Visual analysis of uncertainties in ocean forecasts for planning and operation of off-shore structures

pre-printWe present a novel integrated visualization system that enables interactive visual analysis of ensemble simulations used in ocean forecasting, i.e, simulations of sea surface elevation. Our system enables the interactive planning of both the placement and operation of off-shore structures. We illustrate this using a real-world simulation of the Gulf of Mexico. Off-shore structures, such as those used for oil exploration, are vulnerable to hazards caused by strong loop currents. The oil and gas industry therefore relies on accurate ocean forecasting systems for planning their operations. Nowadays, these forecasts are based on multiple spatio-temporal simulations resulting in multidimensional, multivariate and multivalued data, so-called ensemble data. Changes in sea surface elevation are a good indicator for the movement of loop current eddies, and our visualization approach enables their interactive exploration and analysis. We enable analysis of the spatial domain, for planning the placement of structures, as well as detailed exploration of the temporal evolution at any chosen position, for the prediction of critical ocean states that require the shutdown of rig operations

Semi-automated background removal limits data loss and normalizes imaging mass cytometry data

Imaging mass cytometry (IMC) allows the detection of multiple antigens (approximately 40 markers) combined with spatial information, making it a unique tool for the evaluation of complex biological systems. Due to its widespread availability and retained tissue morphology, formalin-fixed, paraffin-embedded (FFPE) tissues are often a material of choice for IMC studies. However, antibody performance and signal to noise ratios can differ considerably between FFPE tissues as a consequence of variations in tissue processing, including fixation. In contrast to batch effects caused by differences in the immunodetection procedure, variations in tissue processing are difficult to control. We investigated the effect of immunodetection-related signal intensity fluctuations on IMC analysis and phenotype identification, in a cohort of 12 colorectal cancer tissues. Furthermore, we explored different normalization strategies and propose a workflow to normalize IMC data by semi-automated background removal, using publicly available tools. This workflow can be directly applied to previously acquired datasets and considerably improves the quality of IMC data, thereby supporting the analysis and comparison of multiple samples.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Visual cohort comparison for spatial single-cell omics-data

Spatially-resolved omics-data enable researchers to precisely distinguish cell types in tissue and explore their spatial interactions, enabling deep understanding of tissue functionality. To understand what causes or deteriorates a disease and identify related biomarkers, clinical researchers regularly perform large-scale cohort studies, requiring the comparison of such data at cellular level. In such studies, with little a-priori knowledge of what to expect in the data, explorative data analysis is a necessity. Here, we present an interactive visual analysis workflow for the comparison of cohorts of spatially-resolved omics-data. Our workflow allows the comparative analysis of two cohorts based on multiple levels-of-detail, from simple abundance of contained cell types over complex co-localization patterns to individual comparison of complete tissue images. As a result, the workflow enables the identification of cohort-differentiating features, as well as outlier samples at any stage of the workflow. During the development of the workflow, we continuously consulted with domain experts. To show the effectiveness of the workflow, we conducted multiple case studies with domain experts from different application areas and with different data modalities.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Multidimensional analyses of proinsulin peptide-specific regulatory T cells induced by tolerogenic dendritic cells

Induction of antigen-specific regulatory T cells (Tregs) in vivo is the holy grail of current immune-regulating therapies in autoimmune diseases, such as type 1 diabetes. Tolerogenic dendritic cells (tolDCs) generated from monocytes by a combined treatment with vitamin D and dexamethasone (marked by CD52hi and CD86lo expression) induce antigen-specific Tregs. We evaluated the phenotypes of these Tregs using high-dimensional mass cytometry to identify a surface-based T cell signature of tolerogenic modulation. Naïve CD4+ T cells were stimulated with tolDCs or mature inflammatory DCs pulsed with proinsulin peptide, after which the suppressive capacity, cytokine production and phenotype of stimulated T cells were analysed. TolDCs induced suppressive T cell lines that were dominated by a naïve phenotype (CD45RA+CCR7+). These naïve T cells, however, did not show suppressive capacity, but were arrested in their naïve status. T cell cultures stimulated by tolDC further contained memory-like (CD45RA-CCR7-) T cells expressing regulatory markers Lag-3, CD161 and ICOS. T cells expressing CD25lo or CD25hi were most prominent and suppressed CD4+ proliferation, while CD25hi Tregs also effectively supressed effector CD8+ T cells.We conclude that tolDCs induce antigen-specific Tregs with various phenotypes. This extends our earlier findings pointing to a functionally diverse pool of antigen-induced and specific Tregs and provides the basis for immune-monitoring in clinical trials with tolDC.Nephrolog

High-dimensional cytometric analysis of colorectal cancer reveals novel mediators of antitumour immunity

Objective A comprehensive understanding of anticancer immune responses is paramount for the optimal application and development of cancer immunotherapies. We unravelled local and systemic immune profiles in patients with colorectal cancer (CRC) by high-dimensional analysis to provide an unbiased characterisation of the immune contexture of CRC.Design Thirty-six immune cell markers were simultaneously assessed at the single-cell level by mass cytometry in 35 CRC tissues, 26 tumour-associated lymph nodes, 17 colorectal healthy mucosa and 19 peripheral blood samples from 31 patients with CRC. Additionally, functional, transcriptional and spatial analyses of tumour-infiltrating lymphocytes were performed by flow cytometry, single-cell RNA-sequencing and multispectral immunofluorescence.Results We discovered that a previously unappreciated innate lymphocyte population (Lin(-)CD7+(C)D127(-)CD56(+)CD45RO(+)) was enriched in CRC tissues and displayed cytotoxic activity. This subset demonstrated a tissue-resident (CD103(+)CD69(+)) phenotype and was most abundant in immunogenic mismatch repair (MMR)-deficient CRCs. Their presence in tumours was correlated with the infiltration of tumour-resident cytotoxic, helper and gamma delta T cells with highly similar activated (HLA-DR(+)CD38(+)PD(-)1(+)) phenotypes. Remarkably, activated gamma delta T cells were almost exclusively found in MMR-deficient cancers. Non-activated counterparts of tumour-resident cytotoxic and gamma delta T cells were present in CRC and healthy mucosa tissues, but not in lymph nodes, with the exception of tumour-positive lymph nodes.Conclusion This work provides a blueprint for the understanding of the heterogeneous and intricate immune landscape of CRC, including the identification of previously unappreciated immune cell subsets. The concomitant presence of tumour-resident innate and adaptive immune cell populations suggests a multitargeted exploitation of their antitumour properties in a therapeutic setting.Surgical oncolog

The contribution of cytomegalovirus infection to immune senescence is set by the infectious Dose

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity

Controlled human infections provide opportunities to study the interaction between the immune system and malaria parasites, which is essential for vaccine development. Here, we compared immune signatures of malaria-naive Europeans and of Africans with lifelong malaria exposure using mass cytometry, RNA sequencing and data integration, before and 5 and 11 days after venous inoculation with Plasmodium falciparum sporozoites. We observed differences in immune cell populations, antigen-specific responses and gene expression profiles between Europeans and Africans and among Africans with differing degrees of immunity. Before inoculation, an activated/differentiated state of both innate and adaptive cells, including elevated CD161(+)CD4(+) T cells and interferon-gamma production, predicted Africans capable of controlling parasitemia. After inoculation, the rapidity of the transcriptional response and clusters of CD4(+) T cells, plasmacytoid dendritic cells and innate T cells were among the features distinguishing Africans capable of controlling parasitemia from susceptible individuals. These findings can guide the development of a vaccine effective in malaria-endemic regions.Malaria immunity can be acquired through natural infection, but the correlates of protection are still being determined. Yazdanbakhsh and colleagues combine experimental infection of volunteers with Plasmodium falciparum with systems analysis to throw light on the nature of protective immune responses.Radiolog

Comparative cellular analysis of motor cortex in human, marmoset and mouse

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals(1). Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.Cardiovascular Aspects of Radiolog

Sadutus turvapaikanhakijalasten kanssa

Opinnäytetyömme aiheena oli turvapaikanhakijalasten sadutus vastaanottokeskuksessa. Työssämme käytimme sadutusta työvälineenä turvapaikanhakijalasten kanssa. Sovimme vastaanottokeskukseen neljä sadutuskertaa. Opinnäytetyömme tarkoituksena oli tutkia, millaisia teemoja lasten saduista nousee ja miten saduista näkyy lasten kokemusmaailma. Tarkoituksenamme oli myös tutkia, millaisia haasteita sadutuksen käytännön toteutuksessa on turvapaikanhakijalasten kanssa. Yhteistyökumppaninamme toimi eräs vastaanottokeskus Suomesta. Tutkimuksemme kohderyhmänä oli neljä lasta vastaanottokeskuksesta. Tutkimusotteemme oli laadullinen ja aineistona tutkimuksessamme ovat lasten sadut ja piirustukset, vastaanottokeskuksen työntekijän haastattelu sekä meidän tutkijoiden omat muistiinpanot ja havainnot sadutuskerroista. Tutkimuksen tulosten perusteella turvapaikanhakijalasten saduista heijastuu lasten kokemusmaailmaa. Teemoina lasten saduista nousivat esimerkiksi uhat, menetykset ja traumaattiset kokemukset. Toisaalta saduissa näkyy myös lasten arkipäivä, perhe ja itselle tärkeät asiat sekä tapahtumat. Satujen kautta lapset voivat käsitellä mielikuvituksen turvin vaikeita ja traumaattisiakin asioita. Tuloksissa ja käytännön toteuttamisen myötä tuli myös ilmi haasteiden läsnäolo sadutuksen toteuttamisessa turvapaikanhakijalasten kanssa. Haasteina olivat esimerkiksi yhteisen kielen puute ja kulttuurierot. Tutkimuksemme perusteella sadutus soveltuu käytettäväksi turvapaikanhakijalasten kanssa. Vaikka kohderyhmänä turvapaikanhakijalapset ovat erityisen suojelun tarpeessa, sadutus on turvallinen ja lapsilähtöinen tapa kuulla lasta. Sadutus antaa lapselle mahdollisuuden tulla kuulluksi. Menetelmä kannustaa ja rohkaisee lasta kertomaan omia ajatuksiaan, sillä sadutuksessa ei ole oikeaa tai väärää satua. Sadutus työmenetelmänä on toimiva ja siirrettävissä kaikkiin asiakasryhmiin. Toimintaa voi kuitenkin olla tarpeen muokata kohderyhmän mukaan. Työntekijän tulee tiedostaa mahdolliset haasteet sadutusmenetelmän käytössä kyseisen asiakasryhmän kanssa työskenneltäessä. Opinnäytetyömme tulokset eivät ole luotettavasti yleistettävissä pienen otannan ja aineiston takia. Kirjallisuus, saduista nousseet teemat ja kohtaamamme haasteet kuitenkin tukevat toinen toisiaan. Jotta tulokset olisivat luotettavampia, olisi otannan oltava isompi ja tarvittaisiin pidempi työskentelyjakso lasten kanssa sadutuksen äärellä. Lasten osallistuminen tutkimukseen perustui vapaaehtoisuuteen, mutta on huomioitava lasten rajallinen kyky ymmärtää tutkimuksen kohteena oleminen.The theme of this thesis is storycrafting as a working method with asylum seeking children. The purpose was to study themes of stories told by asylum seeking children and how these fairy tales depict their experiences. The aim was to gather information about the challenges of using storycrafting as a method with asylum seeking children. The study was qualitative in nature, and based on children’s fairy tales, drawings, semi-structured interview of an employee and researchers notes and free observation. The data were collected in four storycrafting sessions. The research group included four asylum seeking children living in the reception centre. The results revealed that fairy tales reflect children’s experiences. The main themes that arose from the fairy tales were threats, losses and traumatic experiences. However, the fairy tales also showed children’s everyday life, family and meaning full events. After the study the challenges of using storycrafting method with asylum seeking children became clear. Some of the challenges were lack of common language and cultural differences. Based on the observations made in this study storycrafting method can be used as a working method with asylum seeking children. Storycrafting is a safe and childoriented way of hearing a child. Storycrafting gives a child a chance to be heard. As a working method storycrafting is an effective and assignable method for all kind of client work. Although the results of this thesis are not necessarily reliable because of the low number of participants. The results would be more reliable with higher number of participants. It would also take more time with using the method