A positive SeHCAT test results in fewer subsequent investigations in patients with chronic diarrhoea.

Chronic diarrhoea is a common condition, resulting from a number of different disorders. Bile acid diarrhoea, occurring in about a third of these patients, is often undiagnosed. We hypothesised that a positive diagnosis of bile acid diarrhoea would reduce the need for subsequent investigations for alternative diagnoses. METHODS: Patients previously recruited to a study of chronic diarrhoea who had selenium homocholic acid taurine (SeHCAT) testing and subsequent follow-up at our institution were identified. In a retrospective analysis, the numbers of defined investigations undertaken from the first 3 months after SeHCAT in the following 5 years were compared. RESULTS: 90 patients were identified with primary bile acid diarrhoea (SeHCAT retention 15%, n=54). Follow-up had been performed on 29 and 39 subjects, respectively, with no differences in previous investigations or the last contact date. In the follow-up period, the proportions of these patients who had undergone endoscopic procedures (gastroscopy, colonoscopy and sigmoidoscopy) were the same. However, there was a higher proportion of patients in the SeHCAT-negative group who had other investigations, including imaging, physiological tests and blood tests (p=0.037). The use of cross-sectional imaging was significantly higher in this group (p=0.015) with greater proportions having CT (0.44 vs 0.10) and MRI (0.26 vs 0.07). Ultrasound use and the number of blood tests were higher in the SeHCAT-negative group whereas the SeHCAT-positive group attended more clinic appointments (p=0.013). CONCLUSION: A positive diagnosis of bile acid diarrhoea, made by a SeHCAT test, resulted in reduced use of diagnostic investigations over the subsequent 5 years

Fermi-surface topology and the effects of intrinsic disorder in a class of charge-transfer salts containing magnetic ions: β" — (BEDT — TTF)₄ [(H₃O)M(C₂O₄)₃]Υ (M = Ga, Cr, Fr; Υ = C₅H₅N)

We report high-field magnetotransport measurements on β" — (BEDT — TTF)₄ [(H₃O)M(C₂O₄)₃]Υ, where M =Ga, Cr and Fe and Υ = C₅H₅N. We observe similar Shubnikov–de Haas oscillations in all compounds, attributable to four quasi-two-dimensional Fermi-surface pockets, the largest of which corresponds to a cross-sectional area ≈ 8.5% of the Brillouin zone. The cross-sectional areas of the pockets are in agreement with the expectations for a compensated semimetal, and the corresponding effective masses are ∼mₑ, rather small compared to those of other BEDT-TTF salts. Apart from the case of the smallest Fermi-surface pocket, varying the M ion seems to have little effect on the overall Fermi-surface topology or on the effective masses. Despite the fact that all samples show quantum oscillations at low temperatures, indicative of Fermi liquid behavior, the sample and temperature dependence of the interlayer resistivity suggest that these systems are intrinsically inhomogeneous. It is thought that intrinsic tendency to disorder in the anions and/or the ethylene groups of the BEDT-TTF molecules leads to the coexistence of insulating and metallic states at low temperatures. A notional phase diagram is given for the general family of β" — (BEDT — TTF)₄ [(H₃O)M(C₂O₄)₃]Υ salts

Alkylated-C-60 based soft materials: regulation of self-assembly and optoelectronic properties by chain branching

Derivatization of fullerene (C60) with branched aliphatic chains softens C60-based materials and enables the formation of thermotropic liquid crystals and room temperature nonvolatile liquids. This work demonstrates that by carefully tuning parameters such as type, number and substituent position of the branched chains, liquid crystalline C60 materials with mesophase temperatures suited for photovoltaic cell fabrication and room temperature nonvolatile liquid fullerenes with tunable viscosity can be obtained. In particular, compound 1, with branched chains, exhibits a smectic liquid crystalline phase extending from 84 °C to room temperature. Analysis of bulk heterojunction (BHJ) organic solar cells with a ca. 100 nm active layer of compound 1 and poly(3-hexylthiophene) (P3HT) as an electron acceptor and an electron donor, respectively, reveals an improved performance (power conversion efficiency, PCE: 1.6 ± 0.1%) in comparison with another compound, 10 (PCE: 0.5 ± 0.1%). The latter, in contrast to 1, carries linear aliphatic chains and thus forms a highly ordered solid lamellar phase at room temperature. The solar cell performance of 1 blended with P3HT approaches that of PCBM/P3HT for the same active layer thickness. This indicates that C60 derivatives bearing branched tails are a promising class of electron acceptors in soft (flexible) photovoltaic devices

Advanced multivariate data analysis to determine the root cause of trisulfide bond formation in a novel antibody-peptide fusion

Product quality heterogeneities, such as a trisulfide bond (TSB) formation, can be influenced by multiple interacting process parameters. Identifying their root cause is a major challenge in biopharmaceutical production. To address this issue, this paper describes the novel application of advanced multivariate data analysis (MVDA) techniques to identify the process parameters influencing TSB formation in a novel recombinant antibody-peptide fusion expressed in mammalian cell culture. The screening dataset was generated with a high-throughput (HT) micro-bioreactor system (Ambr(TM) 15) using a design of experiments (DoE) approach. The complex dataset was firstly analyzed through the development of a multiple linear regression model focusing solely on the DoE inputs and identified the temperature, pH and initial nutrient feed day as important process parameters influencing this quality attribute. To further scrutinize the dataset, a partial least squares model was subsequently built incorporating both on-line and off-line process parameters and enabled accurate predictions of the TSB concentration at harvest. Process parameters identified by the models to promote and suppress TSB formation were implemented on five 7 L bioreactors and the resultant TSB concentrations were comparable to the model predictions. This study demonstrates the ability of MVDA to enable predictions of the key performance drivers influencing TSB formation that are valid also upon scale-up

Impact of Novel Sorghum Bran Diets on DSS-Induced Colitis.

We have demonstrated that polyphenol-rich sorghum bran diets alter fecal microbiota; however, little is known regarding their effect on colon inflammation. Our aim was to characterize the effect of sorghum bran diets on intestinal homeostasis during dextran sodium sulfate (DSS)-induced colitis. Male Sprague-Dawley rats (N = 20/diet) were provided diets containing 6% fiber from cellulose, or Black (3-deoxyanthocyanins), Sumac (condensed tannins) or Hi Tannin Black (both) sorghum bran. Colitis was induced (N = 10/diet) with three separate 48-h exposures to 3% DSS, and feces were collected. On Day 82, animals were euthanized and the colon resected. Only discrete mucosal lesions, with no diarrhea or bloody stools, were observed in DSS rats. Only bran diets upregulated proliferation and Tff3, Tgfβ and short chain fatty acids (SCFA) transporter expression after a DSS challenge. DSS did not significantly affect fecal SCFA concentrations. Bran diets alone upregulated repair mechanisms and SCFA transporter expression, which suggests these polyphenol-rich sorghum brans may suppress some consequences of colitis

Predicting performance of constant flow depth filtration using constant pressure filtration data

This paper describes a method of predicting constant flow filtration capacities using constant pressure datasets collected during the purification of several monoclonal antibodies through depth filtration. The method required characterisation of the fouling mechanism occurring in constant pressure filtration processes by evaluating the best fit of each of the classic and combined theoretical fouling models. The optimised coefficients of the various models were correlated with the corresponding capacities achieved during constant flow operation at the specific pressures performed during constant pressure operation for each centrate. Of the classic and combined fouling models investigated, the Cake-Adsorption fouling model was found to best describe the fouling mechanisms observed for each centrate at the various different pressures investigated. A linear regression model was generated with these coefficients and was shown to predict accurately the capacities at constant flow operation at each pressure. This model was subsequently validated using an additional centrate and accurately predicted the constant flow capacities at three different pressures (0.69, 1.03 and 1.38 bar). The model used the optimised Cake-Adsorption model coefficients that best described the flux decline during constant pressure operation. The proposed method of predicting depth filtration performance proved to be faster than the traditional approach whilst requiring significantly less material, making it particularly attractive for early process development activities

Advanced control strategies for bioprocess chromatography: Challenges and opportunities for intensified processes and next generation products

Recent advances in process analytical technologies and modelling techniques present opportunities to improve industrial chromatography control strategies to enhance process robustness, increase productivity and move towards real-time release testing. This paper provides a critical overview of batch and continuous industrial chromatography control systems for therapeutic protein purification. Firstly, the limitations of conventional industrial fractionation control strategies using in-line UV spectroscopy and on-line HPLC are outlined. Following this, an evaluation of monitoring and control techniques showing promise within research, process development and manufacturing is provided. These novel control strategies combine rapid in-line data capture (e.g. NIR, MALS and variable pathlength UV) with enhanced process understanding obtained from mechanistic and empirical modelling techniques. Finally, a summary of the future states of industrial chromatography control systems is proposed, including strategies to control buffer formulation, product fractionation, column switching and column fouling. The implementation of these control systems improves process capabilities to fulfil product quality criteria as processes are scaled, transferred and operated, thus fast tracking the delivery of new medicines to market

Valuing the unpaid contribution of community health volunteers to mass drug administration programs

Community health volunteers (CHVs) are being used within a growing number of healthcare interventions, and they have become a cornerstone for the delivery of mass drug administration within many neglected tropical disease control programs. However, a greater understanding of the methods used to value the unpaid time CHVs contribute to healthcare programs is needed. We outline the two main approaches used to value CHVs' unpaid time (the opportunity cost and the replacement cost approaches). We found that for mass drug administration programs the estimates of the economic costs relating to the CHVs' unpaid time can be significant, with the averages of the different studies varying between US$0.05-0.16 per treatment. We estimated that the time donated by CHVs' to the African Programme for Onchocerciasis Control alone would be valued between US$60-90 million. There is a need for greater transparency and consistency in the methods used to value CHVs' unpaid time