Impact of Intrinsic Muscle Weakness on Muscle–Bone Crosstalk in Osteogenesis Imperfecta

Bone and muscle are highly synergistic tissues that communicate extensively via mechanotransduction and biochemical signaling. Osteogenesis imperfecta (OI) is a heritable connective tissue disorder of severe bone fragility and recently recognized skeletal muscle weakness. The presence of impaired bone and muscle in OI leads to a continuous cycle of altered muscle–bone crosstalk with weak muscles further compromising bone and vice versa. Currently, there is no cure for OI and understanding the pathogenesis of the skeletal muscle weakness in relation to the bone pathogenesis of OI in light of the critical role of muscle–bone crosstalk is essential to developing and identifying novel therapeutic targets and strategies for OI. This review will highlight how impaired skeletal muscle function contributes to the pathophysiology of OI and how this phenomenon further perpetuates bone fragility.     

Activity of Riminophenazines against Mycobacterium tuberculosis: A Review of Studies that Might be Contenders for Use as Antituberculosis Agents

Tuberculosis is one of the leading cause of death in the world, mainly due to the increasing number of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. Factors such as the HIV pandemic contribute further. Also, the ineffectiveness of the chemotherapy in current use increases the mortality rate. Therefore, new and repurposed antituberculosis drugs are urgently needed for the treatment of MDR-TB, and riminophenazines are among those drugs that are being reinvestigated for their potential in the treatment of TB. This review delivers a brief historical account of riminophenazines, their general synthesis, mechanisms of action, and their physicochemical properties. The discussion is limited to those studies that investigated the activity of these compounds as antituberculosis agents. Given their unique properties, this review will be of great significance in giving direction towards the design and development of new riminophenazine analogues.     

Emissions of VOCs,SVOCs, and mold during the construction process: Contribution to indoor air quality and future occupants’ exposure

Building materials and human activities are important sources of contamination indoors, but little information is available regarding contamination during construction process which could persist during the whole life of buildings. In this study, six construction stages on two construction sites were investigated regarding the emissions of 43 volatile organic compounds (VOCs), 46 semi-volatile organic compounds (SVOCs), and the presence of 4 genera of mold. Results show that the future indoor air quality does not only depend on the emissions of each building product but that it is also closely related to the whole implementation process. Mold spore measurements can reach 1400 CFU/m³, which is particularly high compared with the concentrations usually measured in indoor environments. Relatively low concentrations of VOCs were observed, in relation to the use of low emissive materials. Among SVOCs analyzed, some phthalates, permethrin, and hydrocarbons were found in significant concentrations upon the delivery of building as well as triclosan, suspected to be endocrine disruptor, and yet prohibited in the treatment of materials and construction since 2014. As some regulations exist for VOC emissions, it is necessary to implement them for SVOCs due to their toxicity.     

Developing English domestic occupancy profiles

ABSTRACT

Occupancy patterns are necessary to estimate energy demand and evaluate thermal comfort in households. Because of this, many European countries are developing representative domestic schedules to replace outdated criteria. This paper evaluates the state of knowledge of UK domestic occupancy patterns and develops new domestic occupancy profiles for England. The presented research (1) characterizes methods for collecting occupancy data and inferring patterns; (2) identifies and assesses the quality of categories of occupancy patterns used in building simulation; and (3) develops updated occupancy profiles. A systematic scoping review identified social and monitoring surveys as the most deployed data-collection methods. A systematic literature review also established that the occupancy categories most frequently used in UK building simulation are (a) a family with dependent children where the parents work full time; and (b) a retired elderly couple who spend most of their time indoors. The interview sample from the English Housing Survey 2014–15 was used to map household typologies. Results show that categories (a) and (b) combined amount to only 19% of England’s households, which suggest models are over-reliant on these groups. Considering this result, the paper develops occupancy patterns for England derived from 2015 UK Time Use Survey diaries for each household typology previously identified.     

Analysis of driver roles: modelling the changing role of the driver in automated driving systems using EAST

ABSTRACT

The purpose of this paper is to analyse the role of the driver within automated driving systems using the Event Analysis of Systemic Teamwork (EAST) method. We already know that as the level of automation increases within the driving task, the role of the driver shifts from that of an active operator (i.e. a driver driving) to more of a passive monitor (i.e. a driver monitoring). Task, social and information networks were constructed using the Hierarchical Task Analysis of Driving and evidence from driver verbalisations collected during a previous study to further explore the changing role of the driver using network analysis. A ‘broken links’ approach was conducted to show that momentary engagement in non-driving-related secondary tasks within an automated driving system can dramatically change the structure of driving system.     

A framework for improving the efficiency of operational testing through Bayesian adaptive design

When developing a product, it is important to consider product performance from a user perspective. This type of evaluation can be done through operational testing—assessing the ability of representative users to satisfactorily accomplish tasks with the product in operationally representative environments. This process can be expensive and time-consuming, but is critical to understanding whether the product can adequately do the job for which it was designed. We show how an existing design of experiments (DOEs) process for operational testing can be leveraged to construct a Bayesian adaptive design. This design, nested within the larger design created by the DOE process, allows interim analyses to stop testing early for success or futility. Representative simulations are presented to demonstrate how these interim analyses can be used in an operational test setting, and reductions in necessary test events are shown. The application of Bayesian-adaptive design methods will allow future operational testing to be conducted in less time and at less expense, on average, without compromising the ability of the existing process to verify the product meets the user's needs.     

Yoghurt‐type beverage with partial substitution of milk by a chickpea extract: Effect on physicochemical and flow properties

The objective of this study was to determine the evolution of physicochemical and flow properties of a yoghurt‐type beverage partially replaced with a chickpea extract over a period of 22 days. From two chickpea extracts, Blanco Noroeste was selected for its higher protein content. Six yoghurt‐type formulations were prepared, stored at 4 °C and analysed on days 1, 8, 15 and 22. pH was 4.24–4.75, while brightness was 81.7–94.5. Flow properties of the yoghurt‐type exhibited a non‐Newtonian behaviour. From three formulations that underwent sensory evaluation, the 30:70 mix obtained the highest acceptation. This yoghurt‐type beverage exhibited characteristics similar to natural yoghurt.     

Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.