Discovery of a 29-gene panel in peripheral blood mononuclear cells for the detection of colorectal cancer and adenomas using high throughput real-time PCR.

Colorectal cancer (CRC) is the second leading cause of cancer-related death in developed countries. Early detection of CRC leads to decreased CRC mortality. A blood-based CRC screening test is highly desirable due to limited invasiveness and high acceptance rate among patients compared to currently used fecal occult blood testing and colonoscopy. Here we describe the discovery and validation of a 29-gene panel in peripheral blood mononuclear cells (PBMC) for the detection of CRC and adenomatous polyps (AP). Blood samples were prospectively collected from a multicenter, case-control clinical study. First, we profiled 93 samples with 667 candidate and 3 reference genes by high throughput real-time PCR (OpenArray system). After analysis, 160 genes were retained and tested again on 51 additional samples. Low expressed and unstable genes were discarded resulting in a final dataset of 144 samples profiled with 140 genes. To define which genes, alone or in combinations had the highest potential to discriminate AP and/or CRC from controls, data were analyzed by a combination of univariate and multivariate methods. A list of 29 potentially discriminant genes was compiled and evaluated for its predictive accuracy by penalized logistic regression and bootstrap. This method discriminated AP >1cm and CRC from controls with a sensitivity of 59% and 75%, respectively, with 91% specificity. The behavior of the 29-gene panel was validated with a LightCycler 480 real-time PCR platform, commonly adopted by clinical laboratories. In this work we identified a 29-gene panel expressed in PBMC that can be used for developing a novel minimally-invasive test for accurate detection of AP and CRC using a standard real-time PCR platform.

Wireless e-Business Applications - Methods for Forecasting the Demand of Wireless Services and Technologies

Tämä tutkimus oli osa sähköistä liiketoimintaa ja langattomia sovelluksia tutkivaa projektia ja tutkimuksen tavoitteena oli selvittää ennustamisen rooli päätöksenteko- ja suunnitteluprosessissa ja määrittää parhaiten soveltuvat ja useimmin käytetyt teknologian ennustusmenetelmät. Ennustusmenetelmiä tarkasteltiin erityisesti uuden teknologian ja pitkän aikavälin ennustamisen näkökulmasta. Tutkimus perustui teknologista ennustamista, pitkän aikavälin suunnittelua ja innovaatioprosesseja käsittelevän kirjallisuuden analysointiin. Materiaalin perusteella kuvataan teknologian ennustamista informaation hankkimisvälineenä organisaatioiden suunnitteluprosessin apuna. Työssä arvioidaan myös seuraavat teknologisen ennustamisen menetelmät: trendianalyysi-, Delfoi-, cross-impact analyysi-, morfologinen analyysi- ja skenaario analyysimenetelmä. Työ tuo esille jokaisen ennustusmenetelmä ominaispiirteet, rajoitukset ja sovellusmahdollisuudet. Käyttäen esiteltyjä menetelmiä, saadaan kerättyä hyödyllistä informaatiota tulevaisuuden näkymistä, joita sitten voidaan käyttää hyväksi organisaatioiden suunnitteluprosesseissa.

Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry.

BACKGROUND: Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. METHODS: 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow-up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analysed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40 ng/ml during 12 months of follow-up and several dosage regimens were evaluated by simulation. RESULTS: A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/ritonavir and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the inter-individual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates, and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300,000 IU two times per year. CONCLUSIONS: This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

Evaluation of the indication for surgical extraction of third molars according to the oral surgeon and the primary care dentist. Experience in the Master of Oral Surgery and Implantology at Barcelona University Dental School

Introduction: Third molar extraction is the most frequent procedure in oral surgery. The present study evaluates the indication of third molar extraction as established by the primary care dentist (PCD) and the oral surgeon, and compares the justification for extraction with the principal reason for patient consultation. Patients and method: A descriptive study was made of 319 patients subjected to surgical removal of a third molar in the context of the Master of Oral Surgery and Implantology (Barcelona University Dental School, Barcelona, Spain) between July 2004 and March 2005. The following parameters were evaluated: sex, age, molar, type of impaction, position according to the classifications of Pell and Gregory and of Winter, and the reasons justifying extraction. Results: The lower third molars were the most commonly extracted molars (73.7%). A total of 69.6% of the teeth were covered by soft tissues only. Fifty-six percent of the lower molars corresponded to Pell and Gregory Class IIB, while 42.1% were in the vertical position. The most common reason for patient reference to our Service of Oral Surgery on the part of the PCD was prophylactic removal (51.0% versus 46.1% in the case of the oral surgeon). Discussion and conclusions. Our results show prophylaxis to be the principal indication of third molar extraction, followed by orthodontic reasons. Regarding third molars with associated clinical symptoms or signs, infectious disease-including pericoronitis- was the pathology most often observed by the oral surgeon, followed by caries. This order of frequency was seen to invert in the case of third molars referred for extraction by the PCD. A vertical position predominated among the third molars with associated pathology

The Future of Mobile Services and Wireless Applications in the Finnish Healthcare Sector

Työn päätavoitteena oli tutkia mobiilipalveluita ja langattomia sovelluksia Suomen terveydenhuollon sektorilla. Tutkimus havainnollistaa avain-alueita, missä mobiilipalvelut ja langattomat sovellukset voivat antaa lisäarvoa perinteiseen lääketieteen harjoittamiseen, ja selvittää, mitkä ovat tähän kehitykseen liittyvät suurimmat ongelmat ja uhkat sekä tutkimustuloksiin pohjautuvat mahdolliset palvelut ja sovellukset 5-10 vuoden kuluttua. Tutkimus oli luonteeltaan kvalitatiivinen ja tutkimuksen toteuttamiseen valittiin tulevaisuudentutkimus ja erityisesti yksi sen menetelmistä, delfoi-menetelmä. Tutkimuksen aineisto kerättiin kahdelta puolistrukturoidulta haastattelukierrokselta. Työn empiirinen osuus keskittyi kuvailemaan Suomen terveydenhuollon sektoria, siinä meneillään olevia projekteja sekä teknisiä esteitä. Lisäksi pyrittiin vastaamaan tutkimuksen pääkysymykseen. Tutkimustulokset osoittivat, että tärkeät alueet, joihin langaton kommunikaatio tulisi vaikuttamaan merkittävästi, ovat ensiaputoiminta, kroonisten potilaiden etämonitorointi, välineiden kehittäminen langattomaan kommunikaatioon kotihoidon parantamiseksi ja uusien toimintamallien luomiseksi sekä lääketieteellinen yhteistyö jakamalla terveydenhuoltoon liittyvät informaation lähteet. Työn tulosten perusteellavoitiin antaa myös muutamia toimenpide-ehdotuksia jatkotutkimuksia varten.

Estimating the Price and Demand Development of Some Paperboard Grades

Työn tavoitteena oli luoda malli, jonka avulla voitaisiin ennustaa kartonkituotteiden hinnan ja kysynnän kehitystä. Työssä kerättiin aluksi tietoa kartonkimarkkinoista haastattelujen ja tilastotietojen avulla. Näiden perusteella luotiin malli, joka kuvaa kartonkimarkkinoiden ja -teollisuuden rakennetta. Erityisesti kiinnitettiin huomiota asiakkaiden tilauskäyttäytymiseen, tuotannonohjaukseen sekä hinnan muodostumiseen. Työssä käytettiin ennustemenetelmänä systeemidynamiikkaa. Oleellista oli löytää systeemissä esiintyvät tärkeimmät takaisinkytkennät ja systeemin avainmuuttujat. Kun kaikille mallin muuttujille oli määritetty yhtälöt ja vakioille annettu arvot, voitiin mallia simuloida, ja saada ennusteet halutuille muuttujille. Työssä esitettiin ennusteet kartonkimarkkinoiden tärkeimmille parametreille kahden vuoden päähän. Työssä tarkasteltiin myös, miten muutokset mallin käyttäytymistä säätelevissä muuttujissa vaikuttavat tuloksiin. Jotta pystyttäisiin paremmin selvittämään koko kartonkiteollisuuden dynamiikka, lisätutkimusta tarvittaisiin vielä eri kartonkilajien substituutiomahdollisuuksista ja hintojen riippuvuuksista. Mielenkiintoista olisi myös tietää, miten tuotannon käyttöasteiden muutokset ja hinnan vaihtelut vaikuttavat liiketoiminnan kannattavuuteen valmistajien näkökulmasta.

No Major Differences Found between the Effects of Microwave-Based and Conventional Heat Treatment Methods on Two Different Liquid Foods

Extension of shelf life and preservation of products are both very important for the food industry. However, just as with other processes, speed and higher manufacturing performance are also beneficial. Although microwave heating is utilized in a number of industrial processes, there are many unanswered questions about its effects on foods. Here we analyze whether the effects of microwave heating with continuous flow are equivalent to those of traditional heat transfer methods. In our study, the effects of heating of liquid foods by conventional and continuous flow microwave heating were studied. Among other properties, we compared the stability of the liquid foods between the two heat treatments. Our goal was to determine whether the continuous flow microwave heating and the conventional heating methods have the same effects on the liquid foods, and, therefore, whether microwave heat treatment can effectively replace conventional heat treatments. We have compared the colour, separation phenomena of the samples treated by different methods. For milk, we also monitored the total viable cell count, for orange juice, vitamin C contents in addition to the taste of the product by sensory analysis. The majority of the results indicate that the circulating coil microwave method used here is equivalent to the conventional heating method based on thermal conduction and convection. However, some results in the analysis of the milk samples show clear differences between heat transfer methods. According to our results, the colour parameters (lightness, red-green and blue-yellow values) of the microwave treated samples differed not only from the untreated control, but also from the traditional heat treated samples. The differences are visually undetectable, however, they become evident through analytical measurement with spectrophotometer. This finding suggests that besides thermal effects, microwave-based food treatment can alter product properties in other ways as well.

Management of severe blunt hepatic injury in the era of computed tomography and transarterial embolization: A systematic review and critical appraisal of the literature.

BACKGROUND: During the last decade, the management of blunt hepatic injury has considerably changed. Three options are available as follows: nonoperative management (NOM), transarterial embolization (TAE), and surgery. We aimed to evaluate in a systematic review the current practice and outcomes in the management of Grade III to V blunt hepatic injury. METHOD: The MEDLINE database was searched using PubMed to identify English-language citations published after 2000 using the key words blunt, hepatic injury, severe, and grade III to V in different combinations. Liver injury was graded according to the American Association for the Surgery of Trauma classification on computed tomography (CT). Primary outcome analyzed was success rate in intention to treat. Critical appraisal of the literature was performed using the validated National Institute for Health and Care Excellence "Quality Assessment for Case Series" system. RESULTS: Twelve articles were selected for critical appraisal (n = 4,946 patients). The median quality score of articles was 4 of 8 (range, 2-6). Overall, the median Injury Severity Score (ISS) at admission was 26 (range, 0.6-75). A median of 66% (range, 0-100%) of patients was managed with NOM, with a success rate of 94% (range, 86-100%). TAE was used in only 3% of cases (range, 0-72%) owing to contrast extravasation on CT with a success rate of 93% (range, 81-100%); however, 9% to 30% of patients required a laparotomy. Thirty-one percent (range, 17-100%) of patients were managed with surgery owing to hemodynamic instability in most cases, with 12% to 28% requiring secondary TAE to control recurrent hepatic bleeding. Mortality was 5% (range, 0-8%) after NOM and 51% (range, 30-68%) after surgery. CONCLUSION: NOM of Grade III to V blunt hepatic injury is the first treatment option to manage hemodynamically stable patients. TAE and surgery are considered in a highly selective group of patients with contrast extravasation on CT or shock at admission, respectively. Additional standardization of the reports is necessary to allow accurate comparisons of the various management strategies. LEVEL OF EVIDENCE: Systematic review, level IV.

More than Words? An Analysis on the Language and Structure of General Election Manifestos of the British Labour Party 1983-2005

The topic of this study is the language of the educational policies of the British Labour party in the General Election manifestos between the years 1983-2005. The twenty-year period studied has been a period of significant changes in world politics, and in British politics, especially for the Labour party. The emergence educational policy as a vote-winner of the manifestos of the nineties has been noteworthy. The aim of the thesis is two-fold: to look at the structure of the political manifesto as an example of genre writing and to analyze the content utilizing the approach of critical discourse analysis. Furthermore, the aim of this study is not to pinpoint policy positions but to look at what is the image that the Labour Party creates of itself through these manifestos. The analysis of the content is done by a method of close-reading. Based on the findings, the methodology for the analysis of the content was created. This study utilized methodological triangulation which means that the material is analyzed from several methodological aspects. The aspects used in this study are ones of lexical features (collocation, coordination, euphemisms, metaphors and naming), grammatical features (thematic roles, tense, aspect, voice and modal auxiliaries) and rhetoric (Burke, Toulmin and Perelman). From the analysis of the content a generic description is built. By looking at the lexical, grammatical and rhetorical features a clear change in language of the Labour Party can be detected. This change is foreshadowed already in the 1992 manifesto but culminates in the 1997 manifesto which would lead Labour to a landslide victory in the General Election. During this twenty-year period Labour has moved away from the old commitments and into the new sphere of “something for everybody”. The pervasiveness of promotional language and market inspired vocabulary into the sphere of manifesto writing is clear. The use of the metaphors seemed to be the tool for the creation of the image of the party represented through the manifestos. A limited generic description can be constructed from the findings based on the content and structure of the manifestos: especially more generic findings such as the use of the exclusive we, the lack of certain anatomical parts of argument structure, the use of the future tense and the present progressive aspect can shed light to the description of the genre of manifesto writing. While this study is only the beginning, it proves that the combination of looking at the lexical, grammatical and rhetorical features in the study of manifestos is a promising one.

Estimating 750 years of temperature variations and uncertainties in the Pyrenees by tree-ring reconstructions and climate simulations.

Past temperature variations are usually inferred from proxy data or estimated using general circulation models. Comparisons between climate estimations derived from proxy records and from model simulations help to better understand mechanisms driving climate variations, and also offer the possibility to identify deficiencies in both approaches. This paper presents regional temperature reconstructions based on tree-ring maximum density series in the Pyrenees, and compares them with the output of global simulations for this region and with regional climate model simulations conducted for the target region. An ensemble of 24 reconstructions of May-to-September regional mean temperature was derived from 22 maximum density tree-ring site chronologies distributed over the larger Pyrenees area. Four different tree-ring series standardization procedures were applied, combining two detrending methods: 300-yr spline and the regional curve standardization (RCS). Additionally, different methodological variants for the regional chronology were generated by using three different aggregation methods. Calibration verification trials were performed in split periods and using two methods: regression and a simple variance matching. The resulting set of temperature reconstructions was compared with climate simulations performed with global (ECHO-G) and regional (MM5) climate models. The 24 variants of May-to-September temperature reconstructions reveal a generally coherent pattern of inter-annual to multi-centennial temperature variations in the Pyrenees region for the last 750 yr. However, some reconstructions display a marked positive trend for the entire length of the reconstruction, pointing out that the application of the RCS method to a suboptimal set of samples may lead to unreliable results. Climate model simulations agree with the tree-ring based reconstructions at multi-decadal time scales, suggesting solar variability and volcanism as the main factors controlling preindustrial mean temperature variations in the Pyrenees. Nevertheless, the comparison also highlights differences with the reconstructions, mainly in the amplitude of past temperature variations and in the 20th century trends. Neither proxy-based reconstructions nor model simulations are able to perfectly track the temperature variations of the instrumental record, suggesting that both approximations still need further improvements.

On the Analysis and Control of a Linear Synchronous Servomotor with a Flexible Load

Industry's growing need for higher productivity is placing new demands on mechanisms connected with electrical motors, because these can easily lead to vibration problems due to fast dynamics. Furthermore, the nonlinear effects caused by a motor frequently reduce servo stability, which diminishes the controller's ability to predict and maintain speed. Hence, the flexibility of a mechanism and its control has become an important area of research. The basic approach in control system engineering is to assume that the mechanism connected to a motor is rigid, so that vibrations in the tool mechanism, reel, gripper or any apparatus connected to the motor are not taken into account. This might reduce the ability of the machine system to carry out its assignment and shorten the lifetime of the equipment. Nonetheless, it is usually more important to know how the mechanism, or in other words the load on the motor, behaves. A nonlinear load control method for a permanent magnet linear synchronous motor is developed and implemented in the thesis. The purpose of the controller is to track a flexible load to the desired velocity reference as fast as possible and without awkward oscillations. The control method is based on an adaptive backstepping algorithm with its stability ensured by the Lyapunov stability theorem. As a reference controller for the backstepping method, a hybrid neural controller is introduced in which the linear motor itself is controlled by a conventional PI velocity controller and the vibration of the associated flexible mechanism is suppressed from an outer control loop using a compensation signal from a multilayer perceptron network. To avoid the local minimum problem entailed in neural networks, the initial weights are searched for offline by means of a differential evolution algorithm. The states of a mechanical system for controllers are estimated using the Kalman filter. The theoretical results obtained from the control design are validated with the lumped mass model for a mechanism. Generalization of the mechanism allows the methods derived here to be widely implemented in machine automation. The control algorithms are first designed in a specially introduced nonlinear simulation model and then implemented in the physical linear motor using a DSP (Digital Signal Processor) application. The measurements prove that both controllers are capable of suppressing vibration, but that the backstepping method is superior to others due to its accuracy of response and stability properties.

Molecular dynamics simulation of the spherical electrical double layer of a soft nanoparticle. Effect of the surface and counterion valence

Molecular dynamics simulations were performed to study the ion and water distribution around a spherical charged nanoparticle. A soft nanoparticle model was designed using a set of hydrophobic interaction sites distributed in six concentric spherical layers. In order to simulate the effect of charged functionalyzed groups on the nanoparticle surface, a set of charged sites were distributed in the outer layer. Four charged nanoparticle models, from a surface charge value of −0.035 Cm−2 to − 0.28 Cm−2, were studied in NaCl and CaCl2 salt solutions at 1 M and 0.1 M concentrations to evaluate the effect of the surface charge, counterion valence, and concentration of added salt. We obtain that Na + and Ca2 + ions enter inside the soft nanoparticle. Monovalent ions are more accumulated inside the nanoparticle surface, whereas divalent ions are more accumulated just in the plane of the nanoparticle surface sites. The increasing of the the salt concentration has little effect on the internalization of counterions, but significantly reduces the number of water molecules that enter inside the nanoparticle. The manner of distributing the surface charge in the nanoparticle (uniformly over all surface sites or discretely over a limited set of randomly selected sites) considerably affects the distribution of counterions in the proximities of the nanoparticle surface.

The octagon, the hendecagon and the approximation of pi: the geometric design of the clypeus in the enclosure of Imperial cult in Tarraco

The ancient temple dedicated to the Roman Emperor Augustus on the hilltop of Tarraco (today’s Tarragona), was the main element of the sacred precinct of the Imperial cult. It was a two hectare square, bordered by a portico with an attic decorated with a sequence of clypeus (i.e. monumental shields) made with marble plates from the Luni-Carrara’s quarries. This contribution presents the results of the analysis of a three-dimensional photogrammetric survey of one of these clipeus, partially restored and exhibited at the National Archaeological Museum of Tarragona. The perimeter ring was bounded by a sequence of meanders inscribed in a polygon of 11 sides, a hendecagon. Moreover, a closer geometric analysis suggests that the relationship between the outer meander rim and the oval pearl ring that delimited the divinity of Jupiter Ammon can be accurately determined by the diagonals of an octagon inscribed in the perimeter of the clypeus. This double evidence suggests a combined layout, in the same design, of an octagon and a hendecagon. Hypothetically, this could be achieved by combining the octagon with the approximation to Pi used in antiquity: 22/7 of the circle’s diameter. This method allows the drawing of a hendecagon with a clearly higher precision than with other ancient methods. Even the modelling of the motifs that separate the different decorative stripes corroborates the geometric scheme that we propose.

Evaluation of a new serological test for the detection of anti-Coxiella and anti-Rickettsia antibodies.

Coxiella burnetii and members of the genus Rickettsia are obligate intracellular bacteria. Since cultivation of these organisms requires dedicated techniques, their diagnosis usually relies on serological or molecular biology methods. Immunofluorescence is considered the gold standard to detect antibody-reactivity towards these organisms. Here, we assessed the performance of a new automated epifluorescence immunoassay (InoDiag) to detect IgM and IgG against C. burnetii, Rickettsia typhi and Rickettsia conorii. Samples were tested with the InoDiag assay. A total of 213 sera were tested, of which 63 samples from Q fever, 20 from spotted fever rickettsiosis, 6 from murine typhus and 124 controls. InoDiag results were compared to micro-immunofluorescence. For acute Q fever, the sensitivity of phase 2 IgG was only of 30% with a cutoff of 1 arbitrary unit (AU). In patients with acute Q fever with positive IF IgM, sensitivity reached 83% with the same cutoff. Sensitivity for chronic Q fever was 100% whereas sensitivity for past Q fever was 65%. Sensitivity for spotted Mediterranean fever and murine typhus were 91% and 100%, respectively. Both assays exhibited a good specificity in control groups, ranging from 79% in sera from patients with unrelated diseases or EBV positivity to 100% in sera from healthy patients. In conclusion, the InoDiag assay exhibits an excellent performance for the diagnosis of chronic Q fever but a very low IgG sensitivity for acute Q fever likely due to low reactivity of phase 2 antigens present on the glass slide. This defect is partially compensated by the detection of IgM. Because it exhibits a good negative predictive value, the InoDiag assay is valuable to rule out a chronic Q fever. For the diagnosis of rickettsial diseases, the sensitivity of the InoDiag method is similar to conventional immunofluorescence.

Improving the molecular diagnosis of Chlamydia psittaci and Chlamydia abortus infection with a species-specific duplex real-time PCR.

Chlamydia psittaci and Chlamydia abortus are closely related intracellular bacteria exhibiting different tissue tropism that may cause severe but distinct infection in humans. C. psittaci causes psittacosis, a respiratory zoonotic infection transmitted by birds. C. abortus is an abortigenic agent in small ruminants, which can also colonize the human placenta and lead to foetal death and miscarriage. Infections caused by C. psittaci and C. abortus are underestimated mainly due to diagnosis difficulties resulting from their strict intracellular growth. We developed a duplex real-time PCR to detect and distinguish these two bacteria in clinical samples. The first PCR (PCR1) targeted a sequence of the 16S-23S rRNA operon allowing the detection of both C. psittaci and C. abortus. The second PCR (PCR2) targeted the coding DNA sequence CPSIT_0607 unique to C. psittaci. The two PCRs showed 100 % detection for ≥ 10 DNA copies per reaction (1000 copies ml- 1). Using a set of 120 samples, including bacterial reference strains, clinical specimens and infected cell culture material, we monitored 100 % sensitivity and 100 % specificity for the detection of C. psittaci and C. abortus for PCR1. When PCR1 was positive, PCR2 could discriminate C. psittaci from C. abortus with a positive predictive value of 100 % and a negative predictive value of 88 %. In conclusion, this new duplex PCR represents a low-cost and time-saving method with high-throughput potential, expected to improve the routine diagnosis of psittacosis and pregnancy complication in large-scale screening programs and also during outbreaks.