Mast Cell Accumulation in Glioblastoma with a Potential Role for Stem Cell Factor and Chemokine CXCL12

Glioblastoma multiforme (GBM) is the most common and malignant form of glioma with high mortality and no cure. Many human cancers maintain a complex inflammatory program triggering rapid recruitment of inflammatory cells, including mast cells (MCs), to the tumor site. However, the potential contribution of MCs in glioma has not been addressed previously. Here we report for the first time that MCs infiltrate KRas+Akt-induced gliomas, using the RCAS/TV-a system, where KRas and Akt are transduced by RCAS into the brains of neonatal Gtv-a- or Ntv-a transgenic mice lacking Ink4a or Arf. The most abundant MC infiltration was observed in high-grade gliomas of Arf−/− mice. MC accumulation could be localized to the vicinity of glioma-associated vessels but also within the tumor mass. Importantly, proliferating MCs were detected, suggesting that the MC accumulation was caused by local expansion of the MC population. In line with these findings, strong expression of stem cell factor (SCF), i.e. the main MC growth factor, was detected, in particular around tumor blood vessels. Further, glioma cells expressed the MC chemotaxin CXCL12 and MCs expressed the corresponding receptor, i.e. CXCR4, suggesting that MCs could be attracted to the tumor through the CXCL12/CXCR4 axis. Supporting a role for MCs in glioma, strong MC infiltration was detected in human glioma, where GBMs contained significantly higher MC numbers than grade II tumors did. Moreover, human GBMs were positive for CXCL12 and the infiltrating MCs were positive for CXCR4. In conclusion, we provide the first evidence for a role for MCs in glioma

European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer

BACKGROUND In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications. OBJECTIVE We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa. DESIGN, SETTING, AND PARTICIPANTS The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores. RESULTS AND LIMITATIONS After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [$^{177}$Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [$^{223}$Ra]RaCl$_{2}$ remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [$^{18F}$]FDG and PSMA PET prior to [$^{177}$Lu]Lu-PSMA therapy. CONCLUSIONS There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community. PATIENT SUMMARY There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide

European Association of Nuclear Medicine Focus 5:Consensus on Molecular Imaging and Theranostics in Prostate Cancer

BACKGROUND: In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.OBJECTIVE: We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa.DESIGN, SETTING, AND PARTICIPANTS: The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores.RESULTS AND LIMITATIONS: After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [177Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [223Ra]RaCl2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [18F]FDG and PSMA PET prior to [177Lu]Lu-PSMA therapy.CONCLUSIONS: There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community.PATIENT SUMMARY: There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.</p

European Association of Nuclear Medicine Focus 5 : Consensus on Molecular Imaging and Theranostics in Prostate Cancer

Funding/Support and role of the sponsor: This research was funded by the EANM and supported by unrestricted grants from Advanced Accelerator Applications—a Novartis company, Monrol, Spectrum Dynamics Medical Ltd., Blue Earth Diagnostics, GE HealthCare, ITM Isotope Technologies Munich SE, Siemens Healthineers, and Telix Pharmaceuticals. These sponsors had no direct or indirect influence on the programme and content of the EANM Focus 5 meeting and the writing or content of this consensus statement. Acknowledgements: We would like to thank Evelyn Mansutti, Susanne Koebe, Andrea Csismazia, Jutta Peter, Petra Neubauer, Andreas Felser, and Henrik Silber (all from EANM) for project management. We also acknowledge all who participated in EANM Focus 5 meeting and especially the patients who participated in clinical and research projects, making it possible to inform expert opinion.Peer reviewe

Long-term exposure to transportation noise and risk of incident stroke:A pooled study of nine scandinavian cohorts

BACKGROUND: Transportation noise is increasingly acknowledged as a cardiovascular risk factor, but the evidence base for an association with stroke is sparse. OBJECTIVE: We aimed to investigate the association between transportation noise and stroke incidence in a large Scandinavian population. METHODS: We harmonized and pooled data from nine Scandinavian cohorts (seven Swedish, two Danish), totaling 135,951 participants. We identified residential address history and estimated road, railway, and aircraft noise for all addresses. Information on stroke incidence was acquired through link-age to national patient and mortality registries. We analyzed data using Cox proportional hazards models, including socioeconomic and lifestyle con-founders, and air pollution. RESULTS: During follow-up (median = 19:5 y), 11,056 stroke cases were identified. Road traffic noise (Lden ) was associated with risk of stroke, with a hazard ratio (HR) of 1.06 [95% confidence interval (CI): 1.03, 1.08] per 10-dB higher 5-y mean time-weighted exposure in analyses adjusted for indi-vidual-and area-level socioeconomic covariates. The association was approximately linear and persisted after adjustment for air pollution [particulate matter (PM) with an aerodynamic diameter of ≤2:5 lm (PM2:5 ) and NO2 ]. Stroke was associated with moderate levels of 5-y aircraft noise exposure (40–50 vs. ≤40 dB) (HR = 1:12; 95% CI: 0.99, 1.27), but not with higher exposure (≥50 dB, HR = 0:94; 95% CI: 0.79, 1.11). Railway noise was not associated with stroke. DISCUSSION: In this pooled study, road traffic noise was associated with a higher risk of stroke. This finding supports road traffic noise as an important cardiovascular risk factor that should be included when estimating the burden of disease due to traffic noise. https://doi.org/10.1289/EHP8949

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Risteilymatkustus Helsingissä : Case Helsinki Cruise Network

Tämän opinnäytetyön tavoitteena on tutustua Helsingin risteilymatkustuksen tämänhetkiseen tilaan. Tutkimusongelmana on selvittää Helsingin paikallisen risteilyverkoston, Helsinki Cruise Networkin toiminnan kehittämismahdollisuuksia ja jäsenyritysten mielipiteitä verkostosta. Lisäksi tutkimme Helsingin eri virastojen edustajien mielipiteitä risteilymatkustusta koskien ja selvitämme heidän rooliaan ja sitoutumistan siihen. Myös verkostoituminen on yksi työmme pääelementeistä. Risteilyverkoston jäsenten mielipiteitä selvitettiin sähköpostikyselyllä ja virastojen edustajilta tiedot kerättiin teemahaastattelun avulla. Helsinki Cruise Networkin jäsenet toivoivat verkostolta aiempaa aktiivisempaa toimintaa. Vastaajat uskoivat pystyvänsä verkoston avulla laajentamaan ja kasvattamaan asiakaskuntaansa sekä löytämään uusia liiketoiminnan muotoja. Kiireellisimmiksi kehityskohteiksi havaittiin palvelujen ja tuotteiden parantaminen sekä informaation tehostaminen. Risteilyverkoston jäsenet olivat melko tyytyväisiä Helsingin eri virastojen toimintaan ja yhteistyöhön. Myös virastojen edustajat kertoivat haastatteluissa olevansa tyytyväisiä tämän hetkiseen yhteistyöhön ja sen tiiviyteen virastojen välillä. Tutkimuksen perusteella voidaan todeta, että vähitellen ollaan ymmärtämässä ristelymatkustuksen tärkeys Helsingille. Paljon on jo tehty risteilymatkustuksen kehittämiseksi, muta paljon on vielä tehtävä, jotta Helsinki voisi kilpailla tasavertaisena muiden kokeneempien Itämeren satamakaupunkien kanssa

Toimintaterapeutista lähiesimieheksi : erikoissairaanhoidon toimintaterapeutin lähiesimiehen työnkuvaus ja työtehtävät "vuosikellossa"

Opinnäytetyö oli työelämän kehittämistehtävä, jossa laadittiin Keski-Suomen sairaanhoitopiirin toimintaterapian lähiesimiehen työnkuvaus ja siihen liittyvät työtehtävät sijoitettiin vuosikelloon. Opinnäytteen tarkoituksena oli antaa työvälineitä toimintaterapian lähiesimiehen työhön. Opinnäytteessä hyödynnettiin viittä terveydenhuollon lähiesimiehen työnkuvaa. Työnkuvat analy-soitiin sisällönanalyysillä peilaten niitä teoriasta saatuun tietopohjaan. Teoria-aineisto koostui lähi-johtamisesta, esimiesten työtehtävistä, erikoissairaanhoidon toimintaterapiasta ja lainsäädännön sekä strategisten linjausten vaikutuksesta esimiestyöskentelyyn. Toimintaterapian lähiesimies toimii siltana esimiehen ja työntekijöiden arkitodellisuuden välillä. Lähiesimiehen työn haasteita ovat organisaation odotukset sekä toimintaympäristön jatkuva muutos. Terveyspalvelujen saatavuus lisääntyy, ja työtä tehdään pienillä ja samoilla resursseilla, mikä korostaa johtamisen eettisyyttä. Se vaatii lähiesimieheltä hyvää kliinisen työn tuntemusta ja vuoro-vaikutustaitoja, jotta työntekijöiden osaaminen saadaan kohdennettua tarkoituksenmukaisesti ja tasapuolisesti. Toimintaterapian lähiesimiehen työtä ohjaavat lainsäädäntö ja työpaikan strategia. Keski-Suomen sairaanhoitopiirin strategiassa terveyslähtöisyys ja terveyden edistämisen ovat osa organisaation käytännön toimintaa. Terveyslähtöisessä johtamisessa tavoitteena on turvata ja edistää kaikkien työntekijöiden työhyvinvointia tasapuolisesti. Myös yksilön vastuuta korostetaan oman terveytensä huolehtimisesta. Terveydenhuolto on tällä hetkellä muutosten kourissa, ja tulevaisuudessa kuntoutuksen asema tulee kasvamaan. Toimintamalleja kehitetään uuden sairaalan suunnitteluprosessin rinnalla. Tekniikan ja hoitojen kehittyessä myös potilasryhmät tulevat olemaan monivammaisempia. Esimiestyön kehittäminen tulee olemaan avainasemassa, kun puhutaan toiminnan tehokkuudesta, henkilöstön jaksamisesta ja työelämän laadusta terveydenhuollossa.The thesis was carried out as a development work, in which the job description of the immediate superiors of occupational therapy was drawn up in Central Finland Hospital District and the related duties were placed in the annual clock. The purpose of this thesis was to provide tools for the im-mediate superiors of occupational therapy work. The thesis used five health care line manager job descriptions. The job descriptions were analyzed by reflecting their content to the knowledge base provided by theory. The theory-related material consisted of management, management duties, specialist occupational therapy as well as the impact of strategic policies and legislation on managerial work. The immediate superiors of occupational therapy act as a bridge between the upper level manage-ment and the employees’ reality of daily work. The superiors’ work challenges are the expectations of the organization and the constant change of the operational environment. Health services are increasing, and the work is done with the same small resources, which emphasizes ethical leader-ship. From the immediate superior this requires good knowledge of clinical work and interpersonal skills so that the employees' skills can be targeted appropriately and equitably. The superiors of occupational therapy are guided by legislation and workplace strategy. In the strategy of the Central Finland Hospital District health-orientation and health promotion are parts of the organization’s practical activities. In health-oriented management the objective is to safeguard and promote the wellbeing of all employees equally. It also emphasizes individual responsibility for personal health care. Health care is currently undergoing changes, and the role of rehabilitation will increase in future. Models will be developed in parallel with the planning process of a new hospital. Technology and the development of therapies lead to patient groups being multi-handicapped. Leadership development will play a key role when it comes to operational efficiency, staff coping and quality of working life in health care

"Ikke sint, bare veldig skuffet": Om barn, miljø og medieteknologi

The relationship between children and new media is a recurrent topic of media studies research. This article examines the relationship between children and digital media technologies from an eco-ethical perspective, highlighting how media consumption always involves consumption of material resources. Adopting a visual culture approach to media representations, its discussion focuses on the website and advertising campaign of a Norwegian environmental organisation for children