Information, Experience, and Willingness to Mitigate Mental Health Consequences From Flooding Through Collective Defence

Demand for reducing mental health impacts from flooding through collective flood defence is elicited using a contingent valuation method with a sequential hypothetical scenario, which accounts for human resilience and experience. A two-step model fits the survey data: it combines a binary sample selection rule to distinguish protesters and participants with a Tobit model to accommodate true zero responses among participants. Results show that non-symptoms-specific information on mental health risk may bias the willingness to pay downward. Risk-averse individuals who have taken self-insurance protection measures are willing to pay for additional protection through collective defence. Feelings, such as worries and anxiety related to flooding, drive the demand, which supports the risk-as-feelings hypothesis for mental health protection from flooding. Inexperience rather than experience of flooding is found to increase demand, which indicates that individual mental resilience to flooding may increase after an event as posited by the inoculation hypothesis. © 2022. American Geophysical Union. All Rights Reserved.This paper is supported by María de Maetzu excellence accreditation 2018–2022 (Ref. MDM‐2017‐0714), funded by MCIN/AEI/10.13039/501100011033/; and by the Basque Government through the BERC 2022–2025 program

Determinants of travel mode choice in Europe: Results from a survey on routine mobility

Understanding the differences in travel behaviour across different countries underlined by trip and individual characteristics are paramount to develop effective policies to nudge a shift towards sustainable mobility. In this study we present a descriptive analysis of the results of a mobility household survey, collecting information on citizen travel behaviour, travel mode choices and the factors influencing them. The study involves five European countries: Hungary, Italy, Norway, Poland and Spain. Results describe how travel mode choice fluctuates with users’ heterogeneity and that different mobility transition policies receive different support from citizens. Instruments implying a direct financial cost are much less accepted than technology- and infrastructure-based policies. Support to policies such as road expansion is also observed. The transition in mobility should then have to deal with households’ beliefs to make them revise their travel behaviours. But the mobility transition is also closely linked to the city development and the distribution of workplace and grocery shopping in the cit

Factors affecting energy-efficiency investment in the hotel industry: survey results from Spain

Increasing energy efficiency is a major way of saving energy and thus reducing energy expenses. However, adoption of energy efficiency is generally low, as demonstrated by the energy efficiency gap. To understand that gap, this paper analyses the factors that affect how the energy efficiency attribute is rated in investment in heating, ventilation and air conditioning (HVAC) systems in the hotel industry in Spain. A survey conducted on two hundred owners of hotels, hostels and holiday cottages (referred to jointly here for the sake of convenience as the hotel industry ) shows that the value placed on energy efficiency is influenced not just by climate conditions, environmental concern and type of hotel but also by other attributes of the HVAC system such as brand reliability, price and performance. The hotel industry may also be identifying EE as a proxy for quality rather than savings. Designing the right energy-efficiency policy entails accounting for potential responses by agents, and this analysis helps identify those drivers to which they may or may not respond. © 2021, The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.This study was undertaken as a part of the CONSumer Energy Efficiency Decision making (CONSEED) project, an EU-funded H2020 research project under grant agreement number 723741. This research is also supported by the Spanish State Research Agency through María de Maeztu Excellence Unit accreditation 2018-2022 (Ref. MDM-2017- 0714) and the Basque Government BERC programme. Financial support from the Government of Spain and the European Regional Development Fund through grants RTI2018-093692-B-I00, RTC2019- 007315-3 and RED2018-102794-T is gratefully acknowledged

The contribution of carsharing to low carbon mobility: Complementarity and substitution with other modes

This paper analyses both the attributes of carsharing transport modes (station-based and free-floating) and their relationship with other transport modes. Users' and stakeholders’ perspectives are synthesized from in-depth interviews in Spain. The elicitation of the comparative advantages of the two carsharing modes with respect to public transport and private vehicles helps identifying factors such as availability of parking, road pricing and convenience that drive the complementary and substitution property of carsharing with other transport modes. Interviews show the limited complementarity of carsharing with public transport, as well as the limited substitutability with private vehicles. Potential policy instruments to make carsharing coexist with public transport are discussed.The authors acknowledge support from the European Union Horizon 2020 research and innovations programme under grant agreement N?727524, Project: ?Enabling the Energy Union through understanding the drivers of individual and collective energy choices, in Europe?. This research is also supported by the Spanish State Research Agency through Mar?a de Maeztu Excellence Unit accreditation 2018?2022 (Ref. MDM-2017-0714); and by the Basque Government through the BERC 2018?2021 program. Alberto Ansuategi gratefully acknowledges financial support from the Spanish Ministry of Science and Innovation (grant RTI2018-093352-B-100) and the UPV/EHU (grant GIC18/29). Ibon Galarraga also wishes to acknowledge the financial support from the Government of Spain and the European Regional Development Fund through grant RTI2018-093692-B-I00

Consumers’ preferences regarding energy efficiency: a qualitative analysis based on the household and services sectors in Spain

Informational failures frequently lead consumers to make non-optimal energy-efficient purchasing decisions. Energy efficiency labels seek to influence consumer behaviour at the point of sale by reducing informational failures regarding energy efficiency. However, several informational and behavioural factors contribute to the energy efficiency gap and could render label-oriented policies useless. The purchasing decision model of Allcott and Greenstone (The Journal of Economic Perspectives, 26, 3 28, 2012) is used here to explore the different factors that influence purchasing decisions and understand (i) the importance of energy consumption compared to other attributes; (ii) how consumers weight energy savings and (iii) what other benefits and costs influence the purchase of energy-efficient goods. The analysis reported here is based on qualitative research methods and is conducted in the household and service sectors (the accommodation sector and private service companies), for appliances, heating and cooling systems and cars in Spain. Results show that (i) there is still an informational gap regarding energy labels and (ii) bounded rationality and end-user behaviour are important limiting factors for the purchase of energy-efficient goods in Spain. © 2020, The Author(s).This work was undertaken as a part of the CONSumer Energy Efficiency Decision making (CONSEED) project, an EU-funded H2020 research project under grant agreement number 723741. This research is also supported by the Spanish State Research Agency through María de Maeztu Excellence Unit accreditation 2018-2022 (Ref. MDM-2017-0714). Amaia de Ayala would like to thank the financial support of Fundación Ramón Areces under the project entitled “La toma de decisiones de los hogares en eficiencia energética: determinantes y diseño de políticas”

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic

The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans

Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation

Both fast-cycling and quiescent mouse hematopoietic stem cells (HSCs) can reconstitute lifelong hematopoiesis, and HSC cycling status can fluctuate over time in steady state and accelerate upon inflammation

The pharmacological effect of BGC20-1531, a novel prostanoid EP4 receptor antagonist, in the Prostaglandin E2 human model of headache

Using a human Prostaglandin E2 (PGE2) model of headache, we examined whether a novel potent and selective EP4 receptor antagonist, BGC20-1531, may prevent headache and dilatation of the middle cerebral (MCA) and superficial temporal artery (STA). In a three-way cross-over trial, eight healthy volunteers were randomly allocated to receive 200 and 400 mg BGC20-1531 and placebo, followed by a 25-min infusion of PGE2. We recorded headache intensity on a verbal rating scale, MCA blood flow velocity and STA diameter. There was no difference in headache response or prevention of the dilation of the MCA or the STA (P > 0.05) with either dose of BGC20-1531 relative to placebo, although putative therapeutic exposures were not reached in all volunteers. In conclusion, these data suggest that the other EP receptors may be involved in PGE2 induced headache and dilatation in normal subjects

ERK1 Regulates the Hematopoietic Stem Cell Niches

The mitogen-activated protein kinases (MAPK) ERK1 and ERK2 are among the major signal transduction molecules but little is known about their specific functions in vivo. ERK activity is provided by two isoforms, ERK1 and ERK2, which are ubiquitously expressed and share activators and substrates. However, there are not in vivo studies which have reported a role for ERK1 or ERK2 in HSCs and the bone marrow microenvironment. The present study shows that the ERK1-deficient mice present a mild osteopetrosis phenotype. The lodging and the homing abilities of the ERK1−/− HSC are impaired, suggesting that the ERK1−/−-defective environment may affect the engrafment of HSCs. Serial transplantations demonstrate that ERK1 is involved in the maintenance of an appropriate medullar microenvironment, but that the intrinsic properties of HSCs are not altered by the ERK1−/− defective microenvironment. Deletion of ERK1 impaired in vitro and in vivo osteoclastogenesis while osteoblasts were unaffected. As osteoclasts derive from precursors of the monocyte/macrophage lineage, investigation of the monocytic compartment was performed. In vivo analysis of the myeloid lineage progenitors revealed that the frequency of CMPs increased by approximately 1.3-fold, while the frequency of GMPs significantly decreased by almost 2-fold, compared with the respective WT compartments. The overall mononuclear-phagocyte lineage development was compromised in these mice due to a reduced expression of the M-CSF receptor on myeloid progenitors. These results show that the cellular targets of ERK1 are M-CSFR-responsive cells, upstream to osteoclasts. While ERK1 is well known to be activated by M-CSF, the present results are the first to point out an ERK1-dependent M-CSFR regulation on hematopoietic progenitors. This study reinforces the hypothesis of an active cross-talk between HSCs, their progeny and bone cells in the maintenance of the homeostasis of these compartments