Effective practices during emergency school lockdowns: shared experiences of four Australian schools.

This study investigates common features of a set of diverse schools' responses to the initial school lockdown period during the pandemic in 2020, with a focus on practices supporting learning, inclusion and wellbeing. It comprises a collective case study of four Australian schools that were selected based on their reputation for impactful support of students and teachers during the emergency remote teaching period. Methods included interviews and focus groups with school leaders, teachers and students. The schools had widely differing contexts, technology access and student needs. Despite these varied contexts, the findings provided important insights into common practices supporting effective remote teaching. Emerging principles of effective practice illuminate ways forward to mitigate the significant risks accompanying emergency remote teaching, and guide practices in a variety of school contexts.

High MDR-1 expression by MAIT cells confers resistance to cytotoxic but not immunosuppressive MDR-1 substrates.

High expression of the ATP-binding cassette-multi-drug efflux protein 1 (MDR1) is a striking feature of mucosal-associated invariant T (MAIT) cells, a prominent human innate-like T cell subset. We demonstrate significantly higher MDR1 expression by CD8 + CD161 ++ Vα7.2 + MAIT cells than the phenotypically and functionally related CD8 + CD161 ++ Vα7.2-subset and show MDR1 expression to be similarly high throughout MAIT CD4 + , CD8 + , double-negative (DN) and double-positive (DP) cell subsets. We demonstrate the MAIT cell-predominant CD8+ CD161++ subset to uniquely and efficiently efflux the cytotoxic anthracycline daunorubicin, retain function on daunorubicin exposure and demonstrate MDR1-dependent protection from daunorubicin-induced apoptosis. By contrast, CD8+ CD161++ Vα7.2+ MAIT cells were not protected from the anti-proliferative and cytotoxic effects of the immunosuppressive MDR1 substrates tacrolimus and mycophenoic acid, although function following MAIT cell-specific T cell receptor (TCR)-dependent and -independent stimulation was preserved on in-vitro exposure to these agents. Overall, our data further define MDR1 expression by CD161++ T and MAIT cells and demonstrate the potential for high MDR1 expression by MAIT cells to confer resistance to cytotoxic MDR1 substrates in vivo . As our understanding of the importance of MAIT cells in human immunity and immunopathology grows, this is an important observation for clinical contexts such as the treatment of malignancy, autoimmunity and post-transplant immunosuppression.

Quantifying biomarkers of axonal degeneration in early glaucoma to find the disc at risk.

To evaluate regional axonal-related parameters as a function of disease stage in primary open angle glaucoma (POAG) and visual field (VF) sensitivity. Spectral domain optical coherence tomography was used to acquire 20° scans of POAG (n = 117) or healthy control (n = 52) human optic nerve heads (ONHs). Region specific and mean nerve fibre layer (NFL) thicknesses, border NFL and peripapillary NFL, minimum rim width (MRW)/ area (MRA) and prelamina thickness; and volume were compared across POAG disease stages and with visual field sensitivity. Differences identified between early glaucoma (EG), preperimetric glaucoma (PG) and control (C) ONHs included thinner PG prelamina regions than in controls (p < 0.05). Mean border NFL was thinner in EG (p < 0.001) and PG (p = 0.049) compared to control eyes; and EG mean, and inferior and ST, border NFL was thinner than in PG (p < 0.01). Mean, superior and inferior PG peripapillary NFL were thinner than in controls (p < 0.05), and EG ST peripapillary NFL was thinner than in PG (p = 0.023). MRW differences included: PG SN and inferior less than in controls (p < 0.05); thinner EG mean regional, inferior, nasal, and ST MRW versus PG MRW (p < 0.05). Regional border NFL, peripapillary NFL, MRW, MRA, prelamina thickness (except centre, p = 0.127) and prelamina volume (p < 0.05) were significantly associated with VF mean deviation (MD). Novel axon-derived indices hold potential as biomarkers to detect early glaucoma and identify ONHs at risk.

The optical detection of retinal ganglion cell damage.

We provide an overview of developments in the use optical coherence tomography (OCT) imaging for the detection of retinal ganglion cell (RGC) damage in vivo that avoid use of any exogenous ligands to label cells. The method employs high-resolution OCT using broad spectral light sources to deliver axial resolution of under 5 µm. The resolution approximates that of cellular organelles, which undergo degenerative changes that progress to apoptosis as a result of axon damage. These degenerative changes are manifest as the loss of RGC dendrites and fragmentation of the subcellular network of organelles, in particular, the mitochondria that support dendritic structure. These changes can alter the light-scattering behavior of degenerating neurons. Using OCT imaging techniques to identify these signals in cultured neurons, we have demonstrated changes in cultured cells and in retinal explants. Pilot studies in human glaucoma suggest that similar changes are detectable in the clinical setting. High-resolution OCT can be used to detect optical scatter signals that derive from the RGC/inner plexiform layer and are associated with neuronal damage. These findings suggest that OCT instruments can be used to derive quantitative measurements of RGC damage. Critically, these signals can be detected at an early stage of RGC degeneration when cells could be protected or remodeled to support visual recovery.

Properties of verapamil-hypersensitive multidrug-resistant Chinese hamster ovary cells.

Two vincristine-resistant Chinese hamster ovary cell lines have been shown previously to be hypersensitive to the calcium channel blocker, verapamil. They are now shown to be hypersensitive to the membrane-active agent quinidine sulfate and to the calcium channel blockers diltiazem and nicardipine. Hypersensitivity to quinidine sulfate implies that calcium channels are not the primary target for these drug effects on these cell lines and is consistent with our previous observation that their calcium accumulation is normal in the presence and absence of verapamil. The two cell lines have elevated levels of membrane P-glycoprotein and of two cytosolic proteins, Mr 27,000 and pI 6.0 and 6.4. Revertants have normal levels of these cytosolic proteins, suggesting that these proteins may play a role in conferring resistance. [3H]Verapamil accumulation by the two cell lines is lower than in controls. One of the cell lines has been hybridized to normal cells and the vincristine resistance and verapamil sensitivity of three hybrid clones has been determined. Vincristine resistance is semidominant but verapamil hypersensitivity is completely recessive.

CD161(int)CD8+ T cells: a novel population of highly functional, memory CD8+ T cells enriched within the gut.

The C-type lectin-like receptor CD161 is expressed by lymphocytes found in human gut and liver, as well as blood, especially natural killer (NK) cells, T helper 17 (Th17) cells, and a population of unconventional T cells known as mucosal-associated invariant T (MAIT) cells. The association of high CD161 expression with innate T-cell populations including MAIT cells is established. Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including antiviral populations that display a memory phenotype. These memory CD161(int)CD8+ T cells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence. Furthermore, this population was characterized by enhanced polyfunctionality, increased levels of cytotoxic mediators, and high expression of the transcription factors T-bet and eomesodermin (EOMES). Such populations were induced by novel vaccine strategies based on adenoviral vectors, currently in trial against hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T-cell populations in humans. As induction of such responses represents a major aim of T-cell prophylactic and therapeutic vaccines in viral disease and cancer, analysis of these populations could be of value in the future.

MAIT cells are licensed through granzyme exchange to kill bacterially sensitized targets.

Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell population restricted by the non-polymorphic, major histocompatibility complex class I-related protein 1, MR1. MAIT cells are activated by a broad range of bacteria through detection of riboflavin metabolites bound by MR1, but their direct cytolytic capacity upon recognition of cognate target cells remains unclear. We show that resting human MAIT cells are uniquely characterized by a lack of granzyme (Gr) B and low perforin expression, key granule proteins required for efficient cytotoxic activity, but high levels of expression of GrA and GrK. Bacterial activation of MAIT cells rapidly induced GrB and perforin, licensing these cells to kill their cognate target cells. Using a novel flow cytometry-based killing assay, we show that licensed MAIT cells, but not ex vivo MAIT cells from the same donors, can efficiently kill Escherichia coli-exposed B-cell lines in an MR1- and degranulation-dependent manner. Finally, we show that MAIT cells are highly proliferative in response to antigenic and cytokine stimulation, maintaining high expression of GrB, perforin, and GrA, but reduced expression of GrK following antigenic proliferation. The tightly regulated cytolytic capacity of MAIT cells may have an important role in the control of intracellular bacterial infections, such as Mycobacterium tuberculosis.

Neurofibrillary tangles in progressive supranuclear palsy brains exhibit immunoreactivity to frameshift mutant ubiquitin-B protein.

In Alzheimer's disease (AD) neurofibrillary tangles (NFT) are strongly tau and ubiquitin immunopositive, and contain an aberrant form of ubiquitin derived from the ubiquitin-B gene denoted as UBB+1. We explored whether the tau-related NFT seen in another neurodegenerative disease, progressive supranuclear palsy (PSP), also showed an accumulation of UBB+1. Three cases of PSP were examined immunohistochemically for tau protein, ubiquitin-protein conjugates and UBB+1 using single and double labelling. We conclude that UBB+1 is associated with compact globose tangles rather than dispersed accumulations of tau in PSP, showing that its presence is not unique to AD. We propose that aggregation of ubiquitinated proteins into compact inclusions in PSP might be due to inhibition of the degradation of multiubiquitinated proteins by ubiquitin chains containing proximal UBB+1 rather than normal ubiquitin.

Neurofibrillary tangles of Alzheimer's disease brains contain 14-3-3 proteins.

The localisation of 14-3-3 proteins compared to that of tau and ubiquitin-protein conjugates in sections of hippocampus from Alzheimer's disease (AD) brains was examined by immunohistochemistry. In all cases (n = 10), anti-14-3-3 stained a proportion of neurofibrillary tangles (NFT). In general, NFT stained by anti-14-3-3 were smaller than those stained by anti-tau or anti-ubiquitin-protein conjugates and were more confined to the neuronal cell body. Occasionally, cortical Lewy bodies in cases of Lewy body dementia were also found to be 14-3-3-positive. Since 14-3-3 proteins are central to MAP kinase signalling, the results support the proposal that this pathway is in part responsible for the hyperphosphorylation of tau, which leads to the formation of the paired helical filaments seen in AD brains.

Pathological lesions of Alzheimer's disease and dementia with Lewy bodies brains exhibit immunoreactivity to an ATPase that is a regulatory subunit of the 26S proteasome.

MS73 is one of a family of ATPases that act as regulatory subunits of the 26S proteasome. Localisation of this ATPase in histological sections of hippocampus from Alzheimer's disease (AD) and in cingulate gyrus sections of dementia with Lewy bodies (DLB) brains was examined immunohistochemically. In all cases of AD (n = 10) neurofibrillary tangles (NFT), plaque neurites and neuropil threads were immunoreactive for MS73. In seven out of the nine cases of DLB, distinctive MS73-positive structures were detected within cortical Lewy bodies. The association of MS73 with these neuronal abnormalities provides further evidence that proteolytic processing involving the 26S proteasome occurs in lesions of AD and DLB.

Tubal pregnancy in a 'low-risk' population: occasional association with follicular salpingitis.

Long-standing tubal inflammatory lesions occurred in 35 (14%) of 250 tubal pregnancy patients, aged from 14 to 45 yrs, encountered from 1948 to 1969 in an eastern Canadian population where clinically manifest pelvic inflammation is not prevalent and 1/180 is the approximate ratio of ectopic pregnancy to live births. Present in 24 of these 35 patients was follicular salpingitis. For most of the eccyeses, functional derangements appear likely to have been responsible more often than structural alterations of the oviducts; but possible roles for 'physiological salpingitis' in leading to tubal pregnancy may be worthy of investigation.

Concentrations and sources of cadmium, copper, lead and zinc in house dust in Christchurch, New Zealand.

The amounts (microgram m-2) and concentrations (microgram g-1) of cadmium, copper, lead and zinc have been measured in house dust in Christchurch, New Zealand. For 120 houses surveyed the geometric mean concentrations of the four metals are 4.24 micrograms g-1, 165 micrograms g-1, 573 micrograms g-1 and 10,400 micrograms g-1, respectively. In addition eleven variables, such as house age, carpet wear and traffic density, were recorded for each property and the results analysed with respect to their effects on the amounts and concentrations of the four elements. The amounts of all the metals were highly correlated with the overall dustiness of the houses, which was found to be predominantly determined by the degree of carpet wear. No one dominant source of cadmium was identified, although several minor sources including carpet wear, galvanized iron roofs and red/orange/yellow coloured carpets were implicated. Petrol lead and lead-based paints were identified as significant sources of lead in house dust. Rubber carpet underlays or backings were identified as a significant source of zinc, with some contribution from galvanized iron roofs. Road traffic and probably the existence of a fire place appear to contribute to the copper levels.

Lead in house dust of Christchurch, New Zealand: sampling, levels and sources.

Lead in house dust was determined in different areas of Christchurch, New Zealand. The mean lead level in newer (post-1950) areas of the city was 460 micrograms g-1, whereas in older (pre-1950) areas it was 830 micrograms g-1. These levels also relate to the type of building material (brick or wood, respectively) and type of paint used (non-lead or lead paint, respectively). For the newer areas of the city, it was estimated that approximately 90% of the lead was derived from petrol additives (via street dust and aerosol), whereas in the older areas, approximately 50% of the lead was estimated to come from petrol lead and 45% from paint lead.

Lead in teeth: the influence of the tooth type and the sample within a tooth on lead levels.

Different sections of permanent teeth have been sampled and the lead levels estimated using carbon furnace AAS. Very high levels of lead (500-3400 micrograms g-1) and other trace metals (Cd, Cu, Fe and Zn) occur on the surface of the teeth, falling off rapidly a few micrometers into the teeth. Lead levels in the bulk enamel of incisors vary depending on the position within the tooth, the highest values occur on the lingual side near the gums and the lowest levels on the labial side near the tooth top. The ratio of the concentration of lead in enamel to dentine and to circumpulpal dentine was found to be 1:2:6, and within the dentine the lead levels were highest in the root dentine. The root dentine in the permanent teeth of eight, near complete or representative, sets of teeth was analysed for lead. The ratio ([Pb]tooth/[Pb]total set) decreased in the order: first molars greater than central incisors greater than lateral incisors greater than canines greater than premolars greater than second molars greater than third molars. This order inversely correlates with the age of formation or eruption of the teeth, i.e. the older teeth have the highest levels of lead in the dentine. Dentine appears to be the best material to use to estimate lead, particularly in relation to the integrated lead intake of a person. Dentine lead was determined in a small sample of deciduous teeth obtained from children living in rural areas. The levels were found to be slightly less than for children living in new housing urban areas and significantly less than for children living in older houses of urban areas.

The transport of airborne trace elements copper, lead, cadmium, zinc and manganese from a city into rural areas.

The fluxes of the elements lead, zinc, copper, cadmium and manganese have been measured in the insoluble component of bulk deposition derived from Christchurch, New Zealand. Lead, zinc, copper and cadmium fluxes follow approximately exponential decay curves away from the city whereas manganese deposition showed little spatial variation. A similar composite source originating in the city is indicated for the lead zinc, copper and cadmium and a different major source occurs for manganese. In the city and nearby rural areas soil is not a major source of atmospheric lead, zinc, copper and cadmium, whereas at remote sites atmospheric levels of these elements are mostly soil derived. Seasonal variations in the bulk deposition are large within the city, and at upwind rural sites. The variations are controlled by meteorological conditions, in particular wind speed and the height of the mixing layer. Compared with overseas studies, the proportion of the metals occurring in the soluble fraction of the bulk deposition is low. This may be due to the relatively dry climate of the area.

The concentrations, distribution and sources of cadmium, copper, lead and zinc in the atmosphere of an urban environment.

The four metals Cd, Cu, Pb and Zn have been measured in residential city air in a relatively small urban environment. The atmospheric concentrations are Cd, 0.516, 0.305; Cu, 12.5, 8.22; Pb, 155, 70.2; and Zn 47.4, 22.4 ng m-3 at two different sites. Except for lead the concentrations are low and more typical of rural areas in more industrialised centres. The concentrations were found to be higher in the colder and more stable air conditions existing during the winter season. Also concentrations on the flat were higher than those on a hillside probably reflecting the influence of thermal inversions. Wind direction influences the concentrations, they being greater when the wind flow comes across the industrial areas of the city. Some of the major sources of the elements are coal, soil, tyre wear and automobile emissions.

Trace elements in street and house dusts: sources and speciation.

The sources and speciation of trace elements in street and house dusts are reviewed. Soil is a major component of both dusts, but a number of elements are enriched in both materials. These include Pb, Zn, Cu, Cd, As, Sb, Cr, Ca, Na, Au, Cl and Br. They arise from a number of contributing and polluting sources. In the case of house dust, some elements, such as Cu, Co, As, Sb, Zn, Cd, Au, Cl, C and Pb, are produced in the house. There are a number of problems associated with the determination of the speciation of trace elements in dusts. These include the low concentrations of many of the elements, and the interpretation of the results from selective sequential extractions. The mobility and potential availability of the trace elements from dust lies in the order Cd greater than Zn, Pb greater than Mn, Cu greater Fe.

The use of peat in the historical monitoring of trace metals in the atmosphere.

The concentrations of lead, zinc, copper, manganese, cadmium and calcium have been measured in three peat bogs. The distribution of Pb, Zn, Mn and Ca are dependent on the position and fluctuations of the water table. They all become depleted in the waterlogged, anaerobic zone. Copper and cadmium are uniformly distributed and appear to be immobilised, probably by the formation of metal/organic complexes, and independent of the acid and redox conditions existing in the bogs. The use of the concentration profiles of the metal ions as a means of historical monitoring of trace metal contamination is complex for Pb, Zn, Mn and Ca but may be more straightforward for Cu and Cd.

Seasonal variations in the concentrations of cadmium, copper, lead and zinc in leaves of the horse chesnut (Aesculus hippocastanum L.).

The concentrations of cadmium, copper, lead and zinc have been measured in the leaves of a deciduous tree the horse chestnut (Aesculus hippocastanum L.) over the period of their lifetime (7 months). The average concentrations for the total sample based on ash weight are: (microg g(-1)) cadmium, 0.197; copper, 129; lead, 294; and zinc, 299. The temporal trends in the concentrations of the metals can be related to their dominant source. Copper and zinc concentrations are highest in the new leaves and decrease with time, suggesting the main source of the elements are uptake from the soil. The decrease occurs partly because of dilution by leaf material as it increases over the growing period. In the case of zinc, however, aerial deposits appear to be also a significant source. Lead concentrations, on the other hand, show an increase with time, which can be related to increasing deposits from aerosol lead arising from the combustion of petrol lead. The increase is enough to offset the dilution effect. For cadmium there is no significant trend, but the tendency is a decrease with time. It is not possible, however, to distinguish between soil uptake and aerial deposit as both are small compared with increase in leaf material.

A longitudinal study of dentine lead levels and intelligence, school performance and behaviour: the measurement of dentine lead.

Shed deciduous teeth were obtained from a sample of 996 New Zealand children who were participants in a longitudinal study. For each child, estimates of dentine lead were obtained from two samples of dentine. The information was used to estimate the magnitude of random errors of measurement in dentine lead values and it was estimated that between 15 and 20% of the variance in dentine lead values was attributable to random errors of measurement. In addition, dentine lead levels were influenced by small systematic errors of measurement arising from the age at which the tooth was collected and the type of tooth analysed. These sampling factors, however, accounted for less that 3% of the variance in dentine lead values. The implications of these findings for the interpretation of correlations between dentine lead levels and other variables are discussed.