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Minimal Level (minimal + level)
Selected AbstractsErrors in the Interpretation of Mohs Histopathology Sections Over a 1-Year FellowshipDERMATOLOGIC SURGERY, Issue 12 2008MICHAEL E. MURPHY MD BACKGROUND Errors can occur in the interpretation of Mohs histopathology sections. Errors in histology interpretation can lead to incomplete removal of cancer and cancer persistence or the unnecessary removal of uninvolved tissue. Extensive proctored training is necessary to reduce these errors to an absolute minimum level. OBJECTIVE To analyze and quantify the number of cases and the amount of time required to reach a satisfactory level of expertise in the reading and interpretation of Mohs histopathology. METHODS A single-institution pilot study was designed to track errors in the interpretation and mapping of Mohs histopathology sections. A Mohs surgery fellow independently preread Mohs cases and rendered his interpretation on the Mohs map. One of the Mohs program directors subsequently reviewed and corrected all cases. Errors were scored on a graded scale and tracked over the 1-year fellowship to determine the number of cases and amount of time necessary to reduce errors to a baseline minimal level. RESULTS One thousand four hundred ninety-one Mohs surgery cases were required to generate 1,347 pathology specimens for review and grading over 6 months of Mohs surgery fellowship before reducing errors to a minimum acceptable level of less than 1 critical error per 100 cases read. CONCLUSIONS The number of cases and time required to reduce errors in the interpretation of Mohs histology is substantial. Direct and immediate mentored correction of errors is essential for improvement. These results can act as a guide for Mohs surgery training programs to help determine the minimum number of directly proctored cases required to obtain expertise in this crucial component of Mohs surgery. [source] Calmodulin and profilin coregulate axon outgrowth in DrosophilaDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2001You-Seung Kim Abstract Coordinated regulation of actin cytoskeletal dynamics is critical to growth cone movement. The intracellular molecules calmodulin and profilin actively regulate actin-based motility and participate in the signaling pathways used to steer growth cones. Here we show that in the developing Drosophila embryo, calmodulin and profilin convey complimentary information that is necessary for appropriate growth cone advance. Reducing calmodulin activity by expression of a dominant inhibitor (KA) stalls axon extension of pioneer neurons within the CNS, while a partial loss of profilin function decreases extension of motor axons in the periphery. Yet, surprisingly, when calmodulin and profilin are simultaneously reduced, the ability of both CNS pioneer axons and motor axons to extend beyond the choice points is restored. In the CNS, at the time when growth cones must decide whether to cross or not to cross the midline, a reduction in calmodulin and/or roundabout signaling causes axons to cross the midline inappropriately. These inappropriate crossings are suppressed when profilin activity is simultaneously reduced. Interestingly, the mutual suppression of calmodulin and profilin activity requires a minimal level of profilin. In KA combinations with profilin null alleles, defects in axon extension and midline guidance are synergistically enhanced rather than suppressed. Together, our data indicate that the growth cone must coordinate the activity of both calmodulin and profilin in order to advance past selected choice points, including those dictating midline crossovers. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 26,38, 2001 [source] EVIDENCE THAT GREATER DISCLOSURE LOWERS THE COST OF EQUITY CAPITALJOURNAL OF APPLIED CORPORATE FINANCE, Issue 4 2000Christine A. Botosan The effect of corporate disclosure on the cost of equity capital is a matter of considerable interest and importance to both corporations and the investment community. However, the relationship between disclosure level and cost of capital is not well established and has proved difficult for researchers to quantify. As described in this article, the author's 1997 study (published in The Accounting Review) was the first to measure and detect a direct relationship between disclosure and cost of capital. After examining the annual reports of 122 manufacturing companies, the author concluded that companies providing more extensive disclosure had a lower (forward-looking) cost of equity capital (measured using Value Line forecasts with an EBO valuation formula that derives from the dividend discount model). For companies with extensive analyst coverage, differences in disclosure do not appear to affect cost of capital. But for companies with small analyst followings, differences in disclosure do appear to matter. Among this group of companies, the firms judged to have the highest level of disclosure had a cost of equity capital that was nine-percentage points lower than otherwise similar firms with a minimal level of disclosure. Closer analysis of some of the specific disclosure practices also suggests that, for small firms with limited analyst coverage, there are benefits to providing more forward-looking information, such as forecasts of sales, profits, and capital expenditures, and enhanced disclosure of key non-financial statistics, such as order backlogs, market share, and growth in units sold. In closing, the article also discusses an interesting new study (by Lang and Lundholm) that suggests there is an important distinction between effective corporate disclosure and "hyping the stock." The findings of this study show that while higher levels of disclosures are associated with higher stock prices, sudden increases in the frequency of disclosure are viewed with skepticism. [source] Frequency of nurses' smoking cessation interventions: report from a national surveyJOURNAL OF CLINICAL NURSING, Issue 14 2009Linda Sarna Aims and objectives., To describe the frequency of nurses' delivery of tobacco cessation interventions (,Five A's': Ask, Advise, Assess, Assist, Arrange) and to determine the relationship of interventions to nurses' awareness of the Tobacco Free Nurses initiative. Background., Tobacco cessation interventions can be effectively provided by nurses. The delivery of smoking cessation interventions by healthcare providers is mandated by several organisations in the USA and around the world. Lack of education and resources about tobacco cessation may contribute to the minimal level of interventions. The Tobacco Free Nurses initiative was developed to provide nurses with easy access to web-based resources about tobacco control. Design., Cross-sectional survey of nurses (n = 3482) working in 35 Magnet-designated hospitals in the USA (21% response rate). Method., A valid and reliable questionnaire used in previous studies to assess the frequency of the nurse's delivery of smoking cessation interventions (,Five A's') was adapted for use on the web. Results., The majority of nurses asked (73%) and assisted (73%) with cessation. However, only 24% recommended pharmacotherapy. Only 22% referred to community resources and only 10% recommended use of the quitline. Nurses familiar with TFN (15%) were significantly more likely to report delivery of all aspects of interventions, including assisting with cessation (OR = 1·55, 95% CI 1·27, 1·90) and recommending medications (OR = 1·81, 95% CI 1·45, 2·24). Conclusions., Nurses' delivery of comprehensive smoking cessation interventions was suboptimal. Awareness of Tobacco Free Nurses was associated with increased interventions. Relevance to clinical practice., Further efforts are needed to ensure that nurses incorporate evidence-based interventions into clinical practice to help smokers quit. These findings support the value of Tobacco Free Nurses in providing nurses with information to support patients' quit attempts. [source] Root surface debridement and endotoxin removalJOURNAL OF PERIODONTAL RESEARCH, Issue 3 2003J. Cadosch Objective:, This study assessed associations between the number of standardized scaling strokes and the reduction of endotoxin on the root surface. Background:, Therapy of periodontally involved teeth attempts removal of accretions by scaling and root planing. The amount of mechanical therapy required to free the root surface from etiologic factors remains unknown. Methods:, Twenty-four extracted human caries-free single rooted teeth with at least 5 mm attachment loss were used. A region of interest (ROI) which contained subgingival calculus was defined on the root surface of each tooth. Standardized force instrumentation was applied using a force-measuring curet. Fifty working strokes were applied to every ROI. Forces applied were recorded. The force recordings were converted from Millivolts into Newtons (N). After every unit of 5 strokes, presence of calculus was evaluated and scaling debris was collected. Endotoxin concentration was determined in the debris samples. Results:, The endotoxin values for strokes 1,5 were statistically significantly greater than the values from all other stroke intervals. Complete calculus removal occured after a mean of 9.3 strokes. The endotoxin concentration reached a minimal level with concentrations of 0.03,0.306 EU/ml after calculus removal was complete. Conclusion:, These findings suggest that completion of calculus removal coincides with endotoxin levels associated with clinically healthy teeth. [source] Leading by Example and International Collective ActionJOURNAL OF PUBLIC ECONOMIC THEORY, Issue 1 2005ANDRÉ ROSSI DE OLIVEIRA This paper investigates leading by example as a policy prescription for international collective action to provide summation public goods. A country leads by example by committing to a minimal level of provision, and by matching higher contributions there beyond. In an evolutionary game-theoretic setting, we establish conditions for leading by example to be a neutrally stable strategy; i.e., to noncooperatively implement the cooperative outcome. These conditions are related to the degree of concavity of the contributors' utility functions and the incentives for free riding. They can be tested against empirical estimates of the public benefits of an international regime. [source] Optimal control of work-in-process inventory of a two-station production line,OPTIMAL CONTROL APPLICATIONS AND METHODS, Issue 3 2010A. Kokangul Abstract Most production lines keep a minimal level of inventory stock to save storage costs and buffer space. However, the random nature of processing, breakdown, and repair times can significantly affect the efficiency of a production line and force the stocking of work-in-process inventory. We are interested in the case when starvation and blockage are preferentially avoided. In this study, a mathematical model has been developed using asymptotic approximation and simulation that provides asymptotic results for the expected value and the variance of the stock level in a buffer as a function of time. In addition, the functional relationship between buffer capacity and the first stopping time caused by starvation or blockage has been determined. Copyright © 2009 John Wiley & Sons, Ltd. [source] Developmental regulation of neuron-specific P2X3 receptor expression in the rat cochleaTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2005Lin-Chien Huang Abstract ATP-gated ion channels assembled from P2X3 receptor (P2X3R) subunits contribute to neurotransmission and neurotrophic signaling, associated with neurite development and synaptogenesis, particularly in peripheral sensory neurons. Here, P2X3R expression was characterized in the rat cochlea from embryonic day 16 (E16) to adult (P49,56), using RT-PCR and immunohistochemistry. P2X3R mRNA was strongly expressed in the cochlea prior to birth, declined to a minimal level at P14, and was absent in adult tissue. P2X3R protein expression was confined to spiral ganglion neurons (SGN) within Rosenthal's canal of the cochlea. At E16, immunolabeling was detected in the SGN neurites, but not the distal neurite projection within the developing sensory epithelium (greater epithelial ridge). From E18, the immunolabeling was observed in the peripheral neurites innervating the inner hair cells but was reduced by P6. However, from P2,8, immunolabeling of the SGN neurites extended to include the outer spiral bundle fiber tract beneath the outer hair cells. This labeling of type II SGN afferent fiber declined after P8. By P14, all synaptic terminal immunolabeling in the organ of Corti was absent, and SGN cell body labeling was minimal. In adult cochlear tissue, P2X3R immunolabeling was not detected. Noise exposure did not induce P2X3R expression in the adult cochlea. These data indicate that ATP-gated ion channels incorporating P2X3R subunit expression are specifically targeted to the afferent terminals just prior to the onset of hearing, and likely contribute to the neurotrophic signaling which establishes functional auditory neurotransmission. J. Comp. Neurol. 484:133,143, 2005. © 2005 Wiley-Liss, Inc. [source] Apparent digestibility of nutrients and energy in extruded diets from cultivars of barley and wheat selected for nutritional quality in rainbow trout Oncorhynchus mykissAQUACULTURE NUTRITION, Issue 3 2009T.G. GAYLORD Abstract A digestibility trial was conducted to elucidate potential differences in barley (Hordeum vulgare L.) lines and varieties as a first step in defining their potential for use in aquafeeds. A diverse group of six barley lines having six combinations of selected attributes, normal versus low phytic acid, normal versus waxy, and hulled versus hull-less, were chosen for evaluation along with a waxy wheat (Triticum aestivum L.) and soft white wheat. The experimental diets were manufactured by cooking extrusion and consisted of a 70% reference diet that was formulated to contain a minimal level of phosphorus and 30% test ingredient. Phosphorus availability ranged from 17 to 78% and was influenced by starch type in wheat. Apparent protein digestibility ranged from 53 to 125% and differences were observed between wheat varieties based on starch type. Apparent energy digestibility ranged from 32 to 63%, with waxy barley varieties having higher energy digestibility coefficients than normal starch varieties. Waxy starch varieties had higher starch digestibility in both barley and wheat because of the greater digestibility of amylopectin than amylose. In summary, the higher energy digestibility of waxy barley lines suggests that these varieties warrant further attention as feed ingredients for rainbow trout. [source] Multiparametric analysis of normal and postchemotherapy bone marrow: Implication for the detection of leukemia-associated immunophenotypes,CYTOMETRY, Issue 1 2008D. Olaru Abstract Background: The knowledge of normal marrow is mandatory to assess the malignant counterpart of normal cells and define leukemia-associated immunophenotypes (LAIPs). In this study, the expression of a variety of antigens expressed in normal and postchemotherapy bone marrow (BM) was analyzed to provide a frame of reference for the identification of myeloid LAIPs. Methods: Multiparameter four- and six-color flow cytometry was used to define antigen combinations totally absent or present at very minimal levels in marrow cells of normal individuals (n = 20) and patients receiving chemotherapy for acute lymphoblastic leukemia (n = 20). Immature (blast) cells were gated according to CD45/SSC properties. Fifty-three acute myeloid leukemia (AML) samples were studied in six-color combinations. Results: In six-color flow cytometry, 47 phenotypes were totally absent from blast gate in all normal samples. Forty-one other phenotypes were identified in less than 0.05% of blast cells. There was no difference between normal and postchemotherapy BMs. The four-color panel allowed to identify only 30 phenotypes present at a frequency <0.05%. Using the six-color panel, 58% of the absent or infrequent phenotypes in normal BM were found in at least one of 53 AML samples. All AML cases exhibited at least one LAIP. Conclusion: Our results show that the ability to distinguish leukemic from healthy cells is considerably increased by a six-color approach. Furthermore, these absent or infrequent phenotypes in normal BM are identified in AML and can be utilized for minimal residual disease study. © 2007 Clinical Cytometry Society [source] Operant Self-Administration of Ethanol in Sardinian Alcohol-Preferring RatsALCOHOLISM, Issue 11 2002Giovanni Vacca Background "Work" for ethanol, that is, the ability of a laboratory animal to press a lever to gain access to ethanol, has been proposed as (a) a requirement for definition of an animal model of alcoholism and (b) a measure of ethanol-reinforcing properties. The present study evaluated oral self-administration of ethanol under an operant (lever pressing) procedure in selectively bred Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. Methods Rats from both lines were initiated to self-administer 10% ethanol, on a fixed ratio 1 schedule and in daily 30 min sessions, by using the Samson sucrose fading procedure. Subsequently, rats were exposed to increasing concentrations of ethanol up to 30% on a fixed ratio 4 schedule. Finally, the extinction responding for ethanol, defined as the maximal number of lever responses reached by each rat in the absence of ethanol reinforcement, was determined. Results The results indicated that sP rats acquired and maintained lever pressing for ethanol, self-administering mean amounts of ethanol in the range of 0.6 to 1.1 g/kg/session, which gave rise to mean blood ethanol levels in the 30 to 45 mg% range. Extinction responding for ethanol in sP rats averaged 73. In contrast, once sucrose was faded out, sNP rats displayed minimal levels of responding for ethanol, and extinction responding averaged 6. Conclusions The results of the present study extend to the sP/sNP rat lines the finding that ethanol can be established as a reinforcer in selectively bred alcohol-preferring rats, whereas it has modest, if any, reinforcing properties in alcohol-nonpreferring rats. [source] 9- cis Retinal Increased in Retina of RPE65 Knockout Mice with Decrease in Coat Pigmentation,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2006Jie Fan The protein RPE65 is essential for the generation of the native chromophore, 11- cis retinal, of visual pigments. However, the Rpe65 knockout (Rpe65 -1- ) mouse shows a minimal visual response due to the presence of a pigment, isorhodopsin, formed with 9- cis retinal. Isorhodopsin accumulates linearly with prolonged dark-rearing of the animals. The majority of Rpe65 -/- mice have an agouti coat color. A tan coat color subset of Rpe65 -/- mice was found to have an enhanced visual response as measured by electroretinograms. The enhanced response was found to be due to increased levels of 9- cis retinal and isorhodopsin pigment levels. Animals of both coat colors reared in cyclic light have minimal levels of regenerated pigment and show photoreceptor degeneration. On dark-rearing, pigment accumulates and photoreceptor degeneration is decreased. In the tan Rpe65 -/- mice, the level of photoreceptor degeneration is less than in the agouti animals, which have an increased pigment and decreased free opsin level. Therefore, photoreceptor damage correlates with the amount of the apoprotein present, supporting findings that the activity from unregenerated opsin can lead to photoreceptor degeneration. [source] C4d Deposition and Clearance in Cardiac Transplants Correlates With Alloantibody Levels and Rejection in RatsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5p1 2006K. Minami Antibody-mediated rejection of human cardiac transplants is correlated with C4d deposits and macrophage infiltrates in capillaries of endomyocardial biopsies. We produced an antibody to rat C4d to study C4d deposition and clearance in Lewis rats that were sensitized with a blood transfusion from DA rats 7, 14 or 21 days before cardiac transplantation. Cyclosporin A (CsA) immunosuppression was initiated after transplantation at a dose that inhibited graft rejection, antibody production and C4d deposition in unsensitized recipients. Blood transfusion elicited high levels of circulating IgG alloantibodies, predominantly of the complement-activating IgG2b subclass, that peaked 14 days after transplantation. At this time, macrophages accumulated in capillaries, and C4d deposits were diffuse and intense on arteries, capillaries and veins. Grafts that survived 90 days in sensitized recipients still had deposits of C4d that were associated with increased interstitial fibrosis and vasculopathy in arteries. Clearance of C4d was determined by retransplanting DA cardiac allografts from Lewis recipients back to DA recipients. C4d deposits were decreased to minimal levels within 5 days after retransplantation. Thus, C4d deposition is not limited to the capillaries, but extends throughout the arterial tree, and despite formation of a covalent bond, C4d is cleared within days. [source] Triple light chain antibodies: Factors that influence its formation in cell cultureBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2010Natalia Gomez Abstract THIOMABs are recombinant antibodies engineered with reactive cysteines, which can be covalently conjugated to drugs of interest to generate targeted therapeutics. During the analysis of THIOMABs secreted by stably transfected Chinese Hamster Ovary (CHO) cells, we discovered the existence of a new species,Triple Light Chain Antibody (3LC). This 3LC species is the product of a disulfide bond formed between an extra light chain and one of the engineered cysteines on the THIOMAB. We characterized the 3LC by size exclusion chromatography, mass spectrometry, and microchip electrophoresis. We also investigated the potential causes of 3LC formation during cell culture, focusing on the effects of free light chain (LC) polypeptide concentration, THIOMAB amino acid sequence, and glutathione (GSH) production. In studies covering 12 THIOMABs produced by 66 stable cell lines, increased free LC polypeptide expression,evaluated as the ratio of mRNA encoding for LC to the mRNA encoding for heavy chain (HC),correlated with increased 3LC levels. The amino acid sequence of the THIOMAB molecule also impacted its susceptibility to 3LC formation: hydrophilic LC polypeptides showed elevated 3LC levels. Finally, increased GSH production,evaluated as the ratio of the cell-specific production rate of GSH (qGSH) to the cell-specific production rate of THIOMAB (qp),corresponded to decreased 3LC levels. In time-lapse studies, changes in extracellular 3LC levels during cell culture corresponded to changes in mRNA LC/HC ratio and qGSH/qp ratio. In summary, we found that cell lines with low mRNA LC/HC ratio and high qGSH/qp ratio yielded the lowest levels of 3LC. These findings provide us with factors to consider in selecting a cell line to produce THIOMABs with minimal levels of the 3LC impurity. Biotechnol. Bioeng. 2010. 105: 748,760. © 2009 Wiley Periodicals, Inc. [source] | ||||||||||||||||