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Early Bronze Age [EBA] Keros was a central place in the 3rd millennium cal BC Cycladic islands (Greece). Its material culture attests links with communities throughout the Aegean and beyond. This study uses obsidian sourcing to help reconstruct the socio-economic networks that coalesced at the site. Some 207 artifacts were elementally characterized using portable x-ray fluorescence spectroscopy [pXRF], the material coming from two ritual deposits in the Kavos area (n = 103), and the opposite islet settlement of Dhaskalio (n = 104). The results are consonant with the cosmopolitan character of Keros’ ceramic and metallurgical assemblages with not only the expected Melian sources of Dhemenegaki and Sta Nychia represented, but also handfuls of much rarer material from Giali A in the Dodecanese and East Göllü Dağ in central Anatolia. The study also provides further evidence for a Cycladic and Cretan preference for Sta Nychia raw materials in the EBA. A more complex picture of Melian obsidian consumption locally and regionally is then produced by integrating the sourcing data with the artifacts’ techno-typological and metrical attributes, which enables us to detail several EBA cultural traditions or ‘communities of practice’ across the Aegean region. The small quantities of Giali A and East Göllü Dağ obsidian are testimony to the supra-regional networks that coalesced at the site. Both raw materials likely circulated alongside the flow of Anatolian metals into the Aegean (including tin and gold), a network that introduced socially significant media and knowledge to Keros from as far east as the Indus. This congregation of people, resources, and technical know-how on Keros formed a key mode of social reproduction in Cycladic society with the mortuary and commemorative rituals on Kavos and the commensal gatherings on Dhaskalio comprising important spaces for the initiation, maintenance, and celebration of social relations.

Background KRAS activating mutations are considered the most frequent oncogenic drivers and are correlated with radio-resistance in multiple cancers including non-small cell lung cancer (NSCLC) and colorectal cancer. Although KRAS was considered undruggable until recently, several KRAS inhibitors have recently reached clinical development. Among them, MRTX849 (Mirati Therapeutics) showed encouraging clinical outcomes for the treatment of selected patients with KRAS G12C mutated NSCLC and colorectal cancers. In this work, we explore the ability of MRTX1257, a KRAS G12C inhibitor analogous to MRTX849, to radio-sensitize KRAS G12C + / + mutated cell lines and tumors. Methods Both in vitro and in vivo models of radiotherapy (RT) in association with MRTX1257 were used, with different RAS mutational profiles. We assessed in vitro the radio-sensitizing effect of MRTX1257 in CT26 KRAS G12C+/+ , CT26 WT, LL2 WT and LL2 NRAS KO (LL2 NRAS −/− ) cell lines. In vivo, we used syngeneic models of subcutaneous CT26 KRAS G12C+/+ tumors in BALB/c mice and T cell deficient athymic nu/nu mice to assess both the radio-sensitizing effect of MRTX1257 and its immunological features. Results MRTX1257 was able to radio-sensitize CT26 KRAS G12C+/+ cells in vitro in a time and dose dependent manner. Moreover, RT in association with MRTX1257 in BALB/c mice bearing CT26 KRAS G12C+/+ subcutaneous tumors resulted in an observable cure rate of 20%. However, no durable response was observed with similar treatment in athymic nude mice. The analysis of the immune microenvironment of CT26 KRAS G12C+/+ tumors following RT and MRTX1257 showed an increase in the proportion of various cell subtypes including conventional CD4 + T cells, dendritic cells type 2 (cDC2) and inflammatory monocytes. Furthermore, the expression of PD-L1 was dramatically down-regulated within both tumor and myeloid cells, thus illustrating the polarization of the tumor microenvironment towards a pro-inflammatory and anti-tumor phenotype following the combined treatment. Conclusion This work is the first to demonstrate in vitro as in vivo the radio-sensitizing effect of MRTX1257, a potent KRAS G12C inhibitor compatible with oral administration, in CT26 KRAS G12C mutated cell lines and tumors. This is a first step towards the use of new combinatorial strategies using KRAS inhibitors and RT in KRAS G12C mutated tumors, which are the most represented in NSCLC with 14% of patients harboring this mutational profile.

BackgroundCombining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions.MethodsClinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient’s response.ResultsA total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables.ConclusionsThese results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.

Assessment of morphometric and volumetric changes in lacrimal glands in thyroid eye disease, its clinical manifestations in relation of disease progression. Retrospective volumetric analysis included both genders and was performed on total of 183 patients - 91 patients with diagnosed Grave’s disease and thyroid eye disease and 92 patients without Grave’s disease and thyroid eye disease who underwent multidetector computed tomography (MDCT) examination in routine daily work according to other medical indications. In the group of females, there was statistical significance between patients with thyroid eye disease and controls who were smoking and had body weight gain. We found statistical significance in volumetric enlargements for both orbits in both genders for the patients group when compared to controls. There was also statistical significance in morphometric characteristics for the lacrimal gland diameters measured. Determination planimetric morphometric parameters of importance were coronary height of lacrimal gland of the right eye, coronary height of lacrimal gland of the left eye and coronary width of lacrimal gland of the left eye for the group of males. In a group of females the established determination parameters of importance were the coronary height of lacrimal gland of the left eye, the axial width of lacrimal gland of the left eye, volume of lacrimal gland of the right eye and the volume of lacrimal gland of the left eye. When we compared the displaced lacrimal gland coming forward (proptosis) in time progressing disease between group of patients and controls, we also found statistical significant connection. Evaluation of lacrimal gland volumetric and morphometric data may increase validity of defining this anatomical substrate and its morphology disruption as liable tool for thyroid eye disease progression follow up and treatment planning and outcome.

This study presents the preliminary results of new excavations of Early Minoan III–Middle Minoan IA horizons at Priniatikos Pyrgos in East Crete. It argues that there is cumulative growth at this central settlement throughout the Early Minoan and earliest Middle Minoan phases that is mirrored in the surrounding settled landscape, but that this changed dramatically during the latter phase with declining prosperity at the site. To explore this, the character of occupation and craft traditions at Priniatikos Pyrgos are evaluated. It is concluded that the autonomy of this settlement as a local center was interrupted during Middle Minoan IB–II, reflecting a shift in power and governance.

Despite major research and clinical efforts, lung cancer remains the leading cause of cancer-related death. While the delivery of conformal radiotherapy and image guidance of stereotactic body radiotherapy (SBRT) have revolutionized the treatment of early-stage non-small-cell lung cancer (NSCLC), additional research is needed to elucidate underlying mechanisms of resistance and identify novel therapeutic combinations. Clinical progress relies on the successful translation of pre-clinical work, which so far has not always yielded expected results. Improved clinical modelling involves characterizing the preclinical models and selecting appropriate experimental designs that faithfully mimic precise clinical scenarios. Here, we review the current role of SBRT and the scope of pre-clinical armamentarium at our disposal to improve successful clinical translation of pre-clinical research in the radiation oncology of NSCLC.

Visoko obrazovanje važan je segment pripreme za tržište rada svih studenata koji upisujuci pojedini fakultet žele steci potrebnu edukaciju za rad u odabranom podrucju. Zemlje Europske Unije, pa tako i Hrvatska, ulažu u razvoj visokog obrazovanja kroz razlicite operativne programe koji pridonose dostupnosti obrazovanja za sve kategorije gradana. Otvorenost visokog obrazovanja svakom clanu društva temelj je inkluzivne obrazovne politike Europske Unije. Obrazovne politike postaju podrucje interesa cijele europske zajednice jer se društvo znanja vidi kao temelj gospodarske konkurentnosti Europe na globalnom tržištu. Cilj je rada ispitati kako strucnjaci koji rade u službama podrške za studente s invaliditetom doživljavaju poštovanje prava na visoko obrazovanje studenata s invaliditetom na Sveucilištu u Zagrebu. Rijec je o kvalitativnom istraživanju povedenom u 2019. godini putem polustrukturiranih intervjua, dok su podaci obradeni primjenom tematske analize. U istraživanju je sudjelovalo 10 strucnjaka koji rade u službama podrške za studente s invaliditetom na Sveucilištu u Zagrebu. Rezultati ukazuju na pozitivne primjere poštovanja prava na visoko obrazovanje, ali identifciraju i postojece slabe tocke koje je potrebno unaprijediti u skladu sa suvremenim postavkama inkluzivnog europskog društva. Promjene u buducnosti potrebne su u podrucjima standardizacije asistencije i prijevoza, prilagodbe infrastrukture, redovite edukacije nastavnog osoblja, senzibilizacije studenata te u razvoju ljudskih resursa u uredima za studente s invaliditetom. Kljucne rijeci: studenti s invaliditetom, pravo na visoko obrazovanje, formalna podrška Higher education plays a pivotal role in preparing students for the labour market by providing education at the university level required for work in the chosen feld. The EU member states, including Croatia, invest in higher education through diferent operational programmes to increase access to education for all citizens. Equal access to higher education for all is at the core of EU education policies for inclusion. Moreover, the education policy importance rises on the European agenda as the concept of knowledge society becomes central to European competitiveness on the global market. This paper aimed to examine how professionals employed by support services for students with disabilities perceive the respect of the right to higher education for students with disabilities at the University of Zagreb. The paper is based on qualitative research from 2019, which involved semi-structured interviews and thematic analysis of data. The research included 10 professionals employed by the support services for students with disabilities at the University of Zagreb. Although the results indicated certain good practice examples of respecting the right to higher education, they also pointed out the challenges that ought to be addressed in line with contemporary inclusive practices in Europe. In the future, improvements are recommended in the following areas: standardising assistance and transportation, adapting infrastructure, continuing training of the teaching staf, raising student awareness and human resource development at the Ofce for Students with Disabilities. Keywords: students with disabilities, right to higher education, formal support

Palijativna skrb za djecu aktivna je i potpuna briga za dijete koja djeluje na tjelesnoj, psihickoj, socijalnoj i duhovnoj razini, a takoder ukljucuje i suradnju te aktivan rads obitelji djeteta. Palijativna skrb za djecu svojim trajanjem pokriva razdoblje bolesti, ali i razdoblje nakon smrti djeteta u obliku strucne pomoci obitelji u tugovanju. Ovakva skrb pociva na nacelima više teorijskih sadržaja kao što su individualni pristup, holisticki pristup, transdisciplinarni pristup, biopsihosocijalno-duhovni model koji se objedinjuju u promicanju kvalitete života djeteta i njegove obitelji. Postoje brojni pravni izvori koji su polazište definiranja palijativne skrbi za djecu kao temeljnog ljudskog prava na zdravstvenu zaštitu. Pravo na palijativnu skrb ukljucuje prava iz razlicitih sustava što iziskuje suradnju i povezivanje razlicitih disciplina s ciljem zadovoljavanja specificnih potreba djeteta i njegove obitelji. Cilj je rada prikazivanje kljucnih spoznaja iz podrucja palijativne skrb za djecu, upoznavanje s pravnom regulacijom navedenog prava u Republici Hrvatskoj te samim nacinima ostvarivanja svih elemenata koji cine pravo na palijativnu skrb za djecu. Kljucne rijeci: palijativna skrb za djecu, obitelj, ljudska prava, socijalna podrška Palliative care for children means active, complete care on physical, psychological, social and spiritual levels, and it includes collaboration and active work with the family. Palliative care for children lasts during the period of illness and continues after the death of the child in the form of expert assistance to the family in their grief. Such care follows the principles of individual, holistic, transdisciplinary and biopsychosocial-spiritual approaches that come together in promoting the quality of life of a child and his or her family. Numerous legal sources are the starting point for defining palliative care for children as a fundamental human right to health care, as well as for defining basic actions within this fundamental right. The right to palliative care includes rights from different systems, and collaboration and linking of different disciplines are needed in order to meet the needs of the child and his family. The aim of this paper is to present crucial knowledge in the field of palliative care for children and to examine how this right is implemented and legally regulated in the Republic of Croatia. Key words: palliative care for children, family, human rights, social support

The occurrence of somatic transformation in germ cell tumour (GCT) is rare, with increased incidence in teratomatous tumours. The aim of this study was to understand the clinical outcomes of patients with metastatic GCT with somatic transformation. A retrospective study was conducted in two tertiary cancer centres in London. Between 1998 and 2016, 30 cases of somatic transformation in GCT treated at the Mount Vernon Cancer Centre and St. Bartholomew's Hospital were identified. The median age at diagnosis was 34 years (range=18-56 years). The histological diagnosis at transformation was rhabdomyosarcoma, sarcomatoid yolk sac, sarcoma (non-specified), clear cell carcinoma, adenocarcinoma and primitive neuro ectodermal tumour (PNET). The 5-year survival rate of all patients was 47%, and that of patients with testicular primary (n=26 patients) was 37%. Somatic transformation component in testicular GCTs is generally considered to be an adverse prognostic factor, however, a reasonable 5-year overall survival rate (87.5%) was observed in patients who present with this at first diagnosis.

Higher education plays a pivotal role in preparing students for the labor market by providing education at the university level required for work in the chosen field. The EU member states, including Croatia, invest in higher education through different operational programs to increase access to education for all citizens. Equal access to higher education for all is at the core of EU education policies for inclusion. Moreover, the education policy importance rises on the European agenda as the concept of knowledge society becomes central to European competitiveness on the global market. This paper aimed to examine how professionals employed by support services for students with disabilities perceive the respect of the right to higher education for students with disabilities at the University of Zagreb. The paper is based on qualitative research from 2019, which involved semi-structured interviews and thematic analysis of data. The research included 10 professionals employed by the support services for students with disabilities at the University of Zagreb. Although the results indicated certain good practice examples of respecting the right to higher education, they also pointed out the challenges that ought to be addressed in line with contemporary inclusive practices in Europe. In the future, improvements are recommended in the following areas: standardizing assistance and transportation, adapting infrastructure, continuing training of the teaching staff, raising student awareness and human resource development at the Office for Students with Disabilities.