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Inverse modeling is a widely used top-down method to infer greenhouse gas (GHG) emissions and their spatial distribution based on atmospheric observations. The errors associated with inverse modeling have multiple sources, such as observations and a-priori emission estimates, but they are often dominated by the transport model error. Here, we utilize the Lagrangian Particle Dispersion Model (LPDM) FLEXPART, driven by the meteorological fields of the regional numerical weather prediction model COSMO. The main source of errors in LPDMs is the turbulence diffusion parameterization and the meteorological fields. The latter are outputs of an Eulerian model. Recently, we introduced an improved parameterization scheme of the turbulence diffusion in FLEXPART, which significantly improves FLEXPART-COSMO simulations at 1 km resolution. We exploit F-gases measurements from two extended field campaigns on the Swiss Plateau (in Beromünster and Sottens) and we conduct both high- (1 km) and low-resolution (7 km) FLEXPART transport simulations that are then used in a Bayesian analytical inversion to estimate spatial emission distributions. Our results for four F-gases (HFC-134a, HFC-125, HFC-32, SF6) indicate that both high-resolution inversions and a dense measurement network significantly improve the ability to estimate the spatial distribution of emissions. Furthermore, the total emission estimates from the high-resolution inversions (351±44 Mg yr−1 for HFC-134a, 101±21 Mg yr−1 for HFC-125, 50±8 Mg yr−1 for HFC-32, 9.0±1.1 Mg yr−1 for SF6) are significantly higher compared to the low-resolution inversions (20–40 % increase) and result in total a-posteriori emission estimates that are closer to national inventory values as reported to the UNFCCC (10–20 % difference between high-resolution inversion estimates and inventory values compared to 30–40 % difference between the low-resolution inversion estimates and inventory values). Specifically, we attribute these improvements to a better representation of the atmospheric flow in complex terrain in the high-resolution model, partly induced by the more realistic topography. We further conduct numerous sensitivity inversions, varying different parameters and variables of our Bayesian inversion framework to explore the whole range of uncertainty in the inversion errors (e.g., inversion grid, spatial distribution of a-priori emissions, covariance parameters like baseline uncertainty and spatial correlation length, temporal resolution of the assimilated observations, observation network, seasonality of emissions). From the above-mentioned parameters, we find that the uncertainty of the mole fraction baseline and the spatial distribution of the a-priori emissions have the largest impact on the a-posteriori total emission estimates and their spatial distribution. This study is a step towards mitigating the errors associated with the transport models and better characterizing the uncertainty inherent in the inversion error. Improvements in the latter will facilitate the validation and standardization of the national GHG emission inventories and support policymakers.

Atmospheric measurements can be used as a tool to evaluate national greenhouse gas inventories through inverse modelling. Using 8 years of continuous methane (CH4) concentration data, this work assesses the United Kingdom's (UK) CH4 emissions over the period 2013–2020. Using two different inversion methods, we find mean emissions of 2.10 ± 0.09 and 2.12 ± 0.26 Tg yr−1 between 2013 and 2020, an overall trend of −0.05 ± 0.01 and −0.06 ± 0.04 Tg yr−2 and a 2 %–3 % decrease each year. This compares with the mean emissions of 2.23 Tg yr−1 and the trend of −0.03 Tg yr−2 (1 % annual decrease) reported in the UK's 2021 inventory between 2013 and 2019. We examine how sensitive these estimates are to various components of the inversion set-up, such as the measurement network configuration, the prior emissions estimate, the inversion method and the atmospheric transport model used. We find the decreasing trend to be due, primarily, to a reduction in emissions from England, which accounts for 70 % of the UK CH4 emissions. Comparisons during 2015 demonstrate consistency when different atmospheric transport models are used to map the relationship between sources and atmospheric observations at the aggregation level of the UK. The posterior annual national means and negative trend are found to be consistent across changes in network configuration. We show, using only two monitoring sites, that the same conclusions on mean UK emissions and negative trend would be reached as using the full six-site network, albeit with larger posterior uncertainties. However, emissions estimates from Scotland fail to converge on the same posterior under different inversion set-ups, highlighting a shortcoming of the current observation network in monitoring all of the UK. Although CH4 emissions in 2020 are estimated to have declined relative to previous years, this decrease is in line with the longer-term emissions trend and is not necessarily a response to national lockdowns.

We present a method to infer spatially and spatio-temporally correlated emissions of greenhouse gases from atmospheric measurements and a chemical transport model. The method allows fast computation of spatial emissions using a hierarchical Bayesian framework as an alternative to Markov chain Monte Carlo algorithms. The spatial emissions follow a Gaussian process with a Matérn correlation structure which can be represented by a Gaussian Markov random field through a stochastic partial differential equation approach. The inference is based on an integrated nested Laplacian approximation (INLA) for hierarchical models with Gaussian latent fields. Combining an autoregressive temporal correlation and the Matérn field provides a full spatio-temporal correlation structure. We first demonstrate the method on a synthetic data example and follow this using a well-studied test case of inferring UK methane emissions from tall tower measurements of atmospheric mole fraction. Results from these two test cases show that this method can accurately estimate regional greenhouse gas emissions, accounting for spatio-temporal uncertainties that have traditionally been neglected in atmospheric inverse modelling.

We present a method to infer spatially and spatiotemporally correlated emissions of greenhouse gases from atmospheric measurements and a chemical transport model. The method allows fast computation of spatial emissions using a hierarchical Bayesian framework as an alternative to Markov chain Monte Carlo algorithms. The spatial emissions follow a Gaussian process with a Matérn correlation structure which can be represented by a Gaussian Markov random field through a stochastic partial differential equation approach. The inference is based on an integrated nested Laplacian approximation (INLA) for hierarchical models with Gaussian latent fields. Combining an autoregressive temporal correlation and the Matérn field provides a full spatiotemporal correlation structure. We first demonstrate the method on a synthetic data example and follow this using a well-studied test case of inferring UK methane emissions from tall tower measurements of atmospheric mole fraction. Results from these two test cases show that this method can accurately estimate regional greenhouse gas emissions, accounting for spatiotemporal uncertainties that have traditionally been neglected in atmospheric inverse modelling.

Metal ions, biologically essential or toxic, are present in the surrounding environment of living organisms. Understanding their uptake, homeostasis or detoxification is critical in cell biology and human health. In this study, we investigated the role of protein kinase CK2 in metal toxicity using gene deletion strains of Saccharomyces cerevisiae against a panel of six metal ions. The deletion of CKA2, the yeast orthologue of mammalian CK2α', leads to a pronounced resistant phenotype against Zn2+ and Al3+, whilst the deletion of CKB1 or CKB2 results in tolerance to Cr6+ and As3+. The individual deletion mutants of CK2 subunits (CKA1, CKA2, CKB1 and CKB2) did not have any benefit against Co2+ and Cd2+. The metal ion content in the treated cells was then measured by inductively coupled plasma mass spectrometry. Two contrasting findings were obtained for the CKA2 deletion mutant (cka2Δ) against Al3+ or Zn2+. Upon exposure to Al3+, cka2Δ had markedly lower Al3+ content than the wild type and other CK2 mutants, congruous to the resistant phenotype of cka2Δ against Al3+, indicating that CKA2 is responsible for Al3+ uptake. Upon zinc exposure the same mutant showed similar Zn2+ content to the wild type and cka1Δ. Strikingly, the selective inhibitor of CK2 TBB (4,5,6,7-tetrabromo-1H-benzotriazole) abolished the resistant phenotype of cka2Δ against Zn2+. Hence, the CK2 subunit CKA1 plays a key role in Zn2+ sequestration of the cell. Given that both zinc and CK2 are implicated in cancer development, the findings herein are of significance to cancer research and anticancer drug development.

This study evaluated the prevention of bone fragility fractures in a representative sample of four Irish general practices. The clinical records of 243 patients potentially at risk of bone fragility were studied. One hundred and fourteen (47%) had a dual energy x-ray absorptiometry (DEXA) scan. Osteoporosis was established in 42 (17%) and osteopaenia in 28 (11%). One hundred and fifty-two (63%) were currently being prescribed bisphosphonates. Thirty-four (22%) of those on bisphosphonates did not have a baseline DEXA scan performed prior to commencing treatment and further analysis did not show a clear rationale for initiation of the treatment in this group of patients. Forty-six (30%) patients on bisphosphonates had been prescribed them for over 5 years without any apparent review to see if they were still indicated. There was no record of any of the practices having carried out a fracture risk score assessment prior to commencing bone fragility treatment. The implications are that bone fragility management warrants urgent review.

Arsenic is omnipresent in soil, air, food and water. Chronic exposure to arsenic is a serious problem to human health. In-depth understanding of this metalloid's toxicity is a fundamental step towards development of arsenic-free foods and measures for bioremediation. By screening the complete set of gene deletion mutants (4873) of Saccharomyces cerevisiae, this study uncovered 75 sensitive and 39 resistant mutants against arsenite [As(III)]. Functional analysis of the corresponding genes revealed the molecular details for its uptake, toxicity and detoxification. On the basis of the hypersensitivity of yap3Δ, the transcription factor, Yap3p, is for the first time linked to the cell's detoxification against As(III). Apart from confirming the previously described role of the mitogen-activated protein kinase (MAPK) Hog1 pathway in combating arsenic toxicity, the results show that the regulatory subunits (Ckb1p and Ckb2p) of protein kinase CK2 are also involved in the process, suggesting possible crosstalk between the two key protein kinases. The sensitivity to As(III) conferred by deletion of the genes involved in protein degradation and chromatin remodelling demonstrates protein damage is the key mode of toxicity for the metalloid. Furthermore, the resistant phenotype of fps1Δ, snf3Δ and pho81Δ against As(III) links arsenic uptake with the corresponding plasma membrane-bound transporters-aquaglyceroporin (Fps1p), hexose (Snf3p) and phosphate transporters. The molecular details obtained in this screen for As(III) uptake, detoxification and toxicity provide the basis for future investigations into arsenic-related problems in the environment, agriculture and human health.

Biological age is a better measure of functional capacity than chronological age.1 One of the measures of biological age is telomere length. Telomeres are nucleoprotein complexes that protect chromosome ends from damage. The DNA component of telomeres progressively shortens as biological age increases and thus acts as a read out for ‘miles on the biological clock’. 2 Telomere length progressively shortens as biological age increases. Within health care, ageing is almost exclusively described in terms of chronological age. Recent studies explored using biological age to stratify patients and predict outcomes.3 This project acts as a pilot study to investigate whether biological age is related to intensive care unit (ICU) outcomes and whether ICU patients age biologically at an accelerated rate. This project used blood samples from a previous study where patients underwent cardiac surgery and were admitted to the ICU. Blood samples were obtained before surgery and on days 1, 2, and 3 after surgery. The database contained the following physiological parameters: haemoglobin, urea, creatinine, RIFLE score, length of ICU stay, and whether renal replacement therapy was required. Information on co-morbidities and medication was also provided. DNA was isolated using a Maxwell machine and telomere length determined via quantitative PCR. One hundred and fifty-five blood samples from 46 patients underwent analysis. Telomere length did not differ significantly over the 4 days (P=0.662). No relationship was found between telomere length and any physiological parameter, co-morbidity, or medication. There was a trend towards significance with RIFLE score at day 3 increasing as telomere length decreased, although this was not statistically significant (P=0.09). No relationship between telomere length and the available physiological parameters, comorbidities, or medication was found. Telomere length did not vary during ICU stay. This study was limited by its small sample size. Future studies would benefit from a larger sample size; in addition, blood samples could also be obtained at 6 months after discharge to allow gradual alterations in biological age to be determined. Recent studies give evidence that telomere length is a weak biomarker of ageing,3 and that more meaningful data might be obtained using superior markers, such as CDKN2A expression or expression levels of non-coding RNAs.3

The performance of metal oxides such as titanium dioxide (TiO2), in the conversion of solar energy into chemical energy, is determined by semiconducting properties. The conversion process is closely related to the light-induced reactivity between oxide semiconductors and water, which may lead to partial water oxidation and consequently water disinfection. Key performance-related properties are considered here, including light absorption, light-induced ionisation over the band gap, charge separation, charge transport, charge transfer, and the chemical reactions taking place at anodic and cathodic sites. Optimisation of these interconnected performance-related properties is discussed, along with the photocatalytic application in water disinfection.

Eukaryotic microorganisms are constantly challenged by reactive oxygen species derived endogenously or encountered in their environment. Such adversity is particularly applied to Saccharomyces cerevisiae under harsh industrial conditions. One of the major oxidants to challenge S. cerevisiae is linoleic acid hydroperoxide (LoaOOH). This study, which used genome-wide microarray analysis in conjunction with deletion mutant screening, uncovered the molecular pathways of S. cerevisiae that were altered by an arresting concentration of LoaOOH (75 μM). The oxidative stress response, iron homeostasis, detoxification through PDR transport and direct lipid β-oxidation were evident through the induction of the genes encoding for peroxiredoxins (GPX2, TSA2), the NADPH:oxidoreductase (OYE3), iron uptake (FIT2, ARN2, FET3), PDR transporters (PDR5, PDR15, SNQ2) and β-oxidation machinery (FAA2, POX1). Further, we discovered that Gpx3p, the dual redox sensor and peroxidase, is required for protection against LoaOOH, indicated by the sensitivity of gpx3Δ to a mild dose of LoaOOH (37.5 μM). Deletion of GPX3 conferred a greater sensitivity to LoaOOH than the loss of its signalling partner YAP1. Deletion of either of the iron homeostasis regulators AFT1 or AFT2 also resulted in sensitivity to LoaOOH. These novel findings for Gpx3p, Aft1p and Aft2p point to their distinct roles in response to the lipid peroxide. Finally, the expression of 89 previously uncharacterised genes was significantly altered against LoaOOH, which will contribute to their eventual annotation.

Chromium toxicity is increasingly relevant to living organisms such as humans, due to the environmental contamination of chromium and the application of stainless steel-based medical devices like hip prostheses. Despite the investigations in past years, the molecular details for chromium toxicity remain to be delineated. In this study, we seek to gain insights into the molecular aspects of chromium toxicity by screening a genome-wide deletion set of individual genes in Saccharomyces cerevisiae against hexavalent chromium [Cr(vi)] using chromium trioxide. From the primary data collected in this study, two lists of deletion mutants in response to Cr(vi) exposure were obtained, one for the sensitive phenotype and the other for the resistant phenotype. The functional analysis of the genes corresponding to the sensitive mutants reveals the key features of Cr(vi) toxicity, which include genotoxicity, protein damage, disruption of energy and sulfur metabolisms. DNA repair, ubiquitination-mediated protein degradation, iron homeostasis and growth attenuation are the intrinsic facets of the cell's detoxification mechanisms. Protein kinase CK2 is, for the first time, found to be involved in regulating chromium toxicity by reducing the uptake of Cr(vi). Taken together, the findings provide meaningful details into the basic understanding of chromium toxicity in terms of its uptake, modes of action, cellular detoxification and molecular regulatory mechanisms.

Following our previous finding that the sulfhydryl-oxidising chemical diamide induced a marked elevation of cellular Al(3+) (Wu et al., Int J Mol Sci, 12:8119-8132, 2011), a further investigation into the underlying molecular mechanism was carried out, using the eukaryotic model organism Saccharomyces cerevisiae. The effects of non-toxic dose of diamide (0.8 mM) and a mild dose of aluminium sulphate (Al(3+)) (0.4 mM) were determined prior to the screening of gene deletion mutants. A total of 81 deletion mutants were selected for this study according to the available screening data against Al(3+) only (Kakimoto et al., BioMetals, 18: 467-474, 2005) and diamide only (Thorpe et al., Proc Natl Acad Sci USA, 101: 6564-6569, 2004). On the basis of our screening data and the cluster analysis, a cluster containing the gene deletions (rpe1∆, sec72∆, pdr5∆ and ric1∆) was found to be specifically sensitive to the mixture of diamide and Al(3+). However gnp1∆, mch5∆ and ccc1∆ mutants were resistant. Dithiothreitol (DTT) and ascorbate markedly reversed the diamide-induced Al(3+) toxicity. Inductively-coupled plasma optical emission spectrometry demonstrated that DTT reduced the intracellular Al(3+) content in diamide/Al(3+)-treated yeast cells six-fold compared to the non-DTT controls. These data together revealed that the pleiotropic drug resistance transporter (Pdr5p) and vacuolar/vesicular transport-related proteins (Ric1p and Sec72p) are the targets of diamide. A dysfunctional membrane-bound Pdr5p terminates the detoxification pathway for Al(3+) at the final step, leading to intracellular Al(3+) accumulation and hence toxicity. As Al(3+) toxicity has been a problem in agriculture and human health, this study has provided a significant step forward in understanding Al(3+) toxicity.

Elemental uptake and export of the cell are tightly regulated thereby maintaining the ionomic homeostasis. This equilibrium can be disrupted upon exposure to exogenous reactive oxygen species (ROS), leading to reduction or elevation of the intracellular metal ions. In this study, the ionomic composition in the eukaryotic model organism Saccharomyces cerevisiae was profiled using the inductively-coupled plasma optical emission spectrometer (ICP-OES) following the treatment with individual ROS, including hydrogen peroxide, cumen hydroperoxide, linoleic acid hydroperoxide (LAH), the superoxide-generating agent menadione, the thiol-oxidising agent diamide [diazine-dicarboxylic acid-bis(dimethylamide)], dimedone and peroxynitrite. The findings demonstrated that different ROS resulted in distinct changes in cellular metal ions. Aluminium (Al(3+)) level rose up to 50-fold after the diamide treatment. Cellular potassium (K(+)) in LAH-treated cells was 26-fold less compared to the non-treated controls. The diamide-induced Al(3+) accumulation was further validated by the enhanced Al(3+) uptake along the time course and diamide doses. Pre-incubation of yeast with individual elements including iron, copper, manganese and magnesium failed to block diamide-induced Al(3+) uptake, suggesting Al(3+)-specific transporters could be involved in Al(3+) uptake. Furthermore, LAH-induced potassium depletion was validated by a rescue experiment in which addition of potassium increased yeast growth in LAH-containing media by 26% compared to LAH alone. Taken together, the data, for the first time, demonstrated the linkage between ionomic profiles and individual oxidative conditions.

This report describes a biological screening system to measure the antioxidant capacity of compounds using the oxidant-induced growth arrest response of Saccharomyces cerevisiae. Alternative methods using the nonphysiological free radical compounds such as diphenylpicrylhydrazyl and azinobis ethylbenzothiaziline-6-sulphonate (ABTS) only provide an indication of the ability of a compound to scavenge oxidants. In contrast, this yeast-based method can also measure the ability of a compound to induce cellular resistance to the damaging effects of oxidants. The screening assay was established against a panel of six physiologically relevant oxidants ranging from reactive oxygen species (hydrogen peroxide, cumene peroxide, linoleic acid hydroperoxide), to a superoxide-generating agent (menadione), reactive nitrogen species (peroxynitrite) and a thiol-oxidizing agent (diamide). The antioxidants ascorbate and gallic acid displayed scavenging activity and induced the resistance of cells against a broad range of oxidants using this assay. Lipoic acid, which showed no scavenging activity and thus would not be detected as an antioxidant using a nonphysiological screen was, however, identified in this assay as providing resistance to cells against a range of oxidants. This assay is high throughput, in the format of a 96-well microtitre plate, and will greatly facilitate the search for effective antioxidants.

No current neuroimaging modality offers mechanistic or prognostic information to guide management in paediatric dystonia. We assessed F-fluorodeoxyglucose (¹⁸F-FDG) PET/computed tomography (CT) brain imaging in childhood primary dystonia (PDS) and neurodegeneration with brain iron accumulation (NBIA) to determine whether it would identify altered metabolism and hence constitute a potentially useful 'biomarker' indicating functional disturbances associated with dystonia and severity of the disease.A total of 27 children (15 PDS and 12 NBIA) underwent brain ¹⁸F-FDG PET/CT imaging under anaesthesia during acquisition. The images were assessed visually and the two groups were compared quantitatively with statistical parametric mapping. PET/CT images were spatially transformed to Montreal Neurological Institute standard space. Voxelwise ¹⁸F-FDG uptake was normalized to whole-brain uptake. Data of both groups were correlated separately with duration and severity of dystonia as assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).Visual inspection did not identify any abnormalities in ¹⁸F-FDG uptake within the cerebral cortex, basal ganglia, or thalami in either group. Quantitative analysis identified higher uptake in the posterior cingulate and bilateral posterior putamina but decreased uptake in the occipital cortex and cerebellum in NBIA compared with PDS. The NBIA group had more severe dystonia scores compared with the PDS group. BFMDRS was negatively correlated with age but not with duration of dystonia.Compared with PDS, NBIA is dominated by relative overactivity in the putamen and by cerebellar underactivity, patterns that may reflect the increased severity of dystonia in NBIA cases. Hence, there is a potential role for ¹⁸F-FDG PET/CT imaging in paediatric dystonia, particularly in the NBIA group.

Amino acid biosynthesis forms part of an integrated stress response against oxidants in Saccharomyces cerevisiae and higher eukaryotes. Here we show an essential protective role of the l-lysine biosynthesis pathway in response to the oxidative stress condition induced by the lipid oxidant-linoleic acid hydroperoxide (LoaOOH), by means of transcriptomic profiling and phenotypic analysis, and using the deletion mutant dal80∆ and lysine auxotroph lys1∆. A comprehensive up-regulation of lysine biosynthetic genes (LYS1, LYS2, LYS4, LYS9, LYS12, LYS20 and LYS21) was revealed in dal80Δ following the oxidant challenge. The lysine auxotroph (lys1∆) exhibited a significant decrease in growth compared with that of BY4743 upon exposure to LoaOOH, albeit with the sufficient provision of lysine in the medium. Furthermore, the growth of wild type BY4743 exposed to LoaOOH was also greatly reduced in lysine-deficient conditions, despite a full complement of lysine biosynthetic genes. Amino acid analysis of LoaOOH-treated yeast showed that the level of cellular lysine remained unchanged throughout oxidant challenge, suggesting that the induced lysine biosynthesis leads to a steady-state metabolism as compared to the untreated yeast cells. Together, these findings demonstrate that lysine availability and its biosynthesis pathway play an important role in protecting the cell from lipid peroxide-induced oxidative stress, which is directly related to understanding environmental stress and industrial yeast management in brewing, wine making and baking.

HOM6 is a major gene in the aspartate pathway which leads to biosynthesis of threonine and methionine. The phenotypes of the gene deletion mutant (hom6∆) in a variety of cultural conditions have previously provided meaningful insights into the biological roles of HOM6 and its upstream intermediate metabolites. Here, we conducted a survey on a spectrum of metal ions for their effect on the aspartate pathway and broader sulphur metabolism. We show that manganese (Mn2+) promoted the growth of hom6∆ under both anaerobic and aerobic conditions. Unexpectedly, 4 mmol l−1 hydrogen peroxide (H2O2), a dose normally causing temporary cell growth arrest, enhanced the growth of hom6∆ under the anaerobic condition only, while it had no effect on the wild type strain BY4743. We propose that Mn2+ and H2O2 promote the growth of hom6∆ by reducing the accumulation of the toxic intermediate metabolite—aspartate β-semialdehyde, via directing the aspartate pathway to the central sugar metabolism–tricarboxylic acid cycle. Significance and Impact of the Study This study focuses on the yeast strain which lacks homoserine dehydrogenase encoded by HOM6 gene in aspartate metabolism. The HOM6-deletion mutant (hom6Δ) was analysed in the context of varying environmental parameters such as metal ions and oxidants, under anaerobic and aerobic conditions. We demonstrated that both manganese and hydrogen peroxide can promote the growth of hom6Δ, with the latter exerting such effect only under anaerobic condition. The findings are relevant to the research areas of ageing and anti-fungal drug development. It highlights the importance of interactions between gene expression and environmental factors as well as culture conditions.

A common problem encountered in clinical medicine is the classification of a lung lesion (nodule/opacity) on conventional imaging. Often attempts at biopsy are unsuccessful or are falsely reassuring, and the decision to send the patient for more invasive and potentially morbid procedures can be difficult. Our aim was to investigate the role of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in helping to identify more accurately those patients with malignant lesions. Sixty-three patients underwent FDG-PET scans following unsuccessful biopsy of a lung lesion or, in a lesser number of cases, when an attempt at biopsy was considered too dangerous. Follow-up was by histology or, if this was unavailable, by clinical progress to death or a minimum of 18 months post scan. Visual and quantitative analysis was performed. On visual analysis, positive and negative predictive values were 90% and 100%, respectively. On quantitative (SUV2.5) analysis, positive and negative predictive values were 90% and 85%, respectively. We interpret these results as showing that the use of FDG-PET scans in patients in this circumstance is non-invasive and highly sensitive in diagnosing malignancy. The high positive predictive value suggests that those with a positive scan must undergo further investigation, while the 100% negative predictive value means those with no FDG uptake can safely be spared further invasive investigations

We performed a retrospective analysis to evaluate the ability of whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG PET) to identify local recurrence and pulmonary metastases in patients with soft-tissue tumours after treatment. We compared the results of FDG PET with those of MRI for the detection of local recurrence, and with CT of the chest for pulmonary metastases. We assessed 62 patients of mean age 51 years, who had 15 types of soft-tissue sarcoma, after a mean follow-up of 3 years 2 months. For the detection of local disease, 71 comparisons showed that the sensitivity and specificity of FDG PET were 73.7% and 94.3%, respectively; there were 14 true-positive and five false-negative results. MRI had a sensitivity and specificity of 88.2% and 96.0% respectively. For the identification of lung metastases, 70 comparisons showed that the sensitivity and specificity of FDG PET were 86.7% and 100%, with 13 true-positive results and two false-negative results. CT of the chest had a sensitivity and specificity of 100% and 96.4%. Thirteen other sites of metastases were identified by FDG PET. FDG PET can identify both local and distant recurrence of tumour as a one-step procedure and will detect other metastases. It seems that all three methods of imaging are needed to define accurately the extent of disease, both at initial staging and during follow-up.

Objectif : Etudier les hospitalisations chez les autochtones et les non-autochtones pour des soins psychiatriques aigus dans le nord-ouest de l'Ontario, en 1992. Methode : Reprendre en 1992 une etude qui a eu lieu en 1986-1987 visant a comparer les hospitalisations chez les autochtones et les non-autochtones pour des soins psychiatriques aigus dans le nord-ouest de l'Ontario et examiner les inscriptions des autochtones aupres des organismes de sante mentale communautaires au cours des 6 premiers mois de 1993. Resultats : L'analyse comparative des hospitalisations a revele les suivantes : le nombre d'autochtones hospitalises depasse de 33 % le taux moyen de la population generale ; la depression semble sous-diagnostiquee chez les autochtones ; ceux-ci continuent d'etre hospitalises principalement pour des raisons autres que des troubles psychiatriques graves ; la toxicomanie et les problemes avec la loi ont souvent un role a jouer ; leur sejour a l'hopital est 2 fois plus long que celui du groupe temoin de non-autochtones ; ils sont souvent issus de milieux ruraux ; ils sont moins souvent pris en main par un service aux malades externes et plus souvent par le systeme de justice criminel. L'examen des inscriptions aupres des organismes de sante mentale communautaires a revele les suivantes : une surrepresentation similaire des autochtones ; les troubles de l'humeur et les perturbations de la pensee des autochtones de ce secteur etaient semblables a ceux des non-autochtones ; et la longueur de leur sejour etait semblable. L'hopital psychiatrique semble offrir un traitement de soins aigus non pas pour des troubles psychiatriques graves (ce qui constitue son mandat), mais pour les hospitalisations atypiques qui resultent de problemes economiques, sociaux et culturels. On soupconne un sous-diagnostic de la depression atypique chez la population autochtone hospitalisee. Lorsqu'on pose des questions sur l'origine du traitement, on apprend que le profil de diagnostic des autochtones et des non-autochtones est identique en ce qui a trait aux aspects humeur et pensee. Conclusion : Il n 'y a pas eu de changements considerables au cours de 5 dernieres annees quant au recours aux services psychiatriques hospitaliers chez les autochtones. Il se peut que les stereotypes culturels influencent le diagnostic des autochtones de facon negative. L'amelioration des programmes de controle de traitement chez les autochtones ainsi que le developpement communautaire peuvent resoudre en partie le probleme. Le redressement des mandats et des responsabilites des organismes communautaires (generiques et specifiques a une culture) permettra de reduire le nombre d'hospitalisations inutiles.

An automated gas chromatograph/mass spectrometer is described for the routine field monitoring of the CFC replacement compounds, the hydrofluorocarbons (HFCs) and hydrochlorofluorocarbons (HCFCs). Detection limits of 0.5 pptv are achieved by concentration of a 2-L air sample onto a three-stage adsorbent-filled microtrap. The microtrap is cooled to subambient temperatures (-50 o C) using Peltier thermoelectric devices, without a postdesorption cryofocussing step, thereby eliminating the need for liquid cryogens. The enriched air sample is thermally desorbed by direct ohmic heating of the microtrap, and compounds are separated on a 100-m, 5-μm-thick film high-resolution capillary column. Individual hydrohalocarbons are determined by selected ion masses for quantitation. The instrument is designed to operate automatically at a remote atmospheric research station providing ∼2-h replicate air and calibration analyses

This report describes a biological screening system to measure the antioxidant capacity of compounds using the oxidant-induced growth arrest response of Saccharomyces cerevisiae. Alternative methods using the nonphysiological free radical compounds such as diphenylpicrylhydrazyl and azinobis ethylbenzothiaziline-6-sulphonate (ABTS) only provide an indication of the ability of a compound to scavenge oxidants. In contrast, this yeast-based method can also measure the ability of a compound to induce cellular resistance to the damaging effects of oxidants. The screening assay was established against a panel of six physiologically relevant oxidants ranging from reactive oxygen species (hydrogen peroxide, cumene peroxide, linoleic acid hydroperoxide), to a superoxide-generating agent (menadione), reactive nitrogen species (peroxynitrite) and a thiol-oxidizing agent (diamide). The antioxidants ascorbate and gallic acid displayed scavenging activity and induced the resistance of cells against a broad range of oxidants using this assay. Lipoic acid, which showed no scavenging activity and thus would not be detected as an antioxidant using a nonphysiological screen was, however, identified in this assay as providing resistance to cells against a range of oxidants. This assay is high throughput, in the format of a 96-well microtitre plate, and will greatly facilitate the search for effective antioxidants.

A common cause of morbidity and mortality in diabetic patients are foot infection/complications often leading to amputation of lower extremities. Various radiological and radionuclide techniques are available for the assessment of diabetic patients with bone or soft tissue infections. However, there are several advantages and limitations. The major limitation of all these techniques is their inability to accurately differentiate osteomyelitis from charcot's/neuropathic joints. Radiologically, magnetic resonance imaging (MRI) is the technique of choice and a radiolobeled white cell scan is a useful nuclear medicine technique in the evaluation of diabetic patients with suspected foot infection. In this review we discuss the efficacy of radiological and radionuclide techniques in the assessment of diabetic foot infection.

Aerosolised pentamidine 300 mg in 5 or 6 ml solution was administered via 8 different nebuliser systems to 12 patients with acquired immunodeficiency syndrome. Using 99mTc human serum albumin as an indirect marker for pentamidine, pulmonary, extrapulmonary (gastric and oropharyngeal) and alveolar deposition of pentamidine were measured using a gamma camera. Side effects (visual analogue scales) and changes in lung function associated with each treatment were also quantified. Deposition was completed more rapidly with the ultrasonic than the jet nebulisers. Mean total pulmonary depositions (mg +/- SEM) were Respirgard II, 6.1 +/- 0.5; Centimist, 7.3 +/- 1.0, System 22 Mizer, 14.3 +/- 2.1; System 22 Mizer with particle separator; 4.5 +/- 0.4; System 22 Mizer with Optimist 2, 6.3 +/- 0.9; Fisoneb, 6.0 +/- 1.2; Pentasonic (Portasonic); 4.6 +/- 0.9; Samsonic, 2.9 +/- 0.4. Differences between the nebulisers for peripheral lung and alveolar deposition reflected this pattern. Side effects scores were largest with System 22 Mizer, Pentasonic (Portasonic), and Fisoneb, and these produced the greatest oropharyngeal and gastric deposition. The largest reductions in lung function were associated with System 22 Mizer. A 300 mg dose of pentamidine nebulised via Respirgard II is known to be effective prophylaxis for Pneumocystis carinii pneumonia when given once monthly. Our results show that equivalent pulmonary deposition can be produced by other nebulisers. System 22 Mizer gives over twice the deposition associated with Respirgard II, and used with a pentamidine dose of 150 mg is likely to produce an adequate lung dose for prophylaxis. This nebuliser, however, is associated with more marked side effects.

Neuroendocrine tumours (NETs) are a rare type of tumour that can range from well differentiated slow growing tumours to poorly differentiated aggressive tumours. NETs can arise in different parts of the body. Patients often present with a large spectrum of clinical syndromes, which depend on the presence of hormones secreted by the tumour type or by a mass effect. Several imaging modalities are used in the diagnosis of NETs. Radionuclide imaging plays an important role in diagnosis, staging and treatment of these tumours. Several radiopharmaceuticals are used to image NETs and are based on different cellular uptake mechanisms. This review will focus on the functional imaging of NETs using single photon emission computed tomography and positron emission tomography radiopharmaceuticals.

Australia's rapidly aging population has a high prevalence of chronic disease and disability, leading to an increased social and economic burden. The Enhanced Primary Care program seeks to reduce this burden by promoting preventive and coordinated care. This study aimed to identify unmet needs in community dwelling general practice patients aged 75 years and over through annual health assessments performed by a general practitioner-nurse team.Community dwelling patients of a large suburban general practice aged 75 years and over were invited to participate. Five hundred and forty-six consecutive, eligible patients were recruited. Data were collected by GP-nurse teams on physical and psychosocial variables using a combination of physical examination, self reporting, and rating scales.Fifty percent of the women and 25% of the men lived alone. Over 90% of participants reported one or more health problems, with musculoskeletal issues being most common. Men rated their health more poorly than women. Incontinence affected one-third of patients, mainly women. Women reported more psychological distress. There were age and gender differences in activities of daily living (ADL). Mobility, ADL, visual impairment, bowel problems, use of sleep medications and psychological wellbeing were strongly associated to self reported health.Health assessments were effective in identifying significant physical and psychosocial problems in older adults. The importance of such assessments is underscored by strong associations between various domains and perceived general health. Collaboration between a GP and a practice based community nurse represents a potential solution to identifying (and responding to) unmet physical and psychosocial needs to improve quality of life in community dwelling older adults.

Empathie wird sowohl als individuelle Charaktereigenschaft als auch als beeinflussbarer Zustand beschrieben. Preis und Kroner-Herwig untersuchten, inwieweit verschiedene kontrollierbare Faktoren die Empathie von Probanden beeinflussten, die das Schmerzerleben einer anderen Person beurteilen mussten.

The Sunna dosimeter was introduced for dose determination in the dose range of 50–300 kGy by measuring optically stimulated luminescence. The usefulness of the dosimeter film has already been shown in food irradiation for routine process control. The aim of the present study was to check the performance of the Sunna dosimeter film for process control in radiation sterilization under industrial processing conditions, i.e. at high activity gamma irradiators and at high energy electron beam facilities. To ensure similar irradiation conditions during calibration and routine irradiation “in-plant calibration” was performed by irradiating the Sunna dosimeters together with ethanol–monochlorobenzene transfer standard and alanine reference standard dosimeters. The Sunna dosimeters were then irradiated together with the routine dosimeter of the actual plant during regular production runs and the absorbed doses measured by the different dosimeters agreed within ±2%(1 σ ).

International audience; The results of a field campaign carried out from early spring through to the late summer of 2000, in Bristol, England, are presented. Continuous measurements of over 40 hydrocarbons have been made at an urban background site, located at Bristol University, for approximately nine months using a Gas Chromatography - Flame Ionisation Detection (GC-FID) system and for a selection of halocarbons for approximately one month using a Gas Chromatography - Electron Capture Detection (GC-ECD) system. In this paper we present the time-series of the nine halocarbons and selected hydrocarbons. Daytime and night-time hydroxyl radical concentrations have been estimated based on the diurnal variations of a selection of the measured hydrocarbons. The average summer daytime concentration of OH was found to be 2.5x106 molecules cm-3 and the night-time concentration to be in the range 104 to 105 molecules cm-3. In addition, the role played by certain VOCs in the formation of ozone is assessed using the POCP (Photochemical Ozone Creation Potential) concept.

The results of a field campaign carried out from early spring through to the late summer of 2000, in Bristol, England, are presented. Continuous measurements of over 40 hydrocarbons have been made at an urban background site, located at Bristol University, for approximately nine months using a GC-FID system and for a selection of halocarbons for approximately one month using a GC-ECD system. In this paper we present the time-series of the nine halocarbons and selected hydrocarbons. Daytime and night-time hydroxyl radical concentrations have been estimated based on the diurnal variations of a selection of the measured hydrocarbons. The average summer daytime concentration of OH was found to be 2.5×106 molecules cm?3 and the night-time concentration to be in the range 104 to 105 molecules cm?3. In addition, the role played by certain VOCs in the formation of ozone is assessed using the POCP (Photochemical Ozone Creation Potential) concept.

Genome-wide screening using gene deletion mutants has been widely carried out with numerous toxicants including oxidants and metal ions. The focus of such studies usually centres on identifying sensitive phenotypes against a given toxicant. Here, we screened the complete collection of yeast gene deletion mutants (5047) with increasing concentrations of aluminium sulphate (0.4, 0.8, 1.6 and 3.2 mM) in order to discover aluminium (Al(3+)) tolerant phenotypes. Fifteen genes were found to be associated with Al(3+) transport because their deletion mutants exhibited Al(3+) tolerance, including lem3Δ, hal5Δ and cka2Δ. Deletion of CKA2, a catalytic subunit of tetrameric protein kinase CK2, gives rise to the most pronounced resistance to Al(3+) by showing significantly higher growth compared to the wild type. Functional analysis revealed that both molecular regulation and endocytosis are involved in Al(3+) transport for yeast. Further investigations were extended to all the four subunits of CK2 (CKA1, CKA2, CKB1 and CKB2) and the other 14 identified mutants under a spectrum of metal ions, including Al(3+), Zn(2+), Mn(2+), Fe(2+), Fe(3+), Co(3+), Ga(3+), Cd(2+), In(3+), Ni(2+) and Cu(2+), as well as hydrogen peroxide and diamide, in order to unravel cross-tolerance amongst metal ions and the effect of the oxidants. Finally, the implication of the findings in Al(3+) transport for the other species like plants and humans is discussed.

Testicular cancer is a rare tumour with the potential for cure at diagnosis. It is important, however, to identify those patients with metastases at presentation so as to ensure that the optimum treatment strategy is employed. Many criteria have been used to try to place patients into high- or low-risk groups, with variable success. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management. Here we report on a retrospective study of the use of FDG-PET in the detection of metastatic testicular carcinoma at diagnosis. Thirty-one patients [13 with seminoma and 18 with non-seminomatous germ cell tumours (13 teratomas, 5 mixed)] were staged by FDG-PET scanning. The imaging was performed using a Siemens ECAT 951 scanner. All results were assessed on the basis of histology or clinical follow-up. FDG-PET scan identified metastatic disease in ten and was negative in 16; there were no false-positives and five false-negatives. There were six patients in whom FDG-PET was negative and computed tomography was regarded as suspicious but follow-up was inconclusive. The positive predictive value was 100%. The negative predictive value was 76% or 91%, depending on whether the aforementioned six cases were regarded as true-negatives or false-negatives. It may be concluded that FDG-PET is capable of detecting metastatic disease at diagnosis that is not identified by other imaging techniques. These preliminary results are sufficient to suggest that a large prospective study should be performed to evaluate the role of FDG-PET in primary staging of disease.

Increasingly hospitals are showing an interest in developing their imaging services to include positron emission tomography (PET). There is therefore a need to be aware of the radiation doses to critical groups. To assess the effective whole-body dose received by technologists within our dedicated PET centre, each staff member was issued with a dose rate meter, and was instructed to record the time spent in contact with any radioactive source, the dose received per working day and the daily injected activity. On average each technologist administered 831 MBq per day. The mean whole-body dose per MBq injected was 0.02 microSv/MBq(-1). The average time of close contact (2.0 m) with a radioactive source per day was 32 min. The average effective dose per minute close contact was 0.5 microSv/min(-1), which resulted in a mean daily effective dose of 14.4 microSv. No technologist received greater than 60 microSv (the current UK limit for non-classified workers) in any one day, and in general doses received were less than 24 microSv, the daily dose corresponding to the proposed new annual limit for non-classified workers of 6.0 mSv per annum. However, we recognise that the layout of nuclear medicine departments will not mirror our own. We therefore measured the instantaneous dose rates at 0.1, 0.5, 1.0 and 2.0 m from the mid-thorax on 115 patients immediately after injection, to provide estimates of the likely effective doses that might be received by technologists operating dual-headed coincidence detection systems, and others coming into contact in the waiting room with patients who have been injected with fluorine-18 fluorodeoxyglucose. The mean (95th percentile) dose rates measured at the four aforementioned distances were 391.7 (549.5), 127.0 (199.8), 45.3 (70.0) and 17.1 (30.0) microSv/h(-1), respectively. A number of situations have been modelled showing that, with correct planning, FDG studies should not significantly increase the effective doses to technologists. However, one possible area of concern is that, depending on the number of patients in a waiting area at any one time, accompanying persons may approach the limits set by the new UK IRR 1999 regulations for members of the public.

We have undertaken a retrospective analysis of all positron emission tomography (PET) scans carried out at St Thomas' Hospital, London, since 1994 to establish the sensitivity and specificity of this radiologic technique in cutaneous malignant melanoma. In particular, we have identified those patients with primary cutaneous malignant melanoma in whom PET scanning revealed in-transit or regional spread to nodes and those patients with known regional spread in whom PET scanning revealed distant metastases. We defined our false-negative results as a negative scan result with positive histology or subsequent clinical progression of disease. False-positive results were defined as a suspect scan with negative histology or no subsequent progression of disease. PET scanning had an overall sensitivity of 78% and specificity of 87%; however, subset analysis (M. D. Anderson staging system) showed a sensitivity of 50% for stage I disease (34 patients and 35 scans) and 33% for stage II disease (9 patients and 9 scans) with specificities of 87% and 100%, respectively. For stage III disease (16 patients and 17 scans), PET showed a sensitivity of 93% and specificity of 50%. Overall, 35% of patients with true-positive scans had their disease restaged. We can conclude therefore that PET is valuable as a staging procedure in patients with known regional spread but is suboptimal in the prediction of outcome in stage I or stage II disease.

The problem of residual masses on post-treatment CT scans is a continuing dilemma for the oncologist treating malignant lymphomas. These masses may contain active disease or represent only necrotic tumour which continues to shrink without further treatment or post-treatment fibrosis which remains stable on continued follow-up. 18-FDG-PET offers a novel metabolic imaging modality, which can differentiate malignant from benign tissue on the basis of increased glycolytic activity.Thirty-two patients (15 with Hodgkin's disease (HD) and 17 with aggressive histology non-Hodgkin's lymphoma (NHL)) who had residual masses on their post-treatment CT scans underwent 18-FDG-PET. The post-treatment CT and PET scans were compared and the accuracy of the 18-FDG-PET in assessing residual masses was evaluated using clinical and pathological follow-up data.Nine patients had positive post-treatment 18-FDG-PET, eight (89%) of whom have relapsed. Twenty-three patients had negative post-treatment PET with only two relapses in this group. The 2 patients who relapsed had aggressive NHL while none of the 11 HD patients with negative PET relapsed. The median follow-up of patients in continued complete remission is 38 months.18-FDG-PET can differentiate between residual masses containing viable lymphoma where further treatment will be required to achieve cure and those representing ablated disease, where unnecessary treatment and additional morbidity may be avoided.