Paleomagnetism and astronomically induced cyclicity of the Armantes section; a Miocene continental red sequence in the Calatayud-Daroca basin (Central Sapin)

The Armantes section is a red-bed sequence consisting of a regular altemation (10 m scale) of reddish silts and pink/white limestones.In between these limestones, a smaller-scale bedding (2-3 m scale) is intercalated, characterised by varying carbonate content and related differences in erosion resistance. An earlier correlation of the magnetic polarity sequence of the Armantes section to the geomagnetic polarity time scale (GPTS) suggested a periodicity of 111 kyr for the large-scale cyclicity (Krijgsman et al., 1994b). The carbonate, gamma-ray and susceptibility records indicate that 4 to 5 small-scale cycles are developed in one large-scale cycle, showing that the small-scale cyclicity is related to precession and thus caused by climate forcing. We suggest that the precipitation of the carbonates is most likely related to rising ground-water levels and an increase of evaporation. This implies that the thick limestone beds would correlate to eccentricity maxima and the smaller-scale limestone beds to precession minima. Rock magnetic experiments show that the NRM in the Armantes section results from the presence of hematite and magnetite/maghemite.The relative contribution of hematite is strongly related to the lithology. Hematite is the dominant carrier in the limestones, while in the silts magnetite/maghemite prevail

The 'Tortonian salinity crisis' of the eastern Betics (Spain)

The late Miocene depositional history of the Lorca and Fortuna basins, both occupying an internal position in the eastern Betics of Spain, is marked by a regressive sequence from open marine marls, via diatomites and evaporites, to continental sediments. Based on facies similarities, these evaporites have often been correlated to the well-known Mediterranean evaporites of the Messinian salinity crisis, although this correlation was never substantiated by reliable chronological data. In this paper, we present an integrated stratigraphy of this regressive sequence which shows that the evaporites of the Lorca and Fortuna basins are entirely of late Tortonian age and as such have no relation with the Messinian salinity crisis. The main phase of basin restriction, resulting in deposition of diatomites and evaporites, took place at 7.8 Ma, while the last marine deposits (massive evaporites of the Lorca basin) are dated at 7.6 Ma. Consequently, this `Tortonian salinity crisis' of the eastern Betics had a duration of approximately 200 kyr, while continental deposition prevailed throughout the entire Messinian as also revealed by the fossil mammal record. The `Tortonian salinity crisis' of the eastern Betics is obviously related to a local phase of basin restriction caused by uplift of the metamorphic complexes at the basin margins, probably in concert with strike-slip activity along SW-NE trending fault systems. The development of a submarine sill is of crucial importance for the increase in salinity because it allows marine waters to continuously enter the basin at the surface while it restricts or prevents the outflow of dense saline waters at depth. Furthermore, we show that evaporite and diatomite cyclicity in these restricted basins is predominantly related to precession controlled circum-Mediterranean climate changes and that glacio-eustatic sea level changes only play a minor role. It is remarkable that the lithological sequence of the Tortonian salinity crisis mimics in many aspects that of the Messinian salinity crisis. This suggests that the diatomaceous facies is an essential part of the lithological sequence associated with basin restriction

Post-Eocene coupled oroclines in the Talesh (NW Iran): paleomagnetic constraints

The Talesh Mountains (NW Iran) witnessed a long deformation history from the Triassic Cimmerian orogeny to the ongoing Arabia-Eurasia collision. This protracted multi-stage deformation has generated a remarkably curved orogen with a puzzling kinematic and deformational history. In this study, we investigate the origin of the Talesh curvature through paleomagnetic analyses on rocks of Paleozoic, Mesozoic and Cenozoic age. Our results indicate that at least two major, large-scale, vertical-axis-rotations took place since the Late Cretaceous: 1) a pre-Eocene 73° ± 17° clockwise rotation and 2) post-Eocene differential rotations that formed the Z-shaped mountain belt within a crustal-scale shear zone. The latter involved an increasing amount of clockwise (CW) rotation from south (16°) to north (48°). The orocline formation likely started during the Oligocene where an approximately east-west oriented mountain belt was buckled by the Arabia-Eurasia collision, with Arabia acting as a rigid indenter and the South Caspian basin as a rigid backstop. We hypothesise that the NE-SW oriented Aras and Lahijan fault zones, inherited from transform faults related to the Mesozoic opening of the Caspian-Black Sea back-arc, accommodated the coupled orocline formation

Altered Cigarette Smoke-Induced Lung Inflammation Due to Ablation of Grx1

Glutaredoxins (Grx) are redox enzymes that remove glutathione bound to protein thiols, know as S-glutathionylation (PSSG). PSSG is a reservoir of GSH and can affect the function of proteins. It inhibits the NF-κB pathway and LPS aspiration in Grx1 KO mice with decreased inflammatory cytokine levels. In this study we investigated whether absence of Grx1 similarly repressed cigarette smoke-induced inflammation in an exposure model in mice. Cigarette smoke exposure for four weeks decreased lung PSSG levels, but increased PSSG in lavaged cells and lavage fluid (BALF). Grx1 KO mice had increased levels of PSSG in lung tissue, BALF and BAL cells in response to smoke compared to wt mice. Importantly, levels of multiple inflammatory mediators in the BALF were decreased in Grx1 KO animals following cigarette smoke exposure compared to wt mice, as were levels of neutrophils, dendritic cells and lymphocytes. On the other hand, macrophage numbers were higher in Grx1 KO mice in response to smoke. Although cigarette smoke in vivo caused inverse effects in inflammatory and resident cells with respect to PSSG, primary macrophages and epithelial cells cultured from Grx1 KO mice both produced less KC compared to cells isolated from WT mice after smoke extract exposure. In this manuscript, we provide evidence that Grx1 has an important role in regulating cigarette smoke-induced lung inflammation which seems to diverge from its effects on total PSSG. Secondly, these data expose the differential effect of cigarette smoke on PSSG in inflammatory versus resident lung cells

Toetsing en motivatie: Synergie en balans in formatief handelen en summatief toetsen beïnvloeden vanuit een systemisch perspectief

Leraren in het voortgezet onderwijs die formatief handelen geven informatie over hoe het beoogde doel te bereiken. Leraren die summatief toetsen geven een geïnformeerd oordeel over prestaties. Formatief handelen heeft een motiverende werking, terwijl summatief toetsen niet per se schadelijk is voor de motivatie van leerlingen. Op basis van de resultaten uit het proefschrift van Krijgsman (2021) adviseren we formatief handelen en summatief toetsen te combineren, zodat beide functies elkaar versterken (synergie) zonder eenzijdig de nadruk op een van beiden te leggen (balans). Tot op heden blijft deze synergie en balans uit. Factoren in het gehele onderwijs-ecosysteem beïnvloeden dit. Scholen hebben bijvoorbeeld een grote mate van autonomie op het gebied van toetsing. Tegelijk ontbreekt er een eenduidig landelijk kader voor toetsbeleid en is er behoefte aan professionele ontwikkeling voor schoolleiders, teamleiders en leraren op het gebied van toetsdeskundigheid. Daarnaast worden de behoeften van leerlingen rondom toetsing veelal niet geïnventariseerd bij de ontwikkeling van toetsvisie en -beleid. We pleiten voor een samenwerking tussen leerlingen, leraren, teamleiders, schoolleiders, regionale of nationale leiders, beleidsmakers en wetenschappers, om vanuit een systemisch perspectief dit complexe vraagstuk aan te pakken

Targeting the myeloid microenvironment in neuroblastoma

Myeloid cells (granulocytes and monocytes/macrophages) play an important role in neuroblastoma. By inducing a complex immunosuppressive network, myeloid cells pose a challenge for the adaptive immune system to eliminate tumor cells, especially in high-risk neuroblastoma. This review first summarizes the pro- and anti-tumorigenic functions of myeloid cells, including granulocytes, monocytes, macrophages, and myeloid-derived suppressor cells (MDSC) during the development and progression of neuroblastoma. Secondly, we discuss how myeloid cells are engaged in the current treatment regimen and explore novel strategies to target these cells in neuroblastoma. These strategies include: (1) engaging myeloid cells as effector cells, (2) ablating myeloid cells or blocking the recruitment of myeloid cells to the tumor microenvironment and (3) reprogramming myeloid cells. Here we describe that despite their immunosuppressive traits, tumor-associated myeloid cells can still be engaged as effector cells, which is clear in anti-GD2 immunotherapy. However, their full potential is not yet reached, and myeloid cell engagement can be enhanced, for example by targeting the CD47/SIRPα axis. Though depletion of myeloid cells or blocking myeloid cell infiltration has been proven effective, this strategy also depletes possible effector cells for immunotherapy from the tumor microenvironment. Therefore, reprogramming of suppressive myeloid cells might be the optimal strategy, which reverses immunosuppressive traits, preserves myeloid cells as effectors of immunotherapy, and subsequently reactivates tumor-infiltrating T cells

Ипотека морского судна в контексте восстановление отечественного торгового флота в Украине

Торговельне мореплавство – одна з тих галузей світової економіки, яка має найбільш швидкий розвиток у наш час. Перш за все, це пов’язано із прискоренням міжнародного товарообміну. Наростання обсягів міжнародної торгівлі, у якій прагне приймати участь також Україна, обумовлює необхідність адекватно швидкого зростання її транспортної галузі. Попри значний транспортний потенціал, що має Україна, багато в чому завдячуючи її географічному положенню, стан вітчизняного транспортного комплексу й, особливо, його морської ланки, потребує покращення. Це, в свою чергу, безпосередньо залежить від правового регулювання, що впорядковує такі процеси

Integrated stratigraphy of the Priabonian (upper Eocene) Urtsadzor section, Armenia

The transition from the Bartonian to the Priabonian, as traditionally understood, has long been associated with a series of extinctions and originations in several microfossil groups. The planktonic foraminifer genus Morozovelloides and large species of Acarinina suffered a rapid global extinction, as did many radiolarians. Calcareous nannofossils show several assemblage changes including the acme beginning of Cribrocentrum erbae and the lowest and highest occurrences of Chiasmolithus oamaruensis and C. grandis respectively. In shallow water environments, larger foraminifera also show an extinction among large species of Nummulites, as well as the first occurrences of the stratigraphically important genus Spiroclypeus. However, the correlation between shallow and deep water records remains uncertain, as do the mechanisms driving these biotic events. Here we present the results of a new integrated stratigraphical study (calcareous nannofossils, planktonic foraminifera, larger benthic foraminifera, and low-resolution magnetostratigraphy) of the Urtsadzor section in south-western Armenia which appears to be continuous through this interval. The Urtsadzor section consists of calcareous siltstones rich in micro- and nannofossils, with interbedded limestones containing abundant larger benthic foraminifera. Our new data enable us to correlate larger foraminiferal events with global plankton biostratigraphy, in a section outside of southwest Europe where most previous correlations have been based. At Urtsadzor, the large Nummulites species of N. millecaput-group are present throughout the whole section but decrease in abundance toward the top. The first occurrence of Spiroclypeus, also occurs in the upper part of the section, marking the SBZ 18/19 boundary. These events are associated with the phylogenetic development of the Nummulites fabianii and Heterostegina reticulata lineages. However, the calcareous plankton biostratigraphy indicates the section is well within the Priabonian; within planktonic foraminiferal Zones E14 and E15 and calcareous nannoplankton Zones CNE 18 and CNE 19. These results indicate larger foraminiferal events occur well above the planktonic foraminiferal extinction level and nannofossil assemblage changes indicating the events are not synchronous across groups, with implications for biostratigraphy and recognition of the basal Priabonian in different depositional settings and regions

Lessons learned from a living lab on the broad adoption of eHealth in primary health care

Background: Electronic health (eHealth) solutions are considered to relieve current and future pressure on the sustainability of primary health care systems. However, evidence of the effectiveness of eHealth in daily practice is missing. Furthermore, eHealth solutions are often not implemented structurally after a pilot phase, even if successful during this phase. Although many studies on barriers and facilitators were published in recent years, eHealth implementation still progresses only slowly. To further unravel the slow implementation process in primary health care and accelerate the implementation of eHealth, a 3-year Living Lab project was set up. In the Living Lab, called eLabEL, patients, health care professionals, small- and medium-sized enterprises (SMEs), and research institutes collaborated to select and integrate fully mature eHealth technologies for implementation in primary health care. Seven primary health care centers, 10 SMEs, and 4 research institutes participated. Objective: This viewpoint paper aims to show the process of adoption of eHealth in primary care from the perspective of different stakeholders in a qualitative way. We provide a real-world view on how such a process occurs, including successes and failures related to the different perspectives. Methods: Reflective and process-based notes from all meetings of the project partners, interview data, and data of focus groups were analyzed systematically using four theoretical models to study the adoption of eHealth in primary care. Results: The results showed that large-scale implementation of eHealth depends on the efforts of and interaction and collaboration among 4 groups of stakeholders: patients, health care professionals, SMEs, and those responsible for health care policy (health care insurers and policy makers). These stakeholders are all acting within their own contexts and with their own values and expectations. We experienced that patients reported expected benefits regarding the use of eHealth for self-management purposes, and health care professionals stressed the potential benefits of eHealth and were interested in using eHealth to distinguish themselves from other care organizations. In addition, eHealth entrepreneurs valued the collaboration among SMEs as they were not big enough to enter the health care market on their own and valued the collaboration with research institutes. Furthermore, health care insurers and policy makers shared the ambition and need for the development and implementation of an integrated eHealth infrastructure. Conclusions: For optimal and sustainable use of eHealth, patients should be actively involved, primary health care professionals need to be reinforced in their management, entrepreneurs should work closely with health care professionals and patients, and the government needs to focus on new health care models stimulating innovations. Only when all these parties act together, starting in local communities with a small range of eHealth tools, the potential of eHealth will be enforced