Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score--the CoLaus Study.

AIMS/HYPOTHESIS: Several susceptibility genes for type 2 diabetes have been discovered recently. Individually, these genes increase the disease risk only minimally. The goals of the present study were to determine, at the population level, the risk of diabetes in individuals who carry risk alleles within several susceptibility genes for the disease and the added value of this genetic information over the clinical predictors. METHODS: We constructed an additive genetic score using the most replicated single-nucleotide polymorphisms (SNPs) within 15 type 2 diabetes-susceptibility genes, weighting each SNP with its reported effect. We tested this score in the extensively phenotyped population-based cross-sectional CoLaus Study in Lausanne, Switzerland (n = 5,360), involving 356 diabetic individuals. RESULTS: The clinical predictors of prevalent diabetes were age, BMI, family history of diabetes, WHR, and triacylglycerol/HDL-cholesterol ratio. After adjustment for these variables, the risk of diabetes was 2.7 (95% CI 1.8-4.0, p = 0.000006) for individuals with a genetic score within the top quintile, compared with the bottom quintile. Adding the genetic score to the clinical covariates improved the area under the receiver operating characteristic curve slightly (from 0.86 to 0.87), yet significantly (p = 0.002). BMI was similar in these two extreme quintiles. CONCLUSIONS/INTERPRETATION: In this population, a simple weighted 15 SNP-based genetic score provides additional information over clinical predictors of prevalent diabetes. At this stage, however, the clinical benefit of this genetic information is limited.

3-T direct MR arthrography of the wrist: value of finger trap distraction to assess intrinsic ligament and triangular fibrocartilage complex tears.

PURPOSE: To determine the value of applying finger trap distraction during direct MR arthrography of the wrist to assess intrinsic ligament and triangular fibrocartilage complex (TFCC) tears. MATERIALS AND METHODS: Twenty consecutive patients were prospectively investigated by three-compartment wrist MR arthrography. Imaging was performed with 3-T scanners using a three-dimensional isotropic (0.4 mm) T1-weighted gradient-recalled echo sequence, with and without finger trap distraction (4 kg). In a blind and independent fashion, two musculoskeletal radiologists measured the width of the scapholunate (SL), lunotriquetral (LT) and ulna-TFC (UTFC) joint spaces. They evaluated the amount of contrast medium within these spaces using a four-point scale, and assessed SL, LT and TFCC tears, as well as the disruption of Gilula's carpal arcs. RESULTS: With finger trap distraction, both readers found a significant increase in width of the SL space (mean Δ = +0.1mm, p ≤ 0.040), and noticed more contrast medium therein (p ≤ 0.035). In contrast, the differences in width of the LT (mean Δ = +0.1 mm, p ≥ 0.057) and UTFC (mean Δ = 0mm, p ≥ 0.728) spaces, as well as the amount of contrast material within these spaces were not statistically significant (p = 0.607 and ≥ 0.157, respectively). Both readers detected more SL (Δ = +1, p = 0.157) and LT (Δ = +2, p = 0.223) tears, although statistical significance was not reached, and Gilula's carpal arcs were more frequently disrupted during finger trap distraction (Δ = +5, p = 0.025). CONCLUSION: The application of finger trap distraction during direct wrist MR arthrography may enhance both detection and characterisation of SL and LT ligament tears by widening the SL space and increasing the amount of contrast within the SL and LT joint spaces.

Angiotensin II receptor blockade: is there truly a benefit of adding an ACE inhibitor?

We assessed the blockade of the renin-angiotensin system (RAS) achieved with 2 angiotensin (Ang) antagonists given either alone at different doses or with an ACE inhibitor. First, 20 normotensive subjects were randomly assigned to 100 mg OD losartan (LOS) or 80 mg OD telmisartan (TEL) for 1 week; during another week, the same doses of LOS and TEL were combined with 20 mg OD lisinopril. Then, 10 subjects were randomly assigned to 200 mg OD LOS and 160 mg OD TEL for 1 week and 100 mg BID LOS and 80 mg BID TEL during the second week. Blockade of the RAS was evaluated with the inhibition of the pressor effect of exogenous Ang I, an ex vivo receptor assay, and the changes in plasma Ang II. Trough blood pressure response to Ang I was blocked by 35+/-16% (mean+/-SD) with 100 mg OD LOS and by 36+/-13% with 80 mg OD TEL. When combined with lisinopril, blockade was 76+/-7% with LOS and 79+/-9% with TEL. With 200 mg OD LOS, trough blockade was 54+/-14%, but with 100 mg BID it increased to 77+/-8% (P<0.01). Telmisartan (160 mg OD and 80 mg BID) produced a comparable effect. Thus, at their maximal recommended doses, neither LOS nor TEL blocks the RAS for 24 hours; hence, the addition of an ACE inhibitor provides an additional blockade. A 24-hour blockade can be achieved with an angiotensin antagonist alone, provided higher doses or a BID regimen is used.

Eosinophilie sanguine: quel bilan, quel cheminement diagnostique [Peripheral blood eosinophilia: diagnostic value and further assessment].

Although not specific, an increased in peripheral blood eosinophils may contribute substantially to the diagnosis of numerous infectious, allergic and inflammatory diseases. The scope of this article is to detail pathologies associated with peripheral eosinophilia by order of frequency and to guide further investigations.

Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

AIM: To confirm the accuracy of sentinel node biopsy (SNB) procedure and its morbidity, and to investigate predictive factors for SN status and prognostic factors for disease-free survival (DFS) and disease-specific survival (DSS). MATERIALS AND METHODS: Between October 1997 and December 2004, 327 consecutive patients in one centre with clinically node-negative primary skin melanoma underwent an SNB by the triple technique, i.e. lymphoscintigraphy, blue-dye and gamma-probe. Multivariate logistic regression analyses as well as the Kaplan-Meier were performed. RESULTS: Twenty-three percent of the patients had at least one metastatic SN, which was significantly associated with Breslow thickness (p<0.001). The success rate of SNB was 99.1% and its morbidity was 7.6%. With a median follow-up of 33 months, the 5-year DFS/DSS were 43%/49% for patients with positive SN and 83.5%/87.4% for patients with negative SN, respectively. The false-negative rate of SNB was 8.6% and sensitivity 91.4%. On multivariate analysis, DFS was significantly worsened by Breslow thickness (RR=5.6, p<0.001), positive SN (RR=5.0, p<0.001) and male sex (RR=2.9, p=0.001). The presence of a metastatic SN (RR=8.4, p<0.001), male sex (RR=6.1, p<0.001), Breslow thickness (RR=3.2, p=0.013) and ulceration (RR=2.6, p=0.015) were significantly associated with a poorer DSS. CONCLUSION: SNB is a reliable procedure with high sensitivity (91.4%) and low morbidity. Breslow thickness was the only statistically significant parameter predictive of SN status. DFS was worsened in decreasing order by Breslow thickness, metastatic SN and male gender. Similarly DSS was significantly worsened by a metastatic SN, male gender, Breslow thickness and ulceration. These data reinforce the SN status as a powerful staging procedure

Missing value imputation in longitudinal measures of alcohol consumption

Attrition in longitudinal studies can lead to biased results. The study is motivated by the unexpected observation that alcohol consumption decreased despite increased availability, which may be due to sample attrition of heavy drinkers. Several imputation methods have been proposed, but rarely compared in longitudinal studies of alcohol consumption. The imputation of consumption level measurements is computationally particularly challenging due to alcohol consumption being a semi-continuous variable (dichotomous drinking status and continuous volume among drinkers), and the non-normality of data in the continuous part. Data come from a longitudinal study in Denmark with four waves (2003-2006) and 1771 individuals at baseline. Five techniques for missing data are compared: Last value carried forward (LVCF) was used as a single, and Hotdeck, Heckman modelling, multivariate imputation by chained equations (MICE), and a Bayesian approach as multiple imputation methods. Predictive mean matching was used to account for non-normality, where instead of imputing regression estimates, "real" observed values from similar cases are imputed. Methods were also compared by means of a simulated dataset. The simulation showed that the Bayesian approach yielded the most unbiased estimates for imputation. The finding of no increase in consumption levels despite a higher availability remained unaltered. Copyright (C) 2011 John Wiley & Sons, Ltd.

Association of major and minor ECG abnormalities with coronary heart disease events.

CONTEXT: In populations of older adults, prediction of coronary heart disease (CHD) events through traditional risk factors is less accurate than in middle-aged adults. Electrocardiographic (ECG) abnormalities are common in older adults and might be of value for CHD prediction. OBJECTIVE: To determine whether baseline ECG abnormalities or development of new and persistent ECG abnormalities are associated with increased CHD events. DESIGN, SETTING, AND PARTICIPANTS: A population-based study of 2192 white and black older adults aged 70 to 79 years from the Health, Aging, and Body Composition Study (Health ABC Study) without known cardiovascular disease. Adjudicated CHD events were collected over 8 years between 1997-1998 and 2006-2007. Baseline and 4-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict CHD events. MAIN OUTCOME MEASURE: Adjudicated CHD events (acute myocardial infarction [MI], CHD death, and hospitalization for angina or coronary revascularization). RESULTS: At baseline, 276 participants (13%) had minor and 506 (23%) had major ECG abnormalities. During follow-up, 351 participants had CHD events (96 CHD deaths, 101 acute MIs, and 154 hospitalizations for angina or coronary revascularizations). Both baseline minor and major ECG abnormalities were associated with an increased risk of CHD after adjustment for traditional risk factors (17.2 per 1000 person-years among those with no abnormalities; 29.3 per 1000 person-years; hazard ratio [HR], 1.35; 95% CI, 1.02-1.81; for minor abnormalities; and 31.6 per 1000 person-years; HR, 1.51; 95% CI, 1.20-1.90; for major abnormalities). When ECG abnormalities were added to a model containing traditional risk factors alone, 13.6% of intermediate-risk participants with both major and minor ECG abnormalities were correctly reclassified (overall net reclassification improvement [NRI], 7.4%; 95% CI, 3.1%-19.0%; integrated discrimination improvement, 0.99%; 95% CI, 0.32%-2.15%). After 4 years, 208 participants had new and 416 had persistent abnormalities. Both new and persistent ECG abnormalities were associated with an increased risk of subsequent CHD events (HR, 2.01; 95% CI, 1.33-3.02; and HR, 1.66; 95% CI, 1.18-2.34; respectively). When added to the Framingham Risk Score, the NRI was not significant (5.7%; 95% CI, -0.4% to 11.8%). CONCLUSIONS: Major and minor ECG abnormalities among older adults were associated with an increased risk of CHD events. Depending on the model, adding ECG abnormalities was associated with improved risk prediction beyond traditional risk factors.

Mobile E-commerce business model – A value web based approach to business models in mobile gaming industry

Tämän tutkimuksen tavoitteena oli tutkia langattomien internet palveluiden arvoverkkoa ja liiketoimintamalleja. Tutkimus oli luonteeltaan kvalitatiivinen ja siinä käytettiin strategiana konstruktiivista case-tutkimusta. Esimerkkipalveluna oli Treasure Hunters matkapuhelinpeli. Tutkimus muodostui teoreettisesta ja empiirisestä osasta. Teoriaosassa liitettiin innovaatio, liiketoimintamallit ja arvoverkko käsitteellisesti toisiinsa, sekä luotiin perusta liiketoimintamallien kehittämiselle. Empiirisessä osassa keskityttiin ensin liiketoimintamallien luomiseen kehitettyjen innovaatioiden pohjalta. Lopuksi pyrittiin määrittämään arvoverkko palvelun toteuttamiseksi. Tutkimusmenetelminä käytettiin innovaatiosessiota, haastatteluja ja lomakekyselyä. Tulosten pohjalta muodostettiin useita liiketoimintakonsepteja sekä kuvaus arvoverkon perusmallista langattomille peleille. Loppupäätelmänä todettiin että langattomat palvelut vaativat toteutuakseen useista toimijoista koostuvan arvoverkon.

Development of a Business Model that Supports Mobile Value-Added Services Market Creation in Emerging Countries

Tutkielman tavoitteena on luoda liiketoimintamalli, joka tukee langattomien matkaviestintäpalveluiden markkinoiden luomista kehittyvillä markkinoilla. Teoreettinen osa tarkastelee langattomien matkaviestintäpalveluiden liiketoimintamallin kehittämisen tärkeimpiä elementtejä CIS maissa. Teoreettisen kappaleen tuloksena saadaan puitteet, jonka avulla liiketoimintamalli matkaviestintäpalveluille voidaan kehittää. Tutkielman empiirinen osa on toteutettu case tutkimuksena, jonka tavoitteena on ollut langattomien matkaviestintäpalvelujen markkinoiden luominen CIS maissa. Pääasiallinen empiirisen tiedon lähde on ollut teemahaastattelut. Tuloksena saatuja empiirisen osan tietoja verrataan teoriakappaleen vastaaviin tuloksiin Tulokset osoittavat, että radikaalin korkean teknologian innovaation markkinoiden luominen on hidas prosessi, joka vaatii kärsivällisyyttä yritykseltä. Markkinoiden, teknologian ja strategian epävarmuustekijät tuovat epävarmuutta kehittyvälle toimialalle ja markkinoille, joka vaikeuttaa liiketoimintamallin kehittämistä. Tärkein tekijä on palvelujen markkinointi ennemmin kuin teknologian. Avain kyvykkyys markkinoiden luomisessa on oppiminen, ei tietäminen.

Image and value of product brand in industrial markets: Case Stora Enso Consumer Packaging Boards

TUTKIMUKSEN TAVOITTEET Tutkielman tavoitteena oli luoda ensin yleiskäsitys tuotemerkkimarkkinoinnin roolista teollisilla markkinoilla, sekä suhdemarkkinoinnin merkityksestä teollisessa merkkituotemarkkinoinnissa. Toisena oleellisena tavoitteena oli kuvata teoreettisesti merkkituoteidentiteetin rakenne teollisessa yrityksessä ja sen vaikutukset myyntihenkilöstöön, ja lisäksi haluttiin tutkia tuotemerkkien lisäarvoa sekä asiakkaalle että myyjälle. Identiteetti ja sen vaikutukset, erityisesti imago haluttiin tutkia myös empiirisesti. LÄHDEAINEISTO JA TUTKIMUSMENETELMÄT Tämän tutkielman teoreettinen osuus perustuu kirjallisuuteen, akateemisiin julkaisuihin ja aikaisempiin tutkimuksiin; keskittyen merkkituotteiden markkinointiin, identiteettiin ja imagoon, sekä suhdemarkkinointiin osana merkkituotemarkkinointia. Tutkimuksen lähestymistapa on kuvaileva eli deskriptiivinen ja sekä kvalitatiivinen että kvantitatiivinen. Tutkimus on tapaustutkimus, jossa caseyritykseksi valittiin kansainvälinen pakkauskartonki-teollisuuden yritys. Empiirisen osuuden toteuttamiseen käytettiin www-pohjaista surveytä, jonka avulla tietoja kerättiin myyntihenkilöstöltä case-yrityksessä. Lisäksi empiiristä osuutta laajennettiin tutkimalla sekundäärilähteitä kuten yrityksen sisäisiä kirjallisia dokumentteja ja tutkimuksia. TULOKSET. Teoreettisen ja empiirisen tutkimuksen tuloksena luotiin malli jota voidaan hyödyntää merkkituotemarkkinoinnin päätöksenteon tukena pakkauskartonki-teollisuudessa. Teollisen brandinhallinnan tulee keskittyä erityisesti asiakas-suhteiden brandaukseen – tätä voisi kutsua teolliseksi suhdebrandaukseksi. Tuote-elementit ja –arvot, differointi ja positiointi, sisäinen yrityskuva ja viestintä ovat teollisen brandi-identiteetin peruskiviä, jotka luovat brandi-imagon. Case-yrityksen myyntihenkilöstön tuote- ja yritysmielikuvat osoittautuivat kokonaisuudessaan hyviksi. Paras imago on CKB tuotteilla, kun taas heikoin on WLC tuotteilla. Teolliset brandit voivat luoda monenlaisia lisäarvoja sekä asiakas- että myyjäyritykselle.

Statistical hypothesis testing and common misinterpretations: should we abandon p-value in forensic science applications?

Many people regard the concept of hypothesis testing as fundamental to inferential statistics. Various schools of thought, in particular frequentist and Bayesian, have promoted radically different solutions for taking a decision about the plausibility of competing hypotheses. Comprehensive philosophical comparisons about their advantages and drawbacks are widely available and continue to span over large debates in the literature. More recently, controversial discussion was initiated by an editorial decision of a scientific journal [1] to refuse any paper submitted for publication containing null hypothesis testing procedures. Since the large majority of papers published in forensic journals propose the evaluation of statistical evidence based on the so called p-values, it is of interest to expose the discussion of this journal's decision within the forensic science community. This paper aims to provide forensic science researchers with a primer on the main concepts and their implications for making informed methodological choices.

Drivers and Barriers of Collaboration in the Value Chain of Paperboard-Packed Consumer Goods

Value chain collaboration has been a prevailing topic for research, and there is a constantly growing interest in developing collaborative models for improved efficiency in logistics. One area of collaboration is demand information management, which enables improved visibility and decrease of inventories in the value chain. Outsourcing of non-core competencies has changed the nature of collaboration from intra-enterprise to cross-enterprise activity, and this together with increasing competition in the globalizing markets have created a need for methods and tools for collaborative work. The retailer part in the value chain of consumer packaged goods (CPG) has been studied relatively widely, proven models have been defined, and there exist several best practice collaboration cases. The information and communications technology has developed rapidly, offering efficient solutions and applications to exchange information between value chain partners. However, the majority of CPG industry still works with traditional business models and practices. This concerns especially companies operating in the upstream of the CPG value chain. Demand information for consumer packaged goods originates at retailers' counters, based on consumers' buying decisions. As this information does not get transferred along the value chain towards the upstream parties, each player needs to optimize their part, causing safety margins for inventories and speculation in purchasing decisions. The safety margins increase with each player, resulting in a phenomenon known as the bullwhip effect. The further the company is from the original demand information source, the more distorted the information is. This thesis concentrates on the upstream parts of the value chain of consumer packaged goods, and more precisely the packaging value chain. Packaging is becoming a part of the product with informative and interactive features, and therefore is not just a cost item needed to protect the product. The upstream part of the CPG value chain is distinctive, as the product changes after each involved party, and therefore the original demand information from the retailers cannot be utilized as such – even if it were transferred seamlessly. The objective of this thesis is to examine the main drivers for collaboration, and barriers causing the moderate adaptation level of collaborative models. Another objective is to define a collaborative demand information management model and test it in a pilot business situation in order to see if the barriers can be eliminated. The empirical part of this thesis contains three parts, all related to the research objective, but involving different target groups, viewpoints and research approaches. The study shows evidence that the main barriers for collaboration are very similar to the barriers in the lower part of the same value chain; lack of trust, lack of business case and lack of senior management commitment. Eliminating one of them – the lack of business case – is not enough to eliminate the two other barriers, as the operational model in this thesis shows. The uncertainty of the future, fear of losing an independent position in purchasing decision making and lack of commitment remain strong enough barriers to prevent the implementation of the proposed collaborative business model. The study proposes a new way of defining the value chain processes: it divides the contracting and planning process into two processes, one managing the commercial parts and the other managing the quantity and specification related issues. This model can reduce the resistance to collaboration, as the commercial part of the contracting process would remain the same as in the traditional model. The quantity/specification-related issues would be managed by the parties with the best capabilities and resources, as well as access to the original demand information. The parties in between would be involved in the planning process as well, as their impact for the next party upstream is significant. The study also highlights the future challenges for companies operating in the CPG value chain. The markets are becoming global, with toughening competition. Also, the technology development will most likely continue with a speed exceeding the adaptation capabilities of the industry. Value chains are also becoming increasingly dynamic, which means shorter and more agile business relationships, and at the same time the predictability of consumer demand is getting more difficult due to shorter product life cycles and trends. These changes will certainly have an effect on companies' operational models, but it is very difficult to estimate when and how the proven methods will gain wide enough adaptation to become standards.