Obtaining a marketing authorisation for nitrous oxide

OBJECTIVE: To prepare a Common Technical Document for nitrous oxide (NO) in accordance to European Guidelines, for submission to the Medicine’s Authority to obtain a Marketing Authorisation (MA) and to carry out a project feasibility study. METHOD: Directives and guidelines issued by the European Commission were followed to compile a dossier for NO in the Common Technical Document (CTD) format, in preparation of an abridged application. KEY FINDINGS: The Common Technical Document gave details on the Administrative Information (Module 1), Summaries (Module 2), Quality (Module 3) and Non- Clinical Studies (Module 4) consisting of a detailed scientific bibliography. The active substance manufacturer was inspected and accepted as an approved supplier. A feasibility study which was conducted proved the project feasible. CONCLUSION: The whole manufacturing process of nitrous oxide is well controlled and batches can be produced with a constant level of quality. NO has been used for 150 years for analgesia and anesthesia and has proven safe and effective. Even though its administration is not without risks, it currently has a niche role as an inhalational analgesic and sedative.peer-reviewe

Energy & crack tip stress interactions in mixed mode I/III fracture of DX51 steel sheets

DX51D sheet is subjected to mixed mode I/III loading in a purposely designed fixture apparatus. The resulting stable crack-tip growth, direction, slant angle and typical factory-roof crack were observed and discussed as the loading mixity was varied. The total essential work of fracture or fracture toughness, for each mixity loading, was evaluated adopting energy methods during experimentation, whilst theory details how the total may be separated into its individual mode components. The fracture type and direction of crack path were based on the von Mises failure theory and the fracture criteria of maximum shear stress, maximum hoop stress and maximum normal stress along with the application of Hill’s theory. The findings described clearly establish the link between the applications of the energy based equations governing crack initiation and propagation and the equations describing the stress field surrounding the crack tip in the mixed mode I/III field.peer-reviewe

Postnatal odorant exposure induces peripheral olfactory plasticity at the cellular level

Mammalian olfactory sensory neurons (OSNs) form the primary elements of the olfactory system. Inserted in the olfactory mucosa lining of the nasal cavity, they are exposed to the environment and their lifespan is brief. Several reports say that OSNs are regularly regenerated during the entire life and that odorant environment affects the olfactory epithelium. However, little is known about the impact of the odorant environment on OSNs at the cellular level and more precisely in the context of early postnatal olfactory exposure. Here we exposed MOR23-green fluorescent protein (GFP) and M71-GFP mice to lyral or acetophenone, ligands for MOR23 or M71, respectively. Daily postnatal exposure to lyral induces plasticity in the population of OSNs expressing MOR23. Their density decreases after odorant exposure, whereas the amount of MOR23 mRNA and protein remain stable in the whole epithelium. Meanwhile, quantitative PCR indicates that each MOR23 neuron has higher levels of olfactory receptor transcripts and also expresses more CNGA2 and phosphodiesterase 1C, fundamental olfactory transduction pathway proteins. Transcript levels return to baseline after 4 weeks recovery. Patch-clamp recordings reveal that exposed MOR23 neurons respond to lyral with higher sensitivity and broader dynamic range while the responses' kinetics were faster. These effects are specific to the odorant-receptor pair lyral-MOR23: there was no effect of acetophenone on MOR23 neurons and no effect of acetophenone and lyral on the M71 population. Together, our results clearly demonstrate that OSNs undergo specific anatomical, molecular, and functional adaptation when chronically exposed to odorants in the early stage of life

Audit on doctors’ documentation of overweight and obesity in children attending general children’s outpatient’s clinics in Malta

Background: Childhood obesity is a global epidemic and Malta is no exception. Despite local awareness, not all children seen at the general hospital's children's outpatients (COP) have their height and weight measured. An audit was carried out on the documentation of overweight and obesity in children, along with any advice given in this regard.Methods: The NICE guideline on obesity was used to define overweight and obesity. A cross-sectional study was conducted over 10 weeks between January and March 2020. Data on age, gender, weight, height, percentiles/BMI, doctor grade, presenting complaint, appointment frequency and previous anthropometric documentation were collected from clinical notes. All children attending general COP, between 2-15 years of age and free from chronic medical illnesses affecting BMI were included.Results: In 418 patients, weight and height were documented in 64.8% and 58.1% respectively, while percentiles were documented in 17.0%. Furthermore, BMI was documented in just 1.2% of cases, and 32% no anthropometric measurements documented whatsoever. Moreover, 29.7% of children who were previously flagged up as obese/overweight were not followed-up, and only 12% who were documented as obese, were investigated, albeit incompletely. Only 7% of known overweight children had dietary advice documented in their notes.Conclusion: COP's services are not attaining the standard as per current guidelines, which suggest that all children should be screened for obesity opportunistically. We recommend the distribution of a dietary guidelines leaflet to parents, continuous medical education for doctors, giving sustainable advice during follow ups and the introduction of a child obesity clinic.peer-reviewe

Economic and environmental impacts of antifouling coatings used on the fishing boats in Turkey

Biofouling on a ship hull increases the ship resistance and, consequently, the fuel consumption and greenhouse gas emission. Inadequate antifouling strategies may waste a significant amount of fuel and thus aggravate the profitability of the fishing boats, while resulting environmental problems. This study aims to investigate the economic and environmental impacts of different antifouling strategies with a focus on the fishing boats in Turkish fishing regions. A time-dependant biofouling growth model and the boundary layer similarity law analysis were adopted to predict the added resistance due to the fouling on the hull with different antifouling strategies. In addition, life-cycle analysis and life-cycle cost analysis were performed to estimate the economic and environmental impacts

Identification of new binding partners of the chemosensory signaling protein Gγ13 expressed in taste and olfactory sensory cells

Tastant detection in the oral cavity involves selective receptors localized at the apical extremity of a subset of specialized taste bud cells called taste receptor cells (TRCs). The identification of the genes coding for the taste receptors involved in this process have greatly improved our understanding of the molecular mechanisms underlying detection. However, how these receptors signal in TRCs, and whether the components of the signaling cascades interact with each other or are organized in complexes is mostly unexplored. Here we report on the identification of three new binding partners for the mouse G protein gamma 13 subunit (Gγ13), a component of the bitter taste receptors signaling cascade. For two of these Gγ13 associated proteins, namely GOPC and MPDZ, we describe the expression in taste bud cells for the first time. Furthermore, we demonstrate by means of a yeast two-hybrid interaction assay that the C terminal PDZ binding motif of Gγ13 interacts with selected PDZ domains in these proteins. In the case of the PDZ domain-containing protein zona occludens-1 (ZO-1), a major component of the tight junction defining the boundary between the apical and baso-lateral region of TRCs, we identified the first PDZ domain as the site of strong interaction with Gγ13. This association was further confirmed by co-immunoprecipitation experiments in HEK 293 cells. In addition, we present immunohistological data supporting partial co-localization of GOPC, MPDZ, or ZO-1, and Gγ13 in taste buds cells. Finally, we extend this observation to olfactory sensory neurons (OSNs), another type of chemosensory cells known to express both ZO-1 and Gγ13. Taken together our results implicate these new interaction partners in the sub-cellular distribution of Gγ13 in olfactory and gustatory primary sensory cells

Wind-assisted ship propulsion of a series 60 ship using a static kite sail

Following the International Maritime Organization’s goal to reduce greenhouse gas emissions, the interest in the application of wind-assisted ship propulsion (WASP) in maritime transportation is on the rise. Although a variety of WASP systems exist, the application in maritime shipping is still limited, especially in the case of kite sails. This paper presents a numerical model to carry out a theoretical assessment of the influence of the kite planform area and wind speed on the aerodynamic performance of a kite sail providing propulsive assistance to a 75 m long ship having a Series 60 hull. A static kite sail is assumed, on which a tail wind generates a thrust force to pull the vessel via a tether. While the mass of the kite is neglected, that of the tether is accounted for. A model is implemented for the tensioned tether having a catenary profile. The results generally show a positive correlation between the aerodynamic forces and the kite parameters. As expected, the output parameter values corresponding to the optimal angle of attack for a range of vessel speeds are also found to increase with an increasing relative wind speed. It is concluded that a static 320 m2 kite sail would be sufficient to meet the entire propulsion requirements of the vessel under consideration under appropriate wind conditions.peer-reviewe

Investigating the influence of sheared currents on ship hydrodynamics in confined water using Computational Fluid Dynamics

The field of ship hydrodynamics in confined water has received increased attention by the academic community in recent years. Nevertheless, a number of phenomena occurring in confined waters are yet to be examined using high fidelity Computational Fluid Dynamics (CFD) or experimentally. One particular case is the presence of sheared currents and their impact on the performance of a ship. Such currents can be generated in confined waters as a result of the natural flow of water in rivers or due to the action of tidal influences in long canals. Alternatively, due to the short fetch of many inland waterways, the action of wind may result in the production of a sheared current. This work aims to investigate these effects by making use of a commercially available Reynolds Averaged Navier-Stokes (RANS) solver. A number of current profiles are numerically modelled to determine their influence on ship performance and the manner in which ship waves interact with the background current. The present study will contribute to the understanding of restricted water effects by revealing the impact of shear currents on ship performance

Ric-8A, a Gα Protein Guanine Nucleotide Exchange Factor Potentiates Taste Receptor Signaling

Taste receptors for sweet, bitter and umami tastants are G-protein-coupled receptors (GPCRs). While much effort has been devoted to understanding G-protein-receptor interactions and identifying the components of the signalling cascade downstream of these receptors, at the level of the G-protein the modulation of receptor signal transduction remains relatively unexplored. In this regard a taste-specific regulator of G-protein signaling (RGS), RGS21, has recently been identified. To study whether guanine nucleotide exchange factors (GEFs) are involved in the transduction of the signal downstream of the taste GPCRs we investigated the expression of Ric-8A and Ric-8B in mouse taste cells and their interaction with G-protein subunits found in taste buds. Mammalian Ric-8 proteins were initially identified as potent GEFs for a range of Gα subunits and Ric-8B has recently been shown to amplify olfactory signal transduction. We find that both Ric-8A and Ric-8B are expressed in a large portion of taste bud cells and that most of these cells contain IP3R-3 a marker for sweet, umami and bitter taste receptor cells. Ric-8A interacts with Gα-gustducin and Gαi2 through which it amplifies the signal transduction of hTas2R16, a receptor for bitter compounds. Overall, these findings are consistent with a role for Ric-8 in mammalian taste signal transduction

Preliminary analysis on the hydrostatic stability of a self-aligning floating offshore wind turbine

There exist vast areas of offshore wind resources with water depths greater than 100 m that require floating structures. This paper provides a detailed analysis on the hydrostatic stability characteristics of a novel floating wind turbine concept. The preliminary design supports an 8 MW horizontal-axis wind turbine with a custom self-aligning single-point mooring (SPM) floater, which is to be constructed within the existing shipyard facilities in the Maltese Islands, located in the Central Mediterranean Sea. The theoretical hydrostatic stability calculations used to find the parameters to create the model are validated using SESAM®. The hydrostatic stability analysis is carried out for different ballast capacities whilst also considering the maximum axial thrust induced by the rotor during operation. The results show that the entire floating structure exhibits hydrostatic stability characteristics for both the heeling and pitching axes that comply with the requirements set by the DNV ST-0119 standard. Numerical simulations using partial ballast are also presented.peer-reviewe