Assessment of the incidence of fragmented QRS in electrocardiography in patients with systemic sclerosis and systemic lupus erythematosus.

OBJECTIVE: In systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) cardiac involvement is very common, and it might be asymptomatic. We aimed to assess the presence of fragmented QRS (fQRS) - possible indicator of a scar, diffuse damage or conduction system disturbances in those patients. METHODS: We examined 74 patients with SSc, 77 with SLE and 40 healthy controls. The incidence of fQRS in ECG was examined according to criteria by Das et al. Disease severity was estimated by Rodnan and SLICCC/ACRDI scores in SSc and SLE respectively. RESULTS: Patients with SSc were slightly older than those with SLE (53 ± 14 vs 46 ± 14 yrs), women constituted 91% and 88% of studied groups (p = 0.80). The duration of disease in both groups was similar (p = 0.59). Median of Rodnan and SLICCC/ACR-DI scores were 5 and 4 points, respectively. Left ventricle ejection fraction in both groups was similar (65.5 vs 65.1%, p = 0.51), hypertension incidence was lower in SSc (24 vs 48%, p = 0.004), patients with SLE presented prolonged corrected QT interval (432 vs 424 ms, p = 0.03). Of note, fQRS were observed in 34 (46%) SSc and 29 (38%) SLE patients, p = 0.33. Notched S waves were significantly more frequent in SSc (in 26% vs 10%, p = 0.02). fQRS occurred in 3 (7.5%) of healthy subjects only. CONCLUSION: The incidence of fQRS is similar in SSc and SLE, but is much more common than in healthy subjects. It is possible that fQRS may be considered an additional marker of heart involvement in these rare diseases.

Next-generation phylogeography resolves post-glacial colonization patterns in a widespread carnivore, the red fox (Vulpes vulpes), in Europe.

Carnivores tend to exhibit a lack of (or less pronounced) genetic structure at continental scales in both a geographic and temporal sense and this can confound the identification of post-glacial colonization patterns in this group. In this study we used genome-wide data (using genotyping by sequencing [GBS]) to reconstruct the phylogeographic history of a widespread carnivore, the red fox (Vulpes vulpes), by investigating broad-scale patterns of genomic variation, differentiation and admixture amongst contemporary populations in Europe. Using 15,003 single nucleotide polymorphisms (SNPs) from 524 individuals allowed us to identify the importance of refugial regions for the red fox in terms of endemism (e.g., Iberia). In addition, we tested multiple post-glacial recolonization scenarios of previously glaciated regions during the Last Glacial Maximum using an Approximate Bayesian Computation (ABC) approach that were unresolved from previous studies. This allowed us to identify the role of admixture from multiple source population post-Younger Dryas in the case of Scandinavia and ancient land-bridges in the colonization of the British Isles. A natural colonization of Ireland was deemed more likely than an ancient human-mediated introduction as has previously been proposed and potentially points to a larger mammalian community on the island in the early post-glacial period. Using genome-wide data has allowed us to tease apart broad-scale patterns of structure and diversity in a widespread carnivore in Europe that was not evident from using more limited marker sets and provides a foundation for next-generation phylogeographic studies in other non-model species.

Complex Admixture Preceded and Followed the Extinction of Wisent in the Wild.

Retracing complex population processes that precede extreme bottlenecks may be impossible using data from living individuals. The wisent (Bison bonasus), Europe's largest terrestrial mammal, exemplifies such a population history, having gone extinct in the wild but subsequently restored by captive breeding efforts. Using low coverage genomic data from modern and historical individuals, we investigate population processes occurring before and after this extinction. Analysis of aligned genomes supports the division of wisent into two previously recognized subspecies, but almost half of the genomic alignment contradicts this population history as a result of incomplete lineage sorting and admixture. Admixture between subspecies populations occurred prior to extinction and subsequently during the captive breeding program. Admixture with the Bos cattle lineage is also widespread but results from ancient events rather than recent hybridization with domestics. Our study demonstrates the huge potential of historical genomes for both studying evolutionary histories and for guiding conservation strategies.

The influence of habitat structure on genetic differentiation in red fox populations in north-eastern Poland.

The red fox (Vulpes vulpes) has the widest global distribution among terrestrial carnivore species, occupying most of the Northern Hemisphere in its native range. Because it carries diseases that can be transmitted to humans and domestic animals, it is important to gather information about their movements and dispersal in their natural habitat but it is difficult to do so at a broad scale with trapping and telemetry. In this study, we have described the genetic diversity and structure of red fox populations in six areas of north-eastern Poland, based on samples collected from 2002-2003. We tested 22 microsatellite loci isolated from the dog and the red fox genome to select a panel of nine polymorphic loci suitable for this study. Genetic differentiation between the six studied populations was low to moderate and analysis in Structure revealed a panmictic population in the region. Spatial autocorrelation among all individuals showed a pattern of decreasing relatedness with increasing distance and this was not significantly negative until 93 km, indicating a pattern of isolation-by-distance over a large area. However, there was no correlation between genetic distance and either Euclidean distance or least-cost path distance at the population level. There was a significant relationship between genetic distance and the proportion of large forests and water along the Euclidean distances. These types of habitats may influence dispersal paths taken by red foxes, which is useful information in terms of wildlife disease management.

Cognitive functions in patients with liver cirrhosis: a tendency to commit more memory errors.

BACKGROUND: Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE). For diagnostic purposes, 2 alternative batteries of psychometric screening tests are recommended. They differ from each other in terms of the cognitive domains assessed. The research was designed to provide a profile of cognitive functioning in patients with liver cirrhosis, using an assessment that covers a wider range of cognitive functions than the usual screening battery. MATERIAL AND METHODS: We examined 138 persons, including 88 with liver cirrhosis and 50 healthy volunteers. The Mini Mental State Examination (MMSE) was used for screening and excluding advanced cognitive impairment. Then, to assess cognitive functions in more detail, the following tests were used: Auditory Verbal Learning Test (AVLT), Letter and Semantic Fluency Tests (LF and SF), Trail Making Test (TMT A&B), Digit Symbol Test (DST), Block Design Test (BDT), and Mental Rotation Test (MRT). The MRT task has not been used in MHE diagnosis so far. Finally, 57 patients and 48 controls took part in the entire study. RESULTS: Patients with liver cirrhosis commit significantly more errors of intrusions in the AVLT during the delayed free recall trial. Results significantly deviating from the norm in at least 2 tests were found only in 7 cirrhosis patients. CONCLUSIONS: The results do not provide any specific profile of cognitive disturbances in MHE, but suggest that cirrhosis patients have a tendency to commit more memory errors, probably due to subtle impairments of executive function.

Heart Rate Variability Impairment Is Associated with Right Ventricular Overload and Early Mortality Risk in Patients with Acute Pulmonary Embolism.

The association between heart rate variability (HRV) and mortality risk of acute pulmonary embolism (APE), as well as its association with right ventricular (RV) overload is not well established. We performed an observational study on consecutive patients with confirmed APE. In the first 48 h after admission, 24 h Holter monitoring with assessment of time-domain HRV, echocardiography and NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurement were performed in all participants. We pre-examined 166 patients: 32 (20%) with low risk of early mortality, 65 (40%) with intermediate-low, 65 (40%) with intermediate-high, and 4 (0.02%) in the high risk category. The last group was excluded from further analysis due to sample size, and finally, 162 patients aged 56.3 ± 18.5 years were examined. We observed significant correlations between HRV parameters and echocardiographic signs of RV overload. SDNN (standard deviation of intervals of all normal beats) correlated with echocardiography-derived RVSP (right ventricular systolic pressure; r = -0.31, p = 0.001), TAPSE (tricuspid annulus plane systolic excursion; r = 0.21, p = 0.033), IVC (inferior vena cava diameter; r = -0.27, p = 0.002) and also with NT-proBNP concentration (r = -0.30, p = 0.004). HRV indices were also associated with APE risk stratification, especially in the low-risk category (r = 0.30, p = 0.004 for SDNN). Univariate and multivariate analyses confirmed that SDNN values were associated with signs of RV overload. In conclusion, we observed a significant association between time-domain HRV parameters and echocardiographic and biochemical signs of RV overload. Impaired HRV parameters were also associated with worse a clinical risk status of APE.

Exposing hypersensitivity in quantum chaotic dynamics.

We study hypersensitivity to initial-state perturbation in the unitary dynamics of a multiqubit system. We use the quantum state metric, introduced by Girolami and Anza [Phys. Rev. Lett. 126, 170502 (2021)0031-900710.1103/PhysRevLett.126.170502], which can be interpreted as a quantum Hamming distance. To provide a proof of principle, we take the multiqubit implementation of the quantum kicked top, a paradigmatic system known to exhibit quantum chaotic behavior. Our findings confirm that the observed hypersensitivity corresponds to commonly used signatures of quantum chaos. Furthermore, we demonstrate that the proposed metric can detect quantum chaos in the same regime and under analogous initial conditions as in the corresponding classical case.

Seasonal Adaptation: Geographic Photoperiod-Temperature Patterns Explain Genetic Variation in the Common Vole Tsh Receptor.

The vertebrate photoperiodic neuroendocrine system uses the photoperiod as a proxy to time the annual rhythms in reproduction. The thyrotropin receptor (TSHR) is a key protein in the mammalian seasonal reproduction pathway. Its abundance and function can tune sensitivity to the photoperiod. To investigate seasonal adaptation in mammals, the hinge region and the first part of the transmembrane domain of the Tshr gene were sequenced for 278 common vole (Microtus arvalis) specimens from 15 localities in Western Europe and 28 localities in Eastern Europe. Forty-nine single nucleotide polymorphisms (SNPs; twenty-two intronic and twenty-seven exonic) were found, with a weak or lack of correlation with pairwise geographical distance, latitude, longitude, and altitude. By applying a temperature threshold to the local photoperiod-temperature ellipsoid, we obtained a predicted critical photoperiod (pCPP) as a proxy for the spring onset of local primary food production (grass). The obtained pCPP explains the distribution of the genetic variation in Tshr in Western Europe through highly significant correlations with five intronic and seven exonic SNPs. The relationship between pCPP and SNPs was lacking in Eastern Europe. Thus, Tshr, which plays a pivotal role in the sensitivity of the mammalian photoperiodic neuroendocrine system, was targeted by natural selection in Western European vole populations, resulting in the optimized timing of seasonal reproduction.

Low major histocompatibility complex class I (MHC I) variation in the European bison (Bison bonasus).

Variation in the major histocompatibility complex (MHC) class I of the European bison was characterized in a sample of 99 individuals using both classical cloning/Sanger sequencing and 454 pyrosequencing. Three common (frequencies: 0.348, 0.328, and 0.283) haplotypes contain 1-3 classical class I loci. A variable and difficult to estimate precisely number of nonclassical transcribed loci, pseudogenes, and/or gene fragments were also found. The presence of additional 2 rare haplotypes (frequency of 0.020 each), observed only in heterozygotes, was inferred. The overall organization of MHC I appears similar to the cattle system, but genetic variation is much lower with only 7 classical class I alleles, approximately one-tenth of the number known in cattle and a quarter known in the American bison. An extensive transspecific polymorphism was found. MHC I is in a strong linkage disequilibrium with previously studied MHC II DRB3 gene. The most likely explanation for the low variation is a drastic bottleneck at the beginning of the 20th century. Genotype frequencies conformed to Hardy-Weinberg expectations, and no signatures of selection in contemporary populations but strong signatures of historical positive selection in sequences of classical alleles were found. A quick and reliable method of MHC I genotyping was developed.

Does magnetic resonance spectroscopy identify patients with minimal hepatic encephalopathy?

BACKGROUND AND PURPOSE: The results of a few studies suggest that magnetic resonance spectroscopy of the brain could allow detection of minimal hepatic encephalopathy. The goal of this study was to assess the ability of magnetic resonance spectroscopy to differentiate between cirrhotic patients with and without minimal hepatic encephalopathy. MATERIAL AND METHODS: Localized magnetic resonance spectroscopy was performed in the basal ganglia, occipital gray matter and frontal white matter in 46 patients with liver cirrhosis without overt encephalopathy and in 45 controls. Neurological and neuropsychological examination was performed in each participant. RESULTS: The patients with liver cirrhosis had a decreased ratio of myoinositol to creatine in occipital gray matter and frontal white matter (mean: 0.17 ± 0.05 vs. 0.20 ± 0.04, p = 0.01 and 0.15 ± 0.05 vs. 0.19 ± 0.04, p < 0.01, respectively) and a decreased ratio of choline to creatine in occipital gray matter (mean: 0.32 ± 0.07 vs. 0.36 ± 0.08, p = 0.03). Minimal hepatic encephalopathy was diagnosed in 7 patients. Metabolite ratios did not differ significantly between patients with and without minimal hepatic encephalopathy. Metabolite ratios did not differ significantly between patients with Child-Pugh A and those with Child-Pugh B. CONCLUSIONS: Magnetic resonance spectroscopy does not allow accurate diagnosis of minimal hepatic encephalopathy. A similar profile of metabolites in the brain is observed in cirrhotic patients without cognitive impairment.

Radiomics for the Prediction of Overall Survival in Patients with Bladder Cancer Prior to Radical Cystectomy.

(1) Background: To evaluate radiomics features as well as a combined model with clinical parameters for predicting overall survival in patients with bladder cancer (BCa). (2) Methods: This retrospective study included 301 BCa patients who received radical cystectomy (RC) and pelvic lymphadenectomy. Radiomics features were extracted from the regions of the primary tumor and pelvic lymph nodes as well as the peritumoral regions in preoperative CT scans. Cross-validation was performed in the training cohort, and a Cox regression model with an elastic net penalty was trained using radiomics features and clinical parameters. The models were evaluated with the time-dependent area under the ROC curve (AUC), Brier score and calibration curves. (3) Results: The median follow-up time was 56 months (95% CI: 48−74 months). In the follow-up period from 1 to 7 years after RC, radiomics models achieved comparable predictive performance to validated clinical parameters with an integrated AUC of 0.771 (95% CI: 0.657−0.869) compared to an integrated AUC of 0.761 (95% CI: 0.617−0.874) for the prediction of overall survival (p = 0.98). A combined clinical and radiomics model stratified patients into high-risk and low-risk groups with significantly different overall survival (p < 0.001). (4) Conclusions: Radiomics features based on preoperative CT scans have prognostic value in predicting overall survival before RC. Therefore, radiomics may guide early clinical decision-making.

Extremely large-mode-area photonic crystal fibre with low bending loss.

We report on the design of a novel flexible very large mode area photonic crystal fibre for short pulse high peak power fibre laser and beam delivery applications. This fibre has an extremely large mode area exceeding 2500 microm(2) when kept straight and over 1000 microm(2) when bent over a 10 cm radius at a wavelength of 1064 nm. In addition our fibre exhibits very small fundamental mode bending loss below 10(-2) dB/m. The large difference between the propagation loss levels of fundamental and higher order modes forces efficient single-mode guidance in the fibre core while bent. This allows using the fibre to build compact high power laser systems. The paper further explores the major features of this fibre including: the dependence of the mode field area on the fibre core shape, the influence of the bending radius and of the bending direction as well as the impact of manufacturing tolerances on the fibre specifications.

Highly birefringent microstructured fibers with enhanced sensitivity to hydrostatic pressure.

We designed, manufactured and characterized two birefringent microstructured fibers that feature a 5-fold increase in polarimetric sensitivity to hydrostatic pressure compared to the earlier reported values for microstructured fibers. We demonstrate a good agreement between the finite element simulations and the experimental values for the polarimetric sensitivity to pressure and to temperature. The sensitivity to hydrostatic pressure has a negative sign and exceeds -43 rad/MPa x m at 1.55 microm for both fibers. In combination with the very low sensitivity to temperature, this makes our fibers the candidates of choice for the development of microstructured fiber based hydrostatic pressure measurement systems.

Point-by-point fiber Bragg grating inscription in free-standing step-index and photonic crystal fibers using near-IR femtosecond laser.

We report what we believe to be the first highly symmetric first-order IR femtosecond laser fiber Bragg gratings within the telecommunications C band in free-standing optical fiber, fabricated with a relatively low NA lens and without use of oil immersion techniques. This grating features the smallest dimensions for a point-by-point fiber grating reported so far (to our knowledge). This achievement paves the way to rapid mass manufacturing of highly efficient and stable Bragg gratings using ultrafast lasers in any type of fiber. Mastering this femtosecond grating inscription technique also allowed the fabrication of the first Bragg gratings with direct near-IR femtosecond inscription in photonic crystal fibers, and without the use of techniques that rely on the compensation of the holey structure.

Nonlinear femtosecond pulse propagation in an all-solid photonic bandgap fiber.

Nonlinear femtosecond pulse propagation in an all-solid photonic bandgap fiber is experimentally and numerically investigated. Guiding light in such fiber occurs via two mechanisms: photonic bandgap in the central silica core or total internal reflection in the germanium doped inclusions. By properly combining spectral filtering, dispersion tailoring and pump coupling into the fiber modes, we experimentally demonstrate efficient supercontinuum generation with controllable spectral bandwidth.

Sensing characteristics of rocking filter fabricated in microstructured birefringent fiber using fusion arc splicer.

We demonstrate that higher order rocking filters coupling energy between polarization modes at several wavelengths can be fabricated in a birefringent photonic crystal fiber using a fusion arc splicer. Three resonant couplings were identified, respectively at 855, 1271, and 1623 nm for the filter with a pitch distance of 8 mm characterized in this work. We also measured the filter response to temperature, elongation and hydrostatic pressure at the first and the second resonance. Our results show that the fabricated filter has very low sensitivity to temperature 1.77 and 1.38 pm/K, moderate sensitivity to elongation 1.35 and 1.12 nm/mstrain, and extremely high sensitivity to hydrostatic pressure 6.14 and 3.30 nm/MPa, respectively at the first and the second resonance.

Design and tolerance analysis of a low bending loss hole-assisted fiber using statistical design methodology.

We present the design of a low bending loss hole-assisted fiber for a 180?-bend fiber socket application, including a tolerance analysis for manufacturability. To this aim, we make use of statistical design methodology, combined with a fully vectorial mode solver. Two resulting designs are presented and their performance in terms of bending loss, coupling loss to Corning SMF-28 standard telecom fiber, and cut-off wavelength is calculated.

Pervasive introgression facilitated domestication and adaptation in the Bos species complex.

Species of the Bos genus, including taurine cattle, zebu, gayal, gaur, banteng, yak, wisent and bison, have been domesticated at least four times and have been an important source of meat, milk and power for many human cultures. We sequence the genomes of gayal, gaur, banteng, wisent and bison, and provide population genomic sequencing of an additional 98 individuals. We use these data to determine the phylogeny and evolutionary history of these species and show that the threatened gayal is an independent species or subspecies. We show that there has been pronounced introgression among different members of this genus, and that it in many cases has involved genes of considerable adaptive importance. For example, genes under domestication selection in cattle (for example, MITF) were introgressed from domestic cattle to yak. Also, genes in the response-to-hypoxia pathway (for example, EGLN1, EGLN2 and HIF3a) have been introgressed from yak to Tibetan cattle, probably facilitating their adaptation to high altitude. We also validate that there is an association between the introgressed EGLN1 allele and haemoglobin and red blood cell concentration. Our results illustrate the importance of introgression as a source of adaptive variation and during domestication, and suggest that the Bos genus evolves as a complex of genetically interconnected species with shared evolutionary trajectories.

Selection in a cycling population: differential response among skeletal traits.

Population density cycles influence phenotypic evolution through both density-dependent selection during periods of high density and through enhanced genetic drift during periods of low density. We investigated the response of different phenotypic traits to the same density cycles in a population of the yellow-necked mouse, Apodemus flavicollis, from Bialowieza National Park in Poland. We examined nonmetric skull traits, skull and mandible size, skull and mandible shape, and transferrin allele frequencies. We found that all of the traits changed significantly over the seven-year study period. The greatest changes in nonmetric traits and mandible size occurred during periods of increasing density, and the magnitude of changes in skull and mandible shape was correlated with the magnitude of density changes. Frequencies of transferrin alleles changed the most when population density was in decline. Changes among the five phenotypic traits were generally uncorrelated with one another, except for skull and mandible shape. Nonmetric traits were selectively neutral when assessed with Q(ST)/F(ST) analysis, whereas mandible size, mandible shape, and skull shape showed evidence of fairly strong selection. Selection on skull size was weak or nonexistent. We discuss how different assumptions about the genetic components of variance affect Q(ST) estimates when phenotypic variances are substituted for genetic ones. We also found that change in mandible size, mandible shape, skull size, and skull shape were greater than expected under a neutral model given reasonable assumptions about heritability and effective population size.

Enhanced cross phase modulation instability in birefringent photonic crystal fibers in the anomalous dispersion regime.

We study Cross Phase Modulational Instability (CPMI) -a particular form of vector modulational instability- in the anomalous dispersion regime in highly birefringent, strongly dispersive optical fibers. When the pump power is high, the detuning of the Scalar Modulational Instability (SMI) is comparable to the detuning of the CPMI. The gain of the CPMI -which is usually much smaller than the gain of the SMI-, is then strongly enhanced and becomes much larger than the gain of the SMI. This theoretical prediction is well verified experimentally using small core photonic crystal fibers.