Exploring diurnal variation using piecewise linear splines:an example using blood pressure

Background: There are many examples of physiological processes that follow a circadian cycle and researchers are interested in alternative methods to illustrate and quantify this diurnal variation. Circadian blood pressure (BP) deserves additional attention given uncertainty relating to the prognostic significance of BP variability in relation to cardiovascular disease. However, the majority of studies exploring variability in ambulatory blood pressure monitoring (ABPM) collapse the data into single readings ignoring the temporal nature of the data. Advanced statistical techniques are required to explore complete variation over 24 h. Methods: We use piecewise linear splines in a mixed-effects model with a constraint to ensure periodicity as a novel application for modelling daily blood pressure. Data from the Mitchelstown Study, a cross-sectional study of Irish adults aged 47–73 years (n = 2047) was utilized. A subsample (1207) underwent 24-h ABPM. We compared patterns between those with and without evidence of subclinical target organ damage (microalbuminuria). Results: We were able to quantify the steepest rise and fall in SBP, which occurred just after waking (2.23 mmHg/30 min) and immediately after falling asleep (−1.93 mmHg/30 min) respectively. The variation about an individual’s trajectory over 24 h was 12.3 mmHg (standard deviation). On average those with microalbuminuria were found to have significantly higher SBP (7.6 mmHg, 95% CI 5.0–10.1) after adjustment for age, sex and BMI. Including an interaction term between each linear spline and microalbuminuria did not improve model fit. Conclusion: We have introduced a practical method for the analysis of ABPM where we can determine the rate of increase or decrease for different periods of the day. This may be particularly useful in examining chronotherapy effects of antihypertensive medication. It offers new measures of short-term BP variability as we can quantify the variation about an individual’s trajectory but also allows examination of the variation in slopes between individuals (random-effects)

Research on information systems failures and successes: Status update and future directions

The final publication is available at Springer via http://dx.doi.org/10.1007/s10796-014-9500-yInformation systems success and failure are among the most prominent streams in IS research. Explanations of why some IS fulfill their expectations, whereas others fail, are complex and multi-factorial. Despite the efforts to understand the underlying factors, the IS failure rate remains stubbornly high. A Panel session was held at the IFIP Working Group 8.6 conference in Bangalore in 2013 which forms the subject of this Special Issue. Its aim was to reflect on the need for new perspectives and research directions, to provide insights and further guidance for managers on factors enabling IS success and avoiding IS failure. Several key issues emerged, such as the need to study problems from multiple perspectives, to move beyond narrow considerations of the IT artifact, and to venture into underexplored organizational contexts, such as the public sector. © 2014 Springer Science+Business Media New York

Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis which drives endothelial cell survival, proliferation, and migration while increasing vascular permeability. Playing an important role in the physiology of normal ovaries, VEGF has also been implicated in the pathogenesis of ovarian cancer. Essentially by promoting tumor angiogenesis and enhancing vascular permeability, VEGF contributes to the development of peritoneal carcinomatosis associated with malignant ascites formation, the characteristic feature of advanced ovarian cancer at diagnosis. In both experimental and clinical studies, VEGF levels have been inversely correlated with survival. Moreover, VEGF inhibition has been shown to inhibit tumor growth and ascites production and to suppress tumor invasion and metastasis. These findings have laid the basis for the clinical evaluation of agents targeting VEGF signaling pathway in patients with ovarian cancer. In this review, we will focus on VEGF involvement in the pathophysiology of ovarian cancer and its contribution to the disease progression and dissemination