Lars Munck

Interval Partial Least-Squares Regression (iPLS): A Comparative Chemometric Study with an Example from Near-Infrared Spectroscopy

A new graphically oriented local modeling procedure called interval partial least-squares (iPLS) is presented for use on spectral data. The iPLS method is compared to full-spectrum partial least-squares and the variable selection methods principal variables (PV), forward stepwise selection (FSS), and recursively weighted regression (RWR). The methods are tested on a near-infrared (NIR) spectral data set recorded on 60 beer samples correlated to original extract concentration. The error of the full-spectrum correlation model between NIR and original extract concentration was reduced by a factor of 4 with the use of iPLS (r = 0.998, and root mean square error of prediction equal to 0.17% plato), and the graphic output contributed to the interpretation of the chemical system under observation. The other methods tested gave a comparable reduction in the prediction error but suffered from the interpretation advantage of the graphic interface. The intervals chosen by iPLS cover both the variables found by FSS and all possible combinations as well as the variables found by PV and RWR, and iPLS is still able to utilize the first-order advantage.

Individualised therapy is more cost-effective than dose intensification in patients with Crohn’s disease who lose response to anti-TNF treatment: a randomised, controlled trial

Objective Although the reasons for secondary loss of response to infliximab (IFX) maintenance therapy in Crohn’s disease vary, dose intensification is usually recommended. This study investigated the cost-effectiveness of interventions defined by an algorithm designed to identify specific reasons for therapeutic failure. Design Randomised, controlled, single-blind, multicentre study. 69 patients with secondary IFX failure were randomised to IFX dose intensification (5 mg/kg every 4 weeks) (n=36) or interventions based on serum IFX and IFX antibody levels using the proposed algorithm (n=33). Predefined co-primary end points at week 12 were proportion of patients responding (Crohns Disease Activity Index (CDAI) decrease ≥70, or ≥50% reduction in active fistulas) and accumulated costs related to treatment of Crohn’s disease, expressed as mean cost per patient, based on the Danish National Patient Registry for all hospitalisation and outpatient costs in the Danish healthcare sector. Results Costs for intention-to-treat patients were substantially lower (34%) for those treated in accordance with the algorithm than by IFX dose intensification: €6038 vs €9178, p<0.001. However, disease control, as judged by response rates, was similar: 58% and 53%, respectively, p=0.81; difference 5% (−19% to 28%). For per-protocol patients, treatment costs were even lower (56%) in the algorithm-treated group (€4062 vs €9178, p<0.001) and with similar response rates (47% vs 53%, p=0.78; difference −5% (−33% to 22%)). Conclusions Treatment of secondary IFX failure using an algorithm based on combined IFX and IFX antibody measurements significantly reduces average treatment costs per patient compared with routine IFX dose escalation and without any apparent negative effect on clinical efficacy. Trial Registration No NCT00851565.

Gene for Improved Nutritional Value in Barley Seed Protein

Genetically dependent 20 to 30 percent increase in lysine per 16 grams of nitrogen results in improved nutritional values in feeding trials with mice and rats. The recessive gene was selected from the World Barley Collection. Other amino acids are also influenced by the gene. Protein content segregates independently of the changed amino acid pattern. The gene putatively influences the matrix proteins, which characteristically adhere to the starch grains in meal preparations. The morphological character permits rapid microscopic screening of single seeds without affecting viability. Low yield is considerably improved by crossing and selection.

Prediction of water-holding capacity and composition of porcine meat by comparative spectroscopy

Four spectroscopic instruments, a fibre optical probe (FOP), a visual (VIS) and near infrared (NIR) reflectance spectrophotometer, a reflectance spectrofluorometer and a low-field (1)H nuclear magnetic resonance (LF-NMR) instrument were used to perform measurements on two muscles (longissimus dorsi and semitendinosous) from 39 pigs, 18 of which were carriers of the Halothane gene. Water-holding capacity (drip loss and filter paper wetness) and chemical composition (intramuscular fat and water) of the muscle samples were determined for spectroscopic calibration. Prediction models were established by partial least squares regression to evaluate the potential of using the spectroscopic techniques in an on-line slaughterhouse system. VIS data gave good prediction models, indicating that current industrial colour systems can be advanced into more specific meat evaluation systems by including the entire visible spectral range. The FOP and fluorescence measurements were less successful, and suffered from sampling problems since they measure only a small area. The best regression models were obtained from LF-NMR data for all reference quality measures and yielded a correlation coefficient of 0.75 with drip loss. LF-NMR proved able to distinguish between the two muscles and the results for their longitudinal relaxation times, T(21), were proportional to their average myofibrillar cross-sectional areas reported in the literature.

Chemometrics in food science—a demonstration of the feasibility of a highly exploratory, inductive evaluation strategy of fundamental scientific significance

Abstract At the roots of science lies observation and data collection from the world as is and from which conclusions can be induced after classification. This is far from the present theory-driven, deductive, normative stage of science which depends heavily on modelling discrete functional factors in laboratory experiments and suppresses the aspect of interaction. In spite of its successes, science today has great difficulty in adapting to the changes which technology has created to cope with registering and evaluating real data from the world, such as in food production chains. This paper demonstrates that it is possible and profitable with the help of new technology to reintroduce an explorative, inductive strategy to investigate the chemistry of a complex food process as is with a minimum of a priori assumptions. The food process investigated is a sugar plant and the tools necessary in this strategy include a multivariate screening method (fluorescence spectroscopy), an arsenal of chemometric models (PCA, PLS, principal variables), including multiway models ( parafac , Tucker), and a computer. Not only can chemical criteria and process parameters throughout the process be validly predicted by the screening method, but process irregularities as well as chemical species can also be detected and validated by multiway chemometric techniques. Inspired by examples from the food area, the paper further discusses the nature of the exploration method in the selection of tools and data. The aim is to study complex processes as a whole in order to model interaction of the underlying latent functional factors which may later be defined more precisely by deductive methods. These methods in combination with an appropriate multivariate screening method allow for unique identification of objects—a significant prerequisite for a viable, exploratory, inductive data strategy which is needed as a fundamental complement to prevalent normative research in order to obtain a science on the interdisciplinary level.

Drug Insight: aminosalicylates for the treatment of IBD

Sulfasalazine and mesalazine (also known as mesalamine; 5-aminosalicylic acid) preparations have for many years been used for the treatment of IBD (i.e. ulcerative colitis and Crohns disease), for both active disease and the control of remission. It has also been suggested that mesalazine is a chemoprophylactic agent that protects against the development of colorectal cancer. This Review focuses on the latest clinical evidence for the use of these aminosalicylates for the treatment of IBD, and concludes that sulfasalazine and mesalazine are useful for the treatment of both active and quiescent ulcerative colitis, whereas they have no clinical effect on either active or inactive Crohns disease. Furthermore, evidence is lacking that mesalazine per se is a chemoprophylactic agent.

Exploring the phenotypic expression of a regulatory proteome- altering gene by spectroscopy and chemometrics

Evaluating gene effects on proteomes and the resulting indirect pleiotropic effects through the cell machinery on the chemical phenotype constitutes a formidable challenge to the analytical chemist. This paper demonstrates that near-infrared (NIR) spectroscopy and chemometrics on the level of the barley seed phenotype is able to differentiate between genetic and environmental effects in a PCA model involving normal barley lines and the gene regulator lys3a in different genetic backgrounds. The gene drastically changes the proteome quantitatively and qualitatively, as displayed in two-dimensional electrophoresis, resulting in a radically changed amino acid and chemical composition. A synergy interval partial least squares regression model (si-PLSR) is tested to select combinations of spectral segments which have a high correlation to defined chemical components indicative of the lys3a gene, such as direct effects of the changed proteome, for example, the amide content, or indirect effects due to changes in carbohydrate and fat composition. It is concluded that the redundancy of biological information on the DNA sequence level is also represented at the phenotypic level in the dataset read by the NIR spectroscopic sensor from the chemical physical fingerprint. The PLS algorithm chooses spectral intervals which combine both direct and indirect proteome effects. This explains the robustness of NIR spectral predictions by PLSR for a wide range of chemical components. The new option of using spectroscopy, analytical chemistry and chemometrics in modeling the genetically based covariance of physical/chemical fingerprints of the intact phenotype in plant breeding and biotechnology is discussed.

Irritable Bowel Syndrome–Prognosis and Diagnostic Safety

The irritable bowel syndrome is the commonest diagnosis in gastroenterological clinics, although diagnostic criteria and investigatory programs vary. To elucidate the diagnostic safety and prognosis of the syndrome, a retrospective study was conducted. One hundred and twelve consecutive patients with irritable bowel syndrome as the final and only abdominal diagnosis in the period 1977-79 were followed up in 1984. Seventeen patients died during the follow-up period; two of these were considered diagnostic failures (chronic pancreatitis and pancreatic cancer). Of the remaining 95 patients, 93 were available for the follow-up study. Three diagnostic failures were found (gallbladder stones, kidney stone, thyrotoxicosis). The diagnostic failure rate was accordingly 4.5% (5/110). Half of the patients had unchanged or aggravated symptoms at the follow-up study, independent of treatment. The only predictor of a poor prognosis was abdominal surgery before the diagnosis.

Starch molecular structure and phosphorylation investigated by a combined chromatographic and chemometric approach

Structural features of starch were studied with special emphasis on the relationship between starch phosphorylation and starch chain length distribution comparing a chemometric approach with classic statistics. Starches prepared from 44 plant species were analysed with respect to the degree of phosphorylation and chain length distribution of the neutral unit chains, prepared by enzymic isoamylase debranching, using high performance anion exchange chromatography with pulsed amperometric detection (HPAEC/PAD). Chemometric algorithms such as Principle Component Analysis (PCA), Non-Negative Alternating Least Squares Regression (NNALSR) and Partial Least Squares regression (PLS) were used to analyse the systematic variation in the chromatograms and compared to Gauss decomposition. Detailed relations between chain length data and structural elements of the current cluster/bocklet model of native starch granules were revealed. By using PCA, both crystal polymorphs and botanical origin of the starch were accurately predicted. Using PLS, a strong correlation (0.93) was obtained between the chain length distribution and the degree of phosphorylation in the potato starch group. The use of chemometrics as an efficient tool to classify and predict starch functionality is documented.

Nutritional quality of sorghum and sorghum foods from Sudan

The nutritional quality of whole and decorticated sorghum grains (Tetron, Dabar, Feterita) from Sudan, and various dishes prepared from sorghum, was determined in rat balance tests. From these tests it is concluded that sorghum is low in lysine, and, therefore, has a low biological value. On the other hand, the true digestibility of protein, as well as digestible energy, is very high with values above 90%. True digestibility of the protein decreased when a porridge (ugali) was cooked from the variety Dabar (low polyphenol) but there was an increase in biological value compared with the raw grain. These changes were eliminated if the pH was adjusted to 3·9 before cooking. These effects of cooking were much more pronounced for the variety Feterita (high polyphenol). In pancakes (Kisra) fermented at pH 3·9, there were only minor effects on the nutritional quality due to cooking for all sorghum varieties studied. Cooked, fermented and cooked, unfermented, acid-adjusted Aceda (a thin fermented gruel) had slightly lower digestible energies and lower true protein digestibilities, but higher biological values, than uncooked, fermented Aceda, snowing that the protective effect of acidification observed with Ugali did not occur with Aceda. Marissa, a sorghum beer, had a higher biological value after sieving than did the unsieved brew but true protein digestibility was negatively affected by Marissa preparation.