Logistics challenges of e-grocery last-mile delivery: a literature review

In recent years, e-commerce has been growing globally and online markets have undergone a radical transformation during Covid-19 Pandemic. In this context, Food and Grocery sector has expanded exponentially thus leading to a development of last-mile logistics which is the least efficient supply chain activity in terms of economic and environmental impact. At the moment, B2C e-commerce players face multiple challenges due to logistics complexities and efficiency. On the other side, demand complexities rise from Service Level expectations, and consumers’ willingness to pay for logistics services. Food and Grocery e-commerce has three main configurations: the enogastronomic e-commerce, the on-demand food delivery and the e-grocery. Among these, the third one has reported the highest growth during and after the Pandemic. However, beside complexities of e-commerce logistics, the online purchase of grocery products raises new challenges due to product peculiarities, logistics requirements and complexity of orders. The aim of this work is therefore to investigate which are the main problems associated with last-mile delivery for e-grocery and which are the appropriate variables to describe them. In order to achieve this objective, a Systematic Literature Review has been performed to identify key issues addressed by scholars and existing typologies of last- mile delivery problems in this sector. The contribution of this research is threefold: firstly, it analyses the state of the art of last-mile challenges for e- grocery from an academic perspective and proposes a classification. Secondly, the identification of logistics variables associated with identified problems highlights potential threats for E-grocery players. Therefore, this work supports managers to identify challenges in a structured way before planning appropriate countermeasures for the specific context. Thirdly, it identifies opportunities for future research directions

Urokinase Plasminogen Activator and Gelatinases Are Associated with Membrane Vesicles Shed by Human HT1080 Fibrosarcoma Cells

Membrane vesicles are shed by tumor cells both in vivo and in vitro. Although their functions are not well understood, it has been proposed that they may play multiple roles in tumor progression. We characterized membrane vesicles from human HT1080 fibrosarcoma cell cultures for the presence of proteinases involved in tumor invasion. By gelatin zymography and Western blotting, these vesicles showed major bands corresponding to the zymogen and active forms of gelatinase B (MMP-9) and gelatinase A (MMP-2) and to the MMP-9. tissue inhibitor of metalloproteinase 1 complex. Both gelatinases appeared to be associated with the vesicle membrane. HT1080 cell vesicles also showed a strong, plasminogen-dependent fibrinolytic activity in 125I fibrin assays; this activity was associated with urokinase plasminogen activator, as shown by casein zymography and Western blotting. Urokinase was bound to its high affinity receptor on the vesicle membrane. Addition of plasminogen resulted in activation of the progelatinases associated with the vesicles, indicating a role of the urokinase-plasmin system in MMP-2 and MMP-9 activation. We propose that vesicles shed by tumor cells may provide a large membrane surface for the activation of membrane-associated proteinases involved in extracellular matrix degradation and tissue invasion

Motor imagery training speeds up gait recovery and decreases the risk of falls in patients submitted to total knee arthroplasty

With Motor imagery (MI), movements are mentally rehearsed without overt actions; this procedure has been adopted in motor rehabilitation, primarily in brain-damaged patients. Here we rather tested the clinical potentials of MI in purely orthopaedic patients who, by definition, should maximally benefit of mental exercises because of their intact brain. To this end we studied the recovery of gait after total knee arthroplasty and evaluated whether MI combined with physiotherapy could speed up the recovery of gait and even limit the occurrence of future falls. We studied 48 patients at the beginning and by the end of the post-surgery residential rehabilitation program: half of them completed a specific MI training supported by computerized visual stimulation (experimental group); the other half performed a non-motoric cognitive training (control group). All patients also had standard physiotherapy. By the end of the rehabilitation, the experimental group showed a better recovery of gait and active knee flexion-extension movements, and less pain. The number of falls or near falls after surgery was significantly lower in the experimental group. These results show that MI can improve gait abilities and limit future falls in orthopaedic patients, without collateral risks and with limited costs

Clinical variables associated with late-onset thrombotic and cardiovascular events, after SARS-CoV-2 infection, in a cohort of patients from the first epidemic wave: an 18-month analysis on the “Surviving-COVID” cohort from Bergamo, Italy

Importance: Population studies have recorded an increased, unexplained risk of post-acute cardiovascular and thrombotic events, up to 1 year after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Objectives: To search for clinical variables and biomarkers associated with late post-acute thrombotic and cardiovascular events after SARS-CoV-2 infection.Design: Retrospective cohort study.Setting: Third-level referral hospital in Bergamo (Italy).Participants: Analysis of an existing database of adult patients, who received care for SARS-CoV-2 infection at our institution between 20 February and 30 September 2020, followed up on a single date ("entry date") at 3-6 months.Exposure: Initial infection by SARS-CoV-2.Main outcomes and measures: Primary outcome: occurrence, in the 18 months after entry date, of a composite endpoint, defined by the International Classification of Diseases-9th edition (ICD-9) codes for at least one of: cerebral/cardiac ischemia, venous/arterial thrombosis (any site), pulmonary embolism, cardiac arrhythmia, heart failure. Measures (as recorded on entry date): history of initial infection, symptoms, current medications, pulmonary function test, blood tests results, and semi-quantitative radiographic lung damage (BRIXIA score). Individual clinical data were matched to hospitalizations, voluntary vaccination against SARS-CoV-2 (according to regulations and product availability), and documented reinfections in the following 18 months, as recorded in the provincial Health Authority database. A multivariable Cox proportional hazard model (including vaccine doses as a time-dependent variable) was fitted, adjusting for potential confounders. We report associations as hazard ratios (HR) and 95% confidence intervals (CI).Results: Among 1,515 patients (948 men, 62.6%, median age 59; interquartile range: 50-69), we identified 84 endpoint events, occurring to 75 patients (5%): 30 arterial thromboses, 11 venous thromboses, 28 arrhythmic and 24 heart failure events. From a multivariable Cox model, we found the following significant associations with the outcome: previous occurrence of any outcome event, in the 18 months before infection (HR: 2.38; 95% CI: 1.23-4.62); BRIXIA score >= 3 (HR: 2.43; 95% CI: 1.30-4.55); neutrophils-to-lymphocytes ratio >= 3.3 (HR: 2.60; 95% CI: 1.43-4.72), and estimated glomerular filtration rate < 45 ml/min/1.73 m(2) (HR: 3.84; 95% CI: 1.49-9.91).Conclusions and relevance: We identified four clinical variables, associated with the occurrence of post-acute thrombotic and cardiovascular events, after SARS-CoV-2 infection. Further research is needed, to confirm these results

PET/CT Imaging of Zr-89-N-sucDf-Pembrolizumab in Healthy Cynomolgus Monkeys

PURPOSE: Programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) are the targets for immunotherapy in many cancer types. Although PD-1 blockade has therapeutic effects, the efficacy differs between patients. Factors contributing to this variability are PD-L1 expression levels and immune cells present in tumors. However, it is not well understood how PD-1 expression in the tumor microenvironment impacts immunotherapy response. Thus, imaging of PD-1-expressing immune cells is of interest. This study aims to evaluate the biodistribution of Zirconium-89 (89Zr)-labeled pembrolizumab, a humanized IgG4 kappa monoclonal antibody targeting PD-1, in healthy cynomolgus monkeys as a translational model of tracking PD-1-positive immune cells. PROCEDURES: Pembrolizumab was conjugated with the tetrafluorophenol-N-succinyl desferal-Fe(III) ester (TFP-N-sucDf) and subsequently radiolabeled with 89Zr. Four cynomolgus monkeys with no previous exposure to humanized monoclonal antibodies received tracer only or tracer co-injected with pembrolizumab intravenously over 5 min. Thereafter, a static whole-body positron emission tomography (PET) scan was acquired with 10 min per bed position on days 0, 2, 5, and 7. Image-derived standardized uptake values (SUVmean) were quantified by region of interest (ROI) analysis. RESULTS: 89Zr-N-sucDf-pembrolizumab was synthesized with high radiochemical purity (> 99 %) and acceptable molar activity (> 7 MBq/nmol). In animals dosed with tracer only, 89Zr-N-sucDf-pembrolizumab distribution in lymphoid tissues such as mesenteric lymph nodes, spleen, and tonsils increased over time. Except for the liver, low radiotracer distribution was observed in all non-lymphoid tissue including the lung, muscle, brain, heart, and kidney. When a large excess of pembrolizumab was co-administered with a radiotracer, accumulation in the lymph nodes, spleen, and tonsils was reduced, suggestive of target-mediated accumulation. CONCLUSIONS: 89Zr-N-sucDf-pembrolizumab shows preferential uptake in the lymphoid tissues including the lymph nodes, spleen, and tonsils. 89Zr-N-sucDf-pembrolizumab may be useful in tracking the distribution of a subset of immune cells in non-human primates and humans. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02760225

A novel haemocytometric COVID-19 prognostic score developed and validated in an observational multicentre European hospital-based study

COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration, and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients