Modelling transitions in childrens' development by starting with adults

We present a blocks task in which cognitive change is apparent, and propose that computational modelling can help in examining how cognitive change occurs. We initially examine the performance of adults on the task, and use the results of this experiment to build both an adult model and a simulation of the task. Comparisons of the model with the adult data reveal further completion work regarding the models qualitative behaviour. However, when finished, the model will be able to predict how behaviour changes when domain knowledge is removed, and will provide the basis for models of children’s behaviour on the task

Pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma.

Introduction: Liposarcomas (LPS) are a heterogeneous group of adipocytic soft tissue sarcomas with limited treatment options in the advanced/metastatic setting. Pazopanib is a multi-target tyrosine kinase inhibitor (TKI) with anti-angiogenic and antitumorigenic properties. Whilst targeted agents including TKIs have been extensively studied in other solid tumors and the sarcoma subtype gastrointestinal stromal tumor (GIST), we currently lack effective treatments for the liposarcoma subtype. Several phase II and III studies of oral TKIs in soft tissue sarcomas have excluded liposarcoma because of a reported lack of activity following the EORTC 62043 study. Areas: We review the use of pazopanib in advanced intermediate and high-grade liposarcomas where complete surgical resection is not possible. Expert opinion: The current clinical and pharmacological data demonstrate the efficacy of pazopanib in soft tissue sarcomas, but new data suggest that anti-angiogenic agents may have limited activity in liposarcoma. Anti-angiogenic TKIs are generally well tolerated and liposarcomas vary in their response to systemic chemotherapy; hence, there is a role for further exploration of the efficacy of this treatment amongst the histological subtypes of liposarcoma. This affords further understanding of biomarkers which may be associated with response to pazopanib and other anti-angiogenic TKI treatments

Functional site prediction selects correct protein models

<p>Abstract</p> <p>Background</p> <p>The prediction of protein structure can be facilitated by the use of constraints based on a knowledge of functional sites. Without this information it is still possible to predict which residues are likely to be part of a functional site and this information can be used to select model structures from a variety of alternatives that would correspond to a functional protein.</p> <p>Results</p> <p>Using a large collection of protein-like decoy models, a score was devised that selected those with predicted functional site residues that formed a cluster. When tested on a variety of small <it>α</it>/<it>β</it>/<it>α </it>type proteins, including enzymes and non-enzymes, those that corresponded to the native fold were ranked highly. This performance held also for a selection of larger <it>α</it>/<it>β</it>/<it>α </it>proteins that played no part in the development of the method.</p> <p>Conclusion</p> <p>The use of predicted site positions provides a useful filter to discriminate native-like protein models from non-native models. The method can be applied to any collection of models and should provide a useful aid to all modelling methods from <it>ab initio </it>to homology based approaches.</p

Electromagnetic Form Factors in the hypercentral CQM

We report on the recent results of the hypercentral Constituent Quark Model (hCQM). The model contains a spin independent three-quark interaction which is inspired by Lattice QCD calculations and reproduces the average energy values of the SU(6) multiplets. The splittings are obtained with a SU(6)-breaking interaction, which can include also an isospin dependent term. Concerning Constituent Quark models, we have shown for the first time that the decreasing of the ratio of the elastic form factors of the proton is due to relativistic effects using relativistic corrections to the e.m. current and boosts. Now the elastic nucleon form factors have been recalculated, using a relativistic version of the hCQM and a relativistic quark current showing a very detailed reproduction of all the four form factor existing data over the complete range of 0-4 $GeV^2$. Futhermore, the model has been used for predictions concerning the electromagnetic transverse and longitudinal transition form factors giving a good description of the medium $Q^2$ behaviour. We show that the discrepancies in the reproduction of the helicity amplitudes at low $Q^2$ are due to pion loops. We have calculated the helicity amplitudes for all the 3 and 4 star resonances opening the possibility of application to the evaluation of cross sections.Comment: 5 pages, 7 figures, Invited talk at the ICTP 4th International Conference on Perspectives in Hadronic Physics, Trieste, Italy, 12-16 May 2003. Accepted by Eur. Phys. J.

Micro-scale environment and mental health in later life: Results from the Cognitive Function and Ageing Study II (CFAS II)

$\textit{Background:}$ Poor micro-scale environmental features, such as graffiti and broken windows, have been associated with crime and signs of social disorder with a potential impact on mental health. The aim of this study is to investigate the association between micro-scale environment and mental health problems in later life, including cognitive (cognitive impairment and dementia) and common mental disorders (depressive and anxiety symptoms). $\textit{Methods:}$ The method of visual image audits was used to collect micro-scale environmental data for 3590 participants in the Cognitive Function and Ageing Study II, a population-based multicentre cohort of people aged 65 or above in England. Multilevel logistic regression was used to examine the associations between the quality of micro-scale environment and mental health problems taking into account urban/rural difference. $\textit{Results:}$ Poor quality of micro-scale environment was associated with nearly 20% increased odds of depressive (OR: 1.19; 95% CI: 0.99, 1.44) and anxiety symptoms (OR: 1.17; 95% CI: 0.99, 1.38) while the direction of association for cognitive disorders differed across urban and rural settings. Although higher odds of cognitive disorders were found in rural settings, living in a poor quality environment was associated with nearly twice higher odds of cognitive impairment (OR: 1.88; 95% CI: 1.18, 2.97) in urban conurbations but 20% lower odds in rural areas (OR: 0.80; 95% CI: 0.57, 1.11). $\textit{Limitations:}$ The causal direction could not be fully determined due to the cross-sectional nature of the data. The visual nature of the environmental assessment tool means it likely does not fully capture features related to the availability of local support services, or opportunities for social participation and interaction. $\textit{Conclusions:}$ The quality of micro-scale environment appears to be important to mental health in older people. Interventions may incorporate the environmental aspect to reduce cognitive and common mental disorders.Medical Research Counci

Tranilast increases vasodilator response to acetylcholine in rat mesenteric resistance arteries through increased EDHF participation

Background and Purpose: Tranilast, in addition to its capacity to inhibit mast cell degranulation, has other biological effects, including inhibition of reactive oxygen species, cytokines, leukotrienes and prostaglandin release. In the current study, we analyzed whether tranilast could alter endothelial function in rat mesenteric resistance arteries (MRA). Experimental Approach: Acetylcholine-induced relaxation was analyzed in MRA (untreated and 1-hour tranilast treatment) from 6 month-old Wistar rats. To assess the possible participation of endothelial nitric oxide or prostanoids, acetylcholineinduced relaxation was analyzed in the presence of L-NAME or indomethacin. The participation of endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced response was analyzed by preincubation with TRAM-34 plus apamin or by precontraction with a high K+ solution. Nitric oxide (NO) and superoxide anion levels were measured, as well as vasomotor responses to NO donor DEA-NO and to large conductance calcium-activated potassium channel opener NS1619. Key Results: Acetylcholine-induced relaxation was greater in tranilast-incubated MRA. Acetylcholine-induced vasodilation was decreased by L-NAME in a similar manner in both experimental groups. Indomethacin did not modify vasodilation. Preincubation with a high K+ solution or TRAM-34 plus apamin reduced the vasodilation to ACh more markedly in tranilastincubated segments. NO and superoxide anion production, and vasodilator responses to DEA-NO or NS1619 remained unmodified in the presence of tranilast. Conclusions and Implications: Tranilast increased the endothelium-dependent relaxation to acetylcholine in rat MRA. This effect is independent of the nitric oxide and cyclooxygenase pathways but involves EDHF, and is mediated by an increased role of small conductance calcium-activated K+ channelsThis study was supported by Ministerio de Ciencia e Innovación (SAF 2009-10374), Ministerio de Economía y Competitividad (SAF 2012-38530), and Fundación Mapfre. F.E. Xavier is recipient of research fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil

Comorbid health conditions and their impact on social isolation, loneliness, quality of life, and well-being in people with dementia: longitudinal findings from the IDEAL programme

\ua9 2024, The Author(s).Background: Most people with dementia have multiple health conditions. This study explores (1) number and type of health condition(s) in people with dementia overall and in relation to age, sex, dementia type, and cognition; (2) change in number of health conditions over two years; and (3) whether over time the number of health conditions at baseline is related to social isolation, loneliness, quality of life, and/or well-being. Methods: Longitudinal data from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort were used. Participants comprised people with dementia (n = 1490) living in the community (at baseline) in Great Britain. Health conditions using the Charlson Comorbidity Index, cognition, social isolation, loneliness, quality of life, and well-being were assessed over two years. Mixed effects modelling was used. Results: On average participants had 1.8 health conditions at baseline, excluding dementia; increasing to 2.5 conditions over two years. Those with vascular dementia or mixed (Alzheimer’s and vascular) dementia had more health conditions than those with Alzheimer’s disease. People aged ≥ 80 had more health conditions than those aged &lt; 65 years. At baseline having more health conditions was associated with increased loneliness, poorer quality of life, and poorer well-being, but was either minimally or not associated with cognition, sex, and social isolation. Number of health conditions had either minimal or no influence on these variables over time. Conclusions: People with dementia in IDEAL generally had multiple health conditions and those with more health conditions were lonelier, had poorer quality of life, and poorer well-being

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury