High online engagement is common among adolescents. Besides concerns, not all highly involved adolescents online develop maladaptive patterns of use. The focus of the present qualitative study was to explore the experiences of highly engaged adolescents with signs of internet addictive behaviors. We aimed to uncover the processes differentiating high online engagement, and formulate a typology of users. Semi-structured individual interviews were conducted with 72 adolescents (M-age = 15.7 years; SD = 0.6) living in Greece, Spain, Iceland and Poland. Interviews were analyzed using grounded theory. A typology of highly engaged adolescents emerged based on three processes: satisfying needs across contexts (online-offline), experiencing personal gains and losses and self-regulating use. Four distinct user profiles emerged, ranging from adaptive (juggling it All, Coming Full Cycle) to maladaptive (Stuck Online, Killing Boredom). The developed typology can help parents, teachers and professionals better understand the ways high engagement is experienced within a developmental context. Such knowledge can inform the development of prevention and supportive services. Implications for assessment and intervention are discussed for each profile. (C) 2016 Elsevier Ltd. All rights reserved.

ABSTRACTToday adolescents are highly engaged online. Contrary to common concern, not all highly engaged adolescents develop maladaptive patterns of internet use. The present qualitative study explored the experiences, patterns and impact of use of 124 adolescents (Mage = 16.0) reporting signs of internet addictive behaviors. The focus was to discern adaptive and maladaptive use patterns, which promote or interfere with adolescents' development, respectively. Semi‐structured individual interviews were conducted in seven European countries (Greece, Spain, Poland, Germany, Romania, Netherlands and Iceland) and qualitatively analyzed using grounded theory. Considerable variability emerged in the way adolescents satisfied their personal needs online and offline, in the experienced impact from high online engagement and functional value ascribed to the internet, and in the self‐regulatory processes underlying use. Variability in these discriminating processes was linked to adaptive or maladaptive adolescent internet use patterns. The emerged processes can provide direction for designing prevention and intervention programs promoting adaptive use.

During the last decades internet use has increased significantly and constitutes the norm in daily life for most people, especially for adolescents. Recent technical advances have shifted the ability to access the internet from using a desktop computer to being able to access the internet anywhere and anytime by a wireless connection. Adolescence is a period involving substantial physical, cognitive and socio-emotional growth. During this period, the adolescent’s self-image strengthens and inner and outer boundaries are explored, they expand their social networks and spend more time and experience greater intimacy with friends while interactions with their families may be reduced. Adolescents’ everyday life is to a great extent controlled by what can be done online, they communicate and interact socially online, read blogs, browse the internet for knowledge and information, download music and movies. Some find online communication more comfortable than face-to-face interaction, in particular when sharing information pertaining to them. The internet also allows adolescents to connect to friends and relatives living far away. Although most adolescents regard the internet as a necessity in their everyday life, it may also present harm including exposure to sexually explicit content, violence or cyber bullying. Internet use can also become excessive and addictive. A sign of internet addiction has been described as similar to those of addictive gambling. Symptoms include feelings of conflicts of whether spending time online or seeing friends, or attending a sports practice and users gradually withdraw from social interactions outside of the internet. Other signs involve obsessive thoughts about being Online, irritation when online sessions are being interrupted or not possible and some individuals try to conceal the full extent of their internet use. This paper explores online habits and parental restrictions on internet use among 15–16 years old adolescents in Iceland. The paper builds on data from the EU-NET Addiction Behaviour project (EUNET-ADB). The aim of the EUNET-ADB was to measure prevalence and risk factors for internet addictive behaviours among adolescents in Europe. Data in the EUNET-ADB project was collected by a mix method approach, using a questionnaire and semistructured individual interviews with adolescent scoring 30 points or more on the Internet Addiction Test (IAT) instrument. In this paper we examine how much time adolescents spend online on weekdays and weekends. We also assessed adolescent´s view on their parents´ restrictive measures with respect to their children´s internet use. The results indicate that most adolescents in Iceland use the internet and 2 out of 3 use the internet during most days. Boys stay online to a greater extent than girls, on average two and a half hour per day compared to 2 hours per day among girls. About 1 of 3 respondents reported having used the internet excessively so that other activities had been neglected. Many participants said to have tried to reduce time spent online. Parental mediation of internet use was limited. Freedom of visiting any website of their choice was reported by 67% of respondents. Similarly, almost 60% of adolescents reported that parents never or rarely set any restrictions on how long they were allowed to be online. All of the adolescents that participated in the in-depth interviews were avid internet users and most of them also engaged in social networking, in particular by Facebook. Being active on Facebook was vividly described by participants as necessary to keep up with what was happening. Although data based the quantitative study indicated that parental mediation of internet use was limited, most participants in the in-depth interviews described various strategies parents had implemented to limit time spent online or access to certain websites, such as computer-free days, password protected access or so called “net-nannies”. The participants in the in-depth interviews generally regarded themselves as being in control of their internet use, although many disclosed that their online time was more than they considered “normal”. Boredom, loneliness or escaping from reality was often related with a heavy internet use in adolescent’s narrations.

IntroductionFull findings from the European Commission funded EU-NET-ADB study (Safer Internet Programme) will be presented.ObjectivesEmpirical findings that elucidate the development of an internet addictive behaviour are still incomplete. This is also related to risk as well as protective factors of internet use. Here a process oriented approach to identify underlying conditions of an internet addictive behaviour was chosen.AimsThe aim of the study is to enhance the knowledge and understanding of underlying processes which lead to situation were internet addictive behaviour can evolve.MethodsIn total 124 in-depth interviews were conducted with adolescents with an age of 14-17 year. Adolescents from seven different European countries (Greece, Spain, Poland, Germany, Romania, Netherlands & Iceland) participated in this study. Eligibility was granted when adolescents scored more than 30 point or equal in the Internet Addiction Test (IAT; Young, 1998). Data analysis was conducted by use of a step-wise full version of Grounded Theory (Strauss & Corbin, 1990; 1998).ResultsAdolescents employed maladaptive and adaptive strategies in regard to their involvement in the internet. Thus different Digital Outcomes such as “I am addicted” (Stuck Online) ranging to more adaptive internet behaviour like (Juggling it All) and patterns of self-correcting (Coming Full Cycle) were identified. These Digital Outcomes were consequently linked to adolescent's developmental pathways and can be characterized by the core category “Navigating Adolescent Pathways”.ConclusionsContextual and developmental factors that mediate the development of an internet addictive behaviour could be identified and linked to multiple Digital Outcomes.

Asthma is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. Numerous loci and candidate genes have been reported to show linkage and association of asthma and the asthma-associated phenotypes, atopy, elevated immunoglobulin E (IgE) levels, and bronchial hyper-responsiveness to alleles of microsatellite markers and single nucleotide polymorphisms (SNPs) within specific cytokine/chemokine, and IgE regulating genes. While many studies reporting these observations are compelling, only one asthma gene conferring high risk has been mapped. In this review, we present studies that support linkage and/or associations to the various genetic loci and genes in asthma. The first genome-wide scan for linkage to quantitative traits underlying asthma identified linkage on chromosome 4q, 6, 7, 11q, 13q and 16. A genome scan in American families from three racial groups revealed linkage to chromosome 2q, 5q, 6p, 12q, 13q and 14q. A two-stage scan in Hutterite families from the US found linkage on chromosome 5q, 12q, 19q and 21q. A screen in German families identified linkage to asthma on chromosome 2q, 6p, 9 and 12q and a two-stage genome scan in French families found replicated linkage on chromosomes 1p, 12q and 17q. A study of asthma in Finland showed linkage to high IgE on 7q14. Apart from a European linkage study of 199 families with atopic dermatitis, which demonstrated significant linkage to chromosome 3q21, three other studies have reported linkage results of genome-wide significance, including a linkage study in 175 Icelandic asthma families (14q24), a study in 533 Chinese families with bronchial hyper-responsiveness (chromosome 2) and a study in 47 Japanese families with mite-sensitive atopic asthma (5q31), suggesting that these regions may harbor genes contributing to the development of asthma and allergies. While significant progress has been made in the field of asthma genetics in the past decade, the clinical implications of the genes and genetic variations within the numerous candidate asthma genes that have been found to associate with the expression of the asthmatic phenotype, remain undetermined.

A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to be associated with childhood asthma. We sought to evaluate the effect of rs7216389-T on asthma subphenotypes and its correlation with expression levels of neighboring genes. The association of rs7216389-T with asthma was replicated in six European and one Asian study cohort (N=4917 cases N=34 589 controls). In addition, we found that the association of rs7216389-T was confined to cases with early onset of asthma, particularly in early childhood (age: 0–5 years OR=1.51, P=6.89·10−9) and adolescence (age: 14–17 years OR=1.71, P=5.47·10−9). A weaker association was observed for onset between 6 and 13 years of age (OR=1.17, P=0.035), but none for adult-onset asthma (OR=1.07, P=0.12). Cases were further stratified by sex, asthma severity and atopy status. An association with greater asthma severity was observed among early-onset asthma cases (P=0.0012), but no association with sex or atopy status was observed among the asthma cases. An association between sequence variants and the expression of genes in the 17q21 region was assessed in white blood cell RNA samples collected from Icelandic individuals (n=743). rs7216389 associated with the expression of GSDMB and ORMDL3 genes. However, other sequence variants showing a weaker association with asthma compared with that of rs7216389 were more strongly associated with the expression of both genes. Thus, the contribution of rs7216389-T to the development of asthma is unlikely to operate only through an impact on the expression of ORMDL3 or GSDMB genes.

Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

INTRODUCTION:Asthma is a complex heterogeneous and mutifactorial disease occurring at the interface of multiple genes that interact with various environmental stimuli insulting the immune system at different levels and different times of disease susceptibility.OBJECTIVE:The present paper is a review of the current status of the genetics of asthma.RESULTS:Sequence variants in hundreds of genes have been associated with asthma using both family-based and case control screening methods.CONCLUSION:As the number of genes known to be associated with asthma risk is rapidly growing, it is essential to begin integrating epidemiologic, genetic and genomic strategies to unravel the relationships between genotype and phenotype, and elucidate the pathogenesis of asthma with the goal to make clinical use of these discoveries.

Cysteinyl leukotrienes play an important role in the pathophysiology of many inflammatory disorders, including asthma. The aim of this study was to characterize the mechanisms underlying transcriptional regulation of the human cysteinyl leukotriene receptor 1 (hCYSLTR1) gene. 5′RACE was performed on human airway smooth muscle (HASM) and peripheral blood mononuclear cells. A 1128-bp region of the hCYSLTR1 main putative promoter was screened for polymorphisms by sequencing of 48 individuals. Luciferase reporter gene assays were performed using fragments of the core promoter (232 bp to 1128 bp) in HASM and THP1 cells. Three hCYSLTR1 transcripts were found, one representing 90% of all messenger RNA identified. The genomic location of the transcription start sites suggested there are two putative hCYSLTR1 promoters. The majority of the transcriptional activity of the main putative promoter was detected between −232 and −679 bp. Four single-nucleotide polymorphisms in strong linkage disequilibrium were found in the region studied: −561 (rs7066737), −642 (rs2806489), −781 (rs2637204), and −940 (rs321029), with three haplotypes observed. In THP1 cells, the G allele (−642) caused a twofold decrease in luciferase expression compared to the A allele. These data suggest that the majority of hCYSLTR1 transcripts in HASM and monocytes arise from a single promoter located immediately upstream of the 5′ untranslated region, although rarer transcripts can also occur. This study also raises the possibility that cell-type-dependent differences in transcriptional activity caused by the presence of specific haplotypes within the main CYSLTR1 promoter may be a predictor of disease risk or treatment response.

Single nucleotide polymorphisms (SNP) in genes encoding drug receptors, transporters, metabolizing enzymes or DNA repair genes are known to influence the toxicity and efficacy profile of drugs. While the transition of this information to DNA-based tests in order to improve drug selection, identify optimal dosing, maximize drug efficacy or minimize the risk of toxicity has been slow coming, recent advances in molecular biology have yielded new diagnostic assays, some of which have already been incorporated into therapeutic guidelines such as testing for Herceptin protein in breast cancer patients. Moreover, new high-throughput screening methods and data mining approaches have emerged that could revolutionalise the drug development process and reduce the risk of drug failure, while both lowering costs and delivering faster and better results. In this regard, the powerful coupling of linkage to ultra-high throughput genotyping, gene array or proteomics technology, together with innovative bioinformatics resources, provides a focused integrative strategy for pinpointing disease-causing genes that may generate validated drug targets and genes that are responsible for differential drug response. The new information generated has already sparked the initiation of novel strategies and diagnostic approaches in clinical development that are anticipated to ultimately lead to safer and more efficacious drugs. Keywords: pharmacogenomics, linkage, association, single nucleotide polymorphism, microarray, drug response

Genetic diversity contributes to both disease susceptibility and variability in response to drugs. However, it has proven difficult to isolate genes that underlie common complex disease, and genetic variations that influence clinical responses to drugs remain largely uncovered. The candidate gene approach to uncover genetic variations that contribute to disease susceptibility or variations in response to common drugs has not met expectations. Although the sib-pair linkage approach has certain theoretical advantages in dealing with common/complex disease, success has been slow in coming. Meanwhile family studies including siblings, cousins and second cousins, and studies in well-defined founder populations, have increasingly gained popularity and enabled scientists to map and isolate genes for common complex disease, such as schizophrenia and asthma. The latter method has generated new hope that this approach may also be effective in mapping genes that regulate drug response. Indeed, there is compelling evidence that corticosteroid sensitivity is a mapable trait in patients with asthma. Collectively, these studies support the value of leveraging information available within population-based data systems to map and isolate genes for common complex disease and drug response.

Background: Previous studies of vitamin D binding protein (VDBP, also known as group-specific component, Gc, encoded by the GC gene) have implicated two gene variants, GC*2 and GC*1F, as possible contributors with chronic obstructive pulmonary disease (COPD) protection and susceptibility, respectively. The objective of this study was to examine the association of VDBP to different subtypes of COPD.