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Objective We investigated the association between the pattern and duration of pelvic venous reflux (PVR) and pelvic pain severity in patients with pelvic varicose veins (PVVs). Methods The present retrospective study included 600 female patients with PVVs. Of the 600 patients, 453 had had PVVs and pelvic congestion syndrome (group 1) and 147 had had an asymptomatic disease course (group 2). Pelvic venous pain (PVP) was assessed using a visual analog scale. All the patients had undergone duplex ultrasound of the left and right renal veins, external, internal, and common iliac veins, and parametrial, uterine, gonadal, and vulvar veins (PV, UV, GV, and VV, respectively), with an assessment of their patency and diameter and the presence and duration of reflux. Reflux in the pelvic veins was considered pathologic if it lasted for >1 second. Results In group 1, PVR type I (1-2 seconds), II (3-5 seconds), and III (>5 seconds or spontaneous reflux in the absence of a loading test) was found in 31%, 58%, and 11% of the patients, respectively. Moderate and severe reflux (types II and III) was associated with severe PVP (mean score, 8.3 ± 0.5) in 69% of the group 1 patients. A combination of reflux in the GV, PV, UV, and internal iliac vein was associated with severe PVP (mean score, 8.1 ± 0.3) in 51% of these patients. A combination of reflux in the PVs, UVs, and VVs was associated with moderate pain (mean score, 5.3 ± 0.2) in 49.2% of group 1. In group 2, PVR type I, II, and III was present in 95%, 4%, and 1% of the patients, respectively, and was observed in the PV only in patients with type I; in the GVs, PVs, UVs, and internal iliac veins in those with type II; and in the PVs and GVs in the patients with type III reflux. Reflux in the GVs and UVs was significantly more prevalent in group 1 than in group 2 (GVs, 51% vs 6%; P = .0001; UVs, 57% vs 7%; P = .0001). A combination of reflux in the GVs and UVs was a predictor of severe PVVs (odds ratio, 19.7; 95% confidence interval, 11.3-34.6). Conclusions In patients with PVVs, the presence and severity of pelvic pain will be determined by the type of PVR and its distribution in the pelvic veins. The combination of moderate to severe reflux (types II and III) in the PVs, UVs, and GVs was a predictor of severe PVP. Patients with asymptomatic PVVs were characterized by mild reflux (type I) in the PVs, with rare involvement of the GVs and UVs.

The two species of rock lizards, Darevsia raddei and Darevskia portschinskii, belong to two different phylogenetic clades of the same genus. They are supposed ancestors for the hybrid parthenogenetic, Darevskia rostombekowi. The present study aims to identify morphological features of these two species and the potential gene introgression between them in the area of sympatry. External morphological features provided the evidence of specific morphology in D. raddei and D. portschinskii: the species differed in scalation and ventral coloration pattern, however, they had some proportional similarities within both sexes of the two species. Males of both species had relatively larger heads and shorter bodies than females. Males of D. raddei were slightly larger than males of D. portschinskii and had longer hindlimbs. Microsatellite genotyping revealed no traces of hybridization or gene flow among these species. We suggest that the absence of individuals with combined morphological and genetic features of the studied species reflects existing reproductive barriers. The hybridization between two bisexual rock lizard species from distant clades is rare and only takes place under very specific environmental conditions.

Objective There is growing interest in expanding patient access to Internet-Based Cognitive Behavioral Therapy (ICBT). In order to inform policies to improve ICBT access, this study explored attitudinal (e.g., stigma), structural (e.g., access to care) and ICBT specific (e.g., computer anxiety) barriers to rural and urban patient interest in ICBT. Methods This cross-sectional observational study was conducted among adult (>18 years) urban and rural residents (n = 200) in Saskatchewan, Canada. An online survey assessed interest in ICBT, nine barriers to ICBT, demographics, and depression and anxiety symptoms. Results Multivariable linear regression analyses were conducted and revealed that participants with lower self-stigma of seeking help and higher perceived need for mental health treatment (attitudinal barriers), and participants with lower access to care (structural barrier) and lower computer anxiety (ICBT-specific barrier) showed significantly greater interest in ICBT. Participants with financial concerns, life chaos, and participants who reported greater preference for autonomy (attitudinal barrier) did not report significant interest in ICBT. Conclusions To increase uptake of ICBT, the findings point towards several policy implications, including aligning ICBT towards individuals with lower access to care and higher perceived needs, and allocating resources for strategies to decrease computer anxiety and self-stigma of seeking help.

International audience; Viruses depend on the host cell translation machinery for their replication, and one common strategy is the presence of internal ribosome entry sites (IRESs) in the viral RNAs, using different sets of host translation initiation factors. The hepatitis C virus (HCV) IRES binds eukaryotic translation initiation factor 3 (eIF3), but the exact functional role of the eIF3 complex and of its subunits remains to be precisely defined. Toward this goal, here we focused on eIF3 subunit e. We used an in vitro assay combining a ribosome-depleted rabbit reticulocyte lysate and ribosomes prepared from HeLa or Huh-7.5 cells transfected with either control or eIF3e siRNAs. eIF3e silencing reduced translation mediated by the 5'UTR of various cellular genes and HCV-like IRESs. However, this effect was not observed with the bona fide HCV IRES. Silencing of eIF3e reduced the intracellular levels of the c, d, and l subunits of eIF3 and their association with the eIF3 core subunit a. A pulldown analysis of eIF3 subunits associated with the HCV IRES disclosed similar effects and that the a subunit is critical for binding to the HCV IRES. Carrying out HCV infections of control and eIF3e-silenced Huh-7.5 cells, we found that in agreement with the in vitro findings, eIF3e silencing does not reduce HCV replication and viral protein expression. We conclude that unlike for host cellular mRNAs, the entire eIF3 is not required for HCV RNA translation, favoring viral expression under conditions of low eIF3e levels.

The Gibbard–Satterthwaite theorem roughly states that we have to accept dictatorship or manipulability in case of at least three alternatives. A large strand of the literature estimates the degree of manipulability of social choice functions (e.g. Aleskerov and Kurbanov (1999), Favardin et al. (2002), and Aleskerov et al. (2012)), most of them employing the Nitzan–Kelly index of manipulability. We take a different approach and introduce a non-dictatorship index based on our recent work Bednay et al. (2017), where we have analysed social choice functions based on their distances to the dictatorial rules. By employing computer simulations, we investigate the relationship between the manipulability and non-dictatorship indices of some prominent social choice functions, putting them into a common framework.

In order to understand of the processes controlling phytoplankton successions in the NE Black Sea, long-term data series are needed. We compiled 15 years (2002–2017) of measurements from which the existence emerges of a tight link between phytoplankton species dominance and nutrients concentrations. The latter is strongly influenced by wind direction. The link between algal dominance and nutrients is mediated by the growth strategy adopted by algal species. In spring, when nutrients are abundant, small diatoms such as Pseudo-nitzschia pseudodelicatissima, with a “rapid growth strategy”, prevail. In late spring and early summer, when N is low and P and Si are high, coccolithophorids such as Emiliania huxhleyi dominate, thanks to an “affinity growth strategy”. Large diatoms, especially Pseudosolenia calcar-avis, dominate in summer and autumn, when their “storage growth strategy” allows the exploitation of discontinuous upwelling of nutrients. These seasonal changes of dominant species influence the structure of the food web.

We reveal the main characteristics of noise-induced intermittency in a dynamical system with two coexisting attractors. Both the residence time distributions and the mean residence time versus an asymmetry parameter, are found analytically, for each of the coexisting states, and both of them obey exponential laws. The proposed theory is applied to a bistable energy model, dissipatively coupled logistic maps and bistable Chua generator.

The possible formation of two-dimensional (2D) magnetic biexcitons composed of two 2D magnetoexcitons with electrons and holes on the lowest Landau levels (LLLs) with opposite center-of-mass wave vectors k → and − k → and with antiparallel electric dipole moments perpendicular to the corresponding wave vectors was investigated. Two spinor structures of two electrons and of two holes were considered. In the singlet-singlet state the spins of two electrons as well as the effective spins of two holes create the combinations with the total spin S = 0 and its projection on the magnetic field S z = 0 . The triplet-triplet state corresponds to S = 1 and S z = 0 . Two orbital Gaussian variational wave functions depending on | k → | and describing the relative motion of two magnetoexcitons inside the molecule were used. Analytical calculations show that in the LLLs approximation the stable bound states of bimagnetoexcitons do not exist, but there is a metastable bound state with the orbital wave function, having the maximum on the in-plane ring for the triplet-triplet spin configuration. The metastable bound state has an energy activation barrier comparable with the magnetoexciton ionization potential and gives rise to the new luminescence band due to the metastable biexciton-para exciton conversion with the frequencies higher than those of the para magnetoexciton luminescence line.

Based on the linear perturbation technique, an equation was derived for the prediction of hydrodynamic stability criteria in vapor layers formed at boiling of nanofluids in the inverse annular-dispersed regime. The equations were obtained in two-dimensional and three-dimensional approximations. A solution of the eigenvalue problem enabled determining criteria of hydrodynamic stability. For the first time, a complete analysis of the thermal-hydrodynamic instability of a vapor layer near a vertical surface has been performed based on the Orr-Sommerfeld approach, where not only the perturbed momentum equation, but also the perturbed energy equation and the perturbed convective-diffusion equation for the nanoparticle concentration were analyzed. This approach accounts for the influence of the unperturbed velocity, temperature, and nanoparticle concentration profiles. The analytical solution for the vapor film stability criteria was validated against experimental studies of the effects of nanoparticles on formation and destruction of a vapor film emerged in nanofluid boiling on the surface of a metal probe during unsteady cooling. In experiments, nanoparticles caused destabilizing influence on the vapor film during boiling.

Information on cosmic-ray (CR) composition comes from direct CR measurements while their distribution in the Galaxy is evaluated from observations of their associated diffuse emission in the range from radio to gamma rays. Even though the main interaction processes are identified, more and more precise observations provide an opportunity to study more subtle effects and pose a challenge to the propagation models. GALPROP is a sophisticated CR propagation code that is being developed for about 20 years. It provides a unified framework for interpretations of data from many different types of experiments. It is used for a description of direct CR measurements and associated interstellar emissions (radio to gamma rays), thereby providing important information about CR injection and propagation in the interstellar medium. By accounting for all relevant observables at a time, the GALPROP code brings together theoretical predictions, interpretation of the most recent observations, and helps to reveal the signatures of new phenomena. In this paper we review latest applications of GALPROP and address ongoing and near future improvements. We are discussing effects of different propagation models, and of the transition from cylindrically symmetrical models to a proper 3D description of the components of the interstellar medium and the source distribution., Comment: 6 pages, 5 figures. Proceedings of the Conference "Cosmic Ray Origin - beyond the standard models", San Vito di Cadore (Dolomites, Italy) 18-24 September 2016. Accepted version to be published in Nuclear and Particle Physics (Elsevier)

In attempt to improve the performance of a recently proposed hybrid human-machine interface, the eye-brain-computer interface (EBCI), we applied a compact convolutional neural network, the EEGNet, to short electroencephalogram (EEG) segments obtained during spontaneous and intentional gaze fixations, without the feature extraction step prior to classification. A statistically significant improvement of classification performance was obtained compared to with the results of the classifier previously used in the EBCI paradigm, which was based on shrinkage linear discriminant analysis (sLDA). Computation speed allows for using the EEGNet in the EBCI in online mode.

PURPOSE/OBJECTIVE(S) Recent data support the use of total neoadjuvant therapy (TNT) for treatment of locally advanced rectal cancer (LARC), although the optimal TNT regimen and therapy sequence is unclear for non-operative management (NOM). We performed a multi-institutional comparison of short-course radiation (SCRT) followed by consolidation chemotherapy (SC-TNT) versus long-course chemoradiation (CRT) preceded by induction chemotherapy (LC-TNT), after adoption of NOM at both institutions. MATERIALS/METHODS The records of 187 patients with cT2-4N0-2 rectal cancer treated between 2016-2020 with TNT at two academic institutions were reviewed under an IRB-approved protocol. The SC-TNT cohort (institution 1) included 85 patients treated with SCRT (25-30 Gy in 5 fx) followed by FOLFOX/CAPOX (n = 82) or capecitabine (n = 3). The LC-TNT cohort (institution 2) included 102 patients treated with FOLFOX/CAPOX followed by CRT (45-56 Gy at 1.8-2 Gy/fx) with concurrent fluoropyrimidine-based chemotherapy. Patients with a clinical complete response (cCR) were offered NOM. The rates of cCR were compared between SC- and LC-TNT. Disease-free survival (DFS) was compared using the log-rank test. To account for any differences in NOM selection between institutions, local-only tumor regrowth was censored from DFS if salvaged with R0 resection, and the overall complete response (CR) rate, defined as cCR + pCR rate for patients undergoing surgery, was assessed. Multivariate analysis (MVA) was performed with logistic and Cox regression to determine factors associated with CR and DFS, respectively. RESULTS The median age at diagnosis was 60 and 54 years for SC-TNT and LC-TNT cohorts, respectively (P = 0.002). All other characteristics including performance status, tumor location, and clinical stage were balanced. The median duration of neoadjuvant FOLFOX/CAPOX chemotherapy was 105 vs 98 days for the SC-TNT and LC-TNT cohorts, respectively (P = 0.001). The median follow-up was 27 months. The cCR rate was higher in the SC-TNT cohort (44/85, 52.8% vs 21/102, 20.6%, P < 0.001), with a trend for improved CR rate for SC-TNT (54.1% vs 40.2%, P = 0.057). On MVA, use of SC-TNT was associated with improved CR (HR = 2.24, 95% CI: 1.13-4.45, P = 0.021). Among patients undergoing NOM, 33/39 patients (84.6%) in the SC-TNT group and 10/17 patients (58.8%) in the LC-TNT group (P = 0.27) were free from local recurrence at 1 year. Two-year DFS was 93.4% and 95.4% for the SC-TNT and LC-TNT cohorts with improved DFS on log-rank test for LC-TNT (P = 0.023), but no DFS difference on MVA between SC-TNT and LC-TNT (HR = 2.29, 95% CI: 0.8-6.51, P = 0.121). CONCLUSION SC-TNT demonstrated a greater rate of cCR compared to LC-TNT, without DFS difference on MVA. Although future studies are warranted to compare SC-TNT with a CRT and consolidative chemotherapy TNT approach, our data support SC-TNT as a suitable regimen for LARC NOM.

The major drawback of the Baculovirus/Sf9 system for recombinant adeno-associated viral (rAAV) manufacturing is that most of the Bac-derived rAAV vector serotypes, with few exceptions, demonstrate altered capsid compositions and lower biological potencies. Here, we describe a new insect cell-based production platform utilizing attenuated Kozak sequence and a leaky ribosome scanning to achieve a serotype-specific modulation of AAV capsid proteins stoichiometry. By way of example, rAAV5 and rAAV9 were produced and comprehensively characterized side by side with HEK293-derived vectors. A mass spectrometry analysis documented a 3-fold increase in both viral protein (VP)1 and VP2 capsid protein content compared with human cell-derived vectors. Furthermore, we conducted an extensive analysis of encapsidated single-stranded viral DNA using next-generation sequencing and show a 6-fold reduction in collaterally packaged contaminating DNA for rAAV5 produced in insect cells. Consequently, the re-designed rAAVs demonstrated significantly higher biological potencies, even in a comparison with HEK293-manufactured rAAVs mediating, in the case of rAAV5, 4-fold higher transduction of brain tissues in mice. Thus, the described system yields rAAV vectors of superior infectivity and higher genetic identity providing a scalable platform for good manufacturing practice (GMP)-grade vector production.

Widespread degradation of ice wedges has been observed during the last decades in numerous areas within the continuous permafrost zone of Eurasia and North America. To study ice-wedge degradation, we performed field investigations at Prudhoe Bay and Barrow in northern Alaska during 2011–2016. In each study area, a 250-m transect was established with plots representing different stages of ice-wedge degradation/stabilization. Field work included surveying ground- and water-surface elevations, thaw-depth measurements, permafrost coring, vegetation sampling, and ground-based LiDAR scanning. We described cryostratigraphy of frozen soils and stable isotope composition, analyzed environmental characteristics associated with ice-wedge degradation and stabilization, evaluated the vulnerability and resilience of ice wedges to climate change and disturbances, and developed new conceptual models of ice-wedge dynamics that identify the main factors affecting ice-wedge degradation and stabilization and the main stages of this quasi-cyclic process. We found significant differences in the patterns of ice-wedge degradation and stabilization between the two areas, and the patterns were more complex than those previously described because of the interactions of changing topography, water redistribution, and vegetation/soil responses that can interrupt or reinforce degradation. Degradation of ice wedges is usually triggered by an increase in the active-layer thickness during exceptionally warm and wet summers or as a result of flooding or disturbance. Vulnerability of ice wedges to thermokarst is controlled by the thickness of the intermediate layer of the upper permafrost, which overlies ice wedges and protects them from thawing. In the continuous permafrost zone, degradation of ice wedges rarely leads to their complete melting; and in most cases wedges eventually stabilize and can then resume growing, indicating a somewhat cyclic and reversible process. Stabilization of ice wedges after their partial degradation makes them better protected than before degradation because the intermediate layer is usually 2 to 3 times thicker on top of stabilized ice wedges than on top of initial ice wedges in undisturbed conditions. As a result, the likelihood of formation of large thaw lakes in the continuous permafrost zone triggered by ice-wedge degradation alone is very low.