Pysyvien orgaanisten yhdisteiden (POP) esiintyvyys, tunnistaminen ja erottaminen muovijätteistä

Pysyviksi orgaanisiksi yhdisteiksi (POP) kutsutut aineet ovat erittäin haitallisia ihmisen terveydelle tai ympäristölle. Yhdisteitä on käytetty palontorjunta-aineina, pintakäsittelykemikaaleina sekä lisäaineina erilaisissa muovimateriaaleissa. Yhdisteiden valmistusta ja käyttöä on rajoitettu tai kielletty jo vuosien ajan, mutta aineita esiintyy jätehuoltoon päätyvissä tuotteissa vuosikymmenienkin viiveellä. EU:n POP-asetus kieltää kierrättämästä POP-yhdisteitä sisältäviä jätteitä. Asetuksessa on säädetty kullekin kielletylle aineelle pitoisuusraja, jonka ylittyessä jäte on hävitettävä pysyvästi polttamalla tai fysikaalis-kemiallisin käsittelyin. Käytännössä POP-raja-arvot ylittyvät aina tuotteissa, joihin on lisätty aineita palonestotarkoituksessa. Lisäksi joissakin kierrätysmuovia sisältävissä tuotteissa voi esiintyä vähäisiä jäämiä aineista. Euroopassa on kartoitettu aineiden esiintymistä, mutta mittauksia yhdisteiden esiintymisestä on tehty vähän. Bromi-alkuainetta sisältävien muovikappaleiden yksittäinen ja jatkuvatoiminenkin tunnistaminen on mahdollista röntgenfluoresenssiin (XRF) tai röntgentransmissioon (XRT) perustuvien mittausten avulla, mutta kumpaakaan menetelmää ei toistaiseksi ole otettu Suomessa käyttöön taloudellisista syistä. SER:ssä kiellettyjä yhdisteitä tiedetään esiintyvän etenkin kuvaputkitelevisioiden ja tietokonemonitoreiden koteloissa, mutta myös kuumenevassa kodin- ja konttorielektroniikassa. Romuajoneuvoissa yhdisteitä tiedetään esiintyvän eniten istuinten pehmusteissa ja päällyksissä ja etenkin aasialaisvalmisteisissa ajoneuvoissa. Rakennusalalla HBCD:n kierrätyskielto on huomioitava etenkin EPS-eristeteollisuudessa. Purkukohteiden tuottamat muut kumiset ja muoviset jätejakeet päätyvät polttoon, jolloin mahdolliset POP-yhdisteet eivät pääse kiertoon. Jätteistä löydetyt POP-yhdistepitoisuudet asettavat haasteen sekä kierrätysalalle että alan valvojille. Kierrätystavoitteet edellyttävät kierrätyksen lisäämistä ja samanaikaisesti näistä materiaalivirroista pitäisi saada eroteltua ne jakeet, joissa POP-pitoisuudet ylittävät asetetut raja-arvot. Kierrätettävän materiaalin maksimoimiseksi ja kierrätysvirran puhtauden turvaamiseksi olisi parannettava jätehuoltoketjussa toimivien tietotasoa ja edellytyksiä liittää laitteistoihin uutta mittaustekniikkaa. Bromipitoisuuden mittaus olisi usein riittävä toimenpide. Valistusta tulisi lisäksi suunnata kotitalouksille, jotta SER:ä ja romuajoneuvoja ei varastoitaisi kotitalouksissa pidentämässä POP-yhdisteitä sisältävien jätteiden poistumisaikaa

Agile workflow for interactive analysis of mass cytometry data

Motivation: Single-cell proteomics technologies, such as mass cytometry, have enabled characterization of cell-tocell variation and cell populations at a single-cell resolution. These large amounts of data, require dedicated, interactive tools for translating the data into knowledge. Results: We present a comprehensive, interactive method called Cyto to streamline analysis of large-scale cytometry data. Cyto is a workflow-based open-source solution that automates the use of state-of-the-art single-cell analysis methods with interactive visualization. We show the utility of Cyto by applying it to mass cytometry data from peripheral blood and high-grade serous ovarian cancer (HGSOC) samples. Our results show that Cyto is able to reliably capture the immune cell sub-populations from peripheral blood and cellular compositions of unique immune- and cancer cell subpopulations in HGSOC tumor and ascites samples.Peer reviewe

qSNE: quadratic rate t-SNE optimizer with automatic parameter tuning for large datasets

Peer reviewe

PRISM : recovering cell-type-specific expression profiles from individual composite RNA-seq samples

Motivation: A major challenge in analyzing cancer patient transcriptomes is that the tumors are inherently heterogeneous and evolving. We analyzed 214 bulk RNA samples of a longitudinal, prospective ovarian cancer cohort and found that the sample composition changes systematically due to chemotherapy and between the anatomical sites, preventing direct comparison of treatment-naive and treated samples. Results: To overcome this, we developed PRISM, a latent statistical framework to simultaneously extract the sample composition and cell-type-specific whole-transcriptome profiles adapted to each individual sample. Our results indicate that the PRISM-derived composition-free transcriptomic profiles and signatures derived from them predict the patient response better than the composite raw bulk data. We validated our findings in independent ovarian cancer and melanoma cohorts, and verified that PRISM accurately estimates the composition and cell-type-specific expression through whole-genome sequencing and RNA in situ hybridization experiments.Peer reviewe

Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer

Chemotherapy resistance is a critical contributor to cancer mortality and thus an urgent unmet challenge in oncology. To characterize chemotherapy resistance processes in high-grade serous ovarian cancer, we prospectively collected tissue samples before and after chemotherapy and analyzed their transcriptomic profiles at a single-cell resolution. After removing patient-specific signals by a novel analysis approach, PRIMUS, we found a consistent increase in stress-associated cell state during chemotherapy, which was validated by RNA in situ hybridization and bulk RNA sequencing. The stress-associated state exists before chemotherapy, is subclonally enriched during the treatment, and associates with poor progression-free survival. Co-occurrence with an inflammatory cancer-associated fibroblast subtype in tumors implies that chemotherapy is associated with stress response in both cancer cells and stroma, driving a paracrine feed-forward loop. In summary, we have found a resistant state that integrates stromal signaling and subclonal evolution and offers targets to overcome chemotherapy resistance.Peer reviewe

Substance Use and Sleep Problems in Patients With Psychotic Disorders

sgac073Substance use and sleep problems are common in patients with psychotic disorders, but their associations in these patients have not been evaluated. We aimed to investigate associations between substance use and sleep problems in a large nationwide cohort of patients with a psychotic disorder.This study is part of the Finnish SUPER study, which belongs to the Stanley Global Neuropsychiatric Genomics Initiative. In this cross-sectional, multicenter study, participants (N = 8616) were recruited from primary and specialized healthcare. Patients with schizophrenia, schizoaffective disorder, bipolar disorder, and psychotic depression were included. Information on current alcohol (Alcohol Use Disorders Identification Test-Concise) and cigarette use as well as on lifetime illicit drug use, including cannabis, benzodiazepines, amphetamines, and opioids, was collected using questionnaires. The sleep outcomes in our logistic regression analysis were short (≤6 h) and long sleep (≥10 h) duration, difficulties initiating asleep, early morning awakenings, fatigue, and poor sleep quality (SQ).Self-reported substance use was associated with a higher prevalence of sleep problems. After adjustments with age, gender, diagnostic group, and living status, hazardous alcohol use (eg, poor SQ odds ratio [OR] = 1.80, 95\ 1.49 to 2.16, P \lt; .001), current smoking (short sleep duration OR = 1.28, 95\ 1.08 to 1.52, P = .005), and lifetime benzodiazepine misuse (difficulties initiating sleep OR = 2.00, 95\ 1.55 to 2.48, P \lt; .001) were associated with sleep problems.Substance use was associated with sleep problems. Our findings underline the potential benefits of screening substance use when treating sleep problems in patients with psychotic disorders.Peer reviewe

Sleep in psychotic disorders: Results from nationwide SUPER Finland study

Peer reviewe

Reaction Time and Visual Memory in Connection with Alcohol Use in Schizophrenia and Schizoaffective Disorder

The purpose of this study was to explore the association between cognition and hazardous drinking and alcohol use disorder in schizophrenia and schizoaffective disorder. Cognition is more or less compromised in schizophrenia, and schizoaffective disorder and alcohol use might aggravate this phenomenon. The study population included 3362 individuals from Finland with diagnoses of schizophrenia or schizoaffective disorder. Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Alcohol use disorder (AUD) diagnoses were obtained from national registrar data. Participants performed two computerized tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB) on a tablet computer: The Five-Choice Serial Reaction Time Task (5-CSRTT) or the reaction time (RT) test and the Paired Associative Learning (PAL) test. The association between alcohol use and the RT and PAL tests was analyzed with log-linear regression and logistic regression, respectively. After adjustment for age, education, housing status, and the age at which the respondents had their first psychotic episodes, hazardous drinking was associated with a lower median RT in females and less variable RT in males, while AUD was associated with a poorer PAL test performance in terms of the total errors adjusted scores (TEASs) in females. Our findings of positive associations between alcohol and cognition in schizophrenia and schizoaffective disorder are unique.Peer reviewe

Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder

We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.Peer reviewe