Mutational drivers of a dysfunctional local immune response in resected non-small cell lung cancer (NSCLC) patients

Background: Patients with KEAP1 and STK11 alterations have shown poor response to immunotherapy in non-small cell lung cancer (NSCLC) due to unknown underlying mechanisms. In a sub-study of the TNM-I trial (NCT03299478), we discovered that lung adenocarcinomas (LUAD) with concurrent KEAP1 and STK11 mutations exhibit predominantly non-inflamed immunological features, potentially contributing to immunotherapy resistance (PMID: 37100205). However, it is unclear whether single mutations or co-mutations drive this phenomenon. Methods: Among 215 patients (stage I-IIIA) who underwent genomic profiling, tumor tissue from 23 LUAD patients with STK11 and KEAP1 mutations were included in this thesis. NanoString gene expression analysis with the nCounter PanCancer IO 360™ Panel was performed and analyzed. Comparisons of gene expression and metagene changes were assessed across single versus co-mutations. Results: 44% (n = 10) of the cohort had co-mutations, while 56% (n = 13) had a single mutation with either KEAP1 or STK11. In STK11 vs co-mutation, pathway analysis revealed up-regulation of genes associated with adaptive immunity. Specifically, B cells were generally upregulated (p-adj < 0.05) in STK11 altered cases. In KEAP1 vs co-mutation, matrix remodeling and metastasis pathways were highly enriched, with the highest fold changes for MMP7 and MMP9 (5.19, 3.34, respectively; p-adj < 0.05). Additionally, we found up-regulation of chemoresistant pathways in KEAP1 mutated patients (p-adj < 0.05). In STK11 vs KEAP1, NF-kappaB was the most altered pathway. Conclusion: KEAP1 mutation is the main driver of the non-inflamed phenotype in LUAD compared to STK11 mutation, and it contributes to a more aggressive disease through activation of metastatic pathways and chemoresistance features. These results need to be validated in larger datasets

Sewage sludge biochars as effective PFAS-sorbents

publishedVersio

A New Insight of Phycoremdiation Study: Using Filamentous Algae for the Treatment of Tertiary Municipal Wastewater

This book chapter demonstrated that the filamentous algae could be used as a promising phycoremediation approach to purify municipal tertiary wastewater. Initial screening of 25 algae strains across multiple genera revealed that Spirogyra sp. and Klebsormidium sp. were suitable to treat the tertiary effluent from a modern wastewater treatment plant (WWTP), and their co-culture was validated in three consecutive outdoor pilot tests. In the first two pilot tests, the nutrient concentrations of phosphorous and ammonium were depleted close to zero within 24 hours, whereas the pH value increased from 7 to 9 in the wastewater. Therefore, CO2 was added for pH control in the 3rd batch, but the nutrient removal efficacy indicated that fresh algae inoculum was critical to maintain treatment efficiency. The biomass accumulated notable amounts of Ca, Mg, K, Fe, Al, and heavy metals from the effluent, while the algae production increased by two to three times over 7 days with an average algae biomass productivity of 1.68 g m2 d−1. The derived biomass can be used for biogas production and biofertilizer applications based on the biochemical constituent. Given a great potential for further optimization and improvement, we provide a new insight to use phycoremediation approach to facilitate the green transition of wastewater treatment plants

Towards Responsible Media Recommendation

Reading or viewing recommendations are a common feature on modern media sites. What is shown to consumers as recommendations is nowadays often automatically determined by AI algorithms, typically with the goal of helping consumers discover relevant content more easily. However, the highlighting or filtering of information that comes with such recommendations may lead to undesired effects on consumers or even society, for example, when an algorithm leads to the creation of filter bubbles or amplifies the spread of misinformation. These well-documented phenomena create a need for improved mechanisms for responsible media recommendation, which avoid such negative effects of recommender systems. In this research note, we review the threats and challenges that may result from the use of automated media recommendation technology, and we outline possible steps to mitigate such undesired societal effects in the future.publishedVersio

Setting a baseline for global urban virome surveillance in sewage

The rapid development of megacities, and their growing connectedness across the world is becoming a distinct driver for emerging disease outbreaks. Early detection of unusual disease emergence and spread should therefore include such cities as part of risk-based surveillance. A catch-all metagenomic sequencing approach of urban sewage could potentially provide an unbiased insight into the dynamics of viral pathogens circulating in a community irrespective of access to care, a potential which already has been proven for the surveillance of poliovirus. Here, we present a detailed characterization of sewage viromes from a snapshot of 81 high density urban areas across the globe, including in-depth assessment of potential biases, as a proof of concept for catch-all viral pathogen surveillance. We show the ability to detect a wide range of viruses and geographical and seasonal differences for specific viral groups. Our findings offer a cross-sectional baseline for further research in viral surveillance from urban sewage samples and place previous studies in a global perspective

Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use meta-genomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.Peer reviewe

Setting a baseline for global urban virome surveillance in sewage

The rapid development of megacities, and their growing connectedness across the world is becoming a distinct driver for emerging disease outbreaks. Early detection of unusual disease emergence and spread should therefore include such cities as part of risk-based surveillance. A catch-all metagenomic sequencing approach of urban sewage could potentially provide an unbiased insight into the dynamics of viral pathogens circulating in a community irrespective of access to care, a potential which already has been proven for the surveillance of poliovirus. Here, we present a detailed characterization of sewage viromes from a snapshot of 81 high density urban areas across the globe, including in-depth assessment of potential biases, as a proof of concept for catch-all viral pathogen surveillance. We show the ability to detect a wide range of viruses and geographical and seasonal differences for specific viral groups. Our findings offer a cross-sectional baseline for further research in viral surveillance from urban sewage samples and place previous studies in a global perspective

Fører bruk av en ny prosedyre for legemiddelsamstemming i sykehus til mer nøyaktige legemiddellister? En kvantitativ studie ved fire sykehus i Helse Nord RHF

Bakgrunn og formål: Prosedyre for legemiddelsamstemming (LMS) skal innføres ved alle sykehus i Helse Nord RHF og kliniske farmasøyter fra Sykehusapotek Nord HF skal gjøre kontrollmålinger for å undersøke om prosedyren fører til mer korrekte legemiddellister. Formålet med oppgaven er å 1) karakterisere uoverensstemmelser (UO) identifisert ved kontrollmålinger på fire sykehus i Helse Nord, 2) undersøke hvilke faktorer som påvirker om en legemiddelliste inneholder UO, og 3) undersøke sammenhengen mellom samstemming av legemiddellister og UOr identifisert ved kontrollmåling. Metode: Kontrollmålinger ble utført i perioden juli 2014 til januar 2015. Resultat: De 249 legemiddellistene som ble samstemt tilhørte en pasientpopulasjon med 53% menn og en gjennomsnittsalder på 61 år. Det ble identifisert minst én UO i 59% av legemiddellistene, og gjennomsnittlig antall UOr per liste med UO var 2,4. Hyppigst identifisert UO var ”Bruker annet legemiddel i tillegg til det som er oppgitt på kurven” (56% av totalt antall UOr). Regresjonsanalysen viste at kvinner hadde økt odds for at en UO ble identifisert i legemiddellisten. I tillegg økte oddsen med økt antall legemidler i bruk. Det ble observert en trend for færre identifiserte UOr i legemiddellistene som var dokumentert samstemte sammenlignet med de som ikke var dokumentert samstemte, men forskjellen var ikke statistisk signifikant. Samstemming av legemiddellister etter prosedyre innført ved de aktuelle sykehusene ser dermed ikke ut til å påvirke antall identifiserte UOr ved kontrollmålinger. Konklusjon: Selv om vi observerte en trend der dokumentert samstemte legemiddellister fra avdeling inneholdt færre uoverensstemmelser enn listene som ikke var dokumentert samstemte, var dette ikke statistisk signifikant. Muligvis kan trenden bli signifikant med et større datamateriale. For å øke riktighet av legemiddellister i sykehus i Helse Nord må antakelig prosedyre for LMS enten implementeres bedre eller endres

Methods for Paper Structure Characterisation by Means of Image Analysis

Paper is a complex, disordered porous media. The complexity makes it difficult to obtain more than empirical knowledge of the relationship between papermaking variables and the resulting paper structural properties. It is known that the alteration of the paper structure is decisive for many paper properties, but the appropriate tools for visualising and assessing the changes to the paper structure after varying physical treatments of the paper have until recently not been available. Scanning electron microscope in backscatter mode (SEM-BEI) and X-ray microtomography allows acquisition of respectively cross-sectional and 3D images of the detailed paper structure with sufficient contrast and resolution to clearly discern the structural constituents. The access to detailed images of the paper structure allows quantification of the changes made to the detailed paper structure through application of suitable image analysis routines. The microscopy techniques combined with image analysis thus provide the tools needed to improve the knowledge of how various papermaking variables may improve the paper properties through alteration of the paper structure. Improvement of the knowledge of the structural mechanisms governing the paper properties may help to give a more knowledge based operation of the paper machines and may be applied for process and product optimization. This thesis work has considered different aspects of how the physics governing the SEM-BEI technique, image acquisition and sample preparation may affect the quality of the cross-sectional images of the paper structure with regard to the subsequent image analysis. The effect of the applied filtering and segmentation routines to obtain the binary representation needed for image analysis are also considered. It was found that the applied methodology yielded realistic binary cross-sectional representations of the paper structure and thus representative structural assessments. However, to obtain assessments that are representative for the paper grade and not only the small cross section, at least 15 independent cross-sectional images were needed. Then umber of necessary replicates varied somewhat depending on the structural characteristics. This study involved improvement of existing image analysis techniques. The main contribution from this work in this aspect is the application of the rolling ball algorithm for an objective surface definition of the physically small and often uneven paper cross sections. The objective surface definition enables the division of the structure into locally uniformly thick layers, for which the material distribution in the z-direction of the paper can be determined. The material distributions that may be determined include solid/void fractions, fillers and fines content. The improved image analysis routines also include measurement of local thickness, density and basis weight, pore chords and specific surface area. The practical application of the SEM technique for obtaining new knowledge of papermaking variables: paper structure: paper properties relationships included assessment of the pore geometry and the material distribution in the z-direction. The z-directional material distribution was determined in order to assess the effect of temperature gradient calendering on a SC-paper grade. The results obtained for the z-directional material distributions combined with surface topography techniques revealed that the temperature gradient effect was concentrated to the very few outermost micrometers of the paper structure. The pore geometry was assessed by both the 2D and 3D techniques. The determined pore chord distributions followed the theoretically derived pore height distribution of Dodson for the z-direction. The pore chord distribution for any spatial direction appeared to follow a log-normal distribution, when including all pore chord sizes to allow a “continuous” distribution. The mean and standard deviation were proven to be proportional, as earlier observed from physical pore size measurements and theoretical deductions. The width of the pore chord distributions for the different spatial directions changed with the structural anisotropy. The wider the pore height distribution, the more different are the pore chord mean and standard deviation. Most of the information obtained for the pore geometry from assessment of pore chords can be summarized in the equivalent pore representation. The ellipsoid shape of the equivalent pore, constructed as a warped surface of the mean pore chords for all spatial directions, was confirmed from the assessments of 3D images of three different paper grades having distinctly different structural properties. The ellipsoid shape was also found for the pore chord standard deviation. Additionally, it was found that the ellipsoid constructed for the solid phase had the same shape as for the porous phase and their relative size was proportional to the solid fraction of the assessed paper structure. The equivalent pore ellipsoid thus contain all information about the pore/fibre chord distributions in all spatial directions in addition to the structural anisotropy. The studies of the pore geometry prove that the solid fraction and the structural anisotropy are the major determinants for the pore geometry. The results reveal that there is clear differences between the pore size distribution determined by image analysis and physical assessments like mercury porosimetry, which is affected by narrow pore necks limiting the intrusion from the surfaces. This thesis work have applied three different applications of X-ray microtomography. The three different applications include both phase contrast and absorption mode contrasting for high resolution synchrotron source X-ray microtomography and low resolution X-ray microtomography provided by a stationary source commercial scanner. The experiences from this work have proven that the synchrotron source X-ray microtomography can be applied successfully to obtain high quality digital representations of the 3D paper structure with sufficient contrast and resolution to detect and quantify the details of the fibre network. The current technology at the applied beam lines at the ESRF, France, allows spatial resolution down to approximately 1 µm. This resolution is sufficient for obtaining realistic structural assessments that are suited for determining how the paper structure is affected by papermaking variables and itself influences the paper properties. The high resolution also provides insight into the detailed paper characteristics from visualization of the 3D paper structure. The resolution provided by the stationary X-ray source is not sufficient to preserve the fibre network topology. However, the signal is of sufficient quality to make comparative structural assessments possible, although the numerical results from the structural assessments are not physically reasonable. This thesis work have considered different aspects of how the working principles, image acquisition, sample preparation, sample mounting and volume reconstruction of the three applied X-ray microtomography techniques may affect the quality of the 3D images of the paper structure with regard to the subsequent image analysis. It was found that the sample mounting for the high resolution absorption mode images was clearly affecting the digital representation of the paper structure. An alternative sample mounting, avoiding the melt glue penetrating into the paper structure, is recommended for future application of X-ray microtomography. However, it must be emphasized that restricting sample movement during the image acquisition is of outmost importance to obtain 3Dimages with a minimal content of noise. The applied routines for image filtering and segmentation to obtain binary representations are presented and the quality of the resulting binary structures are evaluated. The results prove that the applied image processing preserves most of the information provided by the greyscale images. However, the applied routines are not optimised. Exploiting more of the three-dimensional connectivity in the images and applying edge preserving filtering techniques may improve the image processing for future experiments. The image processing of the phase contrast images is difficult, semi-automatic, laborious and computationally demanding due to the relatively low contrast and the contrasting technique detects only the phase borders. The image processing of the absorption mode images is considerably more straightforward. The quality of the binary absorption mode images is almost as good as the binary phase contrast images, despite the lower resolution. The absorption mode is therefore recommended for the future application of high resolution X-ray microtomography. Additional benefits of the absorption mode imaging is the ability to discern mineral particles and coating and that it has no principal problems in acquiring images of high density paper grades. A benefit only provided by the phase contrast technique is that it provides sufficient contrast between wood fibres and water to acquire 3D images of soaked paper samples. This study has applied and looked into the details of many image analysis routines and transport simulations to determine the characteristics of the imaged paper structures. Most of these routines have already been applied to low resolution 3D images of paper or to 3D images of geological samples. The main contribution from this study regarding the analysis of the structure is thus modification of some of the image analysis routines to include the surface layers after defining the surface using the rolling ball algorithm. The practical application of the X-ray microtomography technique showed that calendering of a newsprint-like paper grade had a dominating effect on the paper structure compared to addition of reinforcement pulp, addition of retention aid and alteration of the head box consistency. The calendering resulted in a denser sheet having smaller pores and a higher resistance against transport through the porous phase, especially for the z-directional flow. The analysis of the applied factorial design yielded indicative results for the other papermaking variables. The few significant effects revealed that the addition of reinforcement fibres yielded slightly larger average pores and the addition of retention aid resulted in a slightly more complex structure. The alteration of the head box consistency seemed to have an insignificant effect on the small paper volumes. Additionally, the assessments showed that the standard deviation for the assessed structural characteristics were less than ±10% of the mean value. The mean values for the determined transport properties showed a higher standard deviation. However, the size of the 3D digital paper volumes render division of the volumes into sufficiently large sub volumes to maintain representative scales possible. Assessment of the transport properties of a number of sub volumes enabled a determination of the transport property: porosity relationship instead of a single mean value. In this way more information was extracted from the volume and the results were less affected by normal variation. The results from the practical study of X-ray microtomography confirm the hypothesis that the density/solid fraction of the paper structure is a major determinant of the paper properties. An important part of this study has been to consider which is the right technique of the2D and 3D methods for various structural characterization applications. There is a clear differentiation between the practical applications of the techniques. The SEM technique is the preferred technique for more repetitive and routine type assessments, for characterizations where the 3D extension of the objects are not of crucial interest or for assessments where the nature of fines and fibrils are of high importance. The X-ray microtomography is a natural choice for more complex structural assessments where the extension of the fibres and pores are of high interest, as for e.g. assessment of transport properties. The 3D extension of the structure may also be needed to obtain a better knowledge of how the paper structure influences the bulk paper performance properties than provided by the cross-sectional approach. X-ray microtomography is thus a powerful research tool that can provide information which is difficult or impossible to access applying other methods. However, the technique has its clear limitations when it comes to availability, representativity and resolution. It is also important keep in mind that the technique will not in the near future be an everyday technique that many scientists will have access to. This study have helped establishing the SEM-BEI and X-ray microtomography microscopy combined with image analysis for paper structure characterisation. The tools provide many possible applications for the paper researchers that see the available possibilities. However, the results from application of the techniques for determining relationships between papermaking variables and paper structure characteristics, and possible relationships between structural characteristics and paper properties, are never better than the applied experimental scheme. Future application of the techniques for structural characterisation will hopefully add to the knowledge of the detailed properties of the paper material and thus assist in product and process optimization

Real-time annotation of video streams using staged processing

Real-time media rich applications rely on live streams of rich and accurate meta-data describing the video content to provide personal user experiences. Unfortunately, the general amount of video meta-data today is often limited to titles, synopsis and a few keywords. A wildly used approach for extraction of meta-data from video is computer vision. It has been developed a number of different video processing algorithms which can analyse and retrieve useful data from video. However, the computational cost of current computer vision algorithms is considerable. This thesis presents a software architecture that aims to enable real-time annotation of multiple live video streams. The architecture is intended for use within media rich applications where extraction of video semantics in real-time is necessary. Our conjecture was that staging video processing in levels will make room for a more scalable video annotation system. To evaluate our thesis we have developed the prototype runtime Árvdadus. Our experiments show that staged processing can decrease the computation time of meta-data extraction. The evaluation of the architecture suggests that the architecture is applicable in a wide range of domains where extraction of meta-data in real-time is necessar