Metallurgical Pilot Plants

In this presentation, a brief review is made of the theory and practice of piloting industrial prototypes and attention is particularly focussed on methods of scale-up and their usefulness in equipment and plant design. There exist prolific references in the literature on general Pilot Plant engineering and Scale-up Fundamentals. What may be considered a 'Bible' on the subject is a recent volume by R.E. Johnstone and M.W. Thring on "Pilot Plants, Models, and Scale-up Methods in Chemical Engin-eering"

Measuring visual cortical oxygenation in diabetes using functional near-infrared spectroscopy

Aims: Diabetes mellitus affects about 6% of the world’s population, and the chronic complications of the disease may result in macro- and micro-vascular changes. The purpose of the current study was to shed light on visual cortical oxygenation in diabetic individuals. We then aimed to compare the haemodynamic response (HDR) to visual stimulation with glycaemic control, given the likelihood of diabetic individuals suffering from such macro- and micro-vascular insult. Methodology: Thirty participants took part in this explorative study, fifteen of whom had diabetes and fifteen of whom were non-diabetic controls. The HDR, measured as concentrations of oxyhaemoglobin [HbO] and deoxyhaemoglobin [HbR], to visual stimulation was recorded over the primary visual cortex (V1) using a dual-channel oximeter. The stimulus comprised a pattern-reversal checkerboard presented in a block design. Participants’ mean glycated haemoglobin (HbA1c) level (±SD) was 7.2±0.6% in the diabetic group and 5.5±0.4% in the non-diabetic group. Raw haemodynamic data were normalised to baseline, and the last 15 s of data from each ‘stimulus on’ and ‘stimulus off’ condition were averaged over seven duty cycles for each participant. Results: There were statistically significant differences in ∆[HbO] and ∆[HbR] to visual stimulation between diabetic and non-diabetic groups (p<0.05). In the diabetic group, individuals with type 1 diabetes displayed an increased [HbO] (p<0.01) and decreased [HbR] (p<0.05) compared to their type 2 counterparts. There was also a linear relationship between both ∆[HbO] and ∆[HbR] as a function of HbA1c level (p<0.0005). Conclusions: Our findings suggest that fNIRS can be used as a quantitative measure of cortical oxygenation in diabetes. Diabetic individuals have a larger HDR to visual stimulation compared to non-diabetic individuals. This increase in ∆[HbO] and decrease in ∆[HbR] appears to be correlated with HbA1c level

Tau aggregation and progressive neuronal degeneration in the absence of changes in spine density and morphology after targeted expression of Alzheimer's disease-relevant tau constructs in organotypic hippocampal slices

Alzheimer's disease (AD) is characterized by progressive loss of neurons in selected brain regions, extracellular accumulations of amyloid beta, and intracellular fibrils containing hyperphosphorylated tau. Tau mutations in familial tauopathies confirmed a central role of tau pathology; however, the role of tau alteration and the sequence of tau-dependent neurodegeneration in AD remain elusive. Using Sindbis virus-mediated expression of AD-relevant tau constructs in hippocampal slices, we show that disease-like tau modifications affect tau phosphorylation at selected sites, induce Alz50/MC1-reactive pathological tau conformation, cause accumulation of insoluble tau, and induce region-specific neurodegeneration. Live imaging demonstrates that tau-dependent degeneration is associated with the development of a "ballooned" phenotype, a distinct feature of cell death. Spine density and morphology is not altered as judged from algorithm-based evaluation of dendritic spines, suggesting that synaptic integrity is remarkably stable against tau-dependent degeneration. The data provide evidence that tau-induced cell death involves apoptotic as well as nonapoptotic mechanisms. Furthermore, they demonstrate that targeted expression of tau in hippocampal slices provides a novel model to analyze tau modification and spatiotemporal dynamics of tau-dependent neurodegeneration in an authentic CNS environment

Effects of glaucoma and snoring on cerebral oxygenation in the visual cortex: a study using functional Near Infrared Spectroscopy (fNIRS)

Purpose: The purpose of this study was to investigate the effects of snoring and glaucoma on the visual Haemodynamic Response (HDR) using functional Near Infrared Spectroscopy (fNIRS). Methods: We recruited 8 glaucoma patients (aged 56-79), 6 habitual snorers (aged 26-61) and 10 healthy control participants (aged 21-78). Glaucoma patients were of varying subtypes and under care of ophthalmologists. Prior to testing visual acuity, blood pressure, heart rate and a medical history were taken. HDRs were recorded over the primary visual cortex (V1) using a reversing checkerboard paradigm. Results & Discussion: All participants showed the characteristic increase of Oxyhaemoglobin concentration ([HbO]) and decrease of Deoxyhaemoglobin concentration ([HbR]) during visual stimulation (p < 0.001, η2 = 0.78). Despite this, there were signifi cant group differences with a large effect size (η2 = 0.28). During visual stimulation normal participants had greater [HbO] compared to snorers and glaucoma patients (p < 0.01). Both glaucoma patients and snorers presented with comparable HDR for [HbO] and [HbR] in V1. Importantly, during visual stimulation, the increased [HbO] in glaucoma patients correlated well with their visual fi elds and self-reported activities of daily living (r = -0.98, r = -0.82, p < 0.05). Both glaucoma patients and snorers presented with an attenuated HDR in V1. Our results suggest a possible vascular link between these conditions

Measuring the foveal avascular zone in diabetes: a study using optical coherence tomography angiography

AIMS/INTRODUCTION: Diabetes is a global issue that currently affects 425 million people worldwide. One observable microvascular complication of this condition is a change in the foveal avascular zone (FAZ). In this study, we used optical coherence tomography angiography to investigate the effect of diabetes on the FAZ. MATERIALS AND METHODS: A total of 11 participants with diabetes and 11 participants without diabetes took part in this study. Participants in both groups were matched for age (P = 0.217) and sex (P = 0.338), and had no history of ocular disease. Macular optical coherence tomography angiography (OCT‐A) scans of participants’ right and left eyes were taken. Glycosylated hemoglobin (HbA(1c)) and blood glucose levels were also measured. The FAZ area was manually segmented at the levels of the superficial capillary plexus (FAZ(SCP)) and deep capillary plexus (FAZ(DCP)). RESULTS: There was a strong relationship between the FAZ area of participants’ right and left eyes (P ≤ 0.001) in both diabetes and non‐diabetes groups. In the diabetes group, the FAZ(SCP) (P = 0.047) and FAZ(DCP) (P = 0.011) areas was significantly larger than in the non‐diabetes group. Moreover, multiple linear regression analysis predicted a 0.07‐mm(2) increase in the FAZ(SCP) and FAZ(DCP) areas of individuals with diabetes for every 1% increase in their HbA(1c) level. CONCLUSIONS: Our findings show that there is enlargement of the FAZ in individuals with diabetes compared with individuals without diabetes. In the diabetes group, this enlargement appears to be correlated with HbA(1c) level. OCT‐A imaging could, therefore, be a useful tool to monitor the FAZ and identify potential early microvasculopathy in diabetes

A new displacement-based approach to calculate stress intensity factors with the boundary element method

The analysis of cracked brittle mechanical components considering linear elastic fracture mechanics is usually reduced to the evaluation of stress intensity factors (SIFs). The SIF calculation can be carried out experimentally, theoretically or numerically. Each methodology has its own advantages but the use of numerical methods has be-come very popular. Several schemes for numerical SIF calculations have been developed, the J-integral method being one of the most widely used because of its energy-like formulation. Additionally, some variations of the J-integral method, such as displacement-based methods, are also becoming popular due to their simplicity. In this work, a simple displacement-based scheme is proposed to calculate SIFs, and its performance is compared with contour integrals. These schemes are all implemented with the Boundary Element Method (BEM) in order to exploit its advantages in crack growth modelling. Some simple examples are solved with the BEM and the calculated SIF values are compared against available solutions, showing good agreement between the different schemes

Measurement protocols and determinants of peak oxygen consumption in adults with Down syndrome:a systematic review

This systematic review aimed to provide an overview of test protocols used to measure peak oxygen uptake (VO2peak) in adults with Down syndrome (DS) and to determine how generalisable the outcomes are for the entire population of adults with DS by describing the sample characteristics of these studies and their impact on VO2peak. A literature search (PROSPERO CRD42022309560) was performed (18 July 2023) using the following databases: PubMed, CINAHL, APA PsycINFO, Web of Science, Embase and SPORTDiscus. For articles to be included, they had to be peer-reviewed pubications, reporting VO2peak or VO2max for individuals with DS separately, with a sample of n ≥ 5 and a mean age ≥18 years. Systematic reviews and meta-analyses were excluded but their reference lists were searched for additional papers to include. Studies were evaluated for risk of bias following the guidelines of Kmet et al. The results were summarised with frequency statistics. Forty-three studies were included in this systematic review. Sample sizes of included adults with DS ranged from n = 4–226, with a total of n = 1498 adults with DS being included. Most studies (29/43) used the same standardised maximal exercise treadmill protocol to measure VO2peak in adults with DS, and 33 out of 43 studies used at least one objective criterion to determine a valid maximal effort. Participants were predominantly male, under 40 years old, and overweight or obese. Additionally, the diversity of study samples was lacking or not reported. The most widely used, standardised, maximal exercise test treadmill protocol is recommended for future use in research and practice, including objective criteria to determine valid maximal effort. The current study samples are not representative of the population of adults with DS in terms of sex, age and diverse backgrounds and therefore likely overestimate VO2peak of this population.</p

T-cell production of matrix metalloproteinases and inhibition of parasite clearance by TIMP-1 during chronic Toxoplasma infection in the brain

Chronic infection with the intracellular protozoan parasite Toxoplasma gondii leads to tissue remodelling in the brain and a continuous requirement for peripheral leucocyte migration within the CNS (central nervous system). In the present study, we investigate the role of MMPs (matrix metalloproteinases) and their inhibitors in T-cell migration into the infected brain. Increased expression of two key molecules, MMP-8 and MMP-10, along with their inhibitor, TIMP-1 (tissue inhibitor of metalloproteinases-1), was observed in the CNS following infection. Analysis of infiltrating lymphocytes demonstrated MMP-8 and -10 production by CD4+ and CD8+ T-cells. In addition, infiltrating T-cells and CNS resident astrocytes increased their expression of TIMP-1 following infection. TIMP-1-deficient mice had a decrease in perivascular accumulation of lymphocyte populations, yet an increase in the proportion of CD4+ T-cells that had trafficked into the CNS. This was accompanied by a reduction in parasite burden in the brain. Taken together, these findings demonstrate a role for MMPs and TIMP-1 in the trafficking of lymphocytes into the CNS during chronic infection in the brain