The effect of rosuvastatin on incident pneumonia: results from the JUPITER trial

Background:

Evidence from observational studies have raised the possibility that statin treatment reduces the incidence of certain bacterial infections, particularly pneumonia. We analyzed data from a randomized controlled trial of rosuvastatin to examine this hypothesis.

Methods:

We analyzed data from the randomized, double-blind, placebo-controlled JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). In this trial, 17 802 healthy participants (men 50 years and older and women 60 and older) with a low-density lipoprotein (LDL) cholesterol level below 130 mg/dL (3.4 mmol/L) and a high-sensitivity C-reactive protein level of 2.0 mg/L or greater were randomly assigned to receive either rosuvastatin or placebo. We evaluated the incidence of pneumonia on an intention-to-treat basis by reviewing reports of adverse events from the study investigators, who were unaware of the treatment assignments.

Results:

Among 17 802 trial participants followed for a median of 1.9 years, incident pneumonia was reported as an adverse event in 214 participants in the rosuvastatin group and 257 in the placebo group (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.69–1.00). In analyses restricted to events occurring before a cardiovascular event, pneumonia occurred in 203 participants given rosuvastatin and 250 given placebo (HR 0.81, 95% CI 0.67–0.97). Inclusion of recurrent pneumonia events did not modify this effect (HR 0.81, 95% CI 0.67–0.98), nor did adjustment for age, sex, smoking, metabolic syndrome, lipid levels and C-reactive protein level.

Interpretation:

Data from this randomized controlled trial support the hypothesis that statin treatment may modestly reduce the incidence of pneumonia.(ClinicalTrials.gov trial register no. NCT0023968.)Randomized trials of statin treatment have consistently shown reductions in the incidence of cardiovascular events.¹ In addition to these proven vascular effects, several observational studies have raised the possibility that statins reduce the incidence and severity of certain bacterial infections,^2–5 particularly pneumonia.^6–9 Mechanistic support for this hypothesis is provided in part by laboratory evidence that statins, in addition to lowering low-density lipoprotein (LDL) cholesterol levels considerably, have a positive effect on inflammation, apoptosis, antioxidant balance and endothelial function.¹⁰ However, a common confounder typical of these observational studies relates to the fact that statin treatment may be a nonspecific marker of improved quality of care (healthy user effect).^11,12 In addition, because infections such as pneumonia are a common complication of myocardial infarction and stroke, any beneficial effect of statin treatment on pneumonia and other infections reported in observational studies may have been due simply to a reduction in these vascular events.We reviewed data from the recently completed JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), a randomized controlled trial involving more than 17 000 men and women randomly assigned to receive either rosuvastatin or placebo, to examine the possibility that statins may reduce the incidence of pneumonia.     

Effect of dimensionality on Lotka-Volterra predator-prey dynamics: Individual based simulation results

The effect of varying habitat dimensionality on the dynamics of a model predator-prey system is examined using an individual-based simulation. The general results are that in one dimension fluctuations in abundance of prey and predators occur over a large range of spatial scales (extinctions occur over many spatial scales). In two dimensions (and low mobilities of prey and predators) the dynamics become more predictably periodic at local scales and constant at larger scales due to statistical stabilization. In three dimensions, the model can become “phase-locked” with prey and predators displaying oscillations in abundance over large spatial scales.     

The ventriloquist effect results from near-optimal bimodal integration

Ventriloquism is the ancient art of making one's voice appear to come from elsewhere, an art exploited by the Greek and Roman oracles, and possibly earlier. We regularly experience the effect when watching television and movies, where the voices seem to emanate from the actors' lips rather than from the actual sound source. Originally, ventriloquism was explained by performers projecting sound to their puppets by special techniques, but more recently it is assumed that ventriloquism results from vision "capturing" sound. In this study we investigate spatial localization of audio-visual stimuli. When visual localization is good, vision does indeed dominate and capture sound. However, for severely blurred visual stimuli (that are poorly localized), the reverse holds: sound captures vision. For less blurred stimuli, neither sense dominates and perception follows the mean position. Precision of bimodal localization is usually better than either the visual or the auditory unimodal presentation. All the results are well explained not by one sense capturing the other, but by a simple model of optimal combination of visual and auditory information.     

The effect of DNA reamplification on RAPD-PCR results

The results of reamplification of flax DNA with random primers are represented. It was shown that eight of 17 decameric primers used in the experiments had an reamplification effect: the intensity of the bands increased; new bands and/or new polymorphic bands appeared in the gel sample. The results confirm the effectiveness and necessity of reamplification in case of uncertain or ambiguous interpretation of RAPD analysis making possible to select the highly-informative primers.     

DNA conformational studies from electron microscopy. I. Excluded volume effect and structure dimensionality

Plots of end-to-end distance (R₀) vs contour length (S) measured from electron micrographs of double-stranded DNA molecules reveal typical power laws (R₀ ～ S^3/5 and S^3/4) and confirm the evident qualitative differences of structure observed when using various spreading techniques. We propose to relate these power laws to the structure dimensionality of DNA as a function of the conditions of spreading. To pursue this idea, our experimental results are compared with models of polymer conformation that incorporate the excluded volume effect.     

The dimensionality of human's electroencephalogram during sleep

In order to perform an analysis of nonlinear EEG-dynamics we investigated the EEG of ten male probands during sleep. According to Rechtschaffen and Kales (1968) we scored the sleep-EEG and applied an algorithm, proposed by Grassberger and Proccaccia (1983) to compute the correlation dimension of different sleep stages. The correlation dimension characterizes the dynamics of the EEG signal and estimates the degrees of freedom of the signal under study. We could demonstrate, that the EEG of slow wave sleep stages depicts a dimensionality, which is two units smaller than that of light or REM sleep.     

The effect of selected drugs on the interpretation of hemostasis- related study results

By applying in vitro and additional in vivo investigations of analysing coagulation in human beings with the routine methods TPZW, PTT and TZ it was possible to exclude influences of hemostasis described in literature and often uncritically generalised in papers and articles as well as assumed influences for such medicaments as acetylsalicylic acid, ascorbic acid, chlorpromazine, fluphenazine, gentamycin, haloperidol, lincomycin, methyldopa, sodium fluoride and penicillin G in therapeutic doses or concentrations in vitro respectively which correspond to therapeutic or toxic doses. For such solutions of infusion as infucoll 6% and gelafusal there exist these influences in the sense of an acceleration of coagulation in vitro. They can be regarded as shiftings within the normal range of methods which have no clinical relevance. Infucoll M 40 will to a concentration of 0.25 mmol/l of blood which corresponds to therapeutic conditions, to a shortening of Tz falling below the normal range of the method. These findings correlate with data in literature and could be identified even in lower concentrations by excluding the effect of dilution. According to literature these relations are identical with those in vivo some minutes after infusion.     

New type of cancer patients based on triangular cubic hesitant fuzzy TOPSIS method

In this paper,we define the new idea of triangular cubic hesitant fuzzy number(TCHFN).We discuss some basic operational laws of triangular cubic hesitant fuzzy number and hamming distance of TCHFNs.We introduce the new concept of triangular cubic hes­itant TOPSIS method.Furthermore,we extend the classical cubic hesitant the tech­nique for order of preference by similarity to ideal solution(TOPSIS)method to solve the Multi-Criteria decision-making(MCDM)method based on triangular cubic hesitant TOPSIS method.The new ranking method for TCHFNs is used to rank the alternatives.Finally,an illustrative example is given to verify and demonstrate the practicality and effectiveness of the proposed method.     

The effect of the receding ice edge on the condition of copepods in the northwestern Weddell Sea: results from biochemical assays

We compared six biochemical measures of nutritional condition: citrate synthase activity (CS), malate and lactate dehydrogenase activity (MDH and LDH), RNA:DNA ratio, and percent body protein and lipid. Adult females of five species of calanoid copepod (Calanoides acutus, Calanus propinquus, Metridia gerlachei, Rhincalanus gigas and Paraeuchaeta antarctica) were collected in the marginal ice zone of the northwestern Weddell Sea at the time of the annual phytoplankton bloom that occurs in association with the receding ice edge during austral spring. Three zones within the marginal ice zone were sampled: heavy-ice-cover pre-bloom, ice-edge bloom and low-ice-cover post-bloom. Lipid generally increased greatly from ice-covered to open water zones, and its importance in the life of polar copepods cannot be overstated. Increases in protein from ice-covered to open water were also observed, but were of less significance. Each species exhibited significant changes in at least one enzyme activity level. Citrate synthase activity in C. acutus, C. propinquus and R. gigas, all herbivores, increased between pre- and post-bloom stations. C. propinquus and M. gerlachei, which feed during winter, had large increases in LDH activity between pre- and post-bloom stations. Rhincalanus gigas and P. antarctica, the two largest species studied, showed variations in MDH activity, with peak enzyme activity occurring in post-bloom stations. RNA:DNA ratio did not change in any species. The effects of size, shipboard handling and freezer storage were easily corrected statistically, and did not alter any conclusions. The patterns observed in copepod nutrition at the Antarctic ice edge were consistent with existing models of life history for each species. The observations reported here, in conjunction with previously reported data, suggested that measurement of metabolic enzyme activity, especially in concert with lipid, enables estimation of nutritional condition in adult copepods. Additional studies comparing metabolic activity and ecology of common species should yield more information on the ecology of rarer species.     

Methodological specifications on the Todd method and preliminary results

In order to measure the potentiality and kinetics tissue fibrinolysis we have modified Todd's histochemical method preparing at least six sections taken from same sample tissue, by infraoperatory biopsy, esponing them to a fibrin film at a constant concentration; we have also chosen to incubate the section at 10, 20, 30, 45, 60 min. The measurement of the areas of fibrin, of tissue and fibrinolysis, at the above mentioned times, has been effected at standard magnification (15 X) by an image analyser (Videoplan) scale 1:8. For each sample we suggest to elaborate an Index of the Potentiality of Fibrinolysis (formula; see text) and an Index of the Kinetics of the Fibrinolysis (formula; see text). Applying this method to two different groups of thyroid disease (struma and adenoma) we have not pointed out any statistically significant difference.     

The effect of early human contact and the separation method from the dam on responses of beef calves to humans

The objectives of this experiment were to evaluate the effect of early human contact and of the separation method from the dam on the future relationships of calves with humans, and to investigate the relationship between dam responses and calf responses. Thirty-three Salers calves aged 2–4 days old and reared outdoors were split into 3-week treatments balanced according to sex and birth dates. Group 1 (long separation from the dam and human contact: LS + H; n = 11) underwent 8 h of separation from the dam per day and 5 min of individual stroking; group 2 (short separation from the dam and human contact: SS + H; n = 11) underwent 1 h of separation and the same amount of human contact as LS + H calves. Group 3 (short separation from the dam and no human contact: SS − H; n = 11) was a control group undergoing the same duration of separation as SS + H but without stroking. At 3, 15 and 45 weeks of age, the calves were tested in a standard arena test (AT) where they were successively left alone (2 min), left with a stationary human (5 min), and left with a human approaching and touching them (2 min). At 15 and 45 weeks, the calves were also tested with the standard docility test (DT: test of restraint). The dams were also tested with DT 2 months before calving. Data analysis via Mann–Whitney tests and Spearman's correlations showed no significant effect of the duration calves were separated from their dams. Just after treatment at 3-week of age, calves given stroking (LS + H and SS + H) were more motionless and more willing to accept human contact (AT: touching) than control calves (SS − H, P < 0.01). At 45 weeks of age, calves given stroking spent also significantly more time (P < 0.05) motionless with the approaching human compared to non-stroked calves (SS − H), suggesting a persistent effect. However, this effect was not reproduced on the other behavioural criteria recorded (e.g., duration of human contact or docility score). In the different tests and at the different ages, the docility scores of the dams were significantly correlated (up to 0.7, P < 0.01) with behaviour towards humans shown by stroked calves but not non-stroked calves (SS − H). Our results suggest that additional human contact at early age, but not duration of the separation from the dam, could be beneficial for the human–animal relationship, but only for calves born to docile dams.     

The effect of water supply on seed-bank analysis using the seedling-emergence method

1. When using the seedling-emergence method to analyse a soil seed bank the greenhouse conditions should match the germination requirements of the species involved. Although the seedling-emergence method is common practice in ecological studies, the germination characteristics of many species are not known, or are only partly known.
2. Before carrying out a large-scale seed-bank study in a wet dune slack, we tested the water requirements of the species in the seed bank, comparing a waterlogged soil with a moist soil. Four species germinated in significantly larger numbers in a waterlogged soil, seven species in a moist soil and 11 species showed no significant difference. When a species was present in low densities, it was often missed using the less appropriate treatment.
3. These results emphasize the need for a preliminary study before carrying out a seed-bank analysis and show the danger of using a 'standard' method to analyse soil samples from different habitats.     

The effect of sample handling on cross sectional HIV incidence testing results

Objective(s)

To determine if mishandling prior to testing would make a sample from a chronically infected subject appear recently infected when tested by cross-sectional HIV incidence assays.

Methods

Serum samples from 31 subjects with chronic HIV infection were tested. Samples were subjected to different handling conditions, including incubation at 4°C, 25°C and 37°C, for 1, 3, 7 or 15 days prior to testing. Samples were also subjected to 1,3, 7 and 15 freeze-thaw cycles prior to testing. Samples were tested using the BED capture enzyme immuno assay (BED-CEIA), Vironostika-less sensitive (V-LS), and an avidity assay using the Genetic Systems HIV-1/HIV-2 plus O EIA (avidity assay).

Results

Compared to the sample that was not subjected to any mishandling conditions, for the BED-CEIA, V-LS and avidity assay, there was no significant change in test results for samples incubated at 4°C or 25°C prior to testing. No impact on test results occurred after 15 freeze-thaw cycles. A decrease in assay results was observed when samples were held for 3 days or longer at 37°C prior to testing.

Conclusions

Samples can be subjected up to 15 freeze-thaw cycles without affecting the results the BED-CEIA, Vironostika-LS, or avidity assays. Storing samples at 4°C or 25°C for up to fifteen days prior to testing had no impact on test results. However, storing samples at 37°C for three or more days did affect results obtained with these assays.     

The effect of replicate number and image analysis method on sweetpotato [Ipomoea batatas (L.) Lam.] cDNA microarray results

Microarray analysis makes it possible to determine the relative expression of thousands of genes simultaneously. It has gained popularity at a rapid rate, but many caveats remain. In an effort to establish reliable microarray protocols for sweetpotato [Ipomoea batatas (L.) Lam.], we compared the effect of replication number and image analysis software with results obtained by quantitative rela-time PCR (Q-RT-PCR). Sweetpotato storage root development is the most economically important process in sweetpotato. In order to identify genes that may play a role in this process, RNA for microarray analysis was extracted from sweetpotato fibrous and storage roots. Four data sets, Spot4, Spot6, Finder4 and Finder6, were created using 4 or 6 replications, and the image analysis software of UCSF Spot or TIGR Spotfinder were used for spot detection and quantification. The ability of these methods to identify significant differential expression between treatments was investigated. The data sets with 6 replications were better at identifying genes with significant differential expression than the ones of 4 replications. Furthermore when using 6 replicates, UCSF Spot was superior to TIGR Spotfinder in identifying genes differentially expressed (18 out of 19) based on Q-RT-PCR. Our study shows the importance of proper replication number and image analysis for microarray studies.