Quantifying cancer patient survival : extensions and applications of cure models and life expectancy estimation

Cancer patient survival is the single most important measure of cancer patient care. By quantifying cancer patient survival in different ways further insights can be gained in terms of temporal trends and differences in cancer patient survival between groups. The objective of this thesis is to develop and apply methods for estimating the cure proportion and loss in expectation of life for cancer patients. In paper I, a cure model was used to study temporal trends in survival of patients with acute myeloid leukaemia in Sweden. Cancer patient survival was estimated in a relative survival setting and quantified as the proportion cured and the median survival time of uncured for different age groups and by calendar time of diagnosis. We found a dramatic increase in the cure proportion for the age group 19-40, although almost no improvement was seen for patients aged 70-79 at diagnosis. In paper II, a flexible parametric cure model was developed to overcome some limitations with standard parametric cure models. This model is a special case of a non-mixture cure model, using splines instead of a parametric distribution for the modeling. The fit of the flexible parametric cure model was compared to the fit of a Weibull non-mixture cure model, and shown to be superior in cases when the standard non-mixture cure model did not give a good fit or did not converge. Software was developed to enable use of the method. In paper III, the possibility of using a flexible parametric relative survival model for estimating life expectancy and loss in expectation of life was evaluated. Extrapolation of the survival function is generally needed, and the flexible parametric relative survival model was shown to extrapolate the survival very well. The method was evaluated by comparing survival functions extrapolated from 10 years past diagnosis to observed survival by the use of data with 40 years of follow-up. Software was developed to enable use of the method. In paper IV, the life expectancy and loss in expectation of life was estimated for colon cancer patients in Sweden. Even though relative survival was similar across age for colon cancer patients, the loss in expectation of life varied greatly by age, since young patients have more years to lose. We also found that the life expectancy of colon cancer patients improved over time. However, the improvement has to a large extent mimicked the improvement seen in the general population, and therefore there were no large changes in the loss in expectation of life. In conclusion, the methods presented in this thesis are additional tools for estimating and quantifying population-based cancer patient survival, that can lead to an improved understanding of different aspects of the prognosis of cancer patients

En studie av spårbarhetssystem i modeindustrin

Allmänheten har blivit mer uppmärksammad vad gäller miljörelaterade frågor och ställer högre krav på företag att arbeta för en hållbar utveckling. Generellt sett har företagen utformade riktlinjer vad gäller arbetsmiljö och arbetsvillkor men sämre insyn i produktionens miljöpåverkan. Samtidigt som medvetenheten om miljöproblemen ökar, ökar konsumtionen av billiga kläder, så kallad ”fast fashion” konsumtion. Detta är inte förenligt med en hållbar utveckling då textilindustrin kräver stora mängder energi, råmaterial och kemikalieutsläpp. Ett svar på komplexiteten modebranschen ställs inför är att kommunicera på ett transparent sätt och på så sätt ta kontrollen över sina produktionskedjor. Ämnet för uppsatsen grundas i problematiken för modeföretag som arbetar med CSR och vill kommunicera detta genom spårbarhetssystem. Ett system som sammanställer information från aktörer i en lång och komplex produktionskedja är inte helt oproblematiska. Modeföretaget Kuyichi använde tidigare ett spårbarhetsystem och har därför varit föremål för denna fallstudie. Undersökningen är av kvalitativ karaktär, där intervjupersoner på företag och organisationer valdes efter expertis inom området. Materialet har analyserats efter aspekterna strategi, risk management, organisationens kultur och transparens. Efter empiriinsamlingen kunde slutsatsen att hållbara modeföretag arbetar med spårbarhetssystem för att kunna kommunicera sitt CSR- arbete och på så sätt få konkurrenskraftiga fördelar. Om förutsättningarna för systemet uppfylls innebär det ökad kontroll och därmed ökad hållbarhet i produktionskedjan. Genom ärlig och transparent kommunikation kan företaget stärka sin trovärdighet men även utbilda konsumenten om produktens påverkan på människor och miljö.Consumers have become more aware of environmental issues, and this creates larger demands on companies to work with sustainable development. Generally speaking, companies have designed policies with regards to health, safety and working conditions, but with less insight regarding the production environment. As awareness of environmental issues increases, so does our consumption of cheap clothes, so-called "fast fashion" consumption. This is not compatible with sustainable development as the textile industry requires large amounts of energy, raw materials and chemical waste. A response to the complexity, which the fashion industry faces, is to communicate in a transparent manner and thus take control of their supply chains. The topic of the essay is based on the complexity for companies that work with CSR issues and want to communicate this through a traceability system. A system that compiles information from actors in a long and complex chain of production is not entirely unproblematic. The fashion company Kuyichi previously worked with a traceability system and have therefore been subject to this case study. This is a qualitative study, where interviews were conducted with companies and organizations selected based on experts in the field. The material was analyzed by the theory of SSCM and the aspects of strategy, risk management, organizational culture and transparency. After completing the empirical data collection, the conclusions show that sustainable fashion companies works with traceability systems in order to be able to communicate their CSR work and gain competitive advantages. If the conditions for the system are met, it leads to increased control and thus increased sustainability in the production chain. The company can through honest and transparent communication be able to increase their credibility but also educate consumers about the product's impact on people and environment

The fertilization effect by common alder in reference to production in a mixed stand consisting of Norway spruce and common alder : a simulation in Heureka

A secondary and a pioneer tree species can with advantage be included in a mixed stand to increase the use of sunlight. Nitrogen-fixing plants have been shown to increase the supply of nitrogen in the soil by, for example, litter fall. This deposition acts as a biological fertilization, which may be used by non-fixing plants. Alder is a nitrogen-fixing, pioneer tree species that loses its nitrogen-rich leaves late in the autumn. The aim of this study was to examine the effect on the total volume of production, when different proportions of nitrogen-fixing Alder were part of spruce stands. A second goal was to identify at which approximate proportion of Alder the highest volume production was achieved. In Heureka StandWise a mixed population consisting of various shares of spruce and alder (0%, 30%, 45%, 60%) with each three different management programs (no thinning, one thinning, two thinnings) were simulated. The results showed that 30% Alder, in the mixed stand, gave the highest total volume production regardless of the management program that was used. This may indicate that the optimum probably lies close to this value. The average amount of nitrogen in the simulations ranged between 9 to 19 kilogram per ha and year. Positive side-effects which follow this type of species mixture is increased frost protection and increased storm resistance for spruce. The results of this study could form an idea and inspire further research on how forests of this type can be established and managed.Ett sekundär- och ett pionjärträdslag kan med fördel ingå i ett blandbestånd för att öka resursutnyttjandet av bland annat solljus. Kvävefixerande växter har visat sig öka kvävetillgången i marken, bland annat genom förnanedfall. Nedfallet fungerar som biologisk gödsling, vilket kan komma icke kvävefixerande växter tillgodo. Klibbal är ett kvävefixerande pionjärträdslag som tappar sina kväverika blad sent på hösten. Syftet med denna studie var att undersöka effekten på den totala volymproduktionen, då olika andelar kvävefixerande klibbal ingick i ett granbestånd. Delmålet var att identifiera vid vilken ungefärlig procentandel klibbal som högst volymproduktion uppnåddes. I Heurekas StandWise simulerades ett blandbestånd bestående av olika andelar gran och klibbal (0 %, 30 %, 45 %, 60 % klibbal) med vardera tre olika skötselprogram (ingen gallring, en gallring, två gallringar). Resultaten visade att 30 % inblandning av klibbal gav den högsta totala volymproduktionen oberoende av vilket skötselprogram som användes. Detta indikerar att optimum antagligen ligger i närheten av detta värde. Medelvärde för kvävegivorna som tillfördes genom alförna i de olika simuleringarna varierade mellan 9 kg/ha/år och 19 kg/ha/år. Positiva sidoeffekter som tillkommer vid brukandet av denna typ av blandbestånd är ökat frostskydd och förhöjd stormtålighet för gran. Resultaten från denna studie skulle kunna utgöra en idé och inspirera till vidare forskning om hur blandskogar av denna typ kan anläggas och skötas

Vändpunkter - Viktiga faktorer i förändringen mot ett liv utan droger och kriminalitet

We have made a qualitative study that started from interviewees with substance abuse problems. All of the interviewees have a background as criminals and addicts and three of them have participated in twelve-step program. There is treatment that is intended to support and help addicts, but it's still not all that manage to get out of their addiction. That makes it important and interesting to find out what is causing this. Our purpose of this study was to investigate witch factors were important for recovering addicts to change their lives by turning points and how it has created a new identity-role. Suppose has also been to examine how they kept their new identity- role. We have used Erving Goffman's theatrical metaphor “The Presentation of Self in Everyday Life” to demonstrate the importance of us as individuals create us a role that becomes our identity and how it interacts with the environment. We have also used” Empowerment” to show the importance of getting help for self-help during treatment. It has become clear from the knowledge gained by the study, that our interviewees gone through a process of change as a turning point in life, a near-death experience. Through it, they have realized that life does not last forever and they have then understood attendant change was the only way out of addiction and the beginning of a new life.Sammanfattning Vi har gjort en kvalitativ studie och intervjuat individer med en tidigare missbruksproblematik och kriminellbakgrund. Alla utom en av intervjupersonerna har deltagit i ett 12-stegsprogram. Det finns hjälp att få som missbrukare genom behandling, men det är ändå inte alla som klarar av att sluta fast den hjälpen finns. Det är viktigt och intressant att undersöka varför det är så. Vårt syfte med studien har varit att undersöka vilka faktorer som ligger bakom tillfrisknandet för före detta missbrukare. Hur de lyckats förändra sina liv och skapa sig en ny identitet, roll och hur de klarat av att bibehålla den. Vi har utgått från Helen Rose Fuchs Ebaugh för att förklara den förändringsprocess våra intervjupersoner gått igenom, då de kommit till en vändpunkt i livet som har varit avgörande för deras framtid. De teorier vi använt är Erving Goffmans teatermetafår för att lyfta fram hur vi människor antar en identitet, en roll och använder oss av den då vi interagerar med vår omgivning. Empowerment valde vi för att mycket av den behandling som ges idag bygger på hjälp till självhjälp. Viktiga slutsatser vi kommit fram till är att våra intervjupersoner har genom en smärtsam upplevelse kommit till insikt att de måste förändra sig. Det har stått mellan liv och död och de har då kommit till en vändpunkt som varit nödvändig, för att de skulle gå igenom en förändringsprocess och anta en ny identitet, roll. Vi har även kommit fram till de faktorer som gör att en individ lyckas att behålla en ny identitet, roll och det genom markant förändra sitt liv i många skeenden

Estimating and modelling cure in population-based cancer studies within the framework of flexible parametric survival models

<p>Abstract</p> <p>Background</p> <p>When the mortality among a cancer patient group returns to the same level as in the general population, that is, the patients no longer experience excess mortality, the patients still alive are considered "statistically cured". Cure models can be used to estimate the cure proportion as well as the survival function of the "uncured". One limitation of parametric cure models is that the functional form of the survival of the "uncured" has to be specified. It can sometimes be hard to find a survival function flexible enough to fit the observed data, for example, when there is high excess hazard within a few months from diagnosis, which is common among older age groups. This has led to the exclusion of older age groups in population-based cancer studies using cure models.</p> <p>Methods</p> <p>Here we have extended the flexible parametric survival model to incorporate cure as a special case to estimate the cure proportion and the survival of the "uncured". Flexible parametric survival models use splines to model the underlying hazard function, and therefore no parametric distribution has to be specified.</p> <p>Results</p> <p>We have compared the fit from standard cure models to our flexible cure model, using data on colon cancer patients in Finland. This new method gives similar results to a standard cure model, when it is reliable, and better fit when the standard cure model gives biased estimates.</p> <p>Conclusions</p> <p>Cure models within the framework of flexible parametric models enables cure modelling when standard models give biased estimates. These flexible cure models enable inclusion of older age groups and can give stage-specific estimates, which is not always possible from parametric cure models.</p

The Effect of Optical Properties on Secchi Depth and Implications for Eutrophication Management

Successful management of coastal environments requires reliable monitoring methods and indicators. Besides Chlorophyll-a concentration (Chl-a), water transparency measured as Secchi Depth (ZSD) is widely used in Baltic Sea management for water quality assessment as eutrophication indicator. However, in many coastal waters not only phytoplankton but also colored dissolved organic matter (CDOM) and suspended particulate matter (SPM) influence the under-water light field, and therefore the ZSD. In this study all three main optical variables (CDOM, Chl-a, and SPM [organic and inorganic]) as well as ZSD were measured in three Swedish regions: the Bothnian Sea, the Baltic Proper, and the Skagerrak in 2010–2014. Regional multiple regressions with Chl-a, CDOM, and inorganic SPM as predictors explained the variations in ZSD well (Radj2 = 0.53–0.84). Commonality analyses of the regressions indicated considerable differences between regions regarding the contribution of each factor to the variance, Radj2, in ZSD. CDOM explained most of the variance in the Bothnian Sea and the Skagerrak; in general, Chl-a contributed only modestly to the ZSD variance. In the Baltic Proper the largest contribution was from the interaction of all three variables. As expected, the link between Chl-a and ZSD was much weaker in the Bothnian Sea with high CDOM absorption and SPM concentration. When applying the Swedish EU Water Framework Directive threshold for Good/Moderate Chl-a status in the models it was shown that ZSD is neither a sufficient indicator for eutrophication, nor for changes in Chl-a. Natural coastal gradients in CDOM and SPM influence the reference conditions for ZSD and other eutrophication indicators, such as the depth distribution of macro-algae. Hence, setting targets for these indicators based on reference Chl-a concentrations and simple Chl-a to ZSD relationships might in some cases be inappropriate and misleading due to overestimation of water transparency under natural conditions

Environmental variation mediates the evolution of anticipatory parental effects

Theory maintains that when future environment is predictable, parents should adjust the phenotype of their offspring to match the anticipated environment. The plausibility of positive anticipatory parental effects is hotly debated and the experimental evidence for the evolution of such effects is currently lacking. We experimentally investigated the evolution of anticipatory maternal effects in a range of environments that differ drastically in how predictable they are. Populations of the nematode Caenorhabditis remanei, adapted to 20°C, were exposed to a novel temperature (25°C) for 30 generations with either positive or zero correlation between parent and offspring environment. We found that populations evolving in novel environments that were predictable across generations evolved a positive anticipatory maternal effect, because they required maternal exposure to 25°C to achieve maximum reproduction in that temperature. In contrast, populations evolving under zero environmental correlation had lost this anticipatory maternal effect. Similar but weaker patterns were found if instead rate-sensitive population growth was used as a fitness measure. These findings demonstrate that anticipatory parental effects evolve in response to environmental change so that ill-fitting parental effects can be rapidly lost. Evolution of positive anticipatory parental effects can aid population viability in rapidly changing but predictable environments

A multi-state model incorporating estimation of excess hazards and multiple time scales

As cancer patient survival improves, late effects from treatment are becoming the next clinical challenge. Chemotherapy and radiotherapy, for example, potentially increase the risk of both morbidity and mortality from second malignancies and cardiovascular disease. To provide clinically relevant population-level measures of late effects, it is of importance to (1) simultaneously estimate the risks of both morbidity and mortality, (2) partition these risks into the component expected in the absence of cancer and the component due to the cancer and its treatment, and (3) incorporate the multiple time scales of attained age, calendar time, and time since diagnosis. Multi-state models provide a framework for simultaneously studying morbidity and mortality, but do not solve the problem of partitioning the risks. However, this partitioning can be achieved by applying a relative survival framework, by allowing is to directly quantify the excess risk. This paper proposes a combination of these two frameworks, providing one approach to address (1)-(3). Using recently developed methods in multi-state modeling, we incorporate estimation of excess hazards into a multi-state model. Both intermediate and absorbing state risks can be partitioned and different transitions are allowed to have different and/or multiple time scales. We illustrate our approach using data on Hodgkin lymphoma patients and excess risk of diseases of the circulatory system, and provide user-friendly Stata software with accompanying example code