Structural characterization of wheat starch granules differing in amylose content and functional characteristics.

Small-angle X-ray scattering (SAXS) together with several complementary techniques such as differential scanning calorimetry and X-ray diffraction, have been employed to investigate the structural features that give diverse functional properties to wheat starches (Triticum aestivum L.) within a narrow range of enriched amylose content (36-43%). For these starches, which come from a heterogeneous genetic background. SAXS analysis of duplicate samples enabled structural information to be obtained about their lamellar architecture where differences in lamellar spacing among samples were only several tenths of nanometer. The SAXS analysis of these wheat starches with increased amylose content has shown that amylose accumulates in both crystalline and amorphous parts of the lamella. Using waxy starch as a distinctive comparison with the other samples confirmed a general trend of increasing amylose content being linked with the accumulation of defects within crystalline lamellae. We conclude that amylose content directly influences the architecture of semi-crystalline lamellae, whereas thermodynamic and functional properties are brought about by the interplay of amylose content and amylopectin architecture. © 2008, Elsevier Ltd

TGF-b2 induction regulates invasiveness of theileria-transformed leukocytes and disease susceptibility

Theileria parasites invade and transform bovine leukocytes causing either East Coast fever (T. parva), or tropical theileriosis (T. annulata). Susceptible animals usually die within weeks of infection, but indigenous infected cattle show markedly reduced pathology, suggesting that host genetic factors may cause disease susceptibility. Attenuated live vaccines are widely used to control tropical theileriosis and attenuation is associated with reduced invasiveness of infected macrophages in vitro. Disease pathogenesis is therefore linked to aggressive invasiveness, rather than uncontrolled proliferation of Theileria-infected leukocytes. We show that the invasive potential of Theileria-transformed leukocytes involves TGF-b signalling. Attenuated live vaccine lines express reduced TGF-b2 and their invasiveness can be rescued with exogenous TGF-b. Importantly, infected macrophages from disease susceptible Holstein-Friesian (HF) cows express more TGF-b2 and traverse Matrigel with great efficiency compared to those from disease-resistant Sahiwal cattle. Thus, TGF-b2 levels correlate with disease susceptibility. Using fluorescence and time-lapse video microscopy we show that Theileria-infected, disease-susceptible HF macrophages exhibit increased actin dynamics in their lamellipodia and podosomal adhesion structures and develop more membrane blebs. TGF-b2-associated invasiveness in HF macrophages has a transcription-independent element that relies on cytoskeleton remodelling via activation of Rho kinase (ROCK). We propose that a TGF-b autocrine loop confers an amoeboid-like motility on Theileria-infected leukocytes, which combines with MMP-dependent motility to drive invasiveness and virulence

Withdrawal rates as a consequence of disclosure of risk associated with manipulation of the cervical spine

<p>Abstract</p> <p>Background</p> <p>The risk associated with cervical manipulation is controversial. Research in this area is widely variable but as yet the risk is not easily quantifiable. This presents a problem when informing the patient of risks when seeking consent and information may be withheld due to the fear of patient withdrawal from care. As yet, there is a lack of research into the frequency of risk disclosure and consequent withdrawal from manipulative treatment as a result. This study seeks to investigate the reality of this and to obtain insight into the attitudes of chiropractors towards informed consent and disclosure.</p> <p>Methods</p> <p>Questionnaires were posted to 200 UK chiropractors randomly selected from the register of the General Chiropractic Council.</p> <p>Results</p> <p>A response rate of 46% (n = 92) was achieved. Thirty-three per cent (n = 30) respondents were female and the mean number of years in practice was 10. Eighty-eight per cent considered explanation of the risks associated with any recommended treatment important when obtaining informed consent. However, only 45% indicated they always discuss this with patients in need of cervical manipulation. When asked whether they believed discussing the possibility of a serious adverse reaction to cervical manipulation could increase patient anxiety to the extent there was a strong possibility the patient would refuse treatment, 46% said they believed this could happen. Nonetheless, 80% said they believed they had a moral/ethical obligation to disclose risk associated with cervical manipulation despite these concerns. The estimated number of withdrawals throughout respondents' time in practice was estimated at 1 patient withdrawal for every 2 years in practice.</p> <p>Conclusion</p> <p>The withdrawal rate from cervical manipulation as a direct consequence of the disclosure of associated serious risks appears unfounded. However, notwithstanding legal obligations, reluctance to disclose risk due to fear of increasing patient anxiety still remains, despite acknowledgement of moral and ethical responsibility.</p

A comparison of prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill: a cohort study

BACKGROUND: This cohort study compared the prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill. METHODS: The relationships between SIG, lactate, anion gap (AG), anion gap albumin-corrected (AG-corrected), base excess or strong ion difference-effective (SIDe), all obtained within the first hour of intensive care unit (ICU) admission, and the hospital mortality of 6878 patients were analysed. The prognostic significance of each acid-base marker, both alone and in combination with the Admission Mortality Prediction Model (MPM0 III) predicted mortality, were assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Of the 6878 patients included in the study, 924 patients (13.4 %) died after ICU admission. Except for plasma chloride concentrations, all acid-base markers were significantly different between the survivors and non-survivors. SIG (with lactate: AUROC 0.631, confidence interval [CI] 0.611-0.652; without lactate: AUROC 0.521, 95 % CI 0.500-0.542) only had a modest ability to predict hospital mortality, and this was no better than using lactate concentration alone (AUROC 0.701, 95 % 0.682-0.721). Adding AG-corrected or SIG to a combination of lactate and MPM0 III predicted risks also did not substantially improve the latter's ability to differentiate between survivors and non-survivors. Arterial lactate concentrations explained about 11 % of the variability in the observed mortality, and it was more important than SIG (0.6 %) and SIDe (0.9 %) in predicting hospital mortality after adjusting for MPM0 III predicted risks. Lactate remained as the strongest predictor for mortality in a sensitivity multivariate analysis, allowing for non-linearity of all acid-base markers. CONCLUSIONS: The prognostic significance of SIG was modest and inferior to arterial lactate concentration for the critically ill. Lactate concentration should always be considered regardless whether physiological, base excess or physical-chemical approach is used to interpret acid-base disturbances in critically ill patients

Optimizing the diagnostic power with gastric emptying scintigraphy at multiple time points

<p>Abstract</p> <p>Background</p> <p>Gastric Emptying Scintigraphy (GES) at intervals over 4 hours after a standardized radio-labeled meal is commonly regarded as the gold standard for diagnosing gastroparesis. The objectives of this study were: 1) to investigate the best time point and the best combination of multiple time points for diagnosing gastroparesis with repeated GES measures, and 2) to contrast and cross-validate Fisher's Linear Discriminant Analysis (LDA), a rank based Distribution Free (DF) approach, and the Classification And Regression Tree (CART) model.</p> <p>Methods</p> <p>A total of 320 patients with GES measures at 1, 2, 3, and 4 hour (h) after a standard meal using a standardized method were retrospectively collected. Area under the Receiver Operating Characteristic (ROC) curve and the rate of false classification through jackknife cross-validation were used for model comparison.</p> <p>Results</p> <p>Due to strong correlation and an abnormality in data distribution, no substantial improvement in diagnostic power was found with the best linear combination by LDA approach even with data transformation. With DF method, the linear combination of 4-h and 3-h increased the Area Under the Curve (AUC) and decreased the number of false classifications (0.87; 15.0%) over individual time points (0.83, 0.82; 15.6%, 25.3%, for 4-h and 3-h, respectively) at a higher sensitivity level (sensitivity = 0.9). The CART model using 4 hourly GES measurements along with patient's age was the most accurate diagnostic tool (AUC = 0.88, false classification = 13.8%). Patients having a 4-h gastric retention value >10% were 5 times more likely to have gastroparesis (179/207 = 86.5%) than those with ≤10% (18/113 = 15.9%).</p> <p>Conclusions</p> <p>With a mixed group of patients either referred with suspected gastroparesis or investigated for other reasons, the CART model is more robust than the LDA and DF approaches, capable of accommodating covariate effects and can be generalized for cross institutional applications, but could be unstable if sample size is limited.</p

FISim: A new similarity measure between transcription factor binding sites based on the fuzzy integral

Background Regulatory motifs describe sets of related transcription factor binding sites (TFBSs) and can be represented as position frequency matrices (PFMs). De novo identification of TFBSs is a crucial problem in computational biology which includes the issue of comparing putative motifs with one another and with motifs that are already known. The relative importance of each nucleotide within a given position in the PFMs should be considered in order to compute PFM similarities. Furthermore, biological data are inherently noisy and imprecise. Fuzzy set theory is particularly suitable for modeling imprecise data, whereas fuzzy integrals are highly appropriate for representing the interaction among different information sources.Results We propose FISim, a new similarity measure between PFMs, based on the fuzzy integral of the distance of the nucleotides with respect to the information content of the positions. Unlike existing methods, FISim is designed to consider the higher contribution of better conserved positions to the binding affinity. FISim provides excellent results when dealing with sets of randomly generated motifs, and outperforms the remaining methods when handling real datasets of related motifs. Furthermore, we propose a new cluster methodology based on kernel theory together with FISim to obtain groups of related motifs potentially bound by the same TFs, providing more robust results than existing approaches.Conclusion FISim corrects a design flaw of the most popular methods, whose measures favour similarity of low information content positions. We use our measure to successfully identify motifs that describe binding sites for the same TF and to solve real-life problems. In this study the reliability of fuzzy technology for motif comparison tasks is proven.This work has been carried out as part of projects P08-TIC-4299 of J. A., Sevilla and TIN2006-13177 of DGICT, Madrid

A case for taking the dual role of counsellor-researcher in qualitative research

This is an Accepted Manuscript of an article published by Taylor & Francis in Qualitative Research in Psychology on 3rd August 2016, available online: https://doi.org/10.1080/14780887.2016.1205694There is ongoing debate about whether the challenges of practice-based research in counselling, with clients’ discourses providing the raw data, can be overcome. This article begins by considering the argument of whether taking a dual role of counsellor-researcher within case study research is a legitimate qualitative approach. A case example using sand-tray in short-term therapy with adults from a pluralistic perspective is provided to demonstrate how the challenges of the dual role can be managed to produce effective research findings. It is suggested that this approach closes the gap between research and practice to produce findings that are highly relevant to the counselling context. The ethical considerations of taking a dual role of counsellor-researcher are considered, and opportunities and challenges when adopting this approach are identified

How patient and community involvement in diabetes research influences health outcomes : a realist review

Background Patient and public involvement in diabetes research is an international requirement, but little is known about the relationship between the process of involvement and health outcomes. Objective This realist review identifies who benefits from different types of involvement across different contexts and circumstances. Search strategies Medline, CINAHL and EMBASE were searched to identify interventions using targeted, embedded or collaborative involvement to reduce risk and promote self‐management of diabetes. People at risk/with diabetes, providers and community organizations with an interest in addressing diabetes were included. There were no limitations on date, language or study type. Data extraction and synthesis Data were extracted from 29 projects using elements from involvement frameworks. A conceptual analysis of involvement types was used to complete the synthesis. Main results Projects used targeted (4), embedded (8) and collaborative (17) involvement. Productive interaction facilitated over a sufficient period of time enabled people to set priorities for research. Partnerships that committed to collaboration increased awareness of diabetes risk and mobilized people to co‐design and co‐deliver diabetes interventions. Cultural adaptation increased relevance and acceptance of the intervention because they trusted local delivery approaches. Local implementation produced high levels of recruitment and retention, which project teams associated with achieving diabetes health outcomes. Discussion and Conclusions Achieving understanding of community context, developing trusting relationships across sectors and developing productive partnerships were prerequisites for designing research that was feasible and locally relevant. The proportion of diabetes studies incorporating these elements is surprisingly low. Barriers to resourcing partnerships need to be systematically addressed

A comparative analysis of predictive models of morbidity in intensive care unit after cardiac surgery – Part I: model planning

<p>Abstract</p> <p>Background</p> <p>Different methods have recently been proposed for predicting morbidity in intensive care units (ICU). The aim of the present study was to critically review a number of approaches for developing models capable of estimating the probability of morbidity in ICU after heart surgery. The study is divided into two parts. In this first part, popular models used to estimate the probability of class membership are grouped into distinct categories according to their underlying mathematical principles. Modelling techniques and intrinsic strengths and weaknesses of each model are analysed and discussed from a theoretical point of view, in consideration of clinical applications.</p> <p>Methods</p> <p>Models based on Bayes rule, <it>k-</it>nearest neighbour algorithm, logistic regression, scoring systems and artificial neural networks are investigated. Key issues for model design are described. The mathematical treatment of some aspects of model structure is also included for readers interested in developing models, though a full understanding of mathematical relationships is not necessary if the reader is only interested in perceiving the practical meaning of model assumptions, weaknesses and strengths from a user point of view.</p> <p>Results</p> <p>Scoring systems are very attractive due to their simplicity of use, although this may undermine their predictive capacity. Logistic regression models are trustworthy tools, although they suffer from the principal limitations of most regression procedures. Bayesian models seem to be a good compromise between complexity and predictive performance, but model recalibration is generally necessary. <it>k</it>-nearest neighbour may be a valid non parametric technique, though computational cost and the need for large data storage are major weaknesses of this approach. Artificial neural networks have intrinsic advantages with respect to common statistical models, though the training process may be problematical.</p> <p>Conclusion</p> <p>Knowledge of model assumptions and the theoretical strengths and weaknesses of different approaches are fundamental for designing models for estimating the probability of morbidity after heart surgery. However, a rational choice also requires evaluation and comparison of actual performances of locally-developed competitive models in the clinical scenario to obtain satisfactory agreement between local needs and model response. In the second part of this study the above predictive models will therefore be tested on real data acquired in a specialized ICU.</p