From Semantics to Pragmatics

The topic of this thesis is the distinction between semantics and pragmatics. Semantics is concerned with the literal meanings of expressions, what is explicitly expressed with expressions and providing truth conditions for sentences. While the subject matter of pragmatics, being the more nebulous one, is focused on non-literal meanings of expressions, what is implicitly conveyed with expressions and non-truth-conditional content. In this thesis I will present two theories: David Kaplan’s theory of indexicals and demonstratives and Robert Stalnaker’s assertion theory. The guiding question of this work is how these theorists distinguish semantics from pragmatics. How does the distinction appear in their theories? To point out, neither of the theories is aimed to specifically solve how the distinction is to be made. Kaplan’s aim is to create semantics for indexical expressions, whereas Stalnaker wants to explain how necessary a posteriori identity statements can be informative according to his two-dimensional semantic theory. Despite the differing goals underlying their theories, Kaplan and Stalnaker are not oblivious of the distinction between semantics and pragmatics. In fact, how the distinction is eventually made by these theorists, strongly depends on how each of the theories is built.Tutkielmassani käsittelen semantiikan ja pragmatiikan välistä erottelua. Karkeasti ottaen semantiikalla tarkoitetaan tutkimusalaa, joka käsittelee ilmaisujen kirjaimellista merkitystä, mitä ilmaisuilla eksplisiittisesti ilmaistaan sekä lauseiden totuusehtojen muodostamista. Pragmatiikan alaan lasketaan perinteisesti kuuluvan ilmaisujen ei-kirjaimellisen merkityksen tarkastelun, mitä ilmaisuilla implisiittisesti välitetään sekä lauseiden ei-totuusehdollisen sisällön tarkastelun. Esittelen tutkielmassani kaksi teoriaa: David Kaplanin teorian indeksikaaleista ja demonstratiiveista sekä Robert Stalnakerin teorian siitä, miten väittämä vaikuttaa kontekstiin. Tutkielmani keskeinen kysymys on, miten semantiikan ja pragmatiikan välinen erottelu ilmenee Kaplanin ja Stalnakerin teorioissa. Mainittakoon, että kumpikaan teoria ei ensisijaisesti pyri vastaamaan asettamaani kysymykseen. Kaplanin tarkoitus on osoittaa, että indeksikaalisille ilmaisuille voidaan luoda semantiikka. Stalnaker pyrkii puolestaan esittämään, miten välttämättömät a posteriori identiteettiväitteet voivat olla informatiivisia hänen kehittämän kaksiulotteisen semanttisen teorian mukaan. Erilaisista päämääristä huolimatta sekä Kaplan että Stalnaker ovat varsin tietoisia erottelusta semantiikan ja pragmatiikan välillä, mikä ilmenee erityisesti luvussa 4

Opportunities and challenges for real-world studies on chronic inflammatory joint diseases through data enrichment and collaboration between national registers : the Nordic example

RMD Open 2018;4:e000655. doi:10.1136/ rmdopen-2018-000655Peer reviewe

Exposure to specific tumour necrosis factor inhibitors and risk of demyelinating and inflammatory neuropathy in cohorts of patients with inflammatory arthritis : a collaborative observational study across five Nordic rheumatology registers

Funding Information: This work was supported by NordForsk and the Foundation for Research in Rheumatology (Foreum) and Vinnova. The research infrastructure was supported by funds from the Swedish Research Council, the Swedish Heart Lung Foundation and the Swedish Cancer Society, and funds from Region Stockholm-Karolinska Institutet (ALF). The Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY) (Norway) is funded as a Centre for Clinical Treatment Research by the Research Council of Norway (project 328657). Publisher Copyright: © 2023 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Objective To compare incidences of neuroinflammatory events, including demyelinating disease (DML), inflammatory polyneuropathies (IPN) and multiple sclerosis (MS), in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA; including psoriatic arthritis) starting a tumour necrosis factor inhibitor (TNFi), investigating whether monoclonal TNFi antibodies (other TNFis (oTNFis)) confer higher risk than etanercept. Methods This is an observational cohort study including patients from the five Nordic countries starting a TNFi in 2001-2020. Time to first neuroinflammatory event was identified through register linkages. We calculated crude incidence rates (cIR) per 1000 person-years and used multivariable-adjusted Cox regression to compare incidences of neuroinflammatory events overall and for DML, IPN and MS with oTNFi versus etanercept. We further examined individual TNFis and indications. Results 33 883 patients with RA and 28 772 patients with SpA were included, initiating 52 704 and 46 572 treatment courses, respectively. In RA, we observed 135 neuroinflammatory events (65% DML) with cIR of 0.38 with oTNFi and 0.34 with etanercept. The HR of oTNFi versus etanercept was 1.07 (95% CI 0.74 to 1.54) for any neuroinflammatory event, 0.79 (95% CI 0.51 to 1.22) for DML, 2.20 (95% CI 1.05 to 4.63) for IPN and 0.73 (95% CI 0.34 to 1.56) for MS. In SpA, we observed 179 events (78% DML) with cIR of 0.68 with oTNFi and 0.65 with etanercept. The HR for any neuroinflammatory event, DML, IPN and MS was 1.06 (95% CI 0.75 to 1.50), 1.01 (95% CI 0.68 to 1.50), 1.28 (95% CI 0.61 to 2.69) and 0.94 (95% CI0.53 to 1.69), respectively. Conclusion The cIRs of neuroinflammatory events are higher in SpA than in RA, but the choice of specific TNFi does not seem to play an important role in the risk of neuroinflammatory events.Peer reviewe

Haematological malignancies in patients with psoriatic arthritis overall and treated with TNF inhibitors : a Nordic cohort study

OBJECTIVES: To evaluate the risk of haematological malignancies in patients with psoriatic arthritis (PsA) overall, and in relation to treatment with tumour necrosis factor inhibitors (TNFi). METHODS: We identified that patients with PsA starting a first TNFi from the clinical rheumatology registers (CRR) in the five Nordic countries (n=10 621) and biologics-naïve PsA patients from (1) the CRR (n=18 705) and (2) the national patient registers (NPR, n=27 286, Sweden and Denmark) from 2006 through 2019. For Sweden and Denmark, general population comparators were matched 5:1 to PsA patients on birth year, year at start of follow-up and sex. By linkage to the national cancer registers in all countries, we collected information on haematological malignancies overall, and categorised into lymphoid or myeloid types. We estimated incidence rate ratios (IRRs) with 95% CIs using modified Poisson regression for TNFi-treated versus biologics-naïve PsA patients and versus the general population adjusted for age, sex, calendar period and country. RESULTS: During 59 827 person-years, 40 haematological malignancies occurred among TNFi-treated patients with PsA resulting in a pooled IRR of 0.96 (0.68-1.35) versus biologics-naïve PsA from CRR and an IRR of 0.84 (0.64-1.10) versus biologics-naïve PsA from NPR. The IRR of haematological malignancies in PsA overall versus general population comparators was 1.35 (1.17-1.55). The estimates were largely similar for lymphoid and myeloid malignancies. CONCLUSIONS: Treatment with TNFi in patients with PsA was not associated with an increased incidence of haematological malignancies. Conversely, a moderately increased underlying risk was seen in patients with PsA compared with the general population.publishedVersionPeer reviewe

Sähkömoottoripyörämuunnos: akku ja akunhallintajärjestelmä

Opinnäytetyö on osa Kaakkois-Suomen ammattikorkeakoulun sähkömoottoripyörämuunnosprojektia, jossa polttomoottorikäyttöinen moottoripyörä muunnetaan täyssähköiseksi. Tarkoituksena oli rakentaa tieliikennekelpoinen sekä suorituskykyinen sähkömoottoripyörä. Tämä osuus keskittyy akun rakentamiseen ja akunhallintajärjestelmään. Tavoitteina oli pitää akusto mahdollisimman kevyenä sekä sähkökapasiteetiltaan ja purkuvirraltaan riittävänä. Jotta sähkömoottoripyörä pysyisi mahdollisimman kevyenä, oli akustoon saatava mahdollisimman paljon energiaa painoa kasvattamatta. Myös akuston purkuvirta tulee olla riittävä suorituskyvyn kannalta. Akuston rakentamiseen vaikuttaa moottoripyörän runko, joka toimii akuston kokoa rajoittavana raamina. Useista markkinoilla olevista akunhallintajärjestelmistä puuttuu parametrejä, joiden säädöillä voi vaikuttaa sähkömoottoripyörän suoritustehoon, tästä syystä tavoitteena oli rakentaa akunhallintajärjestelmä alusta alkaen itse. Akunhallintajärjestelmän rakennus aloitettiin prototyypin valmistamisesta. Rakennetusta akunhallintajärjestelmästä suunniteltiin hajautettu akunhallinta, jossa jokaista valvottavaa akkua kohden on yksi mikrokontrolleriyksikkö, joka keskustelee pääyksikön kanssa. Tiedonsiirtoon käytettiin I2C-tiedonsiirtoväylää. Prototyyppilevyjä valmistettiin muutamia kappaleita piirilevyjyrsimellä, ja pääyksikkönä toimi Arduino-mikrokontrolleri. Opinnäytetyön tuloksena syntyi akusto, akunhallintajärjestelmä sekä akkukotelo sähkömoottoripyörään. Akunhallintajärjestelmästä tehtiin myös oma versio, josta tehtiin prototyyppi. Käyttöön omatekoista akunhallintajärjestelmää ei kuitenkaan otettu. Sähkömoottoripyörä katsastettiin, ja se on tieliikennekelpoinen

Risk of solid cancers overall and by subtypes in patients with psoriatic arthritis treated with TNF inhibitors - a Nordic cohort study.

To access publisher's full text version of this article click on the hyperlink belowObjectives: To investigate whether TNF inhibitors (TNFi) are associated with increased risk of solid cancer in patients with psoriatic arthritis (PsA). Methods: From the Nordic clinical rheumatology registers (CRR) here: SRQ/ARTIS (Sweden), DANBIO (Denmark), NOR-DMARD (Norway), ROB-FIN (Finland) and ICEBIO (Iceland) we identified PsA patients who started a first TNFi 2001-2017 (n = 9655). We identified patients with PsA not treated with biologics from (i) the CRR (n = 14 809) and (ii) the national patient registers (PR, n = 31 350). By linkage to the national cancer registers, we collected information on incident solid cancer overall and for eight cancer types. We used Cox regression to estimate hazard ratio (HR) with 95% CI of cancer (per country and pooled) in TNFi-exposed vs biologics-naïve, adjusting for age, sex, calendar period, comorbidities and disease activity. We also assessed standardized incidence ratios (SIR) in TNFi-exposed PsA vs the general population (GP). Results: We identified 296 solid cancers among the TNFi-exposed PsA patients (55 850 person-years); the pooled adjusted HR for solid cancer overall was 1.0 (0.9-1.2) for TNFi-exposed vs biologics-naïve PsA from the CRR, and 0.8 (0.7-1.0) vs biologics-naïve PsA from the PRs. There were no significantly increased risks for any of the cancer types under study. The pooled SIR of solid cancer overall in TNFi treated PsA vs GP was 1.0 (0.9-1.1). Conclusion: In this large cohort study from five Nordic countries, we found no increased risk of solid cancer in TNFi-treated PsA patients, neither for solid cancer overall nor for eight common cancer types.NordForsk FOREUM Det Frie Forskningsrad (DFF) DFF -6110-00608 OAK foundation HUCH Institutional grant Finland Finska Lakaresallskapet Swedish Cancer Society Stockholm County Council Swedish Research Council European Commissio

Effectiveness of a Second Biologic After Failure of a Non-tumor Necrosis Factor Inhibitor As First Biologic in Rheumatoid Arthritis.

To access publisher's full text version of this article click on the hyperlink belowObjective: In rheumatoid arthritis (RA), evidence regarding the effectiveness of a second biologic disease-modifying antirheumatic drug (bDMARD) in patients whose first-ever bDMARD was a non-tumor necrosis factor inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of a second bDMARD (non-TNFi: rituximab [RTX], abatacept [ABA], or tocilizumab [TCZ], separately; and TNFi) after failure of a non-TNFi bDMARD as first bDMARD. Methods: We identified patients with RA from the 5 Nordic biologics registers who started treatment with a non-TNFi as first-ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed drug survival (at 6 and 12 months) and primary response (at 6 months). Results: We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67, and TNFi 427) following failure of a first non-TNFi bDMARD. At 6 and 12 months after start of their second bDMARD, approximately 70% and 60%, respectively, remained on treatment, and at 6 months, less than one-third of patients were still on their second bDMARD and had reached low disease activity or remission according to the Disease Activity Score in 28 joints. For those patients whose second bMDARD was a TNFi, the corresponding proportion was slightly higher (40%). Conclusion: The drug survival and primary response of a second bDMARD in patients with RA switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD. Keywords: biologics; disease-modifying antirheumatic drugs; rheumatoid arthritis; therapy.Nord-Forsk FOREU