Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

Background: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. Patients and methods: Eighty-five mRCC patients received everolimus at Helsinki University Hospital (cohort A). Computed tomography (CT) verified pneumonitis was correlated with outcome using Kaplan-Meier, Cox regression and logistic regression. An independent cohort of 148 everolimus treated mRCC patients (cohort B) at Aarhus University Hospital was assessed for validation. Results: In cohort A, CT-verified pneumonitis (N = 29, 34.1%) was associated with improved overall survival (OS) (24.7 versus 8.5 months; P <0.001), progression-free survival (PFS) (5.5 versus 3.2 months; P = 0.002) and clinical benefit rate (CBR) 57.1% versus 24.1% (P = 0.003). In multivariate analyses pneumonitis was associated with improved OS (hazard ratio [HR], 0.22; 95% confidence interval [CI] 0.12-0.44; P <0.001), PFS (HR 0.37; 95% CI 0.21-0.66; P = 0.001) and CBR (odds ratio [OR] 4.11; 95% CI 1.42-11.95; P = 0.01). In cohort B, CT-verified pneumonitis (N = 29, 19.6%) was associated with improved OS (12.9 versus 6.0 months; P = 0.02), PFS (6.0 versus 2.8 months; P = 0.02) and CBR (79.3% versus 39.5%; P <0.001). In multivariate analyses pneumonitis was associated with improved OS (HR 0.58; 95% CI 0.36-0.94; P = 0.03), PFS (HR 0.61; 95% CI 0.39-0.95; P = 0.03) and CBR (OR 5.65; 95% CI 2.10-15.18; P = 0.001). In a combined multivariate analysis (N = 233), with pneumonitis as a time-dependent covariate, CT-verified pneumonitis was associated with longer OS (HR, 0.67; 95% CI 0.46-0.97; P = 0.03). Furthermore, in a landmark analysis, pneumonitis was associated with longer OS (17.4 versus 7.8 months; P = 0.01). Conclusions: Everolimus-induced pneumonitis is associated with improved outcome in patients with mRCC and may serve as a biomarker of everolimus efficacy. (C) 2017 Elsevier Ltd. All rights reserved.Peer reviewe

Enfoques recientes para modelizar el riesgo de tormentas y fuego en los bosques europeos y su integración

The aim of this paper is to discuss the different recently developed empirical and mechanistic modelling approaches for assessing the risk of wind and fire damage to forests. Additionally the work will explore possible ways to integrate these approaches, including feedback mechanisms, into growth and yield models and decision support tools used in forestry. The integration of mechanistic and empirical storm risk models, as well as an empirical/mechanistic fire risk model into growth simulators is demonstrated and future challenges and options for risk modelling and for creating complex decision support tools, including growth simulators, meteorological components and risk modules, are discussed.El objetivo de este trabajo es analizar los diferentes modelos empíricos y mecanicistas que se han desarrollado recientemente para evaluar el riesgo de daños por el viento y el fuego en los bosques. Además, el trabajo explora las posibles formas de integrar estos enfoques, incluyendo mecanismos de retroalimentación, en los modelos de crecimiento y produccion y en las herramientas de apoyo a la toma de decisiones utilizadas en el sector forestal. Se muestra la integración de modelos mecanicistas y empíricos de riesgo a tormentas, así como un modelo empírico/mecanicista de riesgo de incendio en los simuladores de crecimiento y se discuten los retos futuros y las opciones para la modelización de riesgos y para la creación de complejas herramientas de apoyo a la toma de decisiones, incluyendo simuladores de crecimiento, componentes meteorológicos y módulos de riesgo

Musiikkikeskus Oulun keskustaan

Tiivistelmä. Suunnittelin kandidaatintyössäni musiikkikeskuksen Oulun keskustan Pakkahuoneenkadulle. Tavoitteenani oli luoda musiikin ystäville arvokas paikka Oulun keskustaan. Musiikkikeskus toimisi modernina kohtaamispaikkana niin musiikin soittajille, opettajille, harrastajille kuin ohikulkijoillekin. Suunnitelmani oli korvata olemassa oleva toimistorakennus kaupunkikuvaa elävöittävällä keskuksella, jossa yhdistyvät musiikkiopiston konservatoriotilat sekä kamarimusiikkisali. Vuoden teemana Nykyaikaisen arkkitehtuurin III -kurssilla käsittelimme kiertotalouden ja kestävän kehityksen kysymysten ratkaisuja nykyarkkitehtuurin keinoin. Kohde oli arkkitehti Reijo Kerolan suunnittelema 1962 valmistunut konttori- ja liiketalo, joka on jo pitkään ollut purku-uhan alla. Tontin ahtaus on hankaloittanut kannattavan uudisrakennuksen sovittamista kortteliin. Vanhan rakennuksen rungon hyödyntäminen täysin uudistuvassa toiminnossa jäi muilta osin omaksi valinnakseni, mutta kantavat seinät sekä pilarit ja palkit tuli säilyttää. Projekti laittoi minut ajattelemaan korjausrakentamisen haasteita. Kuinka uudet, enemmän tilaa vievät toiminnot saadaan sijoitettua vanhaan runkoon muuttuvan käyttötarkoituksen ja kehittyvän talotekniikan myötä? Päätin laajentaa rakennusta sekä kadun että sisäpihan suuntaan sekä lisäämällä yhden, korkean kerroksen. Musiikkikeskus koostuu suorakulmaisesta massasta, joka tekee porrastuksen sisäpihan suuntaan luoden luontevan syvennyksen pääsisäänkäynnille kadun puolelle. Ensimmäiseen kerrokseen sijoittuva ravintolasali avautuu lasiseinän kautta sekä kadulle että sisäpihan terassille. Ylimpään kerrokseen sijoittuu työssäni näyttävä kamarimusiikkisali, jota ympäröi lasinen lämpiö kaupunkinäköalalla. Tukitilat, kuten keittiö ja tekniset tilat ovat kellarikerroksessa, ja 2.–4. kerroksen konservatorion kaikista opetustiloista ja toimistoista avautuu näkymä kadulle tai sisäpihalle. Metallinhohde julkisivussa ja avara katutason kerros kutsuvat kulkijan sisälleen musiikin ihmeelliseen maailmaan

A comparison of the DNA binding and bending capacities and the oligomeric states of the immunity repressors of heteroimmune coliphages P2 and WPhi

Bacteriophages P2 and WΦ are heteroimmune members of the P2-like family of temperate Escherichia coli phages. Temperate phages can grow lytically or form lysogeny after infection. A transcriptional switch that contains two con-vergent promoters, Pe and Pc, and two repressors regulate what life mode to enter. The immunity repressor C is the first gene of the lysogenic operon, and it blocks the early Pe promoter. In this work, some characteristics of the C proteins of P2 and WΦ are compared. An in vivo genetic analysis shows that WΦ C, like P2 C, has a strong dimerization activity in the absence of its DNA target. Both C proteins recognize two directly repeated sequences, termed half-sites and a strong bending is induced in the respective DNA target upon binding. P2 C is unable to bind to one half-site as opposed to WΦ, but both half-sites are required for repression of WΦ Pe. A reduction from three to two helical turns between the centers of the half-sites in WΦ has no significant effect on the capacity to repress Pe. However, the protein–DNA complexes formed differ, as determined by electrophoretic mobility shift experiments. A difference in spontaneous phage production is observed in isogenic lysogens

Effects of intensified silviculture on timber production and its economic profitability in boreal Norway spruce and Scots pine stands under changing climatic conditions

201

Effects of Initial Age Structure of Managed Norway Spruce Forest Area on Net Climate Impact of Using Forest Biomass for Energy

We investigated how the initial age structure of a managed, middle boreal (62A degrees N), Norway spruce-dominated (Picea abies L. Karst.) forest area affects the net climate impact of using forest biomass for energy. The model-based analysis used a gap-type forest ecosystem model linked to a life cycle assessment (LCA) tool. The net climate impact of energy biomass refers to the difference in annual net CO2 exchange between the biosystem using forest biomass (logging residues from final felling) and the fossil (reference) system using coal. In the simulations over the 80-year period, the alternative initial age structures of the forest areas were (i) skewed to the right (dominated by young stands), (ii) normally distributed (dominated by middle-aged stands), (iii) skewed to the left (dominated by mature stands), and (iv) evenly distributed (same share of different age classes). The effects of management on net climate impacts were studied using current recommendations as a baseline with a fixed rotation period of 80 years. In alternative management scenarios, the volume of the growing stock was maintained 20% higher over the rotation compared to the baseline, and/or nitrogen fertilization was used to enhance carbon sequestration. According to the results, the initial age structure of the forest area affected largely the net climate impact of using energy biomass over time. An initially right-skewed age structure produced the highest climate benefits over the 80-year simulation period, in contrast to the left-skewed age structure. Furthermore, management that enhanced carbon sequestration increased the potential of energy biomass to replace coal, reducing CO2 emissions and enhancing climate change mitigation.Peer reviewe

Genetics, recombination and clinical features of human rhinovirus species C (HRV-C) infections; interactions of HRV-C with other respiratory viruses

To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV), 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR) for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV) and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%). Infections predominantly targeted the very young (median age 6–12 months; 80% of infections in those &#60;2 years), occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT) and upper respiratory tract (URT) disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV) in both disease presentations (6.9% and 7.8% of all cases respectively). HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5′untranslated region (5′UTR), the majority grouped with species A (n = 96; 68%, described as HRV-Ca), the remainder forming a phylogenetically distinct 5′UTR group (HRV-Cc). Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to other respiratory virus infections. HRV-C's disease associations, its prevalence and evidence for interfering effects on other respiratory viruses mandates incorporation of rhinoviruses into future diagnostic virology screening

Can models for forest attributes based on airborne laser scanning be generalized for different silvicultural management systems?

In Finland, interest in continuous cover forestry (CCF) has increased rapidly in recent years. During those years CCF has been examined from various viewpoints but not from the perspective of forest inventories. This holds especially true for applications based on remote sensing. Conversely, airborne laser scanning (ALS) data have been widely used to predict forest characteristics such as size distribution and vertical forest structure, which are closely related to the forest information needs of CCF. In this study we used the area-based approach to predict a set of stand attributes from ALS data (5 pulses per m2) in a CCF forest management experiment in Katajama & BULL;ki, eastern Finland. In addition to the CCF stands, the experiment included shelterwood stands and untreated stands. The predicted attributes included volume, biomass, basal area, number of stems, mean diameter, Lorey's height, dominant height, standing dead wood volume, parameters of the theoretical stem diameter distribution model, understory height and number of understory stems. Our main aim was to test whether the same model could be used across different management systems. The accuracy of the attributes predicted for the CCF stands was compared with the predictions for the other management systems in the same experiment. We also compared and discussed our results in relation to the even-aged stand attribute predictions that were conducted by using separate operational forest data collected from sites surrounding Katajama & BULL;ki. The results showed that forest data from the different management systems could be combined into a single model of a stand attribute, i.e., ALS metrics were found to be suitable for comparing different management systems in regard to differences in forest structure. The accuracy of the predicted attributes in the CCF plots was comparable to that of the other management alternatives in the experiment. The accuracy was also comparable to that of even-aged forests. The results of this study were promising; the stand attributes of CCF-managed forests could be predicted analogously to those of other management systems. This indicates that for the purposes of forest inventories there may not be a need to stratify forest lands by management system. It should be noted, however, that the study area was relatively small, that the forest stands were harvested in the 1980 s, and that the attributes may not have been completely exhaustive for CCF