Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors.

The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH-No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH

A comparison of methodological frameworks for digital learning game design

Methodological frameworks guide the design of digital learning game based on well founded learning theories and instructional strategies. This study presents a comparison of five methodological frameworks for digital learning game design, highlighting their similarities and differences. The objective is to support the choice of an adequate framework, aiming to promote them as a way to foster principled digital learning games design. This paper concludes that: (i) interactivity, engagement and increasing complexity of challenges are fundamental factors to digital learning game design; (ii) the pedagogical base, the target, the possibility of doing game assessment and the presence of practical guidelines are the selection criteria that influence most the choice of a methodological framework, and (iii) the development of digital learning games - preferably by different research teams - is needed to provide empirical evidence of the utility of framework-based design

Friendship as a Political Concept: A Groundwork for Analysis

What kind of a concept is friendship, and what is its connection to politics? Critics sometimes claim that friendship does not have a role to play in the study of politics. Such objections misconstrue the nature of the concept of friendship and its relation to politics. In response, this article proposes three approaches to understanding the concept of friendship: (1) as a ‘family resemblance’ concept, (2) as an instance of an ‘essentially contested’ concept, and (3) as a concept indicating a problématique. The article thus responds to the dismissal of friendship by undertaking the groundwork for understanding what kind of a concept friendship might be, and how it might serve different purposes. In doing so, it opens the way for understanding friendship’s relation to politics

Primary skin fibroblasts as a model of Parkinson's disease

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

Pharmacological basis and clinical evidence of dabigatran therapy

Dabigatran is an emerging oral anticoagulant which is a direct inhibitor of thrombin activity. It has been approved in the European Union and the United States of America for the prevention of thrombosis after major orthopedic surgery. It has also been approved by the American Food and Drug Administration and the European Medicines Agency for the prevention of stroke in chronic atrial fibrillation. Dabigatran provides a stable anticoagulation effect without any need to perform periodical laboratory controls. Of note, there is a growing amount of clinical evidence which shows its safety and efficacy. For these reasons, dabigatran may suppose a revolution in oral anticoagulation. However, two important limitations remain. First, it is contraindicated in patients with end-stage renal disease. Second, there is no evidence of the prevention of thrombosis in mechanical heart valves

Complex Precipitation Pathways in Multi-Component Alloys

One usual way to strengthen a metal is to add alloying elements and to control the size and the density of the precipitates obtained. However, precipitation in multicomponent alloys can take complex pathways depending on the relative diffusivity of solute atoms and on the relative driving forces involved. In Al-Zr-Sc alloys, atomic simulations based on first-principle calculations combined with various complementary experimental approaches working at different scales reveal a strongly inhomogeneous structure of the precipitates: owing to the much faster diffusivity of Sc compared with Zr in the solid solution, and to the absence of Zr and Sc diffusion inside the precipitates, the precipitate core is mostly Sc-rich, whereas the external shell is Zr-rich. This explains previous observations of an enhanced nucleation rate in Al-Zr-Sc alloys compared with binary Al-Sc alloys, along with much higher resistance to Ostwald ripening, two features of the utmost importance in the field of light high-strength materials

Other-Sex Friendships in Late Adolescence: Risky Associations for Substance Use and Sexual Debut?

Adolescents’ friendships with other-sex peers serve important developmental functions, but they may also facilitate engagement in problem behavior. This study examines the unique contributions of other-sex friendships and friends’ behavior to alcohol use, smoking, and initiation of sexual intercourse among late adolescent girls and boys. A total of 320 adolescents (53% girls; 33% racial/ethnic minorities) provided sociometric nominations of friendships annually in grades 10–12. Friendship networks were derived using social network analysis in each grade. Adolescents and their friends also reported on their alcohol use, smoking, and sexual debut at each assessment. After controlling for demographics, previous problem behavior, and friends’ behavior, other-sex friendships in 10th grade were associated with initiation of smoking among girls over the following year, and other-sex friendships in 11th grade were linked with lower levels of subsequent alcohol use among boys. Additionally, friends’ smoking and sexual experience in 10th grade predicted the same behaviors for all adolescents over the following year. Other-sex friendships thus appear to serve as a risk context for adolescent girls’ smoking and a protective context for adolescent boys’ drinking. Promoting mixed-gender activities and friendships among older high school students may be helpful in reducing males’ alcohol use, but may need to incorporate additional components to prevent increases in females’ smoking

Global impression of perceived difficulties in children and adolescents with attention-deficit/hyperactivity disorder: Reliability and validity of a new instrument assessing perceived difficulties from a patient, parent and physician perspective over the day

<p>Abstract</p> <p>Background</p> <p>The objective of this analysis was to evaluate the psychometric properties of a brief scale developed to assess the degree of difficulties in children with Attention-Deficit/Hyperactivity Disorder (ADHD). The Global Impression of Perceived Difficulties (GIPD) scale reflects overall impairment, psychosocial functioning and Quality of Life (QoL) as rated by patient, parents and physician at various times of the day.</p> <p>Methods</p> <p>In two open-label studies, ADHD-patients aged 6–17 years were treated with atomoxetine (target-dose 0.5–1.2 mg/kg/day). ADHD-related difficulties were assessed up to week 24 using the GIPD. Data from both studies were combined to validate the scale.</p> <p>Results</p> <p>Overall, 421 patients received atomoxetine. GIPD scores improved over time. All three GIPD-versions (patient, parent, physician) were internally consistent; all items showed at least moderate item-total correlation. The scale showed good test-retest reliability over a two-week period from all three perspectives. Good convergent and discriminant validity was shown.</p> <p>Conclusion</p> <p>GIPD is an internally consistent, reliable and valid measure to assess difficulties in children with ADHD at various times of the day and can be used as indicator for psychosocial impairment and QoL. The scale is sensitive to treatment-related change.</p

Dabigatran in patients with atrial fibrillation: perioperative and periinterventional management

In any type of invasive surgery, the patient’s individual risk of thromboembolism has to be weighed against the risk of bleeding. Based on various everyday situations in clinical routine, the purpose of the present expert recommendations is to provide appropriate perioperative and periinterventional management for patients with atrial fibrillation undergoing long-term treatment with the thrombin inhibitor dabigatran. As we currently have no routine laboratory test to measure therapeutic levels of the substance or the risk of bleeding, general measures such as a standardized documentation of the patient’s history, a sufficient time interval between the last preoperative dose and the procedure, and careful control of local hemostasis should be given special attention

The Role of Important Non-Parental Adults (VIPs) in the Lives of Older Adolescents: A Comparison of Three Ethnic Groups

Previous research has consistently documented the importance of VIPs (mentors or important non-parental adults) in the lives of adolescents. Little is known, however, about whether VIPs play the same important roles across ethnic groups and whether VIPs remain influential when adolescents are older and involved in romantic relationships. The present study compared VIPs of 355 Hispanic, Asian, and European American older adolescents (age range = 17–19 years; M = 18.7 years; 62% female). Results indicated that, despite ethnic differences in their social capital, VIPs’ psychological characteristics (e.g., warmth and acceptance, depressive symptoms, and problem behavior) were similar. VIPs were perceived to have more positive psychological profiles than parents and peers, and in some cases, romantic partners. Moreover, with a few exceptions, the associations between VIP characteristics and adolescent adjustment (e.g., self-esteem, depressive symptoms, and problem behavior) were largely similar across ethnic groups. Finally, VIPs made unique contributions to adolescents’ self-esteem and problem behaviors even after the effects of romantic partners were considered. Implications of the findings are discussed