Persistence of Transmitted HIV-1 Drug Resistance Mutations Associated with Fitness Costs and Viral Genetic Backgrounds.

Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS). All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR) determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V) to 2.7/100-person-years;[0.7, 10.9] (for 215D). RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs). When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

Observations on Software Project Deviations

Software projects have proved to be troublesome to be implemented and as the size of software keeps increasing it is more and more important to follow-up the projects. The proportion of succeeded software projects is still quite low in spite of the research and the development of the project control methodologies. The success and failure factors of projects are known, as well as the project risks but nevertheless the projects still have problems with keeping the schedule and the budget and achieving the defined functionality and adequate quality. The purpose of this thesis was to find out what deviations are there in projects at the moment, what causes them, and what is measured in projects. Also project deviation was defined in the viewpoint of literature and field experts. The analysis was made using a qualitative research approach. It was found out that there are still deviations in software projects with schedule, budget, quality, requirements, documenting, effort, and resources. In addition also changes in requirements were identified. It was also found out that for example schedule deviations can be affected by reducing the size of a task and adding measurements.

A comparative study of ballpoint ink ageing parameters using GC/MS.

For more than a decade scientists tried to develop methods capable of dating ink by monitoring the loss of phenoxyethanol (PE) over time. While many methods were proposed in the literature, few were really used to solve practical cases and they still raise much concern within the scientific community. In fact, due to the complexity of ink drying processes it is particularly difficult to find a reliable ageing parameter to reproducibly follow ink ageing. Moreover, systematic experiments are required in order to evaluate how different factors actually influence the results over time. Therefore, this work aimed at evaluating the capacity of four different ageing parameters to reliably follow ink ageing over time: (1) the quantity of solvent PE in an ink line, (2) the relative peak area (RPA) normalising the PE results using stable volatile compounds present in the ink formulation, (3) the solvent loss ratio (R%) calculated from PE results obtained by the analyses of naturally and artificially aged samples, (4) a modified solvent loss ratio version (R%*) calculated from RPA results. After the determination of the limits of reliable measurements of the analytical method, the repeatability of the different ageing parameters was evaluated over time, as well as the influence of ink composition, writing pressure and storage conditions on the results. Surprisingly, our results showed that R% was not the most reliable parameter, as it showed the highest standard deviation. Discussion of the results in an ink dating perspective suggests that other proposed parameters, such as RPA values, may be more adequate to follow ink ageing over time.

Pyörösahakoneen adaptiivinen teräohjaus

Diplomityössä tarkastellaan pyörösahalinjan adaptiivista teräohjausta. Työllä on kaksi tavoitetta. Lisätä mittausjärjestelmään sahatavaroiden keskiarvon mittaamisen lisäksi keskihajonnan mittaus ja selvittää mittausjärjestelmään sekä sahalinjan ohjausjärjestelmään tarvittavat muutokset niiden välisen automaattisen tiedonsiirron toteuttamiseksi. Sahatavaroiden paksuudet selvitetään optisen mittausjärjestelmän avulla. Sahatavaroille on määrätty tuoremitta. Suunniteltu järjestelmä käyttää hyväkseen keskihajontaa tarvittavan sahausvaran laskemiseen sahatavaroille. Sahausvara tarvitaan raaka-aineen ja sahakoneiden sahatavarapaksuuteen aiheuttaman vaihtelun vuoksi. Tuoremitan tulee ilmaista sahatavaran pienintä tarvittavaa paksuutta, jotta se on kuivauksen jälkeen asiakasmitassa. Mittausjärjestelmä määrittää sahausvaran reaaliaikaisen tarpeen mukaan. Sahausvara lisätään minimituoremitan päälle ja sitä ohjataan sahauksessa tapahtuvien muutosten perusteella. Adaptiivinen teräohjaus tarvitsee mittausjärjestelmän ja sahalinjan ohjausjärjestelmän välistä tiedonsiirtoa. Diplomityössä on selvitetty kahden laitevalmistajan järjestelmiin tarvittavat muutokset, jotta ne pystyvät adaptiiviseen teräohjaukseen ilman sahuria välittämässä terien siirtoarvoja. Muutosten jälkeen automaattinen tiedonsiirto onnistuu järjestelmien välillä. Sahalaitos, jossa järjestelmät ovat käytössä, ei ole tehnyt päätöstä järjestelmien tiedonsiirron automatisoinnista.

Natural history of growth hormone deficiency in a pediatric cohort.

BACKGROUND/AIMS: Controversies still exist regarding the evaluation of growth hormone deficiency (GHD) in childhood at the end of growth. The aim of this study was to describe the natural history of GHD in a pediatric cohort. METHODS: This is a retrospective study of a cohort of pediatric patients with GHD. Cases of acquired GHD were excluded. Univariate logistic regression was used to identify predictors of GHD persisting into adulthood. RESULTS: Among 63 identified patients, 47 (75%) had partial GHD at diagnosis, while 16 (25%) had complete GHD, including 5 with multiple pituitary hormone deficiencies. At final height, 50 patients underwent repeat stimulation testing; 28 (56%) recovered and 22 (44%) remained growth hormone (GH) deficient. Predictors of persisting GHD were: complete GHD at diagnosis (OR 10.1, 95% CI 2.4-42.1), pituitary stalk defect or ectopic pituitary gland on magnetic resonance imaging (OR 6.5, 95% CI 1.1-37.1), greater height gain during GH treatment (OR 1.8, 95% CI 1.0-3.3), and IGF-1 level <-2 standard deviation scores (SDS) following treatment cessation (OR 19.3, 95% CI 3.6-103.1). In the multivariate analysis, only IGF-1 level <-2 SDS (OR 13.3, 95% CI 2.3-77.3) and complete GHD (OR 6.3, 95% CI 1.2-32.8) were associated with the outcome. CONCLUSION: At final height, 56% of adolescents with GHD had recovered. Complete GHD at diagnosis, low IGF-1 levels following retesting, and pituitary malformation were strong predictors of persistence of GHD. © 2015 S. Karger AG, Basel.

PulpExpert-massa-analysaattorin arkinmuodostus

Laboratoriossa tutkittiin rainaussakeuden ja neliömassan vaikutusta formaatioon ja muiden paperin ominaisuuksien hajontoihin sakeusalueella 0,036 %- 0,067 % ja neliömassa-alueella 65 g/m2- 125 g/m2. Havaittiin, että rainaussakeudella oli vaikutusta vain mäntysellusta valmistettujen arkkien formaatioon. Neliömassan noustessa kaikista tutkituista massoista valmistettujen arkkien formaatiot huononivat. Pulseeraus tai alipaine vedenpoiston aikana ei parantanut Turbulence Pulse Sheet Former-laitteella valmistettujen kuumahierrearkkien formaatiota. Kahdella koelaitteella tehtiin sakeusajo, toistokoe ja vuorottelukoe. Laite A mittasi tiettyihin sakeuksiin valmistettujen massojen sakeudet tarkasti. Laitteen B sakeusmittauksessa havaittiin säännöllinen poikkeama. Toistokokeen tuloksista tarkasteltiin mitattujen arvojen hajontoja, laitteiden massanerotuskykyä ja arkkien formaatiota. Laite A teki silmämääräisesti tasaisempia arkkeja, mutta niiden formaatio oli huonompi. Laitteella A saavutettiin pienemmät näytepisteiden sisäiset hajonnat repäisylujuusmittauksessa ja laitteella B vaaleuden mittauksessa. Laite A erotteli massat paremmin vaaleusmittauksessa ja laite B ilmanläpäisevyyden mittauksessa. Vuorottelukokeessa havaittiin, ettei massojen nopea vuorottelu kasvata olennaisesti mittaustuloksien hajontoja.

Phyllochron estimation in intercropped strawberry and monocrop systems in a protected environment

The phyllochron is defined as the time required for the appearance of successive leaves on a plant; this characterises plant growth, development and adaptation to the environment. To check the growth and adaptation in cultivars of strawberry grown intercropped with fig trees, it was estimated the phyllochron in these production systems and in the monocrop. The experiment was conducted in greenhouses at the University of Passo Fundo (28º15'41'' S, 52º24'45'' W and 709 m) from June 8th to September 4th, 2009; this comprised the period of transplant until the 2nd flowering. The cultivars Aromas, Camino Real, Albion, Camarosa and Ventana, which seedlings were originated from the Agrícola LLahuen Nursery in Chile, as well as Festival, Camino Real and Earlibrite, originated from the Viansa S.A. Nursery in Argentina, were grown in white polyethylene bags filled with commercial substrate (Tecnomax®) and evaluated. The treatments were arranged in a randomised block design and four replicates were performed. A linear regression was realized between the leaf number (LN) in the main crown and the accumulated thermal time (ATT). The phyllochron (degree-day leaf-1) was estimated as the inverse of the angular coefficient of the linear regression. The data were submitted to ANOVA, and when significance was observed, the means were compared using the Tukey test (p < 0.05). The mean and standard deviation of phyllochrons of strawberry cultivars intercropped with fig trees varied from 149.35ºC day leaf-1 ± 31.29 in the Albion cultivar to 86.34ºC day leaf-1 ± 34.74 in the Ventana cultivar. Significant differences were observed among cultivars produced in a soilless environment with higher values recorded for Albion (199.96ºC day leaf-1 ± 29.7), which required more degree-days to produce a leaf, while cv. Ventana (85.76ºC day leaf-1 ± 11.51) exhibited a lower phyllochron mean value. Based on these results, Albion requires more degree-days to issue a leaf as compared to cv. Ventana. It was conclude that strawberry cultivars can be grown intercropped with fig trees (cv. Roxo de Valinhos).

Paperikoneen laatusäätöjärjestelmän uusinnan vaikutukset laatusäätöjen suorituskykyyn

Tutkimuksen kohteena olleen UPM-Kymmene Oyj Kajaanin tehtaan PK3:n laatusäätöjärjestelmä ja mittapalkki uusittiin, jolloin haluttiin selvittää uusinnan vaikutuksia laatusäätöjen suorituskykyyn ja paperin laatuun. Työn kirjallisessa osassa perehdyttiin paperinvalmistusprosessin osiin kyseisen sanomalehtipaperikoneen tapauksessa sekä keskeisimpiin paperin laatuominaisuuksiin liittyviin mittaus- ja säätölaitteisiin sekä niiden toimintaan. Seurattaviksi paperin laatusuureiksi valittiin neliömassa, kuivamassa, kosteus ja paksuus, jotka ovat sanomalehtipaperin tärkeimpiä online-mitattavia ominaisuuksia. Paperin laatusuureiden seurantaan käytetään erilaisia tunnuslukuja ja työkaluja, joita on esitelty tässä työssä. Laatusuureiden konesuuntaisen ja poikkisuuntaisen seurannan tunnusluvuksi valittiin yleisesti käytössä oleva 2σ-keskiarvohajonta. Säätöjen suorituskykyä seurattiin suorituskykykolmion ohjausmatkaindeksien (CTI) ja erosuureen integraalien (IAE) avulla. Kokeellisessa osassa kerättiin mittaustietoja sekä vanhan että uuden laatusäätöjärjestelmän aikana. Seurattavat ajotilanteet paperikoneella jaettiin stabiiliin ajoon ja muutostilanteisiin, jotka käsittävät katkot ja lajinvaihtotilanteet. Stabiilin ajon aikana selvitettiin laatusuureiden hajontojen ja säätöjen suorituskykyindeksien normaaleissa tasoissa tapahtuneet muutokset. Muutostilanteiden osalta haluttiin selvittää, nopeuttaako järjestelmäuusinta katkoista toipumista ja lajinvaihtoaikaa. Stabiilin ajon seurannasta saatujen tulosten perusteella neliömassan ja kuivamassan konesuuntaiset hajonnat kasvoivat järjestelmäuusinnan myötä, mutta kosteuden konesuuntaiset hajonnat pienenivät. Laatusuureiden poikkisuuntaisista hajonnoista neliömassan sekä kuivamassan hajonnat kasvoivat ja kosteuden sekä paksuuden hajonnat pienenivät joidenkin lajien osalta. Poikkisuuntaisten laatusuureiden, etenkin paksuuden, toipuminen katkon jälkeen nopeutui. Myös lajinvaihtoon kuluva aika lyheni poikkisuuntaisilla laatusuureilla. Muutostilanteiden konesuuntaisten hajontojen asettumisajat eivät juuri parantuneet.

A comparative study of ballpoint ink ageing parameters using GC/MS

For more than a decade scientists tried to develop methods capable of dating ink by monitoring the loss of phenoxyethanol (PE) over time. While many methods were proposed in the literature, few were really used to solve practical cases and they still raise much concern within the scientific community. In fact, due to the complexity of ink drying processes it is particularly difficult to find a reliable ageing parameter to reproducibly follow ink ageing. Moreover, systematic experiments are required in order to evaluate how different factors actually influence the results over time. Therefore, this work aimed at evaluating the capacity of four different ageing parameters to reliably follow ink ageing over time: (1) the quantity of solvent PE in an ink line, (2) the relative peak area (RPA) normalising the PE results using stable volatile compounds present in the ink formulation, (3) the solvent loss ratio (R%) calculated from PE results obtained by the analyses of naturally and artificially aged samples, (4) a modified solvent loss ratio version (R%*) calculated from RPA results. After the determination of the limits of reliable measurements of the analytical method, the repeatability of the different ageing parameters was evaluated over time, as well as the influence of ink composition, writing pressure and storage conditions on the results. Surprisingly, our results showed that R% was not the most reliable parameter, as it showed the highest standard deviation. Discussion of the results in an ink dating perspective suggests that other proposed parameters, such as RPA values, may be more adequate to follow ink ageing over time.

Nonsurgical treatment of cyclic esotropia.

Cyclic esotropia is characterized by a 24-hour period of straight eye position followed by 24 hours of large-angle esotropia. Possible mechanisms include notably progressive loss of compensation of a latent strabismus. The classic treatment is surgical correction of the angle measured on the days with manifest deviation. We report the first case of cyclic esotropia successfully treated by prismatic correction of the latent strabismus present on "straight" days.

Microscopic-macroscopic approach for binding energies with the Wigner-Kirkwood method. II. Deformed nuclei

The binding energies of deformed even-even nuclei have been analyzed within the framework of a recently proposed microscopic-macroscopic model. We have used the semiclassical Wigner-Kirkwood ̄h expansion up to fourth order, instead of the usual Strutinsky averaging scheme, to compute the shell corrections in a deformed Woods-Saxon potential including the spin-orbit contribution. For a large set of 561 even-even nuclei with Z 8 and N 8, we find an rms deviation from the experiment of 610 keV in binding energies, comparable to the one found for the same set of nuclei using the finite range droplet model of Moller and Nix (656 keV). As applications of our model, we explore its predictive power near the proton and neutron drip lines as well as in the superheavy mass region. Next, we systematically explore the fourth-order Wigner-Kirkwood corrections to the smooth part of the energy. It is found that the ratio of the fourth-order to the second-order corrections behaves in a very regular manner as a function of the asymmetry parameter I=(N−Z)/A. This allows us to absorb the fourth-order corrections into the second-order contributions to the binding energy, which enables us us to simplify and speed up the calculation of deformed nuclei.

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients.

PURPOSE: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. METHODS AND MATERIALS: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. RESULTS: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). CONCLUSIONS: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.

Tukin asemointi sahausta varten

Diplomityössä tutkittiin tukinpyörityksen yleisimpiä ongelmia. Tutkimus selvitti tukinpyörityksen ongelmien syitä, sekä määritti kahden tukinpyörityslaitteiston takuuarvot. Tutkimuksen kohteena oli myös prosessiparametrien muutoksen vaikutus pyöritystarkkuuteen. Tukin pyöritysvirheen ja saannon yhteyttä tutkittiin teorian perusteella. Tukin onnistuneessa asemoinnissa sahaukseen täytyy hallita tukinpyöritys sekä -suuntaus. Tukin virheellinen asemointi heikentää saantoa. Raaka-ainekustannukset ovat suurimmat yksittäiset kustannukset sahoilla, siksi tukin virheellinen asemointi heikentää sahan taloudellista tulosta voimakkaasti. Työn tuloksista käy ilmi, ettei tukinpyörityksen onnistuminen riipu ainoastaan mekaanisista ratkaisuista, järjestelmän kaikkien komponenttien on toimittava moitteettomasti. Mekaniikka ei toteuta pyörityskäskyjä oikein, jos käskyt ovat epätarkkoja. Tukinpyörityksen tarkkuuden mittaukseen on kiinnitetty huomiota vasta äskettäin. Tunnusluvut, jotka kuvaavat tukinpyöritystarkkuutta ovat vakiintumassa yleiseen käyttöön. Työn tulosten perusteella voidaan tukinpyörityslaitteistojen myynti perustaa tutkimustiedolle.

Characteristics of 2D convective structures in Catalonia (NE Spain): an analysis using radar data and GIS

Flood simulation studies use spatial-temporal rainfall data input into distributed hydrological models. A correct description of rainfall in space and in time contributes to improvements on hydrological modelling and design. This work is focused on the analysis of 2-D convective structures (rain cells), whose contribution is especially significant in most flood events. The objective of this paper is to provide statistical descriptors and distribution functions for convective structure characteristics of precipitation systems producing floods in Catalonia (NE Spain). To achieve this purpose heavy rainfall events recorded between 1996 and 2000 have been analysed. By means of weather radar, and applying 2-D radar algorithms a distinction between convective and stratiform precipitation is made. These data are introduced and analyzed with a GIS. In a first step different groups of connected pixels with convective precipitation are identified. Only convective structures with an area greater than 32 km2 are selected. Then, geometric characteristics (area, perimeter, orientation and dimensions of the ellipse), and rainfall statistics (maximum, mean, minimum, range, standard deviation, and sum) of these structures are obtained and stored in a database. Finally, descriptive statistics for selected characteristics are calculated and statistical distributions are fitted to the observed frequency distributions. Statistical analyses reveal that the Generalized Pareto distribution for the area and the Generalized Extreme Value distribution for the perimeter, dimensions, orientation and mean areal precipitation are the statistical distributions that best fit the observed ones of these parameters. The statistical descriptors and the probability distribution functions obtained are of direct use as an input in spatial rainfall generators.

Flokkulaation seuraaminen partikkelikokoanalysaattorilla

Tässä työssä tutkittiin kahden erilaisen partikkelikokoanalysaattorin, PSyA:n ja PIA:n soveltuvuutta flokkuloinnin online-seurantaan. Kummallekin menetelmälle määritettiin raja-arvot, kuten lietteen maksimisakeus. Lisäksi tutkittiin flokkulanttiannostuksen, sekoitusnopeuden, sekoitusajan ja lietteen kiintoainepitoisuuden vaikutusta flokkikokojakaumaan. Kirjallisuusosassa tarkasteltiin kolloidisen suspension ominaispiirteitä, koaguloinnin ja flokkuloinnin teoriaa, flokkulaation kokeellista tutkimista sekä prosessin jatkuvatoimiseen seurantaan soveltuvia laitteita. Lisäksi esitettiin taustaa hydrometallurgisesta prosessista, johon työ liittyy. Flokkauskokeissa käytettiin jätevettä, jonka koostumus vastasi metalliteollisuuden peittausjätevesien tyypillistä koostumusta. Tutkittava jätevesimäärä käsiteltiin ensin kalkkimaidolla, jonka jälkeen saostunut kiintoaine flokattiin synteettisellä polymeeriflokkulantilla. Lietteen keskimääräinen kiintoainepitoisuus oli n. 10 g/l. Esikokeiden perusteella PSyA:lla voitiin mitata ilman laimennusta, mutta PIA:lla tuloksia ei saatu ilman laimentamista kiintoainepitoisuuteen n. 2,5 g/l. Kokeiden aikana havaittiin, että flokit muodostuivat erittäin nopeasti. Flokkien hajoaminen alkoi pian sen jälkeen, kun flokkulantin annostelu lopetettiin. Sekoitusnopeudella 40 r/min tai alle flokit alkoivat laskeutua astian pohjalle sekoituksesta huolimatta ja ne pysyivät pitempään koossa kuin suuremmilla sekoitusnopeuksilla. 5 - 10 minuutin kuluttua flokkulantin lisäämisestä saavutettiin tasapaino, jolloin flokkien kokojakauma ei enää muuttunut. Sekoitusnopeuksilla 80 r/min ja 120 r/min tasapainotilanteen koko-jakauma oli selvästi kapeampi kuin pienimmällä sekoitusnopeudella. Alkuperäisessä lietteessä flokit olivat suurempia kuin laimennetussa lietteessä. PSyA:lla jännepituusjakaumien määrittäminen oli varsin hidasta prosessissa tapahtuviin muutoksiin verrattuna, ja tuloksissa oli suurta hajontaa. PIA:lla saadut partikkelikokojakaumat sitä vastoin olivat johdonmukaisempia, vaikka suurimpien flokkien määrittäminen osoittautuikin epämääräiseksi. Menetelmän suurimmaksi puutteeksi todettiin soveltumattomuus sakeiden lietteiden analysointiin. Kumpikaan menetelmä ei ilman modifiointia sovellu tutkitun lietteen kaltaisten prosessilietteiden flokkuloinnin seurantaan.