Life-cycle analysis of last-mile parcel delivery using autonomous delivery robots

The acceleration of global e-commerce brings an increasing environmental burden to urban last-mile logistics. Autonomous delivery robots (ADRs) have often been considered as an attractive solution to this challenge but, to date, their environmental impact had not been fully assessed. To fill this gap, a life-cycle analysis of two-echelon and business-as-usual distribution strategies is proposed in this paper. To model ADR production, primary data from an actual prototype is used. The mathematical formulation of the use stage is done using the continuous approximation methodology. Finally, some managerial insights are obtained. Two-echelon operations would generate between 60 and 130 gCO2-eq per parcel delivery depending on the considered operation scenario. The ADR fleet production and renewal are the biggest contributors to this total global warming potential (GWP). As a consequence, the three main leverages to decrease the GWP of an ADR-based two-echelon delivery scheme are an improvement of the ADR production processes, the maximization of the robot lifespan (both for mechanical parts and battery), and the optimization of delivery operations to minimize the robot fleet size.The first author would like to personally acknowledge CARNET for the funding of this research article, developed in the framework of his PhD thesis. The second author also thanks the funding by the DFG, German Research Foundation, under Germany's Excellence Strategy - EXC 2163/1 – SE2A. The participation of the last author of this paper was made under the project PID2020-118641RB-I00, funded by the Spanish Ministry of Science and Innovation, MCIN/AEI/10.13039/501100011033. The authors also acknowledge the comments of anonymous reviewers that greatly helped in improving and clarifying the paper.Peer ReviewedObjectius de Desenvolupament Sostenible::11 - Ciutats i Comunitats SosteniblesObjectius de Desenvolupament Sostenible::9 - Indústria, Innovació i InfraestructuraObjectius de Desenvolupament Sostenible::12 - Producció i Consum ResponsablesObjectius de Desenvolupament Sostenible::13 - Acció per al ClimaObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No ContaminantPostprint (published version

The novel antipsychotic cariprazine stabilizes gamma oscillations in rat hippocampal slices

Background and purpose: Gamma oscillations are fast rhythmic fluctuations of neuronal network activity ranging from 30 to 90 Hz that establish a precise temporal background for cognitive processes such as perception, sensory processing, learning, and memory. Alterations of gamma oscillations have been observed in schizophrenia and are suggested to play crucial roles in the generation of positive, negative, and cognitive symptoms of the disease. Experimental approach: In this study, we investigated the effects of the novel antipsychotic cariprazine, a D3 -preferring dopamine D3 /D2 receptor partial agonist, on cholinergically induced gamma oscillations in rat hippocampal slices from treatment-naïve and MK-801-treated rats, a model of acute first-episode schizophrenia. Key results: The D3 receptor-preferring agonist pramipexole effectively decreased the power of gamma oscillations, while the D3 receptor antagonist SB-277011 had no effect. In treatment-naïve animals, cariprazine did not modulate strong gamma oscillations but slightly improved the periodicity of non-saturated gamma activity. Cariprazine showed a clear partial agonistic profile at D3 receptors at the network level by potentiating the inhibitory effects when the D3 receptor tone was low and antagonizing the effects when the tone was high. In hippocampal slices of MK-801-treated rats, cariprazine allowed stabilization of the aberrant increase in gamma oscillation power and potentiated resynchronization of the oscillations. Conclusion and implications: Data from this study indicate that cariprazine stabilizes pathological hippocampal gamma oscillations, presumably by its partial agonistic profile. The results demonstrate in vitro gamma oscillations as predictive biomarkers to study the effects of antipsychotics preclinically at the network level

Effects of Hemizygia welwitschii leaf extract fractions on postharvest infestation of maize by Sitophilus zeamais Motsculsky (Coleoptera: Curculionidae): Presentation

As part of on-going efforts to use eco-friendly alternatives to chemical pesticides, leaf powder of Hemizygia welwitschii was sequentially extracted in hexane, acetone and methanol. Bioassays were carried out to establish the most active fraction(s) against Sitophilus zeamais in maize. Maize grains (50 g) were treated with concentrations within the range 2, 4, 6, and 10 g/kg of extract and Azadirachta indica seed oil (positive control) in the laboratory. The total number of progeny emerging from grains infested separately with S. zeamais eggs, larvae and pupae were recorded. Adult mortality counts were carried out 1, 3, 7 and 14 d post-exposure. Acetone extract was more toxic to the eggs, larvae and pupae than the other extracts, inhibiting progeny production by 90.90%, 88.10% and 100%, respectively, at the concentration 10 g/kg. For the same concentration, A. indica seed oil reduced progeny production by 100% for eggs, 96.08% for larvae and 70.93% for pupae. Hexane extract was more potent to the adult weevil than the other extracts, recording 100% mortality for the concentration 10 g/kg within 14 d. LC50 values were 0.78 (Hexane), 5.52 (acetone) and 1.69 g/kg (methanol). Extracts of H. welwitschii leaves had sufficient efficacy to be a component of storage pest management package for S. zeamais.As part of on-going efforts to use eco-friendly alternatives to chemical pesticides, leaf powder of Hemizygia welwitschii was sequentially extracted in hexane, acetone and methanol. Bioassays were carried out to establish the most active fraction(s) against Sitophilus zeamais in maize. Maize grains (50 g) were treated with concentrations within the range 2, 4, 6, and 10 g/kg of extract and Azadirachta indica seed oil (positive control) in the laboratory. The total number of progeny emerging from grains infested separately with S. zeamais eggs, larvae and pupae were recorded. Adult mortality counts were carried out 1, 3, 7 and 14 d post-exposure. Acetone extract was more toxic to the eggs, larvae and pupae than the other extracts, inhibiting progeny production by 90.90%, 88.10% and 100%, respectively, at the concentration 10 g/kg. For the same concentration, A. indica seed oil reduced progeny production by 100% for eggs, 96.08% for larvae and 70.93% for pupae. Hexane extract was more potent to the adult weevil than the other extracts, recording 100% mortality for the concentration 10 g/kg within 14 d. LC50 values were 0.78 (Hexane), 5.52 (acetone) and 1.69 g/kg (methanol). Extracts of H. welwitschii leaves had sufficient efficacy to be a component of storage pest management package for S. zeamais

Concept development of an on-chip PET system.

BACKGROUND Organs-on-Chips (OOCs), microdevices mimicking in vivo organs, find growing applications in disease modeling and drug discovery. With the increasing number of uses comes a strong demand for imaging capabilities of OOCs as monitoring physiologic processes within OOCs is vital for the continuous improvement of this technology. Positron Emission Tomography (PET) would be ideal for OOC imaging, however, current PET systems are insufficient for this task due to their inadequate spatial resolution. In this work, we propose the concept of an On-Chip PET system capable of imaging OOCs and optimize its design using a Monte Carlo Simulation (MCS). MATERIAL AND METHODS The proposed system consists of four detectors arranged around the OOC device. Each detector is made of two monolithic LYSO crystals and covered with Silicon photomultipliers (SiPMs) on multiple surfaces. We use a Convolutional Neural Network (CNN) trained with data from a MCS to predict the first gamma-ray interaction position inside the detector from the light patterns that are recorded by the SiPMs on the detector's surfaces. RESULTS The CNN achieves a mean average prediction error of 0.80 mm in the best configuration. The proposed system achieves a sensitivity of 34.81% for 13 mm thick crystals and does not show a prediction degradation near the boundaries of the detector. We use the trained network to reconstruct an image of a grid of 21 point sources spread across the field-of-view and obtain a mean spatial resolution of 0.55 mm. We show that 25,000 Line of Responses (LORs) are needed to reconstruct a realistic OOC phantom with adequate image quality. CONCLUSIONS We demonstrate that it is possible to achieve a spatial resolution of almost 0.5 mm in a PET system made of multiple monolithic LYSO crystals by directly predicting the scintillation position from light patterns created with SiPMs. We observe that a thinner crystal performs better than a thicker one, that increasing the SiPM size from 3 mm to 6 mm only slightly decreases the prediction performance, and that certain surfaces encode significantly more information for the scintillation-point prediction than others

Combined PARP and Dual Topoisomerase Inhibition Potentiates Genome Instability and Cell Death in Ovarian Cancer

Although ovarian cancer is a rare disease, it constitutes the fifth leading cause of cancer death among women. It is of major importance to develop new therapeutic strategies to improve survival. Combining P8-D6, a novel dual topoisomerase inhibitor with exceptional anti-tumoral properties in ovarian cancer and compounds in preclinical research, and olaparib, a PARP inhibitor targeting DNA damage repair, is a promising approach. P8-D6 induces DNA damage that can be repaired by base excision repair or homologous recombination in which PARP plays a major role. This study analyzed benefits of combining P8-D6 and olaparib treatment in 2D and 3D cultures with ovarian cancer cells. Measurement of viability, cytotoxicity and caspase activity were used to assess therapy efficacy and to calculate the combination index (CI). Further DNA damage was quantified using the biomarkers RAD51 and γH2A.X. The combinational treatment led to an increased caspase activity and reduced viability. CI values partially show synergisms in combinations at 100 nM and 500 nM P8-D6. More DNA damage accumulated, and spheroids lost their membrane integrity due to the combinational treatment. While maintaining the same therapy efficacy as single-drug therapy, doses of P8-D6 and olaparib can be reduced in combinational treatments. Synergisms can be seen in some tested combinations. In summary, the combination therapy indicates benefits and acts synergistic at 100 nM and 500 nM P8-D6

Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes

<p>Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients.</p> <p>Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers.</p> <p>Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance.</p> <p>Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies.</p&gt

Uncovering distinct progression patterns of tau deposition in progressive supranuclear palsy using [18F]Florzolotau PET imaging and subtype/stage inference algorithm.

BACKGROUND Progressive supranuclear palsy (PSP) is a primary 4-repeat tauopathy with diverse clinical phenotypes. Previous post-mortem studies examined tau deposition sequences in PSP, but in vivo scrutiny is lacking. METHODS We conducted [18F]Florzolotau tau positron emission tomography (PET) scans on 148 patients who were clinically diagnosed with PSP and 20 healthy controls. We employed the Subtype and Stage Inference (SuStaIn) algorithm to identify PSP subtype/stage and related tau patterns, comparing clinical features across subtypes and assessing PSP stage-clinical severity association. We also evaluated functional connectivity differences among subtypes through resting-state functional magnetic resonance imaging. FINDINGS We identified two distinct subtypes of PSP: Subtype1 and Subtype2. Subtype1 typically exhibits a sequential progression of the disease, starting from subcortical and gradually moving to cortical regions. Conversely, Subtype2 is characterized by an early, simultaneous onset in both regions. Interestingly, once the disease is initiated, Subtype1 tends to spread more rapidly within each region compared to Subtype2. Individuals categorized as Subtype2 are generally older and exhibit less severe dysfunctions in areas such as cognition, bulbar, limb motor, and general motor functions compared to those with Subtype1. Moreover, they have a more favorable prognosis in terms of limb motor function. We found significant correlations between several clinical variables and the identified PSP SuStaIn stages. Furthermore, Subtype2 displayed a remarkable reduction in functional connectivity compared to Subtype1. INTERPRETATION We present the evidence of distinct in vivo spatiotemporal tau trajectories in PSP. Our findings can contribute to precision medicine advancements for PSP. FUNDING This work was supported by grants from the National Natural Science Foundation of China (number 82272039, 81971641, 82021002, and 92249302); Swiss National Science Foundation (number 188350); the STI2030-Major Project of China (number 2022ZD0211600); the Clinical Research Plan of Shanghai Hospital Development Center of China (number SHDC2020CR1038B); and the National Key R&D Program of China (number 2022YFC2009902, 2022YFC2009900), the China Scholarship Council (number 202006100181); the Deutsche Forschungsgemeinschaft (DFG) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198)

Therapeutic Reference Range for Aripiprazole in Schizophrenia Revised: a Systematic Review and Metaanalysis

Rationale: While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges. Objectives: Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders. Methods: The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated. Results: Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120-270 ng/ml and 180-380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders. Conclusions: High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers