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The accurate representation of multidimensional potential energy surfaces is a necessary requirement for realistic computer simulations of molecular systems. The continued increase in computer power accompanied by advances in correlated electronic structure methods nowadays enables routine calculations of accurate interaction energies for small systems, which can then be used as references for the development of analytical potential energy functions (PEFs) rigorously derived from many-body (MB) expansions. Building on the accuracy of the MB-pol many-body PEF, we investigate here the performance of permutationally invariant polynomials (PIPs), neural networks, and Gaussian approximation potentials (GAPs) in representing water two-body and three-body interaction energies, denoting the resulting potentials PIP-MB-pol, Behler-Parrinello neural network-MB-pol, and GAP-MB-pol, respectively. Our analysis shows that all three analytical representations exhibit similar levels of accuracy in reproducing both two-body and three-body reference data as well as interaction energies of small water clusters obtained from calculations carried out at the coupled cluster level of theory, the current gold standard for chemical accuracy. These results demonstrate the synergy between interatomic potentials formulated in terms of a many-body expansion, such as MB-pol, that are physically sound and transferable, and machine-learning techniques that provide a flexible framework to approximate the short-range interaction energy terms. [ABSTRACT FROM AUTHOR]

We carried out extensive calculations of liquid water at different temperatures and pressures using the BK3 model suggested recently [P. T. Kiss and A. Baranyai, J. Chem. Phys. 138, 204507 (2013)]. In particular, we were interested in undercooled regions to observe the propensity of water to form tetrahedral coordination of closest neighbors around a central molecule. We compared the found tetrahedral order with the number of hydrogen bonds and with the partial pair correlation functions unfolded as distributions of the closest, the second closest, etc. neighbors. We found that contrary to the number of hydrogen bonds, tetrahedrality changes substantially with state variables. Not only the number of tetrahedral arrangements increases with lowering the pressure, the density, and the temperature but the domain size of connecting tetrahedral structures as well. The difference in tetrahedrality is very pronounced between the two sides of the Widom line and even more so between the low density amorphous (LDA) and high density amorphous (HDA) phases. We observed that in liquid water and in HDA, the 5th water molecule, contrary to ice and LDA, is positioned between the first and the second coordination shell. We found no convincing evidence of structural heterogeneity or regions referring to structural transition. [ABSTRACT FROM AUTHOR]

We exploited the possibility to unfold the oxygen–oxygen pair-correlation function of liquid water modeled by the BK3 force field into distributions of the first, second, third, etc. neighbors of the central water molecule. Especially, we were interested in the 5th neighbor because its position is halfway between the first and the second coordination spheres. We found that each molecule has three tightly hydrogen bonded neighbors, a loosely bonded 4th neighbor and sometimes a non-tetrahedral 5th molecule which is a proton donor. We determined lifetimes of first shell molecules, the average reorientation or “jump” time, and the time needed to change the order of neighbors. Certain molecules can be 5th neighbors of more centers which may create multiple overlaps of first coordination shells. The density increase of water relative to hexagonal ice is caused by these overlaps and the hydrogen bond of the 5th molecule. This possibility also plays a role in fluctuations or makes possible the adaptation to high external pressure as well. [ABSTRACT FROM AUTHOR]

Little is known about the development of children’s lying. The present study examined whether observed social and non-social fear in preschoolers predicts children’s consistent cheating (N = 460; M = 4.3 years of age) and consistent lying about cheating. When left alone, 155 (34%) children cheated in both games conducted. Of these consistently cheating children, 54 (35%) children lied about their cheating after both games, whereas the remaining 101 children confessed to cheating after at least one game. Children’s temperamental fear did not predict consistent cheating. However, non-social (but not social) fear did predict consistent lying. Children with lower levels of non-social fear were more likely to lie. These findings suggest that non-social fear plays a role in the development of children’s antisocial lying. [ABSTRACT FROM AUTHOR]

Temperament and psychopathology are intimately related; however, research on the prospective associations between positive emotionality, defined as a child's positive mood states and high engagement with the environment, and psychopathology is inconclusive. We examined the longitudinal relation between positive emotionality and internalizing problems in young children from the general population. Furthermore, we explored whether executive functioning mediates any observed association. Within a population-based Dutch birth cohort, we observed positive emotionality in 802 children using the laboratory temperament assessment battery at age 3 years. Child behavior checklist (CBCL) internalizing problems (consisting of Emotionally Reactive, Anxious/Depressed, and Withdrawn scales) were assessed at age 6 years. Parents rated their children's executive functioning at ages 4 years. Children with a lower positive emotionality at age 3 had a higher risk of withdrawn problems at age 6 years (OR = 1.20 per SD decrease in positive emotionality score, 95 % CI: 1.01, 1.42). This effect was not explained by preexisting internalizing problems. This association was partly mediated by more problems in the shifting domain of executive functioning ( p < 0.001). We did not find any relation between positive emotionality and the CBCL emotionally reactive or anxious/depressed scales. Although the effect sizes were moderate, our results suggest that low levels of positive emotionality at preschool age can result in children's inflexibility and rigidity later in life. The inflexibility and rigidity are likely to affect the child's drive to engage with the environment, and thereby lead to withdrawn problems. Further research is needed to replicate these findings. [ABSTRACT FROM AUTHOR]

The purpose of this study is to examine whether maternal depressive symptoms predict low positive emotionality and high temperamental fearfulness in preschool children. Maternal depressive symptoms were assessed prenatally and at 2, 6, and 36 months postnatally. Positive emotionality and temperamental fearfulness were assessed using laboratory observations in a large cohort of typically developing Dutch preschoolers (N = 799; 404 boys) at age 36 months (M = 37.53,SD = 1.50). Children exposed to elevated levels of maternal depressive symptoms in the first 3 years of life behaved less fearfully at age 3 years in a novel context that primarily elicited a startle response (B = −0.08,SE = 0.03,p = .01). The severity rather than timing of or change in maternal depressive symptoms accounted for the observed effect. In the present sample, maternal depressive symptoms were not associated with positive emotionality in the offspring (p > .05). Findings suggest a relation between maternal depressive symptoms and decreased offspring fearfulness in a low-risk community sample of young children. [ABSTRACT FROM AUTHOR]

Altered patterns of facial expression recognition ( FER) have been linked to internalizing and externalizing problems in school children and adolescents. In a large sample of preschoolers ( N = 727), we explored concurrent and prospective associations between internalizing/externalizing problems and FER. Internalizing/externalizing problems were rated by parents at 18 and 36 months using the Child Behavior Checklist. FER was assessed at 36 months using age-appropriate computer tasks of emotion matching and emotion labeling. Internalizing problems were associated with emotion-specific differences at both ages: at 18 months they predicted more accurate labeling of sadness; at 36 months they were associated with less accurate labeling of happiness and anger. Externalizing problems at both ages were associated with general FER deficits, particularly for matching emotions. Findings suggest that in preschoolers, internalizing problems contribute to emotion-specific differences in FER, while externalizing problems are associated with more general FER deficits. Knowledge of the specific FER patterns associated with internalizing/externalizing problems can be proven useful in the refinement of emotion-centered preventive interventions. [ABSTRACT FROM AUTHOR]

A vast body of literature shows that maternal depression has long-term adverse consequences for children. However, only very few studies have documented the effect of maternal depression on children's ability to process emotional expressions and even fewer incorporated measures of observed maternal sensitivity to further tease apart whether it is the symptoms per se or the associated impact via maternal sensitivity that affects children's developing emotion-processing abilities. In a large community sample of Dutch preschoolers (N = 770), we examined independent and mediated effects of maternal depressive symptoms and sensitivity on children's ability to recognize emotional expressions using a nonverbal and a verbal task paradigm. Maternal depressive symptoms predicted less accurate emotion labeling in children, while maternal sensitivity was associated with more accurate emotion matching, especially for sadness and anger. Maternal sensitivity did not mediate the observed associations between mothers’ depressive symptoms and children's emotion recognition, and effects were similar for boys and girls. Given that maternal depressive symptoms and sensitivity affected nonoverlapping areas of young children's emotion recognition, prevention and intervention efforts should focus on both alleviating maternal depressive symptoms and improving maternal sensitivity at the same time in order to maximize benefit. [ABSTRACT FROM AUTHOR]

Background: Previous research highlights the significance of a functional polymorphism located in the promoter region (5-HTTLPR) of the serotonin transporter gene in emotional behaviour. This study examined the effect of the 5-HTTLPR polymorphism on emotion processing in a large number of healthy preschoolers. Methods: The 5-HTTLPR genotype was classified in 605 children as homozygous for the short allele (SS), homozygous for the long allele (LL), or heterozygous (LS). Emotion-processing was assessed using age-appropriate computer tasks where children matched happy, sad, angry, and fearful facial expressions preceded by a shape-matching task to assess basic matching ability. Results: We found that young children could differentiate between emotion categories ( F = 12.1, p < .001). The effect of 5-HTTLPR genotype depended on the emotion category presented ( F = 2.3, p = .031). This effect was explained by the finding that SS children were less accurate at recognising fearful faces than LL or LS children ( F = 5.3, p = .005). We did not find any significant differences as a result of 5-HTTLPR genotype for happy, sad or angry expressions ( p > .05). Conclusions: Results indicate that 5-HTTLPR allele status selectively impacts the processing of fearful but not other facial expressions. This pattern is already apparent in very young typically developing children. Results may signal an early vulnerability for affective problems before disorders emerge. [ABSTRACT FROM AUTHOR]

From a developmental perspective, it has been reasoned that over the course of development children make differential use of available landmarks in the surroundings to orient in space. The present study examined whether children can learn to apply different spatial strategies, focusing on different landmark cues. Children aged 7 and 10 years were tested on an object-location memory task in which they learned a location relative to a direct cue or to indirect cues. Both age groups performed equally well on the direct test condition. However, children 7 years of age had difficulties with orienting relative to the indirect landmarks. Interestingly, their performance increased significantly with more relevant experience. Different explanations for these findings are discussed. [ABSTRACT FROM AUTHOR]

Splenic hamartoma is a rare benign vascular lesion of the spleen. A splenic mass was incidentally detected in an asymptomatic 65-year-old male during an abdominal ultrasound scan. The workup of the splenic lesion included an abdominal CT angiography (CTA), contrast-enhanced ultrasound (CEUS), and microvascular flow imaging Doppler sonography. The CT scan confirmed that the splenic mass had benign characteristics, and its contrast enhancement was similar to the spleen. The CEUS was able to rule out the possibility of hemangioma. Meanwhile, chronic compression of the celiac trunk and the filling of the splenic artery from collaterals were also detected on CTA. The imaging studies suggested a splenic hamartoma, and the diagnosis was confirmed by the result of a fine needle aspiration biopsy. [ABSTRACT FROM AUTHOR]

Simple Summary: The addition of chromosome 17 polysomy/HER2 amplification status to the updated EAU and AUA scores improves their accuracy, allowing molecular reclassification of EAU high-risk NMIBCs and G2 tumors. Based on this, we propose to reclassify the non-HER2 amplified, non-polysomic EAU 3–4 (high- and very high-risk) cases to the EAU 2 (intermediate) risk group to prevent unnecessarily strict follow-up and treatment for these patients. Furthermore, to classify Chr17 polysomic and/or HER2 amplified G2 tumors as high-grade (HG) and non-HER2 amplified, non-polysomic G2 tumors as low-grade (LG) NMIBCs (G1 and G3 tumors remain graded as low- and high-grade, respectively). Thus, the implementation of Chr17 polysomy/HER2 amplification testing would provide an immediate and simple solution to further refine the prognostic risk assessment of NMIBCs in the uro-oncology practice. Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) significantly worsens life expectancy. Its risk can be assessed by clinicopathological factors according to international guidelines. However, additional molecular markers are needed to refine and improve the prediction. Therefore, in the present study, we aimed to predict the progression of NMIBCs to MIBC by assessing p53 expression, polysomy of chromosome 17 (Chr17) and HER2 status in the tissue specimens of the tumors of 90 NMIBC patients. Median follow-up was 77 months (range 2–158). Patients with Chr17 polysomy or HER2 gene amplification had a higher rate of disease progression (hazard ratio: 7.44; p < 0.001 and 4.04; p = 0.033, respectively; univariate Cox regression). Multivariable Cox regression models demonstrated that the addition of either Chr17 polysomy or HER2 gene amplification status to the European Association of Urology (EAU) progression risk score increases the c-index (from 0.741/EAU/ to 0.793 and 0.755, respectively), indicating that Chr17 polysomy/HER2 amplification status information improves the accuracy of the EAU risk table in predicting disease progression. HER2/Chr17 in situ hybridization can be used to select non-progressive cases not requiring strict follow-up, by reclassifying non-HER2-amplified, non-polysomic NMIBCs from the high- and very high-risk groups of EAU to the intermediate-risk group. [ABSTRACT FROM AUTHOR]

Purpose: The presence of cervical lymph node metastases is one of the most influential prognostic factors in head and neck squamous cell carcinomas. The management of clinically N0 neck in patients with head and neck cancer remains controversial: elective neck dissection has relatively high morbidity, adversely affecting the quality of life, however, abandoning elective neck dissection is known to compromise overall survival in numerous primaries. The purpose of this study was to evaluate the accuracy of the conventional imaging modalities (CT, MRI, US) and fine-needle aspiration cytology (FNAC) in the detection of lymph node metastases in the neck. Methods: Sixty two patients were included in the study, who underwent primary tumor resection and neck dissection. Preoperative nodal status was compared with postoperative histopathology nodal status. In our retrospective study, we reviewed the patient documentation. Statistical analysis of the data—with descriptive statistics and correlation analysis—was performed with Chi-square test. Results: The sensitivity of conventional imaging modalities and FNAC were 82.8% and 81.8%, respectively, while specificity were 73.9% and 100%, respectively. Positive predictive value calculated for imaging modalities and FNAC were 82.8%, 100%, respectively, while negative predictive values were 73.9% and 66.6%, respectively. Conclusion: Neither the sensitivity of imaging modalities (CT, MRI, US) nor FNAC reached 100%, none of these methods can definitively exclude the presence of regional tumor metastasis. According to these data, no permissive alteration should be allowed from the current guidelines (e.g. NCCN) based on imaging/FNAC examinations regarding the need for elective neck dissection. [ABSTRACT FROM AUTHOR]

The authors present the case of a 52-year-old man who had recurring scrotal abscesses resulting in oncotomy being carried out seven times within 2 years. Eventually, it was dissected out totally. Histology proved anaplastic cancer metastasis. The primary tumor was detected in the bronchia; moreover, metastases were found in other organs as well. The patient died 6 weeks after the first diagnosis. We intended to draw attention to frequently occurring scrotal inflammation and thus the underlying diseases. We emphasize the importance of histology examinations. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to predict progression of non-muscle-invasive bladder urothelial carcinomas (NMIUCs) into muscle-invasive disease by assessing cytogenetic abnormality of tumors with a new UroVysion scoring system.Methods: Seventy-five bladder cancer cases (including 57 NMIUCs) were classified according to the quantitatively assessed degree of UroVysion-detected chromosomal abnormalities into urine fluorescence in situ hybridization score (UFS) groups: UFS I, II, and III. Cox time-to-event, Kaplan-Meier, and C-statistics analyses were performed.Results: UFS proved to be an independent prognostic factor of progression-free survival (PFS) and time to progression (TTP). NMIUCs with UFS III had a 34.05-fold increased hazard for progression to muscle-invasive cancer (TTP; 95% confidence interval, 5.841-198.5; P < .001) in comparison with UFS I to II cases. The addition of UFS to conventional risk scores increased the C-index for PFS and TTP.Conclusions: UFS can indicate an increased risk for progression into muscle-invasive disease in patients with NMIUC and improves prognostic accuracy of the current clinical risk assessment systems. [ABSTRACT FROM AUTHOR]

Background Little is known about the genetic determinants of sensitive parenting. Two earlier studies examined the effect of the serotonin transporter polymorphism (5- HTTLPR) on sensitive parenting, but reported opposite results. In a large cohort we further examined whether 5- HTTLPR is a predictor of observed maternal sensitivity and whether observed child social fearfulness moderates the effect of 5- HTTLPR on maternal sensitivity. Methods The population-based cohort consisted of 767 mother-child dyads. Maternal sensitivity was repeatedly observed at the child's age of 14 months, 36 months and 48 months. Sensitivity was coded using the Ainsworth's rating scales for sensitivity and cooperation and the revised Erickson rating scales for Supportive presence and Intrusiveness. Child social fearfulness was observed using the Stranger Approach episode of the Laboratory Temperament Assessment Battery at 36 months. Results Repeated measurement analyses showed a consistent main effect of maternal 5- HTTLPR on sensitivity; mothers carrying the S-allele were more sensitive toward their children ( p = .005). This effect was not explained by the child's 5- HTTLPR genotype. We found no evidence that child social fearfulness moderated the effect of 5- HTTLPR on sensitivity. Conclusions This study suggests that variations in maternal 5- HTTLPR genotype appear to be involved in the etiology of parenting behavior. The observed effects of this genetic variation are consistent with the notion that parenting may have a genetic component, but large studies are needed to find the specific small molecular effects. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the patterns of expression of the junctional proteins β-catenin and claudins in different prognostic groups of patients with prostatic cancer, to determine their value as prognostic markers. PATIENTS AND METHODS We evaluated the samples of 30 patients who had a radical prostatectomy for organ-confined cancer (pT2N0M0), men with clinically advanced cancer, and a control group with benign prostatic hyperplasia. Using immunohistochemistry applied to tissue microarrays, each group was evaluated for claudin-1, -2, -3, -4, -5, -7, -8 and -10, and β-catenin expression. RESULTS There were differences among the three groups in the expression of claudin-1 ( P = 0.001), -2 ( P = 0.014), -3 ( P = 0.027), -4 ( P = 0.001), -8 ( P = 0.001) and β-catenin ( P = 0.002), regardless of Gleason score. By contrast, claudin-5, -7 and -10 patterns were not significantly different among the groups. Furthermore, claudin-1 ( P = 0.014) and -4 ( P = 0.004) could be used to distinguish between those patients who had metastases and those who did not. CONCLUSIONS The pattern of claudin expression could be a novel diagnostic marker in re-classifying adenocarcinomas, and an additional sensitive predictive factor for a clinically poor prognosis. Our results suggest that patients with organ-confined and advanced cancer are subsets with distinct claudin expression profiles, and that claudin-4 is related to cellular differentiation in prostate cancer, which is not only the receptor molecule for the Clostridium perfringens enterotoxin, and thus a theoretical future therapeutic target for prostate cancer, but also a marker of progression. [ABSTRACT FROM AUTHOR]

Puberty represents the phase of sexual maturity, signaling the change from childhood into adulthood. During childhood and adolescence, prominent changes take place in the brain. Recently, variation in frontal, temporal, and parietal areas was found to be under varying genetic control between 5 and 19 years of age. However, at the onset of puberty, the extent to which variation in brain structures is influenced by genetic factors (heritability) is not known. Moreover, whether a direct link between human pubertal development and brain structure exists has not been studied. Here, we studied the heritability of brain structures at 9 years of age in 107 monozygotic and dizygotic twin pairs ( N = 210 individuals) using volumetric MRI and voxel-based morphometry. Children showing the first signs of secondary sexual characteristics ( N = 47 individuals) were compared with children without these signs, based on Tanner-stages. High heritabilities of intracranial, total brain, cerebellum, and gray and white matter volumes (up to 91%) were found. Regionally, the posterior fronto-occipital, corpus callosum, and superior longitudinal fascicles (up to 93%), and the amygdala, superior frontal and middle temporal cortices (up to 83%) were significantly heritable. The onset of secondary sexual characteristics of puberty was associated with decreased frontal and parietal gray matter densities. Thus, in 9-year-old children, global brain volumes, white matter density in fronto-occipital and superior longitudinal fascicles, and gray matter density of (pre-)frontal and temporal areas are highly heritable. Pubertal development may be directly involved in the decreases in gray matter areas that accompany the transition of our brains from childhood into adulthood. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objectives: Cisplatin-based chemotherapy represents the gold standard in the treatment of advanced bladder cancer (BC) both in the neoadjuvant and adjuvant setting. Since novel immunooncologic agents are available for cisplatin-resistant or ineligible patients, biological markers for the prediction of cisplatin resistance become more important in treatment decisions. Therefore, we aimed to assess the therapy predictive value of 8 promising tissue biomarkers with regard to cisplatin therapy.Methods: Emmprin, survivin, HMGA2, MTA1, RhoGDI, PEG10, TGM2, and TLN1 expressions were analyzed in paraffin-embedded bladder cancer tissue samples of 106 patients who underwent adjuvant or salvage cisplatin-based chemotherapy by using immunohistochemistry. Results were correlated with the clinicopathological and follow-up data by performing both univariable and multivariable survival analyses.Results: Higher HMGA2 nuclear staining intensity and positive survivin nuclear staining were associated with worse overall survival (OS) (P = 0.045 and P = 0.002, respectively). In accordance, survivin nuclear staining also significantly correlated with shorter progression free survival (PFS, P = 0.024), while HMGA2 nuclear positivity tended to correlate with shorter PFS (P = 0.069) after at least 2 cycles of chemotherapy. In the multivariable analyses only survivin remained as an independent predictor of both OS and PFS (P = 0.008 and P = 0.025). None of the other markers proved to be significant predictors of adjuvant or salvage cisplatin-based chemotherapy.Conclusions: Our results demonstrate that survivin represents a promising marker for the prediction of cisplatin resistance in BC. In addition the therapy predictive role of HMGA2 should be further investigated. Immunohistochemical analysis of BC samples provides a feasible way for the prediction of cisplatin-resistance and may therefore provide a valuable tool for optimizing treatment decisions in advanced BC. [ABSTRACT FROM AUTHOR]