Social life cycle assessment of green methanol and benchmarking against conventional fossil methanol.

Green methanol could play a major role in decarbonising both the chemical and energy sectors. While techno-economic and environmental studies on green methanol following a life-cycle perspective are available, its social implications from a supply-chain standpoint remain largely unexplored. In order to fill this gap, this work presents the first social life cycle assessment of green methanol produced with CO2 directly captured from the air and hydrogen from wind power electrolysis. When compared to conventional methanol from natural gas, the results suggest an unfavourable performance of green methanol under negative social indicators (forced labour, women in the sectoral labour force, health expenditure, social responsibility promotion, and fair salary) due to the increased supply-chain complexity of the green system. In contrast, green methanol would outperform its conventional counterpart in terms of sectoral contribution to economic development, a positive social indicator which would benefit from the increase in working hours. Besides future consideration of a higher number of positive indicators and potential improvements in country- and sector-specific risk levels towards high-quality social and working conditions, an enhanced social life-cycle performance of green methanol requires technical improvements to reduce the high demand for energy inputs and equipment across its supply chain. Acknowledging decarbonisation as the actual driver of green methanol deployment, future social studies are suggested to focus on the comparison of renewable alternatives for its production and the effect of social regulations.

Life cycle sustainability assessment of synthetic fuels from date palm waste.

The use of biowaste feedstock is often suggested for sustainable production of synthetic fuels through gasification followed by the Fischer-Tropsch process. While the technical performance of this type of bioenergy system has significantly been investigated, comprehensive sustainability analyses are still required. The present study evaluates the life cycle sustainability performance of synthetic diesel and gasoline from Tunisian date palm waste, and compares it with that of conventional fossil fuels. Life cycle inventories are elaborated to subsequently characterise the performance of the synthetic biofuels under a set of 12 environmental, economic and social indicators. Both environmental and economic hotspots were found to be associated with the need for electricity and oxygen. Direct emissions to the air and the investment in the plant's power section were also found to significantly affect the environmental and economic performances, respectively. Potential social impacts were found to be mainly linked to the supply chain of equipment and infrastructure, while electricity arose as the most contributing operational element. Overall, the evaluated synthetic biofuels could be considered competitive with conventional fossil fuels and contribute to the achievement of sustainable development goals only if environmentally- and socially-friendly (renewable) electricity and oxygen sources are implemented and the scale and configuration of the plant are optimised.

Comparative Social Life Cycle Assessment of Two Biomass-to-Electricity Systems.

Biomass plays a fundamental role in numerous decarbonisation strategies that seek to mitigate the short- and long-term effects of climate change. Within this context, decision-makers' choices need to comprehensively consider potential sustainability effects associated with bioenergy systems. In particular, due to the lack of studies addressing the social sustainability of bioelectricity, the present work applies the Social Life Cycle Assessment (S-LCA) methodology to compare the social performance of two biomass-to-electricity systems located in Portugal based on either fluidised-bed or grate furnace technology. S-LCA involves a comprehensive approach for holistic evaluation and data interpretation of social aspects. Six social indicators were benchmarked: child labour, forced labour, gender wage gap, women in the sectoral labour force, health expenditure, and contribution to economic development. The results show that the implementation of fluidised-bed furnaces as a more efficient conversion technology could reduce by 15-19% the selected negative social impacts, except women in the sectoral labour force. When enlarging the interpretation to a sustainability perspective, the general suitability of the fluidised-bed furnace system would be further emphasised under environmental aspects while jointly providing valuable insights for informed decision-making and sustainability reporting.

Discovery and Targeting of the Signaling Controls of PNPLA3 to Effectively Reduce Transcription, Expression, and Function in Pre-Clinical NAFLD/NASH Settings.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging worldwide epidemics, projected to become the leading cause of liver transplants. The strongest genetic risk factor for NAFLD/NASH susceptibility and progression is a single-nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 gene (PNPLA3), rs738409, encoding the missense mutation I148M. This aminoacidic substitution interferes with the normal remodeling of lipid droplets in hepatocytes. It is also thought to play a key role in promoting liver fibrosis by inhibiting the release of retinol from hepatic stellate cells. Reducing PNPLA3 levels in individuals homozygous for 148M may be an effective treatment for the entire spectrum of NAFLD, based on gene dosage analysis in the human population, as well as the protective effect of another naturally occurring SNP (rs2294918) in PNPLA3 which, when co-inherited, reduces PNPLA3 mRNA levels to 50% and counteracts disease risk. By screening a clinical compound library targeting specific signaling pathways active in primary human hepatocytes, we identified momelotinib, a drug evaluated in clinical trials to treat myelofibrosis, as a potent down-regulator of PNPLA3 expression, across all genotypes. We found that momelotinib treatment yielded >80% reduction in PNPLA3 mRNA in human primary hepatocytes and stellate cells, as well as in vivo via acute and chronic treatment of WT mice. Using a human multilineage 3D spheroid model of NASH homozygous for the PNPLA3 mutant protein, we additionally show that it decreases PNPLA3 mRNA as well as intracellular lipid content. Furthermore, we show that the effects on PNPLA3 coincide with changes in chromatin accessibility within regulatory regions of the PNPLA3 locus, consistent with inhibition occurring at the level of transcription. In addition to its primary reported targets, the JAK kinases, momelotinib inhibits several non-JAK kinases, including ACVR1. Using a combination of targeted siRNA knockdowns and signaling pathway perturbations, we show that momelotinib reduces the expression of the PNPLA3 gene largely through the inhibition of BMP signaling rather than the JAK/STAT pathway. Overall, our work identified momelotinib as a potential NASH therapeutic and uncovered previously unrecognized connections between signaling pathways and PNPLA3. These pathways may be exploited by drug modalities to "tune down" the level of gene expression, and therefore offer a potential therapeutic benefit to a high at-risk subset of NAFLD/NASH patients.

Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids.

Epithelial organoids derived from human donor tissues are important tools in fields ranging from regenerative medicine to drug discovery. Organoid culture requires expansion of stem/progenitor cells in Matrigel, a tumor-derived extracellular matrix (ECM). An alternative completely synthetic ECM could improve reproducibility, clarify mechanistic phenomena, and enable human implantation of organoids. We designed synthetic ECMs with tunable biomolecular and biophysical properties to identify gel compositions supporting human tissue-derived stem/progenitor epithelial cells as enteroids and organoids starting with single cells rather than tissue fragments. The synthetic ECMs consist of 8-arm PEG-macromers modified with ECM-binding peptides and different combinations of integrin-binding peptides, crosslinked with peptides susceptible to matrix metalloprotease (MMP) degradation, and tuned to exhibit a range of biophysical properties. A gel containing an α2ß1 integrin-binding peptide (GFOGER) and matrix binder peptides grafted to a 20 kDa 8-arm PEG macromer showed the most robust support of human duodenal and colon enteroids and endometrial organoids. In this synthetic ECM, human intestinal enteroids and endometrial organoids emerge from single cells and show cell-specific and apicobasal polarity markers upon differentiation. Intestinal enteroids, in addition, retain their proliferative capacity, are functionally responsive to basolateral stimulation, express canonical markers of intestinal crypt cells including Paneth cells, and can be serially passaged. The success of this synthetic ECM in supporting human postnatal organoid culture from multiple different donors and from both the intestine and endometrium suggests it may be broadly useful for other epithelial organoid culture.

Sensitivity of operational and environmental benchmarks of retail stores to decision-makers' preferences through Data Envelopment Analysis.

Within the framework of multi-criteria decision analysis (MCDA), weighting methods are typically used to capture decision-makers' preferences. In this regard, the increasing use of the combined LCA (Life Cycle Assessment) + DEA (Data Envelopment Analysis) methodology as an MCDA tool requires an in-depth analysis of how the preferences of decision-makers could affect the outcomes of LCA + DEA studies. This work revisits a case study of 30 retail stores/supply chains located in Spain by applying alternative weighted DEA approaches to evaluate the influence of decision-makers' preferences (weights) on the final outcomes, with a focus on efficiency scores and operational and environmental benchmarks. The ultimate goal is to effectively capture the view of stakeholders when applying LCA + DEA for the sound, sustainability-oriented management of multiple similar entities. Different weight vectors are separately applied to three types of DEA elements: operational inputs, time terms, and divisions. Besides, preferences from three alternative standpoints are considered: company manager through direct rating, and environmental policy-maker and local community through AHP (analytic hierarchy process). A significant influence on efficiency scores and sustainability benchmarks was found when weighting decision-makers' preferences on operational inputs. Additionally, a moderate influence was observed when weighting divisions according to a policy-maker or local community perspective. Although the results are case-specific, they lead to the general recommendation to enrich LCA + DEA studies by following not only an equal-weight approach but also approaches that include the preferences of the stakeholders effectively involved in the study.

Sustainability-oriented efficiency of retail supply chains: A combination of Life Cycle Assessment and dynamic network Data Envelopment Analysis.

Assessing the efficiency of retail supply chains (RSCs) requires analytical tools that address the different activities involved in these chains. In this sense, dynamic network Data Envelopment Analysis (DEA) arises as a suitable method to evaluate the operational performance of RSCs over a period of time. However, its use for sustainability-oriented efficiency assessment constitutes a knowledge gap that limits its applicability for thorough decision-making processes, e.g. at the retail company level. This article fills this gap through the combination of Life Cycle Assessment (LCA) and dynamic network DEA. A novel five-step LCA + DEA approach is proposed and applied to a case study of 30 RSCs in Spain for the period 2015-2017. In this case, the supply chain structure involves three divisions: central distribution, operation of retail stores, and home delivery. Both overall- and term-efficiency scores were found to widely range from 0.38 to 1.00, with only 1 RSC deemed efficient. Regarding divisional efficiency, store operation was found to generally show significantly higher efficiency scores than the distribution divisions. The link between long distribution distances and low efficiency stresses the relevance of integrating a network perspective into the efficiency assessment. In addition to efficiency scores, the LCA + DEA approach enriches the assessment by providing environmental, operational and socio-economic benchmarks to further support the management of RSCs from a sustainability perspective.

Life cycle assessment of wood pellets and wood split logs for residential heating.

Wood-fuelled systems are commonly used all over the world for residential heating, and recently wood pellets have been replacing traditional firewood. This article presents an environmental life cycle assessment of five wood-based combustion systems for residential heating: i) a pellet stove using maritime pine pellets; a wood stove using ii) eucalyptus (Eucalyptus globulus Labill.) and iii) maritime pine (Pinus pinaster Ait.) split logs; and a fireplace using iv) eucalyptus and v) maritime pine split logs. The functional unit is 1 MJ of thermal energy for residential heating. System boundaries include four stages: (1) forest management; (2) pellet and wood split log production; (3) distribution; and (4) thermal energy generation. Environmental impacts were calculated for seven impact categories from the ReCiPe 2016 midpoint method, and a sensitivity analysis was performed using the Product Environmental Footprint (PEF) life cycle impact assessment method and modifying the distances travelled. Of the five heating systems analysed, the fireplace presents the worst performance for all the impact categories with the exception of freshwater eutrophication and marine eutrophication, when maritime pine split logs are burned in the fireplace. Comparing the pellet stove with the wood stove, neither system is better for all the impact categories analysed. Regarding sensitivity analysis, the use of an alternative characterisation method leads to similar trends in the results in comparison with those obtained from the ReCiPe method, while changes in transport distances do not affect the total impacts to a large extent.

Sustainability-oriented management of retail stores through the combination of life cycle assessment and dynamic data envelopment analysis.

A sound management of retail stores is a crucial aspect in the path towards a sustainable commercial sector, with a lack of research studies in the field of joint efficiency and sustainability assessment within this sector. In this sense, this work delves into the role of operational efficiency in the sustainability-oriented management of retail stores through the case study of 30 groceries in Spain over the period 2015-2017. With this purpose, and given the current knowledge gap in period-oriented sustainability benchmarking for management plans, for the first time a five-step methodological framework based on the combination of Life Cycle Assessment (LCA) and dynamic Data Envelopment Analysis (DEA) was proposed and applied to a case study within the service sector. The overall- and term-efficiency scores calculated through this method led to the general conclusion of a relatively good performance of the set of grocery stores over the evaluated period, which is associated with the centralised management strategy followed by the retail company. Furthermore, operational, socio-economic and environmental benchmarks were calculated as target values that could assist decision-makers at the retail company level in setting the path for a sustainable operation of the company's stores. Overall, the proposed period-oriented LCA + DEA method proved to be a feasible and valuable tool for sustainability management of retail stores, being preferred over the static (i.e., single term) alternative provided that time-series data are available at the company level.

Combined use of Data Envelopment Analysis and Life Cycle Assessment for operational and environmental benchmarking in the service sector: A case study of grocery stores.

Ensuring sustainable production patterns doing more and better with less is a key sustainable development goal. In this sense, the joint use of Life Cycle Assessment and Data Envelopment Analysis (i.e., the LCA+DEA methodology) arises as a quantitative tool for the eco-efficiency assessment of multiple similar entities. To date, the LCA+DEA methodology has been widely applied to case studies within the primary and secondary sectors. However, the applicability of this combined methodology to case studies within the tertiary (service) sector is still unexplored, which constitutes a current knowledge gap in this field. This work contributes to filling this gap by benchmarking the operational and environmental performance of a sample of 30 groceries located in Spain. All the evaluated groceries were found to involve relative efficiency scores above 0.60, with one third of the groceries deemed fully efficient. Average reductions of 3-26% in the consumption of operational inputs were calculated, leading to average reductions of 9% in the carbon footprint and 10% in the energy footprint. Furthermore, economic savings of up to 3% of the annual turnover were estimated. These results were further enriched through the application of a super-efficiency DEA model for a refined identification of the best-performers, as well as through the novel use of a specific model for the gradual operational and environmental benchmarking of the sample. Overall, a high applicability of the LCA+DEA methodology for eco-efficiency assessment within the service sector is concluded, facilitating the identification and quantification of sustainable operational patterns.

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies.

Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS "physiome-on-a-chip" approaches in drug discovery.

Environmental impact efficiency of natural gas combined cycle power plants: A combined life cycle assessment and dynamic data envelopment analysis approach.

The energy sector is still dominated by the use of fossil resources. In particular, natural gas represents the third most consumed resource, being a significant source of electricity in many countries. Since electricity production in natural gas combined cycle (NGCC) plants provides some benefits with respect to other non-renewable technologies, it is often seen as a transitional solution towards a future low­carbon power generation system. However, given the environmental profile and operational variability of NGCC power plants, their eco-efficiency assessment is required. In this respect, this article uses a novel combined Life Cycle Assessment (LCA) and dynamic Data Envelopment Analysis (DEA) approach in order to estimate -over the period 2010-2015- the environmental impact efficiencies of 20 NGCC power plants located in Spain. A three-step LCA+DEA method is applied, which involves data acquisition, calculation of environmental impacts through LCA, and the novel estimation of environmental impact efficiency (overall- and term-efficiency scores) through dynamic DEA. Although only 1 out of 20 NGCC power plants is found to be environmentally efficient, all plants show a relatively good environmental performance with overall eco-efficiency scores above 60%. Regarding individual periods, 2011 was -on average- the year with the highest environmental impact efficiency (95%), accounting for 5 efficient NGCC plants. In this respect, a link between high number of operating hours and high environmental impact efficiency is observed. Finally, preliminary environmental benchmarks are presented as an additional outcome in order to further support decision-makers in the path towards eco-efficiency in NGCC power plants.

Delving into sensible measures to enhance the environmental performance of biohydrogen: A quantitative approach based on process simulation, life cycle assessment and data envelopment analysis.

A novel approach is developed to evaluate quantitatively the influence of operational inefficiency in biomass production on the life-cycle performance of hydrogen from biomass gasification. Vine-growers and process simulation are used as key sources of inventory data. The life cycle assessment of biohydrogen according to current agricultural practices for biomass production is performed, as well as that of target biohydrogen according to agricultural practices optimised through data envelopment analysis. Only 20% of the vineyards assessed operate efficiently, and the benchmarked reduction percentages of operational inputs range from 45% to 73% in the average vineyard. The fulfilment of operational benchmarks avoiding irregular agricultural practices is concluded to improve significantly the environmental profile of biohydrogen (e.g., impact reductions above 40% for eco-toxicity and global warming). Finally, it is shown that this type of bioenergy system can be an excellent replacement for conventional hydrogen in terms of global warming and non-renewable energy demand.

Eficacia del control de larvas de vectores de la malaria con peces larvívoros nativos en San Martín, Perú / Efficacy of malaria vector control with native larvae feeding fish in San Martin, Peru

Objetivo: Determinar la eficacia del control larvario de vectores de la malaria con peces larvívoros nativos en San Martín, Perú. Material y métodos: Estudio experimental que se llevó a cabo en las localidades de Yumbatos, Alianza y San Juan de Shanusi con ocho criaderos cada uno, identificándose las especies nativas Rivulus urophtalmus <> y Pyrrulina brevis <> comparados con la eficacia ejercida por Poecilia reticulata <>. Se midieron variables como temperatura, pH, concentración de electrolitos en el agua, densidad de los peces y presencia de otros depredadores. Resultados: Los peces nativos alcanzaron una eficacia de 98 por ciento en el control de larvas de Anopheles, cuando se mantuvieron en densidades entre 10 y 15 peces/m2; estos peces alcanzan longitudes hasta de 8 cm, y tienen similar o mayor voracidad que Poecilia reticulata. Asimismo, se evidenció la existencia de peces depredadores, Hoplias malabaricus <> y Simbranchus marmoratus <>, los que se alimentan de estos peces pequeños. Conclusiones: Los peces nativos son eficaces para el control de larvas de Anopheles; asimismo, se deben tener en cuenta la existencia de otras especies depredadoras, así como la limpieza de la maleza de los criaderos para incrementar la eficacia del control.

Tamoxifeno y cáncer de mama / Tamoxifen and breast cancer

El tamoxifeno ha sido un pilar importante en la terapia adyuvante del cáncer mamario. Utilizado inicialmente como un antiestrógeno, el tamoxifeno demostró ser un modulador selectivo de receptores de estrógeno, es decir, ejerce un agonismo estrogénico en ciertos tejidos junto con una acción antagónica estrogénica en otros. Probada su utilidad en la terapia paliativa del cáncer mamario avanzado, investigaciones posteriores indicaron que el tamoxifeno produce efectos benéficos significativos en la terapia adyuvante de los tumores mamarios invasores e in situ como también su uso profiláctico en mujeres con riesgo elevado de desarrollar un cáncer de mama. En está revisión analizamos la utilidad del tamoxifeno en la terapia del cáncer de mama, sus efectos benéficos sobre el sistema óseo y cardiovascular y el efecto adverso en el endometrio

Moduladores selectivos de receptores de estrógeno / Selective estrogen receptor modulators

Los beneficios de la estrogenoterapia en la mujer posmenopáusica son indiscutibles, especialmente por su acción sobre el sistema óseo y cardiovascular. Presentan el inconveniente de estar asociados con un aumento del riesgo de desarrollar cáncer de la mama y endometrio. En esta revisión se analizan nuevos preparados denominados moduladores selectivos de estrógenos (MSRE), que ejercen una acción estrogénica selectiva sobre ciertos sistemas y evitan la estimulación sobre el sistema reproductivo. Se analizan su mecanismo de acción y las perpectivas de desarrollo a futuro