Performance of Sri Lankan FRAX algorithm without bone mineral density and with Quantitative Ultrasound data input

Introduction: Fracture risk assessment algorithm (FRAX) is the most validated method available to predict fracture risk. Its use is restricted due to limited availability of Dual Energy X-ray Absorptiometry (DXA). FRAX has the option of assessing facture risk without BMD data. Objectives: To assess the ability of Sri Lankan FRAX algorithm without BMD input in evaluating fracture risk. The possibility of replacing the BMD input with Quantitative Ultrasound (QUS) data of radius in calculating fracture risk also assessed. Method: Data of clinical risk factors associated with fractures were collected from community dwelling postmenopausal women (n=339). DXA scans were performed in all subjects and QUS scans (in radius) were performed in a randomly selected sample (n=207). Ten-year risks of major osteoporotic fracture (MOFR) and hip fracture (HFR) were calculated with BMD, without BMD (FRAX-FN0) and with US T score instead of BMD (FRAX-UST). Result and conclusions: Nearly 35.7% had high risk of fractures. FRAX-FN0 had 79.2% sensitivity, 80.1% specificity, 68.8% positive predictive value (PPV) and 87.4% negative predictive value (NPV). FRAX-UST showed 78.4% sensitivity, 70% specificity, 59.8% PPV and 85% NPV. ROC AUCs were above 0.80 in both FRAX-FN0 and FRAX-UST. The standard errors of estimate (SEE) were less in FRAX-FN0 (3.96 and 2.76 for MOFR-FN0 and HFR-FN0 respectively) compared to FRAX-UST (6.13 and 4.83 for MOFR-UST and HFR-UST, respectively). In conclusion, Sri Lankan FRAX without BMD is an acceptable alternative in areas with restricted DXA facility. Radial QUS data cannot be used as a substitute to FN-BMD in Sri Lankan FRAX.

The decision-making processes of pharmacists in inland Australia--a pilot study.

INTRODUCTION: Little research has been conducted analysing the organisational risks that compound and trigger dispensing and medication errors. This pilot study appraises the attitudes to and behaviours related to the dispensing errors of pharmacists practising in diverse venues and roles in inland Australia. METHODS: Twelve pharmacists working in the Riverina (Wiradjuri country) participated in a structured interview consisting of a brief survey and open-ended questions. The interviews were audio-recorded for transcription, then analysed by the interviewer for emerging themes. In this pilot study, the attitudes and actions of pharmacists in response to dispensing errors were explored to determine the nature of organisational strategies implemented to detect and recover 'slips, lapses and mistakes'. The rationale behind investigating attitudes and actions stems from the theory of planned behaviour. RESULTS: While many common themes emerged, the attitudes of each pharmacist were unique. The strategies implemented to prevent errors were venue-specific and purpose-designed to the training level of the staff and physical environment. A diverse mix of attitudes was represented by the sample, with no correlation between worksite, sex, age or role identified. Trends may emerge because, in regard to dispensing errors, subjective norms and perceived behavioural control play a greater role in forming the intention to act, rather than personal attitudes. The majority of examples given by participants was discussion of recorded errors and near misses, which included changes to procedures implemented to prevent the same error occurring. This culture of continuous quality improvement was the overarching common theme. Other common themes were the role of technology in the supply of medicines, privacy implications when drawing staff from a rural or regional centre, workload concerns with regard to management responsibility and the impact of the way error management was demonstrated during the formative early years of practice. Distraction from dispensing, through management roles in pharmacies with moderate prescription volumes, was a common contributor to errors. CONCLUSION: A culture of continuous quality improvement exists amongst pharmacists in Inland Australia, which would benefit from improved dialogue about the impact of organisational risks on the rate of dispensing errors. The safety culture, and behaviour modelling experienced during the internship program has a profound impact on the perceived behavioural control of young pharmacists. This year instils mores, which may be the result of independent survival in remote and regional settings, rather than compliance with professional practice standards. While many of the pressures and demands of minimising errors are common across the profession; unique, venue specific strategies are commonly implemented in the cycle of continuous quality improvement in regional and remote settings.

Global influence of mantle temperature and plate thickness on intraplate volcanism.

The thermochemical structure of lithospheric and asthenospheric mantle exert primary controls on surface topography and volcanic activity. Volcanic rock compositions and mantle seismic velocities provide indirect observations of this structure. Here, we compile and analyze a global database of the distribution and composition of Neogene-Quaternary intraplate volcanic rocks. By integrating this database with seismic tomographic models, we show that intraplate volcanism is concentrated in regions characterized by slow upper mantle shear-wave velocities and by thin lithosphere (i.e. <100 km). We observe a negative correlation between shear-wave velocities at depths of 125-175 km and melt fractions inferred from volcanic rock compositions. Furthermore, mantle temperature and lithospheric thickness estimates obtained by geochemical modeling broadly agree with values determined from tomographic models that have been converted into temperature. Intraplate volcanism often occurs in regions where uplifted (but undeformed) marine sedimentary rocks are exposed. Regional elevation of these rocks can be generated by a combination of hotter asthenosphere and lithospheric thinning. Therefore, the distribution and composition of intraplate volcanic rocks through geologic time will help to probe past mantle conditions and surface processes.

Wildfire and charcoal enhance nitrification and ammonium-oxidizing bacterial abundance in dry montane forest soils.

All forest fire events generate some quantity of charcoal, which may persist in soils for hundreds to thousands of years. However, few studies have effectively evaluated the potential for charcoal to influence specific microbial communities or processes. To our knowledge, no studies have specifically addressed the effect of charcoal on ammonia-oxidizing bacteria (AOB) in forest soils. Controlled experiments have shown that charcoal amendment of fire-excluded temperate and boreal coniferous forest soil increases net nitrification, suggesting that charcoal plays a major role in maintaining nitrification for extended periods postfire. In this study, we examined the influence of fire history on gross nitrification, nitrification potential, and the nature and abundance of AOB. Soil cores were collected from sites in the Selway-Bitterroot wilderness area in northern Idaho that had been exposed twice (in 1910, 1934) or three times (1910, 1934, and 1992) in the last 94 yr, allowing us to contrast soils recently exposed to fire to those that experienced no recent fire (control). Charcoal content was determined in the O horizon by hand-separation and in the mineral soil by a chemical digestion procedure. Gross and net nitrification, and potential rates of nitrification were measured in mineral soil. Analysis of the AOB community was conducted using primer sets specific for the ammonia mono-oxygenase gene (amoA) or the 16S rRNA gene of AOB. Denaturing gradient gel electrophoresis was used to analyze the AOB community structure, while AOB abundance was determined by quantitative polymerase chain reaction. Recent (12-yr-old) wildfire resulted in greater charcoal contents and nitrification rates compared with sites without fire for 75 yr, and the more recent fire appeared to have directly influenced AOB abundance and community structure. We predicted and observed greater abundance of AOB in soils recently exposed to fire compared with control soils. Interestingly, sequence data revealed that Clusters 3 and 4, and not Cluster 2, of genus Nitrosospira dominated these forest soils, with a shift toward Cluster 3 in recently burned sites.

Self-assembly of a one-dimensional iron(II) coordination polymer with p-phenylenebis(picolinaldimine).

catena-Poly[[[dichloridoiron(II)]-mu-N,N'-bis(2-pyridylmethylene)benzene-1,4-diamine] methanol disolvate], [FeCl(2)(C(18)H(14)N(4))].2CH(3)OH, forms a one-dimensional coordination polymer. The polymeric chains run parallel to the c axis. O-H...Cl-Fe and C-H...O hydrogen-bonding interactions with methanol solvent molecules stabilize the open supramolecular framework. Each Fe(II) atom adopts an octahedral geometry coordinated by four N atoms from two N,N'-bis(2-pyridylmethylene)benzene-1,4-diamine ligands and completed by two cis Cl atoms. The compound has C(2) (and C(i)) molecular symmetry, which is coincident with the crystallographic twofold symmetry at (0, y, 1/4). The one-dimensional structure is propagated via the crystallographic inversion center located at the benzene ring centroid (0, 1/2, 0).

Developing sustainable models of rural health care: a community development approach.

Globally, small rural communities frequently are demographically similar to their neighbours and are consistently found to have a number of problems linked to the international phenomenon of rural decline and urban drift. For example, it is widely noted that rural populations have poor health status and aging populations. In Australia, multiple state and national policies and programs have been instigated to redress this situation. Yet few rural residents would agree that their town is the same as an apparently similar sized one nearby or across the country. This article reports a project that investigated the way government policies, health and community services, population characteristics and local peculiarities combined for residents in two small rural towns in New South Wales. Interviews and focus groups with policy makers, health and community service workers and community members identified the felt, expressed, normative and comparative needs of residents in the case-study towns. Key findings include substantial variation in service provision between towns because of historical funding allocations, workforce composition, natural disasters and distance from the nearest regional centre. Health and community services were more likely to be provided because of available funding, rather than identified community needs. While some services, such as mental illness intervention and GPs, are clearly in demand in rural areas, in these examples, more health services were not needed. Rather, flexibility in the services provided and work practices, role diversity for health and community workers and community profiling would be more effective to target services. The impact of industry, employment and recreation on health status cannot be ignored in local development.

The cost-effectiveness of cardiac computed tomography for patients with stable chest pain.

OBJECTIVE: To assess the cost-effectiveness of cardiac CT compared with exercise stress testing (EST) in improving the health-related quality of life of patients with stable chest pain. METHODS: A cost-utility analysis alongside a single-centre randomised controlled trial carried out in Northern Ireland. Patients with stable chest pain were randomised to undergo either cardiac CT assessment or EST (standard care). The main outcome measure was cost per quality adjusted life year (QALY) gained at 1 year. RESULTS: Of the 500 patients recruited, 250 were randomised to cardiac CT and 250 were randomised to EST. Cardiac CT was the dominant strategy as it was both less costly (incremental total costs -£50.45; 95% CI -£672.26 to £571.36) and more effective (incremental QALYs 0.02; 95% CI -0.02 to 0.05) than EST. At a willingness-to-pay threshold of £20 000 per QALY the probability of cardiac CT being cost-effective was 83%. Subgroup analyses indicated that cardiac CT appears to be most cost-effective in patients with a likelihood of coronary artery disease (CAD) of <30%, followed by 30%-60% and then >60%. CONCLUSIONS: Cardiac CT is cost-effective compared with EST and cost-effectiveness was observed to vary with likelihood of CAD. This finding could have major implications for how patients with chest pain in the UK are assessed, however it would need to be validated in other healthcare systems. TRIAL REGISTRATION NUMBER: (ISRCTN52480460); results.

Effects of breed and feed supplementation on the fertility of cows developed for milk production in Zimbabwe.

Forty-six indigenous Sanga-type (Nkone and Tuli breeds) cows and 46 crossbred (Nkone x Jersey and Tuli x Jersey) cows were randomly allocated to four treatment combinations in a 2 x 2 factorial arrangement with two breeds and two dietary levels, a control diet and a diet supplemented with dairy meal containing 14 per cent crude protein at the rate of 2 kg per cow per day. The progesterone concentration was measured in milk samples taken three times a week from 10 days postpartum for up to 200 days, and the cows' bodyweights and body condition scores were recorded fortnightly. The pregnancy rate in the crossbred cows was significantly higher (P<0.05) than in the indigenous cows, and the assumed pregnancy loss rate 30 days after conception was significantly higher (P<0.05) in the indigenous cows than in the crossbred cows. The supplemented crossbred cows had a lower pregnancy loss rate than the supplemented indigenous cows (P<0.05). All the supplemented indigenous cows that lost pregnancies were in their first parity, whereas all the crossbred cows that lost pregnancies were multiparous and were not supplemented. The indigenous cows weighed significantly more (P<0.05) than the crossbred cows irrespective of diet, and the supplemented cows of both breeds weighed more (P<0.05) than the control cows. The supplemented indigenous cows had significantly higher (P<0.05) body condition scores than the control cows. The mean dairy milk yield of all the breeds was generally low but significantly higher (P<0.05) in the crossbred than in the indigenous cows.

A comparison of cardiac computerized tomography and exercise stress electrocardiogram test for the investigation of stable chest pain: the clinical results of the CAPP randomized prospective trial.

AIMS: To determine the symptomatic and prognostic differences resulting from a novel diagnostic pathway based on cardiac computerized tomography (CT) compared with the traditional exercise stress electrocardiography test (EST) in stable chest pain patients. METHODS AND RESULTS: A prospective randomized controlled trial compared selected patient outcomes in EST and cardiac CT coronary angiography groups. Five hundred patients with troponin-negative stable chest pain and without known coronary artery disease were recruited. Patients completed the Seattle Angina Questionnaires (SAQ) at baseline, 3, and 12 months to assess angina symptoms. Patients were also followed for management strategies and clinical events. Over the year 12 patients withdrew, resulting in 245 in the EST cohort and 243 in the CT cohort. There was no significant difference in baseline demographics. The CT arm had a statistical difference in angina stability and quality-of-life domains of the SAQ at 3 and12 months, suggesting less angina compared with the EST arm. In the CT arm, there was more significant disease identified and more revascularizations. Significantly, more inconclusive results were seen in the EST arm with a higher number of additional investigations ordered. There was also a longer mean time to management. There were no differences in major adverse cardiac events between the cohorts. At 1 year in the EST arm, there were more Accident and Emergency (A&E) attendances and cardiac admission. CONCLUSION: Cardiac CT as an index investigation for stable chest pain improved angina symptoms and resulted in fewer investigations and re-hospitalizations compared with EST. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN52480460.

Isolation and characterization of a Rhizobium loti gene required for effective nodulation of Lotus pedunculatus.

A Rhizobium loti gene required for effective invasion of the host Lotus pedunculatus has been identified by transposon Tn5 mutagenesis. Cosmids that complemented a previously isolated mutation (239) at this invasion (inv) locus were identified by in planta complementation and used to construct a physical map of the gene region. The insertion site of Tn5 in PN239 was mapped to a 7.5-kb EcoRI fragment, which complemented the mutation when subcloned into pLAFR1. Further Tn5 mutagenesis of the 7.5-kb fragment was carried out in Escherichia coli using bacteriophage lambda 467, and the mutations homogenotized into R. loti NZP2037. Three additional Fix- mutations were isolated, and these were found to map adjacent to the position of the original mutation in strain PN239. All the other Tn5 insertions isolated in the 7.5-kb fragment gave a Fix+ phenotype on L. pedunculatus. Electron microscopic examination of the L. pedunculatus nodules induced by the isolated Fix- mutants showed that bacteria were either blocked in release from the infection threads or were unable to undergo normal bacteroid development. The inv locus as defined by the Tn5 insertions was sequenced, and a single open-reading frame (ORF) of 576 bp, corresponding to a polypeptide of 21.3 kDa, was identified. The position and orientation of this ORF were consistent with those of the isolated Tn5 Fix- insertions.

4-Hydroxyestradiol-17 beta and 4-hydroxyestradiol-17 alpha: comparative studies on central and peripheral effects of two epimeric catecholestrogens.

4-Hydroxyestradiol-17 beta and 4-hydroxyestradiol-17 alpha (5 or 20 microgram/d) were continuously s.c. infused for 3 days into ovariectomized adult rats. The serum levels of either epimer were virtually identical when the same dose was administered. 4-Hydroxyestradiol-17 beta significantly altered body and uterus weight and LH serum levels (negative and positive effects) at both doses tested. 4-Hydroxyestradiol-17 alpha showed no effects even at the 20 microgram/d dose. As both epimers have similar affinities for catechol O-methyltransferase, but their potencies regarding effects on lH serum levels differ markedly, it is concluded that the interaction of catecholestrogens with this enzyme is not essential for their effects on LH release.

Metabolic clearance rates of catechol estrogens in rats.

MCRs of the catechol estrogens 4-hydroxyestradiol (4-OHE2) and 2-hydroxyestradiol (2-OHE2) and of the parent estrogen 17 beta-estradiol (E2) were determined in rats. Long term ovariectomized Wistar rats were infused with the steroids at a constant rate for 3 days via a catheter placed in the abdominal aorta. Blood samples were drawn discontinually by retroorbital puncture, and the serum concentrations of E2, 4-OHE2, and 2-OHE2 were measured by RIA. Steady state was reached within 24 h of infusion. Mean serum MCRs were calculated to be 740 +/- 117 ml/h for E2, 2700 +/- 1000 ml/h for 4-OHE2, and 8300 +/- 1700 ml/h for 2-OHE2. Thus, the MCRs of the catechol estrogens were definitely higher than the MCR of E2 resulting in an apparent ratio of 1:4:11 (E2:4-OHE2:2-OHE2).

Effects of catecholestrogens on luteinizing hormone levels in long tem ovariectomized adult rats.

The long term ovariectomized adult rat was used to test the effects of exogenous estradiol, 4-hydroxyestradiol, and 2-hydroxyestradiol on LH secretion. To this end, different doses of estradiol 3-benzoate, 4-hydroxyestradiol 3,4-dibenzoate, and 2-hydroxyestradiol 2,3-dibenzoate were injected daily at 0800 h, and the LH serum levels were measured on 4 experimental days. At a dose of 1 micrograms/day, estradiol benzoate lowered LH secretion, beginning 48 h after the first injection (morning of day 2), and induced a characteristic LH surge 10 h later. 4-Hydroxyestradiol dibenzoate at the same dose produced less suppression of LH on the morning of day 3, but caused a comparable and highly significant surge on the same evening. Higher doses (3 and 10 micrograms/day) resulted in the same pattern seen with estradiol benzoate. 2-Hydroxyestradiol dibenzoate at comparable doses had no effect. Only extremely high doses (129 micrograms/day) caused slight suppression of tonic LH secretion 72 h after the first injection, and inconsistent LH elevations occurred on the same evening. It is concluded that in this model, catecholestrogens act as estrogens with respect to LH suppression and release, with 4-hydroxyestradiol being a potent estrogen and 2-hydroxyestradiol a weak estrogen.

Formation of 2- and 4-hydroxyestrogens by brain, pituitary, and liver of the human fetus.

When [6,7-3H]estradiol was incubated with tissue homogenates of the brain, the pituitary, and the liver of two human female fetuses, a number of radioactive metabolites more "polar" than the incubated substrate were detected. Among these, the identification of two types of catecholestrogens, i.e. the 2- and 4-hydroxyestrogens, was of major interest. Compared on the basis of wet weight of tissues (250 mg), the conversion of estradiol to 2-hydroxyestrogens (2-hydroxyestradiol and 2-hydroxyestrone) was 0.8% in the frontal cortex, 1.0% in the hypothalamus, 2.1% in the pituitary, and 7.8% in the liver. For the first time, the formation of 4-hydroxyestrogens was demonstrated. The percentages of incubated estradiol hydroxylated at C-atom 4 (4-hydroxyestradiol and 4-hydroxyestrone) were 0.5 in the cortex, 0.4% in the hypothalamus, .1% in the pituitary, and 0.5% in the liver. The results show that fetal brain and pituitary tissue can hydroxylate estradiol in positions 2 and 4 to a similar extent, whereas in the liver, about 15 times more 2-hydroxy than 4-hydroxy compounds are formed. Moreover, the 2-hydroxylating capacity of the liver is definitely greater than that of the brain, whereas the 4-hydroxylating capacity is about the same as that of the brain.

The excretion of 2-hydroxyestrone during the menstrual cycle.

A double isotope derivative determination technique was developed to investigate the excretion of 2-hydroxyestrone inhuman menstrual cycle. The method is highly specific, accurate and precise within the range of 0.2-20 nmol 2-hydroxyestrone/20ml of urine. The amounts of 2-hydroxyestrone excreted during menstrual cycle varied between 10 (proliferation phase) and 60 mug/24 h urine (ovulatory peak), which is comparable to that of estriol, supposed hitherto to be the main excretion product of estrogen metabolism.

Responses of catecholestrogen metabolism to acute graded exercise in normal menstruating women before and after training.

It has been hypothesized that exercise-related hypo-estrogenemia occurs as a consequence of increased competition of catecholestrogens (CE) for catechol-O-methyltransferase (COMT). This may result in higher norepinephrine (NE) concentrations, which could interfere with normal gonadotropin pulsatility. The present study investigates the effects of training on CE responses to acute exercise stress. Nine untrained eumenorrheic women (mean percentage of body fat +/-SD: 24.8 +/- 3.1%) volunteered for an intensive 5-day training program. Resting, submaximal, and maximal (tmax) exercise plasma CE, estrogen, and catecholamine responses were determined pre- and post training in both the follicular (FPh) and luteal phase (LPh). Acute exercise stress increased total primary estrogens (E) but had little effect on total 2-hydroxyestrogens (2-OHE) and 2-hydroxyestrogen-monomethylethers (2-MeOE) (= O-methylated CE after competition for catechol-O-methyltransferase). This pattern was not significantly changed by training. However, posttraining LPh mean (+/-SE) plasma E, 2-OHE, and 2-MeOE concentrations were significantly lower (P < 0.05) at each exercise intensity (for 2-OHE: 332 +/- 47 vs. 422 +/- 57 pg/mL at tmax; for 2-MeOE: 317 +/- 26 vs. 354 +/- 34 pg/mL at tmax). Training produced opposite effects on 2-OHE:E ratios (an estimation of CE formation) during acute exercise in the FPh (reduction) and LPh (increase). The 2-MeOE:2-OHE ratio (an estimation of CE activity) showed significantly higher values at tmax in both menstrual phases after training (FPh: +11%; LPh: +23%; P < 0.05). After training, NE values were significantly higher (P < 0.05). The major findings of this study were that: training lowers absolute concentrations of plasma estrogens and CE; the acute exercise challenge altered plasma estrogens but had little effect on CE; estimation of the formation and activity of CE suggests that formation and O-methylation of CE proportionately increases. These findings may be of importance for NE-mediated effects on gonadotropin release.

Formation and metabolism of catecholestrogens in depressed patients.

The evidence that catecholestrogens are formed in the brain and exert behavioral effects in animal models suggest that these steroids might have psychotropic activities. In the present investigation, the formation and metabolism of catecholestrogens were studied in depressed patients. Twenty-four-hr urine samples were collected from 6 male patients (59 +/- 8 years) with endogenous retarded depression (subtype primary, endogenous, and recurrent according to Research Diagnostic Criteria) and from 12 male control subjects (51 +/- 4 years). The patients were treated with the monoamine oxidase inhibitor tranylcypromine (10-40 mg/day for 3-4 weeks). The concentrations of primary estrogens, 4- and 2-hydroxyestrogens and 2-methoxyestrogens, were measured in the urine samples after multiple chromatographic separation steps by radioimmunoassay. In the depressed patients, the excretion rates of 4-hydroxyestrogens were significantly lower than in control subjects. The ratio 2-methoxyestrogens:2-hydroxyestrogens as an index for 2-O-methylation was 3.8 +/- 1.6 in patients and 1.8 +/- 0.7 in controls. The increased methylation and reduced 4-hydroxylation rates of patients were not affected by treatment with tranylcypromine though the psychopathological state was improved by 46%. Therefore, it seemed unlikely that the observed alterations were pathognomonically relevant in these depressed patients. The alterations in the formation and methylation of catecholestrogens show that the depressed patients exhibited remarkable metabolic disturbances. The functional role of these disturbances remains to be clarified.