Mutations in LONP1, a mitochondrial matrix protease, cause CODAS syndrome.

Cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome (MIM 600373) was first described and named by Shehib et al, in 1991 in a single patient. The anomalies referred to in the acronym are as follows: cerebral-developmental delay, ocular-cataracts, dental-aberrant cusp morphology and delayed eruption, auricular-malformations of the external ear, and skeletal-spondyloepiphyseal dysplasia. This distinctive constellation of anatomical findings should allow easy recognition but despite this only four apparently sporadic patients have been reported in the last 20 years indicating that the full phenotype is indeed very rare with perhaps milder or a typical presentations that are allelic but without sufficient phenotypic resemblance to permit clinical diagnosis. We performed exome sequencing in three patients (an isolated case and a brother and sister sib pair) with classical features of CODAS. Sanger sequencing was used to confirm results as well as for mutation discovery in a further four unrelated patients ascertained via their skeletal features. Compound heterozygous or homozygous mutations in LONP1 were found in all (8 separate mutations; 6 missense, 1 nonsense, 1 small in-frame deletion) thus establishing the genetic basis of CODAS and the pattern of inheritance (autosomal recessive). LONP1 encodes an enzyme of bacterial ancestry that participates in protein turnover within the mitochondrial matrix. The mutations cluster at the ATP-binding and proteolytic domains of the enzyme. Biallelic inheritance and clustering of mutations confirm dysfunction of LONP1 activity as the molecular basis of CODAS but the pathogenesis remains to be explored.

1D.03: Inactive matrix GLA protein is associated with renal resistive index in a population-based study

OBJECTIVE: Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI correlates positively with arteriolosclerosis in damaged kidneys and predicts progressive renal dysfunction. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular (CV) markers, CV outcomes and mortality. In this study we hypothesize that increased RRI is associated with high levels of dp-ucMGP. DESIGN AND METHOD: We recruited participants via a multi-center family-based cross-sectional study in Switzerland exploring the role of genes and kidney hemodynamics in blood pressure regulation. Dp-ucMGP was quantified in plasma samples by sandwich ELISA. Renal doppler sonography was performed using a standardized protocol to measure RRIs on 3 segmental arteries in each kidney. The mean of the 6 measures was reported. Multiple regression analysis was performed to estimate associations between RRI and dp-ucMGP adjusting for sex, age, pulse pressure, mean pressure, renal function and other CV risk factors. RESULTS: We included 1035 participants in our analyses. Mean values were 0.64 ± 0.06 for RRI and 0.44 ± 0.21 (nmol/L) for dp-ucMGP. RRI was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, pulse pressure, mean pressure, heart rate, renal function, low and high density lipoprotein, smoking status, diabetes, blood pressure and cholesterol lowering drugs, and history of CV disease (P < 0.001). CONCLUSIONS: RRI is independently and positively associated with high levels of dp-ucMGP after adjustment for pulse pressure and common CV risk factors. Further studies are needed to determine if vitamin K supplementation can have a positive effect on renal vascular stiffness and kidney function.

Matrix Analytic Analysis of Delays in Communication Systems

Tässä päättötyössä annetaan kuvaus kehitetystä sovelluksesta Quasi Birth Death processien ratkaisuun. Tämä ohjelma on tähän mennessä ainutlaatuinen ja sen avulla voi ratkaista sarjan tehtäviä ja sitä tarvitaan kommunikaatio systeemien analyysiin. Mainittuun sovellukseen on annettu kuvaus ja määritelmä. Lyhyt kuvaus toisesta sovelluksesta Quasi Birth Death prosessien tehtävien ratkaisuun on myös annettu

Customer relationship management and central bank payment system services

Tutkimuksen tavoitteena on selvittää, miten kirjallisuudessa kuvattua asiakkuuden hallintaa voitaisiin soveltaa keskuspankin maksuliikepalveluissa. Tarkasteltavana ovat yleiset toimintatavat, sekä asiakkuuden hallintaa tukevat järjestelmät. Tutkimuksen päätavoitteena on Help Desk toiminnan kehittäminen. Tutkimuksessa tarkastellaan asiakkuuden hallinnan eri osa-alueita ottaen huomioon sekä asiakkaan, että palvelun tarjoajan näkökulmat. Asiakkuuden hallinta ymmärretään strategiana, jolla kyetään kuvaamaan kuinka koko organisaatio toimii asiakkaiden kanssa. Asiakkuuden hallinnan ydin on asiakkaan arvontuotantoprosessin ymmärtäminen. Käytettyjä lähdeaineistoja ovat olleet alan kirjallisuus, artikkelit sekä Internet-lähteet. Empirian taustan ovat muodostaneet asiantuntijahaastattelut sekä keskuspankin julkaisut, sisäiset toimintaohjeet ja vakiintuneet käytännöt. Tutkimuksen keskeinen tulos on, että asiakkuudenhallinnan perusajatukset ovat monin tavoin sovellettavissa keskuspankin melko ainutkertaiseen, teknisesti ja viestinnällisesti vaativaan maksuliikepalveluympäristöön, vaikka asiakkaiden lukumäärä onkin pieni. Hyötyjä voidaan saavuttaa jo asiakkuudenhallinnan peruskomponenttien ml. strategianäkökulma tuntemuksella ja melko pieniltäkin näyttävillä toimintatapa-, työnkulku- ja asennemuutoksilla. Asiakkuuden hallintaa tukevan tietoteknologian jonkinasteinen käyttöönotto voi tuoda lisäarvoa, mutta sen kustannukset ja hyödyt on punnittava tämäntyyppisessä ympäristössä tarkoin.

Self-Organising Maps and Correlation Analysis as a Tool to Explore Patterns in Excitation-Emission Matrix Data Sets and to Discriminate Dissolved Organic Matter Fluorescence Components

Dissolved organic matter (DOM) is a complex mixture of organic compounds, ubiquitous in marine and freshwater systems. Fluorescence spectroscopy, by means of Excitation-Emission Matrices (EEM), has become an indispensable tool to study DOM sources, transport and fate in aquatic ecosystems. However the statistical treatment of large and heterogeneous EEM data sets still represents an important challenge for biogeochemists. Recently, Self-Organising Maps (SOM) has been proposed as a tool to explore patterns in large EEM data sets. SOM is a pattern recognition method which clusterizes and reduces the dimensionality of input EEMs without relying on any assumption about the data structure. In this paper, we show how SOM, coupled with a correlation analysis of the component planes, can be used both to explore patterns among samples, as well as to identify individual fluorescence components. We analysed a large and heterogeneous EEM data set, including samples from a river catchment collected under a range of hydrological conditions, along a 60-km downstream gradient, and under the influence of different degrees of anthropogenic impact. According to our results, chemical industry effluents appeared to have unique and distinctive spectral characteristics. On the other hand, river samples collected under flash flood conditions showed homogeneous EEM shapes. The correlation analysis of the component planes suggested the presence of four fluorescence components, consistent with DOM components previously described in the literature. A remarkable strength of this methodology was that outlier samples appeared naturally integrated in the analysis. We conclude that SOM coupled with a correlation analysis procedure is a promising tool for studying large and heterogeneous EEM data sets.

Inactive Matrix Gla-Protein is associated with arterial stiffness in an adult population-based study

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.

Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium.

OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes. PARTICIPANTS: 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio. RESULTS: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele. CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.

Relationship between oral cancer and implants: clinical cases and systematic literature review

The use of implants for oral rehabilitation of edentulous spaces has recently been on the increase, which has also led to an increase in complications such as peri-implant inflammation or peri-implantitis. Chronic inflammation is a risk factor for developing oral squamous cell carcinoma (OSCC). Objectives: To review the literature of cases that associate implant placement with the development of oral cancer. Study design: We present two clinical cases and a systematic review of literature published on the relationship between oral cancer and implants. Results: We found 13 articles published between the years 1996 and 2009, referencing 18 cases in which the osseointegrated implants are associated with oral squamous cell carcinoma. Of those, 6 articles were excluded because they did not meet the inclusion criteria. Of the 18 cases reported, only 7 cases did not present a previous history of oral cancer or cancer in other parts of the body. Conclusions: Based on the review of these cases, a clear cause-effect relationship cannot be established, although it can be deduced that there is a possibility that implant treatment may constitute an irritant and/or inflammatory cofactor which contributes to the formation and/or development of OSCC.

Genetic origin of the relationship between parental negativity and behavior problems from early childhood to adolescence: A longitudinal genetically sensitive study.

Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added as a covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors.

Mueller matrix microscope with a dual continuous rotating compensator setup and digital demodulation

In this paper we describe a new Mueller matrix (MM) microscope that generalizes and makes quantitative the polarized light microscopy technique. In this instrument all the elements of the MU are simultaneously determined from the analysis in the frequency domain of the time-dependent intensity of the light beam at every pixel of the camera. The variations in intensity are created by the two compensators continuously rotating at different angular frequencies. A typical measurement is completed in a little over one minute and it can be applied to any visible wavelength. Some examples are presented to demonstrate the capabilities of the instrument.

Relationship between diet and reproductive success in the Israeli barn owl

The effect of diet on barn owl (Tyto alba) breeding biology has been well studied in the temperate regions but not in the more arid Middle East. In temperate regions, barn owls are darker colored and mainly prey upon Cricetidae rodents, whereas in arid regions, they are lighter colored and prey to a larger degree upon Muridae rodents. In this study we analyzed the diet and breeding success of 261 barn owl pairs nesting in Israel. The reproductive success of barn owls declined from March to August, and fledged more young when they consumed a larger proportion of social voles (Microtus socialis guentheri). Although the diet of the lighter colored barn owls in Israel comprises more Muridae than that of the darker morphs in temperate regions, in both regions the number of barn owl young increases with an increased proportion of voles in the diet.

Database Marketing from the Customer Relationship ManagementPerspective

Tietokantamarkkinointi voi olla vain apuväline markkinointitoimenpiteiden suorittamisessa, mutta se voidaan toisaalta nähdä myös olennaisena osana asiakassuhdehallintaa. Tietokantamarkkinointi asiakassuhdehallinnan näkökulmasta tähtää asiakastyytyväisyyteen ja asiakasuskollisuuteen, sekä asiakassuhteen tuottavuuteen ja kannattavuuteen, mikä voidaan saavuttaa tehokkaan tiedonhallinnan avulla. Tämä mahdollistaa räätälöityjen toimenpiteiden suorittamisen ja tehostaa kohdentamista ja segmentointia, myös asiakkaiden tuottavuuden perusteella. Normatiivinen case-tutkimus, joka tehtiin Alankomaissa Eurooppalaisessa tietotekniikan lisäarvoa tuottavassa jälleenmyyntikanavassa osoittaa, että tietokantamarkkinointi etenkin asiakas- suhdehallinnan näkökulmasta olisi sopiva keino lisätä asiakastyytyväisyyttä ja –tuottavuutta. Se myös tehostaisi sisäisiä tietovirtoja ja markkinointitoimenpiteitä, kuten esimerkiksi markkinointiviestintää, kampanjanhallintaa ja myyntiprosesseja yritysten välisessä kaupankäynnissä.

Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study.

BACKGROUND: Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue. AIMS: To investigate whether higher BMI increases the risk of major depression. METHOD: Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case-control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI. RESULTS: Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient -0.03, 95% CI -0.18 to 0.13, P = 0.73; GRS: coefficient -0.02, 95% CI -0.11 to 0.07, P = 0.62). CONCLUSIONS: Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.

Relationship between sedimentation sign and morphological grade in symptomatic lumbar spinal stenosis

Introduction Le canal lombaire étroit symptomatique est de plus en plus fréquent. Le traitement dépend des signes cliniques et des résultats radiologiques. Mais actuellement il n'y a pas de consensus concernant la classification radiologique. Le but de notre article est d'étudier la relation entre deux paramètres morphologiques radiologiques récemment décrits sur des examens par IRM. Le premier est le « signe de sédimentation » (Sedimentation Sign) et le second est le grade morphologique de la sténose lombaire (Morphological Grade), tous deux décrit en 2010. Matériel et méthode Nous avons étudié des examens IRM de 137 patients suivit dans notre établissement. De ces 137, 110 étaient issus d'une base de donnée de patients avec une sténose lombaire dont la Symptomatologie était typique. Dans ce groupe, 73 patients avaient été traité chirurgicalement et 37 conservativement, dépendant de la sévérité des symptômes. Un troisième groupe, le groupe contrôle, était formé de 27 patients ne présentant que des douleurs lombaires basses sans sciatalgie. La sévérité de la sténose a été évaluée sur les examens IRM au niveau du disque en utilisant les 4 grades de la classification morphologique, de A à D. La présence d'un signe de sédimentation a été, quand à lui, notée au niveau du pédicule, au-dessus et au-dessous du niveau présentant la sténose maximale, comme décrit dans l'article original. Résultat La présence d'un signe de sédimentation positif a été observée chez 58% des patients présentant un grade morphologique B, 69% chez les patients avec un grade C et 76% des patients avec un grade D. Dans le groupe de patient traité chirurgicalement pour une sténose canalaire, 67% des patients présentaient un signe de sédimentation positif, 35% dans le groupe du traitement conservateur, et 8 % dans le groupe contrôle. En ce qui concerne la classification du grade morphologique, nous avons regroupé les grade C et D. Il y avait 97% de patients avec un grade C et D dans le groupe du traitement chirurgical, 35 % dans le groupe du traitement conservateur et 18% dans le groupe contrôle. Nous avons donc calculé que la présence d'un signe de sédimentation positif chez les patients avec une sténose lombaire symptomatique augmente le risque d'avoir besoin d'une intervention de l'ordre de 3.5 fois (OR=3.5). En utilisant la classification du grade morphologique, nous avons calculé un risque encore plus élevé. Un patient avec une sténose canalaire de grade C ou D a 65 fois plus de risque d'avoir besoin d'une intervention (OR=65). Conclusion : Les résultats montrent une corrélation entre ces deux paramètres morphologiques. Mais la prédiction du besoin d'une intervention n'est pas équivalente. Un tiers des patients dans le groupe du traitement chirurgical n'avaient pas de signe de sédimentation positif. Ce signe apparaît donc comme un moins bon prédicteur pour le choix du traitement comparé à la sévérité de la sténose jugée avec le grade morphologique (OR 3.5 vs 65).