Home About us Contact
|
Home About us Contact | ||
|
|
||
Initial Application (initial + application)
Selected AbstractsBiotic ligand model of the acute toxicity of metals.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2001Abstract The biotic ligand model (BLM) of acute metal toxicity to aquatic organisms is based on the idea that mortality occurs when the metal,biotic ligand complex reaches a critical concentration. For fish, the biotic ligand is either known or suspected to be the sodium or calcium channel proteins in the gill surface that regulate the ionic composition of the blood. For other organisms, it is hypothesized that a biotic ligand exists and that mortality can be modeled in a similar way. The biotic ligand interacts with the metal cations in solution. The amount of metal that binds is determined by a competition for metal ions between the biotic ligand and the other aqueous ligands, particularly dissolved organic matter (DOM), and the competition for the biotic ligand between the toxic metal ion and the other metal cations in solution, for example, calcium. The model is a generalization of the free ion activity model that relates toxicity to the concentration of the divalent metal cation. The difference is the presence of competitive binding at the biotic ligand, which models the protective effects of other metal cations, and the direct influence of pH. The model is implemented using the Windermere humic aqueous model (WHAM) model of metal,DOM complexation. It is applied to copper and silver using gill complexation constants reported by R. Playle and coworkers. Initial application is made to the fathead minnow data set reported by R. Erickson and a water effects ratio data set by J. Diamond. The use of the BLM for determining total maximum daily loadings (TMDLs) and for regional risk assessments is discussed within a probabilistic framework. At first glance, it appears that a large amount of data are required for a successful application. However, the use of lognormal probability distributions reduces the required data to a manageable amount. [source] High-throughput screening of chemical exchange saturation transfer MR contrast agentsCONTRAST MEDIA & MOLECULAR IMAGING, Issue 3 2010Guanshu Liu Abstract A new high-throughput MRI method for screening chemical exchange saturation transfer (CEST) agents is demonstrated, allowing simultaneous testing of multiple samples with minimal attention to sample configuration and shimming of the main magnetic field (B0). This approach, which is applicable to diamagnetic, paramagnetic and liposome CEST agents, employs a set of inexpensive glass or plastic capillary tubes containing CEST agents put together in a cheap plastic tube holder, without the need for liquid between the tubes to reduce magnetic susceptibility effects. In this setup, a reference image of direct water saturation spectra is acquired in order to map the absolute water frequency for each volume element (voxel) in the sample image, followed by an image of saturation transfer spectra to determine the CEST properties. Even though the field over the total sample is very inhomogeneous due to air,tube interfaces, the shape of the direct saturation spectra is not affected, allowing removal of susceptibility shift effects from the CEST data by using the absolute water frequencies from the reference map. As a result, quantitative information such as the mean CEST intensity for each sample can be extracted for multiple CEST agents at once. As an initial application, we demonstrate rapid screening of a library of 16 polypeptides for their CEST properties, but in principle the number of tubes is limited only by the available signal-noise-ratio, field of view and gradient strength for imaging. Copyright © 2010 John Wiley & Sons, Ltd. [source] Defining the moment of erosion: the principle of thermal consonance timingEARTH SURFACE PROCESSES AND LANDFORMS, Issue 13 2005D. M. LawlerArticle first published online: 9 DEC 200 Abstract Geomorphological process research demands quantitative information on erosion and deposition event timing and magnitude, in relation to fluctuations in the suspected driving forces. This paper establishes a new measurement principle , thermal consonance timing (TCT) , which delivers clearer, more continuous and quantitative information on erosion and deposition event magnitude, timing and frequency, to assist understanding of the controlling mechanisms. TCT is based on monitoring the switch from characteristically strong temperature gradients in sediment, to weaker gradients in air or water, which reveals the moment of erosion. The paper (1) derives the TCT principle from soil micrometeorological theory; (2) illustrates initial concept operationalization for field and laboratory use; (3) presents experimental data for simple soil erosion simulations; and (4) discusses initial application of TCT and perifluvial micrometeorology principles in the delivery of timing solutions for two bank erosion events on the River Wharfe, UK, in relation to the hydrograph. River bank thermal regimes respond, as soil temperature and energy balance theory predicts, with strong horizontal thermal gradients (often >1 K cm,1 over 6·8 cm). TCT fixed the timing of two erosion events, the first during inundation, the second 19 h after the discharge peak and 13 h after re-emergence from the flow. This provides rare confirmation of delayed bank retreat, quantifies the time-lag involved, and suggests mass failure processes rather than fluid entrainment. Erosion events can be virtually instantaneous, implying ,catastrophic retreat' rather than ,progressive entrainment'. Considerable potential exists to employ TCT approaches for: validating process models in several geomorphological contexts; assisting process identification and improving discrimination of competing hypotheses of process dominance through high-resolution, simultaneous analysis of erosion and deposition events and driving forces; defining shifting erodibility and erosion thresholds; refining dynamic linkages in event-based sediment budget investigations; and deriving closer approximations to ,true' erosion and deposition rates, especially in self-concealing scour-and-fill systems. Copyright © 2005 John Wiley & Sons, Ltd. [source] Successful angiographic embolization of recurrent elbow and knee joint bleeds in seven patients with severe haemophiliaHAEMOPHILIA, Issue 1 2009R. KLAMROTH Summary., In haemophilic joints with high-grade arthropathy, bleeds occur that do not respond to replacement therapy of the deficient coagulation factor. The reason may be pathologically reactive angiogenesis in chronic synovitis. Seven patients with severe haemophilia A or haemophilia B experienced recurrent massive bleeds of one elbow joint or knee joint in the absence of trauma. After initial application of factor VIII or IX (fVIII/fIX; 50 IU kg,1 bodyweight), there was only slow and never complete relief of symptoms. Despite intensive secondary prophylaxis maintaining the plasma level of factor concentrate at minimum 50%, new massive bleeds at the same location occurred. Vascular bleeding was suspected. Angiography of the arteries was performed via the femoral artery. Vessels identified as potential bleeding sources were embolized with embolization fluid (ONYX) in eight joints (six elbow and two knee joints). Under low-dose prophylactic treatment (15 IU fVIII or fIX per kg bodyweight for three times per week), no recurrent severe bleed unresponsive to coagulation factor replacement occurred after a mean observation time of 16 months after embolization. The consumption of factor concentrate decreased to one-third of the amount consumed before embolization. In conclusion, angiographic embolization with a non-adhesive liquid embolic agent might be considered as a promising therapeutic and coagulation factor saving option in joint bleeds not responding to replacement of coagulation factor to normal levels. [source] Testing effective connectivity changes with structural equation modeling: What does a bad model tell us?HUMAN BRAIN MAPPING, Issue 12 2006Andrea B. Protzner Abstract Structural equation modeling (SEM) is a statistical method that can assess changes in effective connectivity across tasks or between groups. In its initial application to neuroimaging data, anatomical connectivity provided the constraints to decompose interregional covariances to estimate effective connections. There have been concerns expressed, however, with the validity of interpreting effective connections for a model that does not adequately fit the data. We sought to address this concern by creating two population networks with different patterns of effective connectivity, extracting three samples sizes (N = 100, 60, 20), and then assessing whether the ability to detect effective connectivity differences depended on absolute model fit. Four scenarios were assessed: (1) elimination of a region showing no task differences; (2) elimination of connections with no task differences; (3) elimination of connections that carried task differences, but could be expressed through alternative indirect routes; (4) elimination of connections that carried task differences, and could not be expressed through indirect routes. We were able to detect task differences in all four cases, despite poor absolute model fit. In scenario 3, total effects captured the overall task differences even though the direct effect was no longer present. In scenario 4, task differences that were included in the model remained, but the missing effect was not expressed. In conclusion, it seems that when independent information (e.g., anatomical connectivity) is used to define the causal structure in SEM, inferences about task- or group-dependent changes are valid regardless of absolute model fit. Hum Brain Mapp, 2006. © 2006 Wiley-Liss, Inc. [source] Participation in a national, means-tested school voucher programJOURNAL OF POLICY ANALYSIS AND MANAGEMENT, Issue 3 2005David E. Campbell We use data from a sample of applicants to a national means-tested school voucher program and a national sample of the population eligible for the program to evaluate the factors leading families to use school vouchers. Our analysis divides the process of voucher usage into two distinct stages: initial application and subsequent take-up. Using a nested logit model, we find that some factors, like religious affiliation and religious service attendance, affect both stages. Others, like mother's education, affect only one (application). Still others, like ethnicity, have opposite effects at the two stages. Compared to Whites, minorities are more likely to apply for vouchers, but less likely to take them when given the opportunity. © 2005 by the Association for Public Policy Analysis and Management [source] ,, T cells assist ,, T cells in the adoptive transfer of contact hypersensitivity to para-phenylenediamineCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2001H. Yokozeki Para-phenylenediamine (PPD) is known to be a common sensitizer of allergic contact dermatitis and contact urticaria. To clarify the mechanism of contact hypersensitivity (CHS) to PPD, we established a mouse model of PPD-induced CHS. BALB/c mice were immunized for 3 consecutive days by painting topically a 2·5% PPD solution on their shaved abdominal skin. On days 5, 7 or 9 after the initial application, the mice were challenged by applications of a 2·5% PPD solution. Maximal ear swelling was determined at 24 h but another statistically significant and smaller ear swelling was observed 1 h after challenge with PPD in a hapten-specific manner. Adoptive cell transfer experiments demonstrated that the ear swelling of the adoptive cell transferred mice displayed an early response at 6 h and a late response from 12 h to 24 h when the recipient mice were challenged immediately after transfer. Both MoAbs and complement treatment of the transferred cells demonstrated that the phenotype of the early response cells which elicited a response at 6 h after challenge was Thy1+, B220+, ,, TCR, ,, TCR, CD3, CD4, CD5+ and CD8. The in vitro treatment of effector cells with MoAbs against not only ,, TCR but also ,, TCR, together with complement, was found to diminish substantially the late response, elicited 12,24 h after challenge. ,, T cells reconstituted the ability of ,, T cells to transfer 24 h CHS responsiveness. The phenotype of the ,, T cells that assist CHS effector ,, T cells was CD3+, CD4 and CD8+ and these regulatory ,, T cells were neither Ag-specific nor MHC-restricted. Furthermore, ,, T cells from normal spleen could also assist ,, T cells in adoptive transfer of the 24 h CHS response in a non-MHC-restricted manner. RT-PCR demonstrated that ,, T cells strongly expressed mRNA IFN- ,, whereas ,, T cells expressed not only IFN- , but also IL-4 and IL-10. These data indicate that not only early response cells and ,, T cells but also Th2 type ,, T cells may play an important role in the elicitation of CHS to PPD. [source] Exploring therapeutic alliance in brief inpatient psychotherapy: a preliminary studyCLINICAL PSYCHOLOGY AND PSYCHOTHERAPY (AN INTERNATIONAL JOURNAL OF THEORY & PRACTICE), Issue 5 2010Mark A. Blais Abstract Background: Therapeutic alliance is one of the most widely investigated variables in psychotherapy research but few studies have explored its role in inpatient psychotherapy. Many factors likely contribute to the lack of inpatient alliance research including the short length of hospital stays, complexity of patient psychopathology and the burdensome quality of most alliance scales. This paper reports on the development and initial application of two comparable brief scales designed to capture patient and therapist alliance ratings. Method: Participants were 20 patients receiving supportive,expressive inpatient psychotherapy. The patients were predominantly depressed women. Baseline measures of distress, symptom severity and functioning were obtained at the first and third sessions. Measures of alliance were obtained at the second session. Results: The brief alliance scales demonstrated adequate internal consistency and the individual items had good adjusted item-to-scale correlations. Consistent with the broad alliance literature, we found that patients rated alliance higher than therapists, patient and therapist alliance ratings were not significantly correlated, and level of functioning was significantly associated with both patients and therapists' alliance ratings. The perceived depth of psychotherapy was also significantly associated with alliance. Unexpectedly, alliance ratings were also negatively associated with improvement during hospitalization. Conclusions: Overall, the study demonstrates both the feasibility and potential benefit of conducting inpatient psychotherapy research.,Copyright © 2009 John Wiley & Sons, Ltd. Key Practitioner Message: This paper shows that inpatient psychotherapy can be studied and potentially improved through the application of brief targeted instruments. [source] Semiconducting Thienothiophene Copolymers: Design, Synthesis, Morphology, and Performance in Thin-Film Organic TransistorsADVANCED MATERIALS, Issue 10-11 2009Iain McCulloch Abstract Organic semiconductors are emerging as a viable alternative to amorphous silicon in a range of thin-film transistor devices. With the possibility to formulate these p-type materials as inks and subsequently print into patterned devices, organic-based transistors offer significant commercial advantages for manufacture, with initial applications such as low performance displays and simple logic being envisaged. Previous limitations of both air stability and electrical performance are now being overcome with a range of both small molecule and polymer-based solution-processable materials, which achieve charge carrier mobilities in excess of 0.5,cm2 V,1 s,1, a benchmark value for amorphous silicon semiconductors. Polymer semiconductors based on thienothiophene copolymers have achieved amongst the highest charge carrier mobilities in solution-processed transistor devices. In this Progress Report, we evaluate the advances and limitations of this class of polymer in transistor devices. [source] Variation in Institutional Review Board Responses to a Standard, Observational, Pediatric Research ProtocolACADEMIC EMERGENCY MEDICINE, Issue 4 2007Jonathan Mansbach MD Abstract Background: Multicenter studies are becoming more common, and variability in local institutional review board (IRB) assessments can be problematic. Objective: To investigate the variability of IRB responses to a multicenter observational study of children presenting to emergency departments. Methods: The authors collected the original IRB applications, subsequent correspondence, and a survey assessing submission timing and response and the nature of IRB queries. The study was conducted as part of the Emergency Medicine Network http://www.emnet-usa.org Results: Of 37 sites initiating the IRB process, 34 (92%) participated in this IRB-approved study. Institutional review boards returned initial applications in a median of 19 days (IQR, 11,34 d), and 91% considered the protocol to be minimal risk. Of 34 submissions, 13 required no changes, 18 received conditional approvals, and 3 were deferred. The median time from initial submission to final approval was 42 days (IQR, 27,61 d). Seven sites did not participate in patient recruitment: two had institutional issues, one obtained IRB approval too late for participation, and four sites (12%) reported that IRB hurdles contributed to their lack of participation. Nonetheless, 68% of sites that recruited patients reported that the overall experience made them more likely to participate in future multicenter research. Conclusions: There was substantial variation in IRB assessment of a standard protocol in this study. The burden of the application process contributed to some investigators not participating, but the majority of investigators remain enthusiastic about multicenter research. A national IRB may streamline the review process and facilitate multicenter clinical research. [source] | |||||||||||||