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Effect of prior and first-line immunotherapy on baseline immune biomarkers and modulation of the tumor microenvironment in response to nivolumab and relatlimab combination therapy in patients with melanoma from RELATIVITY-020
No full textBackground Some patients with melanoma experience disease progression during immunotherapy (IO) and may benefit from novel combinations of immune checkpoint inhibitors (ICIs). We report results from exploratory biomarker analyses to characterize the responses of patients with advanced melanoma to treatment with nivolumab (anti-programmed cell death-1 (PD-1)) and relatlimab (anti-lymphocyte-activation gene 3 (LAG-3)) combination therapy in RELATIVITY-020 (NCT01968109). Methods Tumor biopsies collected at baseline and ≤4 weeks after treatment initiation were evaluated for % LAG-3-positive and % CD8-positive immune cells and % programmed death-ligand 1 (PD-L1) expression on tumor cells. Baseline biomarker expression was compared among patients with IO-refractory melanoma based on last prior therapy and IO-resistance type, and between patients with IO-refractory and IO-naïve melanoma. Change in biomarker expression after treatment was evaluated in patients with IO-refractory and IO-naïve melanoma. Immune-related gene expression was compared among resistance groups and by the last prior treatment. Results Among patients with IO-refractory melanoma (N=505), elevated baseline LAG-3, PD-L1, and CD8 expression (p≤0.01, p≤0.05, p≤0.001, respectively) was observed in patients whose last prior therapy was IO versus non-IO, and in those who responded (complete/partial per Response Evaluation Criteria in Solid Tumors V.1.1) to nivolumab and relatlimab combination therapy versus those who did not (stable/progressive disease). Inflammation-related gene expression was significantly higher (p<0.05) in patients with secondary versus primary resistance to prior IO treatment, and in those whose last prior therapy was IO versus non-IO. IO-refractory patients whose tumors responded to nivolumab and relatlimab combination therapy had higher inflammation-related gene expression than non-responders (p<0.05); proliferation and hypoxia-related gene expression were enriched in non-responders. During treatment with nivolumab and relatlimab combination therapy, LAG-3 expression increased significantly in patients with IO-refractory (p≤0.01) and IO-naïve melanoma (p≤0.001), and PD-L1 and CD8 increased significantly (p≤0.01 and p≤0.05, respectively) in patients with IO-naïve melanoma. Conclusions Nivolumab and relatlimab combination therapy can modulate the tumor microenvironment in patients with both IO-refractory and IO-naïve melanoma. Further research is needed to identify patients who will most benefit from anti-LAG-3/PD-(L)1 agents, and to elucidate the mechanisms of action of, and resistance to, this combination therapy in patients with advanced melanoma. Trial registration number NCT01968109.Peer reviewe
Wetland deposit in the hinterland : Kihliä flint find assemblage (southeast Finland) in the framework of hunter–fisher–gatherer ritual practices in northeastern Europe in the early 4th millennium BC
No full textMore than a century ago, a collection of flint artefacts dating to the early 4th millennium BC was discovered in Kihliä, SE Finland. In this paper, we revisit the Kihliä assemblage by reconstructing the original findspot and examining its environmental context during the suggested time of deposition. As a result, we suggest that the Kihliä artefacts were deposited in a wetland area situated in a forested hinterland, distant from known Stone Age settlement sites in the region. By placing the Kihliä assemblage within the broader context of early 4th millennium BC ritual depositional practices in northeastern Europe and by comparing these practices to those from preceding periods in the surrounding regions of Finland, we propose that the Kihliä deposit was likely a ritually marked deposit. Remarkably, landscape-wise, the Kihliä deposit differs from other ritual deposits or sites from the same period in Finland, which are typically found in shore-bound locations. Consequently, this study suggests that small inland water bodies or wetlands, as well as water routes leading into the hinterland, could also serve as significant locations for ritual activitiesMore than a century ago, a collection of flint artefacts dating to the early 4th millennium BC was discovered in Kihliä, SE Finland. In this paper, we revisit the Kihliä assemblage by reconstructing the original findspot and examining its environmental context during the suggested time of deposition. As a result, we suggest that the Kihliä artefacts were deposited in a wetland area situated in a forested hinterland, distant from known Stone Age settlement sites in the region. By placing the Kihliä assemblage within the broader context of early 4th millennium BC ritual depositional practices in northeastern Europe and by comparing these practices to those from preceding periods in the surrounding regions of Finland, we propose that the Kihliä deposit was likely a ritually marked deposit. Remarkably, landscape-wise, the Kihliä deposit differs from other ritual deposits or sites from the same period in Finland, which are typically found in shore-bound locations. Consequently, this study suggests that small inland water bodies or wetlands, as well as water routes leading into the hinterland, could also serve as significant locations for ritual activities.Peer reviewe
More than agriculture. The possibilities of acquiring wild animal fauna in the medieval and early modern hamlets in Espoo and Vantaa, Finland
No full textPeer reviewe
Vision Transformers in Brain Image Segmentation
No full textImage segmentation is a challenging task that involves partitioning an image into regions based on a specific criteria. For brain images, segmentation methods can be used for visualization of structures, delineation of injuries, analysis of brain development, and planning of surgical procedures. These methods aid medical professionals with early detection of diseases, precise diagnoses, and effective treatment planning.
Approaches based on Convolutional Neural Networks (CNNs) have shown significant progress in automating brain image segmentation. However, these methods often struggle with capturing longrange dependencies and contextual information, leading to limitations in segmentation accuracy. Recent advances in Vision Transformers (ViTs) have demonstrated superior performance in computer vision tasks by modeling global spatial relationships.
This thesis reviews the application of Transformer-based architectures in brain image segmentation, focusing on their integration with existing CNN models, particularly the U-Net. A review of state-ofthe-art Transformer-based segmentation models, including UNETR, TransBTS, Swin-UNETR, and VT-UNet, is presented. The advantages of these models over CNN-based approaches, particularly in brain tumor and brain tissue segmentation, are also discussed.
An experiment is conducted to evaluate the impact of Transformer integration using a small brain MRI dataset. The findings indicate that the Transformer-integrated architectures may not necessarily improve the performance of the U-Net architecture on limited data. However, with further refinement, including more suitable loss functions, larger datasets, and improved model designs, Transformer-based models could still show potential advantages in small-scale testin
Religion and Hate Victimisation among Youth: A Comprehensive Approach from Methodology to Theory and Practical Solutions
No full textThe modern world is full of rapid changes, with wars, conflicts, hostilities, and immigration. In this context, the concept of religion, what it means in people’s lives and how it is perceived by the people outside of it, changes as well. Religious and religiously non-affiliated people often define themselves in contrast to what they are not, which can create polarisation between the I and the other. This polarisation often leads to fear, misunderstandings, resentment, hostility, and violence. Societal and cultural developments have thus increased the need for research on the links between religion and victimisation.
While criminologists have quite often studied the religion-offending link, the connection between religion and victimisation remains far less studied. This thesis examines the risk and patterns of hate crime victimisation motivated by the religion or religious views of the victim, especially among youth. To understand if and how religion modulates the risk of hate crime victimisation and to find means to prevent it, the right questions should be asked. In the criminological quest to understand religion-targeting victimisation, this thesis dissects how religious affiliation impacts risk in various contexts while analysing more closely the various aspects of religion, such as practices, visibility, and adaptation, as modulators of risk. Therefore, this dissertation makes a meaningful contribution to what is known and unknown regarding religious hate crime victimisation, and it builds a bridge that connects theory to practical solutions. The dissertation comprises four substudies, which build on each other to deliver a cohesive understanding of religious hate crime victimisation phenomenon.
The first substudy constituted a systematic literature review of hate crime victimisation prevention methods and strategies. It focused on hate crime victimisation of young religious individuals from all religious spectra. In the review, three prevention/adaptation levels – the personal (what individuals do), the collective (what communities/congregations/neighbourhoods do) and the institutional (what governments do) – were formed to better understand the nature of the victimisation prevention. Altogether, after reviewing 19,200 articles, 44 peer-reviewed articles published between 2002 and 2022 were found suitable. The review showed that the most common personal adaptation was blending in (trying to hide one’s religious affiliation), while the most common collective measures were community resilience and stereotype reduction. The very few papers on the institutional level focused on improving the connection between victims and different authorities, mostly the police. The review included qualitative, quantitative, and mixed-methods studies.
The second substudy used the 2020 sweep of the Finnish Self-Report Delinquency Study (FSRD), a nationally representative survey aimed at 15–16-year-old adolescents (N = 5482). The substudy explored the prevalence of hate crime victimisation among different religious groups and examined the mediating role of routines and lifestyle on the connection between religious affiliation and religion-based hate crime victimisation. The results indicated that Muslim and religiously unaffiliated youth have an above-average risk of hate crime victimisation. Furthermore, the victimisation patterns differed across religious groups. In addition to religious affiliation, risky lifestyle (i.e. substance use, interacting with delinquent peers) was strongly associated with hate crime risk. Comparing these results with general assault victimisation indicated that the observed patterns are specific to hate crime victimisation, and thus points out the uniqueness of that type of victimisation.
Substudies I and II indicated research lacunae that could be explored in a comparative international manner, given the right tools. The third substudy aimed at creating an instrument for such an analysis, a survey module deployable in the context of the International Self-Report Delinquency Study (ISRD) framework. The substudy charted the degree to which existing (repeated) international surveys factor in religion – and how. The substudy began by describing how religion is present in the latest ISRD version (fourth sweep). The substudy then illustrated how other surveys have studied dimensions of religiosity relevant to victimisation risk, focusing on young people. The knowledge gained from examining the surveys and their outcome variables was then used as the basis for developing an ISRD-compatible survey module to study the religion-victimisation link, especially in surveys with limited space. In sum, this substudy laid the ground for a new ISRD survey module based on prior studies to understand the link between religion and victimisation more comprehensively and deeply.
The fourth substudy deployed the survey module developed in Substudy 3 in a four-country online survey: 4122 participants aged 18–29 from the USA, Finland, Israel, and Germany responded to it. The main goals of the substudy were to see what aspects of religion are connected to hate victimisation risk and how hate crime victimisation is associated with various risk aversion techniques. The results revealed that religious visibility and public religious practices are associated with an elevated risk of hate crime victimisation. In contrast, friends from the same religious group serve as a protective factor. Further analysis showed the level of mediation of the religion-related factors on the connection between religious affiliation and religiously motivated hate crime victimisation. Individuals who have experienced hate crime victimisation showed a higher tendency of general avoidance, weapon-carrying, and seeking religious friends. Those patterns were more prevalent among Jews and Muslims than non-affiliated individuals. This analysis was conducted on the complete dataset and separately for each of the four countries, showing each country’s different victimisation profile and adaptive strategies.
The substudies collectively portray the uniqueness of hate crime victimisation and, more precisely, religious hate crime victimisation while demonstrating the need to ask the right question and discover more about this phenomenon, in order to understand how to prevent it in practice and help those whose voices have long been silent.Nykymaailma on täynnä nopeita muutoksia, joita sodat, konfliktit, vihamielisyys ja maahanmuutto tuovat mukanaan. Tässä kontekstissa myös uskonnon käsite, sen merkitys ihmisten elämässä ja uskonnosta erillään toimivien ihmisten käsitys siitä muuttuvat. Uskonnolliset ja ei-uskonnolliset ihmiset määrittelevät usein itsensä suhteessa siihen, mitä he eivät ole, mikä voi luoda vastakkainasettelua minuuden ja muiden välillä. Tämä vastakkainasettelu johtaa usein pelkoon, väärinkäsityksiin, katkeruuteen, vihamielisyyteen ja väkivaltaan. Yhteiskunnalliset ja kulttuuriset muutokset ovat näin ollen lisänneet tarvetta tutkia uskonnon ja uhriksi joutumisen välistä yhteyttä.
Vaikka kriminologit ovat melko usein tutkineet uskonnon ja rikollisuuden välistä yhteyttä, uskonnon ja uhriksi joutumisen välinen yhteys on jäänyt huomattavasti vähemmälle huomiolle. Tämä väitöskirja tutkii uskonnon tai uhrin uskonnollisten näkemysten motivoiman viharikoksen uhriksi joutumisen riskiä ja kyseisen ilmiön kaavoja erityisesti nuorten keskuudessa. Oikeiden kysymysten esittäminen on tärkeää ymmärtääksemme miten ja missä määrin uskonto vaikuttaa viharikoksen uhriksi joutumisen riskiin ja löytääksemme keinoja sen estämiseksi. Pyrkien ymmärtämään uskontoon kohdistuvaa uhriksi joutumista, tämä väitöskirja tarkastelee miten uskonnollinen vakaumus vaikuttaa riskiin eri konteksteissa, analysoiden samalla tarkemmin uskonnon eri ulottuvuuksia, kuten käytäntöjä, näkyvyyttä ja sopeutumista, jotka toimivat riskin säätelijöinä. Näin ollen tämä väitöskirja tarjoaa merkittävän lisäyksen siihen, mitä tiedämme ja mitä emme vielä tiedä uskonnollisiin viharikoksiin liittyvästä uhriksi joutumisesta, ja rakentaa sillan teorian ja käytännön ratkaisujen välille. Väitöskirja koostuu neljästä osatutkimuksesta, jotka muodostavat yhtenäisen kokonaiskuvan uskonnollisten viharikosten uhriksi joutumisesta.
Ensimmäinen osatutkimus sisälsi järjestelmällisen kirjallisuuskatsauksen viharikosten uhriksi joutumisen ehkäisemisen menetelmistä ja strategioista. Se keskittyi kaikista uskonnollisista taustoista tulevien uskonnollisten nuorten viharikosten uhriksi joutumiseen. Katsauksessa muodostettiin kolme ehkäisy-/sopeutumistasoa – henkilökohtainen (mitä yksilöt tekevät), kollektiivinen (mitä yhteisöt/seurakunnat/naapurustot tekevät) ja institutionaalinen (mitä hallitukset tekevät) – uhriksi joutumisen ehkäisemisen luonteen ymmärtämiseksi paremmin. Tarkastelluista 19 200 artikkelista 44 vuosina 2002–2022 julkaistua vertaisarvioitua artikkelia soveltui katsaukseen. Katsaus osoitti, että yleisin henkilökohtainen sopeutumiskeino oli sulautuminen joukkoon (uskonnollisen identiteetin piilottaminen), kun taas yleisimmät kollektiiviset toimenpiteet olivat yhteisön resilienssi ja stereotypioiden vähentäminen. Institutionaaliselle tasolle luokiteltuja artikkeleita oli hyvin vähän, ja ne keskittyivät parantamaan uhrien ja eri viranomaisten, erityisesti poliisin, välistä yhteyttä. Katsaus sisälsi laadullisia, määrällisiä ja monimenetelmätutkimuksia.
Toinen osatutkimus käytti vuoden 2020 Suomen nuorisorikollisuuskyselyä (NRK), joka on kansallisesti edustava 15–16-vuotiaille nuorille suunnattu kyselytutkimus (N = 5482). Osatutkimus tutki viharikosten uhriksi joutumisen yleisyyttä eri uskonnollisten ryhmien keskuudessa ja tarkasteli elämäntapojen ja rutiinien selittävää roolia uskonnollisuuden ja uskonnon perusteella motivoituneen viharikoksen uhriksi joutumisen yhteydessä. Tulokset osoittivat, että muslimi- ja ei-uskonnollisilla nuorilla on keskimääräistä suurempi riski joutua viharikoksen uhriksi. Lisäksi uhriksi joutumisen kaavat erosivat uskonnollisten ryhmien välillä. Uskonnollisuuden lisäksi riskialtis elämäntapa (esim. päihteiden käyttö, rikollisten ystävien kanssa oleilu) oli vahvasti yhteydessä viharikoksen riskiin. Verrattaessa näitä tuloksia yleiseen pahoinpitelyyn liittyvään uhriksi joutumiseen havaittiin, että havaitut kaavat ovat ominaisia viharikoksille ja siten korostavat kyseisen uhriksi joutumisen tyypin ainutlaatuisuutta.
Osatutkimukset I ja II osoittivat tutkimusaukkoja, joita voitaisiin oikeilla puitteilla tutkia kansainvälisesti vertaillen. Kolmas osatutkimus pyrki luomaan välineeksi tällaista analyysiä varten Kansainvälisen nuorisorikollisuuskyselyn (ISRD) viitekehykseen sopivan kyselymoduulin. Osatutkimus kartoitti, missä määrin olemassa olevat (toistuvat) kansainväliset kyselyt huomioivat uskonnon – ja miten. Osatutkimus kuvasi aluksi, miten uskonto on esillä ISRD:n uusimmassa versiossa (neljäs kierros). Osatutkimus havainnollisti tämän jälkeen, miten muut kyselytutkimukset ovat tutkineet uhriksi joutumisen riskille merkityksellisiä uskonnollisuuden ulottuvuuksia, keskittyen nuoriin. Kyselyistä ja niiden tulosmuuttujista saatu tieto muodosti perustan ISRD-yhteensopivan kyselymoduulin kehittämiselle uskonnon ja uhriksi joutumisen välisen yhteyden tutkimiseksi, erityisesti kyselyissä, joissa tilaa on rajoitetusti. Yhteenvetona tämä osatutkimus luo perustan uudelle ISRD-kyselymoduulille uskonnon ja uhriksi joutumisen välisen yhteyden ymmärtämiseksi kattavammin ja syvällisemmin.
Neljäs osatutkimus hyödynsi osatutkimuksessa 3 kehitettyä kyselymoduulia neljä maata kattavassa sähköisessä kyselyssä: 4122 iältään 18–29-vuotiasta osallistujaa Yhdysvalloista, Suomesta, Israelista ja Saksasta vastasi kyselyyn. Osatutkimuksen päätavoitteena oli selvittää, mitkä uskonnon osa-alueet ovat yhteydessä viharikoksen uhriksi joutumisen riskiin ja miten viharikoksen uhriksi joutuminen liittyy erilaisiin riskin välttämisen tekniikoihin. Tulokset paljastivat, että uskonnollinen näkyvyys ja julkiset uskonnolliset käytännöt liittyvät kohonneeseen viharikoksen uhriksi joutumisen riskiin. Sen sijaan ystävät samasta uskonnollisesta ryhmästä toimivat suojaavana tekijänä. Lisäanalyysi osoitti, missä määrin uskontoa koskevat tekijät selittävät uskonnollisuuden ja uskonnon perusteella motivoituneen viharikoksen uhriksi joutumisen välistä yhteyttä. Viharikoksen uhriksi joutuneet osoittivat suurempaa taipumusta yleiseen välttämiseen, aseiden kantamiseen ja uskonnollisten ystävien seuraan hakeutumiseen. Nämä kaavat ovat yleisempiä juutalaisten ja muslimien keskuudessa kuin ei-uskonnollisilla yksilöillä. Analyysi suoritettiin täydelle aineistolle ja erikseen kullekin neljälle maalle, kuvaten kunkin maan erilaisen uhriprofiilin ja sopeutumisstrategiat.
Yhdessä osatutkimukset kuvaavat viharikoksen uhriksi joutumisen ainutlaatuisuutta ja tarkemmin uskonnollisten viharikosten uhriksi joutumista. Samalla ne osoittavat tarpeen esittää oikeita kysymyksiä ja tutkia tätä ilmiötä lisää viharikosten estämiseksi käytännön tasolla ja niiden auttamiseksi, joiden äänet ovat pitkään jääneet kuulumattomiin.ei saavutettav
Contrasting Seasonal Distribution Patterns of Two Boreal Aerial Hawking Bat Species in Finland
No full textClimate change poses significant consequences for temperate bat species, potentially altering their distribution ranges and generating novel interactions among species sharing similar ecological niches. Recent observations suggest distribution range expansion in the Palearctic aerial hawking bat, Pipistrellus nathusii, prompting an investigation into its interaction with Eptesicus nilssonii, a northern Palearctic species overlapping with the previous in many ecological characteristics. This study examines the spatiotemporal variations between the two boreal bat species to form an evidence-based background onto which future research on, e.g., resource competition, can be built. A comprehensive community science project engaged over 470 participants from 45 high schools to collect acoustic data on bat echolocation calls across Finland, in northern Europe, during the summers of 2019–2020. Our modelling approach reveals distinct spatiotemporal patterns for each species. In early summer, E. nilssonii activity is concentrated in the southern region, whereas by late summer, observations are distributed across our study area, though predominantly in the south. This pattern suggests that E. nilssonii could exhibit post-breeding vagrant behaviour, an observation only recently evidenced in bats. Conversely, the activity of P. nathusii remains notably low throughout the season, with observations concentrated along the south coast during both early and late seasons, making it challenging to fully model its distribution. Despite initial expectations of overlap given their similar foraging behaviour and habitat preferences, the limited activity and coastal association of P. nathusii suggest low competitive interaction with E. nilssonii. These findings contribute to our understanding of bat spatial ecology amid changing environmental conditions, emphasising the necessity for ongoing monitoring to ascertain the long-term implications of shifting species distributions.Peer reviewe
Impact of winter warming on CO2 fluxes in evergreen needleleaf forests
No full textCompared to drought and heat waves, the impact of winter warming on forest CO2 fluxes has been less studied, despite its significant relevance in colder regions with higher soil carbon content. Our objective was to test the effect of the exceptionally warm winter of 2020 on the winter CO2 budget of cold-adapted evergreen needleleaf forests across Europe and identify the contribution of climate factors to changes in winter CO2 fluxes. Our hypothesis was that warming in winter leads to higher emissions across colder sites due to increased ecosystem respiration. To test this hypothesis, we used 98 site-year eddy covariance measurements across 14 evergreen needleleaf forests (ENFs) distributed from the north to the south of Europe (from Sweden to Italy). We used a data-driven approach to quantify the effect of radiation, air temperature, and soil temperature on changes in CO2 fluxes during the warm winter of 2020. Our results showed that warming in winter decreased forest net ecosystem productivity (NEP) significantly across most sites. The contribution of climate variables to CO2 fluxes varied across the sites: in southern regions with warmer mean temperatures, radiation had a greater influence on NEP. Conversely, at colder sites, air temperature played a more critical role in affecting NEP. During the warm winter of 2020, colder regions experienced larger air temperature anomalies compared to the other sites; however we did not observe a significantly larger increase at colder sites due to winter warming. The varying responses of NEP across different sites highlight the complex interactions between climate variables such as air temperature, soil temperature, and radiation. These findings underscore the importance of integrating winter warming effects to more accurately predict the impacts of climate change on forest carbon dynamics