Mimicking the Human Tympanic Membrane: The Significance of Scaffold Geometry

The human tympanic membrane (TM) captures sound waves from the environment and transforms them into mechanical motion. The successful transmission of these acoustic vibrations is attributed to the unique architecture of the TM. However, a limited knowledge is available on the contribution of its discrete anatomical features, which is important for fabricating functional TM replacements. This work synergizes theoretical and experimental approaches toward understanding the significance of geometry in tissue-engineered TM scaffolds. Three test designs along with a plain control are chosen to decouple some of the dominant structural elements, such as the radial and circumferential alignment of the collagen fibrils. In silico models suggest a geometrical dependency of their mechanical and acoustical responses, where the presence of radially aligned fibers is observed to have a more prominent effect compared to their circumferential counterparts. Following which, a hybrid fabrication strategy combining electrospinning and additive manufacturing has been optimized to manufacture biomimetic scaffolds within the dimensions of the native TM. The experimental characterizations conducted using macroindentation and laser Doppler vibrometry corroborate the computational findings. Finally, biological studies with human dermal fibroblasts and human mesenchymal stromal cells reveal a favorable influence of scaffold hierarchy on cellular alignment and subsequent collagen deposition

Copper for the Pharaoh: Identifying multiple metal sources for Ramesses' workshops from bronze and crucible remains

The origin of copper used in Late Bronze Age (LBA) Egypt is very poorly understood despite its cultural and economic importance attested in archaeological and historical sources. Extensive literature discusses major LBA copper sources such as Cyprus (oxhide ingots), Oman (bun ingots) and Egyptian-controlled sites in the Sinai. This paper presents new chemical and lead isotope data for Egyptian copper alloys excavated in several bronze production workshops from the New Kingdom capital Pi-Ramesse, expanding on earlier data from Amarna. Supporting data is obtained from the analysis of crucible remains from the same context, for which the potential contribution of lead isotope analysis is critically evaluated. Diachronic changes in the provisioning of these Egyptian workshops are discussed, incorporating an extensive overview of currently known Egyptian mining and metallurgy. The results have major implications for our understanding of LBA copper circulation in the wider region, for the first time analysing a major Egyptian ‘consumer’ assemblage. The analytical results reveal a complex picture of variable copper supply to the Ramesside workshops, which involved both the recycling of existing bronzes and the use of freshly smelted copper from various origins to produce fresh alloys. Importantly, this includes crucial new evidence for the melting of (Cypriot) oxhide ingot fragments in crucibles for alloying. The royal, internationally connected nature of these workshops makes Pi-Ramesse an exceptional case study of LBA metal trade, and hypotheses raised in this paper highlight the need for more extensive analysis of ancient Egyptian copper artefacts to grasp metal circulation throughout Egypt's long history. More refined frameworks, incorporating the variety of private as well as royal contexts, will improve understanding of Egypt's ancient economic organisation. This paper offers new perspectives onto LBA metal supply and consumption networks, with broader archaeological interpretative models of economic and political interactions across the wider ancient Near East

Bronze metallurgy in the Late Phrygian settlement of Gordion, Turkey

A detailed understanding of bronze production remains absent in most archaeological contexts, despite the fundamental importance of this alloy. Here, we present a comprehensive discussion of the bronze production remains from Late Phrygian/Achaemenid Gordion: crucibles, moulds and casting waste and their find contexts. A detailed microscopic analysis of crucibles is complemented by chemical characterisation of their main materials (ceramic and slag) in order to discuss the technical performance of the crucibles and to evaluate the materials used for the metallurgical process. Given the lack of contemporary parallels, repeated reference is made to the Egyptian crucibles from Pi-Ramesse, for which similarly detailed descriptions are available. The crucible analyses are then connected to the other production remains to obtain a more holistic understanding of the metallurgical process. Finally, these technical observations are interpreted in their particular archaeological context at Gordion and discussed from a wider perspective. The results presented here offer the first detailed overview of bronze production for ancient Phrygia, as well as the wider region. Through the inclusion of extensive online supplementary data, this paper offers a detailed technical overview of ancient (bronze) crucible analysis, of which very few examples are currently available in the wider literature

Rates of lobar atrophy in asymptomatic MAPT mutation carriers.

IntroductionThe aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule-associated protein tau (MAPT) mutation carriers.MethodsMAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor-based morphometry with symmetric normalization algorithm.ResultsThe rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers.DiscussionAccelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers

Temporal course of cognitive and behavioural changes in motor neuron diseases

Background Cognitive and behavioural dysfunction may occur in people with motor neuron disease (MND), with some studies suggesting an association with the C9ORF72 repeat expansion. Their onset and progression, however, is poorly understood. We explored how cognition and behaviour change over time, and whether demographic, clinical and genetic factors impact these changes. Methods Participants with MND were recruited through the Phenotype-Genotype-Biomarker study. Every 3–6 months, the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was used to assess amyotrophic lateral sclerosis (ALS) specific (executive functioning, verbal fluency, language) and ALS non-specific (memory, visuospatial) functions. Informants reported on behaviour symptoms via semi-structured interview. Results Participants with neuropsychological data at ≥3 visits were included (n=237, mean age=59, 60% male), of which 18 (8%) were C9ORF72 positive. Baseline cognitive impairment was apparent in 18 (8%), typically in ALS specific domains, and associated with lower education, but not C9ORF72 status. Cognition, on average, remained stable over time, with two exceptions: (1) C9ORF72 carriers declined in all ECAS domains, (2) 8%–9% of participants with baseline cognitive impairment further declined, primarily in the ALS non-specific domain, which was associated with less education. Behavioural symptoms were uncommon. Conclusions In this study, cognitive dysfunction was less common than previously reported and remained stable over time for most. However, cognition declines longitudinally in a small subset, which is not entirely related to C9ORF72 status. Our findings raise questions about the timing of cognitive impairment in MND, and whether it arises during early clinically manifest disease or even prior to motor manifestations