry season. It results in significant alteration of the profiles of soil moisture and water uptake as well as increase in the canopy transpiration, carbon assimilation, and the associated water-use-efficiency during the dry summer season. This also makes the presence of roots in deeper soil layers much more important than their proportional abundance would otherwise dictate. Comparison with observations of latent heat from a flux tower demonstrates improved predictability and provides validation of the model results. Hydraulic redistribution serves as a mechanism for the interaction between the variability of deep layer soil-moisture and the land-surface climatology and could have significant implications for seasonal and sub-seasonal climate prediction.
The acquisition of psychotherapeutic skill: an empirical study.

The acquisition of psychotherapy skillfulness is an important aspect of training programs in psychiatry and clinical psychology. Psychotherapy supervision is employed to teach and monitor the development of these clinical skills. The Supervisor Report (SR) is a questionnaire designed to systematically assess therapeutic behaviors and global psychotherapeutic skillfulness of therapists conducting psychodynamic psychotherapy. SRs were employed to examine changes in trainees' skillfulness over the course of training. T-tests were applied to evaluate differences between the average scores of trainees in the first half of their training compared to the last half of their training. Comparisons of the scores for Psychotherapeutic Techniques and assessments of Global Skillfulness were in the predicted direction: Trainees in the advanced portion of their training were rated as more skillful than at the beginning. This study provides some evidence that psychotherapy skillfulness is acquired over time in training. © 1998 John Wiley & Sons, Inc. J Clin Psychol 54: 895–903, 1998.
Use of the tetrazolium salt MTT to measure cell viability effects of the bacterial antagonist Lysobacter enzymogenes on the filamentous fungus Cryphonectria parasitica

Despite substantial interest investigating bacterial mechanisms of fungal growth inhibition, there are few methods available that quantify fungal cell death during direct interactions with bacteria. Here we describe an in vitro cell suspension assay using the tetrazolium salt MTT as a viability stain to assess direct effects of the bacterial antagonist Lysobacter enzymogenes on hyphal cells of the filamentous fungus Cryphonectria parasitica. The effects of bacterial cell density, fungal age and the physiological state of fungal mycelia on fungal cell viability were evaluated. As expected, increased bacterial cell density correlated with reduced fungal cell viability over time. Bacterial effects on fungal cell viability were influenced by both age and physiological state of the fungal mycelium. Cells obtained from 1-week-old mycelia lost viability faster compared with those from 2-week-old mycelia. Likewise, hyphal cells obtained from the lower layer of the mycelial pellicle lost viability more quickly compared with cells from the upper layer of the mycelial pellicle. Fungal cell viability was compared between interactions with L. enzymogenes wildtype strain C3 and a mutant strain, DCA, which was previously demonstrated to lack in vitro antifungal activity. Addition of antibiotics eliminated contributions to MTT-formazan production by bacterial cells, but not by fungal cells, demonstrating that mutant strain DCA had lost complete capacity to reduce fungal cell viability. These results indicate this cell suspension assay can be used to quantify bacterial effects on fungal cells, thus providing a reliable method to differentiate strains during bacterial/fungal interactions.
Noninvasive markers of hepatic fibrosis: are they ready for prime time in the management of HIV/HCV co-infected patients?

Hepatitis C virus (HCV) infection is associated with increased morbidity and mortality in HIV-infected patients; up to one-third of HIV-infected patients are co-infected with HCV. In addition, HIV alters the natural history of HCV as indicated by increased serum HCV RNA concentration, accelerated fibrosis progression, and increased prevalence of end stage liver disease and hepatocellular carcinoma [1]. In chronic HCV infection, only a minority (w20–30%) of patients will progress to fibrosis and cirrhosis over a period of 20–30 years [2]. In HIV/HCV co-infection, fibrosis progression is increased two-fold [3]; over a period of 10–15 years, 15–25% of co-infected patients will develop cirrhosis compared to 2.6–6.5% of HIV negative patients [4,5]. In most patients with chronic HCV infection, a dynamic process is established whereby inflammatory cells are attracted to the liver in an attempt to clear infected hepatocytes. Retention and prolonged survival of intrahepatic inflammatory cells can promote tissue damage that can eventually lead to liver fibrosis. Fibrosis, an excessive accumulation of collagen and other extra-cellular matrix (ECM) proteins, is part of a wound healing process that develops in response to liver injury. Progressive ECM deposition alters hepatic morphology and function ultimately culminating in hepatic impairment, portal hypertension, and the clinical sequela of end stage liver disease. The rate of fibrosis progression varies considerably between patients. Immunodeficiency, as in patients infected with HIV and post-transplantation, steatosis, and alcohol use are important co-factors that promote accelerated fibrogenesis. Fibrosis assessment is a necessary step in determining the severity of HCV-associated liver disease and whether treatment is indicated. The majority of studies have
Growth models of cultures with two liquid phases. III. Continuous cultures

Some mathematical models, which have been used to describe batch growth in fermentations with two liquid phases present, are used to predict the behavior of continuous fermentations in a chemostat. Two types of dispersed systems are considered in this investigation. In the first, type, it is assumed that the composition of the dispersed phase is such that, increased substrate utilization results in a decreased substrate concentration with no change in the interfacial area. In the second type of system, the dispersed phase is assumed to be pure substrate; therefore, the substrate concentration in the dispersed phase remains constant but the interfacial area is affected by changes in dilution rate. Three special cases are examined for each type of system in order to examine the effect of the interfacial area, the phase equilibrium constant, and the mass transfer coefficient on system performance. Comparison of two of the models with available experimental data shows fair agreement, between model and data.
Preserving Continence During Robotic Prostatectomy

Preservation of postoperative urinary continence remains the primary concern of all men and their surgeons following robot-assisted radical prostatectomy (RARP). Without doubt, continence is the most important quality of life issue following radical prostatectomy. Identification of difficulties and lessons learned over time has helped focus efforts in order to improve urinary quality of life and continence. This review will examine definitions of continence and urinary quality of life evaluation, technical aspects and the impact of patient-related factors affecting time to and overall continence.
The distance from the equator as an instrumental variable

Abstract To attack the problem of measurement errors in independent variables, the distance from the equator is used as an instrumental variable for per capita income. Application of this idea to the estimation of a demand system from the cross-country data of Kravis et al. (1982) yields promising results.
Assessment of 10 years of CO2 fumigation on soil microbial communities and function in a sweetgum plantation

Abstract Increased vegetative growth and soil carbon (C) storage under elevated carbon dioxide concentration ([CO 2 ]) has been demonstrated in a number of experiments. However, the ability of ecosystems, either above- or belowground, to maintain increased C storage relies on the response of soil processes, such as those that control nitrogen (N) mineralization, to climatic change. These soil processes are mediated by microbial communities whose activity and structure may also respond to increasing atmospheric [CO 2 ]. We took advantage of a long-term (ca 10 y) CO 2 enrichment experiment in a sweetgum plantation located in the southeastern United States to test the hypothesis that observed increases in root production in elevated relative to ambient CO 2 plots would alter microbial community structure, increase microbial activity, and increase soil nutrient cycling. We found that elevated [CO 2 ] had no detectable effect on microbial community structure using 16S rRNA gene clone libraries, on microbial activity measured with extracellular enzyme activity, or on potential soil N mineralization and nitrification rates. These results support findings at other forested Free Air [CO 2 ] Enrichment (FACE) sites.
Focus issue: uncovering the mechanisms of neurological disease.

This week, Science Signaling highlights research that uses computational and cell biology approaches to uncover the molecular mechanisms underlying diseases of the central nervous system. In particular, research featured explores the neuronal response to stress due to excess excitatory stimuli, multiple roles for presenilin in Alzheimer’s disease, and mechanisms through which autism may arise. In addition, new molecular targets for treating an aggressive form of brain cancer are presented. Not only do these articles provide potential mechanisms for the development of therapies, they also illuminate the intricacies of synaptic signaling and the complexity of forming and maintaining appropriate synaptic connections.
Endothelin-1–Induced Vasospasms of Spiral Modiolar Artery Are Mediated by Rho-Kinase–Induced Ca2+ Sensitization of Contractile Apparatus and Reversed by Calcitonin Gene–Related Peptide

Background and Purpose—Vasospasms of the spiral modiolar artery may cause an ischemic stroke of the inner ear that manifests itself by a sudden hearing loss. Previously we have shown that endothelin-1 (ET-1) induces vasospasms of the spiral modiolar artery. Here we tested the hypotheses that ET-1–induced vasospasms are (1) reversible by ETA receptor antagonists; (2) mediated by a Ca 2 sensitization of the contractile apparatus via a Rho-kinase–induced inhibition of myosin light chain phosphatase; and (3) reversible by the vasodilator calcitonin gene–related peptide (CGRP). Methods—The Ca 2 sensitivity of the contractile apparatus was evaluated by correlation between the smooth muscle cell Ca 2 concentration and the vascular diameter, which were measured by microfluorometry with the fluorescent dye fluo-4 and videomicroscopy, respectively. Results—ET-1–induced vasospasms were prevented but not reversed by the ETA receptor antagonists BQ-123 and BMS-182874. The Ca 2 sensitivity of the contractile apparatus was increased by ET-1 and by inhibition of myosin light chain phosphatase with calyculin A and was decreased by CGRP. ET-1–induced vasospasms and Ca 2 sensitization were prevented and reversed by the Rho-kinase antagonist Y-27632 and by CGRP. Conclusions—ET-1 induces vasospasms of the spiral modiolar artery via ETA receptor–mediated activation of Rho-kinase, inhibition of myosin light chain phosphatase, and an increase in Ca 2 sensitivity, which is reversed by CGRP. The observation that vasospasms were reversed by Y-27632 but not by BQ-123 or BMS-182874 suggests that Rho-kinase, rather than the ETA receptor, is the most promising pharmacological target for the treatment of ET-1–induced vasospasms, ischemic strokes, and sudden hearing loss. (Stroke. 2002;33:2965-2971.)
FlashFQ: a fair queueing I/O scheduler for flash-based SSDs

On Flash-based solid-state disks (SSDs), different I/O operations (reads vs. writes, operations of different sizes) incur substantially different resource usage. This presents challenges for fair resource management in multi-programmed computer systems and multitenant cloud systems. Existing timeslice-based I/O schedulers achieve fairness at the cost of poor responsiveness, particularly when a large number of tasks compete for I/O simultaneously. At the same time, the diminished benefits of I/O spatial proximity on SSDs motivate fine-grained fair queueing approaches that do not enforce task-specific timeslices. This paper develops a new Flash I/O scheduler called FlashFQ. It enhances the start-time fair queueing schedulers with throttled dispatch to exploit restricted Flash I/O parallelism without losing fairness. It also employs I/O anticipation to minimize fairness violation due to deceptive idleness. We implemented FlashFQ in Linux and compared it with several existing I/O schedulers--Linux CFQ [2], an Argon [19]-inspired quanta scheduler, FIOS timeslice scheduler [17], FIOS with short timeslices, and 4-Tag SFQ(D) [11]. Results on synthetic I/O benchmarks, the Apache web server, and Kyoto Cabinet key-value store demonstrate that only FlashFQ can achieve both fairness and high responsiveness on Flash-based SSDs.
Visual model structures and synchrony constraints for audio-visual speech recognition

This paper presents the design and evaluation of a speaker-independent audio-visual speech recognition (AVSR) system that utilizes a segment-based modeling strategy. The audio and visual feature streams are integrated using a segment-constrained hidden Markov model, which allows the visual classifier to process visual frames with a constrained amount of asynchrony relative to proposed acoustic segments. The core experiments in this paper investigate several different visual model structures, each of which provides a different means for defining the units of the visual classifier and the synchrony constraints between the audio and visual streams. Word recognition experiments are conducted on the AV-TIMIT corpus under variable additive noise conditions. Over varying acoustic signal-to-noise ratios, word error rate reductions between 14% and 60% are observed when integrating the visual information into the automatic speech recognition process.