Modelling an industrial anaerobic granular reactor using a multi-scale approach.

The objective of this paper is to show the results of an industrial project dealing with modelling of anaerobic digesters. A multi-scale mathematical approach is developed to describe reactor hydrodynamics, granule growth/distribution and microbial competition/inhibition for substrate/space within the biofilm. The main biochemical and physico-chemical processes in the model are based on the Anaerobic Digestion Model No 1 (ADM1) extended with the fate of phosphorus (P), sulfur (S) and ethanol (Et-OH). Wastewater dynamic conditions are reproduced and data frequency increased using the Benchmark Simulation Model No 2 (BSM2) influent generator. All models are tested using two plant data sets corresponding to different operational periods (#D1, #D2). Simulation results reveal that the proposed approach can satisfactorily describe the transformation of organics, nutrients and minerals, the production of methane, carbon dioxide and sulfide and the potential formation of precipitates within the bulk (average deviation between computer simulations and measurements for both #D1, #D2 is around 10%). Model predictions suggest a stratified structure within the granule which is the result of: 1) applied loading rates, 2) mass transfer limitations and 3) specific (bacterial) affinity for substrate. Hence, inerts (XI) and methanogens (Xac) are situated in the inner zone, and this fraction lowers as the radius increases favouring the presence of acidogens (Xsu,Xaa, Xfa) and acetogens (Xc4,Xpro). Additional simulations show the effects on the overall process performance when operational (pH) and loading (S:COD) conditions are modified. Lastly, the effect of intra-granular precipitation on the overall organic/inorganic distribution is assessed at: 1) different times; and, 2) reactor heights. Finally, the possibilities and opportunities offered by the proposed approach for conducting engineering optimization projects are discussed.

Skeletal health in adult patients with classic galactosemia.

SUMMARY: This study evaluated bone health in adults with galactosemia. Associations between bone mineral density (BMD) and nutritional and biochemical variables were explored. Calcium level predicted hip and spine BMD, and gonadotropin levels were inversely associated with spinal BMD in women. These results afford insights into management strategies for these patients. INTRODUCTION: Bone loss is a complication of galactosemia. Dietary restriction, primary ovarian insufficiency in women, and disease-related alterations of bone metabolism may contribute. This study examined relationships between clinical factors and BMD in patients with galactosemia. METHODS: This cross-sectional sample included 33 adults (16 women) with classic galactosemia, mean age 32.0 ± 11.8 years. BMD was measured by dual-energy X-ray absorptiometry, and was correlated with age, height, weight, fractures, nutritional factors, hormonal status, and bone biomarkers. RESULTS: There was a significant difference in hip BMD between women and men (0.799 vs. 0.896 g/cm(2), p = 0.014). The percentage of subjects with BMD-Z <-2.0 was also greater for women than men [33 vs. 18 % (spine), 27 vs. 6 % (hip)], and more women reported sustaining fractures. Bivariate analyses yielded correlations between BMI and BMD-Z [at the hip in women (r = 0.58, p < 0.05) and spine in men (r = 0.53, p < 0.05)]. In women, weight was also correlated with BMD-Z (r = 0.57, p < 0.05 at hip), and C-telopeptides (r = -0.59 at spine and -0.63 hip, p < 0.05) and osteocalcin (r = -0.71 at spine and -0.72 hip, p < 0.05) were inversely correlated with BMD-Z. In final regression models, higher gonadotropin levels were associated with lower spinal BMD in women (p = 0.017); serum calcium was a significant predictor of hip (p = 0.014) and spine (p = 0.013) BMD in both sexes. CONCLUSIONS: Bone density in adults with galactosemia is low, indicating the potential for increased fracture risk, the etiology of which appears to be multifactorial.

International Life Sciences Institute (Health and Environmental Sciences Institute, HESI) initiative on moving towards better predictors of drug-induced torsades de pointes.

Knowledge of the cardiac safety of emerging new drugs is an important aspect of assuring the expeditious advancement of the best candidates targeted at unmet medical needs while also assuring the safety of clinical trial subjects or patients. Present methodologies for assessing drug-induced torsades de pointes (TdP) are woefully inadequate in terms of their specificity to select pharmaceutical agents, which are human arrhythmia toxicants. Thus, the critical challenge in the pharmaceutical industry today is to identify experimental models, composite strategies, or biomarkers of cardiac risk that can distinguish a drug, which prolongs cardiac ventricular repolarization, but is not proarrhythmic, from one that prolongs the QT interval and leads to TdP. To that end, the HESI Proarrhythmia Models Project Committee recognized that there was little practical understanding of the relationship between drug effects on cardiac ventricular repolarization and the rare clinical event of TdP. It was on that basis that a workshop was convened in Virginia, USA at which four topics were introduced by invited subject matter experts in the following fields: Molecular and Cellular Biology Underlying TdP, Dynamics of Periodicity, Models of TdP Proarrhythmia, and Key Considerations for Demonstrating Utility of Pre-Clinical Models. Contained in this special issue of the British Journal of Pharmacology are reports from each of the presenters that set out the background and key areas of discussion in each of these topic areas. Based on this information, the scientific community is encouraged to consider the ideas advanced in this workshop and to contribute to these important areas of investigations over the next several years.

Low prevalence of vitamin D deficiency among adolescents with anorexia nervosa.

UNLABELLED: Fifty adolescents with AN and 200 healthy girls underwent vitamin D screening. Girls with AN reported exceptional compliance with vitamin D supplementation and PTH concentrations were lower. Vitamin D deficiency was less common in the group with AN, but when race was considered, the trend was no longer significant. INTRODUCTION: The objective of this study was to determine whether patients with anorexia nervosa (AN) are more compliant with supplementation and have a lower prevalence of vitamin D deficiency than healthy controls. METHODS: Fifty adolescents with AN and 200 controls were compared using anthropometric and lifestyle data, serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and prevalence of vitamin D deficiency. RESULTS: The prevalence of deficiency (<20 ng/mL) was 2% in the AN group vs. 24% among controls (p = 0.003). 25OHD was similar among white participants with AN and white controls (39.5 vs. 36.0 ng/mL, p = 0.20), but higher than in non-white controls (20.6 ng/mL). Significantly more girls with AN reported vitamin D supplementation (86%) than the full control (14%) or white subgroup (27%) (p < 0.001). Participants with AN had lower PTH concentrations than controls, (27.8 vs. 47.4 pg/mL, p = 0.009), a trend that lost significance after age and race adjustment (41.7 pg/mL, p = 0.12). CONCLUSIONS: Compared to healthy controls, adolescents with AN had a lower prevalence of vitamin D deficiency and PTH concentration. However, 25OHD and PTH concentrations were similar after adjustment for race and age. The trend of lower PTH levels in adolescents with AN, accompanied by exceptional compliance with supplementation, may have bone health implications for these patients.

Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study.

The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been characterized as "protective" against ischemic heart disease (IHD), especially in men, on the basis of sparse epidemiologic evidence. The authors used data from the Massachusetts Male Aging Study, a random sample prospective study of 1,709 men aged 40-70 years at baseline, to test whether serum levels of DHEA or DHEAS could predict incident IHD over a 9-year interval. At baseline (1987-1989) and follow-up (1995-1997), an interviewer-phlebotomist visited each subject in his home to obtain comprehensive health information, body measurements, and blood samples for hormone and lipid analysis. Incident IHD between baseline and follow-up was ascertained from hospital records and death registries, supplemented by self-report and evidence of medication. In the analysis sample of 1,167 men, those with serum DHEAS in the lowest quartile at baseline (<1.6 microg/ml) were significantly more likely to incur IHD by follow-up (adjusted odds ratio = 1.60, 95 percent confidence interval: 1.07, 2.39; p = 0.02), independently of a comprehensive set of known risk factors including age, obesity, diabetes, hypertension, smoking, serum lipids, alcohol intake, and physical activity. Low serum DHEA was similarly predictive. These results confirm prior evidence that low DHEA and DHEAS can predict IHD in men.

Developmental and lesion effects in brain activation during sentence comprehension and mental rotation.

The development of neurocognitive networks was examined in 2 cognitive paradigms: auditory sentence comprehension and mental rotation of alphanumeric stimuli. Patterns of brain activation were measured with whole brain echoplanar functional magnetic resonance imaging at 3 Tesla in 5 adults (20-28 years old), 7 children (9-12 years old), and 6 pediatric patients (9-12 years old) with perinatal strokes or periventricular hemorrhages. Healthy children and adults activated similar neurocognitive networks, but there were developmental differences in the distribution of activity across these networks. In the sentence task, children showed more activation in the inferior visual area suggesting an imagery strategy rather than a linguistic strategy for sentence processing. Furthermore, consistent use of a sentence comprehension strategy, whether correct or incorrect as compared to chance performance, was associated with greater activation in the inferior frontal area (Broca's) in both children and pediatric patients. In the mental rotation task, healthy adults showed more activation in the superior parietal and middle frontal areas and less activation in the supramarginal gyrus, suggesting adults were primarily engaged in visual-spatial manipulation and less engaged in the recognition of noncanonical views of stimuli. The pediatric patients showed patterns of activation consistent with organization of cognitive processing into homologous areas of the contralateral hemisphere.

Providing medical marijuana: the importance of cannabis clubs.

In 1996, shortly after the San Francisco Cannabis Club was raided and (temporarily) closed by state authorities, the authors conducted an ethnographic study by interviewing selected former members to ascertain how they had benefited from the use of medical marijuana and how they had utilized the clubs. Interviews were augmented by participant observation techniques. Respondents reported highly positive health benefits from marijuana itself, and underscored even greater benefits from the social aspects of the clubs, which they described as providing important emotional supports. As such, cannabis clubs serve as crucial support mechanisms/groups for people with a wide variety of serious illnesses and conditions. The authors concluded that of the various methods so far proposed, the cannabis clubs afford the best therapeutic setting for providing medical cannabis and for offering a healing environment composed of like-minded, sympathetic friends.

Treatment of acute systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious dog.

Two groups of six beagle dogs received rapid intravenous (IV) injections of ropivacaine or bupivacaine on two occasions in a blinded random fashion. Initially, a dose sufficient to cause convulsions (CD) was given followed by twice the CD (2 x CD), which was administered 48 h later. The CD of bupivacaine (4.3 mg/kg) and ropivacaine (4.9 mg/kg) caused significant (P less than 0.05) increases in heart rate and mean arterial blood pressure. There was no difference between drug groups. Seizures were abolished by 10 mg/kg of intravenous thiamylal. Endotracheal intubation and controlled respiration with O2-enriched air with no other treatment resulted in rapid and complete recovery in all dogs. All dogs receiving 2 x CD of bupivacaine (8.6 mg/kg) or ropivacaine (9.8 mg/kg) were initially treated with thiamylal and mechanical ventilation. Two dogs in the bupivacaine group developed hypotension, respiratory arrest, ventricular tachycardia, and ventricular fibrillation, which were resistant to closed chest cardiac massage, treatment with epinephrine, bretylium, and atropine, and direct current cardioversion. The four remaining dogs in the infusion group were successfully resuscitated. All of the animals in the ropivacaine-treated group survived the administration of the 2 x CD dose. Mild hypotension developed in one dog and was treated with intravenous epinephrine (0.75 mg). This resulted in nodal tachycardia, which was abolished after treatment with bretylium. Another dog had two 1-s bursts of premature ventricular contractions requiring no treatment. The rapid treatment of convulsions and cardiovascular toxicity resulted in a decreased number of deaths in both groups when compared with dogs from a previously published study in which no therapy was instituted. Thus, early aggressive treatment of central nervous system and cardiovascular system toxicity is capable of reducing the incidence of mortality associated with the rapid intravenous administration of excessive doses of local anesthetics.

The presence of urinary cellular sediment and albuminuria in newspaper pressworkers exposed to solvents.

To investigate the relationship between exposure to organic solvents and the presence of increased urinary cellular sediment, we conducted a cross-sectional study of 215 newspaper pressroom workers who were exposed to solvent and lubricant mixtures. Thirty-two compositors were surveyed as referents. Industrial hygiene measurements showed low-level airborne exposures to organic solvents (primarily naphthas) and minimal airborne exposure to glycol ethers. There was a high prevalence of solvent-related dermatitis indicating there was significant dermal exposure to these substances. Pressworkers were exposed to solvent mixtures that were associated with dose-related increases in leukocyturia alone or in urinary cellular sediment (erythrocyturia and/or leukocyturia). The presence of urinary cellular sediment was associated with increasing frequency of use of five particular organic solvent mixtures. These results suggest that the increase in urinary cellular sediment may be due, at least in part, to the effects of solvents on the kidney. Consistent with this hypothesis, 16% of pressmen and no compositors were found to have primarily low-grade albuminuria detectable by dipstick. Workers with urinary cellular sediment were significantly more likely to have detectable albuminuria. Albuminuria was more likely to occur with increased frequency of use of four particular solvent mixtures. The presence of urinary cellular sediment was less likely to occur with occasional use of analgesics suggesting a possible etiologic role for acute or chronic urinary tract inflammation.

The effects of relaxation training on clinical symptoms: a meta-analysis.

Forty-eight experimental studies of nonmechanically assisted relaxation techniques used to control a variety of clinical symptoms were synthesized using meta-analysis. Effect sizes for three types of comparisons, experimental-control, experimental-placebo, and pre-post, ranged from .43 to .66, demonstrating that treatment of any type included in the analysis moved the client from the 50th to the 67th percentile of an untreated group at minimum and from the 50th to the 75th percentile at maximum. All treatments included in the analysis except Benson's relaxation technique demonstrated evidence of effectiveness, particularly for nonsurgical samples with chronic problems such as hypertension, headache, and insomnia.

Comparative motor-blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog.

Ropivacaine (S-(-)-1-propyl-2',6'-pipecoloxylidide) is a new local anesthetic that is structurally related to mepivacaine and bupivacaine. The comparative effects of ropivacaine and bupivacaine on motor function were assessed in the laboratory rat and dog. (It was not possible to accurately evaluate sensory blockade in these models.) Several concentrations of both agents were injected in the region of the sciatic nerve of the rat and into the lumbar epidural or subarachoid space in the dog. Epidural blockade was also performed utilizing solutions of ropivacaine and bupivacaine which contained epinephrine (1:200,000). The rat sciatic block studies indicate that at concentrations of 0.5 and 0.75%, ropivacaine had a slightly shorter time of onset and duration of motor blockade than did bupivacaine. In the epidural and spinal studies in the dog, ropivacaine was less potent and had a shorter duration of motor blockade than did bupivacaine at equal drug concentrations. A 1.0% solution of ropivacaine produced epidural motor blockade similar in onset and duration to that achieved with a 0.75% solution of bupivacaine. Epinephrine did not significantly prolong the duration of motor blockade of either agent after epidural administration.

Bupivacaine for intercostal nerve blocks in children: blood concentrations and pharmacokinetics.

A pharmacokinetic evaluation of bupivacaine was carried out after intercostal nerve blocks performed on 28 occasions in 27 children varying in age from 3 months to 16 yr. Bupivacaine HCl, 0.5%, with epinephrine 1:200,000 was employed. Doses of 2 mg/kg, 3 mg/kg, and 4 mg/kg resulted in peak whole blood arterial bupivacaine (base) concentrations (mean +/- SD) of 0.77 +/- 0.25 microgram/ml, 1.37 +/- 0.23 microgram/ml, and 1.87 +/- 0.53 microgram/ml, respectively. Calculated pharmacokinetic parameters (mean +/- SD) were the following: apparent volume of distribution (VD beta), 2.8 +/- 0.8 L/kg; steady-state volume of distribution (VDss), 2.7 +/- 0.7 L/kg; elimination half-life (t1/2 beta), 147 +/- 80 min; and total body clearance (Cl), 16.0 +/- 7.4 ml X min-1 X kg-1, or 382 +/- 201 ml X min-1 X m-2. Compared with data reported for adult patients, our data indicate that the volume of distribution is greater and clearance is more rapid in children than in adults. The absorption of local anesthetic from the intercostal space appears to be more rapid in children than adults. In an additional group of 11 children, the relationship of the bupivacaine blood:plasma concentration ratio (lambda) to hematocrit was investigated. Hematocrit in this group ranged from 30 to 59, and lambda varied from 0.47 to 0.82. There was a significant relationship between lambda and hematocrit defined by the equation lambda = -0.0079 Hct + 1.028 (r = 0.72, P less than 0.05). Reporting bupivacaine concentration in terms of plasma concentration may introduce an artifact that is dependent on the hematocrit, and we therefore suggest that whole blood concentration values be reported by investigators in the future.

A trial of deglycyrrhizinated liquorice in the treatment of duodenal ulcer.

A double-blind trial of deglycyrrhizinated liquorice was performed in 47 patients with active duodenal ulcer. Twenty-four patients received a placebo and 23 the trial medication (Caved-S) for one month. Both groups were clinically similar. No advantage of deglycyrrhizinated liquorice over placebo was found.