Narrow trenches are a common technique for the installation of utility pipelines of small diameter. The excavated soil is not always appropriate as landfill and, in those cases, an appropriate soil ...from somewhere else (ex. a borrow pit or another construction site) should be used instead (classical solution, CS). Another common solution is to use a controlled low-strength (cementitious) material (CLSM) as backfill instead of compacted soil. However, both solutions lead to increased raw material consumption, waste generation, need for transportation, and CO2 emissions. In an attempt to address these issues, researchers developed an eco-trench (ECO) that reuses the excavated soil of narrow trenches to produce a controlled low-strength material to be used as landfill. Although technically viable, the sustainability of this solution versus the traditional solution has not been properly addressed. Hence, this paper aims to develop a method for the sustainability assessment of trenches. The Sustainability Index of Trenches (SIT), based on the MIVES decision-making method, enables the assessment and prioritisation of different types of trenches according to sustainability criteria. Criteria, indicators, weights and value functions were specifically defined based on seminars with experts in the field of utility services and construction. A case study was performed in which four types of trenches (CS, CS with recycling CS + R, CLSM and ECO) were assessed and prioritised according to SIT. ECO resulted in the most sustainable alternative with a SIT of 0.80 out of 1 followed by CS + R, CS and CLSM with SITs of 0.63, 0.40 and 0.38 respectively. The sensitivity analysis showed consistent results in different scenarios. These findings demonstrate the capability and reliability of SIT as a decision-making tool for the evaluation of the sustainability of different construction processes for trenches and the prioritisation of the most suitable solution for different situations.
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•A Sustainability Index for Trenches (SIT) is defined.•SIT is based on MIVES multi-criteria decision-making method.•SIT enables the assessment and prioritisation of different types of trenches.•Four type of trenches including the new eco-trench have been evaluated with the SIT.•The sensitivity analysis proved the method to be robust and repeatable
The carcinogenic role of high-risk human papillomavirus (HR-HPV) types in the increasing subset of vulvar intraepithelial neoplasia and vulvar cancer in young women has been established. However, the ...actual number of vulvar cancer cases attributed to HPV is still imprecisely defined. In an attempt to provide a more precise definition of HPV-driven vulvar cancer, we performed HPV-type-specific E6*I mRNA analyses available for 20 HR-/possible HR (pHR)-HPV types, on tissue samples from 447 cases of vulvar cancer. HPV DNA genotyping was performed using SPF10-LiPA25 assay due to its high sensitivity in formalin-fixed paraffin-embedded tissues. Data on p16INK4a expression was available for comparative analysis via kappa statistics. The use of highly sensitive assays covering the detection of HPV mRNA in a broad spectrum of mucosal HPV types resulted in the detection of viral transcripts in 87% of HPV DNA+ vulvar cancers. Overall concordance between HPV mRNA+ and p16INK4a upregulation (strong, diffuse immunostaining in >25% of tumor cells) was 92% (K=0.625, 95% confidence interval (CI)=0.531–0.719). Among these cases, 83% were concordant pairs of HPV mRNA+ and p16INK4a+ and 9% were concordant pairs of HPV mRNA− and p16INK4a−. Our data confirm the biological role of HR-/pHR-HPV types in the great majority of HPV DNA+ vulvar cancers, resulting in an HPV-attributable fraction of at least 21% worldwide. Most HPV DNA+ vulvar cancers were associated with HPV16 (85%), but a causative role for other, less frequently occurring mucosal HPV types (HPV26, 66, 67, 68, 70 and 73) was also confirmed at the mRNA level for the first time. These findings should be taken into consideration for future screening options as HPV-associated vulvar preneoplastic lesions have increased in incidence in younger women and require different treatment than vulvar lesions that develop from rare autoimmune-related mechanisms in older women.
Infrastructure construction, one of the biggest driving forces of the economy nowadays, requires a huge analysis and clear transparency to decide what projects have to be executed with the few ...resources available. With the aim to provide the public administrations a tool with which they can make their decisions easier, the Sustainability Index of Infrastructure Projects (SIIP) has been defined, with a multi-criteria decision system called MIVES, in order to classify non-uniform investments. This index evaluates, in two inseparable stages, the contribution to the sustainable development of each infrastructure project, analyzing its social, environmental and economic impact. The result of the SIIP allows to decide the order with which projects will be prioritized. The case of study developed proves the adaptability and utility of this tool for the ordinary budget management.
•A new specific methodology to prioritize buildings for public services is presented.•Sustainability is the basis of the Sustainable Building index (Bs).•Bs is compared with other two ...methodologies.•Analytic hierarchy process (AHP) is used to establish the weight of the indicators.
A Multi-Criteria Decision-Making (MCDM) methodology is presented in this paper that is used to analyse and to assess public-service building projects for the promotion of smart sustainable cities. Its main purpose is to compare different types of projects (hospitals, schools, museums, etc.) and to prioritize the investments that present the most favourable global results. The methodology, known as MIVES, constructs a model that assists decision-making on the basis of consistent and transparent criteria. It incorporates the value function concept that attaches a value to different types of variables for the purpose of arriving at a final value in relation to pre-defined criteria. In this study, the model is based on the three basic pillars of sustainability (economy, environment, and society) presented in a triple-layer decision tree. Its application to four urban projects, presented as examples, showed encouraging results with a wide range of values.
Human Papillomavirus (HPV) prophylactic vaccination has proven effective in preventing new infections, but it does not treat existing HPV infections or associated diseases. Hence, there is still an ...important reservoir of HPV in adults, as vaccination programs are mainly focused on young women. The primary objective of this non-randomized, open-label trial is to evaluate if a 3-dose regimen of Gardasil-9 in HPV16/18-positive women could reduce the infective capacity of their body fluids. We aim to assess if vaccine-induced antibodies could neutralize virions present in the mucosa, thus preventing the release of infective particles and HPV transmission to sexual partners. As our main endpoint, the E1^E4-HaCaT model will be used to assess the infectivity rate of cervical, anal and oral samples, obtained from women before and after vaccination. HPV DNA positivity, virion production, seroconversion, and the presence of antibodies in the exudates, will be evaluated to attribute infectivity reduction to vaccination. Our study will recruit two different cohorts (RIFT-HPV1 and RIFT-HPV2) of non-vaccinated adult women. RIFT-HPV1 will include subjects with an HPV16/18 positive cervical test and no apparent cervical lesions or cervical lesions eligible for conservative treatment. RIFT-HPV2 will include subjects with an HPV16/18 positive anal test and no apparent anal lesions or anal lesions eligible for conservative treatment, as well as women with an HPV16/18 positive cervical test and HPV-associated vulvar lesions. Subjects complying with inclusion criteria for both cohorts will be recruited to the main cohort, RIFT-HPV1. Three doses of Gardasil-9 will be administered intramuscularly at visit 1 (0 months), visit 2 (2 months) and visit 3 (6 months). Even though prophylactic HPV vaccines would not eliminate a pre-existing infection, our results will determine if HPV vaccination could be considered as a new complementary strategy to prevent HPV-associated diseases by reducing viral spread. Trial registration: https://clinicaltrials.gov/ct2/show/NCT05334706.
Maintenance management of the hydraulic structures requires the selection of the most necessary maintenance intervention to ensure their proper operation and structural safety. Given the ...characteristics of these structures, many types of damage may appear, so it is not easy to take a decision. The purpose of this paper is to present the Prioritisation Index for the Management of Hydraulic Structures (PIMHS), a multi-criteria decision-making system based on the three axioms of sustainability (social, environmental and economic), which orders and prioritises non-similar maintenance investments in hydraulic structures. The results obtained show that PIMHS can be used by decision-makers to prioritise, in hydraulic structures, all kinds of maintenance interventions where the damages cannot lead to dam break.
Many countries, mainly high- and upper-middle income, have implemented human papillomavirus (HPV) vaccination programs, with 47 million women receiving the full course of vaccine (three doses) in ...2014. To evaluate the potential impact of HPV vaccines in the reduction of HPV-related disease, we aimed to estimate the HPV type distribution and burden of anogenital and head and neck cancers attributable to HPV types (HPVs 16/18/31/33/45/52/58/6/11) included in currently licensed HPV vaccines.
In all, 18 247 formalin-fixed paraffin-embedded specimens were retrieved from 50 countries. HPV DNA detection and typing were performed with the SPF-10 PCR/DEIA/LiPA25 system. With the exception of cervical cancer, HPV DNA-positive samples were additionally subjected to HPV E6*I mRNA detection and/or p16
immunohistochemistry. For cervical cancer, estimates were based on HPV DNA, whereas for other sites, estimates were based on HPV DNA, E6*I mRNA, and p16
biomarkers.
The addition of HPVs 31/33/45/52/58 to HPVs 16/18/6/11 in the nonavalent HPV vaccine could prevent almost 90% of cervical cancer cases worldwide. For other sites, the nonavalent HPV vaccine could prevent 22.8% of vulvar, 24.5% of penile, 60.7% of vaginal, 79.0% of anal cancers, 21.3% of oropharyngeal, 4.0% of oral cavity, and 2.7% of laryngeal cancer cases.
Our estimations suggest a potential impact of the nonavalent HPV vaccine in reducing around 90% of cervical cancer cases and a global reduction of 50% of all the cases at HPV-related cancer sites.
Chimeric antigen receptor (CAR) T-cell therapy provides long-term remissions in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Total metabolic tumor volume (TMTV) assessed ...by 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) has a confirmed prognostic value in the setting of chemoimmunotherapy, but its predictive role with CAR T-cell therapy is not fully established. Thirty-five patients with R/R LBCL who received CAR T-cells were included in the study. TMTV and maximum standardized uptake value (SUVmax) were measured at baseline and 1-month after CAR T-cell infusion. Best response included 9 (26%) patients in complete metabolic response (CMR) and 16 (46%) in partial metabolic response (PMR). At a median follow-up of 7.6 months, median PFS and OS were 3.4 and 8.2 months, respectively. A high baseline TMTV (≥ 25 cm
3
) was associated with a lower PFS (median PFS, 2.3 vs. 8.9 months; HR = 3.44 95% CI 1.18–10.1, p = 0.02). High baseline TMTV also showed a trend towards shorter OS (HR = 6.3 95% CI 0.83–47.9, p = 0.08). Baseline SUVmax did not have a significant impact on efficacy endpoints. TMTV and SUVmax values showed no association with adverse events. Metabolic tumor burden parameters measured by 18FDG-PET before CAR T-cell infusion can identify LBCL patients who benefit most from this therapy.
To repurpose compounds for diffuse large B cell lymphoma (DLBCL), we screened a library of drugs and other targeted compounds approved by the US Food and Drug Administration on 9 cell lines and ...validated the results on a panel of 32 genetically characterized DLBCL cell lines. Dasatinib, a multikinase inhibitor, was effective against 50% of DLBCL cell lines, as well as against in vivo xenografts. Dasatinib was more broadly active than the Bruton kinase inhibitor ibrutinib and overcame ibrutinib resistance. Tumors exhibiting dasatinib resistance were commonly characterized by activation of the PI3K pathway and loss of PTEN expression as a specific biomarker. PI3K suppression by mTORC2 inhibition synergized with dasatinib and abolished resistance in vitro and in vivo. These results provide a proof of concept for the repurposing approach in DLBCL, and point to dasatinib as an attractive strategy for further clinical development in lymphomas.
Patients receiving an allogeneic hematopoietic cell transplantation (allo-HCT) after the use of PD-1 inhibitors seem to be at a higher risk of developing acute graft-versus-host disease (aGHVD) ...through etiopathogenetic mechanisms not fully elucidated. Herein, we investigated the effect of nivolumab administered prior to allo-HCT on the following early T-cell reconstitution and its modulation by the GVHD prophylaxis (tacrolimus/sirolimus vs. posttransplant cyclophosphamide PTCY). In all nivolumab-exposed patients we detected circulating nivolumab in plasma for up to 56 days after allo-HCT. This residual nivolumab was able to bind and block PD-1 on T-cells at day 21 after allo-HCT, inducing a T cell activation that was differentially modulated depending on the GVHD prophylactic regimen. Among patients receiving tacrolimus/sirolimus, nivolumab-exposed patients had a higher incidence of severe aGVHD and a more effector T-cell profile compared with anti-PD-1-naïve patients. Conversely, patients receiving PTCY-based prophylaxis showed a similar risk of aGVHD and T-cell profile irrespective of the previous nivolumab exposure. In conclusion, nivolumab persists in plasma after transplantation, binds to allogeneic T cells and generates an increased T-cell activation. This T-cell activation status can be mitigated with the use of PTCY, thus reducing the risk of aGVHD.
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