Network Design Model with Evacuation Constraints Under Uncertainty

Abstract: Nepal earthquake, have shown the need for quick response evacuation and assistance routes. Evacuation routes are, mostly, based on the capacities of the roads network. However, in extreme cases, such as earthquakes, roads network infrastructure may adversely affected, and may not supply their required capacities. If for various situations, the potential damage for critical roads can be identify in advance, it is possible to develop an evacuation model, that can be used in various situations to plan the network structure in order to provide fast and safe evacuation. This paper focuses on the development of a model for the design of an optimal evacuation network which simultaneously minimizes construction costs and evacuation time. The model takes into consideration infrastructures vulnerability (as a stochastic function which is dependent on the event location and magnitude), road network, transportation demand and evacuation areas. The paper presents a mathematic model for the presented problem. However, since an optimal solution cannot be found within a reasonable timeframe, a heuristic model is presented as well. The heuristic model is based on evolutionary algorithms, which also provides a mechanism for solving the problem as a stochastic and multi-objective problem

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

L'emergenza dell'alterità: a scuola per una nuova etica di liberazione

Il periodo emergenziale che stiamo globalmente vivendo ha centralizzato alcune riflessioni che riguardano ampi aspetti della vita sociale e culturale; in particolare ha interrogato le finalità educative e pedagogiche di un sistema complesso come la scuola. Si riflette sull’urgenza di alcune ri-significazioni: un riposizionamento di ciò che viene riconosciuto come “altro”, come punto di vista necessario per creare prospettiva; e di ciò che viene considerata “distanza” come fattore fondamentale per il rispetto della condizione umana. L’urgenza ha riposizionato l’emergenza dell’alterità (come bisogno di riconoscimento grazie ad una distanza virtuosa e prospettica) e la scuola è luogo educativo che – in uno scambio cerimoniale dialogico – deve fare propria questa chiamata, nel suo esserci come spazio reale e concreto, nel suo promuovere una nuova etica di liberazione

Plant-Based Systems for Vaccine Production

Plant systems have been used as biofactories to produce recombinant proteins since 1983. The huge amount of data, collected so far in this framework, suggests that plants display several key advantages over existing traditional platforms when they are intended for therapeutic uses, including safety, scalability, and the speed in obtaining the final product. Here, we describe a method that could be applied for the expression and production of a candidate subunit vaccine in Nicotiana benthamiana plants by transient expression, defining all the protocols starting from plant cultivation to target recombinant protein purification

Perspectives for autoimmune diabetes prevention using plants

Autoimmune diabetes is the most frequent chronic disease of childhood and it is characterised by long-term and severe complications; different therapeutic approaches have been used in order to prevent and to suppress the disease at an experimental level but no one of them reached so far positive results in human trials. However, the results of clinical trials using autoantigen-based therapies suggested new insight for the research of a vaccine. The 65 kDa isoform of human glutamic acid decarboxylase, one of the major autoantigen associated with the disease, is regarded as crucial for future studies on diabetes prevention and suppression. GAD65 is actually produced using conventional expression systems (mainly based on yeast and baculovirus/insect cell) and the final product is characterised by high costs. We exploited plants as a platform for the production of human GAD65 by using stable and transient expression and by engineering the protein at different degrees. Our results indicate that plants are a feasible and versatile system for the production of this recombinant protein. The results obtained in the perspective of new therapeutic approaches are described and discussed

PVX a powerful tool for autoimmune disease diagnosis

We explored the use of Potato Virus X as a scaffold for the expression of an immunodominant peptide associated to Sjogren\u2019s syndrome. Sj\uf6gren's syndrome (SjS) is a chronic autoimmune disease in which the body's white cells destroy the exocrine glands, specifically the salivary and lacrimal glands, that produce saliva and tears, respectively. Human lipocalin was recently identified as a primary autoantigen associated to the disease and the immunodominant peptide associated to the protein was discovered using the sera of SjS patients. Autoantibodies directed to the peptide allow to identify in the population patients whose sera was negative to anti nuclear antibodies and to the rheumatoid factor. The lipocalin peptide was cloned into a PVX-based vector which mediates the peptide display on the virus coat protein, yielding Chimeric Virus Particles (CVPs). CVPs allow a high-density exposure of the peptide on the viral surface. The CVPs were used for coating an ELISA plate giving an assay which reproducibility, stability and sensitive was compared to the use of the peptide alone

Expression of a mutated form of GAD65 in heterologous systems

Type 1 insulin-dependent diabetes mellitus (T1DM) which afflicts 0.2-0.3% of population is caused by autoimmune destruction of insulin-secreting beta cells. The young age of affected patients, the need for life-long insulin therapy and the high prevalence of late-onset complications make T1DM a major health problem. The smaller isoform of glutamic acid decarboxylase of 65 kDa (GAD65) is the major autoantigen in human T1DM and it has recently demonstarated that two injections of the molecule can give protection against this autoimmune disease. T1DM requires a primary prevention because the disease has a complex genetic basis, making difficult to identify in the population people at risk of developing it. Vaccination studies and subsequent vaccination treatment of a lot of people need large quantity of purified protein, but the current production systems are too much expensive and unable to provide enough GAD65 to meet global demand. We have previously shown that GAD65 can be expressed in transgenic tobacco plants but yields are disappointing. In order to improve its expression level we use different heterologous systems such as Nicotiana tabacum plants, E.coli inducible system and insect cells/Baculovirus to express two different forms of the recombinant human GAD65: the wild type form of the enzyme (hGAD65) and the mutated form with no catalytic activity (hGAD65mut), hypothesising that the enzymatic activity might interfere with its accumulation in heterologous systems. In previous studies it has been demonstrated in vitro the lack of the enzymatic activity for the hGAD65mut and we show that GAD65mut accumulates to higher levels in transgenic plants and in E.coli inducible system than its enzymatically active counterpart, indicating that the catalytic properties of GAD65 contribute to its poor yields. To demonstrated the absence of enzymatic activity of the mutated form of GAD65 (GAD65mut) also in the heterologous systems we perform an enzymatic assay in vivo,. The results of the assay and the difference among the expression levels obtained in the heterologous systems are discussed