292 research outputs found

    Impaired Competence for Pretense in Children with Autism: Exploring Potential Cognitive Predictors.

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    Lack of pretense in children with autism has been explained by a number of theoretical explanations, including impaired mentalising, impaired response inhibition, and weak central coherence. This study aimed to empirically test each of these theories. Children with autism (n=60) were significantly impaired relative to controls (n=65) when interpreting pretense, thereby supporting a competence deficit hypothesis. They also showed impaired mentalising and response inhibition, but superior local processing indicating weak central coherence. Regression analyses revealed that mentalising significantly and independently predicted pretense. The results are interpreted as supporting the impaired mentalising theory and evidence against competing theories invoking impaired response inhibition or a local processing bias. The results of this study have important implications for treatment and intervention

    Evolutionary trade-off between vocal tract and testes dimensions in howler monkeys.

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    Males often face a trade-off between investments in precopulatory and postcopulatory traits [1], particularly when male-male contest competition determines access to mates [2]. To date, studies of precopulatory strategies have largely focused on visual ornaments (e.g., coloration) or weapon morphology (e.g., antlers, horns, and canines). However, vocalizations can also play an important role in both male competition and female choice [3-5]. We investigated variation in vocal tract dimensions among male howler monkeys (Alouatta spp.), which produce loud roars using a highly specialized and greatly enlarged hyoid bone and larynx [6]. We examined the relative male investment in hyoids and testes among howler monkey species in relation to the level of male-male competition and analyzed the acoustic consequences of variation in hyoid morphology. Species characterized by single-male groups have large hyoids and small testes, suggesting high levels of vocally mediated competition. Larger hyoids lower formant frequencies, probably increasing the acoustic impression of male body size and playing a role analogous to investment in large body size or weaponry. Across species, as the number of males per group increases, testes volume also increases, indicating higher levels of postcopulatory sperm competition, while hyoid volume decreases. These results provide the first evidence of an evolutionary trade-off between investment in precopulatory vocal characteristics and postcopulatory sperm production.We are grateful to Alexander Sliwa, Catalina Gomez, Robert Wallace, Michael Plavkan, Zelinda Braga Hirano, and Julio Cesar de Souza, Jr. for sharing data, Andrew Kitchener (National Museums Scotland) for loaning whole animal specimens, Michaela Gumpenberger and Jaap Saers for support with CT and MRI, Carolyn M. Crockett, Mariana Raño, and La Senda Verde Animal Refuge Bolivia for providing photographs and videos, Nadja Kavcik for help with the figures, and Dieter Lukas for help with statistical analyses. J.C.D. was funded by a Cambridge Humanities Research Grant. W.T.F. acknowledges support of ERC Advanced Grant SOMACCA (#230604) and Austrian Science Fund (FWF) grant W1234-G17.This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.cub.2015.09.02

    A Prospective Observational Study of Antihemophilic Factor (Recombinant) Prophylaxis Related to Physical Activity Levels in Patients with Hemophilia A in the United States (SPACE)

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    Introduction: High collision-risk physical activity can increase bleeding risk in people with hemophilia A, as can increasing the time between factor VIII (FVIII) administration and physical activity. FVIII prophylaxis may be tailored to planned activities to prevent activity-related bleeding. Aim: To explore the relationship between physical activity levels, FVIII infusion timing, and occurrence of bleeding in patients with severe/moderately severe hemophilia A without FVIII inhibitors receiving antihemophilic factor (recombinant) (rAHF; ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA). Methods: SPACE was a 6-month, prospective, multicenter, observational outcomes study (NCT02190149). Enrolled patients received an eDiary application and a wearable activity tracker, which recorded physical activity, rAHF infusion, and occurrence of bleeding. Physical activity risks were ranked using National Hemophilia Foundation criteria. Results: Fifty-four patients aged 11– 58 years (n = 47 prophylaxis, n = 7 on-demand) were included in the analysis. Patients had a mean (SD) 8.14 (10.94) annualized bleeding rate, and recorded 4980 intervals between an rAHF infusion and physical activity; 1759 (35.3%) of these intervals were ≤ 24 hours. Analysis of recorded eDiary data showed that the risk of activity-related bleeding did not significantly increase with time between last infusion and activity, but did increase with higher-risk physical activities. Analysis of activity tracker recorded data showed that the risk of bleeding reported by patients as spontaneous increased with prolonging time (≤ 24 to \u3e 24 hours) from last infusion to physical activity start (odds ratio 2.65, p \u3c 0.05). Joint health data collected at baseline were not included in the regression analysis because of small sample size; therefore the study could not assess whether patients with more joint disease at baseline were at higher risk of injury-related and reported spontaneous occurrence of bleeding. Conclusion: These results show that activities with a high risk of collision lead to an increased risk of bleeding. Further investigation is warranted to explore potential benefits of FVIII infusion timing to reduce the risks of activity-related occurrence of bleeding

    The Ursinus Weekly, November 23, 1964

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    Write me a murder, a skillful presentation of a weak play • Junior class announces \u27S no ball turnabout • WSGA report on women\u27s programs • Judy Collins to appear in campus folk concert: Performance tickets remain on sale • Ursinus receives $1,500 grant from Sears-Roebuck Foundation • Work camps topic of slide lecture • Debaters prepare for Temple novice tournament • Ursinus students attend Sheraton collegiate council • Human Relations Commission starts tutoring program • SWC abandons Sunday vespers • Editorial: Hats off! • Progress keyword in dining hall construction • Annual college music competition • Spotlight: UC abroad; Student\u27s stay in Stockholm • Letters to the editor • Advice column • U.C. history: The pipe dream • Volleyball league begins • Soccermen split 0-5 and 4-3 • Soccermen finish season with 5-5-1 record • UC drops final game to F&M, 20-6 • Bible fellowship sponsors Paul Little, speaker • Greek gleaningshttps://digitalcommons.ursinus.edu/weekly/1235/thumbnail.jp

    CK1ε Is Required for Breast Cancers Dependent on β-Catenin Activity

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    Background: Aberrant β\beta-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate β\beta-catenin activity for therapeutic purposes have proven elusive to date. Methodology: To uncover genetic dependencies in breast cancer cells that harbor active β\beta-catenin signaling, we performed RNAi-based loss-of-function screens in breast cancer cell lines in which we had characterized β\beta-catenin activity. Here we identify CSNK1E, the gene encoding casein kinase 1 epsilon (CK1ε\varepsilon) as required specifically for the proliferation of breast cancer cells with activated β\beta-catenin and confirm its role as a positive regulator of β\beta-catenin-driven transcription. Furthermore, we demonstrate that breast cancer cells that harbor activated β\beta-catenin activity exhibit enhanced sensitivity to pharmacological blockade of Wnt/β\beta-catenin signaling. We also find that expression of CK1ε\varepsilon is able to promote oncogenic transformation of human cells in a β\beta-catenin-dependent manner. Conclusions/Significance: These studies identify CK1ε\varepsilon as a critical contributor to activated β\beta-catenin signaling in cancer and suggest it may provide a potential therapeutic target for cancers that harbor active β\beta-catenin. More generally, these observations delineate an approach that can be used to identify druggable synthetic lethal interactions with signaling pathways that are frequently activated in cancer but are difficult to target with the currently available small molecule inhibitors

    Children's Divergent Thinking Improves When They Understand False Beliefs

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    This research utilized longitudinal and cross sectional methods to investigate the relation between the development of a representational theory of mind and children's growing ability to search their own minds for appropriate problem solutions. In the first experiment 59 pre-school children were given three false-belief tasks and a divergent thinking task. Those children who passed false-belief tasks produced significantly more items, as well as more original items, in response to divergent thinking questions than those children who failed. This significant association persisted even when chronological age, verbal and nonverbal general ability were partialed out. In a second study 20 children who failed the false-belief tasks in the first experiment were re-tested three months later. Again, those who now passed the false-belief tasks were significantly better at the divergent thinking task than those who continued to fail. The associations between measures of divergent thinking and understanding false-beliefs remained significant when controlling for the covariates. Earlier divergent thinking scores did not predict false-belief understanding three months later. Instead, children who passed false-belief tasks on the second measure improved significantly in relation to their own earlier performance and improved significantly more than children who continued to fail. False-belief task performance was significantly correlated to the amount of intra-individual improvement in divergent thinking even when age, verbal and nonverbal skills were partialed out. These findings suggest that developments in common underlying skills are responsible for the improvement in understanding other minds and searching one's own. Changes in representational and executive skills are discussed as potential causes for the improvement

    Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

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    INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma
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