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.

Optimized Water Demand Management Through Intelligent Sensing And Analytics: The WISDOM Approach

New business and technology platforms are required to sustainably manage urban water resources [1,2]. However, any proposed solutions must be cognisant of security, privacy and other factors that may inhibit adoption and hence impact. The FP7 WISDOM project (funded by the European Commission - GA 619795) aims to achieve a step change in water and energy savings via the integration of innovative Information and Communication Technologies (ICT) frameworks to optimize water distribution networks and to enable change in consumer behavior through innovative demand management and adaptive pricing schemes [1,2,3]. The WISDOM concept centres on the integration of water distribution, sensor monitoring and communication systems coupled with semantic modelling (using ontologies, potentially connected to BIM, to serve as intelligent linkages throughout the entire framework) and control capabilities to provide for near real-time management of urban water resources. Fundamental to this framework are the needs and operational requirements of users and stakeholders at domestic, corporate and city levels and this requires the interoperability of a number of demand and operational models, fed with data from diverse sources such as sensor networks and crowsourced information. This has implications regarding the provenance and trustworthiness of such data and how it can be used in not only the understanding of system and user behaviours, but more importantly in the real-time control of such systems. Adaptive and intelligent analytics will be used to produce decision support systems that will drive the ability to increase the variability of both supply and consumption [3]. This in turn paves the way for adaptive pricing incentives and a greater understanding of the water-energy nexus. This integration is complex and uncertain yet being typical of a cyber-physical system, and its relevance transcends the water resource management domain. The WISDOM framework will be modeled and simulated with initial testing at an experimental facility in France (AQUASIM – a full-scale test-bed facility to study sustainable water management), then deployed and evaluated in in two pilots in Cardiff (UK) and La Spezia (Italy). These demonstrators will evaluate the integrated concept providing insight for wider adoption.

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.

The benefits and pitfalls of participating in a corporate inversion: a case study of two companies on two different paths

Even though the term corporate inversion has been heard globally for decades, it has only become more prevalent in the United States during the past two years. This case study examines two United States companies that recently had very high profile and public corporate inversion experiences. Complicated tax laws and high tax rales have long eroded the ability of United States companies to remain competitive on a global scale. During the past two years, tax reform has been elevated to the Presidential and Congressional levei. Because these reform efforts have stalled, however, and in the constant search for ways to become more competitive and profitable, United States dorniciled companies have begun to more aggressively explore corporate inversion. This case study of Walgreens Alliance Boots and Mylan N.V., is undertaken because while the reasons to pursue a corporate inversion for both companies were very similar and done during the same time period, the internai process and final outcome were dramatically different. The other dynamic studied is the role both internai and externai politics had on these two cornpanies and how they influenced the decisions made by the executives. Lastly, the Obama Administration continues to threaten so called "corporate America" to remain in the country through regulatory pressure, but this has not stopped companies frorn pursing corporate inversions. Legislatively, attempts at corporate tax reform, another way to encourage Untied States companies to remain, have also failed. I will not try to determine i f a corporate inversion is the right path for a company to take. I am examining how the rise o f the practice o f corporate inversions has been elevated in boardroorns, on Wall Street, in Congress and at the White House during the past two years.

Headspace solid-phase microextraction combined with mass spectrometry as a powerful analytical tool for profiling the terpenoid metabolomic pattern of hop-essential oil derived from Saaz variety

Hop(HumuluslupulusL.,Cannabaceaefamily)isprizedforitsessentialoilcontents,usedin beer production and, more recently, in biological and pharmacological applications. In this work,a methodinvolvingheadspace solid-phase microextractionand gas chromatography– mass spectrometry was developed and optimized to establish the terpenoid (monoterpenes and sesquiterpenes) metabolomic pattern of hop-essential oil derived from Saaz variety as a mean to explore this matrix as a powerful biological source for newer, more selective, biodegradable and naturally produced antimicrobial and antioxidant compounds. Different parameters affecting terpenoid metabolites extraction by headspace solid-phase microextraction were considered and optimized: type of fiber coatings, extraction temperature, extraction time, ionic strength, and sample agitation. In the optimized method, analytes were extracted for 30 min at 40 C in the sample headspace with a 50/30 m divinylbenzene/carboxen/polydimethylsiloxane coating fiber. The methodology allowed the identification of a total of 27 terpenoid metabolites, representing 92.5% of the total Saaz hop-essential oil volatile terpenoid composition. The headspace composition was dominated by monoterpenes (56.1%, 13 compounds), sesquiterpenes (34.9%, 10), oxygenated monoterpenes (1.41%, 3), and hemiterpenes (0.04%, 1) some of which can probably contribute to the hop of Saaz variety aroma. Mass spectrometry analysis revealed that the main metabolites are the monoterpene -myrcene (53.0±1.1% of the total volatile fraction), and the cyclic sesquiterpenes, -humulene (16.6 ± 0.8%), and -caryophyllene (14.7 ± 0.4%), which together represent about 80% of the total volatile fraction from the hop-essential oil. Thesefindingssuggestthatthismatrixcanbeexploredasapowerfulbiosourceofterpenoid metabolites.

Plant or fungal sequences? An alternative optimized PCR protocol to avoid ITS (nrDNA) misamplification

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of matrix metalloproteinases, type IV collagen, and interleukin-10 in rabbits treated with morphine after lamellar keratectomy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)