Intermittent atrial tachycardia promotes repolarization alternans and conduction slowing during rapid rates, and increases susceptibility to atrial fibrillation in a free-behaving sheep model.

INTRODUCTION: Paroxysmal atrial fibrillation (AF) may be triggered by intermittent atrial tachycardia, and ultimately lead to persistent AF. However, the mechanisms by which intermittent atrial tachycardia promotes sustained AF are not well understood. METHODS AND RESULTS: Eight sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms, and for the delivery of electrophysiological stimulation protocols and intermittent right atrial tachycardia. Right atrial kinetics of activation recovery interval (ARI) as a surrogate for action potential duration, of conduction time and velocity, and of repolarization alternans were analyzed at incremental pacing rates during the remodeling process induced by weeks of intermittent atrial tachycardia until the development of sustained AF. Intermittent atrial tachycardia decreased ARI and blunted its rate adaptation, facilitated atrial capture, and slowed conduction at high rates, and increased susceptibility to pacing-induced AF. In spite of blunted ARI rate adaptation, right atrial repolarization alternans was maintained during remodeling, and further increased in magnitude just before rapid pacing-induced AF. CONCLUSION: This study suggests that weeks of intermittent right atrial tachycardia result in a gradual electrical remodeling favorable for wavebreaks and reentry that may facilitate fibrillation.

Economic crisis and recovery: changes in second birth rates within occupational classes and educational groups

This study assesses the decline in second birth rates for men and women across different skill levels in transitional Russia. Changes within educational groups and occupational classes are observed over three distinct time periods: the Soviet era, economic crisis, and economic recovery. The most remarkable finding is the similarity in the extent second birth rates declined within educational groups and occupational classes during the economic crisis. Although further decline occurred in the recovery period, more variation emerged across groups.

Differentiated evolutionary rates in alternative exons and the implications for splicing regulation

Background: Alternatively spliced exons play an important role in the diversification of gene function in most metazoans and are highly regulated by conserved motifs in exons and introns. Two contradicting properties have been associated to evolutionary conserved alternative exons: higher sequence conservation and higher rate of non-synonymous substitutions, relative to constitutive exons. In order to clarify this issue, we have performed an analysis of the evolution of alternative and constitutive exons, using a large set of protein coding exons conserved between human and mouse and taking into account the conservation of the transcript exonic structure. Further, we have also defined a measure of the variation of the arrangement of exonic splicing enhancers (ESE-conservation score) to study the evolution of splicing regulatory sequences. We have used this measure to correlate the changes in the arrangement of ESEs with the divergence of exon and intron sequences. Results: We find evidence for a relation between the lack of conservation of the exonic structure and the weakening of the sequence evolutionary constraints in alternative and constitutive exons. Exons in transcripts with non-conserved exonic structures have higher synonymous (dS) and non-synonymous (dN) substitution rates than exons in conserved structures. Moreover, alternative exons in transcripts with non-conserved exonic structure are the least constrained in sequence evolution, and at high EST-inclusion levels they are found to be very similar to constitutive exons, whereas alternative exons in transcripts with conserved exonic structure have a dS significantly lower than average at all EST-inclusion levels. We also find higher conservation in the arrangement of ESEs in constitutive exons compared to alternative ones. Additionally, the sequence conservation at flanking introns remains constant for constitutive exons at all ESE-conservation values, but increases for alternative exons at high ESE-conservation values. Conclusion: We conclude that most of the differences in dN observed between alternative and constitutive exons can be explained by the conservation of the transcript exonic structure. Low dS values are more characteristic of alternative exons with conserved exonic structure, but not of those with non-conserved exonic structure. Additionally, constitutive exons are characterized by a higher conservation in the arrangement of ESEs, and alternative exons with an ESE-conservation similar to that of constitutive exons are characterized by a conservation of the flanking intron sequences higher than average, indicating the presence of more intronic regulatory signals.

Non-peaky signals in wideband fading channels: achievable bit rates and optimal bandwidth

In the context of fading channels it is well established that, with a constrained transmit power, the bit rates achievable by signals that are not peaky vanish as the bandwidth grows without bound. Stepping back from the limit, we characterize the highest bit rate achievable by such non-peaky signals and the approximate bandwidth where that apex occurs. As it turns out, the gap between the highest rate achievable without peakedness and the infinite-bandwidth capacity (with unconstrained peakedness) is small for virtually all settings of interest to wireless communications. Thus, although strictly achieving capacity in wideband fading channels does require signal peakedness, bit rates not far from capacity can be achieved with conventional signaling formats that do not exhibit the serious practical drawbacks associated with peakedness. In addition, we show that the asymptotic decay of bit rate in the absence of peakedness usually takes hold at bandwidths so large that wideband fading models are called into question. Rather, ultrawideband models ought to be used.

The political economy of childcare in OECD countries : Explaining cross-national variation in spending and coverage rates

If childcare policy has become topical in most OECD countries over the last ten years or so, actual developments display huge cross-national variations. Countries like Sweden and Denmark spend around 2 per cent of GDP on this service, and provide affordable childcare places to most children below school age. At the other extreme, in Southern Europe, only around 10 per cent of this age group has access to formal daycare. Against this background, this article aims to account for cross-national variations in childcare services. It distinguishes two dependent variables: the coverage rate and the proportion of GDP spent subsidising childcare services. Using a mix of cross-sectional and pooled times-series methods, it tests a series of hypotheses concerning the determinants of the development of this policy. Its main conclusion for the coverage rate is that key factors are public spending and wage dispersion (both positive). For spending, key factors are the proportion of women in parliaments (positive) and spending on age-related policies (negative).

Rates of cultural change and patterns of cultural accumulation in stochastic models of social transmission.

Cultural variation in a population is affected by the rate of occurrence of cultural innovations, whether such innovations are preferred or eschewed, how they are transmitted between individuals in the population, and the size of the population. An innovation, such as a modification in an attribute of a handaxe, may be lost or may become a property of all handaxes, which we call "fixation of the innovation." Alternatively, several innovations may attain appreciable frequencies, in which case properties of the frequency distribution-for example, of handaxe measurements-is important. Here we apply the Moran model from the stochastic theory of population genetics to study the evolution of cultural innovations. We obtain the probability that an initially rare innovation becomes fixed, and the expected time this takes. When variation in cultural traits is due to recurrent innovation, copy error, and sampling from generation to generation, we describe properties of this variation, such as the level of heterogeneity expected in the population. For all of these, we determine the effect of the mode of social transmission: conformist, where there is a tendency for each naïve newborn to copy the most popular variant; pro-novelty bias, where the newborn prefers a specific variant if it exists among those it samples; one-to-many transmission, where the variant one individual carries is copied by all newborns while that individual remains alive. We compare our findings with those predicted by prevailing theories for rates of cultural change and the distribution of cultural variation.

Simple estimation of incident HIV infection rates in notification cohorts based on window periods of algorithms for evaluation of line-immunoassay result patterns.

BACKGROUND: Tests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods. METHODS: We classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship 'Prevalence = Incidence x Duration' in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship 'incident = true incident + false incident' and also to the IIR derived from the BED incidence assay. RESULTS: Window periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R(2) = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods. CONCLUSIONS: IIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.

Obesity and overweight associated with lower rates of colorectal cancer screening in Switzerland.

Screening for colorectal cancer (CRC) is associated with reduced CRC mortality, but low screening rates have been reported in several settings. The aim of the study was to assess predictors of low CRC screening in Switzerland. A retrospective cohort of a random sample of 940 patients aged 50-80 years followed for 2 years from four Swiss University primary care settings was used. Patients with illegal residency status and a history of CRC or colorectal polyps were excluded. We abstracted sociodemographic data of patients and physicians, patient health status, and indicators derived from RAND's Quality Assessment Tools from medical charts. We defined CRC screening as colonoscopy in the last 10 years, flexible sigmoidoscopy in the last 5 years, or fecal occult blood testing in the last 2 years. We used bivariate and multivariate logistic regression analyses. Of 940 patients (mean age 63.9 years, 42.7% women), 316 (33.6%) had undergone CRC screening. In multivariate analysis, birthplace in a country outside of Western Europe and North America [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.45-0.97], male sex of the physician in charge (OR 0.67, 95% CI 0.50-0.91), BMI 25.0-29.9 kg/m (OR 0.66, CI 0.46-0.96) and at least 30.0 kg/m (OR 0.61, CI 0.40-0.90) were associated with lower CRC screening rates. Obesity, overweight, birthplace outside of Western Europe and North America, and male sex of the physician in charge were associated with lower CRC screening rates in Swiss University primary care settings. Physician perception of obesity and its impact on their recommendation for CRC screening might be a target for further research.

In vivo loading increases mechanical properties of scaffold by affecting bone formation and bone resorption rates.

A successful bone tissue engineering strategy entails producing bone-scaffold constructs with adequate mechanical properties. Apart from the mechanical properties of the scaffold itself, the forming bone inside the scaffold also adds to the strength of the construct. In this study, we investigated the role of in vivo cyclic loading on mechanical properties of a bone scaffold. We implanted PLA/β-TCP scaffolds in the distal femur of six rats, applied external cyclic loading on the right leg, and kept the left leg as a control. We monitored bone formation at 7 time points over 35 weeks using time-lapsed micro-computed tomography (CT) imaging. The images were then used to construct micro-finite element models of bone-scaffold constructs, with which we estimated the stiffness for each sample at all time points. We found that loading increased the stiffness by 60% at 35 weeks. The increase of stiffness was correlated to an increase in bone volume fraction of 18% in the loaded scaffold compared to control scaffold. These changes in volume fraction and related stiffness in the bone scaffold are regulated by two independent processes, bone formation and bone resorption. Using time-lapsed micro-CT imaging and a newly-developed longitudinal image registration technique, we observed that mechanical stimulation increases the bone formation rate during 4-10 weeks, and decreases the bone resorption rate during 9-18 weeks post-operatively. For the first time, we report that in vivo cyclic loading increases mechanical properties of the scaffold by increasing the bone formation rate and decreasing the bone resorption rate.

Active intravenous drug use during chronic hepatitis C therapy does not reduce sustained virological response rates in adherent patients.

SUMMARY: Reluctance has been expressed about treating chronic hepatitis C in active intravenous (IV) drug users (IDUs), and this is found in both international guidelines and routine clinical practice. However, the medical literature provides no evidence for an unequivocal treatment deferral of this risk group. We retrospectively analyzed the direct effect of IV drug use on treatment outcome in 500 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study. Patients were eligible for the study if they had their serum hepatitis C virus (HCV) RNA tested 6 months after the end of treatment and at least one visit during the antiviral therapy, documenting the drug use status. Five hundred patients fulfilled the inclusion criteria (199 were IDU and 301 controls). A minimum exposure to 80% of the scheduled cumulative dose of antivirals was reached in 66.0% of IDU and 60.5% of controls (P = NS). The overall sustained virological response (SVR) rate was 63.6%. Active IDU reached a SVR of 69.3%, statistically not significantly different from controls (59.8%). A multivariate analysis for treatment success showed no significant negative influence of active IV drug use. In conclusion, our study shows no relevant direct influence of IV drugs on the efficacy of anti-HCV therapy among adherent patients.

The Effect of Four-Lane to Three-Lane Conversion on the Number of Crashes and Crash Rates in Iowa Roads, June 2005

We analyze crash data collected by the Iowa Department of Transportation using Bayesian methods. The data set includes monthly crash numbers, estimated monthly traffic volumes, site length and other information collected at 30 paired sites in Iowa over more than 20 years during which an intervention experiment was set up. The intervention consisted in transforming 15 undivided road segments from four-lane to three lanes, while an additional 15 segments, thought to be comparable in terms of traffic safety-related characteristics were not converted. The main objective of this work is to find out whether the intervention reduces the number of crashes and the crash rates at the treated sites. We fitted a hierarchical Poisson regression model with a change-point to the number of monthly crashes per mile at each of the sites. Explanatory variables in the model included estimated monthly traffic volume, time, an indicator for intervention reflecting whether the site was a “treatment” or a “control” site, and various interactions. We accounted for seasonal effects in the number of crashes at a site by including smooth trigonometric functions with three different periods to reflect the four seasons of the year. A change-point at the month and year in which the intervention was completed for treated sites was also included. The number of crashes at a site can be thought to follow a Poisson distribution. To estimate the association between crashes and the explanatory variables, we used a log link function and added a random effect to account for overdispersion and for autocorrelation among observations obtained at the same site. We used proper but non-informative priors for all parameters in the model, and carried out all calculations using Markov chain Monte Carlo methods implemented in WinBUGS. We evaluated the effect of the four to three-lane conversion by comparing the expected number of crashes per year per mile during the years preceding the conversion and following the conversion for treatment and control sites. We estimated this difference using the observed traffic volumes at each site and also on a per 100,000,000 vehicles. We also conducted a prospective analysis to forecast the expected number of crashes per mile at each site in the study one year, three years and five years following the four to three-lane conversion. Posterior predictive distributions of the number of crashes, the crash rate and the percent reduction in crashes per mile were obtained for each site for the months of January and June one, three and five years after completion of the intervention. The model appears to fit the data well. We found that in most sites, the intervention was effective and reduced the number of crashes. Overall, and for the observed traffic volumes, the reduction in the expected number of crashes per year and mile at converted sites was 32.3% (31.4% to 33.5% with 95% probability) while at the control sites, the reduction was estimated to be 7.1% (5.7% to 8.2% with 95% probability). When the reduction in the expected number of crashes per year, mile and 100,000,000 AADT was computed, the estimates were 44.3% (43.9% to 44.6%) and 25.5% (24.6% to 26.0%) for converted and control sites, respectively. In both cases, the difference in the percent reduction in the expected number of crashes during the years following the conversion was significantly larger at converted sites than at control sites, even though the number of crashes appears to decline over time at all sites. Results indicate that the reduction in the expected number of sites per mile has a steeper negative slope at converted than at control sites. Consistent with this, the forecasted reduction in the number of crashes per year and mile during the years after completion of the conversion at converted sites is more pronounced than at control sites. Seasonal effects on the number of crashes have been well-documented. In this dataset, we found that, as expected, the expected number of monthly crashes per mile tends to be higher during winter months than during the rest of the year. Perhaps more interestingly, we found that there is an interaction between the four to three-lane conversion and season; the reduction in the number of crashes appears to be more pronounced during months, when the weather is nice than during other times of the year, even though a reduction was estimated for the entire year. Thus, it appears that the four to three-lane conversion, while effective year-round, is particularly effective in reducing the expected number of crashes in nice weather.

On the term structure of Interbank interest rates: Jump-diffusion processes and option pricing

In this paper we study the dynamic behavior of the term structureof Interbank interest rates and the pricing of options on interest ratesensitive securities. We posit a generalized single factor model withjumps to take into account external influences in the market. Daily datais used to test for jump effects. Qualitative examination of the linkagebetween Monetary Authorities' interventions and jumps are studied. Pricingresults suggests a systematic underpricing in bonds and call options ifthe jumps component is not included. However, the pricing of put optionson bonds presents indeterminacies.