Dental Shape Variation and Phylogenetic Signal in the Rattini Tribe Species of Mainland Southeast Asia

We would like to thank Pierre-Henri Fabre for providing the phylogeny for this study. The collection of specimens used was funded by the French ANR Biodiversity, grant ANR 07 BDIV 012 CERoPath project (www.ceropath.org), and by the French ANR CP&ES, grant ANR 11 CPEL 002 BiodivHealthSEA project (www.biodivhealthsea.org). We also thank Madoudou Garba and Gauthier Dobigny (CBGP-IRD) for providing additional specimens. We greatly thank all local communities and their leaders for permission and invaluable help during field trapping. Special thanks to the CERoPath and BiodivHealthSEA teams and the drivers for their invaluable help during fieldwork. We would also like to thank Maeve McMahon for help with manuscript editing and preparation.Peer reviewedPublisher PD

Annex 65, Long-Term Performance of Super-Insulating-Materials in Building Components and Systems. Report of Subtask II: Scientific Information for Standardization Bodies dealing with Hygro-Thermo-Mechanical Properties and Ageing

This subtask is divided in two actions:Action 2A: Materials Assessment & Ageing Procedures (Experiments & Simulation)Action 2B: Components & Systems Assessment (Experiments & Simulation)As their structures and microstructures are completely different, Super-Insulating Materials (SIMs) cannot be compared directly to traditional insulating materials. Worldwide acceptance of these materials will be improved if the hygro-thermal and mechanical properties of SIM can be clearly articulated and reproduced. In particular, nano-structured materials used to manufacture a SIM are characterized by a high specific area (m\ub2/g) and narrow pores (smaller than 1 μm) which make them very sensitive to gas adsorption and condensation, especially in contact with water molecules.Therefore, methods of characterization must be adapted, or new methods developed to measure the microstructural, hygro-thermal and mechanical properties of these materials and their barrier films.In parallel, modelling methods to describe heat, moisture and air transfer through nano-structured materials and films will have to be developed (adsorption and desorption models, diffusion models, freeze-thawing …).Of course, a few methods will be common to all SIMs, but due to their structural differences some specific modelling methods have to be developed.SIMs can offer considerable advantages (low thickness, low Uvalue) ; however potential drawback effects should be considered in the planning process in order to optimise the development of these extraordinary properties (very low thermal conductivity) and to prevent negative publicity which could be detrimental to this sector of emerging products. This is why ageing tests will be set according to realistic conditions (temperature, moisture, pressure, load …) as set out in SubTask 3A. One objective of artificial ageing is to understand potential degradation processes that could occur. The durability of hydrophobic treatment is one of these processes and will also be subject to discussion and investigation.At the component scale, additional characterizations are needed as panels or rolls are sold by manufacturers. In particular, thermal bridges will be carefully investigated, as the extraordinary thermal performance of SIMs are sensitive to the influence of thermal bridges

Treatment sequences and drug costs from diagnosis to death in multiple myeloma

Novel therapies for multiple myeloma (MM) have improved patient survival, but their high costs strain healthcare budgets. End-of-life phases of treatment are generally the most expensive, however, these high costs may be less justifiable in the context of a less pronounced clinical benefit. To manage drug expenses effectively, detailed information on end-of-life drug administration and costs are crucial. In this retrospective study, we analysed treatment sequences and drug costs from 96 MM patients in the Netherlands who died between January 2017 and July 2019. Patients received up to 16 lines of therapy (median overall survival: 56.5 months), with average lifetime costs of €209 871 (€3111/month; range: €3942–€776 185) for anti-MM drugs. About 85% of patients received anti-MM treatment in the last 3 months before death, incurring costs of €20 761 (range: €70–€50 122; 10% of total). Half of the patients received anti-MM treatment in the last 14 days, mainly fully oral regimens (66%). End-of-life treatment costs are substantial despite limited survival benefits. The use of expensive treatment options is expected to increase costs further. These data serve as a reference point for future cost studies, and further research is needed to identify factors predicting the efficacy and clinical benefit of continuing end-of-life therapy.</p

Stochastic hydrogeology's biggest hurdles analyzed and its big blind spot

This paper considers questions related to the adoption of stochastic methods in hydrogeology. It looks at factors affecting the adoption of stochastic methods including environmental regulations, financial incentives, higher education, and the collective feedback loop involving these factors. We begin by evaluating two previous paper series appearing in the stochastic hydrogeology literature, one in 2004 and one in 2016, and identifying the current thinking on the topic, including the perceived data needs of stochastic methods, the attitude in regulations and the court system regarding stochastic methods, education of the workforce, and the availability of software tools needed for implementing stochastic methods in practice. Comparing the state of adoption in hydrogeology to petroleum reservoir engineering allowed us to identify quantitative metrics on which to base our analysis. For impediments to the adoption of stochastic hydrology, we identified external factors as well as self-inflicted wounds. What emerges is a picture much broader than current views. Financial incentives and regulations play a major role in stalling adoption. Stochastic hydrology's blind spot is in confusing between uncertainty with risk and ignoring uncertainty. We show that stochastic hydrogeology comfortably focused on risk while ignoring uncertainty, to its own detriment and to the detriment of its potential clients. The imbalance between the treatment on risk on one hand and uncertainty on the other is shown to be common to multiple disciplines in hydrology that interface with risk and uncertainty.</p

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

Reconsidering domestication from a process archaeology perspective

Process philosophy offers a metaphysical foundation for domestication studies. This grounding is especially important given the European colonialist origin of ‘domestication’ as a term and 19th century cultural project. We explore the potential of process archaeology for deep-time investigation of domestication relationships, drawing attention to the variable pace of domestication as an ongoing process within and across taxa; the nature of domestication ‘syndromes’ and ‘pathways’ as general hypotheses about process; the importance of cooperation as well as competition among humans and other organisms; the significance of non-human agency; and the ubiquity of hybrid communities that resist the simple wild/domestic dichotomy

Observation of Large Topologically Trivial Fermi-Arcs in the Candidate Type-II Weyl Semimetal WTe2

We report angle-resolved photoemission experiments resolving the distinct electronic structure of the inequivalent top and bottom (001) surfaces of WTe2. On both surfaces, we identify a surface state that forms a large Fermi-arc emerging out of the bulk electron pocket. Using surface electronic structure calculations, we show that these Fermi arcs are topologically trivial and that their existence is independent of the presence of type-II Weyl points in the bulk band structure. This implies that the observation of surface Fermi arcs alone does not allow the identification of WTe2 as a topological Weyl semimetal. We further use the identification of the two different surfaces to clarify the number of Fermi surface sheets in WTe2.Comment: Accepted in Physical Review B Rapid Communication on 16 Aug 201

Direct evidence for flat bands in twisted bilayer graphene from nano-ARPES

Transport experiments in twisted bilayer graphene revealed multiple superconducting domes separated by correlated insulating states. These properties are generally associated with strongly correlated states in a flat mini-band of the hexagonal moir\'e superlattice as it was predicted by band structure calculations. Evidence for such a flat band comes from local tunneling spectroscopy and electronic compressibility measurements, reporting two or more sharp peaks in the density of states that may be associated with closely spaced van Hove singularities. Direct momentum resolved measurements proved difficult though. Here, we combine different imaging techniques and angle resolved photoemission with simultaneous real and momentum space resolution (nano-ARPES) to directly map the band dispersion in twisted bilayer graphene devices near charge neutrality. Our experiments reveal large areas with homogeneous twist angle that support a flat band with spectral weight that is highly localized in momentum space. The flat band is separated from the dispersive Dirac bands which show multiple moir\'e hybridization gaps. These data establish the salient features of the twisted bilayer graphene band structure.Comment: Submitted to Nature Materials. Nat. Phys. (2020

Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4(+) T Cell Metabolic Rewiring

Accumulation of lactate in the tissue microenvironment is a feature of both inflammatory disease and cancer. Here, we assess the response of immune cells to lactate in the context of chronic inflammation. We report that lactate accumulation in the inflamed tissue contributes to the upregulation of the lactate transporter SLC5A12 by human CD4+ T&nbsp;cells. SLC5A12-mediated lactate uptake into CD4+ T&nbsp;cells induces a reshaping of their effector phenotype, resulting in increased IL17 production via nuclear PKM2/STAT3 and enhanced fatty acid synthesis. It also leads to CD4+ T&nbsp;cell retention in the inflamed tissue as a consequence of reduced glycolysis and enhanced fatty acid synthesis. Furthermore, antibody-mediated blockade of SLC5A12 ameliorates the disease severity in a murine model of arthritis. Finally, we propose that lactate/SLC5A12-induced metabolic reprogramming is a distinctive feature of lymphoid synovitis in rheumatoid arthritis patients and a potential therapeutic target in chronic inflammatory disorders

Quality of life gains in frail and intermediate-fit patients with multiple Myeloma:Findings from the prospective HOVON123 clinical trial

Background: Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. Methods: The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p &lt; 0.005) and clinically relevant (&gt;MID). Results: 137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. Conclusion: HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.</p