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)

Clinical Features of Cardio-Renal Syndrome in a Cohort of Consecutive Patients Admitted to an Internal Medicine Ward

Introduction: Cardiorenal syndrome (CRS) is a disorder of the heart and kidney whereby interactions between the 2 organs can occur. We recorded the clinical features of CRS in patients consecutively admitted to an Internal Medicine ward. Patients and Methods: We retrospectively analyzed the anthropometric, history, clinical, biochemical and treatment characteristics in 438 out of 2,998 subjects (14.6%) admitted to our unit (from June 2007 to December 2009), diagnosed with CRS, according to Acute Dialysis Quality Initiative (ADQI) recommendations. Estimated glomerular filtration (eGFR) was calculated using several equations: MDRD (Modification of Diet in Renal Disease; 2 variations GFRMDRD186, GFRMDRD175), Mayo, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockroft-Gault. Results: Mean age was 80±8 years, 222 (50.6%) were males, 321 (73.2%) were smokers, 229 (52.2%) were diabetic, 207 (47.2%) had a history of acute myocardial infarction, 167 (38.1%) had angina, 135 (30.8%) were affected by cerebrovascular disease, 339 (77.3%) had peripheral arterial disease. CRS was type 1 in 211 cases (48.2%), type 2 in 96 (21.9%), type 3 in 88 (20.1%), type 4 in 29 (6.6%) and type 5 in 14 (3.2%). eGFR, calculated by different formulae, ranged between 31 and 36 ml/min/1.73 m2. GFR was lower in CRS type 3 than in the other types, and the values ranged between 24 and 27 ml/min/1.73 m2. Mean hospital length-of-stay (LOS) was 9.8±6.3 days. Diuretics were the most prescribed medication (78.7%); only 5 patients underwent haemodialysis. Conclusions: CRS is common, especially in the elderly. CRS Type 1 was the prevalent subset and patients had stage 3-4 renal insufficiency. Results obtained from the GFR equations were similar although the Mayo equation tended to overestimate the eGFR

Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory blood pressure in moderate-to-severe hypertensive patients not controlled by amlodipine alone

Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory blood pressure in moderate-to-severe hypertensive patients not controlled by amlodipine alon

Euclid preparation. XXIX. Water ice in spacecraft part I:The physics of ice formation and contamination

Molecular contamination is a well-known problem in space flight. Water is the most common contaminant and alters numerous properties of a cryogenic optical system. Too much ice means that Euclid's calibration requirements and science goals cannot be met. Euclid must then be thermally decontaminated, a long and risky process. We need to understand how iced optics affect the data and when a decontamination is required. This is essential to build adequate calibration and survey plans, yet a comprehensive analysis in the context of an astrophysical space survey has not been done before. In this paper we look at other spacecraft with well-documented outgassing records, and we review the formation of thin ice films. A mix of amorphous and crystalline ices is expected for Euclid. Their surface topography depends on the competing energetic needs of the substrate-water and the water-water interfaces, and is hard to predict with current theories. We illustrate that with scanning-tunnelling and atomic-force microscope images. Industrial tools exist to estimate contamination, and we must understand their uncertainties. We find considerable knowledge errors on the diffusion and sublimation coefficients, limiting the accuracy of these tools. We developed a water transport model to compute contamination rates in Euclid, and find general agreement with industry estimates. Tests of the Euclid flight hardware in space simulators did not pick up contamination signals; our in-flight calibrations observations will be much more sensitive. We must understand the link between the amount of ice on the optics and its effect on Euclid's data. Little research is available about this link, possibly because other spacecraft can decontaminate easily, quenching the need for a deeper understanding. In our second paper we quantify the various effects of iced optics on spectrophotometric data

Euclid preparation. XXIX. Water ice in spacecraft part I: The physics of ice formation and contamination

Molecular contamination is a well-known problem in space flight. Water is the most common contaminant and alters numerous properties of a cryogenic optical system. Too much ice means that Euclid's calibration requirements and science goals cannot be met. Euclid must then be thermally decontaminated, a long and risky process. We need to understand how iced optics affect the data and when a decontamination is required. This is essential to build adequate calibration and survey plans, yet a comprehensive analysis in the context of an astrophysical space survey has not been done before. In this paper we look at other spacecraft with well-documented outgassing records, and we review the formation of thin ice films. A mix of amorphous and crystalline ices is expected for Euclid. Their surface topography depends on the competing energetic needs of the substrate-water and the water-water interfaces, and is hard to predict with current theories. We illustrate that with scanning-tunnelling and atomic-force microscope images. Industrial tools exist to estimate contamination, and we must understand their uncertainties. We find considerable knowledge errors on the diffusion and sublimation coefficients, limiting the accuracy of these tools. We developed a water transport model to compute contamination rates in Euclid, and find general agreement with industry estimates. Tests of the Euclid flight hardware in space simulators did not pick up contamination signals; our in-flight calibrations observations will be much more sensitive. We must understand the link between the amount of ice on the optics and its effect on Euclid's data. Little research is available about this link, possibly because other spacecraft can decontaminate easily, quenching the need for a deeper understanding. In our second paper we quantify the various effects of iced optics on spectrophotometric data.Comment: 35 pages, 22 figures, A&A in press. Changes to previous version: language edits, added Z. Bolag as author in the arxiv PDF (was listed in the ASCII author list and in the journal PDF, but not in the arxiv PDF). This version is identical to the journal versio

Transmission of Chronic Wasting Disease Identifies a Prion Strain Causing Cachexia and Heart Infection in Hamsters

Chronic wasting disease (CWD) is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrPSc, prion infection of the central and peripheral neuroendocrine system, and PrPSc deposition in cardiac muscle. There was also prominent PrPSc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the ‘wasting’ or WST strain of hamster CWD