A methodology based on benchmarking to learn across megaprojects: the case of nuclear decommissioning

Purpose: The literature lacks a single and universally accepted definition of major and megaprojects: usually, these projects are described as projects with a budget above $1 billion and a high level of innovation, complexity & uniqueness both in terms of physical infrastructure and stakeholder network. Moreover, they often provide fewer benefits than what were originally expected and are affected by delays and cost overruns. Despite this techno-economic magnitude, it is still extremely hard to gather lessons learned from these projects in a systematic way. This paper presents an innovative methodology based on benchmarking to investigate good and bad practices and learn from a portfolio of unique megaprojects. Design/methodology/approach: The methodology combines quantitative & qualitative cross-comparison of case studies and statistical analysis into an iterative process. Findings: Indeed, benchmarking offers significant potential to identify good and bad practices and improve the performance of project selection, planning and delivery. Research limitations/implications: The methodology is exemplified in this paper using the case of Nuclear Decommissioning Projects and Programmes (NDPs). Originality/value: Indeed, due to their characteristics, NDPs can be addressed as megaprojects, and are a relevant example for the application of the methodology presented here that collects and investigates the characteristics that mostly impact the performance of (mega)projects, through a continuous learning process

Open challenges in the management of autoimmune hepatitis

Autoimmune Hepatitis (AIH) is a rare autoimmune disease of the liver with many open questions as regards its aetiopathogenesis, natural history and clinical management. The classical picture of AIH is chronic hepatitis with fluctuating elevation of serum transaminases and Immunoglobulin G levels, the presence of circulating autoantibodies and typical histological features. However, atypical presentations do occur and are not well captured by current diagnostic scores, with important consequences in terms of missed diagnoses and delayed treatments. AIH is treated with corticosteroids and immunosuppressive drugs but up to 40% of patients do not achieve full biochemical response and are at risk of progressing to cirrhosis and liver failure. Moreover, standard therapies are associated by significant side-effects which may impair the quality of life of patients living with AIH. However, advances in the understanding of the underlying immunology of AIH is raising the prospect of novel therapies and optimisation of existing therapeutic approaches to reduce side-effect burdens and potentially restore immunological tolerance. In this review we outline the clinical characteristics, aetiopathogenesis and management of AIH and current challenges in the diagnosis and management of AIH and provide evidence underlying the evolution of diagnostic and clinical management protocols

Microstructural Visual Pathway White Matter Alterations in Primary Open-Angle Glaucoma:A Neurite Orientation Dispersion and Density Imaging Study

BACKGROUND AND PURPOSE: DTI studies of patients with primary open-angle glaucoma have demonstrated that glaucomatous degeneration is not confined to the retina but involves the entire visual pathway. Due to the lack of direct biologic interpretation of DTI parameters, the structural nature of this degeneration is still poorly understood. We used neurite orientation dispersion and density imaging (NODDI) to characterize the microstructural changes in the pregeniculate optic tracts and the postgeniculate optic radiations of patients with primary open-angle glaucoma, to better understand the mechanisms underlying these changes.& nbsp;MATERIALS AND METHODS: T1- and multishell diffusion-weighted scans were obtained from 23 patients with primary open-angle glaucoma and 29 controls. NODDI parametric maps were produced from the diffusion-weighted scans, and probabilistic tractography was used to track the optic tracts and optic radiations. NODDI parameters were computed for the tracked pathways, and the measures were compared between both groups. The retinal nerve fiber layer thickness and visual field loss were assessed for the patients with glaucoma.& nbsp;RESULTS: The optic tracts of the patients with glaucoma showed a higher orientation dispersion index and a lower neurite density index compared with the controls (

Identifying cues for self-organized nest wall-building behaviour in the rock ant, Temnothorax rugatulus, using hidden Markov models

Funding: E.I.’s Ph.D. was funded by the John Templeton Foundation as part of the research collaboration grant ‘Putting the extended evolutionary synthesis to the test’ (grant no. 60501). The postdoctoral research project that followed this initial work was funded by an ASAB research grant to M.W. and E.I.European Temnothorax albipennis and its American counterpart Temnothorax rugatulus build circular walls to limit their nest area within a rock crevice. To determine wall position, workers are thought to rely on a distance template (from the cluster of brood and nurses at the nest centre) and on indirect social (i.e. stigmergic) information found in the aggregations of already-deposited building material. Analytical and simulation models of this behaviour predict that the combination of these two mechanisms can produce the observed wall structure, but there is so far no empirical evidence of either mechanism. Here, we find statistical evidence in support of the stigmergic relationship between stone density and deposition behaviour. We apply hidden Markov models (HMMs) to analyse wall-building data from four colonies of T. rugatulus. We show that material deposition activity changes following a parabolic relationship with the density of building material at building sites, different from the linear relationship hypothesized previously. This parabolic curve is similar to behavioural response curves identified in the nest enlargement process of several ant species. In addition, HMM analysis indicates the existence of two distinct states in T. rugatulus building activity. These states are associated with different mean building rates (that is, the two states can be described as a high and a low activity state) and might be caused by changes in task priorities during the colony process of settling into a new nest. This study updates one of the earliest models of self-organized animal behaviour.Peer reviewe

Benign hereditary chorea and deletions outside NKX2-1 : what's the role of MBIP?

Heterozygous point mutations or deletions of the NKX2-1 gene cause benign hereditary chorea (BHC) or a various combinations of primary hypothyroidism, respiratory distress and neurological disorders. Deletions proximal to, but not encompassing, NKX2-1 have been described in few subjects with brain-lung-thyroid syndrome. We report on a three-generation Italian family, with 6 subjects presenting BHC and harboring a genomic deletion adjacent to NKX2-1 and including the gene MBIP, recently proposed to be relevant for the pathogenesis of brain-lung-thyroid syndrome. We observed a clear reduction of NKX2-1 transcript levels in fibroblasts from our patients compared to controls; this finding suggests that MBIP deletion affects NKX2-1 expression, mimicking haploinsufficiency caused by classical NKX2-1 related mutations

Implanted Microsensor Continuous IOP Telemetry Suggests Gaze and Eyelid Closure Effects on IOP-A Preliminary Study

PurposeTo explore the effect of gaze direction and eyelid closure on intraocular pressure (IOP).MethodsEleven patients with primary open-angle glaucoma previously implanted with a telemetric IOP sensor were instructed to view eight equally-spaced fixation targets each at three eccentricities (10°, 20°, and 25°). Nine patients also performed eyelid closure. IOP was recorded via an external antenna placed around the study eye. Differences of mean IOP between consecutive gaze positions were calculated. Furthermore, the effect of eyelid closure on gaze-dependent IOP was assessed.ResultsThe maximum IOP increase was observed at 25° superior gaze (mean ± SD: 4.4 ± 4.9 mm Hg) and maximum decrease at 25° inferonasal gaze (-1.6 ± 0.8 mm Hg). There was a significant interaction between gaze direction and eccentricity (P = 0.003). Post-hoc tests confirmed significant decreases inferonasally for all eccentricities (mean ± SEM: 10°: -0.7 ± 0.2, P = 0.007; 20°: -1.1 ± 0.2, P = 0.006; and 25°: -1.6 ± 0.2, P = 0.006). Eight of 11 eyes showed significant IOP differences between superior and inferonasal gaze at 25°. IOP decreased during eyelid closure, which was significantly lower than downgaze at 25° (mean ± SEM: -2.1 ± 0.3 mm Hg vs. -0.7 ± 0.2 mm Hg, P = 0.014).ConclusionsOur data suggest that IOP varies reproducibly with gaze direction, albeit with patient variability. IOP generally increased in upgaze but decreased in inferonasal gaze and on eyelid closure. Future studies should investigate the patient variability and IOP dynamics

Urban food waste for soil amendment? Analysis and characterisation of waste-based compost for soil fertility management in agroecological horticultural production systems in the city of Rosario, Argentina

Urban and peri-urban lands can be an important source of food production for localised and sustainable food systems, however, their soils can be of poor quality, degraded or damaged by anthropic activities, and little is known about their suitability or safety. This paper aims to contribute to this knowledge gap by assessing the soil remediation capacity and qualities of different types of compost made from urban and peri-urban organic wastes for agroecological food production. Prepared over the course of 2021, and used in 2022 for food growing, five different composts were observed and analysed, in two different farms in the city of Rosario, Argentina. Four raw materials generated largely by local industries were used to make the composts: chicken manure, rumen (cow’s stomachs), brewer’s bagasse (byproducts of the beer industry) and urban leaves collected from the municipality waste collection. These were mixed in different proportions (all reaching the 20–30 C/N ratio, typical of quality compost) to produce viable growing substrates where radishes and lettuces were grown. The aim of the study was to assess the possibility, quality and limitations to use locally available organic inputs for soil fertility management in agroecological farming, in the context of urbanisation and to assess pathways to develop closed-cycle agroecological agriculture at metropolitan level. Natural manure substrates (raw and composted) were analysed, as well as crops grown and fertilised with each of the substrates. The attributes and limiting factors of each substrate and their response to local soil conditions were compared and physicochemical, biochemical, and microbiological analyses were performed, including among others, the study of microbial biomass, biological activity, biophytotoxicity, pH, aerobic heterotrophs, nitrogen fixation, and the presence of antibiotics, agrochemicals and heavy metals. The results of the analyses show that all the composted materials improved the physical, chemical and biological properties. However, in some cases, pollutants were present even after composting. Analysis carried out on the vegetables generally indicate undetectable levels or levels below the admissible limits, demonstrating the filtering capacity of the different composts and the soil

Correlation between cognitive functions and motor coordination in children with different cognitive levels

Cognitive development is related with central nervous system maturation and plays a crucial role for the definition of executive functions such as movement imagination, movement planning and problem-solving. In particular, executive functions are required during complex interactions between players/environment and are also fundamental for motor skills coordination. Although the complex interaction between cognitive and physical outcomes was recognized by several authors, few studies examined the magnitude of the relation between executive functions and motor development according to dif- ferent stages of cognitive maturation. Thus the aim was the assessment of the relationships between motor skills coordination and executive functions in children with different cognitive level. Ninety healthy male participants were involved in the study where children affected by Down syndrome were, also, recruited. The participants were divided into three groups according to classi- fication of Piaget: concrete, formal operational groups and Down syndrome individuals. Executive functions were assessed using a validated computerized battery tests while motor skills was evaluated using the K\uf6rperkoordinations Test f\ufcr Kinder. Analysis of variance by ranks (Kruskal-Wallis nonparametric test) and Mann-Whitney U pairwise comparisons with Dunn\u2019s correction for multiple contrasts were applied to assess the differences concerning the two kinds of outcome. The Pearson product-moment correlation coefficient was used to calculate the correlation between physical performance and the outcomes of the cognitive tests. A Spearman correlation was used to analyze the data when the assumption of normality was violated. The three groups showed differences in both executive functions and motor coordination outcomes. The highest number of significant correlations was found in the formal operational group (correlation coefficients ranging between 120.999 and 120.520, and between 0.970 and 0.759, all p values < 0.05) while a small number of correlations were found in the concrete operational group (correlation coefficients equal to 120.527, 120.461, 120.436 and 0.468, all p values < 0.05). No correlations between executive function and motor coordination were found in Down syndrome group. High executive function seems to affect the coordination skills

Pten alterations and their role in cancer management: Are we making headway on precision medicine?

Alterations in the tumor suppressor phosphatase and tensin homolog (PTEN) occur in a substantial proportion of solid tumors. These events drive tumorigenesis and tumor progression. Given its central role as a downregulator of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, PTEN is deeply involved in cell growth, proliferation, and survival. This gene is also implicated in the modulation of the DNA damage response and in tumor immune microenvironment modeling. Despite the actionability of PTEN alterations, their role as biomarkers remains controversial in clinical practice. To date, there is still a substantial lack of validated guidelines and/or recommendations for PTEN testing. Here, we provide an update on the current state of knowledge on biologic and genetic alterations of PTEN across the most frequent solid tumors, as well as on their actual and/or possible clinical applications. We focus on possible tailored schemes for cancer patients\u2019 clinical management, including risk assessment, diagnosis, prognostication, and treatment