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    Zero retinal vein pulsation amplitude extrapolated model in non-invasive intracranial pressure estimation

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    Intracranial pressure (ICP) includes the brain, optic nerve, and spinal cord pressures; it influences blood flow to those structures. Pathological elevation in ICP results in structural damage through various mechanisms, which adversely affects outcomes in traumatic brain injury and stroke. Currently, invasive procedures which tap directly into the cerebrospinal fluid are required to measure this pressure. Recent fluidic engineering modelling analogous to the ocular vascular flow suggests that retinal venous pulse amplitudes are predictably influenced by downstream pressures, suggesting that ICP could be estimated by analysing this pulse signal. We used this modelling theory and our photoplethysmographic (PPG) retinal venous pulse amplitude measurement system to measure amplitudes in 30 subjects undergoing invasive ICP measurements by lumbar puncture (LP) or external ventricular drain (EVD). We estimated ICP from these amplitudes using this modelling and found it to be accurate with a mean absolute error of 3.0 mmHg and a slope of 1.00 (r = 0.91). Ninety-four percent of differences between the PPG and invasive method were between − 5.5 and + 4.0 mmHg, which compares favourably to comparisons between LP and EVD. This type of modelling may be useful for understanding retinal vessel pulsatile fluid dynamics and may provide a method for non-invasive ICP measurement

    Comparative accuracy of two veterinary‐calibrated point‐of‐care glucometres for measurement of blood glucose concentration in dogs

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    Objectives To investigate and compare the accuracy of two veterinary portable blood glucose metres (AccuTell; AccubioTech; and AlphaTrak2; Abbott Laboratories). Materials and Methods One hundred twenty venous blood samples were obtained for immediate whole blood glucose concentration measurement using two portable blood glucose metres designed for use in dogs. Plasma glucose concentration was measured by a laboratory analyser using a hexokinase reaction method. Packed cell volume was measured for each sample. Linear regression analysis was performed and Bland–Altman plots constructed with International Standards Organisation 15197:2013 standards applied to assess relationship and agreement between results of portable blood glucose metres and laboratory analyser methods, respectively. Clarke's error grid analysis was used to assess clinical accuracy and usefulness. Results The AccuTell and the AlphaTrak2 had mean differences of −0.69 ± 0.70 mmol/L (bias ±sd) and −1.09 ± 1.22 mmol/L (bias ± sd) with the reference analyser, respectively. Eighty-eight of 120 (73.3%) samples for the AccuTell, and 73 of 120 (60.8%) samples for the AlphaTrak2 were plotted in the zone of the error grid analysis that indicated less clinical risk of misdiagnosis of glucose status. Neither device fulfilled the International Standards Organisation 15197:2013 standards for system accuracy. A statistically significant effect of packed cell volume was identified on the difference between blood glucose concentration obtained by the AlphaTrak2 and the hexokinase reaction method, but not for the AccuTell. Clinical Significance Both devices do not meet International Standards Organisation 15197:2013 standards. Users should expect 95% of the samples measured with the AccuTell to be between −0.7 and +2.1 mmol/L higher than actual values, and 95% of the samples measured with the AlphaTrak2 to be between −1.3 and +3.5 mmol/L higher than actual values

    Magmatic-hydrothermal evolution of the El Laco iron deposit revealed by trace element geochemistry and high-resolution chemical mapping of magnetite assemblages

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    The Plio-Pleistocene El Laco magnetite ore bodies in the Chilean Altiplano represent an unusual subvolcanic/aerial type of an iron oxide-apatite (IOA) deposit. The textures of these magnetite ore bodies have sustained a long-standing geological controversy on the origin of iron oxide deposits with models spanning the spectrum from purely igneous to magmatic-hydrothermal processes. In particular, the link between the geochemical processes taking place in the source magma and the subsequent evolution of the overlying magmatic-hydrothermal system are still not well understood. Here we address this problem by focusing on microtextural and geochemical features of iron ore and silicate gangue minerals retrieved from drill core samples from El Laco ore bodies, as well as from the andesite volcanic host rocks. We report a comprehensive geochemical dataset of magnetite assemblages at El Laco obtained using a combination of EPMA, LA-ICP-MS, and synchrotron radiation µ-XRF methods. Microtextural and geochemical data of magnetite reveal consistent variations with depth. Magnetite in the andesitic host rocks and from deep/intermediate levels of the ore bodies have a high concentration of trace elements including Ti, V, Ni, Mn, Zn, Cr, Al, Ga, Cu and Co in comparison with magnetite from the upper sections of the ore bodies. Clinopyroxene is present in the andesite host rocks as well as the ore bodies, showing chemical differences between both types, with Mn and Fe contents that are higher in the former, and Na and Ca concentrations enriched in the latter. We interpret the enriched-to-depleted compositional trends in magnetite and clinopyroxene as resulting from a transition from purely igneous conditions to a fluid-dominated, cooling magmatic-hydrothermal system. Detailed microtextural analysis of magnetite and clinopyroxene from the ore bodies support this notion, revealing multiple growth stages punctuated by dissolution-reprecipitation processes. Our data further supports a genetic model that explains the formation of the El Laco iron oxide deposit through the injection, upward migration and venting of magmatically-derived Fe-rich fluids

    Herbicide residues in Australian grain cropping soils at sowing and their relevance to crop growth

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    Herbicides are used extensively in Australian grain cropping systems. Despite occasional observations of herbicide-induced phytotoxicity, there is little information on the persistence and carryover of multiple herbicide classes in cropping soils and the risk to subsequent crops. Two soil surveys were conducted in 2015 (n = 40) and 2016 (n = 42) across different Australian grain cropping fields prior to sowing of winter crops, and soil samples analysed for herbicide residues (16 analytes in 2015 and 22 analytes in 2016). Samples in 2015 were taken at two depth (0–10 cm and 10-30 cm), whilst samples in 2016 were taken in topsoil (0–10 cm) only, but from two discrete locations in each field. Our research in both years found at least one herbicide (or herbicide metabolite) residue at all sites, with a median of 6 analytes detected in 2015 and 7 analytes detected in 2016. The most frequently detected residues were glyphosate and its primary breakdown product aminomethylphosphonic acid (AMPA), in 87 and 100%, respectively, of topsoil (0–10 cm) samples in 2015, and 67 and 93% of samples in 2016. The median concentration of glyphosate in 2015 was 0.12 mg kg−1, while AMPA was 0.41 mg kg−1. In 2016, median concentrations of glyphosate and AMPA were 0.22 mg kg−1 and 0.31 mg kg−1. Residues of 2,4-dichlorophenoxyacetic acid, trifluralin and diflufenican were also detected in >40% of topsoil samples in both seasons, but with median concentrations of <0.05 mg kg−1. A literature review found limited availability of phytotoxicity thresholds for major grain crops exposed to soilborne herbicide residues. A risk assessment using available thresholds suggested that although up to 29% of fields contained trifluralin residues that could constrain cereal crop growth, and 24% of fields contained residues of phenoxy or sulfonylureas that could affect dicotyledonous crops, the majority of these fields when planted with tolerant crops would be unlikely to be affected by herbicide residues. More work is required to ascertain the spatial distribution, bioavailability and phytotoxicity of residues and residue mixtures to enable a more accurate agronomic risk assessment

    The Proximal Tubule as the Pathogenic and Therapeutic Target in Acute Kidney Injury

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    Background: In 2004, the term acute kidney injury (AKI) was introduced with the intention of broadening our understanding of rapid declines in renal function and to replace the historical terms of acute renal failure and acute tubular necrosis (ATN). Despite this evolution in terminology, the mechanisms of AKI have stayed largely elusive with the pathophysiological concepts of ATN remaining the mainstay in our understanding of AKI. Summary: The proximal tubule (PT), having the highest mitochondrial content in the kidney and relying heavily on oxidative phosphorylation to generate ATP, is vulnerable to ischaemic insults and mitochondrial dysfunction. Histologically, pathological changes in the PT are more consistent than changes to the glomeruli or the loop of Henle in AKI. Physiologically, activation of tubuloglomerular feedback due to PT dysfunction leads to an increase in preglomerular afferent arteriole resistance and a reduction in glomerular filtration. Pharmacologically, frusemide – a drug commonly used in the setting of oliguric AKI – is actively secreted by the PT and its diuretic effect is compromised by its failure to be secreted into the urine and thus be delivered to its site of action at the loop of Henle in AKI. Increases in the urinary, but not plasma biomarkers, of PT injury within 1 h of shock suggest that the PT as the initiation pathogenic target of AKI. Key Message: Therapeutic agents targeting specifically the PT epithelial cells, in particular its mitochondria – including amino acid ergothioneine and superoxide scavenger MitoTEMPO – show great promises in ameliorating AKI

    Cat got your tongue? The misnomer of ‘community cats’ and its relevance to conservation

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    The choice of words we use often conveys specific meanings and tone to a topic. Hence, the words that we use in conservation science often have important ramifications in scientific, legal, and social contexts. The management of free-ranging cats is an important example, because of the animal welfare, predation, and public health implications. In this context, one set of words that has recently arisen outside of conservation but has particular relevance for it and many other fields is ‘community cat.’ As we note, through an evaluation of the literature, ‘community cat’ is almost always used as a synonym for unowned, free-ranging cats. Such rebranding is significant for conservation, policy, and management because it implies community ownership of animals without, in many cases, explicit agreement from the community. As such, there is a need to understand the history of the term, what it really means, and its implications for the advancement of conservation biology, natural resource management, veterinary medicine, and animal welfare

    Determination of tidal volume by electrical impedance tomography (EIT) after indirect two-point calibration

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    Objective. A linear relationship between impedance change (ΔZ) measured by thoracic electrical impedance tomography (EIT) and tidal volume (VT) has been demonstrated. This study evaluated the agreement between the displayed VT calculated by the EIT software (VTEIT) and spirometry (VTSPIRO) after an indirect two-point calibration. Approach. The EIT software was programmed to execute a bedside two-point calibration from the subject-specific, linear equation defining the relationship between ΔZ and VTSPIRO and displaying VTEIT breath-by-breath in 20 neutered male, juvenile pigs. After EIT calibration VTs of 8, 12, 16 and 20 ml kg−1 were applied to the lungs. VTEIT and VTSPIRO were recorded and analysed using Bland–Altman plot for multiple subject measurements. Volumetric capnography (VCap) and spirometry data were explored as components of variance using multiple regression. Main results. A mean relative difference (bias) of 0.7% with 95% confidence interval (CI) of −10.4% to 10.7% were found between VTEIT and VTSPIRO for the analysed data set. The variance in VTEIT could not be explained by any of the measured VCap or spirometry variables. Significance. The narrow CI estimated in this study allows the conclusion that EIT and its software can be used to measure and accurately convert ΔZ into mililitre VT at the bedside after applying an indirect two-point calibration

    Phosphorothioate modification improves exon-skipping of antisense oligonucleotides based on sulfonyl phosphoramidates in mdx mouse myotubes

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    2′-O-Methyl (2′-OMe) antisense oligonucleotides (AOs) possessing a various number of 4-(trimethylammonio)butylsulfonyl or tosyl phosphoramidates (N+ and Ts-modifications, respectively) instead of a native phosphodiester linkage were designed to skip exon-23 in dystrophin pre-mRNA transcript in mdx mice myotubes. AOs bearing several zwitterionic N+ modifications in the sequence had remarkably increased thermal stability towards complementary mRNA in comparison with 2′-OMe-RNAs having negatively charged Ts and phosphorothioate (PS) linkages. However, only Ts-modified AOs exhibited a similar level of exon skipping in comparison with fully modified PS-containing 2′-OMe-RNA, whereas the exon skipping induced by N+ modified AOs was much lower with no exon-skipping detected for AOs having seven N+ modifications. The level of exon-skipping was improved once Ts and especially N+ moieties were used in combination with PS-modification, most likely through improved cellular and nuclear uptake of AOs. These results provide new insights on expanding the design of novel chemically modified AOs based on phosphate modifications

    Australian Group on Antimicrobial Resistance (AGAR) Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) Annual Report 2020

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    From 1 January to 31 December 2020, forty-nine institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aims of ASSOP 2020 were to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that were antimicrobial resistant, with particular emphasis on susceptibility to methicillin; and to characterise the molecular epidemiology of the methicillin-resistant isolates. A total of 2,734 SAB episodes were reported, of which 79.7% were community-onset. Of S. aureus isolates, 17.6% were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 14.2%, which was not significantly different from the 13.3% mortality associated with methicillin-susceptible SAB (p = 0.6). With the exception of the β-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However, in addition to the β-lactams, approximately 35% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin, 33% to ciprofloxacin, 13% to tetracycline, 13% to gentamicin and 4% to co-trimoxazole. When applying the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, teicoplanin resistance was detected in four S. aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to two healthcare-associated MRSA (HA-MRSA) clones: ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). The ST22-IV [2B] (EMRSA-15) clone is the predominant HA-MRSA clone in Australia. However, 85% percent of methicillin-resistant SAB isolates were community-associated MRSA (CA-MRSA) clones. Although polyclonal, approximately 77% of CA-MRSA clones were characterised as: ST93-IV [2B] (Queensland CA-MRSA); ST5-IV [2B]; ST45-V [5C2&5]; ST1-IV [2B]; ST30-IV [2B]; ST8-IV [2B]; and ST97-IV [2B]. The CA-MRSA clones, in particular ST45-V [5C2&5], have acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. The multi-resistant ST45-V [5C2&5] clone accounted for 11.0% of CA-MRSA. As CA-MRSA is well established in the Australian community, it is important to monitor antimicrobial resistance patterns in community- and healthcare-associated SAB as this information will guide therapeutic practices in treating S. aureus sepsis

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