Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction and cause-specific mortality : cohort study

Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective. Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991–1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163). Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03–1.19; and 1.11, 1.02–1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09–1.37; and 1.18, 1.04–1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample. Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.

Estimation of Parameters in Random Effect Models with Incidence Matrix Uncertainty

Random effect models have been widely applied in many fields of research. However, models with uncertain design matrices for random effects have been little investigated before. In some applications with such problems, an expectation method has been used for simplicity. This method does not include the extra information of uncertainty in the design matrix is not included. The closed solution for this problem is generally difficult to attain. We therefore propose an two-step algorithm for estimating the parameters, especially the variance components in the model. The implementation is based on Monte Carlo approximation and a Newton-Raphson-based EM algorithm. As an example, a simulated genetics dataset was analyzed. The results showed that the proportion of the total variance explained by the random effects was accurately estimated, which was highly underestimated by the expectation method. By introducing heuristic search and optimization methods, the algorithm can possibly be developed to infer the 'model-based' best design matrix and the corresponding best estimates.

Assessing the physical environment of older people’s residential care facilities: development of the Swedish version of the Sheffield Care Environment Assessment Matrix (S-SCEAM)

Background There is emerging evidence that the physical environment is important for health, quality of life and care, but there is a lack of valid instruments to assess health care environments. The Sheffield Care Environment Assessment Matrix (SCEAM), developed in the United Kingdom, provides a comprehensive assessment of the physical environment of residential care facilities for older people. This paper reports on the translation and adaptation of SCEAM for use in Swedish residential care facilities for older people, including information on its validity and reliability. Methods SCEAM was translated into Swedish and back-translated into English, and assessed for its relevance by experts using content validity index (CVI) together with qualitative data. After modification, the validity assessments were repeated and followed by test-retest and inter-rater reliability tests in six units within a Swedish residential care facility that varied in terms of their environmental characteristics. Results Translation and back translation identified linguistic and semantic related issues. The results of the first content validity analysis showed that more than one third of the items had item-CVI (I-CVI) values less than the critical value of 0.78.  After modifying the instrument, the second content validation analysis resulted in I-CVI scores above 0.78, the suggested criteria for excellent content validity. Test-retest reliability showed high stability (96% and 95% for two independent raters respectively), and inter-rater reliability demonstrated high levels of agreement (95% and 94% on two separate rating occasions). Kappa values were very good for test-retest (κ= 0.903 and 0.869) and inter-rater reliability (κ= 0.851 and 0.832). Conclusions Adapting an instrument to a domestic context is a complex and time-consuming process, requiring an understanding of the culture where the instrument was developed and where it is to be used. A team, including the instrument’s developers, translators, and researchers is necessary to ensure a valid translation and adaption. This study showed preliminary validity and reliability evidence for the Swedish version (S-SCEAM) when used in a Swedish context. Further, we believe that the S-SCEAM has improved compared to the original instrument and suggest that it can be used as a foundation for future developments of the SCEAM model.

A simple demonstration of the existence of the jordan canonical form for any square matrix

All the demonstrations known to this author of the existence of the Jordan Canonical Form are somewhat complex - usually invoking the use of new spaces, and what not. These demonstrations are usually too difficult for an average Mathematics student to understand how he or she can obtain the Jordan Canonical Form for any square matrix. The method here proposed not only demonstrates the existence of such forms but, additionally, shows how to find them in a step by step manner. I do not claim that the following demonstration is in any way “elegant” (by the standards of elegance in fashion nowadays among mathematicians) but merely simple (undergraduate students taking a fist course in Matrix Algebra would understand how it works).

A class of improved heteroskedasticity-consistent covariance matrix estimators

The heteroskedasticity-consistent covariance matrix estimator proposed by White (1980), also known as HC0, is commonly used in practical applications and is implemented into a number of statistical software. Cribari–Neto, Ferrari & Cordeiro (2000) have developed a bias-adjustment scheme that delivers bias-corrected White estimators. There are several variants of the original White estimator that also commonly used by practitioners. These include the HC1, HC2 and HC3 estimators, which have proven to have superior small-sample behavior relative to White’s estimator. This paper defines a general bias-correction mechamism that can be applied not only to White’s estimator, but to variants of this estimator as well, such as HC1, HC2 and HC3. Numerical evidence on the usefulness of the proposed corrections is also presented. Overall, the results favor the sequence of improved HC2 estimators.

A new and improved strategy combining a dispersive-solid phase extraction-based multiclass method with ultra high pressure liquid chromatography for analysis of low molecular weight polyphenols in vegetables

This paper reports on the development and optimization of a modified Quick, Easy, Cheap Effective, Rugged and Safe (QuEChERS) based extraction technique coupled with a clean-up dispersive-solid phase extraction (dSPE) as a new, reliable and powerful strategy to enhance the extraction efficiency of free low molecular-weight polyphenols in selected species of dietary vegetables. The process involves two simple steps. First, the homogenized samples are extracted and partitioned using an organic solvent and salt solution. Then, the supernatant is further extracted and cleaned using a dSPE technique. Final clear extracts of vegetables were concentrated under vacuum to near dryness and taken up into initial mobile phase (0.1% formic acid and 20% methanol). The separation and quantification of free low molecular weight polyphenols from the vegetable extracts was achieved by ultrahigh pressure liquid chromatography (UHPLC) equipped with a phodiode array (PDA) detection system and a Trifunctional High Strength Silica capillary analytical column (HSS T3), specially designed for polar compounds. The performance of the method was assessed by studying the selectivity, linear dynamic range, the limit of detection (LOD) and limit of quantification (LOQ), precision, trueness, and matrix effects. The validation parameters of the method showed satisfactory figures of merit. Good linearity (View the MathML sourceRvalues2>0.954; (+)-catechin in carrot samples) was achieved at the studied concentration range. Reproducibility was better than 3%. Consistent recoveries of polyphenols ranging from 78.4 to 99.9% were observed when all target vegetable samples were spiked at two concentration levels, with relative standard deviations (RSDs, n = 5) lower than 2.9%. The LODs and the LOQs ranged from 0.005 μg mL−1 (trans-resveratrol, carrot) to 0.62 μg mL−1 (syringic acid, garlic) and from 0.016 μg mL−1 (trans-resveratrol, carrot) to 0.87 μg mL−1 ((+)-catechin, carrot) depending on the compound. The method was applied for studying the occurrence of free low molecular weight polyphenols in eight selected dietary vegetables (broccoli, tomato, carrot, garlic, onion, red pepper, green pepper and beetroot), providing a valuable and promising tool for food quality evaluation.

Allergic asthma exhaled breath metabolome: a challenge for comprehensive two-dimensional gas chromatography

Allergic asthma represents an important public health issue, most common in the paediatric population, characterized by airway inflammation that may lead to changes in volatiles secreted via the lungs. Thus, exhaled breath has potential to be a matrix with relevant metabolomic information to characterize this disease. Progress in biochemistry, health sciences and related areas depends on instrumental advances, and a high throughput and sensitive equipment such as comprehensive two-dimensional gas chromatography–time of flight mass spectrometry (GC × GC–ToFMS) was considered. GC × GC–ToFMS application in the analysis of the exhaled breath of 32 children with allergic asthma, from which 10 had also allergic rhinitis, and 27 control children allowed the identification of several hundreds of compounds belonging to different chemical families. Multivariate analysis, using Partial Least Squares-Discriminant Analysis in tandem with Monte Carlo Cross Validation was performed to assess the predictive power and to help the interpretation of recovered compounds possibly linked to oxidative stress, inflammation processes or other cellular processes that may characterize asthma. The results suggest that the model is robust, considering the high classification rate, sensitivity, and specificity. A pattern of six compounds belonging to the alkanes characterized the asthmatic population: nonane, 2,2,4,6,6-pentamethylheptane, decane, 3,6-dimethyldecane, dodecane, and tetradecane. To explore future clinical applications, and considering the future role of molecular-based methodologies, a compound set was established to rapid access of information from exhaled breath, reducing the time of data processing, and thus, becoming more expedite method for the clinical purposes.