SwePub
Sök i SwePub databas

  Extended search

Träfflista för sökning "WFRF:(Borg David) "

Search: WFRF:(Borg David)

  • Result 1-50 of 101
Sort/group result
   
EnumerationReferenceCoverFind
1.
  • Hudson, Thomas J., et al. (author)
  • International network of cancer genome projects
  • 2010
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
  • Journal article (peer-reviewed)abstract
    • The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
  •  
2.
  • Ademuyiwa, Adesoji O., et al. (author)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Journal article (peer-reviewed)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
  •  
3.
  • Jones, Robert P., et al. (author)
  • Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
  • 2019
  • In: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
  • Journal article (peer-reviewed)abstract
    • Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
  •  
4.
  • Alexandrov, Ludmil B., et al. (author)
  • Signatures of mutational processes in human cancer
  • 2013
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
  • Journal article (peer-reviewed)abstract
    • All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
  •  
5.
  • Neoptolemos, John P., et al. (author)
  • Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4) : a multicentre, open-label, randomised, phase 3 trial
  • 2017
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 389:10073, s. 1011-1024
  • Journal article (peer-reviewed)abstract
    • Background: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer.Methods: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1: 1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m(2) gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m(2) oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434.Findings: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28.0 months (95% CI 23.5-31.5) compared with 25.5 months (22.7-27.9) in the gemcitabine group (hazard ratio 0.82 [95% CI 0.68-0.98], p=0.032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group.Interpretation: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma.
  •  
6.
  • Nik-Zainal, Serena, et al. (author)
  • Mutational Processes Molding the Genomes of 21 Breast Cancers
  • 2012
  • In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 149:5, s. 979-993
  • Journal article (peer-reviewed)abstract
    • All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis,'' was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.
  •  
7.
  • Nik-Zainal, Serena, et al. (author)
  • The Life History of 21 Breast Cancers
  • 2012
  • In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 149:5
  • Journal article (peer-reviewed)abstract
    • Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.
  •  
8.
  • Beaty, D.W, et al. (author)
  • The potential science and engineering value of samples delivered to Earth by Mars sample return : International MSR Objectives and Samples Team (iMOST)
  • 2019
  • In: Meteoritics and Planetary Science. - : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 54:S1, s. 3-152
  • Journal article (peer-reviewed)abstract
    • Executive Summary: Return of samples from the surface of Mars has been a goal of the international Mars science community for many years. Affirmation by NASA and ESA of the importance of Mars exploration led the agencies to establish the international MSR Objectives and Samples Team (iMOST). The purpose of the team is to re-evaluate and update the sample-related science and engineering objectives of a Mars Sample Return (MSR) campaign. The iMOST team has also undertaken to define the measurements and the types of samples that can best address the objectives. Seven objectives have been defined for MSR, traceable through two decades of previously published international priorities. The first two objectives are further divided into sub-objectives. Within the main part of the report, the importance to science and/or engineering of each objective is described, critical measurements that would address the objectives are specified, and the kinds of samples that would be most likely to carry key information are identified. These seven objectives provide a framework for demonstrating how the first set of returned Martian samples would impact future Martian science and exploration. They also have implications for how analogous investigations might be conducted for samples returned by future missions from other solar system bodies, especially those that may harbor biologically relevant or sensitive material, such as Ocean Worlds (Europa, Enceladus, Titan) and others. Summary of Objectives and Sub-Objectives for MSR Identified by iMOST: Objective 1 Interpret the primary geologic processes and history that formed the Martian geologic record, with an emphasis on the role of water. Intent To investigate the geologic environment(s) represented at the Mars 2020 landing site, provide definitive geologic context for collected samples, and detail any characteristics that might relate to past biologic processesThis objective is divided into five sub-objectives that would apply at different landing sites. 1.1 Characterize the essential stratigraphic, sedimentologic, and facies variations of a sequence of Martian sedimentary rocks. Intent To understand the preserved Martian sedimentary record. Samples A suite of sedimentary rocks that span the range of variation. Importance Basic inputs into the history of water, climate change, and the possibility of life 1.2 Understand an ancient Martian hydrothermal system through study of its mineralization products and morphological expression. Intent To evaluate at least one potentially life-bearing “habitable” environment Samples A suite of rocks formed and/or altered by hydrothermal fluids. Importance Identification of a potentially habitable geochemical environment with high preservation potential. 1.3 Understand the rocks and minerals representative of a deep subsurface groundwater environment. Intent To evaluate definitively the role of water in the subsurface. Samples Suites of rocks/veins representing water/rock interaction in the subsurface. Importance May constitute the longest-lived habitable environments and a key to the hydrologic cycle. 1.4 Understand water/rock/atmosphere interactions at the Martian surface and how they have changed with time. Intent To constrain time-variable factors necessary to preserve records of microbial life. Samples Regolith, paleosols, and evaporites. Importance Subaerial near-surface processes could support and preserve microbial life. 1.5 Determine the petrogenesis of Martian igneous rocks in time and space. Intent To provide definitive characterization of igneous rocks on Mars. Samples Diverse suites of ancient igneous rocks. Importance Thermochemical record of the planet and nature of the interior. Objective 2 Assess and interpret the potential biological history of Mars, including assaying returned samples for the evidence of life. Intent To investigate the nature and extent of Martian habitability, the conditions and processes that supported or challenged life, how different environments might have influenced the preservation of biosignatures and created nonbiological “mimics,” and to look for biosignatures of past or present life.This objective has three sub-objectives: 2.1 Assess and characterize carbon, including possible organic and pre-biotic chemistry. Samples All samples collected as part of Objective 1. Importance Any biologic molecular scaffolding on Mars would likely be carbon-based. 2.2 Assay for the presence of biosignatures of past life at sites that hosted habitable environments and could have preserved any biosignatures. Samples All samples collected as part of Objective 1. Importance Provides the means of discovering ancient life. 2.3 Assess the possibility that any life forms detected are alive, or were recently alive. Samples All samples collected as part of Objective 1. Importance Planetary protection, and arguably the most important scientific discovery possible. Objective 3 Quantitatively determine the evolutionary timeline of Mars. Intent To provide a radioisotope-based time scale for major events, including magmatic, tectonic, fluvial, and impact events, and the formation of major sedimentary deposits and geomorphological features. Samples Ancient igneous rocks that bound critical stratigraphic intervals or correlate with crater-dated surfaces. Importance Quantification of Martian geologic history. Objective 4 Constrain the inventory of Martian volatiles as a function of geologic time and determine the ways in which these volatiles have interacted with Mars as a geologic system. Intent To recognize and quantify the major roles that volatiles (in the atmosphere and in the hydrosphere) play in Martian geologic and possibly biologic evolution. Samples Current atmospheric gas, ancient atmospheric gas trapped in older rocks, and minerals that equilibrated with the ancient atmosphere. Importance Key to understanding climate and environmental evolution. Objective 5 Reconstruct the processes that have affected the origin and modification of the interior, including the crust, mantle, core and the evolution of the Martian dynamo. Intent To quantify processes that have shaped the planet's crust and underlying structure, including planetary differentiation, core segregation and state of the magnetic dynamo, and cratering. Samples Igneous, potentially magnetized rocks (both igneous and sedimentary) and impact-generated samples. Importance Elucidate fundamental processes for comparative planetology. Objective 6 Understand and quantify the potential Martian environmental hazards to future human exploration and the terrestrial biosphere. Intent To define and mitigate an array of health risks related to the Martian environment associated with the potential future human exploration of Mars. Samples Fine-grained dust and regolith samples. Importance Key input to planetary protection planning and astronaut health. Objective 7 Evaluate the type and distribution of in-situ resources to support potential future Mars exploration. Intent To quantify the potential for obtaining Martian resources, including use of Martian materials as a source of water for human consumption, fuel production, building fabrication, and agriculture. Samples Regolith. Importance Production of simulants that will facilitate long-term human presence on Mars. Summary of iMOST Findings: Several specific findings were identified during the iMOST study. While they are not explicit recommendations, we suggest that they should serve as guidelines for future decision making regarding planning of potential future MSR missions. The samples to be collected by the Mars 2020 (M-2020) rover will be of sufficient size and quality to address and solve a wide variety of scientific questions. Samples, by definition, are a statistical representation of a larger entity. Our ability to interpret the source geologic units and processes by studying sample sub sets is highly dependent on the quality of the sample context. In the case of the M-2020 samples, the context is expected to be excellent, and at multiple scales. (A) Regional and planetary context will be established by the on-going work of the multi-agency fleet of Mars orbiters. (B) Local context will be established at field area- to outcrop- to hand sample- to hand lens scale using the instruments carried by M-2020. A significant fraction of the value of the MSR sample collection would come from its organization into sample suites, which are small groupings of samples designed to represent key aspects of geologic or geochemical variation. If the Mars 2020 rover acquires a scientifically well-chosen set of samples, with sufficient geological diversity, and if those samples were returned to Earth, then major progress can be expected on all seven of the objectives proposed in this study, regardless of the final choice of landing site. The specifics of which parts of Objective 1 could be achieved would be different at each of the final three candidate landing sites, but some combination of critically important progress could be made at any of them. An aspect of the search for evidence of life is that we do not know in advance how evidence for Martian life would be preserved in the geologic record. In order for the returned samples to be most useful for both understanding geologic processes (Objective 1) and the search for life (Objective 2), the sample collection should contain BOTH typical and unusual samples from the rock units explored. This consideration should be incorporated into sample selection and the design of the suites. The retrieval missions of a MSR campaign should (1) minimize stray magnetic fields to which the samples would be exposed and carry a magnetic witness plate to record exposure, (2) collect and return atmospheric gas sample(s), and (3) collect additional dust and/or regolith sample mass if possible.
  •  
9.
  • Goldstein, Alisa M., et al. (author)
  • High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL
  • 2006
  • In: Cancer Research. - 1538-7445 .- 0008-5472. ; 66:20, s. 9818-9828
  • Journal article (peer-reviewed)abstract
    • GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM). This study included 466 families (2,137 patients) with at least three melanoma patients from 17 GenoMEL centers. Overall, 41% (n = 190) of families had mutations; most involved p16 (n = 178). Mutations in CDK4 (n = 5) and ARF (n = 7) occurred at similar frequencies (2-3%). There were striking differences in mutations across geographic locales. The proportion of families with the most frequent founder mutation(s) of each locale differed significantly across the seven regions (P = 0.0009). Single founder CDKN2A mutations were predominant in Sweden (p.R112_L113insR, 92% of family's mutations) and the Netherlands (c.225_243del19, 90% of family's mutations). France, Spain, and Italy had the same most frequent mutation (p.G101W). Similarly, Australia and United Kingdom had the same most common mutations (p.M53I, cdVS2-105A > G, p.R24P, and p.L32P). As reported previously, there was a strong association between PC and CDKN2A mutations (P < 0.0001). This relationship differed by mutation. In contrast, there was little evidence for an association between CDKN2A mutations and NST (P = 0.52) or UM (P = 0.25). There was a marginally significant association between NST and ARF (P = 0.05). However, this particular evaluation had low power and requires confirmation. This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available.
  •  
10.
  • Micke, Patrick, et al. (author)
  • The prognostic impact of the tumour stroma fraction : A machine learning-based analysis in 16 human solid tumour types
  • 2021
  • In: EBioMedicine. - : Elsevier. - 2352-3964. ; 65
  • Journal article (peer-reviewed)abstract
    • Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed.Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns.Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR (95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59 (1.49-8.62)) associations of the tumour stroma fraction with survival.Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance.
  •  
11.
  • Nik-Zainal, Serena, et al. (author)
  • Landscape of somatic mutations in 560 breast cancer whole-genome sequences
  • 2016
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
  • Journal article (peer-reviewed)abstract
    • We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
  •  
12.
  • Peloso, Paul M, et al. (author)
  • Critical evaluation of the existing guidelines on mild traumatic brain injury.
  • 2004
  • In: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 43, s. 106-
  • Journal article (peer-reviewed)abstract
    • The purpose of guidelines is to reduce practice variability, but they need to be evidence-based. We examine current mild traumatic brain injury guidelines, critique their basis in evidence and examine their variability in recommendations. A systematic search of the literature found 38,806 abstracts, with 41 guidelines. There were 18 sports-related guidelines, 13 related to admission policies, 12 related to imaging and 5 related to neuropsychological assessment. Some guidelines addressed several areas. Only 5 guidelines reported a methodology for the assembly of evidence used to develop the guideline. After appraising the guidelines against a validated index, we found that 3 of the 41 guidelines could be categorized as evidence-based. Two of these focused on paediatric patients and 1 on adult patients. Limited methodological quality in the current guidelines results in conflicting recommendations amongst them.
  •  
13.
  • Reyna, Matthew A, et al. (author)
  • Pathway and network analysis of more than 2500 whole cancer genomes
  • 2020
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
  • Journal article (peer-reviewed)abstract
    • The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
  •  
14.
  • Shlien, Adam, et al. (author)
  • Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer
  • 2016
  • In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 16:7, s. 2032-2046
  • Journal article (peer-reviewed)abstract
    • Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER)-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation.
  •  
15.
  • Sparv, David, et al. (author)
  • The Analgesic Effect of Oxygen in Suspected Acute Myocardial Infarction : A Substudy of the DETO2X-AMI Trial
  • 2018
  • In: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798 .- 1876-7605. ; 39, s. 546-546
  • Journal article (peer-reviewed)abstract
    • Objectives: In this substudy of the DETO2X-AMI (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction) trial, the authors aimed to assess the analgesic effect of moderate-flow oxygen supplementation in patients with suspected acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI) and to study the effect of oxygen supplementation on the use of opiates and sedatives during PCI. Background: Routine oxygen in normoxemic patients with AMI does not provide clinical benefit. However, oxygen may relieve ischemic pain. Methods: Patients were randomly allocated to oxygen or ambient air according to the main study protocol. After PCI, peak level of pain during PCI was measured by the Visual Analogue Scale. The total amount of opiates and sedatives was reported. Results: A total of 622 patients were enrolled: 330 in the oxygen group and 292 in the ambient air group. There was no significant difference in peak level of pain (oxygen 4.0 [1.0 to 6.0] vs. air 3.0 [0.6 to 6.0]; p = 0.37), use of opiates (mg) (oxygen 0.0 [0.0 to 3.0] vs. air 0.0 [0.0 to 3.0]; p = 0.31), or use of sedatives between the groups (median [interquartile range]) (oxygen 2.5 [0.0 to 2.5] vs. air 2.5 [0.0 to 2.5]; p = 0.74). Conclusions: In the present study, the authors did not find any analgesic effect of routine oxygen as compared with ambient air, and no differences in the use of sedatives and opiates during PCI. Our results indicate that moderate-flow oxygen supplementation does not relieve pain in normoxemic patients with suspected AMI undergoing treatment with PCI and should thus not be used for this purpose.
  •  
16.
  • Alexandrov, Ludmil B, et al. (author)
  • The repertoire of mutational signatures in human cancer
  • 2020
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 94-101
  • Journal article (peer-reviewed)abstract
    • Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3-15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.
  •  
17.
  • Andersson, Anna, et al. (author)
  • Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations
  • 2005
  • In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 19:6, s. 1042-1050
  • Journal article (peer-reviewed)abstract
    • Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14) [IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11) [PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.
  •  
18.
  • Ansari, Daniel, et al. (author)
  • Pancreatic cancer : Yesterday, today and tomorrow
  • 2016
  • In: Future Oncology. - : Future Medicine Ltd. - 1479-6694 .- 1744-8301. ; 12:16, s. 1929-1946
  • Journal article (peer-reviewed)abstract
    • Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology.
  •  
19.
  • Antoniou, Antonis C., et al. (author)
  • Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers
  • 2011
  • In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:16, s. 3304-3321
  • Journal article (peer-reviewed)abstract
    • Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
  •  
20.
  • Aoude, Lauren G, et al. (author)
  • Nonsense Mutations in the Shelterin Complex Genes ACD and TERF2IP in Familial Melanoma.
  • 2015
  • In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:2, s. 408-408
  • Journal article (peer-reviewed)abstract
    • The shelterin complex protects chromosomal ends by regulating how the telomerase complex interacts with telomeres. Following the recent finding in familial melanoma of inactivating germline mutations in POT1, encoding a member of the shelterin complex, we searched for mutations in the other five components of the shelterin complex in melanoma families.
  •  
21.
  • Bailey, Matthew H., et al. (author)
  • Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
  • 2020
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
  •  
22.
  • Balciuniene, Jorune, et al. (author)
  • Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with cognitive and behavioral abnormalities
  • 2007
  • In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 80:5, s. 938-947
  • Journal article (peer-reviewed)abstract
    • Low-copy repeats (LCRs) are genomic features that affect chromosome stability and can produce disease-associated rearrangements. We describe members of three families with deletions in 10q22.3-q23.31, a region harboring a complex set of LCRs, and demonstrate that rearrangements in this region are associated with behavioral and neurodevelopmental abnormalities, including cognitive impairment, autism, hyperactivity, and possibly psychiatric disease. Fine mapping of the deletions in members of all three families by use of a custom 10q oligonucleotide array-based comparative genomic hybridization (NimbleGen) and polymerase chain reaction - based methods demonstrated a different deletion in each family. In one proband, the deletion breakpoints are associated with DNA fragments containing noncontiguous sequences of chromosome 10, whereas, in the other two families, the breakpoints are within paralogous LCRs, removing similar to 7.2 Mb and 32 genes. Our data provide evidence that the 10q22-q23 genomic region harbors one or more genes important for cognitive and behavioral development and that recurrent deletions affecting this interval define a novel genomic disorder.
  •  
23.
  •  
24.
  • Birgegard, Andreas, et al. (author)
  • Longitudinal experiences and impact of the COVID-19 pandemic among people with past or current eating disorders in Sweden
  • 2021
  • In: Eating Disorders. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 1064-0266 .- 1532-530X. ; 30:6, s. 602-617
  • Journal article (peer-reviewed)abstract
    • The study aimed to document the impact of the COVID-19 pandemic on the health and well-being of individuals with past and current eating disorders (ED) in Sweden. We re-contacted participants with a known lifetime history of ED from two previous Swedish studies. Participants completed an online survey about health and functioning at baseline early in the pandemic (Wave 1 ca May/June 2020; N= 982) and six months later (Wave 2 Dec/Jan 2020/21; N= 646). Three important patterns emerged: 1) higher current ED symptoms were associated with greater anxiety, worry, and pandemic-related ED symptom increase; 2) patterns were fairly stable across time, although a concerning percentage (23%) who were symptom-free at Wave 1 reported the re-emergence of symptoms at Wave 2; and 3) only a minority of participants (<50%) with a current ED were in treatment, and of those in treatment, many reported fewer treatment sessions and decreased quality of care. The COVID-19 pandemic appears to pose serious health challenges for individuals with an ED, whether currently symptomatic or in remission. We encourage health service providers and patient advocates to be alert to the needs of individuals with ED and to take active measures to ensure access to appropriate evidence-based care both during and following the pandemic.
  •  
25.
  • Borg, Alexander, et al. (author)
  • Obesity is associated with pain and impaired mobility despite therapy in systemic lupus erythematosus
  • 2023
  • In: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 10
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To investigate whether abnormal BMI is associated with health-related quality of life (HRQoL) impairments, defined as patient-reported problems within the different dimensions of the three-level EQ-5D (EQ-5D-3L), before and after treatment for active systemic lupus erythematosus (SLE).PATIENTS AND METHODS: We conducted a post-hoc analysis of data from two phase III clinical trials of belimumab in SLE, i.e., BLISS-52 (n = 865) and BLISS-76 (n = 819). Underweight was defined as BMI <18.5 kg/m2, normal weight as BMI ≥18.5 but <25 kg/m2, pre-obesity as BMI ≥25 but <30 kg/m2, and obesity as BMI ≥30 kg/m2. We investigated associations between BMI groups and problems (level 2 or 3) within each one of the five EQ-5D dimensions before treatment initiation and at week 52, using logistic regression analysis adjusting for age, ethnicity, disease activity, and glucocorticoid dose, and for the post-treatment analysis also for belimumab treatment and baseline EQ-5D-3L responses.RESULTS: Of 1,684 patients included, 73 (4%) were classified as underweight, 850 (50%) as normal weight, 438 (26%) as pre-obese, and 323 (19%) as obese. At baseline, obesity was associated with mild to severe problems in all EQ-5D dimensions (p < 0.05 for all), yielding the strongest association with problems in mobility (adjusted odds ratio, aOR: 2.1; 95% confidence interval, CI: 1.6-2.8; p < 0.001). Pre-obesity was also associated with problems in mobility (aOR: 1.4; 95% CI: 1.1-1.8; p = 0.005). Post-intervention, obesity was associated with problems in mobility and pain/discomfort, and pre-obesity with problems in mobility and self-care (p < 0.05 for all).CONCLUSION: Our study adds to the evidence that high BMI negatively affects SLE patients' HRQoL, with obesity being associated with pain and impaired mobility despite therapy.
  •  
26.
  • BORG, DAVID, et al. (author)
  • Expression of IFITM1 as a prognostic biomarker in resected gastric and esophageal adenocarcinoma
  • 2016
  • In: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 4
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: There is an increasing amount of reports on IFITM1 (interferon-inducible transmembrane protein 1) in various malignancies. The aim of this study was to examine the expression of IFITM1 and its prognostic significance in gastroesophageal adenocarcinoma.METHODS: Tissue samples were obtained from a consecutive cohort of 174 patients surgically treated between 2006 and 2010 for gastroesophageal (gastric, gastroesophageal junction and esophageal) adenocarcinoma, not subjected to neoadjuvant therapy. Expression of IFITM1 was examined using immunohistochemistry on tissue microarrays of primary tumors and paired samples of adjacent normal epithelium, intestinal metaplasia and lymph node metastases.RESULTS: Expression of IFITM1 was significantly elevated in primary tumors and lymph node metastases compared to adjacent normal epithelium and intestinal metaplasia, regardless of tumor location. Overexpression of IFITM1 was associated with M0-disease (no distant metastases). In gastric cancer IFITM1 expression was significantly associated with improved TTR (time to recurrence) in Kaplan-Meier analysis and Cox regression, both in the unadjusted analysis (HR 0.33, 95 % CI 0.12-0.88) and in the adjusted analysis (HR 0.32, 95 % CI 0.12-0.87) but there was no significant impact on OS (overall survival). In esophageal adenocarcinoma expression of IFITM1 had no impact on TTR or OS in Kaplan-Meier-analyses, but in the adjusted Cox regression IFITM1 expression had a negative impact on both TTR (HR 3.05, 95 % CI 1.09-8.53) and OS (HR 2.71, 95 % CI 1.11-6.67).CONCLUSIONS: IFITM1 was overexpressed in gastroesophageal adenocarcinoma and associated with M0-disease. In gastric cancer IFITM1 expression had a positive impact on TTR but in esophageal cancer it seemed to have an adverse impact on survival. The reason for the diverging prognostic impact of IFITM1 in esophageal and gastric cancer is unclear and warrants further studies.
  •  
27.
  • Borg, David, et al. (author)
  • Expression of podocalyxin-like protein is an independent prognostic biomarker in resected esophageal and gastric adenocarcinoma
  • 2016
  • In: BMC Clinical Pathology. - : Springer Science and Business Media LLC. - 1472-6890. ; 16:1
  • Journal article (peer-reviewed)abstract
    • Background: Podocalyxin-like protein (PODXL) is a cell surface transmembrane glycoprotein, the expression of which has been associated with poor prognosis in a range of malignancies. The aim of this study was to investigate the impact of PODXL expression on survival in esophageal and gastric adenocarcinoma. Methods: The study cohort consists of a consecutive series of 174 patients with esophageal (including the gastroesophageal junction) or gastric adenocarcinoma, surgically treated between 2006 and 2010 and not subjected to neoadjuvant treatment. Immunohistochemical expression of PODXL was assessed in tissue microarrays with cores from primary tumors, lymph node metastases, intestinal metaplasia and adjacent normal epithelium. Survival analyses were performed on patients with no distant metastases and no macroscopic residual tumor. Results: In the majority of cases, expression of PODXL was significantly higher in cancer cells compared to normal epithelial cells and was significantly associated with lymph node metastases and high grade tumors. In esophageal adenocarcinoma, Kaplan-Meier analyses revealed that patients with PODXL negative tumors had a superior time to recurrence (TTR) and overall survival (OS) compared to patients with PODXL positive tumors. In gastric adenocarcinoma, patients with PODXL negative tumors had a superior TTR and a trend towards an improved OS. In esophageal and gastric adenocarcinoma combined, the prognostic significance of PODXL expression on TTR was confirmed in unadjusted Cox regression analysis (HR = 5.36, 95 % CI 1.68-17.06, p = 0.005) and remained significant in the adjusted model (HR = 3.39, 95 % CI 1.01-11.35, p = 0.048). Moreover, the impact of PODXL expression on OS was also confirmed in unadjusted analysis (HR = 2.52, 95 % CI 1.31-4.85, p = 0.006) and remained significant in the adjusted model (HR = 2.03, 95 % CI 1.04-3.98, p = 0.039). Conclusions: In esophageal and gastric adenocarcinoma, PODXL expression is an independent prognostic biomarker for reduced time to recurrence and poor overall survival. This is the first report on the prognostic role of PODXL in esophageal adenocarcinoma and validates recent findings in gastric cancer.
  •  
28.
  • Borg, David N, et al. (author)
  • Bicycling and tricycling road race performance in international para-cycling events between 2011 and 2019.
  • 2022
  • In: American Journal of Physical Medicine & Rehabilitation. - : Lippincott Williams & Wilkins. - 0894-9115 .- 1537-7385. ; 101:4, s. 384-388
  • Journal article (peer-reviewed)abstract
    • ABSTRACT: This study described bicycling (C-classes) and tricycling (T-classes) performance in International Cycling Federation road race events between 2011 and 2019. A total of 3,243 race results from 33 events were analyzed. Race velocity was calculated for each result. Bicycling and tricycling data were separately modelled using a linear mixed-effects model. Bicycling velocity was statistically different between all adjacent men's classes (Cohen's d = 0.14 to 0.73), and between the women's C1 and C2 (d = 1.15), and C3 and C4 (d = 0.48) classes. The absence of statistical differences between some women's bicycling classes may be due to a limited number of observations in these classifications. As expected, velocity was statistically different between men's (d = 1.64) and women's (d = 1.38) T1 and T2 classes. Road race performance was hierarchical within the disciplines of bicycling and tricycling, although not all adjacent women's bicycling classes were statistically different. The existence of a performance hierarchy does not necessarily validate the classification system. The integration of information regarding athlete impairment type and severity, with performance data, would provide greater insight into the validity of the classification system, and should be prioritized as an area of future research.
  •  
29.
  • Borg, David, et al. (author)
  • Palliative short-course hypofractionated radiotherapy followed by chemotherapy in esophageal adenocarcinoma : the phase II PALAESTRA trial
  • 2020
  • In: Acta Oncologica. - 0284-186X. ; 59:2, s. 212-218
  • Journal article (peer-reviewed)abstract
    • Background: The majority of patients with incurable esophageal adenocarcinoma suffer from dysphagia. We assessed a novel treatment strategy with initial short-course radiotherapy followed by chemotherapy with the primary aim to achieve long-term relief of dysphagia. Methods: This phase II trial included treatment-naîve patients with dysphagia due to esophageal adenocarcinoma not eligible for curative treatment. External beam radiotherapy with 20 Gy in five fractions to the primary tumor was followed by four cycles of chemotherapy (FOLFOX regimen). Dysphagia was assessed using a five-grade scale. Results: From October 2014 to May 2018 a total of 29 patients were enrolled. The rate of dysphagia improvement was 79%, median duration of improvement 6.7 months (12.2 months for responders) and median overall survival 9.9 months. In the pre-specified per protocol analysis (23 patients) the rate of dysphagia improvement was 91%, median duration of improvement 12.2 months (14.0 months for responders) and median overall survival 16.0 months. The most common grade 3–4 adverse events were neutropenia (29%), infection (25%), anorexia (11%), esophagitis (11%) and fatigue (11%). Conclusion: Initial palliative short-course radiotherapy followed by chemotherapy is a promising treatment strategy that can provide long-lasting relief of dysphagia in patients with esophageal adenocarcinoma.
  •  
30.
  • Borg, David, et al. (author)
  • Podocalyxin-like protein as a predictive biomarker for benefit of neoadjuvant chemotherapy in resectable gastric and esophageal adenocarcinoma
  • 2018
  • In: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 16:1
  • Journal article (peer-reviewed)abstract
    • Background: We have previously shown that podocalyxin-like protein (PODXL) is a prognostic biomarker for poor survival in gastric and esophageal adenocarcinoma treated with surgery up-front. The aim of the present study was to assess PODXL expression in tumors from patients treated with neoadjuvant ± adjuvant (i.e. preoperative with or without postoperative) chemotherapy, with regard to histopathologic response, time to recurrence (TTR) and overall survival (OS). Methods: The neoadjuvant cohort encompasses 148 consecutive patients who received neoadjuvant ± adjuvant chemotherapy for resectable gastric or esophageal adenocarcinoma between 2008 and 2014. Immunohistochemical expression of PODXL was assessed in pre-neoadjuvant biopsies, resected primary tumors and lymph node metastases. Histopathologic response was evaluated using the Chirieac grading. TTR and OS were estimated using Kaplan-Meier and Cox regression analyses. To investigate a potential predictive role for PODXL, the neoadjuvant cohort was pooled with the previously reported surgery up-front cohort. Results: The majority (> 95%) of the patients were treated with fluoropyrimidine- and oxaliplatin-based chemotherapy. Patients with high PODXL expression in their pre-neoadjuvant biopsies had a superior histopathologic response (notably 36% with no residual cancer cells) compared to those with negative or low PODXL expression, and were all recurrence-free at last follow-up. In the pooled cohort, no benefit of chemotherapy could be shown for PODXL negative cases, whereas PODXL positive (low or high) cases had a prolonged TTR and OS when treated with neoadjuvant ± adjuvant chemotherapy compared to surgery alone. The potential predictive role of PODXL was further strengthened for TTR in Cox regression analyses, especially for patients treated with neoadjuvant fluoropyrimidine and oxaliplatin for a minimum of 8 weeks, with a significant interaction term in both unadjusted (p = 0.006) and adjusted (p = 0.024) analyses. The interaction term was not statistically significant for overall survival. Conclusions: Patients with resectable gastric or esophageal adenocarcinoma with high PODXL expression in their diagnostic biopsies have an excellent prognosis when treated with neoadjuvant ± adjuvant fluoropyrimidine- and oxaliplatin-based chemotherapy. If the suggested predictive role of PODXL for benefit of chemotherapy can be confirmed, patients with PODXL negative tumors could be spared chemotherapy and treated with surgery alone.
  •  
31.
  • Borg, David (author)
  • Towards improved oncological treatment of esophageal and gastric cancer. Clinical and translational studies.
  • 2019
  • Doctoral thesis (other academic/artistic)abstract
    • BackgroundThe overall aim of this thesis was to improve the oncological treatment strategies in esophageal and gastric adenocarcinoma (EGAC). Podocalyxin-like protein 1 (PODXL) has been associated with poor prognosis in other cancers and we wanted to investigate its potential role as a prognostic and predictive biomarker in resectable EGAC. Another aim was to assess how dose reductions and treatment delays of neoadjuvant chemotherapy affect outcome. Lastly we aimed to explore a novel palliative treatment strategy in esophageal adenocarcinoma with the primary objective to achieve durable improvement of dysphagia. MethodsExpression of PODXL was assessed using immunohistochemistry on material from two patient cohorts with EGAC: one with 174 patients treated with surgery up-front and the other with 148 patients treated with neoadjuvant chemotherapy ± adjuvant chemotherapy. For 63 patients in the neoadjuvant cohort, treated with EOX (epirubicin, oxaliplatin and capecitabine) followed by resection, we calculated the ratio of actual to planned cumulative dose and the ratio of planned to actual total duration and then associations of these measures with histopathologic response were assessed.In the phase II PALAESTRA trial the treatment consisted of external beam radiotherapy with 20 Gy in five fractions followed by four cycles of chemotherapy. ResultsIn paper I we show that PODXL expression is an independent prognostic biomarker in EGAC and the results in paper II indicate that PODXL expression is predictive for benefit of neoadjuvant ± adjuvant chemotherapy. In paper III it is suggested that treatment delays of neoadjuvant chemotherapy should be avoided in order to achieve a major histopathologic response. In the PALAESTRA study (paper IV) with 29 patients enrolled, 79% experienced improvement of dysphagia and for these the median duration of improvement was 12 months.ConclusionsPromising steps have been taken towards improved treatment strategies but confirmation in additional studies is warranted.
  •  
32.
  • Borg, Mikael, et al. (author)
  • Experimental and theoretical surface core-level shifts of aluminum (100) and (111)
  • 2004
  • In: Physical Review B. - 1550-235X. ; 69
  • Journal article (peer-reviewed)abstract
    • The surface core-level shifts of Al(111) and Al(100) have been measured using high-resolution core-level photoemission spectroscopy and calculated using density functional theory (DFT). For Al(100), the 2p core-level shift of the first (second) layer was determined to be –75 meV (+20 meV) from experiment and –71 meV (+20 meV) from the DFT calculations. For Al(111), the corresponding values are –27 meV (0 meV) from experiment and –14 meV (–) from the DFT calculations. Core-level splittings caused by the low-symmetry crystal fields at the (111) and (100) surfaces have also been studied. These splittings turn out to be much smaller than previously reported provided proper care is taken of the influence of the core hole screening and of core–valence exchange beyond the DFT level. Finally, the experimental Al 2p line shape was found to contain structure caused by a sharp no-phonon line and a broad and weak phonon replica.
  •  
33.
  • Callele, David, et al. (author)
  • Confounding Factors When Conducting Industrial Replications in Requirements Engineering
  • 2013
  • In: Proceedings of the 1st International Workshop on Conducting Empirical Studies in Industry. ; , s. 55-58
  • Conference paper (peer-reviewed)abstract
    • Despite the widely recognized importance of replications in software engineering, industrial replications in software engineering are still rarely reported. Although the literature provides some evidence about the issues and challenges related to conducting experiments and replications the practitioner's view of the issues and challenges has not been fully explored. This paper reports an industrial practitioner's review of a replicated experiment on linguistic tool support for consolidation of requirements from multiple sources. The review identified potential confounding factors from a perspective that differed significantly from that of the designers of the experiment. The results suggest that industrial practice may focus upon specific process aspects that are not necessarily reflected in academic practice.
  •  
34.
  • Cancelliere, Carol, et al. (author)
  • Protocol for a systematic review of prognosis after mild traumatic brain injury : an update of the WHO Collaborating Centre Task Force findings
  • 2012
  • In: Systematic Reviews. - : Springer Science and Business Media LLC. - 2046-4053. ; :1, s. 17-
  • Journal article (peer-reviewed)abstract
    • Background: Mild traumatic brain injury (MTBI) is a major public-health concern and represents 70-90% of all treated traumatic brain injuries. The last best-evidence synthesis, conducted by the WHO Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation in 2002, found few quality studies on prognosis. The objective of this review is to update these findings. Specifically, we aim to describe the course, identify modifiable prognostic factors, determine long-term sequelae, and identify effects of interventions for MTBI. Finally, we will identify gaps in the literature, and make recommendations for future research.Methods: The databases MEDLINE, PsychINFO, Embase, CINAHL and SPORTDiscus were systematically searched (2001 to date). The search terms included 'traumatic brain injury', 'craniocerebral trauma', 'prognosis', and 'recovery of function'. Reference lists of eligible papers were also searched. Studies were screened according to pre-defined inclusion and exclusion criteria. Inclusion criteria included original, published peer-reviewed research reports in English, French, Swedish, Norwegian, Danish and Spanish, and human participants of all ages with an accepted definition of MTBI. Exclusion criteria included publication types other than systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case-control studies; as well as cadaveric, biomechanical, and laboratory studies. All eligible papers were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers performed independent, in-depth reviews of each eligible study, and a third reviewer was consulted for disagreements. Data from accepted papers were extracted into evidence tables, and the evidence was synthesized according to the modified SIGN criteria.Conclusion: The results of this study form the basis for a better understanding of recovery after MTBI, and will allow development of prediction tools and recommendation of interventions, as well as informing health policy and setting a future research agenda.
  •  
35.
  • Cancelliere, Carol, et al. (author)
  • Systematic review of prognosis and return to play after sport concussion : results of the international collaboration on mild traumatic brain injury prognosis
  • 2014
  • In: Archives of Physical Medicine and Rehabilitation. - : Elsevier. - 0003-9993 .- 1532-821X. ; 95:3, Suppl, s. S210-S229
  • Research review (peer-reviewed)abstract
    • ObjectiveTo synthesize the best available evidence on prognosis after sport concussion.Data SourcesMEDLINE and other databases were searched (2001–2012) with terms including “craniocerebral trauma” and “sports.” Reference lists of eligible articles were also searched.Study SelectionRandomized controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 concussion cases.Data ExtractionEligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed and extracted data from accepted studies into evidence tables.Data SynthesisEvidence was synthesized qualitatively according to modified SIGN criteria, and studies were categorized as exploratory or confirmatory based on the strength of their design and evidence. After 77,914 records were screened, 52 articles were eligible for this review, and 24 articles (representing 19 studies) with a low risk of bias were accepted. Our findings are based on exploratory studies of predominantly male football players at the high school, collegiate, and professional levels. Most athletes recover within days to a few weeks, and American and Australian professional football players return to play quickly after mild traumatic brain injury. Delayed recovery appears more likely in high school athletes, in those with a history of previous concussion, and in those with a higher number and duration of postconcussion symptoms.ConclusionsThe evidence concerning sports concussion course and prognosis is very preliminary, and there is no evidence on the effect of return-to-play guidelines on prognosis. Our findings have implications for further research. Well-designed, confirmatory studies are urgently needed to understand the consequences of sport concussion, including recurrent concussion, across different athletic populations and sports.
  •  
36.
  • Cancelliere, Carol, et al. (author)
  • Systematic review of return to work after mild traumatic brain injury : results of the international collaboration on mild traumatic brain injury prognosis
  • 2014
  • In: Archives of Physical Medicine and Rehabilitation. - : Elsevier. - 0003-9993 .- 1532-821X. ; 95:3, Suppl, s. S201-S209
  • Research review (peer-reviewed)abstract
    • ObjectiveTo synthesize the best available evidence on return to work (RTW) after mild traumatic brain injury (MTBI).Data SourcesMEDLINE and other databases were searched (2001–2012) with terms including “craniocerebral trauma” and “employment.” Reference lists of eligible articles were also searched.Study SelectionControlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to assess RTW or employment outcomes in at least 30 MTBI cases.Data ExtractionEligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network criteria. Two reviewers independently reviewed and extracted data from accepted studies into evidence tables.Data SynthesisEvidence was synthesized qualitatively according to modified Scottish Intercollegiate Guidelines Network criteria and prioritized according to design as exploratory or confirmatory. After 77,914 records were screened, 299 articles were found eligible and reviewed; 101 (34%) of these with a low risk of bias were accepted as scientifically admissible, and 4 of these had RTW or employment outcomes. This evidence is preliminary and suggests that most workers RTW within 3 to 6 months after MTBI; MTBI is not a significant risk factor for long-term work disability; and predictors of delayed RTW include a lower level of education (<11y of formal education), nausea or vomiting on hospital admission, extracranial injuries, severe head/bodily pain early after injury, and limited job independence and decision-making latitude.ConclusionsOur findings are based on preliminary evidence with varied patient characteristics and MTBI definitions, thus limiting firm conclusions. More well-designed studies are required to understand RTW and sustained employment after MTBI in the longer term (≥2y post-MTBI).
  •  
37.
  • Carroll, L. J., et al. (author)
  • Prognosis for mild traumatic brain injury : Results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury
  • 2004
  • In: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 43, s. 61-
  • Research review (peer-reviewed)abstract
    • We searched the literature on the epidemiology, diagnosis, prognosis, treatment and costs of mild traumatic brain injury. Of 428 studies related to prognosis after mild traumatic brain injury, 120 (28%) were accepted after critical review. These comprise our best-evidence synthesis on prognosis after mild traumatic brain injury. There was consistent and methodologically sound evidence that children's prognosis after mild traumatic brain injury is good, with quick resolution of symptoms and little evidence of residual cognitive, behavioural or academic deficits. For adults, cognitive deficits and symptoms are common in the acute stage, and the majority of studies report recovery for most within 3-12 months. Where symptoms persist, compensation/litigation is a factor, but there is little consistent evidence for other predictors. The literature on this area is of varying quality and causal inferences are often mistakenly drawn from cross-sectional studies.
  •  
38.
  • Couch, Fergus J., et al. (author)
  • AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A consortium of investigators of modifiers of BRCA1/2 study
  • 2007
  • In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:7, s. 1416-1421
  • Journal article (peer-reviewed)abstract
    • The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 311 allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.
  •  
39.
  • Delker, Collin J., et al. (author)
  • 1/f Noise Sources in Dual-Gated Indium Arsenide Nanowire Transistors
  • 2012
  • In: IEEE Transactions on Electron Devices. - 0018-9383. ; 59:7, s. 1980-1987
  • Journal article (peer-reviewed)abstract
    • 1/f noise is studied in dual-gated InAs nanowire transistors consisting of an omega top gate with high-k atomic layer deposited dielectric and silicon dioxide to substrate back gate. Noise spectra at varying gate bias combinations are compared from devices with differing top-gate lengths to separate the noise contributions of the top-gated channel from the ungated access portion, including the metal-nanowire contacts. For a given device geometry, it is possible to bias the device into four different regimes where the resistance and the noise amplitude can each be independently dominated by either the channel or the access/contact regions. When the device is fully in the on state, the access/contact regions dominate both resistance and noise. When the device is operating near or below threshold, the channel dominates resistance and noise. For the lowest amount of overall 1/f noise, most of the nanowire should be covered by the top gate, minimizing the access region length.
  •  
40.
  • Drake, Thomas M., et al. (author)
  • Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction
  • 2019
  • In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 45:12, s. 2319-2324
  • Journal article (peer-reviewed)abstract
    • © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology Introduction: Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods: A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results: 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions: Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups.
  •  
41.
  • Emamikia, Sharzad, et al. (author)
  • Impact of remission and low disease activity on health-related quality of life in patients with systemic lupus erythematosus
  • 2022
  • In: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 61:12, s. 4752-4762
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To investigate the impact of remission and lupus low disease activity state (LLDAS) on health-related quality of life (HRQoL) in systemic lupus erythematosus.METHODS: SF-36, EQ-5D-3L and FACIT-Fatigue data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials were used. Duration in remission/LLDAS required to reach a HRQoL benefit ≥ minimal clinically important differences (MCIDs) during and post-treatment was determined using quantile regression and generalised estimating equations.RESULTS: Patients (N = 1684) were assessed every 4th week (15 visits). Four cumulative (β = 0.60) or four consecutive (β = 0.66) visits in remission were required to achieve a benefit ≥MCID in SF-36 physical component summary (PCS) scores, and six cumulative (β = 0.44) or five consecutive (β = 0.49) for a benefit ≥MCID in mental component summary (MCS) scores. Eight cumulative (β = 0.30 for both) or eight consecutive (β = 0.32 for both) visits in LLDAS were required for a benefit in PCS/MCS ≥MCID, respectively.For EQ-5D-3L index scores ≥MCID, six cumulative (β = 0.007) or five consecutive (β = 0.008) visits in remission were required, and eight cumulative (β = 0.005) or six consecutive (β = 0.006) visits in LLDAS. For FACIT-Fatigue scores ≥MCID, 12 cumulative (β = 0.34) or 10 consecutive (β = 0.39) visits in remission were required, and 17 cumulative (β = 0.24) or 16 consecutive (β = 0.25) visits in LLDAS.CONCLUSION: Remission and LLDAS contribute to a HRQoL benefit in a time-dependent manner. Shorter time in remission than in LLDAS was required for a clinically important benefit in HRQoL, and longer time in remission for a benefit in mental compared with physical HRQoL aspects. When remission/LLDAS was sustained, the same benefit was achieved in a shorter time.
  •  
42.
  • Emamikia, Sharzad, et al. (author)
  • The Impact of Remission and Low Disease Activity Attainment on Health-related Quality of Life in Two Phase III Clinical Trials of Belimumab in Systemic Lupus Erythematosus
  • 2021
  • In: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 73:Suppl. 9, s. 2604-2606
  • Journal article (other academic/artistic)abstract
    • Background/Purpose: Health- related quality of life (HRQoL) is considered one of the most important outcomes in clinical trials of systemic lupus erythematosus (SLE), along with reduction in disease activity and safety. We studied the duration and consecutiveness of remission or low disease activity throughout a 52- week long period on standard therapy plus belimumab or placebo in relation to HRQoL outcome.Methods: We analysed pooled 52- week data from the BLISS- 52 (N=865) and BLISS- 76 (N=819) phase III trials. We determined remission using the prevailing Definitions of Remission in SLE (DORIS) definition (1) and low disease activity using the Lupus Low Disease Activity State (LLDAS) (2). Remission required clinical (c)SLEDAI- 2K=0, PhGA (0– 3) <0.5, and prednisone ≤5 mg/day. LLDAS required SLEDAI- 2K ≤4, PhGA (0– 3) ≤1, and prednisone ≤7.5 mg/day. HRQoL was measured with the SF- 36 physical and mental component summary (PCS and MCS), and EQ- 5D- 3L. Minimal clinically important difference (MCID) at week 52 for PCS and MCS was set to 2.5, and for EQ- 5D- 3L utility index to 0.040. Associations were assessed using quantile regression analysis. Adjustments for demographics, disease duration, organ damage and baseline status were incorporated.Results: The minimum cumulative attainment of remission to achieve a benefit in PCS ≥MCID at week 52 was four visits (corresponding to 16 weeks) (β=0.63), while 7 visits (28 weeks) were required for MCS differences ≥MCID (β=0.37). Correspondingly, 9 visits in LLDAS (36 weeks) were required for achieving differences ≥MCID in both PCS (b=0.28) and MCS (β=0.29). Table 1 shows 95% confidence intervals and p values. When analysing the impact of sustained remission and LLDAS, four consecutive visits in remission (16 weeks) were required for PCS ≥MCID (b=0.70), whereas six visits (24 weeks) were required for MCS ≥MCID (b=0.46). Sustained LLDAS for nine consecutive visits (36 weeks) was needed for PCS and MCS ≥MCID (b=0.31 and 0.31, respectively). For EQ- 5D ≥MCID to be reached, a cumulative total of seven visits (28 weeks) in remission (b=0.006), or eight visits (32 weeks) in LLDAS (b=0.005) was required, whereas if sustained, remission for six visits (24 weeks; b=0.008) or LLDAS for seven visits (28 weeks; b=0.006) were sufficient.Conclusion: Attainment of remission or LLDAS in the BLISS- 52 and BLISS- 76 trials of belimumab was associated with improved HRQoL. Less time was required in remission than in LLDAS to achieve clinically important differences in multiple HRQoL aspects. Clinically important differences in HRQoL required shorter total time if the remission or LLDAS was sustained. Clinically important differences in mental aspects of HRQoL required longer time in remission than physical aspects. The impact of cumulative and sustained remission or LLDAS on HRQoL adds evidence on the clinical importance of these treat- to- target endpoints.References:1) van Vollenhoven R. et al. Ann Rheum Dis. 20172) Franklyn K. et al. Ann Rheum Dis. 2016
  •  
43.
  •  
44.
  • Fristedt, Richard, et al. (author)
  • Prognostic impact of tumour-associated B cells and plasma cells in oesophageal and gastric adenocarcinoma
  • 2016
  • In: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 7:6, s. 848-859
  • Journal article (peer-reviewed)abstract
    • Background: While it is well established that the cell-mediated immune response plays an important role in cancer progression and spread, the role of the humoral immune response in this regard has been less studied. According to the existing literature, dense infiltration of B cells or plasma cells appears to correlate mainly with an improved prognosis in several types of cancer, but their prognostic impact in oesophageal and gastric cancer has not yet been described. Methods: Immunohistochemistry was applied on tissue microarrays (TMA) to assess the stromal density of B cells (CD20+) and plasma cells [CD138+ or immunoglobulin kappa C (IGKC+)] in chemo-/radiotherapy-naive tumours from a consecutive cohort of 174 patients with resected oesophageal or gastric adenocarcinoma. Cox proportional hazard's modelling was applied to examine the impact of the investigated markers on overall survival (OS) and time to recurrence (TTR). Results: In curatively treated patients with oesophageal adenocarcinoma, high expression of IGKC was an independent predictor of a prolonged OS [hazard ratio (HR) 0.10; 95% confidence interval (CI), 0.02-0.57], and TTR (HR 0.15; 95% CI, 0.03-0.71). In curatively treated patients with gastric adenocarcinoma, high expression of IGKC independently predicted a prolonged OS (HR 0.46; 95 % CI, 0.24-0.87) and TTR (HR 0.46; 95% CI, 0.21-0.98). Expression of CD20 was not prognostic, and CD138 expression was only prognostic in unadjusted analysis of TTR in gastric cancer. Conclusions: These results demonstrate, for the first time, that abundant infiltration of IGKC+ plasma cells independently predicts a prolonged survival in both oesophageal and gastric cancer.
  •  
45.
  • Gaudet, Mia M., et al. (author)
  • Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
  • 2010
  • In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
  • Journal article (peer-reviewed)abstract
    • The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.
  •  
46.
  • Goodwin, Richard J. A., et al. (author)
  • Conductive carbon tape used for support and mounting of both whole animal and fragile heat-treated tissue sections for MALDI MS imaging and quantitation
  • 2012
  • In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 75:16, s. 4912-4920
  • Journal article (peer-reviewed)abstract
    • Analysis of whole animal tissue sections by MALDI MS imaging (MSI) requires effective sample collection and transfer methods to allow the highest quality of in situ analysis of small or hard to dissect tissues. We report on the use of double-sided adhesive conductive carbon tape during whole adult rat tissue sectioning of carboxymethyl cellulose (CMC) embedded animals, with samples mounted onto large format conductive glass and conductive plastic MALDI targets, enabling MSI analysis to be performed on both TOF and FT-ICR MALDI mass spectrometers. We show that mounting does not unduly affect small molecule MSI detection by analyzing tiotropium abundance and distribution in rat lung tissues, with direct on-tissue quantitation achieved. Significantly, we use the adhesive tape to provide support to embedded delicate heat-stabilized tissues, enabling sectioning and mounting to be performed that maintained tissue integrity on samples that had previously been impossible to adequately prepare section for MSI analysis. The mapping of larger peptidomic molecules was not hindered by tape mounting samples and we demonstrate this by mapping the distribution of PEP-19 in both native and heat-stabilized rat brains. Furthermore, we show that without heat stabilization PEP-19 degradation fragments can detected and identified directly by MALDI MSI analysis.This article is part of a Special Issue entitled: Imaging Mass Spectrometry: A User's Guide to a New Technique for Biological and Biomedical Research.
  •  
47.
  • Guenat, David, et al. (author)
  • Constitutional and somatic deletions of the Williams-Beuren syndrome critical region in Non-Hodgkin Lymphoma
  • 2014
  • In: Journal of Hematology & Oncology. - : Springer Science and Business Media LLC. - 1756-8722. ; 7
  • Journal article (other academic/artistic)abstract
    • Here, we report and investigate the genomic alterations of two novel cases of Non-Hodgkin Lymphoma (NHL) in children with Williams-Beuren syndrome (WBS), a multisystem disorder caused by 7q11.23 hemizygous deletion. Additionally, we report the case of a child with NHL and a somatic 7q11.23 deletion. Although the WBS critical region has not yet been identified as a susceptibility locus in NHL, it harbors a number of genes involved in DNA repair. The high proportion of pediatric NHL reported in WBS is intriguing. Therefore, the role of haploinsufficiency of genes located at 7q11.23 in lymphomagenesis deserves to be investigated.
  •  
48.
  • Hallman, David, 1979-, et al. (author)
  • Symposium: Arbete, individ och nacksmärta : Forskning vid Forte-centret “Kroppen i arbete – från problem till potential”
  • 2018
  • In: FALF KONFERENS 2018 Arbetet - problem eller potential för en hållbar livsmiljö? 10-12 juni 2018 i Gävle. - Gävle : Gävle University Press. - 9789188145284 ; , s. 102-
  • Conference paper (peer-reviewed)abstract
    • Besvär ifrån kroppens muskler och leder såsom nack- och ryggbesvär är fortfarande ett stort problem inom arbetslivet. Muskuloskeletal diagnos är den vanligaste orsaken till lång sjukfrånvaro inom privat sektor och näst vanligast inom kommuner och landsting. Orsakerna till dessa besvär kan vara relaterade till exponering både under arbete och på fritid, men även till individfaktorer. Vår forskargrupp har en bred ansats för att fylla kunskapsluckor inom detta område och kommer att presentera resultat från flera forskningsprojekt i symposiet Arbete, individ och nacksmärta.Långvarigt sittande har blivit alltmer vanligt förekommande i många yrkesgrupper. Långvarigt sittande och låg fysisk aktivitet har också uppmärksammats som ett betydande hälsoproblem i dagens arbetsliv och även som en möjlig riskfaktor för smärta i nacke-skuldra. Men forskningen om betydelsen av långvarigt sittande för smärta i nacke-skuldra är fortfarande begränsad. Likaså är det oklart om huvudets hållning vid sittandet och nackens funktion, exempelvis nackens rörelsefunktion och styrka, har betydelse för besvärsutveckling. Statiskt arbete med nacken i vridna och böjda positioner misstänks vara en riskfaktor för nack-skuldersmärta i yrken såsom tandläkare, men det är oklart varför vissa exponerade individer drabbas medan andra inte får ont. För de med långvarig smärta krävs ofta rehabiliterande åtgärder, och hur väl dessa åtgärder lyckas kan även det vara beroende av individens fysiska och psykosociala arbetsmiljö. Individens arbetsmiljö påverkar således inte bara risken för om man får besvär utan kan också ha betydelse för hur rehabiliteringen av besvären lyckas.Syftet med detta symposium är att presentera studier från Centrum för belastningsskadeforskning som handlar om nacksmärta i arbetslivet, sammanfatta kunskapsläget inom området och diskutera hur arbetet kan utformas för att bli hållbart och inkluderande. De forskningsexempel som presenteras berör stillasittande och hållning i arbetslivet och dess tänkbara konsekvenser för nacksmärta och hälsa, riskfaktorer för nacksmärta i tandläkaryrket och arbetsmiljöns betydelse för resultatet av rehabilitering vid nacksmärta. Symposiet avslutas med en frågestund och gemensam diskussion.
  •  
49.
  •  
50.
  • Hedner, Charlotta, et al. (author)
  • Expression and prognostic significance of human epidermal growth factor receptors 1, 2 and 3 in oesophageal and gastric adenocarcinomas preneoadjuvant and postneoadjuvant treatment
  • 2018
  • In: Journal of Clinical Pathology. - : BMJ. - 1472-4146 .- 0021-9746. ; 71:5, s. 451-462
  • Journal article (peer-reviewed)abstract
    • AIMS: Neoadjuvant treatment has now become the standard of care for oesophageal and gastric cancer. The aim of this study was to investigate the influence of neoadjuvant therapy on the expression of human epidermal growth factor receptor 1 (HER1/EGFR), HER2 and HER3, in oesophageal and gastric adenocarcinoma.METHODS: Immunohistochemical expression of EGFR, HER2 and HER3 was examined and compared in pretreatment biopsies, post-treatment surgical resection specimens and metastases in a retrospective cohort of 166 patients with adenocarcinoma of the oesophagus or stomach. The relationship between expression of the investigative markers and histopathological response to neoadjuvant treatment, overall survival (OS) and recurrence free survival (RFS) was analysed.RESULTS: Conversion of protein expression between pretreatment biopsy and post-treatment surgical resection was seen in 4.6% of the cases for EGFR, 5.9% for HER2% and 19.4% for HER3. Histopathological response to neoadjuvant treatment was significantly and stepwise associated with OS and RFS . High HER3 protein expression in post-treatment surgical resection specimens was significantly associated with a prolonged OS in univariable analysis (HR=0.39; 95% CI 0.17 to 0.93), but did not remain significant in multivariable analysis. Expression of EGFR and HER2 in post-treatment surgical resection specimens was not prognostic. No correlation between pretreatment HER-protein expression and histopathological response was seen.CONCLUSIONS: The results from this study underscore the need for further studies on the influence of neoadjuvant treatment on biomarker expression, as this may influence treatment strategy as well as prognosis. Histopathological response is validated as a useful prognostic factor.
  •  
Skapa referenser, mejla, bekava och länka
  • Result 1-50 of 101
Type of publication
journal article (90)
research review (5)
conference paper (3)
doctoral thesis (2)
other publication (1)
Type of content
peer-reviewed (93)
other academic/artistic (8)
Author/Editor
Borg, Åke (34)
Jirström, Karin (20)
Staaf, Johan (13)
Ringnér, Markus (10)
Höglund, Mattias (8)
Lindgren, David (8)
show more...
Martin, Sancha (8)
Richardson, Andrea L ... (8)
Easton, Douglas F. (7)
Nik-Zainal, Serena (7)
Ramakrishna, Manasa (7)
Chenevix-Trench, Geo ... (6)
Offit, Kenneth (6)
Radice, Paolo (6)
Thomas, Gilles (6)
Alexandrov, Ludmil B ... (6)
Wedge, David C. (6)
Boyault, Sandrine (6)
Davies, Helen R. (6)
Glimelius, Bengt (5)
Caldas, Carlos (5)
Ley, David (5)
Daly, Mary B. (5)
Hamann, Ute (5)
Papaemmanuil, Elli (5)
Raine, Keiran (5)
Vincent-Salomon, Ann ... (5)
Olsson, Håkan (4)
Børresen-Dale, Anne- ... (4)
Nevanlinna, Heli (4)
Pontén, Fredrik (4)
Liedberg, Fredrik (4)
Gudjonsson, Sigurdur (4)
Hellström, Ann, 1959 (4)
John, Esther M (4)
Neuhausen, Susan L (4)
Andrulis, Irene L. (4)
Benitez, Javier (4)
Borresen-Dale, Anne- ... (4)
Devilee, Peter (4)
Evans, D. Gareth (4)
Couch, Fergus J. (4)
Simard, Jacques (4)
Stålnacke, Britt-Mar ... (4)
Parodis, Ioannis, 19 ... (4)
Aparicio, Samuel A. ... (4)
Knappskog, Stian (4)
Lakhani, Sunil R. (4)
Span, Paul N. (4)
Teague, Jon W. (4)
show less...
University
Lund University (73)
Karolinska Institutet (33)
Uppsala University (25)
Umeå University (8)
Royal Institute of Technology (7)
Örebro University (6)
show more...
University of Gothenburg (5)
Luleå University of Technology (2)
University of Gävle (2)
Linköping University (2)
The Swedish School of Sport and Health Sciences (2)
RISE (2)
Högskolan Dalarna (2)
Jönköping University (1)
Mid Sweden University (1)
Södertörn University (1)
Chalmers University of Technology (1)
Red Cross University College (1)
show less...
Language
English (100)
Swedish (1)
Research subject (UKÄ/SCB)
Medical and Health Sciences (87)
Natural sciences (9)
Engineering and Technology (4)
Social Sciences (3)
Humanities (1)

Year

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view