Human mobility patterns at the smallest scales

We present a study on human mobility at small spatial scales. Differently from large scale mobility, recently studied through dollar-bill tracking and mobile phone data sets within one big country or continent, we report Brownian features of human mobility at smaller scales. In particular, the scaling exponents found at the smallest scales is typically close to one-half, differently from the larger values for the exponent characterizing mobility at larger scales. We carefully analyze 12-month data of the Eduroam database within the Portuguese university of Minho. A full procedure is introduced with the aim of properly characterizing the human mobility within the network of access points composing the wireless system of the university. In particular, measures of flux are introduced for estimating a distance between access points. This distance is typically non-Euclidean, since the spatial constraints at such small scales distort the continuum space on which human mobility occurs. Since two different ex- ponents are found depending on the scale human motion takes place, we raise the question at which scale the transition from Brownian to non-Brownian motion takes place. In this context, we discuss how the numerical approach can be extended to larger scales, using the full Eduroam in Europe and in Asia, for uncovering the transi- tion between both dynamical regimes.

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

A Survey of NHS Services for Opiate Dependents in Scotland

The aim of this study was to investigate the range of opiates available within the Scottish NHS for patients with opiate dependancy and to assess the process underlying clinical decision-making. Clinicians, representitives of drug action teams and NHS personnel were apporached and semi-structured phone conversations were the primary means to elicit information. Whilst methadone is almost universally prescribed in Scotland, buprenorphine, dihydrocodeine (not currently licensed for opiate dependance management), lofexidine and naltrexone are also used. Alternative therapies are variably used.This resource was contributed by The National Documentation Centre on Drug Use.

Defining the role of common variation in the genomic and biological architecture of adult human height.

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Discovery and refinement of loci associated with lipid levels.

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

Organization of lin genes and IS6100 among different strains of hexachlorocyclohexane-degrading Sphingomonas paucimobilis: evidence for horizontal gene transfer.

The organization of lin genes and IS6100 was studied in three strains of Sphingomonas paucimobilis (B90A, Sp+, and UT26) which degraded hexachlorocyclohexane (HCH) isomers but which had been isolated at different geographical locations. DNA-DNA hybridization data revealed that most of the lin genes in these strains were associated with IS6100, an insertion sequence classified in the IS6 family and initially found in Mycobacterium fortuitum. Eleven, six, and five copies of IS6100 were detected in B90A, Sp+, and UT26, respectively. IS6100 elements in B90A were sequenced from five, one, and one regions of the genomes of B90A, Sp+, and UT26, respectively, and were found to be identical. DNA-DNA hybridization and DNA sequencing of cosmid clones also revealed that S. paucimobilis B90A contains three and two copies of linX and linA, respectively, compared to only one copy of these genes in strains Sp+ and UT26. Although the copy number and the sequence of the remaining genes of the HCH degradative pathway (linB, linC, linD, and linE) were nearly the same in all strains, there were striking differences in the organization of the linA genes as a result of replacement of portions of DNA sequences by IS6100, which gave them a strange mosaic configuration. Spontaneous deletion of linD and linE from B90A and of linA from Sp+ occurred and was associated either with deletion of a copy of IS6100 or changes in IS6100 profiles. The evidence gathered in this study, coupled with the observation that the G+C contents of the linA genes are lower than that of the remaining DNA sequence of S. paucimobilis, strongly suggests that all these strains acquired the linA gene through horizontal gene transfer mediated by IS6100. The association of IS6100 with the rest of the lin genes further suggests that IS6100 played a role in shaping the current lin gene organization.

Common variants associated with plasma triglycerides and risk for coronary artery disease.

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

Pääkaupunkiseudun perhevalmennus vuonna 2015

Opinnäytetyön tarkoitus on kuvata perhevalmennuksen ennakointia pääkaupunkiseudulla vuoteen 2015 ja kartoittaa siihen vaikuttavia tekijöitä APESTE-analyysin mukaan. Toinen tavoite on luoda visio perhevalmennuksesta vuonna 2015. Opinnäytetyö on rajattu koskemaan vain pääkaupunkiseutua. Opinnäytetyö mukailee delfoi-menetelmää. Työtä varten koottiin perhevalmennuksen asiantuntijaryhmä (n=9), jota ensimmäisellä kyselykierroksella haastateltiin APESTE-analyysin mukaan asiakkaaseen liittyvistä, poliittisista, taloudellisista, sosiaalisista, teknisistä ja ekologisista tekijöistä, jotka vaikuttavat perhevalmennukseen. Lisäksi he visioivat perhevalmennusta vuonna 2015. Haastattelut analysoitiin sisällönanalyysia käyttäen. Toisella kierroksella asiantuntijaryhmä (n=3) vastasi sähköpostikyselyyn, jossa he saivat tarkentaa näkemyksiään. Haastattelut ja kyselyvastaukset muodostivat tutkimusaineiston. Lopullinen analyysi tehtiin kummankin kierroksen vastauksista. Perhevalmennuksen asiakaskunta polarisoituu ja monipuolistuu. Asiakkaiden koulutustaso nousee, mutta myös heikosti pärjäävien määrä lisääntyy. Asiakkaiden arvomaailmat kahtiajakautuvat, heidän tarpeidensa skaala laajenee ja terveysongelmansa lisääntyvät. Perheiden tukiverkot muuttuvat: perinteisten sukulaisyhteisöjen sijaan ihmiset saavat tukea verkostoitumalla samanhenkisten ihmisten kanssa. Yhteistyö julkisen, yksityisen ja kolmannen sektorin sekä eri hallinnonalojen välillä lisääntyy. Resurssit eivät lisäänny ja palveluita karsitaan. Ihmisten oma vastuu pärjäämisestään lisääntyy ja samalla kätilön työ muuttuu vaativammaksi. Internet tulee tärkeäksi osaksi perhevalmennusta. Uusien innovaatioiden käyttöönotto on hidasta. Eettiset kysymykset tulevat entistä tärkeämmiksi tekniikan kehittymisen suomien mahdollisuuksien myötä. Ihmisten ympäristötietoisuus lisääntyy ja ympäristökäyttäytyminen muuttuu. Äitiyshuolto on keskitetty osaamiskeskuksiin. Perhevalmennuksesta vastaa kätilö moniammatillisen tiimin kanssa. Kätilö organisoi perhevalmennusta muun äitiyneuvolatyön ohessa. Näin hän tuntee odottavat perheet ja osaa toteuttaa perhevalmennusta asiakaslähtöisesti, vaikka valmennuksella onkin yhtenäinen rakenne. Valmennus muuttuu toiminnallisemmaksi ja keskustelevammaksi. Ryhmäkoot pienenevät hiukan ja puolisoidenkin toiveet otetaan paremmin huomioon. Perhevalmennus alkaa ensimmäisen raskauskolmanneksen aikana ja jatkuu vielä vauvan syntymän jälkeen. Tärkeitä aiheita synnytykseen valmentautumisen, vauvanhoidon ja imetyksen ohella ovat parisuhde ja seksuaalisuus sekä psyykkinen hyvinvointi. Avainsanat perhevalmennus, ennakointi, APESTE-analyysi

Ohjeita ortoptisiin harjoitteisiin

Teimme opinnäytetyönämme oppaan internetiin ortoptisista harjoitteista. Tavoitteenamme oli tehdä optikoille selkeä ja tiivis opas, jota he voisivat käyttää työvälineenä omassa työssään. Toiveenamme oli, että opas toimisi tukena ortoptisten harjoitteiden valinnassa ja siitä olisi apua annettaessa harjoitteita asiakkaille. Halusimme myös herättää oppaan avulla optikoiden kiinnostuksen ortoptisten harjoitteiden käyttämiseen yhtenä mahdollisuutena lähiongelmien vähentämiseen. Työmme teoriaosuus selvittää silmän ja näköjärjestelmän toimintaperiaatteita, jotka täytyy tietää ymmärtääkseen binokulariteetin ongelmia ja ortoptisten harjoitteiden käyttöä erilaisissa binokulaarisen näkemisen ongelmatilanteissa. Varsinainen opas tehtiin teoriaosuuden pohjalta. Oppaassa esittelemme ortoptisia harjoitteita, joista on apua akkommodaation, konvergenssin ja exoforian aiheuttamiin lähiongelmiin. Kerromme lyhyesti kyseisiin ongelmiin liittyvät oireet ja annamme ohjeet kuhunkin ongelmaan liittyvän harjoitteen suorittamiseen. Lisäksi oppaasta löytyy jokaisesta harjoitteesta tulostettava ohje annettavaksi asiakkaalle kotiharjoittelun tueksi. Yhteistyökumppaninamme toimi Optiikka Media Oy (OMO), joka julkaisee oppaan internetsivuillaan tekemämme luonnoksen pohjalta. Oppaan asiasisällön on tarkastanut optikko, ortoptisti Tuula Kääriäinen Näkökeskus Visiosta.

Suuhygienisti- ja hammaslääkäriopiskelijoiden yhteisöllisen asiantuntijuuden kehittyminen koulutuksen aikana

Opinnäytetyö kartoittaa suuhygienisti- ja hammaslääkäriopiskelijoiden työn organisoinnin ja tehtävä-jaon nykytilannetta ja kehittämistarvetta. Työn tarve pohjautuu lainsäädäntöön, jonka mukaan kaikkien kuntien tulee pystyä järjestämään hammashoito asukkailleen. Suun terveydenhuollossa hoidon tarve on tällä hetkellä suurempi kuin hoidon tarjonta. Kehittämishanke on osa Työn organisointi ja työnjako terveydenhuollon erityisaloilla -hanketta. Opinnäytetyön tarkoituksena on käynnistää yhteisöllisen asiantuntijuuden kehittäminen työn organisoinnin ja tehtäväjaon parantamiseksi. Opinnäytetyön tavoitteena on tuottaa tietoa suuhygienisti- ja hammaslääkäriopiskelijoiden yhteisöllisen asiantuntijuuden nykytilanteesta ja kehitystarpeista potilaiden hoidossa. Opinnäytetyö on kvantitatiivinen, ja se on toteutettu projektin omaisesti. Kyselylomake lähetettiin e-lomake muodossa 149 opiskelijalle. Vastanneita oli 50, joista 26 oli suuhygienisti- ja 24 hammaslääkäriopiskelijaa. Kyselyn tulokset analysoitiin SPSS-ohjelmalla. Teoreettisena viitekehyksenä työssä on Hannanin systemoidun kirjallisuuskatsauksen perusteella tuottama malli. Se on valittu työn teoreettiseksi pohjaksi, koska se toimii koko hankkeen teoreettisena viitekehyksenä. Hannanin mallin keskeisiä käsitteitä ovat työtyytyväisyys, työhönsitoutuminen, sairauspoissaolot, työssä vaikuttamisen mahdollisuudet, työstressi, roolikonfliktit ja -epäselvyydet. Kyselyn tulokset osoittavat, että suuhygienisti- ja hammaslääkäriopiskelijat ovat jokseenkin samaa mieltä siitä, että koulutuksen aikainen yhteistyö on hyvä asia. Tutkimuksen mukaan suuhygienisti- ja hammaslääkäriopiskelijat ovat epätietoisia toistensa osaamisalueista, mutta molemmat opiskelijaryhmät ovat kuitenkin kiinnostuneita yhteistyön tekemisestä. Monien yhteistyön laatua ja määrää koskevien kysymysten osalta suuhygienisti- ja hammaslääkäriopiskelijoiden näkemykset eivät kohtaa. Kyselyyn vastanneet opiskelijat kokevat informaation kulun riittämättömyyden opiskelijaryhmien ja opettajien välillä yhdeksi ongelmaksi. Samoin tietämättömyys suuhygienisti- ja hammaslääkäriopiskelijoiden välillä toistensa työnkuvasta todetaan ongelmalliseksi. Opinnäytetyö sisältää myös jonkin verran konkreettisia kehittämisehdotuksia edellä mainittuihin ongelmiin. Työssä esitetään muun muassa yhteisen keskustelufoorumin perustamista sekä opetussuunnitelmien muutoksia. Opinnäytetyö tarjoaa hyvän pohjan yhteistyön kehittämisen jatkotoimille.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.