Analytic Diffraction Corrections to Ultrasonic Scattering Measurements

Ultrasonic theories generally predict a scattering amplitude which relates a spherically spreading, far-field scattered wave to an incident plane wave. In ultrasonic immersion measurements, the frequency and angular dependences of the scattering amplitude are convolved with those of the transmitting and receiving transducers and the propagation through the liquid-solid and solid-liquid interfaces. This paper presents a set of approximate corrections for these effects for the cases of angle beam inspection through planar, spherically curved or cylindrically curved surfaces. The primary parameters in the correction are the function D, which corrects for the diffraction effects occurring during a transducer calibration experiment, and the function C, which describes the on-axis pressure variation of the beam. Values of C and D are available in the literature for the case of a piston transducer radiating into an infinite fluid medium. The major portion of this paper is concerned with the extension of those results to the aforementioned two media problems in which mode conversion, refraction, diffraction, and focussing all play interrelated roles. Results of preliminary experiments to test the corrections are also included

Do self-reported intentions predict clinicians behaviour: a systematic review.

Background: Implementation research is the scientific study of methods to promote the systematic uptake of clinical research findings into routine clinical practice. Several interventions have been shown to be effective in changing health care professionals' behaviour, but heterogeneity within interventions, targeted behaviours, and study settings make generalisation difficult. Therefore, it is necessary to identify the 'active ingredients' in professional behaviour change strategies. Theories of human behaviour that feature an individual's "intention" to do something as the most immediate predictor of their behaviour have proved to be useful in non-clinical populations. As clinical practice is a form of human behaviour such theories may offer a basis for developing a scientific rationale for the choice of intervention to use in the implementation of new practice. The aim of this review was to explore the relationship between intention and behaviour in clinicians and how this compares to the intention-behaviour relationship in studies of non-clinicians. Methods: We searched: PsycINFO, MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Science/Social science citation index, Current contents (social & behavioural med/clinical med), ISI conference proceedings, and Index to Theses. The reference lists of all included papers were checked manually. Studies were eligible for inclusion if they had: examined a clinical behaviour within a clinical context, included measures of both intention and behaviour, measured behaviour after intention, and explored this relationship quantitatively. All titles and abstracts retrieved by electronic searching were screened independently by two reviewers, with disagreements resolved by discussion. Discussion: Ten studies were found that examined the relationship between intention and clinical behaviours in 1623 health professionals. The proportion of variance in behaviour explained by intention was of a similar magnitude to that found in the literature relating to non-health professionals. This was more consistently the case for studies in which intention-behaviour correspondence was good and behaviour was self-reported. Though firm conclusions are limited by a smaller literature, our findings are consistent with that of the non-health professional literature. This review, viewed in the context of the larger populations of studies, provides encouragement for the contention that there is a predictable relationship between the intentions of a health professional and their subsequent behaviour. However, there remain significant methodological challenges

Cost-effectiveness of oral alitretinoin in patients with severe chronic hand eczema - a long-term analysis from a Swiss perspective

BACKGROUND: The impact on patients suffering from chronic hand eczema (CHE) is enormous, as no licensed systemic treatment option with proven efficacy for CHE is available. Alitretinoin is a novel agent which showed high clinical efficacy in patients with severe, refractory CHE. We assessed the cost-effectiveness of alitretinoin for CHE patient treatment from a Swiss third party payer perspective. A further objective of this study was to determine the burden of disease in Switzerland. METHODS: A long-term Markov cohort simulation model was used to estimate direct medical costs (euro) and clinical effectiveness (quality adjusted life years, QALYs) of treating severe CHE patients with alitretinoin. Comparison was against the standard treatment of supportive care (optimised emollient therapy). Information on response rates were derived from a randomized controlled clinical trial. Costs were considered from the perspective of the Swiss health system. Swiss epidemiological data was derived from official Swiss Statistic institutions. RESULTS: Annual costs of alitretinoin treatment accounted for 2'212 euro. After a time horizon of 22.4 years, average remaining long-term costs accounted for 42'208 euro or 38'795 euro in the alitretinoin and the standard treatment arm, respectively. Compared with the standard therapy, the addition of alitretinoin yielded an average gain of 0.230 QALYs at the end of the simulation. Accordingly, the incremental cost-effectiveness ratio resulted in 14'816 euro/QALY gained. These results were robust to changes in key model assumptions. CONCLUSION: The therapy for CHE patients is currently insufficient. In our long-term model we identified the treatment with alitretinoin as a cost-effective alternative for the therapy of CHE patients in Switzerland

Extracting Safe Thread Schedules from Incomplete Model Checking Results

Model checkers frequently fail to completely verify a concurrent program, even if partial-order reduction is applied. The verification engineer is left in doubt whether the program is safe and the effort toward verifying the program is wasted. We present a technique that uses the results of such incomplete verification attempts to construct a (fair) scheduler that allows the safe execution of the partially verified concurrent program. This scheduler restricts the execution to schedules that have been proven safe (and prevents executions that were found to be erroneous). We evaluate the performance of our technique and show how it can be improved using partial-order reduction. While constraining the scheduler results in a considerable performance penalty in general, we show that in some cases our approach—somewhat surprisingly—even leads to faster executions

Identification of Direct Target Genes Using Joint Sequence and Expression Likelihood with Application to DAF-16

A major challenge in the post-genome era is to reconstruct regulatory networks from the biological knowledge accumulated up to date. The development of tools for identifying direct target genes of transcription factors (TFs) is critical to this endeavor. Given a set of microarray experiments, a probabilistic model called TRANSMODIS has been developed which can infer the direct targets of a TF by integrating sequence motif, gene expression and ChIP-chip data. The performance of TRANSMODIS was first validated on a set of transcription factor perturbation experiments (TFPEs) involving Pho4p, a well studied TF in Saccharomyces cerevisiae. TRANSMODIS removed elements of arbitrariness in manual target gene selection process and produced results that concur with one's intuition. TRANSMODIS was further validated on a genome-wide scale by comparing it with two other methods in Saccharomyces cerevisiae. The usefulness of TRANSMODIS was then demonstrated by applying it to the identification of direct targets of DAF-16, a critical TF regulating ageing in Caenorhabditis elegans. We found that 189 genes were tightly regulated by DAF-16. In addition, DAF-16 has differential preference for motifs when acting as an activator or repressor, which awaits experimental verification. TRANSMODIS is computationally efficient and robust, making it a useful probabilistic framework for finding immediate targets

A Linear Model for Transcription Factor Binding Affinity Prediction in Protein Binding Microarrays

Protein binding microarrays (PBM) are a high throughput technology used to characterize protein-DNA binding. The arrays measure a protein's affinity toward thousands of double-stranded DNA sequences at once, producing a comprehensive binding specificity catalog. We present a linear model for predicting the binding affinity of a protein toward DNA sequences based on PBM data. Our model represents the measured intensity of an individual probe as a sum of the binding affinity contributions of the probe's subsequences. These subsequences characterize a DNA binding motif and can be used to predict the intensity of protein binding against arbitrary DNA sequences. Our method was the best performer in the Dialogue for Reverse Engineering Assessments and Methods 5 (DREAM5) transcription factor/DNA motif recognition challenge. For the DREAM5 bonus challenge, we also developed an approach for the identification of transcription factors based on their PBM binding profiles. Our approach for TF identification achieved the best performance in the bonus challenge

Cyanamide mode of action during inhibition of onion (Allium cepa L.) root growth involves disturbances in cell division and cytoskeleton formation

Cyanamide is an allelochemical produced by hairy vetch (Vicia villosa Roth.). Its phyotoxic effect on plant growth was examined on roots of onion (Allium cepa L.) bulbs. Water solution of cyanamide (2–10 mM) restricted growth of onion roots in a dose-dependent manner. Treatment of onion roots with cyanamide resulted in a decrease in root growth rate accompanied by a decrease in accumulation of fresh and dry weight. The inhibitory effect of cyanamide was reversed by its removal from the environment, but full recovery was observed only for tissue treated with this chemical at low concentration (2–6 mM). Cytological observations of root tip cells suggest that disturbances in cell division may explain the strong cyanamide allelopathic activity. Moreover, in cyanamide-treated onion the following changes were detected: reduction of mitotic cells, inhibition of proliferation of meristematic cells and cell cycle, and modifications of cytoskeleton arrangement

Hippocampus Shape Analysis and Late-Life Depression

Major depression in the elderly is associated with brain structural changes and vascular lesions. Changes in the subcortical regions of the limbic system have also been noted. Studies examining hippocampus volumetric differences in depression have shown variable results, possibly due to any volume differences being secondary to local shape changes rather than differences in the overall volume. Shape analysis offers the potential to detect such changes. The present study applied spherical harmonic (SPHARM) shape analysis to the left and right hippocampi of 61 elderly subjects with major depression and 43 non-depressed elderly subjects. Statistical models controlling for age, sex, and total cerebral volume showed a significant reduction in depressed compared with control subjects in the left hippocampus (F1,103 = 5.26; p = 0.0240) but not right hippocampus volume (F1,103 = 0.41; p = 0.5213). Shape analysis showed significant differences in the mid-body of the left (but not the right) hippocampus between depressed and controls. When the depressed group was dichotomized into those whose depression was remitted at time of imaging and those who were unremitted, the shape comparison showed remitted subjects to be indistinguishable from controls (both sides) while the unremitted subjects differed in the midbody and the lateral side near the head. Hippocampal volume showed no difference between controls and remitted subjects but nonremitted subjects had significantly smaller left hippocampal volumes with no significant group differences in the right hippocampus. These findings may provide support to other reports of neurogenic effects of antidepressants and their relation to successful treatment for depressive symptoms

Advancing the argument for validity of the Alberta Context Tool with healthcare aides in residential long-term care

<p>Abstract</p> <p>Background</p> <p>Organizational context has the potential to influence the use of new knowledge. However, despite advances in understanding the theoretical base of organizational context, its measurement has not been adequately addressed, limiting our ability to quantify and assess context in healthcare settings and thus, advance development of contextual interventions to improve patient care. We developed the Alberta Context Tool (the ACT) to address this concern. It consists of 58 items representing 10 modifiable contextual concepts. We reported the initial validation of the ACT in 2009. This paper presents the second stage of the psychometric validation of the ACT.</p> <p>Methods</p> <p>We used the <it>Standards for Educational and Psychological Testing </it>to frame our validity assessment. Data from 645 English speaking healthcare aides from 25 urban residential long-term care facilities (nursing homes) in the three Canadian Prairie Provinces were used for this stage of validation. In this stage we focused on: (1) advanced aspects of internal structure (e.g., confirmatory factor analysis) and (2) relations with other variables validity evidence. To assess reliability and validity of scores obtained using the ACT we conducted: Cronbach's alpha, confirmatory factor analysis, analysis of variance, and tests of association. We also assessed the performance of the ACT when individual responses were aggregated to the care unit level, because the instrument was developed to obtain unit-level scores of context.</p> <p>Results</p> <p>Item-total correlations exceeded acceptable standards (> 0.3) for the majority of items (51 of 58). We ran three confirmatory factor models. Model 1 (all ACT items) displayed unacceptable fit overall and for five specific items (1 item on <it>adequate space for resident care </it>in the Organizational Slack-Space ACT concept and 4 items on use of electronic resources in the Structural and Electronic Resources ACT concept). This prompted specification of two additional models. Model 2 used the 7 scaled ACT concepts while Model 3 used the 3 count-based ACT concepts. Both models displayed substantially improved fit in comparison to Model 1. Cronbach's alpha for the 10 ACT concepts ranged from 0.37 to 0.92 with 2 concepts performing below the commonly accepted standard of 0.70. Bivariate associations between the ACT concepts and instrumental research utilization levels (which the ACT should predict) were statistically significant at the 5% level for 8 of the 10 ACT concepts. The majority (8/10) of the ACT concepts also showed a statistically significant trend of increasing mean scores when arrayed across the lowest to the highest levels of instrumental research use.</p> <p>Conclusions</p> <p>The validation process in this study demonstrated additional empirical support for construct validity of the ACT, when completed by healthcare aides in nursing homes. The overall pattern of the data was consistent with the structure hypothesized in the development of the ACT and supports the ACT as an appropriate measure for assessing organizational context in nursing homes. Caution should be applied in using the one space and four electronic resource items that displayed misfit in this study with healthcare aides until further assessments are made.</p

Probabilistic Inference of Transcription Factor Binding from Multiple Data Sources

An important problem in molecular biology is to build a complete understanding of transcriptional regulatory processes in the cell. We have developed a flexible, probabilistic framework to predict TF binding from multiple data sources that differs from the standard hypothesis testing (scanning) methods in several ways. Our probabilistic modeling framework estimates the probability of binding and, thus, naturally reflects our degree of belief in binding. Probabilistic modeling also allows for easy and systematic integration of our binding predictions into other probabilistic modeling methods, such as expression-based gene network inference. The method answers the question of whether the whole analyzed promoter has a binding site, but can also be extended to estimate the binding probability at each nucleotide position. Further, we introduce an extension to model combinatorial regulation by several TFs. Most importantly, the proposed methods can make principled probabilistic inference from multiple evidence sources, such as, multiple statistical models (motifs) of the TFs, evolutionary conservation, regulatory potential, CpG islands, nucleosome positioning, DNase hypersensitive sites, ChIP-chip binding segments and other (prior) sequence-based biological knowledge. We developed both a likelihood and a Bayesian method, where the latter is implemented with a Markov chain Monte Carlo algorithm. Results on a carefully constructed test set from the mouse genome demonstrate that principled data fusion can significantly improve the performance of TF binding prediction methods. We also applied the probabilistic modeling framework to all promoters in the mouse genome and the results indicate a sparse connectivity between transcriptional regulators and their target promoters. To facilitate analysis of other sequences and additional data, we have developed an on-line web tool, ProbTF, which implements our probabilistic TF binding prediction method using multiple data sources. Test data set, a web tool, source codes and supplementary data are available at: http://www.probtf.org