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Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time.Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender.Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers.Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.

Spatial and temporal synchrony in abundance or survival trends can be indicative of whether populations are affected by common environmental drivers. In Atlantic salmon (Salmo salar L.), return rates to natal rivers have generally been assumed to be affected primarily by shared oceanic conditions, leading to spatially synchronous trends in mortality. Here, we investigated the existence of parallel trends in salmon sea survival, using data on migrating smolts and returning adults from seven Canadian populations presumed to share feeding grounds. We analysed sea survival, using a Bayesian change-point model capable of detecting non-stationarity in time series data. Our results indicate that while salmon have experienced broadly comparable patterns in survival, finer-scale temporal shifts are not synchronous among populations. Our findings are not consistent with the hypothesis that salmon populations consistently share the same mortality-related stressors in the marine environment. Although populations may have shared greater synchrony in survival patterns in the past, this synchrony may be breaking down. It may be prudent to direct greater attention to smaller-scale regional and population-level correlates of survival. peerReviewed

We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1lp.S78G mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cybp.D254N), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1lp.S78G tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dynamics. In Rhodobacter cytochrome bc1 complex the equivalent substitution causes a kinetics defect with longer occupancy of RISP head domain towards the quinol oxidation site. These findings represent a unique case of spontaneous mitonuclear epistasis and highlight the role of mtDNA variation as modifier of mitochondrial disease phenotypes., A difference in the survival of respiratory chain complex III deficient Bcs1lp.S78G mice was observed between two congenic mouse strains. Here the authors show how in one of the strains the combined effects of a spontaneously arising non-pathogenic variant and the disease-causing Bcs1lp.S78G mutation exacerbate CIII deficiency and disease progression.

This retrospective population-based study examined the impact of age and comorbidity burden on multimodal management and survival from colorectal cancer (CRC). From 2000 to 2015, 1479 consecutive patients, who underwent surgical resection for CRC, were reviewed for age-adjusted Charlson comorbidity index (ACCI) including 19 well-defined weighted comorbidities. The impact of ACCI on multimodal management and survival was compared between low (score 0–2), intermediate (score 3) and high ACCI (score ≥ 4) groups. Changes in treatment from 2000 to 2015 were seen next to a major increase of laparoscopic surgery, increased use of adjuvant chemotherapy and an intensified treatment of metastatic disease. Patients with a high ACCI score were, by definition, older and had higher comorbidity. Major elective and emergency resections for colon carcinoma were evenly performed between the ACCI groups, as were laparoscopic and open resections. (Chemo)radiotherapy for rectal carcinoma was less frequently used, and a higher rate of local excisions, and consequently lower rate of major elective resections, was performed in the high ACCI group. Adjuvant chemotherapy and metastasectomy were less frequently used in the ACCI high group. Overall and cancer-specific survival from stage I-III CRC remained stable over time, but survival from stage IV improved. However, the 5-year overall survival from stage I–IV colon and rectal carcinoma was worse in the high ACCI group compared to the low ACCI group. Five-year cancer-specific and disease-free survival rates did not differ significantly by the ACCI. Cox proportional hazard analysis showed that high ACCI was an independent predictor of poor overall survival (p &lt, 0.001). Our results show that despite improvements in multimodal management over time, old age and high comorbidity burden affect the use of adjuvant chemotherapy, preoperative (chemo)radiotherapy and management of metastatic disease, and worsen overall survival from CRC.

Muscle wasting, i.e., cachexia, frequently occurs in cancer and associates with poor prognosis and increased morbidity and mortality. Anticancer treatments have also been shown to contribute to sustainment or exacerbation of cachexia, thus affecting quality of life and overall survival in cancer patients. Pre-clinical studies have shown that blocking activin receptor type 2 (ACVR2) or its ligands and their downstream signaling can preserve muscle mass in rodents bearing experimental cancers, as well as in chemotherapy-treated animals. In tumor-bearing mice, the prevention of skeletal and respiratory muscle wasting was also associated with improved survival. However, the definitive proof that improved survival directly results from muscle preservation following blockade of ACVR2 signaling is still lacking, especially considering that concurrent beneficial effects in organs other than skeletal muscle have also been described in the presence of cancer or following chemotherapy treatments paired with counteraction of ACVR2 signaling. Hence, here, we aim to provide an up-to-date literature review on the multifaceted anti-cachectic effects of ACVR2 blockade in preclinical models of cancer, as well as in combination with anticancer treatments.

We analyzed the variability in vendace population parameters in the context of a life table. Parameters related to growth, fecundity and survival were estimated for post-recruitment (age > 1 growing season) life stages of Lake Southern Konnevesi vendace in both very high and low population abundance regimes. Pre-recruitment survival producing population stability was then determined. We found a very strong compensatory density dependence in growth, fecundity and survival: during low abundance, a lifetime reproductive output of a female was almost 20 times that of the abundant regime. To maintain the low abundance regime, pre-recruitment survival must counterbalance it by decreasing to a very low level. Potential drivers of high variability in pre-recruit survival and potential for depensation, Allee effect, are discussed, as well as the implications of the results on fisheries management and risk of extinction due to anthropogenic stressors such as global warming or extensive predator stocking. peerReviewed

Background We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated. Methods The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. Results Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5–3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). Conclusions In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.

The effects of multiple stressors are difficult to separate in field studies, and their interactions may be hard to predict if studied in isolation. We studied the effects of decreasing food quality (increase in cyanobacteria from 5 to 95% simulating eutrophication), temperature increase (by 3 °C), and microplastic exposure (1% of the diet) on survival, size, reproduction, and fatty acid composition of the model freshwater cladoceran Daphnia magna. We found that food quality was the major driver of Daphnia responses. When the amount of cyanobacteria increased from 5 to 95% of the diet, there was a drastic decrease in Daphnia survival (from 81 ± 15% to 24 ± 21%), juvenile size (from 1.8 ± 0.2 mm to 1.0 ± 0.1 mm), adult size (from 2.7 ± 0.1 mm to 1.1 ± 0.1 mm), and reproduction (from 13 ± 5 neonates per surviving adult to 0), but the decrease was not always linear. This was most likely due to lower availability of lipids, eicosapentaenoic acid (EPA), and sterols from the diet. Microplastic exposure did not affect Daphnia survival, size, or reproduction. Food quality had an interactive effect with temperature on fatty acid content of Daphnia. Total fatty acid content of Daphnia was almost 2-fold higher at 20 °C than at 23 °C when fed 50% cyanobacteria. This may have implications for higher trophic level consumers, such as fish, that depend on zooplankton for energy and essential lipids. Our findings suggest that as proportions of cyanobacteria increase, in tandem with water temperatures due to climate change, fish may encounter fewer and smaller Daphnia with lower lipid and EPA content. peerReviewed

Experimental studies have shown that overexpression of Rap guanine nucleotide exchange factor 1 (C3G) plays pro‐survival and anti‐apoptotic roles through molecule phosphorylated extracellular signal‐regulated kinase1/2 (p‐ERK1/2) in cardiomyocytes. However, it is still unclear if silencing of C3G may increase cell survival inhibition and apoptosis in cardiomyocytes, and whether C3G silence induced injuries are reduced by the overexpression of C3G through regulation of p‐ERK1/2 and pro‐apoptotic molecule Bax. In this study, the rat‐derived H9C2 cardiomyocytes were infected with C3G small hairpin RNA interference recombinant lentiviruses, which silenced the endogenous C3G expression in the cardiomyocytes. Then, contrary experiments were conducted using C3G overexpression. The cell proliferation and apoptosis were analyzed in the cardiomyocytes which were treated with or without hypoxia/reoxygenation (H/R). Silencing of C3G leaded to significant increase in cell survival inhibition and apoptosis, combined with aggravated the injuries induced by H/R. Overexpression of C3G reduced the injuries induced by the silencing of C3G in the cardiomyocytes via regulation of p‐ERK1/2 and Bax. In conclusion, our results provide new experimental evidence that silencing of C3G can increase cell survival inhibition and apoptosis in cardiomyocytes via regulation of p‐ERK1/2 and Bax. peerReviewed

Kirja-arvostelu teoksesta Primo Levi: Aselepo. Suom. Irma Koistinen, italiankielinen I painos 1963, Like 2019, 213 s. nonPeerReviewed

Intergenerational fitness effects on offspring due to the early life of the parent are well studied from the standpoint of the maternal environment, but intergenerational effects owing to the paternal early life environment are often overlooked. Nonetheless, recent laboratory studies in mammals and ecologically relevant studies in invertebrates predict that paternal effects can have a major impact on the offspring's phenotype. These non‐genetic, environment‐dependent paternal effects provide a mechanism for fathers to transmit environmental information to their offspring, and could allow rapid adaptation. We used the bank vole Myodes glareolus, a wild rodent species with no paternal care, to test the hypothesis that a high population density environment in the early life of fathers can affect traits associated with offspring fitness. We show that the protein content in the diet and/or social environment experienced during the father's early life (prenatal and weaning) influence the phenotype and survival of his offspring and may indicate adaptation to density‐dependent costs. Furthermore, we show that experiencing multiple environmental factors during the paternal early life can lead to a different outcome on the offspring phenotype than stimulated by experience of a single environmental factor, highlighting the need to study developmental experiences in tandem rather than independent of each other. peerReviewed

1.Parasitic diseases represent one of the greatest challenges for aquaculture worldwide and there is an increasing emphasis on ecological solutions to prevent infections. One proposed solution is enriched rearing, where traditional stimulus‐poor rearing tanks are equipped with different types of structures to increase habitat complexity. Such spatial enrichment is known to increase survival of fish during parasite epidemics, but the underlying mechanisms are still unclear. 2.We studied whether enriched rearing affected infection of an important fish pathogen Flavobacterium columnare in young Atlantic salmon (Salmo salar) and sea‐migrating brown trout (Salmo trutta). First, we used natural bacterial exposures and multiple fish populations in a common garden experiment to address the role of host genetic background in effects of enriched rearing. Second, fish from standard and enriched rearing were experimentally exposed to controlled bacterial doses in standard and enriched environments in a full factorial design to explore the relative roles of rearing background and environment of exposure on survival of fish. 3.Enriched rearing significantly increased survival of fish during the natural bacterial outbreak. This effect was also fairly consistent and observed in eight of the ten fish populations. In the controlled exposure, fish exposed in enriched environment had higher survival regardless of their rearing background, suggesting a stronger impact of the environment on the disease progression. Additionally, the survival in the enriched environment was the highest among the fish of enriched rearing background, supporting the idea of their higher resistance. 4.Synthesis and applications. Our study suggests that the enhanced survival of fish in enriched rearing is a result of a combined effect of the environment and improved fish condition and, to a lesser degree, from host genetic background. This has important implications for when and how environmental enrichment should be applied. Overall, these results indicate that environmental enrichment has the potential to improve survival of fish during parasitic epidemics and thus reduce use of antibiotics in aquaculture. peerReviewed

Many boreal rodents are territorial during the breeding season but during winter become social and aggregate for more energy efficient thermoregulation. Communal winter nesting and social interactions are considered to play an important role for the winter survival of these species, yet the topic is relatively little explored. Females are suggested to be the initiators of winter aggregations and sometimes reported to survive better than males. This could be due to the higher social tolerance observed in overwintering females than males. Hormonal status could also affect winter behavior and survival. For instance, chronic stress can have a negative effect on survival, whereas high gonadal hormone levels, such as testosterone, often induce aggressive behavior. To test if the winter survival of females in a boreal rodent is better than that of males, and to assess the role of females in the winter aggregations, we generated bank vole (Myodes glareolus) populations of three different sex ratios (male-biased, female-biased and even density) under semi-natural conditions. We monitored survival, spatial behavior and hormonal status (stress and testosterone) during two winter months. We observed no significant differences in survival between the sexes or among populations with differing sex-ratios. The degree of movement area overlap was used as an indicator of social tolerance and potential communal nesting. Individuals in male biased populations showed a tendency to be solitary, whereas in female biased populations there was an indication of winter aggregation. Females living in male-biased populations had higher stress levels than the females from the other populations. The female-biased sex-ratio induced winter breeding and elevated testosterone levels in males. Thus, our results suggest that the sex-ratio of the overwintering population can lead to divergent overwintering strategies in bank voles. peerReviewed

Recent studies of honeybees and bumblebees have examined combinatory effects of different stressors, as insect pollinators are naturally exposed to multiple stressors. At the same time the potential influences of simultaneously occurring agricultural agents on insect pollinator health remain largely unknown. Due to different farming methods, and the drift of applied agents and manure, pollinators are most probably exposed to insecticides but also bacteria from organic fertilizers at the same time. We orally exposed honeybee workers to sub-lethal doses of the insecticide thiacloprid and two strains of the bacterium Enterococcus faecalis, which can occur in manure from farming animals. Our results show that under laboratory conditions the bees simultaneously exposed to the a bacterium and the pesticide thiacloprid thiacloprid had significant higher survival rates 11 days post exposure than the controls, which surprisingly showed the lowest survival. Bees that were exposed to diet containing thiacloprid showed decreased food intake. General antibacterial activity is increased by the insecticide and the bacteria, resulting in a higher immune response observed in treated individuals compared to control individuals. We thus propose that caloric restriction through behavioural and physiological adaptations may have mediated an improved survival and stress resistance in our tests. However, the decreased food consumption could in long-term also result in possible negative effects at colony level. Our study does not show an additive negative impact of sub-lethal insecticide and bacteria doses, when tested under laboratory conditions. In contrast, we report seemingly beneficial effects of simultaneous exposure of bees to agricultural agents, which might demonstrate a surprising biological capacity for coping with stressors, possibly through hormetic regulation.

Stocking with eggs has been widely used as a management measure to support degraded salmonid stocks. In Finland, Atlantic salmon and both sea-migrating and lake-migrating brown trout are stocked as eggs, alevins, fry, parr, and smolt, whereas trout are also stocked as mature fish. The aim of this stocking is to improve catches and to support collapsed spawning stocks. We assessed the success of stocking with brown trout eggs in a study of 17 Finnish boreal forest rivers, of which 9 were subject to egg stocking. All rivers contained some naturally spawning trout. In 16 rivers, including non-stocking years and unstocked rivers, egg stocking did not increase the total (wild and stocked) density of 0-year-old parr. However, those rivers with higher existing trout densities in non-stocking years seemed to benefit most from stocking, suggesting some role of river-specific extrinsic factors affecting egg-to-parr survival. In one river monitored for 14 years, only a weak correlation was found between the total density of 0-year-old parr and the number of eggs stocked. However, in nine parr samples from five rivers, the mean proportion of parr derived from stocked eggs was 40%. The mean survival to first autumn parr of egg-stocked and wild individuals was 1.0 and 3.3%, respectively. Probable reasons for the detected low to moderate impact of egg-stocking are (i) large variation in total parr density between years and rivers, (ii) small number of stocked eggs, (iii) placing egg boxes and egg pockets in unsuitable microhabitats, and (iv) unsuitable emergence time of egg-stocked individuals, or other extrinsic factors creating extra mortality. We recommend field and laboratory experiments to improve and standardize stocking methods, and monitoring the connection of wild spawning stocks and parr recruitment. Finally, we encourage fishery authorities to create clear management goals for threatened wild salmonid stocks.

In this thesis, two bucephalid trematode parasites Rhipidocotyle campanula and R. fennica, which use the same first (Anodonta anatina) and second intermediate (Rutilus rutilus) host were studied. The aim was to investigate the effect of temperature on one of the key processes in the transmission of these parasites: 1) the emergence of cercarial larvae from A. anatina over short (1 h) and 2) long (throughout the annual cercarial shedding period, from May to October) time periods as well, as on 3) mussel survival and 4) the seasonal timing of cercarial release. In addition, the aim was to study how the cercarial shedding traits are linked to the 5) geographical occurrence and abundance of the Rhipidocotyle species. In the experimental studies, the cercarial emergence by R. fennica increased significantly with increasing temperature over short and long time periods, while that by R. campanula was unaffected by temperature. R. campanula clearly started seasonal cercarial release earlier and at a lower temperature than R. fennica. Survival of mussels, especially cercariae-shedding mussels, was lower at higher temperature, and the shedding of R. campanula cercariae was associated with higher mussel mortality than the shedding of R. fennica. The average duration of the seasonal cercarial release period of both species was unaffected by temperature at the individual host level, but at the host population level the cercarial shedding period of R. fennica (but not of R. campanula) was longer at higher temperature. The field study showed that the occurrence, mean prevalence and abundance of R. fennica – in accordance with the experimentally observed association of cercarial release with high temperature – decreased from the south (61–64 °N) to the low north (65–66 °N), but this pattern was not detected in R. campanula.

Only abstract. Paper copies of master’s theses are listed in the Helka database (http://www.helsinki.fi/helka). Electronic copies of master’s theses are either available as open access or only on thesis terminals in the Helsinki University Library. Vain tiivistelmä. Sidottujen gradujen saatavuuden voit tarkistaa Helka-tietokannasta (http://www.helsinki.fi/helka). Digitaaliset gradut voivat olla luettavissa avoimesti verkossa tai rajoitetusti kirjaston opinnäytekioskeilla. Endast sammandrag. Inbundna avhandlingar kan sökas i Helka-databasen (http://www.helsinki.fi/helka). Elektroniska kopior av avhandlingar finns antingen öppet på nätet eller endast tillgängliga i bibliotekets avhandlingsterminaler. With increasing number of subsequent primary cancers there is a growing concern to know how cancer patients survive with their subsequent cancer compared to those with their respective first cancer. Results of earlier studies have been conflicting and have not lead to firm conclusions. One reason for conflicting results might be a lack appropriate methodology as survival from subsequent cancer has usually not been adjusted for an extra hazard due to an underlying first cancer. This study presents four alternative models for estimating survival of patients with multiple cancers. Models are extensions and modifications to those proposed earlier for estimating relative and cause-specific survival of patients with a single cancer. The assessment of survival from subsequent cancer raised a need for introducing new concepts, especially when survival of patients with their multiple cancers of the same site is concerned. Survival estimates from cancer are compared between the models, and between a first and subsequent tumour of the same site. The importance of adjusting survival from subsequent cancer to that from a underlying first cancer is also highlighted. The results show that survival from cancer as a first and subsequent tumour can be reliably assessed with the newly introduced models based either on the relative and cause-specific survival. The results also show that survival from cancer as a first and subsequent tumour may be dependent on the site of cancer and whether patients' cancers are of the same site or not. Nevertheless, survival from a subsequent cancer is not usually different from that from a respective first cancer. However, even with large population-based data, a lack of power often prevents the detection of modest differences in survival. MONISYÖPÄPOTILAIDEN ELINAIKAENNUSTEET TAUSTA Yhä useammalla syöpäpotilaalla on diagnosoitu kaksi tai useampia primaarisyöpiä. Näiden monisyöpäpotilaiden joukko kasvaa, koska useimpien syöpäpotilaiden elinaikaennusteet ovat parantuneet ja odotettavissa oleva elinikä on pidentynyt. Tämän potilasjoukon kasvaessa on yhä kiinnostavampaa tietää, kuinka monisyöpäpotilaat selviytyvät uudesta primaarisyövästään verrattuna niihin potilaihin, jotka sairastavat samaa syöpää ensimmäisenä syöpänään. Aiheesta tehtyjen aikaisempien tutkimusten tulokset ovat olleet ristiriitaisia. Ristiriitaisten tulosten taustalla saattaa olla käytettyjen analyysimenetelmien heikkous: Seuraajasyöpään liittyvää elinaikaennustetta arvioitaessa ei ole huomioitu taustalla olevan ensimmäisen syövän vaikutusta kuolleisuuteen. TAVOITE: MONISYÖPÄPOTILAIDEN ELINAIKAENNUSTEET MAHDOLLIKSI Väitöskirjassa esitellään neljä vaihtoehtoista tilastollista mallia, joilla monisyöpäpotilaiden eloonjäämistä voidaan arvioida ensimmäisen ja seuraajasyövän osalta. Uudet vaihtoehdot ovat laajennuksia ja mukaelmia malleista, joita käytetään arvioitaessa syöpäpotilaiden suhteellista (relative) ja syykohtaista (cause-specific) eloonjäämistä. Eloonjäämistä vertaillaan mallien välillä sekä saman syövän suhteen ensimmäisenä ja seuraajasyöpänä. Toiseen syöpään liittyvän eloonjäämisen arvioiminen loi tarpeen luoda uusia käsitteitä, erityisesti kun kyse oli kahdesti samaan primaarisyöpään sairastuneista monisyöpäpotilaista: On pystyttävä arvioimaan eloon-jäämistä esim. rintasyövän suhteen sekä ensimmäisenä että seuraajasyöpänä. TULOKSET JA JOHTOPÄÄTÖKSET Eloonjäämistä ensimmäisen ja seuraajasyövän suhteen voidaan arvioida uusilla suhteelliseen ja syykohtaiseen eloonjäämiseen perustuvilla malleilla. Seuraajasyöpään liittyvää eloonjäämistä ei tulisi arvioida, jollei taustalla olevaan ensimmäiseen syöpään liittyvää kuolleisuutta ole otettu huomioon. Eloonjäämisennusteisiin ensimmäisen ja seuraajasyövän suhteen vaikuttavat mm. syövän sijainti ja se, onko monisyöpäpotilaalla kaksi samaa primaarisyöpää vai ei. Useimmiten eloonjäämisennusteet eivät eroa ensimmäisen ja seuraajasyövän välillä. Voimakkaiden päätelmien teko on edelleen vaikeaa, sillä käytettävissä olevat väestöpohjaisetkin aineistot ovat toistaiseksi varsin suppeita.

There are two competing hypotheses explaining how innovativeness influences the survival of startups: On the one hand, innovativeness is argued to foster survival-enhancing attributes (e.g., market power and cost efficiency) and capabilities (e.g., absorptive capacity). On the other hand, an innovative startup faces (and bears the associated risks of) liabilities of newness and smallness that exceed those of its non-innovative counterparts. The available empirical literature addressing this theoretical tension mostly supports the former hypothesis; we suggest that this finding is, in part, driven by the common practice of employing an ex post measure that already embodies a degree of success in innovativeness. We use an ex ante measure and find that a startup's innovativeness is negatively associated with its subsequent survival. We also find that entrepreneurs' greater appetite for risk magnifies this negative association. These findings imply that pursuing innovations is not necessarily associated with survival during the early stages of firm development and entails a more complicated start-up process. peerReviewed