Characterisation and environmental value proposition of reuse models for fast-moving consumer goods: reusable packaging and products

Problem: Fast-Moving Consumer Goods (FMCGs) are products that are purchased and consumed frequently to satisfy continuous consumer demand. In a linear economy, FMCGs are typically offered as single-use and disposable products. Limitations in product design, insufficient collection systems, and inefficient recovery processes prevent high recycling rates. As a result, FMCGs often end up in landfill or the environment, contributing to waste accumulation, and pollution. Whilst recycling is the most common waste prevention strategy practiced by the industry, the process is limited to addressing only the final stage of the product life cycle, omitting the overproduction and consumption of materials typical of FMCGs. Instead, reuse is a strategy that is capable of extending the value of resources by slowing material flows. Novel reuse models that require the consumer to interact with durable primary packaging and products are emerging in the FMCG industry. However, the constituent elements and operation principles of such reuse models are not fully understood. The aim of this research is to develop a comprehensive characterisation of reuse models and to evaluate their potential to deliver environmental value. Method: Ninety-two reuse offerings were selected and analysed to identify their reuse system elements. The analysis led to the identification of a framework including five reuse models, which were also evaluated to establish their capability to deliver environmental value when compared to conventional single-use and disposable FMCGs. Results: Currently in the FMCG sector, reusable products are mostly durable packaging, such as bottles and containers for beverages, foods, personal and home care goods, and are infrequently durable products, such as personal and baby care goods, including razors and nappies. Three reuse models involve exclusive reuse, a behaviour by which a reusable product is used and kept by a single user throughout the product lifetime. In exclusive reuse models, users are provided with either a reusable product (model 1), a reusable product with preparation for reuse infrastructure (model 2), or access to preparation for reuse infrastructure (model 3). Two reuse models involve sequential reuse, a behaviour by which a reusable product is used by multiple users throughout the product lifetime and returned after each use to a provider. In sequential reuse models, users are provided with either a reusable product with preparation for reuse infrastructure and provider-operated recovery services (model 4), or a reusable product and provider-operated services for recovery and preparation for reuse (model 5). Whilst the five reuse models can operate standalone, some offerings were found to embed a multi-model approach. Both exclusive and sequential reuse models are capable of delivering environmental value by reducing the use of natural resources and retaining their value in the economy. In particular, sequential reuse models were found to have a greater capability to increase the share of recyclable resources by offering access to infrastructure for the closure of material loops. Conclusions: Consumers can currently access five reuse models and choose between exclusive and sequential reuse behaviours. When adopted in conjunction with recycling, reuse models can enable a more efficient consumption of FMCGs. Providing the infrastructure necessary to enable reuse and recycling is key to the successful and sustainable deployment of the reuse models

Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds

Background: Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. Methods: Modulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was determined in tissue microarrays of radically resected malignant pleural mesothelioma (MPM, N = 33) and diffuse peritoneal mesothelioma (DMPM, N = 56) patients. Results: Overexpression of hypoxia marker CAIX was associated with low PCFT expression and decreased MPM cell growth inhibition by pemetrexed. Through integration of PCR arrays in hypoxic cells and spheroids and following PCFT silencing, we identified the upregulation of LDH-A, which correlated with shorter survival of MPM and DMPM patients. Novel LDH-A inhibitors enhanced spheroid disintegration and displayed synergistic effects with pemetrexed in MPM and gemcitabine in DMPM cells. Studies with bioluminescent hypoxic orthotopic and subcutaneous DMPM athymic-mice models revealed the marked antitumour activity of the LDH-A inhibitor NHI-Glc-2, alone or combined with gemcitabine. Conclusions: This study provides novel insights into hypoxia/PCFT-dependent chemoresistance, unravelling the potential prognostic value of LDH-A, and demonstrating the preclinical activity of LDH-A inhibitors

Splicing modulation as novel therapeutic strategy against diffuse malignant peritoneal mesothelioma

Introduction: Therapeutic options for diffuse malignant peritoneal mesothelioma (DMPM) are limited to surgery and locoregional chemotherapy. Despite improvements in survival rates, patients eventually succumb to disease progression. We investigated splicing deregulation both as molecular prognostic factor and potential novel target in DMPM, while we tested modulators of SF3b complex for antitumor activity. Methods: Tissue-microarrays of 64 DMPM specimens were subjected to immunohistochemical assessment of SF3B1 expression and correlation to clinical outcome. Two primary cell cultures were used for gene expression profiling and in vitro screening of SF3b modulators. Drug-induced splicing alterations affecting downstream cellular pathways were detected through RNA sequencing. Ultimately, we established bioluminescent orthotopic mouse models to test the efficacy of splicing modulation in vivo. Results: Spliceosomal genes are differentially upregulated in DMPM cells compared to normal tissues and high expression of SF3B1 correlated with poor clinical outcome in univariate and multivariate analysis. SF3b modulators (Pladienolide-B, E7107, Meayamycin-B) showed potent cytotoxic activity in vitro with IC50 values in the low nanomolar range. Differential splicing analysis of Pladienolide-B-treated cells revealed abundant alterations of transcripts involved in cell cycle, apoptosis and other oncogenic pathways. This was validated by RT-PCR and functional assays. E7107 demonstrated remarkable in vivo antitumor efficacy, with significant improvement of survival rates compared to vehicle-treated controls. Conclusions: SF3B1 emerged as a novel potential prognostic factor in DMPM. Splicing modulators markedly impair cancer cell viability, resulting also in potent antitumor activity in vivo. Our data designate splicing as a promising therapeutic target in DMPM

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Planck 2015 results: XXV. Diffuse low-frequency Galactic foregrounds

We discuss the Galactic foreground emission between 20 and 100 GHz based on observations by Planck and WMAP. The total intensity in this part of the spectrum is dominated by free-free and spinning dust emission, whereas the polarized intensity is dominated by synchrotron emission. The Commander component-separation tool has been used to separate the various astrophysical processes in total intensity. Comparison with radio recombination line templates verifies the recovery of the free-free emission along the Galactic plane. Comparison of the high-latitude H\u3b1 emission with our free-free map shows residuals that correlate with dust optical depth, consistent with a fraction (\ue2\u2030 30%) of H\u3b1 having been scattered by high-latitude dust. We highlight a number of diffuse spinning dust morphological features at high latitude. There is substantial spatial variation in the spinning dust spectrum, with the emission peak (in I\u3bd) ranging from below 20 GHz to more than 50 GHz. There is a strong tendency for the spinning dust component near many prominent H ii regions to have a higher peak frequency, suggesting that this increase in peak frequency is associated with dust in the photo-dissociation regions around the nebulae. The emissivity of spinning dust in these diffuse regions is of the same order as previous detections in the literature. Over the entire sky, the Commander solution finds more anomalous microwave emission (AME) than the WMAP component maps, at the expense of synchrotron and free-free emission. This can be explained by the difficulty in separating multiple broadband components with a limited number of frequency maps. Future surveys, particularly at 5-20 GHz, will greatly improve the separation by constraining the synchrotron spectrum. We combine Planck and WMAP data to make the highest signal-to-noise ratio maps yet of the intensity of the all-sky polarized synchrotron emission at frequencies above a few GHz. Most of the high-latitude polarized emission is associated with distinct large-scale loops and spurs, and we re-discuss their structure. We argue that nearly all the emission at 40deg > l >-90deg is part of the Loop I structure, and show that the emission extends much further in to the southern Galactic hemisphere than previously recognised, giving Loop I an ovoid rather than circular outline. However, it does not continue as far as the "Fermi bubble/microwave haze", making it less probable that these are part of the same structure. We identify a number of new faint features in the polarized sky, including a dearth of polarized synchrotron emission directly correlated with a narrow, roughly 20deg long filament seen in H\u3b1 at high Galactic latitude. Finally, we look for evidence of polarized AME, however many AME regions are significantly contaminated by polarized synchrotron emission, and we find a 2\u3c3 upper limit of 1.6% in the Perseus region

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Genetic association study of childhood aggression across raters, instruments, and age

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis AGGoverall was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations rg among rater-specific assessment of AGG ranged from rg= 0.46 between self- and teacher-assessment to rg= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range |rg|: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg=∼-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.</p

Archetypical consumer roles in closing the loops of resource flows for Fast-Moving Consumer Goods

After the depletion of their consumable components, Fast-Moving Consumer Goods (FMCGs) become obsolete. In an attempt to close the loop of resources (i.e. products, components or materials) FMCGs can be designed with revalorisation services. In these product-service systems (PSSs) consumers are assigned a key role in closing the loops of resource flows. To understand and define this role, we dissected eighteen examples of PSSs. From this analysis, four dimensions emerged that characterise distinct aspects of the PSSs: the form of obsolescence; the change of resources from obsolete to operative or recoverable; the prerequisite activities required of consumers for revalorisation; and the facilitators of activities (i.e. investments and incentives). These dimensions were used to model four data-driven archetypical roles of consumers named after the interaction between consumers and the resource in the obsolete state, namely keep, bring, consign or abandon obsolete components. The research concluded that revalorisation always takes place in designated locations. The roles that consumers fulfil in closed-loop PSSs involve carrying out activities to position resources in such locations. The roles always come at a cost, but PSSs can be designed to reduce it. PSSs can also be designed to induce a perceivable value of obsolete resources, which can be used to increase role fulfilment. This research presents a comprehensive understanding of the roles of consumers in the specific context of closed-loop FMCGs, identifies tactics to increase the fulfilment of these roles and suggests further research on behaviours and PSSs to understand the roles of other stakeholders in various type of PSSs

A framework to use product-service systems as plans to produce closed-loop resource flows

The circular economy is a model of production and consumption to address the relentless depletion of resources and the accumulation of waste. In the circular economy literature, there are sparse suggestions that Product-Service Systems (PSSs) have the potential to produce closed-loop resource flows. This study explored this potential using a systematic literature review focused on the use phase and obsolescence. We identified twenty-one PSS elements that contribute to closed loops and categorised them by six architectural levels, i.e. services, resources, stakeholders, contract, value delivery, and systems and tools. We then structured the PSS elements and their contributions to closed loops under four subfunctions and consolidated them in a novel framework. Intercepting and transitioning obsolete resources are subfunctions demanded by a PSS to achieve an operational solution. Stating and governing resource lifetime are subfunctions wanted by a PSS to improve the solution. The results call for a functional approach to PSS design and consideration of obsolescence of products, components and materials. The implications of the results are that PSS elements contribute to achieving circularity by satisfying specific subfunctions and the data in the framework provide a basis for selecting suitable PSS elements

Developing the material service system concept: a case study of steel industrial drums

Within the circular economy, the Product-Service System (PSS) is a key business model to slow down and dematerialise resource consumption between manufacturers or service providers and customers. Material-Service Systems (MSSs) have been proposed as a business model to develop the performance economy focusing on the relationship between material suppliers and manufacturers. The aim of this research is to introduce and develop the MSS concept and to apply it to a real-world case study. The research involved two stages. First, a modelling method is proposed to represent the flow, transformation and ownership of resources by the stakeholders in a supply chain. Second, the method is tested using steel industrial drums as a case. The results indicate that the MSS has the potential to radically transform the steel drums industry and it could work effectively with a PSS within a reuse system to recondition and reintroduce obsolete drums into the market