In situ microfluidic dialysis for biological small-angle X-ray scattering

Owing to the demand for low sample consumption and automated sample changing capabilities at synchrotron small-angle X-ray (solution) scattering (SAXS) beamlines, X-ray microfluidics is receiving continuously increasing attention. Here, a remote-controlled microfluidic device is presented for simultaneous SAXS and ultraviolet absorption measurements during protein dialysis, integrated directly on a SAXS beamline. Microfluidic dialysis can be used for monitoring structural changes in response to buffer exchange or, as demonstrated, protein concentration. By collecting X-ray data during the concentration procedure, the risk of inducing protein aggregation due to excessive concentration and storage is eliminated, resulting in reduced sample consumption and improved data quality. The proof of concept demonstrates the effect of halted or continuous flow in the microfluidic device. No sample aggregation was induced by the concentration process at the levels achieved in these experiments. Simulations of fluid dynamics and transport properties within the device strongly suggest that aggregates, and possibly even higher-order oligomers, are preferentially retained by the device, resulting in incidental sample purification. Hence, this versatile microfluidic device enables investigation of experimentally induced structural changes under dynamically controllable sample conditions

Orthogonality constrained inverse regression to improve model selectivity and analyte predictions from vibrational spectroscopic measurements

In analytical chemistry spectroscopy is attractive for high-throughput quantification, which often relies on inverse regression, like partial least squares regression. Due to a multivariate nature of spectroscopic measurements an analyte can be quantified in presence of interferences. However, if the model is not fully selective against interferences, analyte predictions may be biased. The degree of model selectivity against an interferent is defined by the inner relation between the regression vector and the pure interfering signal. If the regression vector is orthogonal to the signal, this inner relation equals zero and the model is fully selective. The degree of model selectivity largely depends on calibration data quality. Strong correlations may deteriorate calibration data resulting in poorly selective models. We show this using a fructose-maltose model system. Furthermore, we modify the NIPALS algorithm to improve model selectivity when calibration data are deteriorated. This modification is done by incorporating a projection matrix into the algorithm, which constrains regression vector estimation to the null-space of known interfering signals. This way known interfering signals are handled, while unknown signals are accounted for by latent variables. We test the modified algorithm and compare it to the conventional NIPALS algorithm using both simulated and industrial process data. The industrial process data consist of mid-infrared measurements obtained on mixtures of beta-lactoglobulin (analyte of interest), and alpha-lactalbumin and caseinoglycomacropeptide (interfering species). The root mean squared error of beta-lactoglobulin (% w/w) predictions of a test set was 0.92 and 0.33 when applying the conventional and the modified NIPALS algorithm, respectively. Our modification of the algorithm returns simpler models with improved selectivity and analyte predictions. This paper shows how known interfering signals may be utilized in a direct fashion, while benefitting from a latent variable approach. The modified algorithm can be viewed as a fusion between ordinary least squares regression and partial least squares regression and may be very useful when knowledge of some (but not all) interfering species is available

Good Life with osteoArthritis in Denmark (GLA:D™): evidence-based education and supervised neuromuscular exercise delivered by certified physiotherapists nationwide

BACKGROUND: The uptake of evidence-based guidelines in clinical practice is suboptimal in osteoarthritis (OA) and other chronic diseases. Good Life with osteoArthritis in Denmark (GLA:D) was launched in 2013 with the aim of implementing guidelines for the treatment of knee and hip OA in clinical care nationwide. The purpose of this report was to evaluate the effects of the GLA:D intervention from 2013 to 2015, using data from the national GLA:D registry. METHODS: Patients undergo education and supervised exercise delivered by trained physiotherapists. Outcomes evaluated at baseline, 3 and 12 months are pain intensity (0 to 100, best to worst), objective physical function (30-s chair-stand test and 40-m fast-paced walk test), physical activity (number of days per week being physically active for at least 30 min), quality of life (Knee injury and Osteoarthritis Outcome Score (KOOS) and the Hip disability and Osteoarthritis Outcome Score (HOOS) quality of life subscale, 0–100, worst to best), number of patients on painkillers and sick leave, and access to care according to guidelines. RESULTS: Data from 9,825 participants from the GLA:D registry were utilised in the analyses. It was demonstrated that GLA:D improved pain intensity and quality of life by 12.4 points and 5.4 points at 3 months, and 13.7 points and 9.4 points at 12 months, respectively. Furthermore, physical function and physical activity improved (only at 3 months), fewer patients took painkillers following the treatment, and fewer patients were on sick leave at 12 months following GLA:D compared with the year prior to GLA:D. GLA:D is offered in all five health care regions in Denmark via 286 active GLA:D units, but the uptake in the Danish municipalities is still low with only 20% of the municipalities offering GLA:D. CONCLUSION: Three years after its inception, GLA:D has been rolled out nationwide and has a significant impact not only on patient symptoms and physical function, but also on intake of painkillers and sick leave. The lifestyle changes introduced by education and supervised exercise were largely maintained at 1 year and may have the potential to also improve general health and reduce societal costs