Molecular Genetics of Conjunctival Melanoma and Prognostic Value of TERT Promoter Mutation Analysis

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM.     

β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and ¹H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC_50s and EC_90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.     

Defining dimensions of distinctiveness: Group variability makes a difference to differentiation.

We tested the prediction, derived from an integration of social identity and self-categorization principles, that the relation between in-group distinctiveness and positive differentiation is curvilinear. Moderate distinctiveness is argued to provide the critical combination of intergroup difference (self-categorization theory) and intergroup similarity ( social identity theory ) to elicit intergroup differentiation. Intergroup distance (differences in group central tendencies) and group variability were manipulated orthogonally, resulting in different levels of intergroup distinctiveness (low, intermediate, and high). In line with predictions, in-group bias and positive differentiation were greatest, for both minimal and natural groups, when the combination of group variability and intergroup distance produced intermediate levels of group distinctiveness. The potential of this integrative model to account for disparate findings is discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

A decentralized kinematic control architecture for collaborative and cooperative multi-arm systems

In this paper a two-layer decentralized framework for kinematic control of cooperative and collaborative multi-robot systems is developed. The motion of the system is specified at the workpiece level, by adopting a task-oriented formulation for cooperative tasks. The first layer computes the motion of the single arms in the system. In detail, the control unit of each robot computes the end-effector motion references in a decentralized fashion on the basis of the knowledge of the assigned cooperative task and the motion references computed by its neighbors. Then, in the second layer, each control unit computes the reference joint motion of the corresponding manipulator from the end-effector reference motion. The approach is, then, tested in simulation on a work-cell composed by several manipulators, and experimentally on a dual-arm kinematically redundant work-cell composed by industrial manipulators.     

Out of mind but back in sight: Stereotypes on the rebound.

For a variety of reasons, social perceivers may often attempt to actively inhibit stereotypic thoughts before their effects impinge on judgment and behavior. However, research on the psychology of mental control raises doubts about the efficacy of this strategy. Indeed, this work suggests that when people attempt to suppress unwanted thoughts, these thoughts are likely to subsequently reappear with even greater insistence than if they had never been suppressed (i.e., a "rebound" effect). The present research comprised an investigation of the extent to which this kind of rebound effect extends to unwanted stereotypic thoughts about others. The results provide strong support for the existence of this effect. Relative to control Ss (i.e., stereotype users), stereotype suppressors responded more pejoratively to a stereotyped target on a range of dependent measures. We discuss our findings in the wider context of models of mind, thought suppression, and social stereotyping. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

<Emphasis Type="Italic">T</Emphasis><Subscript>2</Subscript> mapping of cerebrospinal fluid: 3 T versus 7 T

Object

Cerebrospinal fluid (CSF) T ₂ mapping can potentially be used to investigate CSF composition. A previously proposed CSF T ₂–mapping method reported a T ₂ difference between peripheral and ventricular CSF, and suggested that this reflected different CSF compositions. We studied the performance of this method at 7 T and evaluated the influence of partial volume and B ₁ and B ₀ inhomogeneity.

Materials and methods

T ₂-preparation-based CSF T ₂-mapping was performed in seven healthy volunteers at 7 and 3 T, and was compared with a single echo spin-echo sequence with various echo times. The influence of partial volume was assessed by our analyzing the longest echo times only. B ₁ and B ₀ maps were acquired. B ₁ and B ₀ dependency of the sequences was tested with a phantom.

Results

T _2,CSF was shorter at 7 T compared with 3 T. At 3 T, but not at 7 T, peripheral T _2,CSF was significantly shorter than ventricular T _2,CSF. Partial volume contributed to this T ₂ difference, but could not fully explain it. B ₁ and B ₀ inhomogeneity had only a very limited effect. T _2,CSF did not depend on the voxel size, probably because of the used method to select of the regions of interest.

Conclusion

CSF T ₂ mapping is feasible at 7 T. The shorter peripheral T _2,CSF is likely a combined effect of partial volume and CSF composition.

     

Breaking the cycle of homelessness: Housing stability and social support as predictors of long-term well-being

It is increasingly acknowledged that homelessness involves more than just being without a house. Indeed, more recent definitions of what constitutes a home highlight the role of social connections and support (including, for example, access to space to engage in social relations). This study examined the role of secure housing and social support as predictors of psychological well-being of individuals following a period of homelessness. Using linear mixed models for longitudinal data, we investigated how changes in social support predicted changes in individuals’ self-reported personal well-being, life satisfaction and mood following a period of homelessness (n = 119), controlling for housing status, alcohol use and employment status. The results showed that remaining homeless predicted poorer personal well-being, life satisfaction and mood. In addition, changes in social support predicted well-being over and above housing stability. Implications of findings for policy and practice in the homeless sector are discussed.     

Ad libitum fluid intake leads to no leg swelling in male Ironman triathlet an observational field study

ABSTRACT: BACKGROUND: An association between fluid intake and limb swelling has been described for 100-km ultra-marathoners. We investigated a potential development of peripheral oedemata in Ironman triathletes competing over 3.8 km swimming, 180 km cycling and 42.2 km running. METHODS: In 15 male Ironman triathletes, fluid intake, changes in body mass, fat mass, skeletal muscle mass, limb volumes and skinfold thickness were measured. Changes in renal function, parameters of skeletal muscle damage, hematologic parameters and osmolality in both serum and urine were determined. Skinfold thicknesses at hands and feet were measured using LIPOMETER(R) and changes of limb volumes were measured using plethysmography. RESULTS: The athletes consumed a total of 8.6 +/- 4.4 L of fluids, equal to 0.79 +/- 0.43 L/h. Body mass, skeletal muscle mass and the volume of the lower leg decreased (p <0.05), fat mass, skinfold thicknesses and the volume of the arm remained unchanged (p >0.05). The decrease in skeletal muscle mass was associated with the decrease in body mass (p >0.05). The decrease in the lower leg volume was unrelated to fluid intake (p >0.05). Haemoglobin, haematocrit and serum sodium remained unchanged (p >0.05). Osmolality in serum and urine increased (p <0.05). The change in body mass was related to post-race serum sodium concentration ([Na+]) (r = -0.52, p <0.05) and post-race serum osmolality (r = -0.60, p <0.05). CONCLUSIONS: In these Ironman triathletes, ad libitum fluid intake maintained plasma [Na+] and plasma osmolality and led to no peripheral oedemata. The volume of the lower leg decreased and the decrease was unrelated to fluid intake. Future studies may investigate ultra-triathletes competing in a Triple Iron triathlon over 11.4 km swimming, 540 km cycling and 126.6 km running to find an association between fluid intake and the development of peripheral oedemata.     

The perception of static colored noise: Detection and masking described by CIE94

We present psychophysical data on the perception of static colored noise. In our experiments, we use the CIE94 color difference formula to quantify the noise strength and for describing our threshold data. In Experiment 1 we measure the visual detection thresholds for fixed pattern noise on a uniform background color. The noise was present in one of three perceptual color dimensions lightness (L*), chroma (C*), or hue (h). Results show that the average detection threshold for noise in L* is independent of hue angle and significantly lower than that for noise in C* or h. Thresholds for noise in C* and h depend on hue angle in an opponent fashion. The measured detection thresholds, expressed in terms of the components ΔL*/k_LS_L, ΔC*/k_CS_C, and ΔH*/k_HS_H that build up the CIE94 color difference formula are used to tune CIE94 to our experimental conditions by adjusting the parametric scaling factors k_L, k_C, and k_H. In Experiment 2, we measure thresholds for recognizing the orientation (left, right, up, down) of a test symbol that was incremental in L*, C*, or h, masked by supra‐threshold background noise levels in L*, C*, or h. On the basis of the CIE94 color difference formula we hypothesized (a) a constant ratio between recognition threshold and noise level when the test symbol and background noise are in the same perceptual dimension, and (b) a constant recognition threshold when in different dimensions. The first hypothesis was confirmed for each color dimension, the second however, was only confirmed for background noise in L*. The L*, C*, h recognition thresholds increase with increasing background noise in C* or h. On the basis of some 16,200 visual observations we conclude that the three perceptual dimensions L*, C*, and h require different scaling factors (hue dependent for C* and h) in the CIE94 color difference formula, to predict detection threshold data for color noise. In addition these dimensions are not independent for symbol recognition in color noise. © 2008 Wiley Periodicals, Inc. Col Res Appl, 33, 178–191, 2008