Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10-8).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

Ash2 acts as an Ecdysone Receptor coactivator by stabilizing the histone methyltransferase Trr.

The molting hormone ecdysone triggers chromatin changes via histone modifica- tions that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with tran- scriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdy- sone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr and is re- quired for its stabilization. Thus we propose that Ash2 functions together with Trr as an ecdysone receptor coactivator.

Assessment of dissolution techniques for the analysis of ceramic samples by plasma spectrometry

In this study, 13 ceramic samples were subjected to dissolution using three different procedures: (a) acid attack in open PTFE vessels with a mixture of HF-HClO4, (b) fusion of the sample with lithium metaborate and (c) microwave digestion in PTFE bombs. The samples used in the study had been previously analyzed by neutron activation analysis (NAA), X-ray fluorescence (XRF) and X-ray diffraction (XRD) and they cover a wide range of ceramics fired in different atmospheres and temperatures as well as different mineralogical and chemical compositions. The effectiveness of each procedure is evaluated in terms of its ability to dissolve the various mineralogical phases of the samples, of the number of elements that can be determined and of the time needed for the whole scheme of analysis to be completed.

Caracterizació arqueomètrica de les ceràmiques tardanes de la plaça del Rei de Barcelona

Un total de 40 ceràmiques tardanes, en la majoria de casos grolleres, que procedeixen de contextos de la segona meitat del segle VI-segle VII de les excavacions de la plaça del Rei de Barcelona, han estat caracteritzades arqueomètricament mitjançant fluorescència de raigs X (FRX), difracció de raigs X (DRX) i microscòpia òptica de làmina prima (MO). A la mostra estudiada, els resultats han permès establir l"existència de fins a 10 grups diferents, alguns dels quals clarament heterogenis, la qual cosa permet pensar que l"anàlisi d"un nombre més elevat de mostres hauria revelat un nombre encara més gran de produccions en el jaciment. Entre les produccions caracteritzades se n"ha identificat una de ceràmica comuna fina de producció local o regional, així com nou de ceràmiques grolleres tant importades com locals i/o regionals.

Tipologies ceràmiques i tècniques quantitatives: apunts d"historiografia i procediments

[cas] Si bien los conceptos de «clasificación» y «tipología» han estado vinculados a la Arqueología desde las primeras seriaciones de materiales puramente descriptivas de los primeros anticuarios y diletantes de los siglos XVII-XVIII, no es menos cierto que su desarrollo ulterior durante los siglos XIX y XX madurado al abrigo del marco cientificista del positivismo decimonónico se ha visto estimulado fundamentalmente por dos factores necesarios. En primer lugar, por el permanente debate librado por las diferentes corrientes teórico-metodológicas que incansablemente han ido sacudiendo uno tras otro, en un imparable proceso dialéctico, los sucesivos paradigmas preexistentes. Y en segundo lugar, por el progreso de la tecnología informática, que permitió el procesamiento más rápido y objetivo del cada vez más numeroso y abrumador conjunto de datos generado por la investigación.

Lisäainetehtaan tuotantoprosessin kehittäminen

Tämän diplomityön tarkoituksena oli Finnsementti osakeyhtiöön kuuluvan betonin lisäaineita valmistavan tehtaan tuotantoprosessin kehittäminen. Työssä laadittiin myynnin kasvuennusteen perusteella suunnitelma, jonka mukaan määriteltiin betonin lisäaineille ja raaka-aineille sopivat varastosäiliöt. Suunnitelman perusteella määriteltiin kiinteät putkilinjat sekä kirkkaille että tummille nesteille, jolloin materiaalihäviöt saatiin pienemmiksi ja putkilinjojen pesun tarve väheni. Lisäksi työssä otettiin huomioon tuotantoprosessin automatisointi. Suunnitellusta projektista laadittiin alustava kustannusarvio, toteutusaikataulu sekä sijoituspiirustus, putkisto-instrumentointikaavio ja 3D-piirrokset. Projektin kustannusarvioksi saatiin noin 290 tuhatta markkaa ja projektin pituudeksi noin 11 viikkoa.

Study on Accuracy of Judgments by Chinese Fingerprint Examiners

The interpretation of fingerprint evidence depends on the judgments of fingerprint examiners. This study assessed the accuracy of different judgments made by fingerprint examiners following the Analysis, Comparison, and Evaluation (ACE) process. Each examiner was given five marks for analysis, comparison, and evaluation. We compared the experts' judgments against the ground truth and used an annotation platform to evaluate how Chinese fingerprint examiners document their comparisons during the identification process. The results showed that different examiners demonstrated different accuracy of judgments and different mechanisms to reach them.

Muovituotteen markkinakartoitus ja markkinoinninsuunnittelu

Oy Finnpak Ab haluaa parantaa valumuovituoteryhmänsä markkina-tuntemusta ja kartoittaa potentiaaliset asiakkaansa Suomen ja Ruotsin markkinoilla. Diplomityön tavoitteena on selvittää edellä olevat asiat, sekä tarkastella yrityksen nykytilaa ja miettiä, mitä kehittämistä yrityksen nykyisessä markkinoinnissa on. Saatujen tietojen perusteella muodos-tetaan toimintorunko, markkinointisuunnitelma, jota käytetään hyväksi lähivuosien liiketoimintastrategioiden suunnittelussa.Potentiaalisista asiakkaista saadut tiedot perustuvat kyselytutkimukseen. Tutkimus suoritettiin soittamalla ensin valitun teollisuussektorin yrityksiin ja kohdeyrityksille lähetettiin tutkimuslomake.Työssä saatujen tulosten mukaan sekä sisäisessä että ulkoisessa markkinoinnissa on huomattavasti parantamisen varaa. Tärkein työssä esiin tullut uudistus valumuovipuolella oli tuotekehityksen maksullistaminen. Ylivoimaisesti suurin työssä esiin tullut projekti on kuitenkin yritysnimen yhtäläistäminen nykyisen tuotenimen kanssa. Yrityksen nimi on tarkoitus uudistaa vuoteen 2003 mennessä, joka on yrityksen neljäskymmenes toimintavuosi.

Detection of Clinically Significant Prostate Cancer Using Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy: A Systematic Review.

CONTEXT: The current standard for diagnosing prostate cancer in men at risk relies on a transrectal ultrasound-guided biopsy test that is blind to the location of the cancer. To increase the accuracy of this diagnostic pathway, a software-based magnetic resonance imaging-ultrasound (MRI-US) fusion targeted biopsy approach has been proposed. OBJECTIVE: Our main objective was to compare the detection rate of clinically significant prostate cancer with software-based MRI-US fusion targeted biopsy against standard biopsy. The two strategies were also compared in terms of detection of all cancers, sampling utility and efficiency, and rate of serious adverse events. The outcomes of different targeted approaches were also compared. EVIDENCE ACQUISITION: We performed a systematic review of PubMed/Medline, Embase (via Ovid), and Cochrane Review databases in December 2013 following the Preferred Reported Items for Systematic reviews and Meta-analysis statement. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. EVIDENCE SYNTHESIS: Fourteen papers reporting the outcomes of 15 studies (n=2293; range: 13-582) were included. We found that MRI-US fusion targeted biopsies detect more clinically significant cancers (median: 33.3% vs 23.6%; range: 13.2-50% vs 4.8-52%) using fewer cores (median: 9.2 vs 37.1) compared with standard biopsy techniques, respectively. Some studies showed a lower detection rate of all cancer (median: 50.5% vs 43.4%; range: 23.7-82.1% vs 14.3-59%). MRI-US fusion targeted biopsy was able to detect some clinically significant cancers that would have been missed by using only standard biopsy (median: 9.1%; range: 5-16.2%). It was not possible to determine which of the two biopsy approaches led most to serious adverse events because standard and targeted biopsies were performed in the same session. Software-based MRI-US fusion targeted biopsy detected more clinically significant disease than visual targeted biopsy in the only study reporting on this outcome (20.3% vs 15.1%). CONCLUSIONS: Software-based MRI-US fusion targeted biopsy seems to detect more clinically significant cancers deploying fewer cores than standard biopsy. Because there was significant study heterogeneity in patient inclusion, definition of significant cancer, and the protocol used to conduct the standard biopsy, these findings need to be confirmed by further large multicentre validating studies. PATIENT SUMMARY: We compared the ability of standard biopsy to diagnose prostate cancer against a novel approach using software to overlay the images from magnetic resonance imaging and ultrasound to guide biopsies towards the suspicious areas of the prostate. We found consistent findings showing the superiority of this novel targeted approach, although further high-quality evidence is needed to change current practice.

Reklamaatioprosessin kehittäminen tavarataloketjussa

Tämän työn tavoitteena oli selvittää Sokoksen reklamaatioprosessin kehittämisessä saavutettavia etuja. Reklamaatiokäytäntö muuttui tämän työn aikana paperiversiosta sähköiseen muotoon, ja tässä on pyritty selvittämään muutosten vaikutuksia seurantaan ja ja toimintaan. Tavoitteena oli myös rakentaa prosessin seurannan kannalta tärkeitä mittareita kehityksen seurantaa varten.Sokos-ketjussa tehtiin vuonna 1999 yli 20 000 virheilmoitusta hankintayhtiöön. Näistä osa oli toimitusvirheitä ja osa tuotevirheitä. Reklamaatioiden arvoksi muodostui ostohinnoin lähes seitsemän miljoonaa markkaa. Reklamaatioiden suuresta määrästä johtuen Sokoksella katsottiin järkeväksi tehostaa reklamointia siirtymällä tekemään virheilmoitukset suoraan tietojärjestelmään ja välittämään ne sitä kautta automaattisesti hankintayhtiöön. Uuteen toimintamalliin siirryttiin 1.5.2000. Prosessissa saavutettuja etuja mitattiin tässä työssä järjestämällä henkilöstölle kysely, sekä mittaamalla ja arvioimalla ajansäästöjä. Investoinnin kannattavuutta tutkittiin erilaisten tulevaisuusnäkymien perusteella. Tutkimuksen perusteella uusi prosessi on helpottanut tekijöiden työtä, seuranta/mittaaminen on huomattavasti aiempaa tehokkaampaa, ja investointi muodostuu melko suurella todennäköisyydellä kannattavaksi tiettyjen hyvityssummiin liittyvien ehtojen täyttyessä.

Fingermark initial composition and aging using Fourier transform infrared microscopy (μ-FTIR)

This study investigated fingermark residues using Fourier transform infrared microscopy (μ- FTIR) in order to obtain fundamental information about the marks' initial composition and aging kinetics. This knowledge would be an asset for fundamental research on fingermarks, such as for dating purposes. Attenuated Total Reflection (ATR) and single-point reflection modes were tested on fresh fingermarks. ATR proved to be better suited and this mode was subsequently selected for further aging studies. Eccrine and sebaceous material was found in fresh and aged fingermarks and the spectral regions 1000-1850 cm-1 and 2700-3600 cm-1 were identified as the most informative. The impact of substrates (aluminium and glass slides) and storage conditions (storage in the light and in the dark) on fingermark aging was also studied. Chemometric analyses showed that fingermarks could be grouped according to their age regardless of the substrate when they were stored in an open box kept in an air-conditioned laboratory at around 20°C next to a window. On the contrary, when fingermarks were stored in the dark, only specimens deposited on the same substrate could be grouped by age. Thus, the substrate appeared to influence aging of fingermarks in the dark. Furthermore, PLS regression analyses were conducted in order to study the possibility of modelling fingermark aging for potential fingermark dating applications. The resulting models showed an overall precision of ±3 days and clearly demonstrated their capability to differentiate older fingermarks (20 and 34-days old) from newer ones (1, 3, 7 and 9-days old) regardless of the substrate and lighting conditions. These results are promising from a fingermark dating perspective. Further research is required to fully validate such models and assess their robustness and limitations in uncontrolled casework conditions.

Impacte tecnològic en el nou món colonial. Aculturació en arqueologia i arqueometria ceràmica (TECNOLONIAL)

El projecte se centra en l"expansió colonial atlàntica espanyola, especialment durant el segle XVI, estudiada a partir del coneixement arqueològic i arqueomètric de la ceràmica de pisa o majòlica, de les ceràmiques vidrades i dels contenidors de transport, però també de les ceràmiques indígenes d"estil europeu. Amb això, l"objectiu bàsic del projecte és aprofundir en els aspectes d"aculturació o de transculturació, de relacions i d"influències que es generen en un procés colonitzador, entre els colonitzadors i els grups humans colonitzats, però també l"aparició de noves identitats que sorgeixen en els espais colonitzats, amb grups humans generalment mixtos i complexos. Aquest objectiu general es concreta en quatre objectius concrets: la caracterització arqueològica i arqueomètrica dels centres productors i de difusió de Barcelona, Sevilla i el País Basc; la caracterització d"aquests materials, i dels materials indígenes d"influència europea, dels centres receptors de Gran Canària, Perú, Colombia i Canadà; la interpretació d"aquests materials ceràmics tant en termes de comerç, intercanvi i difusió, com des de la perspectiva del seu consum, com a artefactes que marquen o confereixen identitat social o estatus, i la seva participació en aspectes com les tradicions culturals, l"etnicitat o la creació de noves identitats; i la derivació de models teòrics aplicables a contextos colonials, basats en els estudis arqueològics i arqueomètrics de les ceràmiques implicades.

Disseny amforal i canvi tecnològic al voltant del canvi d'era: L'aportació de l'Anàlisi d'Elements Finits

[spa] Mediante el Análisis de Elementos Finitos es posible evaluar un diseño cerámico en función de su tipologia y de las propiedades mecánicas del material. Su aplicación permite considerar los factores tecnológicos que puedan haber condicionado el cambio de una tipologia cerámica. Este análisis se ilustra con los primeros tipos anfóricos romanos producidos en la actual Cataluña (Dressel 1, Tarraconense 1 y Pascuai 7).

L'anàlisi arqueomètrica i implicacions estadístiques en l'estudi ceràmic

En aquest text ens centrarem en els fonaments de la metodologia arqueomètrica referent a la caracterització de ceràmiques arqueològiques, així com en la manera en què el treball posterior a qualsevol excavació (inventari del material, interpretació del jaciment) pot condicionar la síntesi d"aquesta caracterització.

La pisa de Barcelona: una aproximació arqueomètrica al seu estudi

El coneixement que es té avui dia de la pisa barcelonina, quant a produccions, formes, decoracions, etc., ha avançat de manera significativa, però resten per resoldre qüestions relacionades amb la tecnologia de producció, l"evolució d"aquesta tecnologia, l"aprovisionament i el tractament de les matèries primeres o les diferències de qualitats entre els diversos tallers existents a la ciutat de Barcelona. Per aquest motiu, s"ha iniciat un programa de caracterització arqueomètrica de la pisa de Barcelona, del qual aquest treball presenta uns primers resultats.