From cell survival to dose response : modeling biological effects in radiation therapy

The main goal in curative radiation therapy is to eradicate the tumor while minimizing radiation-induced damage to normal tissue. Ions, including protons and carbon ions, are increasingly being used for cancer treatment. They allow for a more focused dose to the tumor and exhibit higher effectiveness in cell killing compared to conventional radiation therapy using photons. The aim of this thesis is to develop and evaluate mathematical models for biological effect estimation with the focus on proton and light ion irradiation. Two radiobiological models for ions were developed. Firstly, the repairableconditionally repairable damage (RCR) cell survival model was extended to account for the linear energy transfer (LET). Secondly, a model that estimates the relative biological effectiveness (RBE) of protons based on dose, LET, and cell type was derived. The LET-parameterized RCR model provides an adequate fit to experimental cell survival data derived from irradiation with carbon ions and helium ions. The RBE model predicts a cell-dependent relation between RBE and LET determined by the cell-specific parameter = of the linear-quadratic model of photons. In a separate study, the effect of accounting for variable RBE in treatment plan comparison was investigated using the proposed RBE model. Lower RBE was predicted in the tumor and higher RBE in adjacent organs than the commonly assumed RBE equal to 1.1. Disregarding this variation and instead assuming RBE equal to 1.1 in treatment plan optimization may lead to optimistic estimates for the proton plan and thereby biases treatment plan comparison in its favor. Derived dose-response relations of normal tissue toxicity are uncertain because they are based on limited numbers of patients. A bootstrap method was proposed to assess the uncertainty in clinical outcome data due to sampling variability, and translate this into an uncertainty in the dose-response relation. The method provides confidence intervals of the dose-response relation, suggests model parameter values with confidence intervals and their interrelation, and can be used for model selection

"Han tjänte hvad land som helst, där det betaltes väl" – En kanonkritisk textanalys av arkitekten Ernst B. Lohrmanns (1803 – 1870) exkludering ur kanon

Arkitekten Ernst B. Lohrmann (1803–1870) anlände från Tyskland till Storfurstendömet Finland 1841, för att ta över Carl Ludvig Engels (1778–1840) plats som överintendent på Intendentskontoret. Under sin tjänstetid utvecklade Lohrmann förutsättningarna för arkitekturen i Finland, bland annat genom att etablera länsarkitektsystem och bygga ut förutsättningar för arkitektutbildningen för infödda finländare. Förutom sina administrativa plikter var han som intendent även ansvarig för en stor mängd byggnader runtom i landet, både som upphovsperson och som chef över landets övriga arkitekter. Trots sina bidrag till den finländska arkitekturen och dess förutsättningar, är han idag till stor del exkluderad ur den finländska arkitekturens kanon. Andra arkitekter som var aktiva under Lohrmanns tid är inkluderade, trots att flera av dem inte var lika produktiva eller högt uppsatta. Syftet med avhandlingen är att undersöka varför Lohrmann har en undanskymd plats i den finländska arkitekturens kanon, samt att ta fram en verklista för hans finländska produktion. Till forskningsfrågorna hör: Hur såg Lohrmanns reella bidrag till det finländska arkitekturfältet ut? Vad ansågs det om honom i samtiden och i senare översiktsverk? Varför exkluderas han ur kanon? Dessa frågor kommer att diskuteras genom en diskursanalytisk metod med ett kanonkritiskt läsande där den framväxande nationalromantiken och nationalismen samt bortnämning tas i beaktande. Det huvudsakliga materialet består av samlingsverk om arkitekturen under 1800-talet, och texter och brev skrivna av prevalenta arkitektur- och konstkännare i landet. Även det arkivmaterial som har plockats fram för sammanförandet av en verklista, mestadels från Riksarkivet i Helsingfors samt Helsingfors stadsmuseums digitaliserade arkiv, kommer att användas i avhandlingen. Bland den centrala teoretiska litteraturen räknas både befintlig forskning om skapandet av den finländska identiteten, samt akademiker som diskuterat nationalism och kanonisering på ett bredare plan. Resultatet av undersökningen pekar mot en allmän ovilja att erkänna Lohrmann som en framgångsrik arkitekt och konstnär, samt att han led både som Engels efterträdare och inom kontexten för den rådande nationalismen som letade efter ett nationellt konstuttryck som han inte hade en plats i. Däremot har hans framgångar som byråkrat ovilligt uppskattats. Med tanke på de stora symboliska uppdragen som Engel hade haft under sin intendentsperiod, och hur uppskattad han var både av folket och hans kollegor, var förväntningarna på Lohrmann alldeles för höga för att någonsin kunna mötas. Skrivandet om och runt Lohrmann har skett subjektivt utgående från vad andra tyckte om honom. Det har varit frågan om ideologi före estetik och logik

Adverse event reporting in studies of penetrating acupuncture during pregnancy: a systematic review

Background - Acupuncture within pregnancy has frequently been investigated, often with finding this to be more effective than standard care. However, the adverse event severity, types and occurrence are unclear. Objective - To investigate the quality of reporting adverse events and to attempt to identify occurrence, type and severity of adverse events in acupuncture and non-acupuncture groups. Results - Overall quality of reporting of adverse events was poor, with information describing the adverse events often lacking in detail. A number of trends were noted: adverse events occurring within a treatment session was 3%-17% in the acupuncture groups and 4-25% in the non-acupuncture groups. The percentage of women affected by an adverse event was between 14%-17% in the acupuncture groups and 15-19% in non-acupuncture groups. Conclusions - Adverse event reporting within acupuncture trials is generally poor. The trends noted were that adverse events do occur, but would appear to be largely minor and comparable to non-acupuncture related interventions

Pregnancy-related pelvic girdle pain: an update

A large number of scientists from a wide range of medical and surgical disciplines have reported on the existence and characteristics of the clinical syndrome of pelvic girdle pain during or after pregnancy. This syndrome refers to a musculoskeletal type of persistent pain localised at the anterior and/or posterior aspect of the pelvic ring. The pain may radiate across the hip joint and the thigh bones. The symptoms may begin either during the first trimester of pregnancy, at labour or even during the postpartum period. The physiological processes characterising this clinical entity remain obscure. In this review, the definition and epidemiology, as well as a proposed diagnostic algorithm and treatment options, are presented. Ongoing research is desirable to establish clear management strategies that are based on the pathophysiologic mechanisms responsible for the escalation of the syndrome's symptoms to a fraction of the population of pregnant women

Evaluating Acupuncture and Standard carE for pregnant women with Back pain (EASE Back): a feasibility study and pilot randomised trial

Background: Many pregnant women experience low back pain. Acupuncture appears to be a safe, promising intervention but evidence is needed about its clinical effectiveness and cost-effectiveness. Objectives: To assess the feasibility of a future large randomised controlled trial (RCT) testing the additional benefit of adding acupuncture to standard care (SC) for pregnancy-related back pain.sch_die20pub5270pub3

Negativ styrränta - en Pandoras ask - En studie av den svenska monetära transmissionsmekanismen under positiv och negativ styrränta

As a response to periods of low inflation-rates the central banks of several European countries have chosen to lower their key interest rates below zero. Because of the rarity of this type of action, very little research has been performed on its consequences. The following study examines the monetary transmission mechanism, in particular whether or not its interest rate channel and exchange rate channel is applicable in a Swedish context. It will also evaluate if the channel is applicable after the Swedish central bank lowered its key rate to a negative level. The interest-rate channel implies that lowering the interest rate should result in an increase in lending. The exchange rate channel on the other hand predicts that a lower key interest rate should imply a depreciation of the value of SEK in relation to EUR. The interest-rate channel was tested by examining the relationship between the central bank key interest rate and lending to companies, banks and households. The exchange rate channel was tested by examining the relationship between the key interest rate and the exchange rate. The study shows that the interest rate channel is active in relation to lending to banks and to households. However, it was not applicable to the lending to companies. Furthermore, the effect on lending was maintained during the period of negative interest rate. The study also shows that the exchange rate channel is active. The effect was marginally weakened during the period of negative key interest rate. Because of the inability of the interest rate channel to affect lending to Swedish companies and the ambiguity within the field the study it is recommended that further research should be performed to be able to identify the particulars of the Swedish monetary transmission mechanism