Moist and warm conditions in Eurasia during the last glacial of the Middle Pleistocene Transition

The end of the Middle Pleistocene Transition (MPT, ~ 800-670 thousand years before present, ka) was characterised by the emergence of large glacial ice-sheets associated with anomalously warm North Atlantic sea surface temperatures enhancing moisture production. Still, the direction and intensity of moisture transport across Eurasia towards potential ice-sheets is poorly constrained. To reconstruct late MPT moisture production and dispersal, we combine records of upper ocean temperature and pollen-based Mediterranean forest cover, a tracer of westerlies and precipitation, from a subtropical drill-core collected off South-West Iberia, with records of East Asia summer monsoon (EASM) strength and West Pacific surface temperatures, and model simulations. Here we show that south-western European winter precipitation and EASM strength reached high levels during the Marine Isotope Stage 18 glacial. This anomalous situation was caused by nearly-continuous moisture supply from both oceans and its transport to higher latitudes through the westerlies, likely fuelling the accelerated expansion of northern hemisphere ice-sheets during the late MPT. © 2023, The Author(s).This research used samples collected during the Expedition no. 339 “Mediterranean Outflow“ of the Integrated Ocean Drilling Program (IODP). M.F.S.G. acknowledges funding from the GPR Human Past (University of Bordeaux). A.B. thanks Deutsche Forschungsgemeinschaft (DFG), project BA 3809/8. C.Z. acknowledges funding from IODP France and J.M.P.-M. from the Junta de Castilla y León and the European Regional Development Fund (Grant CLU-2019-03). T.R. acknowledges funding from FCT through projects Hydroshift (PTDC/CTA-CLI/4297/2021), WarmWorld (PTDC/CTA-GEO/29897/2017), UIDB/04326/2020, UIDP/04326/2020, LA/P/0101/2020 and EMSO-PT (POCI-01-0145-FEDER-022157). We thank Vincent Hanquiez for drawing Fig. and Ludovic Devaux for pollen sample preparation

Kinematic analysis of the Large Magellanic Cloud using Gaia DR3

Context: The high quality of the Gaia mission data is allowing to study the internal kinematics of the Large Magellanic Cloud (LMC) in unprecedented detail, providing insights on the non-axisymmetric structure of its disc. Aims: To define and validate an improved selection strategy to distinguish the LMC stars from the Milky Way foreground. To check the possible biases that assumed parameters or sample contamination from the Milky Way can introduce in the analysis of the internal kinematics of the LMC using Gaia data. Methods: Our selection is based on a supervised Neural Network classifier using as much as of the Gaia DR3 data as possible. We select three samples of candidate LMC stars with different degrees of completeness and purity; we validate them using different test samples and we compare them with the Gaia Collaboration paper sample. We analyse the resulting velocity profiles and maps, and we check how these results change when using also the line-of-sight velocities, available for a subset of stars. Results: The contamination in the samples from Milky Way stars affects basically the results for the outskirts of the LMC, and the absence of line-of-sight velocities does not bias the results for the kinematics in the inner disc. For the first time, we perform a kinematic analysis of the LMC using samples with the full three dimensional velocity information from Gaia DR3. Conclusions: The dynamics in the inner disc is mainly bar dominated; the kinematics on the spiral arm over-density seem to be dominated by an inward motion and a rotation faster than that of the disc in the piece of the arm attached to the bar; contamination of MW stars seem to dominate the outer parts of the disc and mainly affects old evolutionary phases; uncertainties in the assumed disc morphological parameters and line-of-sight velocity of the LMC can in some cases have significant effects. [ABRIDGED

Striatal expression of GDNF and differential vulnerability of midbrain dopaminergic cells

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta superfamily that when exogenously administrated exerts a potent trophic action on dopaminergic (DA) cells. Although we know a lot about its signalling mechanisms and pharmacological effects, physiological actions of GDNF on the adult brain remain unclear. Here, we have used morphological and molecular techniques, and an experimental model of Parkinson's disease in rats, to investigate whether GDNF constitutively expressed in the adult mesostriatal system plays a neuroprotective role on midbrain DA cells. We found that although all midbrain DA cells express both receptor components of GDNF (GFRalpha1 and Ret), those in the ventral tegmental area (VTA) and rostromedial substantia nigra (SNrm) also contain GDNF but not GDNFmRNA. The levels of GDNFmRNA are significantly higher in the ventral striatum (vSt), the target region of VTA and SNrm cells, than in the dorsal striatum (dSt), the target region of DA cells in the caudoventral substantia nigra (SNcv). After fluoro-gold injection in striatum, VTA and SNrm DA cells show triple labelling for tyrosine hydroxylase, GDNF and fluoro-gold, and after colchicine injection in the lateral ventricle, they become GDNF-immunonegative, suggesting that GDNF in DA somata comes from their striatal target. As DA cells in VTA and SNrm are more resistant than those in SNcv to intracerebroventricular injection of 6-OHDA, as occurs in Parkinson's disease, we can suggest that the fact that they project to vSt, where GDNF expression is significantly higher than in the dSt, is a neuroprotective factor involved in the differential vulnerability of midbrain DA neurons

Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry

Background and purpose: Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP), (ii) quantify likely long-term benefits by extrapolating results, and (iii) assess the plausibility of extrapolations using an independent real-world cohort (MSBase registry; ACTRN12605000455662). Methods: Post hoc analyses assessing time to 24-week confirmed EDSS ≥7.0 in two cohorts of patients with primary progressive multiple sclerosis (baseline EDSS 3.0–6.5) were investigated in ORATORIO and MSBase. Results: In the ORATORIO DBP+ECP, ocrelizumab reduced the risk of 24-week confirmed EDSS ≥7.0 (hazard ratio = 0.54, 95% confidence interval [CI]: 0.31–0.92; p = 0.022). Extrapolated median time to 24-week confirmed EDSS ≥7.0 was 12.1 and 19.2 years for placebo and ocrelizumab, respectively (7.1-year delay [95% CI: −4.3 to 18.4]). In MSBase, the median time to 24-week confirmed EDSS ≥7.0 was 12.4 years. Conclusions: Compared with placebo, ocrelizumab significantly delayed time to 24-week confirmed wheelchair requirement in ORATORIO. The plausibility of the extrapolated median time to reach this milestone in the placebo group was supported by observed real-world data from MSBase. Extrapolated benefits for ocrelizumab over placebo could represent a truly meaningful delay in loss of ambulation and independence

University–industry collaboration: using meta-rules to overcome barriers to knowledge transfer

This is the final version of the article. Available from Springer Verlag via the DOI in this record.University–industry knowledge transfer is an important source wealth of creation for all partners; however, the practical management of this activity within universities is often hampered by procedural rigidity either through the absence of decision-making protocols to reconcile conflicting priorities or through the inconsistent implementation of existing policies. This is problematic, since it can impede operational effectiveness, prevent inter-organisational knowledge-creation and hamper organisational learning. This paper addresses this issue by adopting a cross-discipline approach and presenting meta-rules as a solution to aid organisational decision making. It is proposed that meta-rules can help resolve tensions arising from conflicting priorities between academics, knowledge transfer offices and industry and help facilitate strategic alignment of processes and policies within and between organisations. This research contributes to the growing debate on the strategic challenges of managing knowledge transfer and presents meta-rules as a practical solution to facilitate strategic alignment of internal and external stakeholder tensions. Meta-rules has previously only been applied in a computer intelligence context however, this research proves the efficacy of meta rules in a university–industry knowledge transfer context. This research also has practical implications for knowledge transfer office managers who can use meta-rules to help overcome resource limitations, conflicting priorities and goals of diverse internal and external stakeholders

Engaging business in curriculum design and delivery: a higher education institution perspective

University-business cooperation has risen to one of the top priorities for many higher education institutions, with its importance mirroring attention from scholars and policy makers worldwide. Despite prolific research in this area, however, few have investigated curriculum-related university-business cooperation or its facilitators. Hence, this study investigates five mechanisms as drivers of business engagement in the design and delivery of the curriculum and the alignment of the curriculum with business needs. Results of a European-wide survey of higher education institution managers show the positive impact of senior management engagement, alumni networks and external com- munication of university-business cooperation, particularly on business engagement in curriculum design and the curriculum meeting industry needs. The higher education institution’s dedication of resources emerged as irrelevant in this context. The conceptual model is validated across higher education institutions with different levels of curriculum- related cooperation with business and across three countries, leading to implications for management and future research directions.Carolin Plewa, Victoria Galan-Muros, Todd Dave

University-business cooperation outcomes and impacts - A European perspective

University-Business Cooperation (UBC) is gaining importance within European HEIs, and increasing amounts of resources are invested in it, by the HEIs themselves and governments at different levels. In the face of rising scrutiny of their contribution to society, universities, and the governments funding them, are increasingly challenged to justify the organisational and societal outcomes and impacts of UBC. However, until now, methods for evaluating UBC have failed to capture its full value and complexity. This paper explores the topic and history of UBC outcome and impact evaluation, highlights some often overlooked factors that require further consideration, and suggests a preliminary framework for standardised evaluation of UBC outcomes and impacts.Todd Davey, Carolin Plewa and Victoria Galan Muro