Browsing by Subject "PERSISTENCE"

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  • Rapo-Pylkkö, Susanna; Haanpää, Maija; Liira, Helena (2017)
    Background: Chronic, mostly musculoskeletal pain is common among older adults. Little is known about the prognosis of chronic pain and the neuropathic pain qualities in older adults. We studied a cohort of community-dwelling older adults, clinically assessed their pain states, classified their type of pain (nociceptive, neuropathic or combined) and followed them up for a year. Methods: At baseline, a geriatrician clinically examined all study patients and classified their type of pain in collaboration with a pain specialist. Pain, quality of life and mental health were measured by questionnaires (BPI, GDS-15, BAI and SF-36) and reassessed after 1 year. Results: Despite chronic pain, all patients from the baseline cohort continued to live independently at 1 year. A total of 92 of 106 (87%) patients returned the follow-up questionnaire. Nociceptive pain on its own was present in 48 patients, whereas 44 patients also had neuropathic pain. Most patients (96%) had several pain states at baseline, and 13 patients reported a new pain state at follow-up. On average, there were no significant changes in the pain intensity, pain interference, mood or quality of life in either group between baseline and follow-up. Changes in pain were observed at the individual level, and both intensity and interference of pain at the follow-up had a negative correlation with the baseline value. Conclusions: On average, chronic pain was persistent in our patients, but they were able to live independently despite their pain. At the individual level, both relief and exacerbation of pain were observed, supporting the notion that pain is not inevitable and unremitting among older adults.
  • MASK Grp; Menditto, Enrica; Costa, Elisio; Midao, Luis; Haahtela, Tari; Toppila-Salmi, S.; Kuitunen, M.; Valovirta, E. (2019)
    Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC = 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
  • Hokynar, K.; Korhonen, Suvi; Norja, P.; Paavonen, J.; Puolakkainen, M. (2017)
    We studied whether antibody to two chlamydial proteins (TroA and HtrA) could be used as biomarkers of Chlamydia trachomatis infection. Methods: Recombinant proteins C. trachomatis TroA and HtrA were used as antigens in enzyme immunoassay (EIA). Both IgG and IgA antibody responses were studied. Results: IgG or IgA antibody to either protein was infrequently detected in sera from healthy blood donors or virgin girls. Patients attending the STI Clinic and patients with perihepatitis had often IgG antibody against TroA (25 and 50 % respectively) and HtrA (21 and 38 % respectively). Especially in sera from patients with chlamydial perihepatitis, the A(450nm) values with TroA were high (mean 1.591). A positive correlation between C. trachomatis MIF antibody and TroA (r = 0.7) as well as HtrA (r = 0.5) antibody was observed in sera from STI clinic patients and perihepatitis patients. Individuals with C. trachomatis infection and positive serology already when seeking medical attention had higher A(450nm) values for TroA (0.638) and HtrA (0.836) than patients with no marker of previous exposure or with no infection (0.208 and 0.234 respectively). Diagnosis of genital C. trachomatis infection is often NAAT-based, whereas serology has little value in testing for uncomplicated genital C. trachomatis infection. TroA and HtrA antibodies are potential biomarkers for evaluation of ascending and repeated C. trachomatis infection.
  • Honkamäki, Jasmin; Piirilä, Päivi; Hisinger-Mölkänen, Hanna; Tuomisto, Leena E.; Andersen, Heidi; Huhtala, Heini; Sovijärvi, Anssi; Lindqvist, Ari; Backman, Helena; Lundbäck, Bo; Rönmark, Eva; Lehtimäki, Lauri; Pallasaho, Paula; Ilmarinen, Pinja; Kankaanranta, Hannu (2021)
    BACKGROUND: Child-onset asthma is known to remit with high probability, but remission in adult-onset asthma is seem-ingly less frequent. Reports of the association between remission and asthma age of onset up to late adulthood are scarce. OBJECTIVE: To evaluate the association between asthma remission, age at diagnosis and gender, and assess risk factors of nonremission. METHODS: In 2016, a random sample of 16,000 subjects aged 20 to 69 years from Helsinki and Western Finland were sent a FinEsS questionnaire. Physician-diagnosed asthma was catego-rized by age at diagnosis to early-(0-11 years), intermediate-(12-39 years), and late-diagnosed (40-69 years) asthma. Asthma remission was defined by not having had asthma symptoms and not having used asthma medication in the past 12 months. RESULTS: Totally, 8199 (51.5%) responded, and 879 reported physician-diagnosed asthma. Remission was most common in early-diagnosed (30.2%), followed by intermediate-diagnosed (17.9%), and least common in late-diagnosed asthma (5.0%) (P < .001), and the median times from diagnosis were 27, 18.5, and 10 years, respectively. In males, the corresponding remission rates were 36.7%, 20.0%, and 3.4%, and in females, 20.4%, 16.6%, and 5.9% (gender difference P < .001). In multivariable binary logistic regression analysis, signifi-cant risk factors of asthma nonremission were intermediate (odds ratio [OR] = 2.15, 95% confidence interval: 1.373.36) and late diagnosis (OR = 11.06, 4.82-25.37) compared with early diagnosis, chronic obstructive pulmonary disease (COPD) (OR = 5.56, 1.26-24.49), allergic rhinitis (OR = 2.28, 1.50-3.46), and family history of asthma (OR = 1.86, 1.22-2.85). Results were similar after excluding COPD. CONCLUSION: Remission was rare in adults diagnosed with asthma after age 40 years in both genders. Late-diagnosed asthma was the most significant independent risk factor for nonremission. (C) 2020 American Academy of Allergy, Asthma & Immunology
  • Toppinen, M.; Perdomo, Maria; Palo, J. U.; Simmonds, P.; Lycett, S. J.; Soderlund-Venermo, M.; Sajantila, A.; Hedman, K. (2015)
    DNA in human skeletal remains represents an important historical source of host genomic information and potentially of infecting viruses. However, little is known about viral persistence in bone. We searched ca. 70-year-old long bones of putative Finnish casualties from World War II for parvovirus B19 (B19V) DNA, and found a remarkable prevalence of 45%. The viral sequences were exclusively of genotypes 2 (n = 41), which disappeared from circulation in 1970's, or genotype 3 (n = 2), which has never been reported in Northern Europe. Based on mitochondrial and Y-chromosome profiling, the two individuals carrying B19V genotype 3 were likely from the Soviet Red Army. The most recent common ancestor for all genotypes was estimated at early 1800s. This work demonstrates the forms of B19V that circulated in the first half of the 20th century and provides the first evidence of the suitability of bone for exploration of DNA viruses.
  • Landberg, Niklas; von Palffy, Sofia; Askmyr, Maria; Lilljebjorn, Henrik; Sanden, Carl; Rissler, Marianne; Mustjoki, Satu; Hjorth-Hansen, Henrik; Richter, Johan; Agerstam, Helena; Jaras, Marcus; Fioretos, Thoas (2018)
    Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34(+) CD38(low)) and progenitor (CD34(+) CD38(+)) chronic phase CML cells, and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells. Focusing on novel markers with increased expression on primitive CML cells, we confirmed upregulation of the scavenger receptor CD36 and the leptin receptor by flow cytometry. We also delineate a subpopulation of primitive CML cells expressing CD36 that is less sensitive to imatinib treatment. Using CD36 targeting anti-bodies, we show that the CD36 positive cells can be targeted and killed by antibody-dependent cellular cytotoxicity. In summary, CD36 defines a subpopulation of primitive CML cells with decreased imatinib sensitivity that can be effectively targeted and killed using an anti-CD36 anti-body.
  • Väisänen, Elina; Fu, Yu; Koskenmies, Sari; Fyhrquist, Nanna; Wang, Yilin; Keinonen, Anne; Mäkisalo, Heikki; Väkevä, Liisa; Pitkänen, Sari; Ranki, Annamari; Hedman, Klaus; Söderlund-Venermo, Maria (2019)
  • Chen, Tingting; Tanner, Laura; Simell, Ville; Hedman, Lea; Makinen, Marjaana; Sadeghi, Mohammadreza; Veijola, Riitta; Hyoty, Heikki; Ilonen, Jorma; Knip, Mikael; Toppari, Jorma; Simell, Olli; Söderlund-Venermo, Maria; Hedman, Klaus (2014)
  • Ruusuvuori, Johanna; Aaltonen, Tarja; Lonka, Eila; Salmenlinna, Inkeri; Laakso, Minna (2020)
    The quality of interaction between hearing health professionals and patients is one prominent, yet under-studied explanation for the low adherence in acquiring and using a hearing aid. This study describes two different ways of introducing hearing aid to the patients at their first visits at the hearing clinic: an inquiry asking patients opinion followed by offer, and an expert evaluation of the necessity of a hearing aid; and shows two different trajectories ensuing from these introductions. The trajectories represent two extreme ends of a continuum of practices of starting a discussion about hearing aid rehabilitation, in terms of how these practices affect patient participation in decision-making. The analysis shows how granting different degrees of deontic and epistemic rights to professionals and patients has different consequences with regard to the activity of reaching shared understanding on the treatment. The data consist of 17 video-recorded encounters at the hearing clinic. The method used is conversation analysis.
  • Aaltonen, K. J.; Joensuu, J. T.; Pirilä, L.; Kauppi, M.; Uutela, T.; Varjolahti-Lehtinen, T.; Yli-Kerttula, T.; Isomäki, P.; Nordström, D.; Sokka, T. (2017)
    Objective: A systematic review found that an average of 27% of rheumatoid arthritis (RA) patients using tumour necrosis factor (TNF) inhibitors discontinue their treatment within 1year. The aim of this study was to assess drug survival on TNF inhibitors among patients with RA.Methods: Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established to monitor the effectiveness and safety of biologic drugs in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patient's first, second, or third biologic treatment between 2004 and 2014. Follow-up was truncated at 36months. The results of a time-dependent Cox proportional hazards model were reported as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs).Results: Of the 4200 TNF-inhibitor treatment periods identified from ROB-FIN, 3443 periods from 2687 patients met the inclusion criteria. Twenty-seven per cent of the patients discontinued their treatment within 12months. Infliximab (HR 1.8, 95% CI 1.3-2.5) and certolizumab pegol (HR 1.7, 95% CI 1.2-2.3) had lower drug survival compared to golimumab. A similar trend was seen with adalimumab (HR 1.2, 95% CI 0.90-1.7) and etanercept (HR 1.2, 95% CI 0.87-1.6). Concomitant use of methotrexate (MTX) was associated with improved drug survival (HR 0.76, 95% CI 0.64-0.90) in comparison with TNF-inhibitor monotherapy.Conclusions: Golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good as adalimumab and etanercept. Concomitant use of MTX improved drug survival on TNF inhibitors.
  • Asikainen, Henna; Blomster, Jaanika; Virtanen, Viivi (2018)
    Teacher support is an important factor affecting academic and social integration into the university. However, studies have been very scarce concerning both students' and teachers' experiences of their relationship in higher education. The purpose of this study is to examine students' and teachers' experiences of communality and interaction as well as the support given by teachers in the academic community. A total of 68 teachers and 104 students participated in this study by answering both Likert-scale and an open-ended question. The results show wide variation in both students' and teachers' experiences. The experiences varied from descriptions of a good and functional communality to a gap between teachers and students or even hostile behaviour towards students. Five main categories emerged from the data: (1) functioning interaction and communality, (2) good quality contacts between students and teachers, (3) variable experiences of interaction and communality, (4) low quality interaction and communality, and (5) dysfunctional contacts between students and teachers. The results indicate that teachers experience the support given to students more positively than the students. In addition, the results concerning the open-ended question also indicated that teachers experience the communality and interaction between teachers and students more positively than the students. More attention should be given to the teacher-student relationship at the higher education level. In addition, general skills such as ability to interact with others and social behaviour should be emphasised to a greater degree when recruiting staff.
  • Pankakoski, Maiju; Heinavaara, Sirpa; Sarkeala, Tytti; Anttila, Ahti (2017)
    Objective: Regular screening and follow-up is an important key to cervical cancer prevention; however, screening inevitably detects mild or borderline abnormalities that would never progress to a more severe stage. We analysed the cumulative probability and recurrence of cervical abnormalities in the Finnish organized screening programme during a 22-year follow-up. Methods: Screening histories were collected for 364,487 women born between 1950 and 1965. Data consisted of 1 207,017 routine screens and 88,143 follow-up screens between 1991 and 2012. Probabilities of cervical abnormalities by age were estimated using logistic regression and generalized estimating equations methodology. Results: The probability of experiencing any abnormality at least once at ages 30-64 was 34.0% (95% confidence interval [CI]: 33.3-34.6%). Probability was 5.4% (95% CI: 5.0-5.8%) for results warranting referral and 2.2% (95% CI: 2.0-2.4%) for results with histologically confirmed findings. Previous occurrences were associated with an increased risk of detecting new ones, specifically in older women. Conclusion: A considerable proportion of women experience at least one abnormal screening result during their lifetime, and yet very few eventually develop an actual precancerous lesion. Re-evaluation of diagnostic criteria concerning mild abnormalities might improve the balance of harms and benefits of screening. Special monitoring of women with recurrent abnormalities especially at older ages may also be needed.
  • Jaakola, Anna; Roger, Michel; Faucher, Marie-Claude; Syrjanen, Kari; Grenman, Seija; Syrjänen, Stina; Louvanto, Karolina (2021)
    BackroundHuman leukocyte antigen (HLA)-G may have an important role in the natural history of human papillomavirus (HPV) infection. Our aim was to evaluate the role of HLA-G in the outcome of genital and oral HPV infections in women.MethodsAnalyses included 306 women from the Finnish Family HPV-study and were followed-up for six years. Genital and oral samples were tested for 24 different HPV types with multiplex HPV genotyping. HLA-G alleles were determined through direct DNA-sequencing. Unconditional logistic regression was used to determine the associations between HLA-G genotypes and HPV infection outcomes.ResultsTen HLA-G alleles were identified. Most common HLA-G genotypes were the wild type G*01:01:01/01:01:01 (31.3%) followed by G*01:01:01/01:01:02 (26.8%). G*01:01:01/01:01:01 genotype was associated with increased risk of oral HPV infections by any HPV type or single-type with OR=1.86 (95% CI 1.14-3.04, P=0.01) and 2.22 (95% CI 1.14-3.71, P=0.02), respectively. G*04:01+ allele and the G*01:01:01/01:04:01 genotype both protected from any and single oral HPV infections; OR=0.46 (95% CI 0.23-0.89, P=0.02) and 0.53 (95% CI 0.23-0.97, P=0.03), respectively. G*01:01:02/01:04:01 genotype increased significantly the risk of infertility and its treatments, with respective OR=5.06 (95% CI 1.22-21.02, P=0.03) and OR=9.07 (95% CI 1.22-39.50, P=0.03). Both HLA-G alleles and genotypes showed several significant associations with the outcomes of oral HPV infections, but none of them had any impact on the outcomes of genital HPV infections in these women.ConclusionsThe host HLA-G genotypes appear to impact the outcomes of oral HPV infections in women but have little if any effect on genital HPV status or infection outcomes.
  • Koivisto, Karoliina; Puhakka, Laura; Lappalainen, Maija; Blomqvist, Soile; Saxen, Harri; Nieminen, Tea (2017)
    Healthcare workers (HCWs) pose a risk to themselves and their patients if not protected against vaccine preventable diseases. Alarmingly, lacking immunity has been reported in several studies. We assessed the immunity against vaccine-preventable diseases in 157 pediatric HCWs in Helsinki Children's Hospital. The HCWs enrolled answered a questionnaire and gave a serum sample. Antibodies were measured with EIA against MMR-diseases, tetanus and diphtheria toxins, Hepatitis B (HBV), Hepatitis A (HAV), varicella zoster and pertussis toxin. Neutralizing antibodies against poliovirus 1, 2 and 3 were measured. All of the HCWs had antibodies against tetanus and 89.8% against diphtheria. All had measurable levels of polio antibodies to all three polioviruses. 41% had suboptimal levels of antibodies against at least one of the antigens tested: MMR-viruses, diphtheria, HBV or polio. Measles, mumps and rubella antibodies were detectable in 81.5%, 89.2% and 93%, respectively. Only one HCW had no varicella-antibodies. Hepatitis B surface antibodies (HBsAb) were detected in 89.8% of the nurses. 67.5% had HAV-antibodies. A poor correlation between detected antibody levels and reported vaccination history was noticed, indicating a need for a universal record system for registering the vaccines given to each individual. (C) 2017 Elsevier Ltd. All rights reserved.
  • Elbasani, Endrit; Gramolelli, Silvia; Günther, Thomas; Gabaev, Ildar; Grundhoff, Adam; Ojala, Päivi M. (2020)
    The anaphase-promoting complex, or cyclosome (APC/C), is a large E3 ubiquitin ligase composed of 14 subunits. The activity of APC/C oscillates during the cell cycle to ensure a timely transition through each phase by promoting the degradation of important cell cycle regulators. Of the human herpesviruses, cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) both impair the activity of APC/C during their lytic replication cycle through virus-encoded protein kinases. Here, we addressed whether the oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) deregulates the activity of APC/C during the lytic replication cycle. To this end, we used the well-characterized iSLK.219 cell model of KSHV infection and established a new infection model of primary lymphatic endothelial cells (LECs) infected with a lytically replicating KSHV BAC16 mutant. In contrast to those of EBV and HCMV, the KSHV lytic cycle occurs while the APC/C is active. Moreover, interfering with the activity of APC/C did not lead to major changes in the production of infectious virus. We further investigated whether rereplication stress induced by the unscheduled activation of the APC/C-CDH1 complex affects the number and integrity of KSHV viral episomes. Deep sequencing of the viral episomes and host chromosomes in iSLK.219 cells revealed that, while distinct regions in the cellular chromosomes were severely affected by rereplication stress, the integrity of the viral episomes remained unaltered. IMPORTANCE DNA viruses have evolved complex strategies to gain control over the cell cycle. Several of them target APC/C, a key cellular machinery that controls the timely progression of the cell cycle, by either blocking or enhancing its activity. Here, we investigated the activity of APC/C during the lytic replication cycle of KSHV and found that, in contrast to that of KSHV's close relatives EBV and HCMV, KSHV lytic replication occurs while the APC/C is active. Perturbing APC/C activity by depleting a core protein or the adaptor proteins of the catalytic domain, and hence interfering with normal cell-cycle progression, did not affect virus replication. This suggests that KSHV has evolved to replicate independently of the activity of APC/C and in various cell cycle conditions.
  • Schulz, Torsti; Vanhatalo, Jarno; Saastamoinen, Marjo (2019)
    Species distribution models are the tool of choice for large-scale population monitoring, environmental association studies and predictions of range shifts under future environmental conditions. Available data and familiarity of the tools rather than the underlying population dynamics often dictate the choice of specific method - especially for the case of presence-absence data. Yet, for predictive purposes, the relationship between occupancy and abundance embodied in the models should reflect the actual population dynamics of the modelled species. To understand the relationship of occupancy and abundance in a heterogeneous landscape at the scale of local populations, we built a spatio-temporal regression model of populations of the Glanville fritillary butterfly Melitaea cinxia in a Baltic Sea archipelago. Our data comprised nineteen years of habitat surveys and snapshot data of land use in the region. We used variance partitioning to quantify relative contributions of land use, habitat quality and metapopulation covariates. The model revealed a consistent and positive, but noisy relationship between average occupancy and mean abundance in local populations. Patterns of abundance were highly variable across years, with large uncorrelated random variation and strong local population stochasticity. In contrast, the spatio-temporal random effect, habitat quality, population connectivity and patch size explained variation in occupancy, vindicating metapopulation theory as the basis for modelling occupancy patterns in fragmented landscapes. Previous abundance was an important predictor in the occupancy model, which points to a spillover of abundance into occupancy dynamics. While occupancy models can successfully model large-scale population structure and average occupancy, extinction probability estimates for local populations derived from occupancy-only models are overconfident, as extinction risk is dependent on actual, not average, abundance.
  • Kaartinen, Tanja; Luostarinen, Annu; Maliniemi, Pilvi; Keto, Joni; Arvas, Mikko; Belt, Heini; Koponen, Jonna; Loskog, Angelica; Mustjoki, Satu; Porkka, Kimmo; Yla-Herttuala, Seppo; Korhonen, Matti (2017)
    Background. Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype. Methods. Lymphocytes were transduced with third-generation lentiviral vectors and expanded using CD3/CD28 microbeads. The effects of altering the IL-2 supplementation (0-300 IU/mL) and length of expansion (10-20 days) on the phenotype of the T-cell products were analyzed. Results. High IL-2 levels led to a decrease in overall generation of early memory T cells by both decreasing central memory T cells and augmenting effectors. T memory stem cells (T-SCM, CD95(+)CD45RO(-)CD45RA(+)CD27(+)) were present variably during T-cell expansion. However, their presence was not IL-2 dependent but was linked to expansion kinetics. CD19-CART cells generated in these conditions displayed in vitro antileukemic activity. In summary, production of CART cells without any cytokine supplementation yielded the highest proportion of early memory T cells, provided a 10 fold cell expansion and the cells were functionally potent. Discussion. The number of early memory T cells in a T-cell preparation can be increased by simply reducing the amount of IL-2 and limiting the length of T-cell expansion, providing cells with potentially higher in vivo performance. These findings are significant for robust and cost:effective T-cell manufacturing.
  • Ovaskainen, Otso; Somervuo, Panu; Finkelshtein, Dmitri (2021)
    In ecology, one of the most fundamental questions relates to the persistence of populations, or conversely to the probability of their extinction. Deriving extinction thresholds and characterizing other critical phenomena in spatial and stochastic models is highly challenging, with few mathematically rigorous results being available for discrete-space models such as the contact process. For continuous-space models of interacting agents, to our knowledge no analytical results are available concerning critical phenomena, even if continuous-space models can arguably be considered to be more natural descriptions of many ecological systems than lattice-based models. Here we present both mathematical and simulation-based methods for deriving extinction thresholds and other critical phenomena in a broad class of agent-based models called spatiotemporal point processes. The mathematical methods are based on a perturbation expansion around the so-called mean-field model, which is obtained at the limit of large-scale interactions. The simulation methods are based on examining how the mean time to extinction scales with the domain size used in the simulation. By utilizing a constrained Gaussian process fitted to the simulated data, the critical parameter value can be identified by asking when the scaling between logarithms of the time to extinction and the domain size switches from sublinear to superlinear. As a case study, we derive the extinction threshold for the spatial and stochastic logistic model. The mathematical technique yields rigorous approximation of the extinction threshold at the limit of long-ranged interactions. The asymptotic validity of the approximation is illustrated by comparing it to simulation experiments. In particular, we show that species persistence is facilitated by either short or long spatial scale of the competition kernel, whereas an intermediate scale makes the species vulnerable to extinction. Both the mathematical and simulation methods developed here are of very general nature, and thus we expect them to be valuable for predicting many kinds of critical phenomena in continuous-space stochastic models of interacting agents, and thus to be of broad interest for research in theoretical ecology and evolutionary biology.
  • Lahdenperä, Sanni; Soilu-Hanninen, Merja; Kuusisto, Hanna-Maija; Atula, Sari; Junnila, Jouni; Berglund, Anders (2020)
    Objectives To explore adherence, persistence, and treatment patterns in patients with multiple sclerosis (MS) in Finland treated with disease-modifying therapies (DMTs) for active MS in 2005-2018. Materials and Methods The study cohort was identified using the Drug Prescription Register of Social Insurance Institute, Finland. All patients had at least one prescription of glatiramer acetate (GA), beta-interferons, teriflunomide, or delayed-release dimethyl fumarate (DMF). Adherence was calculated using proportion of days covered (PDC) (cutoff >= 0.8). Time to non-persistence was calculated by the number of days on index DMT treatment before the first treatment gap (>= 90 days) or switch and analyzed with time-to-event methodology. Results The cohort included 7474 MS patients (72.2% female; mean age 38.9 years). Treatment switches were steady over 2005-2012, peaked in 2015. PDC means (standard deviations) were GA, 0.87 (0.17); beta-interferons, 0.88 (0.15); DMF, 0.89 (0.14); teriflunomide, 0.93 (0.10). Adherence frequencies were GA, 78.4%; beta-interferons, 81.3%; DMF, 86.9%; teriflunomide, 91.7%. Logistic regression showed that age group, DMT and the starting year, sex, and hospital district independently affected adherence. Patients receiving teriflunomide and DMF, males, and older patients were more likely to persist on treatment. There was no difference in persistence between patients prescribed teriflunomide and DMF, or between GA and beta-interferons. Conclusions Oral DMTs had greater adherence and persistence than injectable DMTs.
  • Kudinov, A. A.; Mantysaari, E. A.; Aamand, G. P.; Uimari, P.; Stranden, I. (2020)