Non-Locality and Theories of Causation

The aim of the paper is to investigate the characterization of an unambiguous notion of causation linking single space-llike separated events in EPR-Bell frameworks. This issue is investigated in ordinary quantum mechanics, with some hints to no collapse formulations of the theory such as Bohmian mechanics.Comment: Presented at the NATO Advanced Research Workshop on Modality, Probability and Bell's Theorems, Cracow, Poland, August 19-23, 200

Urban green space and mental health among people living alone: The mediating roles of relational and collective restoration in an 18-country sample

This is the final version. Available on open access from Elsevier via the DOI in this record. Rates of living alone, especially in more urbanised areas, are increasing across many industrialised countries, with associated increases in feelings of loneliness and poorer mental health. Recent studies have suggested that access to nature (e.g. parks and green spaces) can reduce the stressors associated with loneliness, partly through providing opportunities to nurture personal relationships (relational restoration) and engage in normative community activities (collective restoration). Such associations might vary across different household compositions and socio-demographic or geographical characteristics, but these have not been thoroughly tested. Using data collected across 18 countries/territories in 2017-2018, we grouped urban respondents into those living alone (n = 2062) and those living with a partner (n = 6218). Using multigroup path modelling, we tested whether the associations between neighbourhood greenspace coverage (1-km-buffer from home) and mental health are sequentially mediated by: (a) visits to greenspace; and subsequently (b) relationship and/or community satisfaction, as operationalisations of relational and collective restoration, respectively. We also tested whether any indirect associations varied among subgroups of respondents living alone. Analyses showed that visiting green space was associated with greater mental well-being and marginally lower odds of using anxiety/depression medication use indirectly, mediated via both relationship and community satisfaction. These indirect associations were equally strong among respondents living alone and those living with a partner. Neighbourhood green space was, additionally, associated with more visits among respondents living with a partner, whereas among those living alone, this was sensitive to the green space metric. Within subgroups of people living alone, few overall differences were found. Some indirect pathways were, nevertheless, stronger in males, under 60-year-olds, those with no financial strain, and residents in warmer climates. In conclusion, supporting those living alone, as well as those living with a partner, to more frequently access their local greenspaces could help improve mental health via promoting relational and collective restoration.Academy of FinlandTHL foundatio

Nature contact and general health: testing multiple serial mediation pathways with data from adults in 18 countries

This is the final version. Available on open access from Elsevier via the DOI in this record. Data availability: A subset of the data is available at: (Elliott, LR, White, MP. 2022. BlueHealth International Survey Dataset, 2017-2018. [data collection]. UK Data Service. SN: 8874, doi: 10.5255/UKDA-SN-8874-2).The role of neighbourhood nature in promoting good health is increasingly recognised in policy and practice, but consistent evidence for the underlying mechanisms is lacking. Heterogeneity in exposure methods, outcome measures, and population characteristics, little exploration of recreational use or the role of different types of green or blue space, and multiple separate mediation models in previous studies have limited our ability to synthesise findings and draw clear conclusions. We examined multiple pathways linking different types of neighbourhood nature with general health using a harmonised international sample of adults. Using cross-sectional survey data from 18 countries (n = 15,917), we developed a multigroup path model to test theorised pathways, controlling for sociodemographic variables. We tested the possibility that neighbourhood nature (e.g. greenspace, inland bluespace, and coastal bluespace) would be associated with general health through lower air pollution exposure, greater physical activity attainment, more social contact, and higher subjective well-being. However, our central prediction was that associations between different types of neighbourhood nature and general health would largely be serially mediated by recent visit frequency to corresponding environment types, and, subsequently, physical activity, social contact, and subjective well-being associated with these frequencies. Several subsidiary analyses assessed the robustness of the results to alternative model specifications as well as effect modification by sociodemographics. Consistent with this prediction, there was statistical support for eight of nine potential serial mediation pathways via visit frequency which held for a range of alternative model specifications. Effect modification by financial strain, sex, age, and urbanicity altered some associations but did not necessarily support the idea that nature reduced health inequalities. The results demonstrate that across countries, theorised nature-health linkages operate primarily through recreational contact with natural environments. This provides arguments for greater efforts to support use of local green/blue spaces for health promotion and disease prevention.European Union Horizon 202

Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer

In this phase II, multicentre trial, patients with metastatic breast cancer (MBC) were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET). The primary objective of this study was to determine the tolerability and activity in terms of complete responce (CR) and overall response rate of the GET combination in this patient population. Patients with no prior treatment for MBC, and at least one bidimensionally measurable lesion received gemcitabine 1000 mg m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1, every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were enrolled from seven Italian institutions. A total of 297 chemotherapy courses were administered with a median of six cycles patient(-1) (range 1-8). Seven patients (15%) obtained CR and 27 patients (56%) had partial responce, for an overall response rate of 71% (95%; CI: 58.3-83.7). After a median follow-up of 23.7 months (range 7.0-34.4), median progression-free survival was 10.5 months (95%; CI: 9.2-11.7), and median overall survival 25.9 months. The main haematological toxicity consisted of grade 3 or 4 neutropenia that occurred in 62% of cycles (22% grade 4 and 40% grade 3). The GET combination is active and well tolerated as first-line chemotherapy for MBC

Research Note: Residential distance and recreational visits to coastal and inland blue spaces in eighteen countries

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: The data used in this research will be open access in the future under the BlueHealth project's participation in the EU Open Data Pilot (Openaire).Varied categorisations of residential distance to bluespace in population health studies make comparisons difficult. Using survey data from eighteen countries, we modelled relationships between residential distance to blue spaces (coasts, lakes, and rivers), and self-reported recreational visits to these environments at least weekly, with penalised regression splines. We observed exponential declines in visit probability with increasing distance to all three environments and demonstrated the utility of derived categorisations. These categories may be broadly applicable in future research where the assumed underlying mechanism between residential distance to a blue space and a health outcome is direct recreational contact.European Union Horizon 202

Results from an 18 country cross-sectional study examining experiences of nature for people with common mental health disorders

This is the final version. Available on open access from Nature Research via the DOI in this recordExposure to natural environments is associated with a lower risk of common mental health disorders (CMDs), such as depression and anxiety, but we know little about nature-related motivations, practices and experiences of those already experiencing CMDs. We used data from an 18-country survey to explore these issues (n = 18,838), taking self-reported doctor-prescribed medication for depression and/or anxiety as an indicator of a CMD (n = 2698, 14%). Intrinsic motivation for visiting nature was high for all, though slightly lower for those with CMDs. Most individuals with a CMD reported visiting nature ≥ once a week. Although perceived social pressure to visit nature was associated with higher visit likelihood, it was also associated with lower intrinsic motivation, lower visit happiness and higher visit anxiety. Individuals with CMDs seem to be using nature for self-management, but ‘green prescription’ programmes need to be sensitive, and avoid undermining intrinsic motivation and nature-based experiences.European Union Horizon 202

Comparison of the structure and activity of glycosylated and asglycosylated human carboxylesterase 1

Human Carboxylesterase 1 (hCES1) is the key liver microsomal enzyme responsible for detoxification and metabolism of a variety of clinical drugs. To analyse the role of the single N-linked glycan on the structure and activity of the enzyme, authentically glycosylated and aglycosylated hCES1, generated by mutating asparagine 79 to glutamine, were produced in human embryonic kidney cells. Purified enzymes were shown to be predominantly trimeric in solution by analytical ultracentrifugation. The purified aglycosylated enzyme was found to be more active than glycosylated hCES1 and analysis of enzyme kinetics revealed that both enzymes exhibit positive cooperativity. Crystal structures of hCES1 a catalytically inactive mutant (S221A) and the aglycosylated enzyme were determined in the absence of any ligand or substrate to high resolutions (1.86 Å, 1.48 Å and 2.01 Å, respectively). Superposition of all three structures showed only minor conformational differences with a root mean square deviations of around 0.5 Å over all Cα positions. Comparison of the active sites of these un-liganded enzymes with the structures of hCES1-ligand complexes showed that side-chains of the catalytic triad were pre-disposed for substrate binding. Overall the results indicate that preventing N-glycosylation of hCES1 does not significantly affect the structure or activity of the enzyme

Associations between green/blue spaces and mental health across 18 countries

This is the final version. Available on open access from Nature Research via the DOI in this record.Data availability: All data for the BlueHealth International Survey will be made open access in 2025 in accordance with an embargo agreement by research partners. For queries about the specifc data and analysis, including r script, used in the present manuscript please contact the corresponding author.Living near, recreating in, and feeling psychologically connected to, the natural world are all associated with better mental health, but many exposure-related questions remain. Using data from an 18-country survey (n = 16,307) we explored associations between multiple measures of mental health (positive well-being, mental distress, depression/anxiety medication use) and: (a) exposures (residential/recreational visits) to different natural settings (green/inland-blue/coastal-blue spaces); and (b) nature connectedness, across season and country. People who lived in greener/coastal neighbourhoods reported higher positive well-being, but this association largely disappeared when recreational visits were controlled for. Frequency of recreational visits to green, inland-blue, and coastal-blue spaces in the last 4 weeks were all positively associated with positive well-being and negatively associated with mental distress. Associations with green space visits were relatively consistent across seasons and countries but associations with blue space visits showed greater heterogeneity. Nature connectedness was also positively associated with positive well-being and negatively associated with mental distress and was, along with green space visits, associated with a lower likelihood of using medication for depression. By contrast inland-blue space visits were associated with a greater likelihood of using anxiety medication. Results highlight the benefits of multi-exposure, multi-response, multi-country studies in exploring complexity in nature-health associations.European Union’ Horizon 202

De novo design of transmembrane β-barrels

Transmembrane b-barrel proteins (TMBs) are of great interest for single-molecule analytical technologies because they can spontaneously fold and insert into membranes and form stable pores, but the range of pore properties that can be achieved by repurposing natural TMBs is limited. We leverage the power of de novo computational design coupled with a “hypothesis, design, and test” approach to determine TMB design principles, notably, the importance of negative design to slow b-sheet assembly. We design new eight-stranded TMBs, with no homology to known TMBs, that insert and fold reversibly into synthetic lipid membranes and have nuclear magnetic resonance and x-ray crystal structures very similar to the computational models. These advances should enable the custom design of pores for a wide range of applications

A Cytochrome b561 with Ferric Reductase Activity from the Parasitic Blood Fluke, Schistosoma japonicum

Parasites acquire their food from their hosts, either by feeding directly on tissues of the host, or by competing for ingested food. Adult schistosomes live within the vasculature of humans and rely on the blood cells and plasma they ingest and dissolved solutes they derive across their body surface, the tegument, for their nutrition. Schistosomes require host trace elements, notably iron, which is used as a co-factor in many biological reactions. Iron is especially important for schistosomes, for it has a significant role in egg formation and embryogenesis. In human tissues, iron predominates in the trivalent (ferric) form; however, it is the divalent (ferrous) form that is used as an essential co-factor for multiple biomolecules and enzymes. In order to be acquired from the host environment, the valency of iron must be modified to render it suitable for transport across the parasite membrane. This paper describes the molecular characterisation of a schistosome molecule that is crucial for bringing about this change in iron. Schistosoma japonicum Cytb561 is the first ferric reductase characterised in any parasitic helminth and emphasises the importance of iron, and other divalent cations, in these organisms