Attempts to integrate sustainability in the decision-making process for transport infrastructure projects continue to gain momentum. A number of tools and methodological frameworks are available - ...such as rating systems, traditional decision-making techniques, checklists, and different evaluation frameworks and models. While these tools are highly valuable, some practical issues remain unsolved. There is also a need for more standardized tools to appraise the sustainability of transport projects. This paper is a presentation of a review on the current assessment tools of sustainability applied to transport infrastructure projects. The preliminary part of the paper is an explanatory and comparative analysis of the tools and methods in terms of their effectiveness to appraise sustainability. The analysis is a critical evaluation of the current state of the art to identify the limitations of existing approaches, point out new areas of research, and propose a sustainability appraisal agenda for the future.
Objectif Cette étude a pour but de préciser le phénotype des femmes méditerranéennes présentant un diabète gestationnel (DG) ou un risque de DG, diagnostiqués par une HGPO. Patients et méthodes Onze ...centres nationaux ont recruté de 75 à 200 femmes entre la 24éme et la 32éme semaine de grossesse (Grèce, Serbie, Italie, France, Portugal, Malte, Maroc, Tunisie, Algérie, Syrie et Liban). Les principaux facteurs de risque de DG ont été recherchés chez toutes les femmes qui ont aussi bénéficié d’un examen anthropométrique, d’une mesure de la pression artérielle, d’une HPGO avec 75 g de glucose, d’une mesure de l’insulinémie à jeun, et d’un dosage de l’HbA1c; l’insulino-résistance a été quantifiée par le Homeostatic Model Assessment (HOMA-IR). Les patientes chez lesquelles un DG a été dépisté ont été prises en charge selon le protocole utilisé dans chaque pays. Résultats Un total de 1368 femmes enceintes a été recruté et un DG a été mis en évidence chez 119 d’entre elles (8.7 %) selon les critères de l’ADA, chez 268 (19.6 %) selon ceux de l’OMS et chez 364 (26.6 %) selon ceux de I’ADPSG. Les facteurs de risque significativement associés au développement d’un DG étaient un âge > 35 ans, un IMC > 25 kg/m2 , une pression artérielle diastolique > 90 mmHg, la présence d’antécédents personnels de macrosomie et celle d’antécédents familiaux de diabète. Tous ces facteurs avaient une forte spécificité mais une faible sensibilité (sauf l’IMC pré-gestationnel avec une spécificité et une sensibilité modérées). Aucune corrélation significative n’a été retrouvée entre l’IMC et les paramètres biochimiques étudiés. Une corrélation significative a été notée entre le DG et le poids de naissance de l’enfant. Conclusion La discordance notable de la prévalence du DG selon les critères diagnostiques souligne l’importance d’un consensus à ce sujet.
Thyroid dysfunction is known to adversely affect pregnancy. This study evaluates the prevalence of thyroid disorders and explores their association with pregnancy complications/comorbidities and ...modes of delivery in the Maltese pregnant population over a ten year period.
A population based observational study.
We analysed data from the National Obstetrics Information Service of the Department of Health Informations and Research (NOIS) for all births delivered in Malta between 2006 and 2016. Cases identified and recorded by NOIS to have had some form of thyroid dysfunction during pregnancy were confirmed by cross-referencing with laboratory results found in patients' medical records and/or iSOFT® database system. Using the Statistical Package for the Social sciences (SPSS®) demographic data, past obstetric and medical history and obstetric outcomes were analysed for pregnancies with thyroid dysfunction and compared to data pertaining to pregnancies in euthyroid patients, that is those with no recorded thyroid dysfunction on NOIS. Chi square/Fisher's exact test were used to compare categorical variables while ANOVA/Mann-Whitney U test was used to compare continuous variables. Statistical significance was defined by a two-sided p value <0.05.
Data was available for 46,283 women (mean SD age = 29.2 5.4 years). 587 pregnancies (1.3%) suffered from thyroid dysfunction. Of these, 67.3% were hypothyroid, 3.2% had hyperthyroidism, 28.3% had isolated hypothyroxinaemia (IHT) while 1.2% had a history of thyroid carcinoma. Patients with IHT and hypothyroidism were older than euthyroid patients (p < 0.001). IHT and hypothyroid patients had a statistically significant higher body mass index (BMI) than euthyroid women (p=0.001 for hypothyroid women, p = 0.035 for IHT). Hypothyroid and IHT women were more likely to have had a previous lower segment caesarean section (p=0.043, and 0.006 respectively). Type 1 diabetes and gestational diabetes p = 0.012) were more common associated comorbidities in hypothyroid pregnancies. Offspring of patients with IHT had a higher birth weight than those born to euthyroid patients (p=0.009). Patients with hyperthyroidism were found to have a significantly increased risk of early preterm delivery before 34 weeks of gestation and were also more likely to have suspected intrauterine growth restriction and low mean birth weight. We report no significant differences in past history of obstetric loss, antenatal complications, mode of delivery, gestational age at delivery and postpartum haemorrhage rates across thyroid categories.
Available evidence suggests that thyroid dysfunction is more likely in the setting of older age, and higher body mass index. Moreover, it impacts on neonatal birth weight, rates of early preterm delivery and intrauterine growth restriction.
Pituitary adenomas (PA) represent the largest group of intracranial neoplasms and yet the molecular mechanisms driving this disease remain largely unknown. The aim of this study was to use a ...high-throughput screening method to identify molecular pathways that may be playing a significant and consistent role in PA. RNA profiling using microarrays on eight local PAs identified the aryl hydrocarbon receptor (AHR) signalling pathway as a key canonical pathway downregulated in all PA types. This was confirmed by real-time PCR in 31 tumours. The AHR has been shown to regulate cell cycle progression in various cell types; however, its role in pituitary tissue has never been investigated. In order to validate the role of AHR in PA behaviour, further functional studies were undertaken. Over-expression of AHR in GH3 cells revealed a tumour suppressor potential independent of exogenous ligand activation by benzo α-pyrene (BαP). Cell cycle analysis and quantitative PCR of cell cycle regulator genes revealed that both unstimulated and BαP-stimulated AHR reduced E2F-driven transcription and altered expression of cell cycle regulator genes, thus increasing the percentage of cells in G
/G
phase and slowing the proliferation rate of GH3 cells. Co-immunoprecipitation confirmed the interaction between AHR and retinoblastoma (Rb1) protein supporting this as a functional mechanism for the observed reduction. Endogenous Ahr reduction using silencing RNA confirmed the tumour suppressive function of the Ahr. These data support a mechanistic pathway for the putative tumour suppressive role of AHR specifically in PA, possibly through its role as a cell cycle co-regulator, even in the absence of exogenous ligands.
Aims/hypothesis
A high-fat dietary intake induces obesity and subclinical inflammation, which play important roles in insulin resistance. Recent studies have suggested that increased concentrations ...of circulating lipopolysaccharide (LPS), promoted by changes in intestinal permeability, may have a pivotal role in insulin resistance. Thus, we investigated the effect of gut microbiota modulation on insulin resistance and macrophage infiltration.
Methods
Swiss mice were submitted to a high-fat diet with antibiotics or pair-feeding for 8 weeks. Metagenome analyses were performed on DNA samples from mouse faeces. Blood was collected to determine levels of glucose, insulin, LPS, cytokines and acetate. Liver, muscle and adipose tissue proteins were analysed by western blotting. In addition, liver and adipose tissue were analysed, blinded, using histology and immunohistochemistry.
Results
Antibiotic treatment greatly modified the gut microbiota, reducing levels of Bacteroidetes and Firmicutes, overall bacterial count and circulating LPS levels. This modulation reduced levels of fasting glucose, insulin, TNF-α and IL-6; reduced activation of toll-like receptor 4 (TLR4), c-Jun N-terminal kinase (JNK), inhibitor of κ light polypeptide gene enhancer in B cells, kinase β (IKKβ) and phosphorylated IRS-1 Ser307; and consequently improved glucose tolerance and insulin tolerance and action in metabolically active tissues. In addition, there was an increase in portal levels of circulating acetate, which probably contributed to an increase in 5′-AMP-activated protein kinase (AMPK) phosphorylation in mice. We observed a striking reduction in crown-like structures (CLS) and F4/80
+
macrophage cells in the adipose tissue of antibiotic-treated mice.
Conclusions/interpretation
These results suggest that modulation of gut microbiota in obesity can improve insulin signalling and glucose tolerance by reducing circulating LPS levels and inflammatory signalling. Modulation also appears to increase levels of circulating acetate, which activates AMPK and finally leads to reduced macrophage infiltration.
There are now over a thousand nano-containing products on the market and the antibacterial properties of some nanomaterials has created interest in their use as cleaning agents, biocides and ...disinfectants. Engineered nanomaterials (ENMs) are being released into the environment and this raises concerns about their effects on microbes in the receiving ecosystems. This study evaluated the bacterial toxicity of a wide range of nanomaterials with different surface coatings on Escherichia coli K-12 MG1655. The minimum inhibitory concentration (MIC) assay, which quantifies the threshold for growth inhibition in suspensions of bacteria, was used to rank the toxicity of silver (Ag), cupric oxide (CuO), cadmium telluride (CdTe) quantum dots, titanium dioxide (TiO2), nanodiamonds and multi-walled carbon nanotubes (MWCNTs). Bacteria were exposed for 12 h at 37 °C to a dilution series of the test suspensions in 96-well plates. The precision and accuracy of the method was good with coefficients of variation < 10%. In terms of the measured MIC values, the toxicity order of the ENMs was as follows: CdTe quantum dots ammonium-coated, 6 mg L−1 > Ag nanoparticles, 12 mg L−1 > CdTe quantum dots carboxylate-coated, 25 mg L−1 > CdTe quantum dots polyethylene glycol-coated, 100 mg L−1. The MIC values were above the highest test concentration used (100 mg L−1) for CuO, TiO2, nanodiamonds and MWCNTs, indicating low toxicity. The MIC assay can be a useful tool for the initial steps of ENMs hazard assessment.
•The MIC assay was optimised to determine the antibacterial effect of nanomaterials.•The MIC assay displayed good reproducibility as required for regulatory use.•ENMs, metal salts and bulk controls were ranked according to their hazard.•Ag NPs and CdTe QDs displayed more growth inhibition than their bulk equivalents.•There was no consistent ENM-coating effect on bacterial growth inhibition.
•cAMP signalling is an essential messenger system in the regulation of pituitary physiology.•De-regulation of cAMP pathways leads to pituitary tissue proliferation.•cAMP signalling interacts with ...various other cellular cascades.•Somatic mutations and molecular aberrations altering cAMP signalling induce tumorigenesis.•Novel mechanisms of cAMP deregulation are discussed.
cAMP signalling plays a key role in the normal physiology of the pituitary gland, regulating cellular growth and proliferation, hormone production and release. Deregulation of the cAMP signalling pathway has been reported to be a common occurrence in pituitary tumorigenesis. Several mechanisms have been implicated including somatic mutations, gene–gene interactions and gene–environmental interactions. Somatic mutations in G-proteins and protein kinases directly alter cAMP signalling, while malfunctioning of other signalling pathways such as the Raf/MAPK/ERK, PI3K/Akt/mTOR and Wnt pathways which normally interact with the cAMP pathway may mediate indirect effects on cAMP and varying downstream effectors. The aryl hydrocarbon receptor signalling pathway has been implicated in pituitary tumorigenesis and we review its role in general and specifically in relation to cAMP de-regulation.
Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been linked to predisposition to pituitary adenomas. However, the mechanism by which this occurs remains unknown. AIP ...interacts with a number of interesting proteins, including members of the cAMP signalling pathway that has been shown to be consistently altered in pituitary tumours. The functional role of Aip was investigated using both over-expression and knock down of Aip in GH3 cells. cAMP signalling and its downstream effectors, including GH secretion, were then investigated. cAMP signalling was analysed using cAMP assays, cAMP-response element-promoter luciferase reporter assays, real-time PCR and finally secreted GH quantification. Over-expression of wild-type (WT)-Aip reduced forskolin-induced cAMP signalling at the total cAMP level, luciferase reporter activity and target gene expression, when compared with empty vector and the non-functional R304X mutant. Additionally, GH secretion was reduced in WT-Aip over-expressing GH3 cells treated with forskolin. Knock down of endogenous Aip resulted in increased cAMP signalling but a decrease in GH secretion was also noted. Inhibition of phosphodiesterase activity using general and selective inhibitors did not completely ablate the effect of Aip on forskolin-augmented cAMP signalling. A mechanism by which Aip acts as a tumour suppressor, by maintaining a low cAMP signalling and concentration, is suggested. Mutations of Aip render the protein incapable of such activity. This effect appears not to be mediated by the AIP-PDE interaction, suggesting the involvement of other interacting partners in mediating this outcome.
Professional dance is a physically demanding career path with a high injury prevalence, yet an ingrained culture of hiding or pushing through injuries. Developing better knowledge surrounding the ...cultural beliefs and behaviors related to injury reporting is critical to understand their incidence and burden. Therefore, the aim of this study was to investigate injury fear and injury reporting behaviors in professional dancers in Australia.
This study utilized data collected in a cross-sectional survey of professional dancers in Australia. Descriptive analysis of injury fear and reporting stigma are presented with comparisons between subgroups (full-time versus part-time dancers; men versus women) conducted using two-sided Fisher's exact tests.
A total of 146 professional dancers were included. Over half (63%) of the respondents reported that they fear sustaining a dance-related injury, that they believe there is still a stigma surrounding injuries in dance (62%), and that this stigma has led to a delay in reporting or seeking care for an injury (51%). A lower proportion of part-time than full-time dancers reported that they would usually tell someone within their dance employment about an injury (35.1% vs. 59.6%, p = 0.006).
Professional dancers are at risk of losing contracts or roles if they are injured, and therefore, it is common to dance through their occurrence. Many dancers, particularly those dancing part-time, are unwilling to tell their employers about their injuries. Action is required to improve this culture regarding injury reporting and help seeking for more effective injury understanding, prevention, and management in dance.
To evaluate the performance of an artificial intelligence (AI) system (Pegasus, Visulytix Ltd., UK*) at the detection of diabetic retinopathy (DR) from images captured by a handheld portable fundus ...camera.
A cohort of 6404 patients (~80% with diabetes mellitus) was screened for retinal diseases using a handheld portable fundus camera (Pictor Plus, Volk Optical Inc., USA) at the Mexican Advanced Imaging Laboratory for Ocular Research. The images were graded for DR by specialists according to the Scottish DR grading scheme. The performance of the AI system was evaluated, retrospectively, in assessing referable DR (RDR) and proliferative DR (PDR) and compared with the performance on a publicly available desktop camera benchmark dataset.
For RDR detection, Pegasus performed with an 89.4% (95% CI: 88.0-90.7) area under the receiver operating characteristic (AUROC) curve for the MAILOR cohort, compared with an AUROC of 98.5% (95% CI: 97.8-99.2) on the benchmark dataset. This difference was statistically significant. Moreover, no statistically significant difference was found in performance for PDR detection with Pegasus achieving an AUROC of 94.3% (95% CI: 91.0-96.9) on the MAILOR cohort and 92.2% (95% CI: 89.4-94.8) on the benchmark dataset.
Pegasus showed good transferability for the detection of PDR from a curated desktop fundus camera dataset to real-world clinical practice with a handheld portable fundus camera. However, there was a substantial, and statistically significant, decrease in the diagnostic performance for RDR when using the handheld device.
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