Online-based participatory design: A Case Study of Developing International Standards During a Pandemic

Standards are essential instruments to ensure the safety, efficiency and quality of products, services, systems, processes, and environments. In pre-pandemic times, standard development process used to happen through in-person consultation and meetings, however, the COVID-19 pandemic disrupted the whole routine. A team of technical experts from the National Standards Authority of Ireland trialled an online-based participatory design process to support the review and development of a standard through stakeholder engagement. This article introduces the experience of developing a new standard by leveraging on emerging digital technologies, through stakeholder participation. This research offers a framework, outlining the steps undertaken during the process, to support future online-based standard development processes in co-operation with stakeholders, by respecting cultures, backgrounds, skills, and experiences

Carbocations from Arene Hydrates and Arene Oxides

Arene hydrates are water adducts of aromatic molecules that readily dehydrate and aromatise in the presence of acids. The mechanism of this reaction is similar to that for the dehydration of alcohols. Protonation of a hydroxyl group is followed by C-O bond cleavage to form a benzenonium ionlike carbocation intermediate which then loses a proton (in contrast to alcohols, in a fast step) to yield the aromatic product. Rates of reaction are sensitive to the stability of the carbocation. They are also strongly decreased by benzoannelation: thus benzene hydrate is 500 times more reactive than l-hydroxy-l,2-dihydronaphthalene (naphthalene hydrate) which is 100 times more reactive than 9,10-phenanthrene hydrate. For the analogous dehydration of 3-substituted cis-benzenedihydrodiols to phenols p has a normal value of -7.2 but, unexpectedly, rate constants for +M resonance substituents MeO, EtO and Me are correlated by ap rather than a*. Comparison of benzene hydrate with benzene oxide shows, surprisingly, that the latter is the less reactive towards acids despite epoxides normally being 106-107 times more reactive than structurally related alcohols. For a series of arene oxides and hydrates oxide/hydrate rate ratios are inversely related to the resonance energy of the aromatised ring. This behaviour is tentatively ascribed to homoaromatic stabilisation of the arene oxide ring

Recessive mutations in the kinase ZAK cause a congenital myopathy with fibre type disproportion

Congenital myopathies define a heterogeneous group of neuromuscular diseases with neonatal or childhood hypotonia and muscle weakness. The genetic cause is still unknown in many patients, precluding genetic counselling and better understanding of the physiopathology. To identify novel genetic causes of congenital myopathies, exome sequencing was performed in three consanguineous families. We identified two homozygous frameshift mutations and a homozygous nonsense mutation in the mitogen-activated protein triple kinase ZAK. In total, six affected patients carry these mutations. Reverse transcription polymerase chain reaction and transcriptome analyses suggested nonsense mRNA decay as a main impact of mutations. The patients demonstrated a generalized slowly progressive muscle weakness accompanied by decreased vital capacities. A combination of proximal contractures with distal joint hyperlaxity is a distinct feature in one family. The low endurance and compound muscle action potential amplitude were strongly ameliorated on treatment with anticholinesterase inhibitor in another patient. Common histopathological features encompassed fibre size variation, predominance of type 1 fibre and centralized nuclei. A peculiar subsarcolemmal accumulation of mitochondria pointing towards the centre of the fibre was a novel histological hallmark in one family. These findings will improve the molecular diagnosis of congenital myopathies and implicate the mitogen-activated protein kinase (MAPK) signalling as a novel pathway altered in these rare myopathies