Adjust or invest : what is the best option to green a supply chain?

Greening a supply chain can be achieved by considering several options. However, companies lack of clear guidelines to assess and compare these options. In this paper, we propose to use multiobjective optimization to assess operational adjustment and technology investment options in terms of cost and carbon emissions. Our study is based on a multiobjective formulation of the economic order quantity model called the sustainable order quantity model. The results show that both options may be effective to lower the impacts of logistics operations. We also provide analytical conditions under which an option outperforms the other one for two classical decision rules, i.e. the carbon cap and the carbon tax cases. The results allow deriving some interesting and potentially impacting practical insight

Novel high-throughput fluorescence-based assay for the identification of nematocidal compounds that target the blood-feeding pathway

Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model Nippostrongylus brasiliensis (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms

Associations of child and adolescent anxiety with later alcohol use and disorders:a systematic review and meta‐analysis of prospective cohort studies

Background and Aims: Despite a wealth of literature, the relationship between anxiety and alcohol use remains unclear. We examined whether (a) child and adolescent anxiety is positively or negatively associated with later alcohol use and disorders and (b) study characteristics explain inconsistencies in findings. Design and Setting: We conducted a systematic review of 51 prospective cohort studies from 11 countries. Three studies contributed to a meta-analysis. We searched PubMed, Scopus, Web of Science and PsycINFO databases, and studies were included if they met the following criteria: English language publication, human participants, anxiety exposure (predictor variable) in childhood or adolescence and alcohol outcome at least 6months later. Participants: Study sample sizes ranged from 110 to 11 157 participants. Anxiety exposure ages ranged from 3 to 24years, and alcohol outcome ages ranged from 11 to 42years. Measurements: Ninety-seven associations across 51 studies were categorized by anxiety exposure (generalized anxiety disorder, internalizing disorders, miscellaneous anxiety, obsessive compulsive disorder, panic disorder, separation anxiety disorder, social anxiety disorder and specific phobias) and alcohol use outcome (drinking frequency/quantity, binge drinking and alcohol use disorders). Findings: The narrative synthesis revealed some evidence for a positive association between anxiety and later alcohol use disorders. Associations of anxiety with later drinking frequency/quantity and binge drinking were inconsistent. Type and developmental period of anxiety, follow-up duration, sample size and confounders considered did not appear to explain the discrepant findings. The meta-analysis also showed no clear evidence of a relationship between generalized anxiety disorder and later alcohol use disorder (odds ratio=0.94, 95% confidence interval=0.47–1.87). Conclusions: Evidence to date is suggestive, but far from conclusive of a positive association between anxiety during childhood and adolescence and subsequent alcohol use disorder

ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence.

Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent tumor despite intravesical immunotherapy instillation with the bacillus Calmette-Guérin (BCG) vaccine. In a prospective longitudinal study, we took advantage of BCG instillations, which increase local immune infiltration, to characterize immune cell populations in the urine of patients with NMIBC as a surrogate for the bladder tumor microenvironment. We observed an infiltration of neutrophils, T cells, monocytic myeloid-derived suppressor cells (M-MDSCs), and group 2 innate lymphoid cells (ILC2). Notably, patients with a T cell-to-MDSC ratio of less than 1 showed dramatically lower recurrence-free survival than did patients with a ratio of greater than 1. Analysis of early and later time points indicated that this patient dichotomy existed prior to BCG treatment. ILC2 frequency was associated with detectable IL-13 in the urine and correlated with the level of recruited M-MDSCs, which highly expressed IL-13 receptor α1. In vitro, ILC2 were increased and potently expressed IL-13 in the presence of BCG or tumor cells. IL-13 induced the preferential recruitment and suppressive function of monocytes. Thus, the T cell-to-MDSC balance, associated with a skewing toward type 2 immunity, may predict bladder tumor recurrence and influence the mortality of patients with muscle-invasive cancer. Moreover, these results underline the ILC2/IL-13 axis as a targetable pathway to curtail the M-MDSC compartment and improve bladder cancer treatment

The Chemokine CXCL12 Is Essential for the Clearance of the Filaria Litomosoides sigmodontis in Resistant Mice

Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms

Modulation of the immune response by nematode secreted acetylcholinesterase revealed by heterologous expression in Trypanosoma musculi

Nematode parasites secrete molecules which regulate the mammalian immune system, but their genetic intractability is a major impediment to identifying and characterising the biological effects of these molecules. We describe here a novel system for heterologous expression of helminth secreted proteins in the natural parasite of mice, Trypanosoma musculi, which can be used to analyse putative immunomodulatory functions. Trypanosomes were engineered to express a secreted acetylcholinesterase from Nippostrongylus brasiliensis. Infection of mice with transgenic parasites expressing acetylcholinesterase resulted in truncated infection, with trypanosomes cleared early from the circulation. Analysis of cellular phenotypes indicated that exposure to acetylcholinesterase in vivo promoted classical activation of macrophages (M1), with elevated production of nitric oxide and lowered arginase activity. This most likely occurred due to the altered cytokine environment, as splenocytes from mice infected with T. musculi expressing acetylcholinesterase showed enhanced production of IFNγ and TNFα, with diminished IL-4, IL-13 and IL-5. These results suggest that one of the functions of nematode secreted acetylcholinesterase may be to alter the cytokine environment in order to inhibit development of M2 macrophages which are deleterious to parasite survival. Transgenic T. musculi represents a valuable new vehicle to screen for novel immunoregulatory proteins by extracellular delivery in vivo to the murine host

Binge drinking : a pattern associated with a risk of problems of alcohol use among university students

Objective:: to evaluate problems associated with alcohol use among university students who reported binge drinking in comparison to students who consumed alcohol without binging. Method:: a cross-sectional study among university students (N=2,408) who accessed the website about alcohol use. Logistic and linear regression models were included in the statistical analyzes. Results:: alcohol use in the last three months was reported by 89.2% of university students; 51.6% reported binge drinking. Compared to students who did not binge drink, university students who presented this pattern were more likely to report all evaluated problems, among them: black out (aOR: 5.4); having academic problems (aOR: 3.4); acting impulsively and having regrets (aOR: 2.9); getting involved in fights (aOR: 2.6); drinking and driving (aOR: 2.6) and accepting a ride with someone who had drunk alcohol (aOR: 1.8). Students who binged also had higher scores on the Alcohol Use Disorders Identification Test (b=4.6; p<0.001), more negative consequences (b=1.0; p<0.001) and a reduced perception of the negativity of the consequences (b=-0.5; p<0.01). Conclusion:: binge drinking was associated with an increase in the chances of manifesting problems related to alcohol use. The conclusions of this study cannot be generalized for all of the Brazilian population. Objetivo:: avaliar problemas associados ao uso de álcool entre universitários que relataram binge drinking em comparação a estudantes que consumiram álcool sem binge drinking. Método:: estudo transversal entre universitários (N=2.408) que acessaram website sobre o uso de álcool. Nas análises estatísticas incluíram-se modelos de regressão logística e linear. Resultados:: o uso de álcool, nos últimos três meses, foi relatado por 89,2% dos universitários e 51,6% referiram uso binge. Comparados a estudantes que não praticaram binge, universitários que apresentaram esse padrão tiveram maior chance de relatar todos os problemas avaliados, entre eles: incapacidade de lembrar o que aconteceu (aOR:5,4); problemas acadêmicos (aOR:3,4); agir impulsivamente e se arrepender (aOR:2,9); envolver-se em brigas (aOR:2,6); dirigir após beber (aOR:2,6) e pegar carona com alguém que bebeu (aOR:1,8). Estudantes que consumiram álcool no padrão binge também apresentaram maior pontuação no Alcohol Use Disorders Identification Test (b=4,6; p<0,001), mais consequências negativas (b=1,0; p<0,001) e menos percepção da negatividade das consequências (b=-0,5; p<0,01). Conclusão:: a prática de binge drinking esteve associada ao aumento das chances de manifestação de problemas relacionados ao uso de álcool. As conclusões deste estudo não podem ser reproduzidas para toda realidade brasileira. Objetivo:: evaluar problemas asociados al uso de alcohol entre estudiantes universitarios que relataron binge drinking en comparación a estudiantes que consumieron alcohol sin binge drinking. Método:: estudio transversal entre estudiantes universitarios (N=2.408) que visitaron una página web sobre el uso de alcohol. En los análisis estadísticos, fueron incluidos modelos de regresión logística y linear. Resultados:: el uso de alcohol, en los últimos tres meses, fue relatado por 89,2% de los estudiantes universitarios, y entre ellos 51,6% relataron uso binge. En comparación a estudiantes universitarios que no practicaron binge, los estudiantes que presentaron ese estándar tuvieron una mayor oportunidad de relatar todos los problemas evaluados, entre ellos: incapacidad de recordar lo que sucedió (aOR:5,4); problemas académicos (aOR:3,4); actuar por impulso y arrepentirse (aOR:2,9); involucrarse en peleas (aOR:2,6); manejar después de beber (aOR:2,6) y compartieron viaje con alguien que bebió (aOR:1,8). Estudiantes que consumieron alcohol dentro del estándar binge también presentaron una mayor puntuación en el Alcohol Use Disorders Identification Test (b=4,6; p<0,001), más consecuencias negativas (b=1,0; p<0,001) y menor percepción de la negatividad de las consecuencias (b=-0,5; p<0,01). Conclusión:: la práctica de binge drinking estuvo asociada al aumento de las oportunidades de manifestación de problemas relacionados al alcohol. Las conclusiones de este estudio no pueden ser adaptadas a toda la realidad brasileña

Type 2 Innate Lymphoid Cells Treat and Prevent GI Tract GvHD Through Enhanced Accumulation of Myeloid Derived Suppressor Cells

Acute graft-versus-host disease (aGVHD) is the most common complication for patients undergoing allogeneic stem cell transplantation. Despite extremely aggressive therapy targeting donor T cells, patients with grade III or greater aGVHD of the lower GI tract, who do not respond to therapy with corticosteroids, have a dismal prognosis. Thus, efforts to improve understanding of the function of local immune and non-immune cells in regulating the inflammatory process in the GI tract during aGVHD are needed. Here, we demonstrate, using murine models of allogeneic BMT, that type 2 innate lymphoid cells (ILC2s) in the lower GI tract are sensitive to conditioning therapy and show very limited ability to repopulate from donor bone marrow. Infusion of donor ILC2s was effective in reducing the lethality of aGVHD and in treating lower GI tract disease. ILC2 infusion was associated with reduced donor proinflammatory Th1 and Th17 cells, accumulation of donor myeloid-derived suppressor cells (MDSCs) mediated by ILC2 production of IL-13, improved GI tract barrier function, and a preserved graft-versus-leukemia (GVL) response. Collectively, these findings suggest that infusion of donor ILC2s to restore gastrointestinal tract homeostasis may improve treatment of severe lower GI tract aGVHD