987 resultados para rearranged (4 -> 2)-abeo-clerodane


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While dehydration is common in older patients and is associated with poor outcomes, it has been infrequently studied in the hospital setting. Thus, the aim of this study was to identify potential barriers and enablers to the maintenance of adequate hydration in older patients in an acute hospital environment. An observational study, involving patients aged 60 years and older admitted to an acute care hospital in Queensland, Australia, was undertaken. Forty-four patients were observed during mealtimes, and chart and room audits were performed to identify hydration management strategies, weight records and the presence or absence of fluid balance charts. Results revealed a number of system and practice-related barriers including patient difficulties with opening fluid containers and low levels of documentation of hydration management strategies. Addressing these issues is an important first step towards improving the management of hydration in medically ill older hospital patients.

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Hydrogenation of someα, β-unsaturated carbonyl compounds using potassium pentacyanocobaltate (II), K3Co(CN)5, as a homogeneous catalyst has been investigated. Thus, hydrogenation of 1-carvone (I), mesityl oxide (4), 2-cyclohexenone (8) and benzalacetone (6) afforded the corresponding dihydrocompounds. Hydrogenation ofβ-ionone (10) afforded a mixture of theα, β-dihydrocompounds (14) and (15). In all these cases, it was observed that the reaction proceeded to completion only in the presence of added base. Hydrogenation of 5α-androst-l-en-17β-ol-3-one acetate (19) afforded the saturated compound, 5α-androst-17β-ol-3-one (20) in 60% yield. It was found that other steroid enones and dienones were not reduced by this catalyst system.

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This thesis is a collection of three essays on Bangladeshi microcredit. One of the essays examines the effect of microcredit on the cost of crime. The other two analyze the functioning mechanism of microcredit programs, i.e. credit allocation rules and credit recovery policy. In Essay 1, the demand for microcredit and its allocation rules is studied. Microcredit is claimed to be the most effective means of supplying credit to the poorest of the poor in rural Bangladesh. This fact has not yet been examined among households who demand microcredit. The results of this essay show that educated households are more likely to demand microcredit and its demand does not differ by sex. The results also show that microcredit programs follow different credit allocation rules for male and female applicants. Education is an essential characteristic for both sexes that credit programs consider in allocating credit. In Essay 2, the focus is to establish a link between microcredit and the incidence of rural crime in Bangladesh. The basic hypothesis is that microcredit programs jointly hold the group responsibility which provides an incentive for group members to protect each other from criminal gang in order to safeguard their own economic interests. The key finding of this essay is that the average cost of crime for non-borrowers is higher than that for borrowers. In particular, 10% increase in the credit reduces the costs of crime by 4.2%. The third essay analyzes the reasons of high repayment rate amid Bangladeshi microcredit programs. The existing literature argues that credit applicants are able to screen out the high risk applicants in the group formulation stage using their superior local information. In addition, due to the joint liability mechanism of the programs, group members monitor each others economic activities to ensure the minimal misuse of credit. The arguments in the literature are based on the assumption that once the credit is provided, credit programs have no further role in ensuring that repayments are honored by the group. In contrast, using survey data this essay documents that credit programs use in addition organizational pressures such as humiliation and harassment the non-payer to recover the unpaid installments. The results also show that the group mechanisms do not have a significant effect in recovering default dues.

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Ensuring adequate water supply to urban areas is a challenging task due to factors such as rapid urban growth, increasing water demand and climate change. In developing a sustainable water supply system, it is important to identify the dominant water demand factors for any given water supply scheme. This paper applies principal components analysis to identify the factors that dominate residential water demand using the Blue Mountains Water Supply System in Australia as a case study. The results show that the influence of community intervention factors (e.g. use of water efficient appliances and rainwater tanks) on water demand are among the most significant. The result also confirmed that the community intervention programmes and water pricing policy together can play a noticeable role in reducing the overall water demand. On the other hand, the influence of rainfall on water demand is found to be very limited, while temperature shows some degree of correlation with water demand. The results of this study would help water authorities to plan for effective water demand management strategies and to develop a water demand forecasting model with appropriate climatic factors to achieve sustainable water resources management. The methodology developed in this paper can be adapted to other water supply systems to identify the influential factors in water demand modelling and to devise an effective demand management strategy.

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In the present study, we identified a novel asthma susceptibility gene, NPSR1 (neuropeptide S receptor 1) on chromosome 7p14.3 by the positional cloning strategy. An earlier significant linkage mapping result among Finnish Kainuu asthma families was confirmed in two independent cohorts: in asthma families from Quebec, Canada and in allergy families from North Karelia, Finland. The linkage region was narrowed down to a 133-kb segment by a hierarchial genotyping method. The observed 77-kb haplotype block showed 7 haplotypes and a similar risk and nonrisk pattern in all three populations studied. All seven haplotypes occur in all three populations at frequences > 2%. Significant elevated relative risks were detected for elevated total IgE (immunoglobulin E) or asthma. Risk effects of the gene variants varied from 1.4 to 2.5. NPSR1 belongs to the G protein-coupled receptor (GPCR) family with a topology of seven transmembrane domains. NPSR1 has 9 exons, with the two main transcripts, A and B, encoding proteins of 371 and 377 amino acids, respectively. We detected a low but ubiquitous expression level of NPSR1-B in various tissues and endogenous cell lines while NPSR1-A has a more restricted expression pattern. Both isoforms were expressed in the lung epithelium. We observed aberrant expression levels of NPSR1-B in smooth muscle in asthmatic bronchi as compared to healthy. In an experimental mouse model, the induced lung inflammation resulted in elevated Npsr1 levels. Furthermore, we demonstrated that the activation of NPSR1 with its endogenous agonist, neuropeptide S (NPS), resulted in a significant inhibition of the growth of NPSR1-A overexpressing stable cell lines (NPSR1-A cells). To determine which target genes were regulated by the NPS-NPSR1 pathway, NPSR1-A cells were stimulated with NPS, and differentially expressed genes were identified using the Affymetrix HGU133Plus2 GeneChip. A total of 104 genes were found significantly up-regulated and 42 down-regulated 6 h after NPS administration. The up-regulated genes included many neuronal genes and some putative susceptibility genes for respiratory disorders. By Gene Ontology enrichment analysis, the biological process terms, cell proliferation, morphogenesis and immune response were among the most altered. The expression of four up-regulated genes, matrix metallopeptidase 10 (MMP10), INHBA (activin A), interleukin 8 (IL8) and EPH receptor A2 (EPHA2), were verified and confirmed by quantitative reverse-transcriptase-PCR. In conclusion, we identified a novel asthma susceptibility gene, NPSR1, on chromosome 7p14.3. NPS-NPSR1 represents a novel pathway that regulates cell proliferation and immune responses, and thus may have functional relevance in the pathogenesis of asthma.

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Substitution of Sn4+ ion in CeO2 creates activated oxygen in Ce0.8Sn0.2O2 leading to higher oxygen storage capacity compared to Ce0.8Zr0.2O2. With Pd ion substitution in Ce0.8Sn0.2O2,activation of oxygen is further enhanced as observed from the H-2/TPR study. Both EXAFS analysis and DFT calculation reveal that in the solid solution Ceexhibits 4 + 4 coordination, Sri exhibits 4 + 2 + 2 coordination and Pd has 4 + 3 coordination. While the oxygen in the First four coordination with short M-O bonds are strongly held in the lattice, the oxygens in the second and higher coordinations with long M-O bonds are weakly bound, and they are the activated oxygen ill the lattice. Bond valence analysis shows that oxygen with valencies as low its 1.65 are created by the Sn and Pd ion Substitution. Another interesting observation is that H-2/TPR experiment of Ce1-xSnxO2 shows a broad peak starting from 200 to 500 degrees C, while the same reduction is achieved in a single step at similar to 110 degrees C in presence Pd2+ on. Substitution of Pd2+ ion thus facilitates synergistic reduction of the catalyst at lower temperature. We have shown that simultaneous reduction of the Ce4+ and Sr4+ ions by Pd-0 is the synergistic interaction leading to high oxygen storage capacity at low temperature.

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Background Diabetic foot complications are the leading cause of lower extremity amputation and diabetes-related hospitalisation in Australia. Studies demonstrate significant reductions in amputations and hospitalisation when health professionals implement best practice management. Whilst other nations have surveyed health professionals on specific diabetic foot management, to the best of the authors’ knowledge this appears not to have occurred in Australia. The primary aim of this study was to examine Australian podiatrists’ diabetic foot management compared with best practice recommendations by the Australian National Health Medical Research Council. Methods A 36-item Australian Diabetic Foot Management survey, employing seven-point Likert scales (0 = Never; 7 = Always) to measure multiple aspects of best practice diabetic foot management was developed. The survey was briefly tested for face and content validity. The survey was electronically distributed to Australian podiatrists via professional associations. Demographics including sex, years treating patients with diabetes, employment-sector and patient numbers were also collected. Chi-squared and Mann Whitney U tests were used to test differences between sub-groups. Results Three hundred and eleven podiatrists responded; 222 (71%) were female, 158 (51%) from the public sector and 11–15 years median experience. Participants reported treating a median of 21–30 diabetes patients each week, including 1–5 with foot ulcers. Overall, participants registered median scores of at least “very often” (>6) in their use of most items covering best practice diabetic foot management. Notable exceptions were: “never” (1 (1 – 3)) using total contact casting, “sometimes” (4 (2 – 5)) performing an ankle brachial index, “sometimes” (4 (1 – 6)) using University of Texas Wound Classification System, and “sometimes” (4 (3 – 6) referring to specialist multi-disciplinary foot teams. Public sector podiatrists reported higher use or access on all those items compared to private sector podiatrists (p < 0.01). Conclusions This study provides the first baseline information on Australian podiatrists’ adherence to best practice diabetic foot guidelines. It appears podiatrists manage large caseloads of people with diabetes and are generally implementing best practice guidelines recommendations with some notable exceptions. Further studies are required to identify barriers to implementing these recommendations to ensure all Australians with diabetes have access to best practice care to prevent amputations.

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Background: The fecal neutrophil-derived proteins calprotectin and lactoferrin have proven useful surrogate markers of intestinal inflammation. The aim of this study was to compare fecal calprotectin and lactoferrin concentrations to clinically, endoscopically, and histologically assessed Crohn’s disease (CD) activity, and to explore the suitability of these proteins as surrogate markers of mucosal healing during anti-TNFα therapy. Furthermore, we studied changes in the number and expression of effector and regulatory T cells in bowel biopsy specimens during anti-TNFα therapy. Patients and methods: Adult CD patients referred for ileocolonoscopy (n=106 for 77 patients) for various reasons were recruited (Study I). Clinical disease activity was assessed with the Crohn’s disease activity index (CDAI) and endoscopic activity with both the Crohn’s disease index of severity (CDEIS) and the simple endoscopic score for Crohn’s disease (SES-CD). Stool samples for measurements of calprotectin and lactoferrin, and blood samples for CRP were collected. For Study II, biopsy specimens were obtained from the ileum and the colon for histologic activity scoring. In prospective Study III, after baseline ileocolonoscopy, 15 patients received induction with anti-TNFα blocking agents and endoscopic, histologic, and fecal-marker responses to therapy were evaluated at 12 weeks. For detecting changes in the number and expression of effector and regulatory T cells, biopsy specimens were taken from the most severely diseased lesions in the ileum and the colon (Study IV). Results: Endoscopic scores correlated significantly with fecal calprotectin and lactoferrin (p<0.001). Both fecal markers were significantly lower in patients with endoscopically inactive than with active disease (p<0.001). In detecting endoscopically active disease, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for calprotectin ≥200 μg/g were 70%, 92%, 94%, and 61%; for lactoferrin ≥10 μg/g they were 66%, 92%, 94%, and 59%. Accordingly, the sensitivity, specificity, PPV, and NPV for CRP >5 mg/l were 48%, 91%, 91%, and 48%. Fecal markers were significantly higher in active colonic (both p<0.001) or ileocolonic (calprotectin p=0.028, lactoferrin p=0.004) than in ileal disease. In ileocolonic or colonic disease, colon histology score correlated significantly with fecal calprotectin (r=0.563) and lactoferrin (r=0.543). In patients receiving anti-TNFα therapy, median fecal calprotectin decreased from 1173 μg/g (range 88-15326) to 130 μg/g (13-1419) and lactoferrin from 105.0 μg/g (4.2-1258.9) to 2.7 μg/g (0.0-228.5), both p=0.001. The relation of ileal IL-17+ cells to CD4+ cells decreased significantly during anti-TNF treatment (p=0.047). The relation of IL-17+ cells to Foxp3+ cells was higher in the patients’ baseline specimens than in their post-treatment specimens (p=0.038). Conclusions: For evaluation of CD activity, based on endoscopic findings, more sensitive surrogate markers than CDAI and CRP were fecal calprotectin and lactoferrin. Fecal calprotectin and lactoferrin were significantly higher in endoscopically active disease than in endoscopic remission. In both ileocolonic and colonic disease, fecal markers correlated closely with histologic disease activity. In CD, these neutrophil-derived proteins thus seem to be useful surrogate markers of endoscopic activity. During anti-TNFα therapy, fecal calprotectin and lactoferrin decreased significantly. The anti-TNFα treatment was also reflected in a decreased IL-17/Foxp3 cell ratio, which may indicate improved balance between effector and regulatory T cells with treatment.

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Background Many different guidelines recommend people with foot complications, or those at risk, should attend multiple health professionals for foot care each year. However, few studies have investigated the characteristics of those attending health professionals for foot care and if those characteristics match those requiring foot care as per guideline recommendations. The aim of this paper was to determine the associated characteristics of people who attended a health professional for foot care in the year prior to their hospitalisation. Methods Eligible participants were all adults admitted overnight, for any reason, into five diverse hospitals on one day; excluding maternity, mental health and cognitively impaired patients. Participants underwent a foot examination to clinically diagnose different foot complications; including wounds, infections, deformity, peripheral arterial disease and peripheral neuropathy. They were also surveyed on social determinant, medical history, self-care, foot complication history, and, past health professional attendance for foot care in the year prior to hospitalisation. Results Overall, 733 participants consented; mean(±SD) age 62(±19) years, 408 (55.8%) male, 172 (23.5%) diabetes. Two hundred and fifty-six (34.9% (95% CI) (31.6-38.4)) participants had attended a health professional for foot care; including attending podiatrists 180 (24.5%), GPs 93 (24.6%), and surgeons 36 (4.9%). In backwards stepwise multivariate analyses attending any health professional for foot care was independently associated (OR (95% CI)) with diabetes (3.0 (2.1-4.5)), arthritis (1.8 (1.3-2.6)), mobility impairment (2.0 (1.4-2.9)) and previous foot ulcer (5.4 (2.9-10.0)). Attending a podiatrist was independently associated with female gender (2.6 (1.7-3.9)), increasing years of age (1.06 (1.04-1.08), diabetes (5.0 (3.2-7.9)), arthritis (2.0 (1.3-3.0)), hypertension (1.7 (1.1-2.6) and previous foot ulcer (4.5 (2.4-8.1). While attending a GP was independently associated with having a foot ulcer (10.4 (5.6-19.2). Conclusions Promisingly these findings indicate that people with a diagnosis of diabetes and arthritis are more likely to attend health professionals for foot care. However, it also appears those with active foot complications, or significant risk factors, may not be more likely to receive the multi-disciplinary foot care recommended by guidelines. More concerted efforts are required to ensure all people with foot complications are receiving recommended foot care.

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Background: The number of available structures of large multi-protein assemblies is quite small. Such structures provide phenomenal insights on the organization, mechanism of formation and functional properties of the assembly. Hence detailed analysis of such structures is highly rewarding. However, the common problem in such analyses is the low resolution of these structures. In the recent times a number of attempts that combine low resolution cryo-EM data with higher resolution structures determined using X-ray analysis or NMR or generated using comparative modeling have been reported. Even in such attempts the best result one arrives at is the very course idea about the assembly structure in terms of trace of the C alpha atoms which are modeled with modest accuracy. Methodology/Principal Findings: In this paper first we present an objective approach to identify potentially solvent exposed and buried residues solely from the position of C alpha atoms and amino acid sequence using residue type-dependent thresholds for accessible surface areas of C alpha. We extend the method further to recognize potential protein-protein interface residues. Conclusion/Significance: Our approach to identify buried and exposed residues solely from the positions of C alpha atoms resulted in an accuracy of 84%, sensitivity of 83-89% and specificity of 67-94% while recognition of interfacial residues corresponded to an accuracy of 94%, sensitivity of 70-96% and specificity of 58-94%. Interestingly, detailed analysis of cases of mismatch between recognition of interface residues from C alpha positions and all-atom models suggested that, recognition of interfacial residues using C alpha atoms only correspond better with intuitive notion of what is an interfacial residue. Our method should be useful in the objective analysis of structures of protein assemblies when positions of only C alpha positions are available as, for example, in the cases of integration of cryo-EM data and high resolution structures of the components of the assembly.

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Muscle hypertrophy occurs following increased protein synthesis, which requires activation of the ribosomal complex. Additionally, increased translational capacity via elevated ribosomal RNA (rRNA) synthesis has also been implicated in resistance training-induced skeletal muscle hypertrophy. The time course of ribosome biogenesis following resistance exercise (RE) and the impact exerted by differing recovery strategies remains unknown. In the present study, the activation of transcriptional regulators, the expression levels of pre-rRNA, and mature rRNA components were measured through 48 h after a single-bout RE. In addition, the effects of either low-intensity cycling (active recovery, ACT) or a cold-water immersion (CWI) recovery strategy were compared. Nine male subjects performed two bouts of high-load RE randomized to be followed by 10 min of either ACT or CWI. Muscle biopsies were collected before RE and at 2, 24, and 48 h after RE. RE increased the phosphorylation of the p38-MNK1-eIF4E axis, an effect only evident with ACT recovery. Downstream, cyclin D1 protein, total eIF4E, upstream binding factor 1 (UBF1), and c-Myc proteins were all increased only after RE with ACT. This corresponded with elevated abundance of the pre-rRNAs (45S, ITS-28S, ITS-5.8S, and ETS-18S) from 24 h after RE with ACT. In conclusion, coordinated upstream signaling and activation of transcriptional factors stimulated pre-rRNA expression after RE. CWI, as a recovery strategy, markedly blunted these events, suggesting that suppressed ribosome biogenesis may be one factor contributing to the impaired hypertrophic response observed when CWI is used regularly after exercise.

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Oxovanadium(IV) complexes [VO(L)(B)]Cl-2 (1-3), where L is bis(2-benzimidazolylmethyl)amine and B is 1,10-phenanthroline(phen),dipyrido[3,2-d:2',3'-f]quinoxaline(dpq) or dipyrido[3,2-a:2',3'-c]phenazine (dppz), have been prepared, characterized, and their photo-induced DNA and protein cleavage activity studied. The photocytotoxicity of complex 3 has been studied using adenocarcinoma A549 cells, The phen complex 1, structurally characterized by single-crystal X-ray crystallography, shows the presence of a vanadyl group in six-coordinate VON5 coordination geometry. The ligands L and phen display tridentate and bidentate N-donor chelating binding modes, respectively. The complexes exhibit a d-d band near 740 nm in 15% DMF-Tris-HCl buffer (pH 7.2). The phen and dpq complexes display an irreversible cathodic cyclic voltammetric response near -0.8 V in 20% DMF-Tris-HCl buffer having 0.1 M KCl as supporting electrolyte. The dppz complex 3 exhibits a quasi-reversible voltammogram near -0.6 V (vs SCE) that is assignable to the V(IV)-V(III)couple. The complexes bind to calf thymus DNA giving binding constant values in the range of 6.6 x 10(4)-2.9 x 10(5) M-1. The binding site size, thermal melting and viscosity binding data suggest DNA surface and/or groove binding nature of the complexes. The complexes show poor ``chemical nuclease'' activity in dark in the presence of 3-mercaptopropionic acid or hydrogen peroxide. The dpq and dppz complexes are efficient photocleavers of plasmid DNA in UV-A light of 365 nm via a mechanistic pathway that involves formation of both singlet oxygen and hydroxyl radicals. The complexes show significant photocleavage of DNA in near-IR light (>750 nm) via hydroxyl radical pathway. Among the three complexes, the dppz complex 3 shows significant BSA and lysozyme protein cleavage activity in UV-A light of 365 nm via hydroxyl radical pathway. The dppz complex 3 also exhibits photocytotoxicity in non-small cell lung carcinoma/human lung adenocarcinoma A549 cells giving IC50 value of 17 mu M in visible light(IC50 = 175 mu M in dark).

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Septic shock is a common killer in intensive care units (ICU). The most crucial issue concerning the outcome is the early and aggressive start of treatment aimed at normalization of hemodynamics and the early start of antibiotics during the very first hours. The optimal targets of hemodynamic treatment, or impact of hemodynamic treatment on survival after first resuscitation period are less known. The objective of this study was to evaluate different aspects of the hemodynamic pattern in septic shock with special attention to prediction of outcome. In particular components of early treatment and monitoring in the ICU were assessed. A total of 401 patients, 218 with septic shock and 192 with severe sepsis or septic shock were included in the study. The patients were treated in 24 Finnish ICUs during 1999-2005. 295 of the patients were included in the Finnish national epidemiologic Finnsepsis study. We found that the most important hemodynamic variables concerning the outcome were the mean arterial pressures (MAP) and lactate during the first six hours in ICU and the MAP and mixed venous oxygen saturation (SvO2) under 70% during first 48 hours. The MAP levels under 65 mmHg and SvO2 below 70% were the best predictive thresholds. Also the high central venous pressure (CVP) correlated to adverse outcome. We assessed the correlation and agreement of SvO2 and mean central venous oxygen saturation (ScvO2) in septic shock during first day in ICU. The mean SvO2 was below ScvO2 during early sepsis. Bias of difference was 4.2% (95% limits of agreement 8.1% to 16.5%) by Bland-Altman analysis. The difference between saturation values correlated significantly to cardiac index and oxygen delivery. Thus, the ScvO2 can not be used as a substitute of SvO2 in hemodynamic monitoring in ICU. Several biomarkers have been investigated for their ability to help in diagnosis or outcome prediction in sepsis. We assessed the predictive value of N-terminal pro brain natriuretic peptide (NT-proBNP) on mortality in severe sepsis or septic shock. The NT-proBNP levels were significantly higher in hospital nonsurvivors. The NT-proBNP 72 hrs after inclusion was independent predictor of hospital mortality. The acute cardiac load contributed to NTproBNP values at admission, but renal failure was the main confounding factor later. The accuracy of NT-proBNP, however, was not sufficient for clinical decision-making concerning the outcome prediction. The delays in start of treatment are associated to poorer prognosis in sepsis. We assessed how the early treatment guidelines were adopted, and what was the impact of early treatment on mortality in septic shock in Finland. We found that the early treatment was not optimal in Finnish hospitals and this reflected to mortality. A delayed initiation of antimicrobial agents was especially associated with unfavorable outcome.

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A stable Y-doped BaZrO3 electrolyte film, which showed a good performance in proton-conducting SOFCs, was successfully fabricated using a novel ionic diffusion strategy.

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Reverse osmosis is the dominant technology utilized for desalination of saline water produced during the extraction of coal seam gas. Alternatively, ion exchange is of interest due to potential cost advantages. However, there is limited information regarding the column performance of strong acid cation resin for removal of sodium ions from both model and actual coal seam water samples. In particular, the impact of bed depth, flow rate, and regeneration was not clear. Consequently, this study applied Bed Depth Service Time (BDST) models to reveal that increasing sodium ion concentration and flow rates diminished the time required for breakthrough to occur. The loading of sodium ions on fresh resin was calculated to be ca. 71.1 g Na/kg resin. Difficulties in regeneration of the resin using hydrochloric acid solutions were discovered, with 86% recovery of exchange sites observed. The maximum concentration of sodium ions in the regenerant brine was found to be 47,400 mg/L under the conditions employed. The volume of regenerant waste formed was 6.2% of the total volume of water treated. A coal seam water sample was found to load the resin with only 53.5 g Na/kg resin, which was consistent with not only the co-presence of more favoured ions such as calcium, magnesium, barium and strontium, but also inefficient regeneration of the resin prior to the coal seam water test.