Intensive Lifestyle (e)Support to Reverse Diabetes-2

Advanced diabetes-type-2 patients often have high insulin resistance. Over the years their insulin medication rises, which further increases their insulin resistance and glucose management problems. A HINTc (High Intensity Nutrition, Training & coaching) pilot study was conducted with 11 insulin-dependent patients. Hybrid eHealth support was given, with electronic support plus a multi-disciplinary health support team. Based on preliminary 12 week results, attractiveness and feasibility of the intervention were high: recommendation 9,0 out of 10 and satisfaction 9,1 out of 10. TAM (Technology Acceptance Model) surveys showed high usefulness, feasibility and intentions for future use. Acceptance and health behaviours were also reinforced by the rapid results (average 9% weight loss, 20% lower fasting glucose and 71% lower insulin medication, plus a 46% increase on the Quality of Life Physical Health dimension). Our analysis supports three types of conclusions. First, patients’ health literacy and quality of life improved strongly, both supporting healthier behaviours. Second, a virtuous cycle was started, helping patients reverse diabetes-2 progression. Third, a design analysis was conducted regarding service mix efficacy in relation to key requirements for designing ICT-enabled lifestyle interventions

Diabetes Lifestyle (e)Coaching 50 Weeks Follow Up; Technology Acceptance & e-Relationships

We report on the 50 weeks follow up results from a healthy lifestyle pilot (High Intensity Nutrition, Training & coaching), conducted with 11 insulin-dependent Type 2 Diabetes Mellites (DM2) patients. Hybrid eHealth support was given, with electronic support plus a multi-disciplinary health support team. Regarding the pilot goal of long term healthy lifestyle adoption in senior DM2 patients, challenges were: low ICT- and health literacy. This exploratory design analysis formulates design lessons based on 50 weeks follow up. The first 12 weeks contained intensive face-to-face and eSupported coaching. After that, patient self- management and eTools were key. After 50 weeks, attractiveness and feasibility of the intervention were perceived as high: recommendation 9,5 out of 10 and satisfaction 9,6 out of 10. TAM (Technology Acceptance Model) surveys showed high usefulness and feasibility. Acceptance and health behaviours were reinforced by the prolonged health results: Aerobic and strength capacity levels were improved at 50 weeks, plus Health Related Quality of Life (and biometric benefits and medication reductions, reported elsewhere). We draw three types of conclusions. First, patients’ health literacy and quality of life improved strongly, which both supported healthy behaviours, even after 50 weeks. Second, regarding eHealth theory, iterative growth cycles are beneficial for long term adoption and e-relationships. Third, a design analysis was conducted regarding long term service mix efficacy in relation to key requirements for designing ICT-enabled lifestyle interventions. Several suggestions for long term lifestyle eSupport are given

Politics in Spain: A Case of Monitory Democracy

Analysing the current political context in Spain is a major challenge to political theory. Spain is experiencing the accumulation of trends that in recent years have focused the attention of most theorists and political scientists: discrediting of the major parties, falling numbers of party members, disaffection, etc. In parallel, this trend has been accompanied by citizen mobilisations that, since 15 May 2011, are manifest in numerous channels and strategies. The aim of this paper was to analyse the complex Spanish context from the monitory democracy proposal. The results show how in recent years processes of public scrutiny have been consolidated through a range of citizen initiatives. The study offers an in-depth analysis of the main characteristics of the most notable cases and monitoring initiatives, and also reflects on their democratising potential.El análisis del contexto político actual en España es un reto importante para la teoría política. España está experimentando la acumulación de tendencias que en años recientes han centrado la atención de la mayor parte de teóricos y científicos políticos: desacreditación de los principales partidos, caída del número de miembros de los partidos, desafección, etc. Paralelamente, esta tendencia se ha visto acompañada por movilizaciones ciudadanas que, desde el 15 de mayo de 2011, son manifiestas en numerosos canales y estrategias. El objetivo de este documento es analizar el complejo contexto español desde la propuesta de democracia monitorizada. Los resultados muestran que en años recientes se han consolidado los procesos de escrutinio público mediante una serie de iniciativas ciudadanas. El estudio ofrece un análisis en profundidad de las principales características de los casos e iniciativas de monitorización más notables, y reflexiona también sobre su potencial democratizador

Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption we performed a population based genome-wide association study of ‘age at first tooth’ and ‘number of teeth’ using 5998 and 6609 individuals respectively from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2,446,724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of fifteen independent loci, with ten loci reaching genome-wide significance (p<5x10−8) for ‘age at first tooth’ and eleven loci for ‘number of teeth’. Together these associations explain 6.06% of the variation in ‘age of first tooth’ and 4.76% of the variation in ‘number of teeth’. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including a SNP in the protein-coding region of BMP4 (rs17563, P= 9.080x10−17). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes

Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 x 10(-10). Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (r(g) = 0.39, P = 1.68 x 10(-4)). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.Peer reviewe