Characterisation of microneedle replication and flow behaviour in ultrasonic micro-injection moulding through design of experiments

This research investigates the impact of process parameters on ultrasonic micro-injection moulding (u-μIM) by studying microneedle replication efficiency, temperature evolution during moulding, melt flow consistency and sonication behaviour. The experimentation comprises of a full-factorial design of experiments using three process variables: sonication time, mould temperature and injection force. The current study presents that; (i) mould temperature was found to be the most influential parameter to tune and optimise micro-feature replication, (ii) consistent ultrasonic micromoulding flows can be achieved using higher mould temperatures, (iii) injection force is a key parameter influencing sonication frequency, a critical aspect of the ultrasonic method to obtain a repeatable manufacturing process. These outcomes will be a datum during development of the manufacturing processes for specific products using the ultrasonic method. The research presented here takes a unique approach to characterise the ultrasonic method for the development of this novel technique, particularly for microneedle patch and medical device production. With this increased level of understanding of u-μIM process characteristics, the method can become an energy efficient and cost-effective alternative to conventional micro-injection moulding processes for delivering high-quality, miniature components

Characterising termite mounds in a tropical savanna with UAV laser scanning

Termite mounds are found over vast areas in northern Australia, delivering essential ecosystem services, such as enhancing nutrient cycling and promoting biodiversity. Currently, the detection of termite mounds over large areas requires airborne laser scanning (ALS) or high-resolution satellite data, which lack precise information on termite mound shape and size. For detailed structural measurements, we generally rely on time-consuming field assessments that can only cover a limited area. In this study, we explore if unmanned aerial vehicle (UAV)-based observations can serve as a precise and scalable tool for termite mound detection and morphological characterisation. We collected a unique data set of terrestrial laser scanning (TLS) and UAV laser scanning (UAV-LS) point clouds of a woodland savanna site in Litchfield National Park (Australia). We developed an algorithm that uses several empirical parameters for the semi-automated detection of termite mounds from UAV-LS and used the TLS data set (1 ha) for benchmarking. We detected 81% and 72% of the termite mounds in the high resolution (1800 points m−2) and low resolution (680 points m−2) UAV-LS data, respectively, resulting in an average detection of eight mounds per hectare. Additionally, we successfully extracted information about mound height and volume from the UAV-LS data. The high resolution data set resulted in more accurate estimates; however, there is a trade-off between area and detectability when choosing the required resolution for termite mound detection Our results indicate that UAV-LS data can be rapidly acquired and used to monitor and map termite mounds over relatively large areas with higher spatial detail compared to airborne and spaceborne remote sensing

Developing community-based scientific priorities and new drilling proposals in the southern Indian and southwestern Pacific oceans

An International Ocean Discovery Program (IODP) workshop was held at Sydney University, Australia, from 13 to 16 June 2017 and was attended by 97 scientists from 12 countries. The aim of the workshop was to investigate future drilling opportunities in the eastern Indian Ocean, southwestern Pacific Ocean, and the Indian and Pacific sectors of the Southern Ocean. The overlying regional sedimentary strata are underexplored relative to their Northern Hemisphere counterparts, and thus the role of the Southern Hemisphere in past global environmental change is poorly constrained. A total of 23 proposal ideas were discussed, with ~12 of these deemed mature enough for active proposal development or awaiting scheduled site survey cruises. Of the remaining 11 proposals, key regions were identified where fundamental hypotheses are testable by drilling, but either site surveys are required or hypotheses need further development. Refinements are anticipated based upon regional IODP drilling in 2017/2018, analysis of recently collected site survey data, and the development of site survey proposals. We hope and expect that this workshop will lead to a new phase of scientific ocean drilling in the Australasian region in the early 2020s.The organizers gratefully acknowledge generous and critically important funding for participants’ travel to the workshop. Funding came from the Australian and New Zealand IODP Consortium (ANZIC), the US Science Support Program (USSSP), the Magellan-Plus Workshop Program of the European Consortium for Ocean Research Drilling (ECORD), the Japan Drilling Earth Consortium (J-DESC), the Japan Agency for Marine-Earth Science and Technology (JAMSTEC), IODP-India, and the home institutions of numerous scientists

Longitudinal Synaptic Loss in Primary Tauopathies: An In Vivo [11 C]UCB-J Positron Emission Tomography Study

BACKGROUND: Synaptic loss is characteristic of many neurodegenerative diseases; it occurs early and is strongly related to functional deficits. OBJECTIVE: In this longitudinal observational study, we determine the rate at which synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and we test the relationship with disease progression. METHODS: Our cross-sectional cohort included 32 participants with probable PSP and 16 with probable CBD (all amyloid-negative corticobasal syndrome), recruited from tertiary care centers in the United Kingdom, and 33 sex- and age-matched healthy control subjects. Synaptic density was estimated by positron emission tomography imaging with the radioligand [11 C]UCB-J that binds synaptic vesicle 2A. Clinical severity and cognition were assessed by the PSP Rating Scale and the Addenbrooke's cognitive examination. Regional [11 C]UCB-J nondisplaceable binding potential was estimated in Hammersmith Atlas regions of interest. Twenty-two participants with PSP/CBD had a follow-up [11 C]UCB-J positron emission tomography scan after 1 year. We calculated the annualized change in [11 C]UCB-J nondisplaceable binding potential and correlated this with the change in clinical severity. RESULTS: We found significant annual synaptic loss within the frontal lobe (-3.5%, P = 0.03) and the right caudate (-3.9%, P = 0.046). The degree of longitudinal synaptic loss within the frontal lobe correlated with the rate of change in the PSP Rating Scale (R = 0.47, P = 0.03) and cognition (Addenbrooke's Cognitive Examination-Revised, R = -0.62, P = 0.003). CONCLUSIONS: We provide in vivo evidence for rapid progressive synaptic loss, correlating with clinical progression in primary tauopathies. Synaptic loss may be an important therapeutic target and outcome variable for early-phase clinical trials of disease-modifying treatments. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Comparison of crystallization characteristics and mechanical properties of polypropylene processed by ultrasound and conventional micro injection molding

YesUltrasound injection molding has emerged as an alternative production route for the manufacturing of micro-scale polymeric components, where it offers significant benefits over the conventional micro-injection molding process. In this work, the effects of ultrasound melting on the mechanical and morphological properties of micro-polypropylene parts were characterized. The ultrasound injection molding process was experimentally compared to the conventional micro-injection molding process using a novel mold, which allows mounting on both machines and visualization of the melt flow for both molding processes. Direct measurements of the flow front speed and temperature distributions were performed using both conventional and thermal high-speed imaging techniques. The manufacturing of micro-tensile specimens allowed the comparison of the mechanical properties of the parts obtained with the different processes. The results indicated that the ultrasound injection molding process could be an efficient alternative to the conventional process

Scoping potential routes to UK civil unrest via the food system: Results of a structured expert elicitation

We report the results of a structured expert elicitation to identify the most likely typesof potential food system disruption scenarios for the UK, focusing on routes to civil unrest. Wetake a backcasting approach by defining as an end-point a societal event in which 1 in 2000 peoplehave been injured in the UK, which 40% of experts rated as “Possible (20–50%)”, “More likely thannot (50–80%)” or “Very likely (>80%)” over the coming decade. Over a timeframe of 50 years, thisincreased to 80% of experts. The experts considered two food system scenarios and ranked theirplausibility of contributing to the given societal scenario. For a timescale of 10 years, the majorityidentified a food distribution problem as the most likely. Over a timescale of 50 years, the expertswere more evenly split between the two scenarios, but over half thought the most likely route tocivil unrest would be a lack of total food in the UK. However, the experts stressed that the variouscauses of food system disruption are interconnected and can create cascading risks, highlighting theimportance of a systems approach. We encourage food system stakeholders to use these results intheir risk planning and recommend future work to support prevention, preparedness, response andrecovery planning

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data