| 1. |
- Arnarson, Örvar
(författare)
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Emergent colon cancer and postoperative complications - risks and management
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background:Colorectal cancer in the third most diagnosed cancer in Sweden and the second most common cause of cancer-related death in Sweden and worldwide. 10-30% of the cases present as emergencies, of which 80% are caused by large bowel obstruction (LBO). Most of these patients undergo emergency resection which is associated with high rates of morbidity and mortality. To overcome the risk with emergency resection (ER) the patients can be managed with a staged preocedure or bridge to surgery (BTS) which encompasses decompression of the bowel, either with stent or deviating stoma, followed by planned resection surgery. Data in these studies comes from the Swedish Colorectal Cancer Registry (SCRCR) which is proofed to have high validity.Aims:To evaluate the impact of postoperative complications after curative resection of colon cancer on long-term survival.To compare short- and long-terms outcome after management of acute malignant large bowel obstruction with Bridge to Surgery or emergency resection.To evaluate short- and long-term outcomes following emergent colon cancer surgery depending on sub-specialization of the operating team.To evaluate the reliability of data from the Swedish Colorectal Cancer Registry through a validation process.Methods:Study I-II were national retrospective cohort studies of patients operated for colon cancer between 2007-2009. In study I, all patients radically resected for stage I-III colon cancer were included. In study II patients with stage I-IV colon cancer and acute large bowel obstrction managed with either BTS or ER with curative intent. Study III was a regional retrospective cohort study including patients that underwent emergency resection in 2011-2016. In study I-III data on short-and long-term outcomes were collected and analysed. Study IV was a validation study on 700 randomly selected patients operated for CRC in 2015. Data from the medical files were re-abstracted and compared with data in the SCRCR to assess the agreement. Results: Postoperative complication is associated with decreased 5-year overall and 3-year disease free survival but not recurrence rate. BTS is associated with higher 5-year overall survival compared to ER, whereas no difference in the 3-year recurrence free survival. Specialization of surgical team dit not impact short-term outcomes, 3-year recurrence free survival or 5-year overall survival. Validation of register data showed almost perfect agreement of histopathology and recurrence data, whereas postoperative complication variables had moderate to substantial agreement depending on the severity of the complication.Importance: The results of this thesis shows that postoperative complications need to be addressed and treated promptly in attempt to increase survival. BTS has better overall survival and lower stoma rate and may be considered as a primary alternative in the management of malignang LbO. Acute care surgeons treat patient with emergent colon cancer with same result on long-time survival as colorectal surgeons. The validity of data in the SCRCR is very good but care must be taken when interpreting information on postoperative complications.
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| 2. |
- Del Moral, Pablo, 1989-, et al.
(författare)
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Pitfalls of Assessing Extracted Hierarchies for Multi-Class Classification
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Using hierarchies of classes is one of the standard methods to solve multi-class classification problems. In the literature, selecting the right hierarchy is considered to play a key role in improving classification performance. Although different methods have been proposed, there is still a lack of understanding of what makes a hierarchy good and what makes a method to extract hierarchies perform better or worse.To this effect, we analyze and compare some of the most popular approaches to extracting hierarchies. We identify some common pitfalls that may lead practitioners to make misleading conclusions about their methods.To address some of these problems, we demonstrate that using random hierarchies is an appropriate benchmark to assess how the hierarchy's quality affects the classification performance.In particular, we show how the hierarchy's quality can become irrelevant depending on the experimental setup: when using powerful enough classifiers, the final performance is not affected by the quality of the hierarchy. We also show how comparing the effect of the hierarchies against non-hierarchical approaches might incorrectly indicate their superiority.Our results confirm that datasets with a high number of classes generally present complex structures in how these classes relate to each other. In these datasets, the right hierarchy can dramatically improve classification performance.
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| 3. |
- Del Moral, Pablo, 1989-, et al.
(författare)
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Why Is Multiclass Classification Hard?
- 2022
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Ingår i: IEEE Access. - Piscataway, NJ : IEEE. - 2169-3536. ; 10, s. 80448-80462
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Tidskriftsartikel (refereegranskat)abstract
- In classification problems, as the number of classes increases, correctly classifying a new instance into one of them is assumed to be more challenging than making the same decision in the presence of fewer classes. The essence of the problem is that using the learning algorithm on each decision boundary individually is better than using the same learning algorithm on several of them simultaneously. However, why and when it happens is still not well-understood today. This work’s main contribution is to introduce the concept of heterogeneity of decision boundaries as an explanation of this phenomenon. Based on the definition of heterogeneity of decision boundaries, we analyze and explain the differences in the performance of state of the art approaches to solve multi-class classification. We demonstrate that as the heterogeneity increases, the performances of all approaches, except one-vs-one, decrease. We show that by correctly encoding the knowledge of the heterogeneity of decision boundaries in a decomposition of the multi-class problem, we can obtain better results than state of the art decompositions. The benefits can be an increase in classification performance or a decrease in the time it takes to train and evaluate the models. We first provide intuitions and illustrate the effects of the heterogeneity of decision boundaries using synthetic datasets and a simplistic classifier. Then, we demonstrate how a real dataset exhibits these same principles, also under realistic learning algorithms. In this setting, we devise a method to quantify the heterogeneity of different decision boundaries, and use it to decompose the multi-class problem. The results show significant improvements over state-of-the-art decompositions that do not take the heterogeneity of decision boundaries into account. © 2013 IEEE.
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| 4. |
- Del Moral Pastor, Pablo José, 1989-
(författare)
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Hierarchical Methods for Self-Monitoring Systems : Theory and Application
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Self-monitoring solutions first appeared to avoid catastrophic breakdowns in safety-critical mechanisms. The design behind these solutions relied heavily on the physical knowledge of the mechanism and its fault. They usually involved installing specialized sensors to monitor the state of the mechanism and statistical modeling of the recorded data. Mainly, these solutions focused on specific components of a machine and rarely considered more than one type of fault.In our work, on the other hand, we focus on self-monitoring of complex machines, systems composed of multiple components performing heterogeneous tasks and interacting with each other: systems with many possible faults. Today, the data available to monitor these machines is vast but usually lacks the design and specificity to monitor each possible fault in the system accurately. Some faults will show distinctive symptoms in the data; some faults will not; more interestingly, there will be groups of faults with common symptoms in the recorded data.The thesis in this manuscript is that we can exploit the similarities between faults to train machine learning models that can significantly improve the performance of self-monitoring solutions for complex systems that overlook these similarities. We choose to encode these similarity relationships into hierarchies of faults, which we use to train hierarchical supervised models. We use both real-life problems and standard benchmarks to prove the adequacy of our approach on tasks like fault diagnosis and fault prediction.We also demonstrate that models trained on different hierarchies result in significantly different performances. We analyze what makes a good hierarchy and what are the best practices to develop methods to extract hierarchies of classes from the data. We advance the state-of-the-art by defining the concept of heterogeneity of decision boundaries and studying how it affects the performance of different class decompositions.
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| 5. |
- Del Moro, Agnese, et al.
(författare)
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Luminous and Obscured Quasars and Their Host Galaxies
- 2018
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Ingår i: Frontiers in Astronomy and Space Sciences. - : Frontiers Media SA. - 2296-987X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The most heavily-obscured, luminous quasars might represent a specific phase of the evolution of the actively accreting supermassive black holes and their host galaxies, possibly related to mergers. We investigated a sample of the most luminous quasars at z approximate to 1 - 3 in the GOODS fields, selected in the mid-infrared band through detailed spectral energy distribution (SED) decomposition. The vast majority of these quasars (-80%) are obscured in the X-ray band and 30% of them to such an extent, that they are undetected in some of the deepest (2 and 4 Ms) Chandra X-ray data. Although no clear relation is found between the star-formation rate of the host galaxies and the X-ray obscuration, we find a higher incidence of heavily-obscured quasars in disturbed/merging galaxies compared to the unobscured ones, thus possibly representing an earlier stage of evolution, after which the system is relaxing and becoming unobscured.
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| 6. |
- Del Olmo, Gonzalo, et al.
(författare)
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Influence of phosphate dosing on biofilms development on lead in chlorinated drinking water bioreactors
- 2020
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Ingår i: npj Biofilms and Microbiomes. - : Springer Nature. - 2055-5008. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Phosphate dosing is used by water utilities to prevent plumbosolvency in water supply networks. However, there is a lack of knowledge regarding biofilm formation on lead and plastic materials when phosphate concentrations are modified in drinking water systems. In this study, biofilms were grown over lead coupons and PVC tubes in bioreactors supplied with local drinking water treated to provide different phosphate doses (below 1, 1 and 2 mg/L) over a period of 28 days. A range of commercial iron pellets (GEH104 and WARP) were tested aiming to maintain phosphate levels below the average 1 mg/L found in drinking water. Changes in biofilm community structure in response to three different phosphate treatments were characterised by Illumina sequencing of the 16S rRNA gene for bacteria and the ITS2 gene for fungi. Scanning electron microscopy was used to visualise physical differences in biofilm development in two types of materials, lead and PVC. The experimental results from the kinetics of phosphate absorption showed that the GEH104 pellets were the best option to, in the long term, reduce phosphate levels while preventing undesirable turbidity increases in drinking water. Phosphate-enrichment promoted a reduction of bacterial diversity but increased that of fungi in biofilms. Overall, higher phosphate levels selected for microorganisms with enhanced capabilities related to phosphorus metabolism and heavy metal resistance. This research brings new insights regarding the influence of different phosphate concentrations on mixed-species biofilms formation and drinking water quality, which are relevant to inform best management practices in drinking water treatment.
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| 7. |
- Del Padre, M., et al.
(författare)
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Dual stimulation by autoantigen and CpG fosters the proliferation of exhausted rheumatoid factor-specific CD21(low) B cells in hepatitis C virus-cured mixed cryoglobulinemia
- 2023
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Ingår i: FRONTIERS IN IMMUNOLOGY. - : Frontiers Media SA. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionHepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV specificity. These cells display an atypical CD21low phenotype and functional exhaustion evidenced by unresponsiveness to BCR and Toll-like receptor 9 (TLR9) stimuli. Although antiviral therapy is effective on MC vasculitis, pathogenic B cell clones persist long thereafter and can cause virus-independent disease relapses. MethodsClonal B cells from patients with HCV-associated type 2 MC or healthy donors were stimulated with CpG or heath-aggregated IgG (as surrogate immune complexes) alone or in combination; proliferation and differentiation were then evaluated by flow cytometry. Phosphorylation of AKT and of the p65 NF-kB subunit were measured by flow cytometry. TLR9 was quantified by qPCR and by intracellular flow cytometry, and MyD88 isoforms were analyzed using RT-PCR. DiscussionWe found that dual triggering with autoantigen and CpG restored the capacity of exhausted VH1-69pos B cells to proliferate. The signaling mechanism for this BCR/TLR9 crosstalk remains elusive, since TLR9 mRNA and protein as well as MyD88 mRNA were normally expressed and CpG-induced phosphorylation of p65 NF-kB was intact in MC clonal B cells, whereas BCR-induced p65 NF-kB phosphorylation was impaired and PI3K/Akt signaling was intact. Our findings indicate that autoantigen and CpG of microbial or cellular origin may unite to foster persistence of pathogenic RF B cells in HCV-cured MC patients. BCR/TLR9 crosstalk might represent a more general mechanism enhancing systemic autoimmunity by the rescue of exhausted autoreactive CD21low B cells.
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| 8. |
- Del Padre, M., et al.
(författare)
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Rheumatoid factor-producing CD21low anergic clonal B-cells in essential mixed cryoglobulinaemia: a model for autoantigen-driven pathogenesis of infectious and non-infectious cryoglobulinaemias
- 2020
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Ingår i: Clinical and experimental rheumatology. - 0392-856X. ; 38:2, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Essential mixed cryoglobulinaemia (EMC) is a disorder of B-cells producing rheumatoid factor (RF), and is clinically and immunologically similar to mixed cryoglobulinaemia (MC) related to hepatitis C virus (HCV-MC). We report here the first comprehensive analysis of B-cell clonality, phenotype and function in EMC. METHODS: The study population included 16 patients with EMC and 24 patients with HCV-MC. Molecular analysis was done for the detection of circulating clonal B cells and for B cell receptor sequencing. B-cell phenotype, proliferative response, apoptosis and ERK signaling were analysed by flow cytometry. RESULTS: Molecular analysis of immunoglobulin genes rearrangements revealed circulating B-cell clones in about half of patients, on average of smaller size than those found in HCV-MC patients. Sequence analysis showed usage of the same stereotyped RF-encoding B-cell receptors frequently expressed in HCV-MC and in primary Sjögren's syndrome. B-cells with low expression of CD21 (CD21low) and unusual homing and inhibitory receptors were increased in EMC and in HCV-MC, but at a significantly lower extent in the former. The CD21low B-cells of EMC and HCV-MC patients shared functional features of exhaustion and anergy, namely reduced proliferation upon ligation of Toll-like receptor 9, high constitutive expression of phosphorylated ERK, and proneness to spontaneous apoptosis. CONCLUSIONS: Our findings suggest a common pathogenetic mechanism in EMC, HCV-MC and primary Sjögren's syndrome, consisting of autoantigen-driven clonal expansion and exhaustion of selected RF-producing B-cells. The more massive clonal expansion in HCV-MC may be due to co-stimulatory signals provided by the virus.
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| 9. |
- Del Palacio, Santiago, 1990, et al.
(författare)
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Evidence for non-thermal X-ray emission from the double Wolf-Rayet colliding-wind binary Apep
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 672
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Tidskriftsartikel (refereegranskat)abstract
- Context. Massive colliding-wind binaries (CWBs) can be non-thermal sources. The emission produced in their wind-collision region (WCR) encodes information of both the shock properties and the relativistic electrons accelerated in them. The recently discovered system Apep, a unique massive system hosting two Wolf-Rayet stars, is the most powerful synchrotron radio emitter among the known CWBs. It is an exciting candidate in which to investigate the non-thermal processes associated with stellar wind shocks. Aims. We intend to break the degeneracy between the relativistic particle population and the magnetic field strength in the WCR of Apep by probing its hard X-ray spectrum, where inverse-Compton (IC) emission is expected to dominate. Methods. We observed Apep with NuSTAR for 60 ks and combined this with a reanalysis of a deep archival XMM-Newton observation to better constrain the X-ray spectrum. We used a non-thermal emission model to derive physical parameters from the results. Results. We detect hard X-ray emission consistent with a power-law component from Apep. This is compatible with IC emission produced in the WCR for a magnetic field of ≈ 105-190 mG, corresponding to a magnetic-to-thermal pressure ratio in the shocks of ≈ 0.007-0.021, and a fraction of ∼1.5 × 10-4 of the total wind kinetic power being transferred to relativistic electrons. Conclusions. The non-thermal emission from a CWB is detected for the first time in radio and at high energies. This allows us to derive the most robust constraints so far for the particle acceleration efficiency and magnetic field intensity in a CWB, reducing the typical uncertainty of a few orders of magnitude to just within a factor of a few. This constitutes an important step forward in our characterisation of the physical properties of CWBs.
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| 10. |
- Del Peso-Santos, Teresa, et al.
(författare)
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A hyper-mutant of the unusual σ70-Pr promoter bypasses synergistic ppGpp/DksA co-stimulation
- 2011
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Ingår i: Nucleic Acids Research. - London : Information Retrieval Ltd. - 0305-1048 .- 1362-4962. ; 39:14, s. 5853-5865
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Tidskriftsartikel (refereegranskat)abstract
- The activities of promoters can be temporally and conditionally regulated by mechanisms other than classical DNA-binding repressors and activators. One example is the inherently weak σ70-dependent Pr promoter that ultimately controls catabolism of phenolic compounds. The activity of Pr is up-regulated through the joint action of ppGpp and DksA that enhance the performance of RNA polymerase at this promoter. Here, we report a mutagenesis analysis that revealed substantial differences between Pr and other ppGpp/DksA co-stimulated promoters. In vitro transcription and RNA polymerase binding assays show that it is the T at the −11 position of the extremely suboptimal −10 element of Pr that underlies both poor binding of σ70-RNAP and a slow rate of open complex formation—the process that is accelerated by ppGpp and DksA. Our findings support the idea that collaborative action of ppGpp and DksA lowers the rate-limiting transition energy required for conversion between intermediates on the road to open complex formation.
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| 11. |
- del Peso Santos, Teresa, et al.
(författare)
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BipA exerts temperature-dependent translational control of biofilm-associated colony morphology in Vibrio cholerae
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd.. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Adaptation to shifting temperatures is crucial for the survival of the bacterial pathogen Vibrio cholerae. Here, we show that colony rugosity, a biofilm-associated phenotype, is regulated by temperature in V. cholerae strains that naturally lack the master biofilm transcriptional regulator HapR. Using transposon-insertion mutagenesis, we found the V. cholerae ortholog of BipA, a conserved ribosome-associated GTPase, is critical for this temperature-dependent phenomenon. Proteomic analyses revealed that loss of BipA alters the synthesis of >300 proteins in V. cholerae at 22˚C, increasing the production of biofilm-related proteins including the key transcriptional activators VpsR and VpsT, as well as proteins important for diverse cellular processes. At low temperatures, BipA protein levels increase and are required for optimal ribosome assembly in V. cholerae, suggesting that control of BipA abundance is a mechanism by which bacteria can remodel their proteomes. Our study reveals a remarkable new facet of V. cholerae’s complex biofilm regulatory network.
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| 12. |
- del Peso-Santos, Teresa, et al.
(författare)
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Coregulation by phenylacetyl-coenzyme A-responsive PaaX integrates control of the upper and lower pathways for catabolism of styrene by Pseudomonas sp. strain Y2.
- 2006
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Ingår i: J Bacteriol. - 0021-9193. ; 188:13, s. 4812-21
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Tidskriftsartikel (refereegranskat)abstract
- The P(styA) promoter of Pseudomonas sp. strain Y2 controls expression of the styABCD genes, which are required for the conversion of styrene to phenylacetate, which is further catabolized by the products of two paa gene clusters. Two PaaX repressor proteins (PaaX1 and PaaX2) regulate transcription of the paa gene clusters of this strain. In silico analysis of the P(styA) promoter region revealed a sequence located just within styA that is similar to the reported PaaX binding sites of Escherichia coli and the proposed PaaX binding sites of the paa genes of Pseudomonas species. Here we show that protein extracts from some Pseudomonas strains that have paaX genes, but not from a paaX mutant strain, can bind and retard the migration of a P(styA) specific probe. Purified maltose-binding protein (MBP)-PaaX1 fusion protein specifically binds the P(styA) promoter proximal PaaX site, and this binding is eliminated by the addition of phenylacetyl-coenzyme A. The sequence protected by MBP-PaaX1 binding was defined by DNase I footprinting. Moreover, MBP-PaaX1 represses transcription from the P(styA) promoter in a phenylacetyl-coenzyme A-dependent manner in vitro. Finally, the inactivation of both paaX gene copies of Pseudomonas sp. strain Y2 leads to a higher level of transcription from the P(styA) promoter, while heterologous expression of the PaaX1 in E. coli greatly decreases transcription from the P(styA) promoter. These findings reveal a control mechanism that integrates regulation of styrene catabolism by coordinating the expression of the styrene upper catabolic operon to that of the paa-encoded central pathway and support a role for PaaX as a major regulatory protein in the phenylacetyl-coenzyme A catabolon through its response to the levels of this central metabolite.
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| 13. |
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| 14. |
- Edling, Christofer, et al.
(författare)
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Neighborhood and Friendship Composition in Adolescence
- 2012
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Ingår i: SAGE Open. - : SAGE Publications. - 2158-2440.
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Tidskriftsartikel (refereegranskat)abstract
- The social surroundings in which an individual grows up and spends his or her everyday life have an effect on his or her life chances. Much of the research into this phenomenon focuses on so-called neighborhood effects and has put particular emphasis on the negative effects of growing up in a poor neighborhood. Originating from the sociological study of inner-city problems in the United States, the research has recently been embraced by Scandinavian social scientists, who have generally assessed the phenomenon with reference to social network effects and the lock-in effects of ethnic enclaves. We critique the theoretical assumptions that we find in recent Scandinavian research and argue that a straightforward interpretation of neighborhood effects in terms of network effects is problematic. Our argument is based on an empirical analysis of friendship circles of ninth graders in Stockholm (N = 240). We conclude that the friendship networks of ninth graders extend well beyond the neighborhood, thus casting serious doubt on the network effects assumption of previous research. We also conclude that there is nothing in the reality of these ninth graders that confirms the established concept of the ethnic enclave.
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| 15. |
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| 16. |
- Isaksson, Magnus, 1969-, et al.
(författare)
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A Comparative Analysis of Behavioral Models for RF Power Amplifiers
- 2006
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Ingår i: IEEE transactions on microwave theory and techniques. - 0018-9480 .- 1557-9670. ; 54:1, s. 348-359
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Tidskriftsartikel (refereegranskat)abstract
- A comparative study of nonlinear behavioral models with memory for radio-frequency power amplifier (PAs) is presented. The models are static polynomial, parallel Hammerstein (PH), Volterra, and radial basis-function neural network (RBFNN). Two PAs were investigated: one was designed for the third-generation (3G) mobile telecommunication systems and one was designed for the second-generation (2G). The RBFNN reduced the total model error slightly more than the PH, but the error out of band was significantly lower for the PH. The Volterra was found to give a lower model error than did a PH of the same nonlinear order and memory depth. The PH could give a lower model error than the best Volterra, since the former could be identified with a higher nonlinear order and memory depth. The qualitative conclusions are the same for the 2G and 3G PAs, but the model errors are smaller for the latter. For the 3G PA, a static polynomial gave a low model error as low as the best PH and lower than the RBFNN for the hardest cross validation. The models with memory, PH, and RBFNN, showed better cross-validation performance, in terms of lower model errors, than a static polynomial for the hardest cross validation of the 2G PA.
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| 17. |
- Norrgård, Johnny R, 1976-, et al.
(författare)
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Multiplicative loss of landlocked Atlantic salmon Salmo salar L. smolts during downstream migration through multiple dams
- 2013
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Ingår i: Rivers Research and Applications. - : John Wiley & Sons. - 1535-1459 .- 1535-1467. ; 29:10, s. 1306-1317
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Tidskriftsartikel (refereegranskat)abstract
- Relatively little is known about the downstream migration of landlocked stocks of Atlantic salmon Salmo salar L. smolts, as earlier migration studies have generally focused on upstream migration. However, in watersheds with many hydroelectric plants (HEPs), multiplicative loss of downstream-migrating salmon smolts can be high, contributing to population declines or extirpations. Here we report the results from a study of wild landlocked Atlantic salmon smolts in the River Klaralven. Salmon smolts, tagged with acoustic transmitters, were released at different locations and followed as they passed 37 receivers along a 180-km-long river segment, including eight dams as well as free-flowing control stretches. We found that 16% of the smolts successfully migrated along the entire river segment. Most losses occurred during HEP passages, with 76% of the smolts being lost during these passages, which contrasts with the 8% smolt loss along unregulated control stretches. Migration speed was 83% slower along regulated stretches than along unregulated stretches. The observed lower migration speed at regulated stretches was dependent on fish size, with large fish moving slower than small fish. Discharge affected migration speed but not losses. As previously shown for anadromous populations, our study of landlocked salmon demonstrates similar negative effects of multiple passages of HEPs by downstream-migrating smolts. On the basis of this and previous migration studies, we advocate using a holistic approach in the management and conservation of migratory fish in regulated rivers, which includes safe passage for both upstream- and downstream-migrating fish. Copyright (c) 2012 John Wiley & Sons, Ltd.
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| 18. |
- Ny, Tor, 1949-, et al.
(författare)
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The gene for t-PA
- 1988
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Ingår i: Tissue-type plasminogen activator (t-PA). - : CRC Press. - 0849346088 ; , s. 83-100
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Bokkapitel (refereegranskat)
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| 19. |
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