Browsing by Subject "persistence"

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  • Tiili, Paula; Leventis, Ioannis; Kinnunen, Janne; Svedjebäck, Ida; Lehto, Mika; Karagkiozi, Efstathia; Sagris, Dimitrios; Ntaios, George; Putaala, Jukka (2021)
    Background Non-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved. Aims We sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF). Methods We recruited hospitalised patients (2013-2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA(2)DS(2)-VASc and SAMe-TT2R2 scores with poor adherence. Results Among 396 patients (median age 75.0 years, interquartile range [IQR] 70-80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12-33]; median ARMS score 17 [IQR 17-19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA(2)DS(2)-VASc and SAMe-TT2R2 scores were not associated with poor adherence. Conclusions Adherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients. KEY MESSAGES Adherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke. Independent patient-related factors rather than composite scores were associated with poor adherence. The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline.
  • Ben Sita, Bernard (Svenska handelshögskolan, 2002)
    Working Papers
    This paper investigates the persistent pattern in the Helsinki Exchanges. The persistent pattern is analyzed using a time and a price approach. It is hypothesized that arrival times are related to movements in prices. Thus, the arrival times are defined as durations and formulated as an Autoregressive Conditional Duration (ACD) model as in Engle and Russell (1998). The prices are defined as price changes and formulated as a GARCH process including duration measures. The research question follows from market microstructure predictions about price intensities defined as time between price changes. The microstructure theory states that long transaction durations might be associated with both no news and bad news. Accordingly, short durations would be related to high volatility and long durations to low volatility. As a result, the spread will tend to be larger under intensive moments. The main findings of this study are 1) arrival times are positively autocorrelated and 2) long durations are associated with low volatility in the market.
  • Teppo, Konsta; Jaakkola, Jussi; Biancari, Fausto; Halminen, Olli; Linna, Miika; Haukka, Jari; Putaala, Jukka; Tiili, Paula; Lehtonen, Ossi; Niemi, Mikko; Mustonen, Pirjo; Kinnunen, Janne; Hartikainen, Juha; Airaksinen, K. E. Juhani; Lehto, Mika (2022)
    Low socioeconomic status has been associated with poor outcomes in patients with atrial fibrillation (AF). However, little is known about socioeconomic disparities in adherence to stroke prevention with direct oral anticoagulants (DOACs). We assessed the hypothesis that AF patients with higher income or educational levels have better adherence to DOACs in terms of treatment implementation and persistence. The used nationwide registry-based FinACAF cohort covers all patients with incident AF starting DOACs in Finland during 2011-2018. The implementation analyses included 74 222 (mean age 72.7 +/- 10.5 years, 50.8% female) patients, and persistence analyses included 67 503 (mean age 75.3 +/- 8.9 years, 53.6% female) patients with indication for permanent anticoagulation (CHA(2)DS(2)-VASc score >1 in men and >2 in women). Patients were divided into income quartiles and into three categories based on their educational attainment. Therapy implementation was measured using the medication possession ratio (MPR), and patients with MPR >= 0.90 were defined adherent. Persistence was measured as the incidence of therapy discontinuation, defined as the first 135-day period without DOAC purchases after drug initiation. Patients with higher income or education were consistently more likely adherent to DOACs in the implementation phase (comparing the highest income or educational category to the lowest adjusted odds ratios 1.18 (1.12-1.25) and 1.21(1.15-1.27), respectively). No association with income or educational levels was observed on the incidence of therapy discontinuation. In conclusion, we observed that income and educational levels both have independent positive association on the implementation of DOAC therapy but no association on therapy persistence in patients with AF.
  • Savijoki, Kirsi; Miettinen, Ilkka; Nyman, Tuula; Kortesoja, Maarit; Hanski, Leena; Varmanen, Pekka; Fallarero, Adyary (2020)
    The present study investigated Staphylococcus aureus ATCC25923 surfaceomes (cell surface proteins) during prolonged growth by subjecting planktonic and biofilm cultures (initiated from exponential or stationary cells) to label-free quantitative surfaceomics and phenotypic confirmations. The abundance of adhesion, autolytic, hemolytic, and lipolytic proteins decreased over time in both growth modes, while an opposite trend was detected for many tricarboxylic acid (TCA) cycle, reactive oxygen species (ROS) scavenging, Fe-S repair, and peptidolytic moonlighters. In planktonic cells, these changes were accompanied by decreasing and increasing adherence to hydrophobic surface and fibronectin, respectively. Specific RNA/DNA binding (cold-shock protein CspD and ribosomal proteins) and the immune evasion (SpA, ClfA, and IsaB) proteins were notably more abundant on fully mature biofilms initiated with stationary-phase cells (SDBF) compared to biofilms derived from exponential cells (EDBF) or equivalent planktonic cells. The fully matured SDBF cells demonstrated higher viability in THP-1 monocyte/macrophage cells compared to the EDBF cells. Peptidoglycan strengthening, specific urea-cycle, and detoxification enzymes were more abundant on planktonic than biofilm cells, indicating the activation of growth-mode specific pathways during prolonged cultivation. Thus, we show that S. aureus shapes its surfaceome in a growth mode-dependent manner to reach high levofloxacin tolerance (>200-times the minimum biofilm inhibitory concentration). This study also demonstrates that the phenotypic state of the cells prior to biofilm formation affects the immune-evasion and persistence-related traits of S. aureus.
  • Taavitsainen, Eveliina (Helsingfors universitet, 2017)
    Chlamydia pneumoniae is an intracellular human pathogen that causes respiratory infections such as pneumonia. Antibodies have been found in serological samples worldwide and most likely every person gets an infection at least once in lifetime. In particular, persistent C.pneumoniae-infection has been associated with multiple chronic diseases such as atherosclerosis, asthma and neurological diseases. C.pneumoniae has a unique two-stage life cycle with two morphological forms; elementary body and reticulate body. In addition, the bacterium has a chronic persistent form. Persistent infection is very typical. Persistent infection can be produced in many ways in vitro, but it has been also found that C.pneumoniae is spontaneously transformed into persistent form in macrophages and monocytes. The aim of this study was to investigate the effect of anti-chlamydial compounds previously identified in the research group on the persistent infektion of C.pneumoniae. For the study, the growth of the bacteria was monitored by qPCR in different cell lines and the compatibility of the compounds with the used persistence model was studied. Four different cell lines were used in the study; HL epithelial cells, Raw264.7 macrophages, THP1 monocytes and macrophages. The effect of compounds on the used cell line was first examined by viability assays. For further studies, C.pneumoniae growth was studied in different cell lines. An qPCR method was set up and used to monitor C.pneumoniae genome copy numbers in infected samples. Based on the growth curves, the measurement points were determined for further studies. Finally, the effect of suitable compounds on C.pneumoniae infection was investigated in epithelial, monocyte and macrophage cell lines. From the investigated compounds, Schisandra chinensis-lingnans were selected for further studies with Raw264.7 cells. The genome number wa not found to decrease compared to the after schisandrin or schisandrin B treatment. In the experiment of the growth of the bacterium, schisandrin-treated samples showed that the genome number of bacterium would be re-grown. This may potentially mean the persistent infection change back to the active form, whereby the bacterium resumed proliferate in the host cell. Based on the results of this study, schisandrin may be considered a potential compound for further studies and a possible model compound for the development of compound against C.pneumoniae infection. However, further studies on the effect of the compounds on persistent infection are needed.
  • Teppo, Konsta; Jaakkola, Jussi; Airaksinen, K. E. Juhani; Biancari, Fausto; Halminen, Olli; Putaala, Jukka; Mustonen, Pirjo; Haukka, Jari; Hartikainen, Juha; Luojus, Alex; Niemi, Mikko; Linna, Miika; Lehto, Mika (2022)
    BACKGROUND: Mental health conditions (MHCs) are associated with poor outcomes in patients with atrial fibrillation. However, persistence of oral anticoagulation therapy in patients with atrial fibrillation and MHCs is unknown. We aimed to evaluate the effect of MHCs on the persistence of direct oral anticoagulant (DOAC) use in patients with atrial fibrillation based on a nationwide cohort. METHODS AND RESULTS: The nationwide registry-based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) cohort included 67 503 patients with incident atrial fibrillation and indication for permanent oral anticoagulation (CHA(2)DS(2)-VASc score >1 in men and >2 in women) starting DOAC therapy between 2011 and 2018. MHCs of interest were depression, bipolar disorder, anxiety disorder, schizophrenia, and composite of any MHC. The main outcome was nonpersistence of DOAC use, defined as the first 120-day period without DOAC purchases after drug initiation. The mean age of the patients was 75.3 +/- 8.9 years, 53.6% were women, and the prevalence of any MHC was 17.8%. Persistence after 1 year from DOAC initiation was 79.3% in patients without MHCs and 77.2% in patients with any MHC, and after 2 years were 64.4% and 60.6%, respectively (P CONCLUSIONS: MHCs are associated with nonpersistence of DOAC use.
  • Castro, Hanna; Douillard, Francois; Korkeala, Hannu; Lindström, Miia (2021)
    Listeria monocytogenes is a foodborne pathogen and a resilient environmental saprophyte. Dairy farms are a reservoir of L. monocytogenes, and strains can persist on farms for years. Here, we sequenced the genomes of 250 L. monocytogenes isolates to investigate the persistence and mobile genetic elements (MGEs) of Listeria strains inhabiting dairy farms. We performed a single-nucleotide polymorphism (SNP)-based phylogenomic analysis to identify 14 monophyletic clades of L. monocytogenes persistent on the farms for ≥6 months. We found that prophages and other mobile genetic elements were, on average, more numerous among isolates in persistent than nonpersistent clades, and we demonstrated that resistance genes against bacitracin, arsenic, and cadmium were significantly more prevalent among isolates in persistent than nonpersistent clades. We identified a diversity of mobile elements among the 250 farm isolates, including three novel plasmids, three novel transposons, and a novel prophage harboring cadmium resistance genes. Several of the mobile elements we identified in Listeria were identical to the mobile elements of enterococci, which is indicative of recent transfer between these genera. Through a genome-wide association study, we discovered that three putative defense systems against invading prophages and plasmids were negatively associated with persistence on farms. Our findings suggest that mobile elements support the persistence of L. monocytogenes on dairy farms and that L. monocytogenes inhabiting the agroecosystem is a potential reservoir of mobile elements that may spread to the food industry. IMPORTANCE Animal-derived raw materials are an important source of L. monocytogenes in the food industry. Knowledge of the factors contributing to the pathogen's transmission and persistence on farms is essential for designing effective strategies against the spread of the pathogen from farm to fork. An increasing body of evidence suggests that mobile genetic elements support the adaptation and persistence of L. monocytogenes in the food industry, as these elements contribute to the dissemination of genes encoding favorable phenotypes, such as resilience against biocides. Understanding of the role of farms as a potential reservoir of these elements is needed for managing the transmission of mobile elements across the food chain. Because L. monocytogenes coinhabits the farm ecosystem with a diversity of other bacterial species, it is important to assess the degree to which genetic elements are exchanged between Listeria and other species, as such exchanges may contribute to the rise of novel resistance phenotypes.
  • Kulp-Tåg, Sofie (Svenska handelshögskolan, 2008)
    Economics and Society
    Financial time series tend to behave in a manner that is not directly drawn from a normal distribution. Asymmetries and nonlinearities are usually seen and these characteristics need to be taken into account. To make forecasts and predictions of future return and risk is rather complicated. The existing models for predicting risk are of help to a certain degree, but the complexity in financial time series data makes it difficult. The introduction of nonlinearities and asymmetries for the purpose of better models and forecasts regarding both mean and variance is supported by the essays in this dissertation. Linear and nonlinear models are consequently introduced in this dissertation. The advantages of nonlinear models are that they can take into account asymmetries. Asymmetric patterns usually mean that large negative returns appear more often than positive returns of the same magnitude. This goes hand in hand with the fact that negative returns are associated with higher risk than in the case where positive returns of the same magnitude are observed. The reason why these models are of high importance lies in the ability to make the best possible estimations and predictions of future returns and for predicting risk.
  • VIZIONS Consortium; Nguyen Thi Kha Tu; Deng, Xutao; Nguyen Thi Thu Hong; Nguyen Thi Han Ny; Tran My Phuc; Pham Thi Thanh Tam; Duong An Han; Luu Thi Thu Ha; Thwaites, Guy; van Doorn, H. Rogier; Virtala, Anna-Maija K.; Delwart, Eric; Baker, Stephen; Vapalahti, Olli; Tan, Le Van (2021)
    Redondoviridae is a recently discovered DNA virus family consisting of two species, vientovirus and brisavirus. Here we used PCR amplification and sequencing to characterize redondoviruses in nasal/throat swabs collected longitudinally from a cohort of 58 individuals working with animals in Vietnam. We additionally analyzed samples from animals to which redondovirus DNA-positive participants were exposed. Redondoviruses were detected in approximately 60% of study participants, including 33% (30/91) of samples collected during episodes of acute respiratory disease and in 50% (29/58) of baseline samples (with no respiratory symptoms). Vientovirus (73%; 24/33) was detected more frequently in samples than brisaviruses (27%; 9/33). In the 23 participants with at least 2 redondovirus-positive samples among their longitudinal samples, 10 (43.5%) had identical redondovirus replication-gene sequences detected (sampling duration: 35-132 days). We found no identical redondovirus replication genes in samples from different participants, and no redondoviruses were detected in 53 pooled nasal/throat swabs collected from domestic animals. Phylogenetic analysis described no large-scale geographical clustering between viruses from Vietnam, the US, Spain, and China, indicating that redondoviruses are highly genetically diverse and have a wide geographical distribution. Collectively, our study provides novel insights into the Redondoviridae family in humans, describing a high prevalence, potentially associated with chronic shedding in the respiratory tract with lack of evidence of zoonotic transmission from close animal contacts. The tropism and potential pathogenicity of this viral family remain to be determined.
  • Räsänen, Matti; Merbold, Lutz; Vakkari, Ville; Aurela, Mika; Laakso, Lauri; Beukes, Johan P.; Zyl, Pieter G. Van; Josipovic, Miroslav; Feig, Gregor; Pellikka, Petri; Rinne, Janne; Katul, Gabriel (2020)
    The main source of soil moisture variability in savanna ecosystems is pulsed rainfall. Rainfall pulsing impacts water-stress durations, soil moisture switching between wet-to-dry and dry-to-wet states, and soil moisture spectra as well as derived measures from it such as soil moisture memory. Rainfall pulsing is also responsible for rapid changes in grassland leaf area and concomitant changes in evapotranspirational (ET) losses, which then impact soil moisture variability. With the use of a hierarchy of models and soil moisture measurements, temporal variability in root-zone soil moisture and water-stress periods are analysed at four African sites ranging from grass to miombo savannas. The normalized difference vegetation index (NDVI) and potential ET (PET)-adjusted ET model predict memory timescale and dry persistence in agreement with measurements. The model comparisons demonstrate that dry persistence and mean annual dry periods must account for seasonal and interannual changes in maximum ET represented by NDVI and to a lesser extent PET. Interestingly, the precipitation intensity and soil moisture memory were linearly related across three savannas with ET/infiltration similar to 1.0. This relation and the variability of length and timing of dry periods are also discussed.
  • Savijoki, Kirsi; Myllymäki, Henna; Luukinen, Hanna; Paulamäki, Lauri; Vanha-aho, Leena-Maija; Svorjova, Aleksandra; Miettinen, Ilkka; Fallarero, Adyary; Ihalainen, Teemu O; Yli-Kauhaluoma, Jari; Nyman, Tuula A.; Parikka, Mataleena (2021)
    The complex cell wall and biofilm matrix (ECM) act as key barriers to antibiotics in mycobacteria. Here, the ECM and envelope proteins of Mycobacterium marinum ATCC 927, a nontuberculous mycobacterial model, were monitored over 3 months by label-free proteomics and compared with cell surface proteins on planktonic cells to uncover pathways leading to virulence, tolerance, and persistence. We show that ATCC 927 forms pellicle-type and submerged-type biofilms (PBFs and SBFs, respectively) after 2 weeks and 2 days of growth, respectively, and that the increased CelA1 synthesis in this strain prevents biofilm formation and leads to reduced rifampicin tolerance. The proteomic data suggest that specific changes in mycolic acid synthesis (cord factor), Esx1 secretion, and cell wall adhesins explain the appearance of PBFs as ribbon-like cords and SBFs as lichen-like structures. A subpopulation of cells resisting 64x MIC rifampicin (persisters) was detected in both biofilm subtypes and already in 1-week-old SBFs. The key forces boosting their development could include subtype-dependent changes in asymmetric cell division, cell wall biogenesis, tricarboxylic acid/glyoxylate cycle activities, and energy/redox/iron metabolisms. The effect of various ambient oxygen tensions on each cell type and nonclassical protein secretion are likely factors explaining the majority of the subtype-specific changes. The proteomic findings also imply that Esx1-type protein secretion is more efficient in planktonic (PL) and PBF cells, while SBF may prefer both the Esx5 and nonclassical pathways to control virulence and prolonged viability/persistence. In conclusion, this study reports the first proteomic insight into aging mycobacterial biofilm ECMs and indicates biofilm subtype-dependent mechanisms conferring increased adaptive potential and virulence of nontuberculous mycobacteria. IMPORTANCE Mycobacteria are naturally resilient, and mycobacterial infections are notoriously difficult to treat with antibiotics, with biofilm formation being the main factor complicating the successful treatment of tuberculosis (TB). The present study shows that nontuberculous Mycobacterium marinum ATCC 927 forms submergedand pellicle-type biofilms with lichen- and ribbon-like structures, respectively, as well as persister cells under the same conditions. We show that both biofilm subtypes differ in terms of virulence-, tolerance-, and persistence-conferring activities, highlighting the fact that both subtypes should be targeted to maximize the power of antimycobacterial treatment therapies.
  • Ben Sita, Bernard (Svenska handelshögskolan, 2002)
    Working Papers
    This paper investigates the clustering pattern in the Finnish stock market. Using trading volume and time as factors capturing the clustering pattern in the market, the Keim and Madhavan (1996) and the Engle and Russell (1998) model provide the framework for the analysis. The descriptive and the parametric analysis provide evidences that an important determinant of the famous U-shape pattern in the market is the rate of information arrivals as measured by large trading volumes and durations at the market open and close. Precisely, 1) the larger the trading volume, the greater the impact on prices both in the short and the long run, thus prices will differ across quantities. 2) Large trading volume is a non-linear function of price changes in the long run. 3) Arrival times are positively autocorrelated, indicating a clustering pattern and 4) Information arrivals as approximated by durations are negatively related to trading flow.