Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. I: Investigation of mobile phase and MS conditions.

The conditions for the analysis of selected doping substances by UHPSFC-MS/MS were optimized to ensure suitable peak shapes and maximized MS responses. A representative mixture of 31 acidic and basic doping agents was analyzed, in both ESI+ and ESI- modes. The best compromise for all compounds in terms of MS sensitivity and chromatographic performance was obtained when adding 2% water and 10mM ammonium formate in the CO2/MeOH mobile phase. Beside mobile phase, the nature of the make-up solvent added for interfacing UHPSFC with MS was also evaluated. Ethanol was found to be the best candidate as it was able to compensate for the negative effect of 2% water addition in ESI- mode and provided a suitable MS response for all doping agents. Sensitivity of the optimized UHPSFC-MS/MS method was finally assessed and compared to the results obtained in conventional UHPLC-MS/MS. Sensitivity was improved by 5-100-fold in UHPSFC-MS/MS vs. UHPLC-MS/MS for 56% of compounds, while only one compound (bumetanide) offered a significantly higher MS response (4-fold) under UHPLC-MS/MS conditions. In the second paper of this series, the optimal conditions for UHPSFC-MS/MS analysis will be employed to screen >100 doping agents in urine matrix and results will be compared to those obtained by conventional UHPLC-MS/MS.

Screening of papaya accessions resistant to Papaya lethal yellowing virus and capacity of Tetranychus urticae to transmit the virus

The objective of this work was to produce a polyclonal antiserum against the coat protein (CP) of Papaya lethal yellowing virus (PLYV) and to determine its specificity and sensibility in the diagnosis of the virus, as well as to evaluate the genetic resistance to PLYV in papaya (Carica papaya) accessions and to investigate the capacity of the two-spotted spider mite Tetranychus urticae to acquire and transmit PLYV to the plants. Sixty-five papaya accessions were evaluated. For each accession, ten plants were mechanically inoculated using PLYV-infected plant extracts, and three plants were mock inoculated with phosphate buffer alone and used as negative controls. Ninety days after inoculation, newly-emerging systemic leaves were collected from the inoculated plants, and viral infection was diagnosed by indirect Elisa, using polyclonal antiserum sensible to the in vitro-expressed PLYV CP. Viral transmission by T. urticae was evaluated in greenhouse. The experiments were repeated twice. Polyclonal antiserum recognized the recombinant PLYV CP specifically and discriminated PLYV infection from infections caused by other plant viruses. Out of the 65 papaya accessions evaluated, 15 were considered resistant, 18 moderately resistant, and 32 susceptible. The two-spotted spider mite T. urticae was capable of acquiring PLYV, but not of transmitting it to papaya.

Can Orthopantomography be used as a tool for screening of carotid atheromatous pathology and thus be used to help reduce the prevalence of ischemic stroke within the population?

Objective: To assess the possibility of Dentists being able to screen patients with higher risk of vascular diseases. Materials: Kodak 8000C Orthopantomographer, eco-Doppler Logiq-500 General Electric at the Lisbon Hospital Particular. Methods: Assessment of orthopantomographies made to 142 patients aged 50 or more, as well as the existing risk factors. Conduction of carotid eco-Doppler to patients who appear to have calcified plaques of the atheroma. Results: Strong dependence between dichotomised age and having the pathology (p = 0.02).Smokers are twice more likely to present plaques (OR= 2). Being hypertensive increases in about 1.4 the likelihood of having a stroke (OR= 1.4). Of the 27 individuals who presented calcifications in the Orthopantomography, they were all submitted to an eco-Doppler and 21 had the pathology confirmed. 27 individuals, who did not show any plaques in the Orthopantomography, were randomly selected to be the control group. They were submitted to an eco-Doppler. And 23 confirmed the non-existence of plaques. Conclusions: Orthopantomography used for assessing the oral cavity reveals more information which should be the object of the Dentist"s attention

Kasvihuonekaasujen päästökaupan ohjausvaikutus sellutehtaan prosessien ja laitteiden kehityksessä

EU:n päästökaupan ensimmäinen jakso alkoi 1.1.2005. Päästökauppa on aiheuttanut sen piiriin kuuluvalle teollisuudelle monia haasteita ja riskejä kasvavien kustannusten muodossa. Massa- ja paperiteollisuus on päästökaupanpiiriin kuuluva teollisuudenala, johon päästökaupan kustannukset vaikuttavat haitallisesti globaalin hinnoittelun vuoksi. Massa- ja paperiteollisuudelle päästökaupasta voi koitua kustannuksia päästöoikeuksien ostamisesta, sähkön, polttoaineiden ja kemikaalien hinnan noususta sekä raaka-ainehuollon vaikeutumisesta. Toisaalta tehtaat voivat hyötyä päästökaupasta alittaessaan päästöoikeutensa tai myydessään sähköä ulkopuoliseen verkkoon. Massa- ja paperiteollisuudessa sähköä kuluu enimmäkseen pumppauksiin eli massan siirtoon ja mekaanisen massan valmistukseen. Suurimpia sähköenergian kuluttajia sellun valmistuksessa ovat soodakattila, puunkäsittely, valkaisu ja lajittelu. Lämpöä tarvitaan haihdutus-, kuivaus- ja keittoprosesseissa. Kemikaaleista klooridioksidin valmistuksessa käytettävä natriumkloraatti on kustannusten kannalta merkittävin kemikaali. Tässä työssä tutkittiin päästökaupan aiheuttamien kustannusten vähentämismahdollisuuksia kohdetehtaalla. Suurin potentiaali liittyy meesauunissa poltettavan maakaasun korvaamiseen mäntyöljyllä tai biomassan kaasutuskaasulla. Kemikaalikulutuksen osalta happidelignifiointi on merkittävin mahdollisuuskustannusten alentamiseksi. Lisäksi päästökaupan kustannuksia voidaan alentaa muun muassa oikealla mitoituksella ja sekundäärilämpöjen optimaalisella käytöllä.

Financial Analysis of the Pulp and Paper Industry: Performance and value creation of the world's pulp and paper companies

Tutkimuksen tavoitteena on analysoida 74 sellu- ja paperiyrityksen taloudellista suorituskykyä kannattavuutta, maksuvalmiutta, vakavaraisuutta ja arvonluontikykyä kuvaavilla tunnusluvuilla. Tutkimuksen teoriaosa esittelee liiketoiminta-analyysin välineet, jonka jälkeen esitellään taloudelliset tunnusluvut. Empiriaosassa käydään läpi vuoden 2005 tunnusluvut yritystasolla. Jotta voidaan tarkastella tunnuslukujen muutoksia pitkällä aikavälillä, yritykset ryhmitellään maantieteellisen sijainnin sekä liiketoimintaorientaation mukaan. Tutkimus on kuvaileva. Tunnusluvuista voidaan todeta sellu- ja paperiteollisuudessa meneillään oleva toimialan rakennemuutos. Eteläamerikkalaiset yritykset, jotka hyötyvät uudesta ja kustannustehokkaasta raaka-aineesta, ovat siirtyneet lähemmäs arvonluontia, kun taas suurin osa pohjoisamerikkalaisista yrityksistä, jotka olivat toimialan johtavia arvonluojia, ovat nyt arvon tuhoajia. Toimiala kärsii myös alhaisesta kannattavuudesta, joka vaikuttaa eniten pohjoisamerikkalaisiin yrityksiin. Samaan aikaan eteläamerikkalaiset yritykset ovat nostaneet kannattavuuttaan, mikä puolestaan korostaa meneillään olevaa muutosta.

Effect of Mechanical and Geometric Mismatching on Fatigue and Damage of Welded Joints

The future of high technology welded constructions will be characterised by higher strength materials and improved weld quality with respect to fatigue resistance. The expected implementation of high quality high strength steel welds will require that more attention be given to the issues of crack initiation and mechanical mismatching. Experiments and finite element analyses were performed within the framework of continuum damage mechanics to investigate the effect of mismatching of welded joints on void nucleation and coalescence during monotonic loading. It was found that the damage of undermatched joints mainly occurred in the sandwich layer and the damageresistance of the joints decreases with the decrease of the sandwich layer width. The damage of over-matched joints mainly occurred in the base metal adjacent to the sandwich layer and the damage resistance of the joints increases with thedecrease of the sandwich layer width. The mechanisms of the initiation of the micro voids/cracks were found to be cracking of the inclusions or the embrittled second phase, and the debonding of the inclusions from the matrix. Experimental fatigue crack growth rate testing showed that the fatigue life of under-matched central crack panel specimens is longer than that of over-matched and even-matched specimens. Further investigation by the elastic-plastic finite element analysis indicated that fatigue crack closure, which originated from the inhomogeneousyielding adjacent to the crack tip, played an important role in the fatigue crack propagation. The applicability of the J integral concept to the mismatched specimens with crack extension under cyclic loading was assessed. The concept of fatigue class used by the International Institute of Welding was introduced in the parametric numerical analysis of several welded joints. The effect of weld geometry and load condition on fatigue strength of ferrite-pearlite steel joints was systematically evaluated based on linear elastic fracture mechanics. Joint types included lap joints, angle joints and butt joints. Various combinations of the tensile and bending loads were considered during the evaluation with the emphasis focused on the existence of both root and toe cracks. For a lap joint with asmall lack-of-penetration, a reasonably large weld leg and smaller flank angle were recommended for engineering practice in order to achieve higher fatigue strength. It was found that the fatigue strength of the angle joint depended strongly on the location and orientation of the preexisting crack-like welding defects, even if the joint was welded with full penetration. It is commonly believed that the double sided butt welds can have significantly higher fatigue strength than that of a single sided welds, but fatigue crack initiation and propagation can originate from the weld root if the welding procedure results in a partial penetration. It is clearly shown that the fatigue strength of the butt joint could be improved remarkably by ensuring full penetration. Nevertheless, increasing the fatigue strength of a butt joint by increasing the size of the weld is an uneconomical alternative.

Performance of parental history for the targeted screening of hypertension in children.

OBJECTIVES: Several guidelines recommend universal screening for hypertension in childhood and adolescence. Targeted screening to children with parental history of hypertension could be a more efficient strategy than universal screening. Therefore, we assessed the association between parental history of hypertension and hypertension in children, and estimated the sensitivity, specificity, negative, and positive predictive values of parental history of hypertension for hypertension in children. METHODS: The present study was a school-based cross-sectional study including 5207 children aged 10-14 years from all public 6th grade classes in the Canton of Vaud, Switzerland. Children had hypertension if they had sustained elevated blood pressure over three separate visits. RESULTS: In children, the prevalence of hypertension was 2.2%. Some 8.5% of mothers and 12.9% of fathers reported to be hypertensive. Maternal history of hypertension (odds ratio 2.0, 95% confidence interval 1.2-3.3) and paternal history of hypertension (odds ratio 2.2, 95% confidence interval 1.4-3.6) were independent risk factors for hypertension in children. Nevertheless, the sensitivity of parental history of hypertension for the identification of hypertension in children was low (from 4% for both parents' positive history up to 41% for at least one parent's positive history). Positive predictive values were also low (between 4 and 5%). CONCLUSION: Children with hypertensive parents were at higher risk of hypertension. Nevertheless, parental history of hypertension helped only marginally to identify hypertension in offspring. Targeting screening only toward children with a parental history of hypertension may not be a substantially better strategy to identify hypertension in children compared with universal screening.

Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort.

We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real-time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440-13_c.1440-1del in intron 14 of ITGA2B causing exon skipping in seven unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits, thereby interfering with integrin maturation and/or function. Our study extends knowledge of GT and the pathophysiology of an integrin.

Anaerobic treatment of deinking pulp plant effluents

Anaerobic treatment as a first biological stage in wastewater treatment is nowadays a well-established technology in recycled paper processing mills using closed water circuits. Today further developed high-rate processes and especially high-tower reactors are also able to handle lower organic loads and become therefore feasible for deinking pulp plant effluents. The interest in the anaerobic method is based on a positive energy balance in form of biogas production and low biomass yield from the process. The anaerobic treatment method was researched and its suitability for the deinking pulp plant effluents was tested experimentally at Stora Enso Maxau mill. In the theory, the deinking pulp process is introduced and the effluents from the deinking process are characterized. The anaerobic treatment is brought up in depth in terms of its use for the deinking effluents, and different kind of reactor types are presented. In addition, other wastewater treatment methods are shortly introduced with the focus on tertiary treatment. Static biodegradability tests were carried out for the wastewaters both anaerobically and aerobically. Based on the results, the deinking effluents can be degraded anaerobically, and inhibition to the methanogenic bacteria was not noticed. In the aerobic static test a good performance of the existing wastewater treatment plant at Maxau mill was proved. Later on pilot trials with sequential anaerobic-aerobic treatment were carried out for the deinking effluents. The anaerobic reactor used was a so called internal circulation reactor. The results confirmed that the combination of the anaerobic treatment and the aerobic activated sludge process is a suitable method for deinking wastewaters with a COD reduction as good as with a two stage aerobic method. When combined with the outstanding quality of the produced biogas and the cost savings acquired from the lower sludge production, the anaerobic treatment was found to be an especially favorable treatment method.

Cost efficient extractive removal of birch pulp

Tämän diplomityön tarkoituksena oli selvittää kustannustehokkaita keinoja uuteaineiden vähentämiseksi koivusulfaattimassasta. Uuteaineet voivat aiheuttaa ongelmia muodostaessaan saostumia prosessilaitteisiin. Saostumat aiheuttavat tukkeumia ja mittaushäiriöitä, mutta irrotessaan ne myös huonontavat sellun laatua. Lopputuotteeseen joutuessaan ne voivat lisäksi aiheuttaa haju- ja makuhaittoja, joilla on erityistä merkitystä esimerkiksi valmistettaessa elintarvikekartonkeja. Tämä työ tehtiin Stora Enson sellutehtaalla, Enocell Oy:llä, Uimaharjussa. Teoriaosassa käsiteltiin uuteaineiden koostumusta ja niiden aiheuttamia ongelmia sellu– ja paperitehtaissa. Lisäksi koottiin aikaisempien tehdaskokeiden fysikaalisia ja kemiallisia keinoja vähentää koivu-uutetta. Tarkastelualueina olivat puunkäsittely, keitto, pesemö ja valkaisu. Kokeellisessa osassa suoritettiin esikokeita laboratorio- ja tehdasmittakaavassa, jotta saavutettaisiin käytännöllistä tietoa itse lopuksi tehtävää tehdasmittakaavan koetta varten. Laboratoriokokeissa tutkittiin mm. keiton kappaluvun, lisäaineiden ja hartsisaippuan vaikutusta koivu-uutteeseen. Lisäksi suoritettiin myös happo- (A) ja peretikkahappovaiheen (Paa) laboratoriokokeet. Tehdasmittakaavassa tarkasteltiin mm. keiton kappaluvun, pesemön lämpötilan, A-vaiheen, valkaisun peroksidi- ja Paa-vaiheen vaikutusta koivu-uutteeseen. Uutteenpoistotehokkuutta eri menetelmien välillä vertailtiin niin määrällisesti kuin rahallisesti. Uutteenpoistotehokkuudella mitattuna vertailuvaihe oli tehokkain pesemön loppuvaiheessa ja valkaisun alkuvaiheessa. Pesemön loppuvaiheessa uutteenpoistoreduktiot olivat noin 30 % ja valkaisun alkuvaiheessa 40 %. Peroksidivaihe oli tehokkain käytettynä valkaisun loppuvaiheessa noin 40 % reduktiolla. Kustannustehokkuudella mitattuna tehokkaimmaksi osoittautui A-vaihe yhdessä peroksidivaiheen kanssa. Säästöt vertailujaksoon verrattuna olivat noin 0.3 €/ADt. Lisäksi kyseinen yhdistelmä osoittautui hyväksi keinoksi säilyttää uutetaso alle maksimirajan kuitulinja 2:lla, kun kuitulinjalla 1 tuotettiin samanaikaisesti armeeraussellua.

Screening of mental health and substance users in frequent users of a general Swiss emergency department.

BACKGROUND: The objectives of this study were to determine the proportions of psychiatric and substance use disorders suffered by emergency departments' (EDs') frequent users compared to the mainstream ED population, to evaluate how effectively these disorders were diagnosed in both groups of patients by ED physicians, and to determine if these disorders were predictive of a frequent use of ED services. METHODS: This study is a cross-sectional study with concurrent and retrospective data collection. Between November 2009 and June 2010, patients' mental health and substance use disorders were identified prospectively in face-to-face research interviews using a screening questionnaire (i.e. researcher screening). These data were compared to the data obtained from a retrospective medical chart review performed in August 2011, searching for mental health and substance use disorders diagnosed by ED physicians and recorded in the patients' ED medical files (i.e. ED physician diagnosis). The sample consisted of 399 eligible adult patients (≥18 years old) admitted to the urban, general ED of a University Hospital. Among them, 389 patients completed the researcher screening. Two hundred and twenty frequent users defined by >4 ED visits in the previous twelve months were included and compared to 169 patients with ≤4 ED visits in the same period (control group). RESULTS: Researcher screening showed that ED frequent users were more likely than members of the control group to have an anxiety, depressive disorder, post-traumatic stress disorder (PTSD), or suffer from alcohol, illicit drug abuse/addiction. Reviewing the ED physician diagnosis, we found that the proportions of mental health and substance use disorders diagnosed by ED physicians were low both among ED frequent users and in the control group. Using multiple logistic regression analyses to predict frequent ED use, we found that ED patients who screened positive for psychiatric disorders only and those who screened positive for both psychiatric and substance use disorders were more likely to be ED frequent users compared to ED patients with no disorder. CONCLUSIONS: This study found high proportions of screened mental health and/or substance use disorders in ED frequent users, but it showed low rates of detection of such disorders in day-to-day ED activities which can be a cause for concern. Active screening for these disorders in this population, followed by an intervention and/or a referral for treatment by a case-management team may constitute a relevant intervention for integration into a general ED setting.

Screening of breast lesions: a comparative study between mammography, B-mode ultrasonography, sonoelastography and histological results

Objective To compare the capacity of mammography, sonoelastography, B-mode ultrasonography and histological analysis to differentiate benign from malignant breast lesions. Materials and Methods A total of 12 histopathologically confirmed breast lesions were documented. The lesions were assessed by means of mammography, B-mode ultrasonography and sonoelastography, and histopathological analysis was utilized as a gold standard. Sensitivity and specificity were calculated. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of the mentioned techniques. Results Sensitivity and specificity in the differentiation between benign and malignant lesions were respectively 100% and 50% for mammography, 100% and 71% for B-mode ultrasonography, and 67% and 83% for sonoelastography. The area under the ROC curve was calculated for the three imaging modalities and corresponded to 0.792 for mammography, 0.847 for B-mode ultrasonography, and 0.806 for sonoelastography. Conclusion Sonoelastography demonstrated higher specificity and lower sensitivity as compared with mammography and B-mode ultrasonography. On the other hand, B-mode ultrasonography had the largest area under the ROC curve. Sonoelastography has demonstrated to be a promising technique to detect and evaluate breast lesions, and could potentially reduce the number of unnecessary biopsies.

Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogs

The first total synthesis of the indole alkaloids ()-aplicyanins A, B and E, plus seventeen analogs, all in racemic form is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the groups on the indole nitrogen (H, Me or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and fourteen of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the acetyl group moiety on the imine nitrogen, and the bromine at position 5 of the indole, are both critical to activity.

Thioflavin-S staining of bacterial inclusion bodies for the fast, simple, and inexpensive screening of amyloid aggregation inhibitors

Amyloid aggregation is linked to a large number of human disorders, from neurodegenerative diseases as Alzheimer"s disease (AD) or spongiform encephalopathies to non-neuropathic localized diseases as type II diabetes and cataracts. Because the formation of insoluble inclusion bodies (IBs) during recombinant protein production in bacteria has been recently shown to share mechanistic features with amyloid self-assembly, bacteria have emerged as a tool to study amyloid aggregation. Herein we present a fast, simple, inexpensive and quantitative method for the screening of potential anti-aggregating drugs. This method is based on monitoring the changes in the binding of thioflavin-S to intracellular IBs in intact Eschericchia coli cells in the presence of small chemical compounds. This in vivo technique fairly recapitulates previous in vitro data. Here we mainly use the Alzheimer"s related beta-amyloid peptide as a model system, but the technique can be easily implemented for screening inhibitors relevant for other conformational diseases simply by changing the recombinant amyloid protein target. Indeed, we show that this methodology can be also applied to the evaluation of inhibitors of the aggregation of tau protein, another amyloidogenic protein with a key role in AD.