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- Crippa, Alessio, et al.
(author)
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The ProBio trial : molecular biomarkers for advancing personalized treatment decision in patients with metastatic castration-resistant prostate cancer
- 2020
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In: Trials. - : BioMed Central. - 1745-6215. ; 21:1
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Journal article (peer-reviewed)abstract
- Background: Multiple therapies exist for patients with metastatic castration-resistant prostate cancer (mCRPC). However, their improvement on progression-free survival (PFS) remains modest, potentially explained by tumor molecular heterogeneity. Several prognostic molecular biomarkers have been identified for mCRPC that may have predictive potential to guide treatment selection and prolong PFS. We designed a platform trial to test this hypothesis.Methods: The Prostate-Biomarker (ProBio) study is a multi-center, outcome-adaptive, multi-arm, biomarker-driven platform trial for tailoring treatment decisions for men with mCRPC. Treatment decisions in the experimental arms are based on biomarker signatures defined as mutations in certain genes/pathways suggested in the scientific literature to be important for treatment response in mCRPC. The biomarker signatures are determined by targeted sequencing of circulating tumor and germline DNA using a panel specifically designed for mCRPC.Discussion: Patients are stratified based on the sequencing results and randomized to either current clinical practice (control), where the treating physician decides treatment, or to molecularly driven treatment selection based on the biomarker profile. Outcome-adaptive randomization is implemented to early identify promising treatments for a biomarker signature. Biomarker signature-treatment combinations graduate from the platform when they demonstrate 85% probability of improving PFS compared to the control arm. Graduated combinations are further evaluated in a seamless confirmatory trial with fixed randomization. The platform design allows for new drugs and biomarkers to be introduced in the study.Conclusions: The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care.
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| 3. |
- Eriksson, Anders, et al.
(author)
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Rotation Averaging with the Chordal Distance: Global Minimizers and Strong Duality
- 2021
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In: IEEE Transactions on Pattern Analysis and Machine Intelligence. - 1939-3539 .- 0162-8828. ; 43:1, s. 256-268
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Journal article (peer-reviewed)abstract
- In this paper we explore the role of duality principles within the problem of rotation averaging, a fundamental task in a wide range of applications. In its conventional form, rotation averaging is stated as a minimization over multiple rotation constraints. As these constraints are non-convex, this problem is generally considered challenging to solve globally. We show how to circumvent this difficulty through the use of Lagrangian duality. While such an approach is well-known it is normally not guaranteed to provide a tight relaxation. Based on spectral graph theory, we analytically prove that in many cases there is no duality gap unless the noise levels are severe. This allows us to obtain certifiably global solutions to a class of important non-convex problems in polynomial time. We also propose an efficient, scalable algorithm that outperforms general purpose numerical solvers by a large margin and compares favourably to current state-of-the-art. Further, our approach is able to handle the large problem instances commonly occurring in structure from motion settings and it is trivially parallelizable. Experiments are presented for a number of different instances of both synthetic and real-world data.
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| 4. |
- Eriksson, Maria, 1969, et al.
(author)
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Införandeår för risk-/skyddsintervju vid våld i familjen
- 2020
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Reports (other academic/artistic)abstract
- Under 2019 har dessa intervjuer införts i ordinarie socialtjänst under handledning från forskarteamet bakom modellen, genom ett så kallat införandeår finansierat av Socialstyrelsen. Införandeåret är en fortsättning av tidigare satsningar med särskilt fokus på att höja riskbedömningarnas kvalitet, särskilt inom den sociala barnavården. Syftet med föreliggande projekt var att pröva att införa iRiSk-intervjuerna inom ramen för ordinarie arbete i socialtjänsten, inom barnavårdsutredningar avseende barn som varit utsatta för våld, direkt och/eller bevittnat mellan barnets föräldrar. I syftet ingick att samla erfarenheter av införandet av betydelse för det fortsatta arbetet med att introducera iRiSk risk och skyddsintervjuer i ordinarie socialtjänst.
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| 5. |
- Heuman, Anna, 1990-
(author)
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Negotiating standard language ideology : Metalinguistic discussions in mundane, online interaction
- 2022
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Doctoral thesis (other academic/artistic)abstract
- This thesis investigates how ordinary language users enact language policy and thus negotiate (standard) language ideology in mundane, online interaction. The language policy work is found in metalinguistic discussions on various social media. The discussions have been triggered by deviations from standard written language, mostly on the level of orthography. The discussions mainly target different aspects of standard language ideology. The three studies included in this compilation thesis identify discursive strategies and reveal the contradictory ideologies underpinning the discussions.The discussions are analysed with an interactional and procedural focus, highlighting the unfolding negotiations of standard language ideology. The results show that standard language ideology is prevailing which, in turn, enables certain realisations. When drawing on standard norms, the participants can use strategies that do not include explicit arguments. However, the discussions also include contradictions and strategies that challenge traditional standard beliefs. These results illustrate the mundane, vivid metalinguistic negotiations in which standard language ideology is primarily enforced, but also challenged.The results illuminate how standardisation is not a mythical and imperceptible process, but one of constant and visible iteration, also in very mundane situations. Furthermore, the pervasiveness of standard language ideology could make it harder for those who deviate from it to be listened to or even to participate at all. In this way, everyday metalinguistic discussions are one among many language policy activities that can enforce loyalty to the standard variety and its position as unmarked.
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| 6. |
- Visuri, Isabella, 1991-, et al.
(author)
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Predictors of drug survival : A cohort study comparing anti-tumour necrosis factor agents using the Swedish inflammatory bowel disease quality register
- 2021
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In: Alimentary Pharmacology and Therapeutics. - : Blackwell Science Ltd.. - 0269-2813 .- 1365-2036. ; 54:7, s. 931-943
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Journal article (peer-reviewed)abstract
- Background: Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown.Aims: To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF.Methods: Biologic-naive patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).Results: In Crohn's disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration >= 10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates.Conclusions: Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohn's disease, suggests a potential difference between the two drugs.
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