Improving sustainability through intelligent cargo and adaptive decision making

In the current society, logistics is faced with the challenge to meet more stringent sustainability goals. Shippers and transport service providers both aim to reduce the carbon footprint of their logistic operations. To do so, optimal use of logistics resources and physical infrastructure should be aimed for. An adaptive decision making process for the selection of a specific transport modality, transport provider and timeslot (aimed at minimisation of the carbon footprint) enables shippers to achieve this. This requires shippers to have access to up-to-date capacity information from transport providers (e.g. current and scheduled loading status of the various transport means and information on carbon footprint) and traffic information (e.g. city logistics and current traffic information). A prerequisite is an adequate infrastructure for collaboration and open exchange of information between the various stakeholders in the logistics value chain to obtain the up-to-date information. This paper gives a view on how such an advanced information infrastructure can be realised, currently being developed within the EU iCargo project. The paper describes a reference logistics value chain, including business benefits for each of the roles in the logistics value chain of aiming for sustainability. A case analysis is presented that reflects a practical situation in which the various roles collaborate and exchange information for realizing sustainability goals, using adaptive decision making for selecting a transport modality, transport provider, and timeslot. A high-level overview is provided of the requirements on and technical implementation of the supporting advanced infrastructure for collaboration and open information exchange.In the current society, logistics is faced with the challenge to meet more stringent sustainability goals. Shippers and transport service providers both aim to reduce the carbon footprint of their logistic operations. To do so, optimal use of logistics resources and physical infrastructure should be aimed for. An adaptive decision making process for the selection of a specific transport modality, transport provider and timeslot (aimed at minimisation of the carbon footprint) enables shippers to achieve this. This requires shippers to have access to up-to-date capacity information from transport providers (e.g. current and scheduled loading status of the various transport means and information on carbon footprint) and traffic information (e.g. city logistics and current traffic information). A prerequisite is an adequate infrastructure for collaboration and open exchange of information between the various stakeholders in the logistics value chain to obtain the up-to-date information. This paper gives a view on how such an advanced information infrastructure can be realised, currently being developed within the EU iCargo project. The paper describes a reference logistics value chain, including business benefits for each of the roles in the logistics value chain of aiming for sustainability. A case analysis is presented that reflects a practical situation in which the various roles collaborate and exchange information for realizing sustainability goals, using adaptive decision making for selecting a transport modality, transport provider, and timeslot. A high-level overview is provided of the requirements on and technical implementation of the supporting advanced infrastructure for collaboration and open information exchange.In the current society, logistics is faced with the challenge to meet more stringent sustainability goals. Shippers and transport service providers both aim to reduce the carbon footprint of their logistic operations. To do so, optimal use of logistics resources and physical infrastructure should be aimed for. An adaptive decision making process for the selection of a specific transport modality, transport provider and timeslot (aimed at minimisation of the carbon footprint) enables shippers to achieve this. This requires shippers to have access to up-to-date capacity information from transport providers (e.g. current and scheduled loading status of the various transport means and information on carbon footprint) and traffic information (e.g. city logistics and current traffic information). A prerequisite is an adequate infrastructure for collaboration and open exchange of information between the various stakeholders in the logistics value chain to obtain the up-to-date information. This paper gives a view on how such an advanced information infrastructure can be realised, currently being developed within the EU iCargo project. The paper describes a reference logistics value chain, including business benefits for each of the roles in the logistics value chain of aiming for sustainability. A case analysis is presented that reflects a practical situation in which the various roles collaborate and exchange information for realizing sustainability goals, using adaptive decision making for selecting a transport modality, transport provider, and timeslot. A high-level overview is provided of the requirements on and technical implementation of the supporting advanced infrastructure for collaboration and open information exchange

The rejected self : young people’s experiences of self-hatred, self-harm and finding acceptance

The aim of this study was to investigate how individuals with a history of adolescent self-harm perceive their experience of repetitive self-harm. This study explores the experiences of young people who engaged in repetitive self-harm during adolescence but have subsequently stopped. Due to the lack of qualitative research on this topic and the potential for stigma relating to self harm, it was considered pertinent to focus on individuals’ lived experience. Seven female participants (aged 22 to 30 years old) gave accounts of their experiences via face-to-face semi structured interviews. The interview transcripts were then analysed using interpretative phenomenological analysis (IPA). Five superordinate themes emerged from the data: ‘Isolation’, ‘Others don’t understand’, ‘Rejection and Acceptance”, ‘Relationship with the self’ and ‘Autonomy’. Situated within these themes were subthemes capturing specific different facets of the experience, including certain transformations related to the cessation of their self-harm. The findings revealed that participants began to stop self-harming towards late adolescence when factors in their lives began to shift, particularly in the areas of acceptance and autonomy. The findings shed light on resolution of the behaviour. The findings support existing theoretical models of self-harm and previous research, and are discussed in the context of the developmental stage of adolescence. This study offers concluding thoughts around the implications of the findings in relation to the practice of counselling psychology, specifically when working therapeutically with adolescents who self-harm

Positron emission tomography to image cerebral neuroinflammation in ischaemic stroke: a pilot study

Background Activated microglia play a complex role in neuroinflammation associated with acute ischaemic stroke. As a potential target for anti-inflammatory therapy, it is crucial to understand the association between intensity, extent and the clinical outcome of a stroke. The 18-kDa translocator protein is a marker of cerebral microglial activation and of macrophage infiltration after damage to the brain. It can be imaged by positron emission tomography. Therefore, the recently developed radiopharmaceutical [18F]-GE180 was used in patients after a mild to moderate stroke and compared with [11C]-(R)-PK11195, which has already been established in research but cannot be used in routine clinical settings because of its very short half-life. Objectives Objectives for phase 1 were to evaluate the tolerability of positron emission tomography scanning, to assess the technical feasibility of imaging the 18-kDa translocator protein using [18F]-GE180 as radiopharmaceutical, to compare [18F]-GE180 with [11C]-(R)-PK11195 as reference. Objectives for phase 2 were examining the relation of positron emission tomography imaging with clinical outcome, magnetic resonance imaging and systemic inflammation. However, the study was ended after phase 1 because of the results obtained in that phase and did not enter phase 2. Methods Ten participants (aged 24–89 years, median 68 years) (eight male and two female) with a history of recent ischaemic stroke of mild to moderate severity (modified Rankin scale score of 2–3) in the middle cerebral artery territory were scanned 18 to 63 days (median 34.5 days) after the stroke by magnetic resonance imaging (Philips 1.5 T; Philips, Amsterdam, the Netherlands), [18F]-GE180 (200 MBq, 30-minute dynamic scan) and [11C]-(R)-PK11195 (740 MBq, 60-minute dynamic scan) positron emission tomography (Siemens HRRT; Siemens, Munich, Germany). The two positron emission tomography scans were performed on 2 separate days (mean 3.4 days apart). Five patients were randomised to receive the [18F]-GE180 scan at the first session and five patients were randomised to receive it at the second session. Participants were genotyped for the rs6971 18-kDa translocator protein polymorphism, which is known to affect binding of [18F]-GE180 but not of [11C]-(R)-PK11195. All positron emission tomography and magnetic resonance data sets were co-registered with T1-weighted magnetic resonance image scans. Binding of [18F]-GE180 was compared with [11C]-(R)-PK11195 for the infarct and contralateral reference regions. Spearman’s rank-order correlation was used to compare tracers, t-tests to compare patient subgroups. Results Tolerability of scans was rated as 4.36 (range 4–5) out of a maximum of 5 by participants, and there were no serious adverse events. There was a close correlation between [18F]-GE180 and [11C]-(R)-PK11195 (r = 0.79 to 0.84). The 18-kDa translocator protein polymorphism had a significant impact on the uptake of [18F]-GE180, which was very low in normal cortex. Ischaemic lesions with contrast enhancement on magnetic resonance as an indicator of blood–brain barrier damage showed a significantly higher uptake of [18F]-GE180 than the lesions without enhancement, even in low-affinity binders. Conclusions [18F]-GE180 was safe and well tolerated. However, strong dependency of uptake on blood–brain barrier damage and a genetic 18-kDa translocator protein polymorphism, as well as a high contribution of vascular signal to the uptake and evidence of non-specific binding in ischaemic lesions with blood–brain barrier damage, limits the clinical applicability of [18F]-GE180 as a diagnostic marker of neuroinflammation. Limitations As the study was ended after phase 1, this was only a small pilot trial. Further studies are warranted to fully understand the influence of blood–brain barrier damage on positron emission tomography microglia imaging. Trial registration Registered as a clinical trial with EudraCT 2014-000591-26. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 1. See the NIHR Journals Library website for further information. It was also supported by GE Healthcare (Chicago, IL, USA) by free production and delivery of [18F]-GE180 and by supply of regulatory documents (Investigational Medical Product Dossier, Investigator’s Brochure). There was partial support by the European Commission (INMiND, grant #278850) and the NIHR Sheffield Biomedical Research Centre

The cost-effectiveness of antenatal and postnatal education and support interventions for women aimed at promoting breastfeeding in the UK

Background: Breastfeeding is associated with health benefits to mothers and babies and cost-savings to the health service. Breastfeeding rates in the UK are low for various reasons including cultural barriers, inadequate support to initiate and sustain breastfeeding, lack of information, or choice not to breastfeed. Education and support interventions have been developed aiming at promoting breastfeeding rates. The objective of this study was to assess the cost-effectiveness of such interventions for women, initiated antenatally or in the first 8 weeks postnatally, aiming at improving breastfeeding rates, in the UK. Methods: A decision-analytic model was constructed to compare costs and quality-adjusted life-years (QALYs) of a breastfeeding intervention from the perspective of health and personal social services in England. Data on intervention effectiveness and the benefits of breastfeeding were derived from systematic reviews. Other model input parameters were obtained from published sources, supplemented by expert opinion. Results: The incremental cost-effectiveness ratio (ICER) of the modelled intervention added on standard care versus standard care was £51,946/QALY, suggesting that the intervention is not cost-effective under National Institute for Health and Care Excellence (NICE) criteria in England. Sensitivity analysis suggested that the cost-effectiveness of the intervention improved as its effectiveness increased and intervention cost decreased. At the base-case effect (increase in breastfeeding rates 16–26 weeks after birth by 19%), the intervention was cost-effective (<£20,000/QALY) if its cost per woman receiving the intervention became ≈£40–£45. At the base-case cost (£84), the intervention was cost-effective if it increased breastfeeding rates by at least 35–40%. Conclusions: Available breastfeeding interventions do not appear to be cost-effective under NICE criteria in England. Future breastfeeding interventions need to have higher effectiveness or lower cost compared with currently available interventions in order to become cost-effective. Public health and other societal interventions that protect, promote and support breastfeeding may be key in improving breastfeeding rates in the UK

Regulation of mutagenic DNA polymerase V activation in space and time

Spatial regulation is often encountered as a component of multi-tiered regulatory systems in eukaryotes, where processes are readily segregated by organelle boundaries. Well-characterized examples of spatial regulation are less common in bacteria. Low-fidelity DNA polymerase V (UmuD′2C) is produced in Escherichia coli as part of the bacterial SOS response to DNA damage. Due to the mutagenic potential of this enzyme, pol V activity is controlled by means of an elaborate regulatory system at transcriptional and posttranslational levels. Using single-molecule fluorescence microscopy to visualize UmuC inside living cells in space and time, we now show that pol V is also subject to a novel form of spatial regulation. After an initial delay (~ 45 min) post UV irradiation, UmuC is synthesized, but is not immediately activated. Instead, it is sequestered at the inner cell membrane. The release of UmuC into the cytosol requires the RecA* nucleoprotein filament-mediated cleavage of UmuD→UmuD′. Classic SOS damage response mutants either block [umuD(K97A)] or constitutively stimulate [recA(E38K)] UmuC release from the membrane. Foci of mutagenically active pol V Mut (UmuD′2C-RecA-ATP) formed in the cytosol after UV irradiation do not co-localize with pol III replisomes, suggesting a capacity to promote translesion DNA synthesis at lesions skipped over by DNA polymerase III. In effect, at least three molecular mechanisms limit the amount of time that pol V has to access DNA: (1) transcriptional and posttranslational regulation that initially keep the intracellular levels of pol V to a minimum; (2) spatial regulation via transient sequestration of UmuC at the membrane, which further delays pol V activation; and (3) the hydrolytic activity of a recently discovered pol V Mut ATPase function that limits active polymerase time on the chromosomal template

The Tourist Experience of Heritage Urban Spaces: Valletta as a Case Study

This article provides an understanding of how tourists experience heritage urban spaces by investigating features that influence tourist experiences most. It is framed within urban design literature which refers to three elements of urban space namely physical setting (or form), activity, and meaning. These elements are used to explore how urban spaces are experienced by tourists. Its findings are derived from an in-depth qualitative analysis of interviews with tourists to Valletta, Malta. The research suggests that the intrinsic qualities of the space are relevant to the tourist experience but what is even more relevant are the interactions of the tourist with different elements within that space, namely interactions with surroundings, interactions with others, and interactions with self/meaning. Within this broad conceptual model, the research identifies important sub-themes. Some of these reinforce the findings of existing work on tourist experiences, but others are often under-estimated or neglected

Cigarette smoke induces pulmonary arterial dysfunction through an imbalance in the redox status of the soluble guanylyl cyclase

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking (CS), is one of the most common diseases globally. Some COPD patients also develop pulmonary hypertension (PH), a severe complication that leads to premature death. Evidence suggests reactive oxygen species (ROS) involvement in COPD and PH, especially regarding pulmonary artery smooth muscle cells (PASMC) dysfunction. However, the effects of CS-driven oxidative stress on the pulmonary vasculature are not completely understood. Herein we provide evidence on the effects of CS extract (CSE) exposure on PASMC regarding ROS production, antioxidant response and its consequences on vascular tone dysregulation. Our results indicate that CSE exposure promotes mitochondrial fission, mitochondrial membrane depolarization and increased mitochondrial superoxide levels. However, this superoxide increase did not parallel a counterbalancing antioxidant response in human pulmonary artery (PA) cells. Interestingly, the mitochondrial superoxide scavenger mitoTEMPO reduced mitochondrial fission and membrane potential depolarization caused by CSE. As we have previously shown, CSE reduces PA vasoconstriction and vasodilation. In this respect, mitoTEMPO prevented the impaired nitric oxide-mediated vasodilation, while vasoconstriction remained reduced. Finally, we observed a CSE-driven downregulation of the Cyb5R3 enzyme, which prevents soluble guanylyl cyclase oxidation in PASMC. This might explain the CSE-mediated decrease in PA vasodilation. These results provide evidence that there might be a connection between mitochondrial ROS and altered vasodilation responses in PH secondary to COPD, and strongly support the potential of antioxidant strategies specifically targeting mitochondria as a new therapy for these diseasesThe Spanish Ministerio de Ciencia e Innovacion, ´ Programa Retos en Investigacion ´ (grant number PID2019-104406RB-100) to MJC provided the financial support for the conduct of the research included in this manuscript. Garantia Juvenil program from Comunidad de Madrid contributed with the research assistant contract to M-R,

Women and Haunted Houses in the Films of Jaume Balagueró: The Nightmares of Presence

Jaume Balagueró has developed a successful resumé of horror films that show a decided preference for the classic Gothic motif of the haunted house and the Gothic heroine who investigates its interior. This paper touches first on the Derridean concept of ‘dreams of presence’ (as theorized by cultural geographer Mitch Rose), in order to propose the ‘nightmares of presence’ in which the relationship, the call to care or commitment, between the subject and the space in which the subject dwells or moves is Gothicised but nonetheless remains to tie the subject to the space concerned. It then focuses on Balagueró’s Los sin nombre, Fragile and [REC] to consider three very different Gothic heroines: the mother of a dead daughter, a nurse in a children’s hospital, and a television reporter. The antagonistic call to care of the ‘nightmare of presence’ will be used to interrogate spatial aspects of the Gothic heroine. Keywords: Jaume Balagueró; haunted house; Spanish Gothic; Spanish horror; Spanish film Jaume Balagueró ha desarrollado un grupo de películas exitosas que demuestra una preferencia hacia el escenario clásico de lo gótico, la casa encantada tanto como la heroína gótica que la investiga. Este ensayo estudia en primer lugar el concepto derrideano de ‘los sueños de presencia’ (según la teoría de geógrafo cultural Mitch Rose), para proponer las ‘pesadillas de presencia’ en que el vínculo, la llamada a compromiso, entre el sujeto y el espacio en que se mueve o que habita, llega a ser gotizado; pero que fija al sujeto en el espacio relevante. El argumento se enfoca en Los sin nombre, Fragile y [REC] para considerar tres heroínas distintas: la madre de una hija muerta, una enfermera en un hospital para niños, y una locutora para un programa televisivo. La llamada antagonista de la pesadilla de presencia se usa para interrogar los aspectos espaciales de la heroína gótica

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy