Multivisceral resection of advanced colon and rectal cancer: a prospective multicenter observational study with propensity score analysis of the morbidity, mortality, and survival.

Objectives: In the surgical treatment of colorectal carcinoma (CRC), 1 in 10 patients has a peritumorous adhesion or tumor infiltration in the adjacent tissue or organs. Accordingly, multivisceral resection (MVR) must be performed in these patients. This prospective multicenter observational study aimed to analyze the possible differences between non-multivisceral resection (nMVR) and MVR in terms of early postoperative and long-term oncological treatment outcomes. We also aimed to determine the factors influencing overall survival. Methods: The data of 25,321 patients from 364 hospitals who had undergone surgery for CRC (the Union for International Cancer Control stages I-III) during a defined period were evaluated. MVR was defined as (partial) resection of the tumor-bearing organ along with resection of the adherent and adjacent organs or tissues. In addition to the patients' personal, diagnosis (tumor findings), and therapy data, demographic data were also recorded and the early postoperative outcome was determined. Furthermore, the long-term survival of each patient was investigated, and a "matched-pair" analysis was performed. Results: From 2008 to 2015, the MVR rates were 9.9 % (n=1,551) for colon cancer (colon CA) and 10.6 % (n=1,027) for rectal cancer (rectal CA). CRC was more common in men (colon CA: 53.4 %; rectal CA: 62.0 %) than in women; all MVR groups had high proportions of women (53.6 % vs. 55.2 %; pairs of values in previously mentioned order). Resection of another organ frequently occurred (75.6 % vs. 63.7 %). The MVR group had a high prevalence of intraoperative (5.8 %; 12.1 %) and postoperative surgical complications (30.8 % vs. 36.4 %; each p<0.001). Wound infections (colon CA: 7.1 %) and anastomotic insufficiencies (rectal CA: 8.3 %) frequently occurred after MVR. The morbidity rates of the MVR groups were also determined (43.7 % vs. 47.2 %). The hospital mortality rates were 4.9 % in the colon CA-related MVR group and 3.8 % in the rectal CA-related MVR group and were significantly increased compared with those of the nMVR group (both p<0.001). Results of the matched-pair analysis showed that the morbidity rates in both MVR groups (colon CA: 42.9 % vs. 34.3 %; rectal CA: 46.3 % vs. 37.2 %; each p<0.001) were significantly increased. The hospital lethality rate tended to increase in the colon CA-related MVR group (4.8 % vs. 3.7 %; p=0.084), while it significantly increased in the rectal CA-related MVR group (3.4 % vs. 3.0 %; p=0.005). Moreover, the 5-year (yr) overall survival rates were 53.9 % (nMVR: 69.5 %; p<0.001) in the colon CA group and 56.8 % (nMVR: 69.4 %; p<0.001) in the rectal CA group. Comparison of individual T stages (MVR vs. nMVR) showed no significant differences in the survival outcomes (p<0.05); however, according to the matched-pair analysis, a significant difference was observed in the survival outcomes of those with pT4 colon CA (40.6 % vs. 50.2 %; p=0.017). By contrast, the local recurrence rates after MVR were not significantly different (7.0 % vs. 5.8 %; both p>0.05). The risk factors common to both tumor types were advanced age (>79 yr), pT stage, sex, and morbidity (each hazard ratio: >1; p<0.05). Conclusions: MVR allows curation by R0 resection with adequate long-term survival. For colon or rectal CA, MVR tended to be associated with reduced 5-year overall survival rates (significant only for pT4 colon CA based on the MPA results), as well as, with a significant increase in morbidity rates in both tumor entities. In the overall data, MVR was associated with significant increases in hospital lethality rates, as indicated by the matched-pair analysis (significant only for rectal CA).

Assessing environmental enteric dysfunction via multiplex assay and its relation to growth and development among HIV-exposed uninfected Tanzanian infants.

BACKGROUND: Environmental enteric dysfunction (EED) may contribute to poor growth and development in young children. While validated EED biomarkers are currently lacking, multiplex assays are able to capture multiple domains of the condition. The purpose of this exploratory study was to examine the relationship between biomarkers of EED and subsequent growth and development among Tanzanian HIV-exposed uninfected (HEU) infants. METHODOLOGY: We enrolled 467 infants of mothers living with HIV who had participated in a trial of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks (n = 365) and 6 months (n = 266) were analyzed for anti-flagellin and anti-lipopolysaccharide (LPS) IgA and IgG via ELISA as well as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), which incorporates two biomarkers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14)]. Outcomes were 12-month growth [length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and weight-for-age z-score (WAZ)] and development [Caregiver Reported Early Development Instruments (CREDI) z-scores] and were assessed using linear regression. FINDINGS: In primary analyses, higher quartiles of 6-month anti-LPS IgG concentrations were significantly associated with lower LAZ at 12 months (ptrend = 0.040). In secondary analyses, higher log2-transformed 6-week anti-flagellin IgA and 6-month anti-LPS IgA concentrations were significantly associated with lower LAZ at 12 months. No associations were observed between I-FABP or sCD14 and infant growth. However, higher log2-transformed 6-week sCD14 concentrations were significantly associated with lower overall CREDI z-scores, while higher log2-transformed 6-month I-FABP concentrations were significantly associated with higher overall CREDI z-scores. CONCLUSIONS: Unlike anti-flagellin and anti-LPS Igs, MEEDAT's biomarkers of EED (I-FABP and sCD14) were not associated with subsequent linear growth among HEU infants in Tanzania. The relationship between EED and infant development warrants further study.

Biomarkers of environmental enteric dysfunction and adverse birth outcomes: An observational study among pregnant women living with HIV in Tanzania.

BACKGROUND: Environmental enteric dysfunction (EED) may contribute to adverse birth outcomes in low-resource settings. We examined the associations of EED biomarkers with birth outcomes in pregnant women living with human immunodeficiency virus in Dar es Salaam, Tanzania. METHODS: We performed a cohort study of 706 HIV-infected pregnant women. Maternal serum samples collected at 32 weeks gestation were analyzed for markers of EED (anti-flagellin and anti-LPS immunoglobulins, intestinal fatty acid-binding protein [I-FABP] and soluble CD14), systemic inflammation (C-reactive protein and α1-acid glycoprotein [AGP]), and growth hormone resistance (insulin-like growth factor 1 [IGF-1] and fibroblast growth factor 21 [FGF21]. Associations of biomarkers categorized into quartiles with birth outcomes (birthweight, gestational duration, birthweight-for-gestational age, and stillbirth) were assessed using linear and log-binomial regression models adjusted for multiple sociodemographic and clinical variables. FINDINGS: Maternal EED biomarkers were not significantly associated with birthweight, gestation duration, or birthweight-for-gestational age. However, higher quintiles of I-FABP concentrations were associated with greater risk of stillbirth (ptrend=0·02). Higher AGP was associated with lower birthweight and was associated with increased risk of small-for-gestational age births. Higher IGF-1 was associated with higher birthweight and birthweight-for-gestational age while higher FGF21 was associated with shorter gestation and higher risk of preterm birth. INTERPRETATION: Maternal biomarkers of EED, systemic inflammation, and growth hormones were differentially associated with birth outcomes. Biomarkers of EED may be useful to identify pregnant women at risk of adverse birth outcomes, but further research is needed to confirm these findings and elucidate biological mechanisms. FUNDING: National Institutes of Health.

Current dichotomous metrics obscure trends in severe and extreme child growth failure.

Historically, the prevalence of child growth failure (CGF) has been tracked dichotomously as the proportion of children more than 2 SDs below the median of the World Health Organization growth standards. However, this conventional "thresholding" approach fails to recognize child growth as a spectrum and obscures trends in populations with the highest rates of CGF. Our analysis presents the first ever estimates of entire distributions of HAZ, WHZ, and WAZ for each of 204 countries and territories from 1990 to 2020 for children less than 5 years old by age group and sex. This approach reflects the continuous nature of CGF, allows us to more comprehensively assess shrinking or widening disparities over time, and reveals otherwise hidden trends that disproportionately affect the most vulnerable populations.

Improvement in appetite among stunted children receiving nutritional intervention in Bangladesh: results from a community-based study.

BACKGROUND/OBJECTIVES: Stunted children often have poor appetite, which may limit their response to nutritional interventions. We investigated the effect of a nutritional intervention on the appetite status of stunted children. METHODS: A longitudinal prospective intervention study was conducted with 50 stunted (length for age; LAZ < -2) (age and sex matched) aged 12-18 months and their mothers in Bauniabadh slum of Dhaka city. The stunted children received the following intervention package: one boiled egg and 150 ml milk daily 6 days a week for 3 months; psychosocial stimulation including structured play activities and parental counseling for 6 months; routine clinical care. Appetite status was measured using an interview-based tool "Early Childhood Appetite and Satiety Tool." RESULTS: Over the period of nutritional intervention, the mean appetite score increased from 49 to 60 in the stunted children and was associated with increased food consumption. Over the intervention period, both egg and milk consumption increased (40.3-49.6 g and 83.8-138.5 ml, respectively). CONCLUSIONS: Assessment of appetite status using EACST appears to be a useful tool for monitoring a nutritional intervention in stunted children. This tool may be useful for programs in managing child stunting in low-income countries and an important way to assess the efficacy of a nutritional intervention in these children.

Validation of the Micronutrient and Environmental Enteric Dysfunction Assessment Tool and evaluation of biomarker risk factors for growth faltering and vaccine failure in young Malian children.

Environmental enteric dysfunction (EED) is an intestinal disorder common among children in low-resource settings and is associated with increased risk of growth stunting, cognitive deficits, and reduced oral vaccine immunogenicity. The Micronutrient and EED Assessment Tool (MEEDAT) is a multiplexed immunoassay that measures biomarkers previously associated with child growth faltering and/or oral vaccine immunogenicity: intestinal fatty acid-binding protein (I-FABP), soluble CD14 (sCD14), insulin-like growth factor 1 (IGF-1), and fibroblast growth factor 21 (FGF21). MEEDAT also measures systemic inflammation (α1-acid glycoprotein, C-reactive protein), ferritin, soluble transferrin receptor, retinol binding protein 4, thyroglobulin, and Plasmodium falciparum antigenemia (histidine-rich protein 2). The performance of MEEDAT was compared with commercially available enzyme-linked immunosorbent assays (ELISAs) using 300 specimens from Malian infant clinical trial participants. Regression methods were used to test if MEEDAT biomarkers were associated with seroconversion to meningococcal A conjugate vaccine (MenAV), yellow fever vaccine (YFV), and pentavalent rotavirus vaccine (PRV) after 28 days, or with growth faltering over 12 weeks. The Pearson correlations between the MEEDAT and ELISA results were 0.97, 0.86, 0.80, and 0.97 for serum I-FABP, sCD14, IGF-1, and FGF21, respectively. There were significant associations between I-FABP concentration and the probability of PRV IgG seroconversion and between IGF-1 concentration and the probability of YFV seroconversion. In multivariable models neither association remained significant, however there was a significant negative association between AGP concentration and YFV seroconversion. GLP-2 and sCD14 concentrations were significantly negatively associated with 12-week change in weight-for-age z-score and weight-for-height z-score in multivariable models. MEEDAT performed well in comparison to commercially-available ELISAs for the measurement of four analytes for EED and growth hormone resistance. Adoption of MEEDAT in low-resource settings could help accelerate the identification of interventions that prevent or treat child stunting and interventions that boost the immunogenicity of child vaccinations.

Serum Adipokines, Growth Factors, and Cytokines Are Independently Associated with Stunting in Bangladeshi Children.

Growth in young children is controlled through the release of several hormonal signals, which are affected by diet, infection, and other exposures. Stunting is clearly a growth disorder, yet limited evidence exists documenting the association of different growth biomarkers with child stunting. This study explored the association between different growth biomarkers and stunting in Bangladeshi children. A quasi-experimental study was conducted among 50 stunted (length-for-age Z-score (LAZ) < -2 SD) and 50 control (LAZ ≥ -2 SD) children, aged 12-18 months, residing in a Bangladeshi slum. The enrolled stunted children received an intervention package, which included food supplementation for three months, psychosocial stimulation for six months, and routine clinical care on community nutrition center at the study field site. The controls received routine clinical care only. All children were clinically screened over the study period. Length, weight, fasting blood and fecal biomarkers were measured. All biomarkers levels were similar in both groups except for oxyntomodulin at enrolment. Leptin (adjusted odds ratio, AOR: 4.0, p < 0.01), leptin-adiponectin ratio (AOR 5.07 × 108, p < 0.01), insulin-like growth factor-1 (IGF-1) (AOR 1.02, p < 0.05), and gamma interferon (IFN-γ) (AOR 0.92, p < 0.05) levels were independently associated with stunting at enrolment. Serum leptin, leptin-adiponectin ratio, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and fecal alpha-1-antitrypsin (AAT) levels increased significantly (p < 0.001), while IFN-γ levels significantly decreased among stunted children after six months of intervention. Leptin, leptin-adiponectin ratio, IGF-1, and IFN-γ are independently associated with stunting in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT02839148.

Plasma Fibroblast Growth Factor 21 Is Associated with Subsequent Growth in a Cohort of Underweight Children in Bangladesh.

BACKGROUND: Current nutritional intervention strategies have not proven effective in improving childhood ponderal and linear growth in underweight and stunted children. Novel markers are needed to classify children who are likely to respond to available interventions and to identify those requiring additional interventions. Fibroblast Growth Factor 21 (FGF21), an endocrine hormone that regulates metabolism and growth during periods of reduced protein intake, may be useful in this context. OBJECTIVES: We aimed to determine the associations between plasma FGF21 concentrations and subsequent growth, and the association between change in FGF21 concentrations and concurrent growth, in children receiving nutritional supplementation. METHODS: A total of 120 children between ages 6 and 13 mo with weight-for-age z score (WAZ) between -3 and -2 were enrolled from an urban slum in Dhaka, Bangladesh. Children received 376-kcal feeding supplements daily for 5 mo and were followed for 5 additional mo. FGF21 was measured in plasma collected at enrollment and month 5. FGF21 values that fell above the 90th percentile of baseline concentrations (1056.5 pg/mL) were considered high. Linear regression was used to examine the association between baseline FGF21 status and 5-mo change in WAZ and length-for-age z score (LAZ), and the association between 5-mo change in FGF21 and concurrent WAZ and LAZ change. RESULTS: The median baseline FGF21 concentration was 241.4 pg/mL (IQR: 111.7, 451.3 pg/mL). On average, children with high baseline FGF21 gained 0.58 WAZ (95% CI: 0.28, 0.88) and 0.54 LAZ (95% CI: 0.23, 0.84) more during supplementation than those with low values. Change in FGF21 concentration during supplementation was negatively associated with change in WAZ (-0.48; 95% CI: -0.67, -0.29) and LAZ (-0.31; 95% CI: -0.52, -0.11). CONCLUSIONS: FGF21 may be a useful marker of growth faltering and may allow identification of children who are more or less likely to respond to nutritional supplementation. This trial was registered at clinicaltrials.gov as NCT02441426.

Pediatric cryptosporidiosis: An evaluation of health care and societal costs in Peru, Bangladesh and Kenya.

Cryptosporidium is a leading cause of pediatric diarrhea in resource-limited settings; yet, few studies report the health care costs or societal impacts of this protozoan parasite. Our study examined direct and indirect costs associated with symptomatic cryptosporidiosis in infants younger than 12 months in Kenya, Peru and Bangladesh. Inputs to the economic burden model, such as disease incidence, population size, health care seeking behaviour, hospital costs, travel costs, were extracted from peer-reviewed literature, government documents, and internationally validated statistical tools for each country. Indirect losses (i.e. caregiver income loss, mortality, and growth faltering) were also estimated. Our findings suggest that direct treatment costs per symptomatic cryptosporidiosis episode were highest in Kenya ($59.01), followed by Peru ($23.32), and Bangladesh ($7.62). The total annual economic impacts for the 0-11 month cohorts were highest in Peru ($41.5M; range $0.88-$599.3M), followed by Kenya ($37.4M; range $1.6-$804.5M) and Bangladesh ($9.6M, range $0.28-$91.5M). For all scenarios, indirect societal costs far outweighed direct treatment costs. These results highlight the critical need for innovative improvements to current prevention, diagnostic and treatment strategies available in resource poor settings, as well as the need for solutions that span multiple disciplines including food and water safety, sanitation and livestock production.

Biomarkers to Stratify Risk Groups among Children with Malnutrition in Resource-Limited Settings and to Monitor Response to Intervention.

Despite global efforts to reduce childhood undernutrition, current interventions have had little impact on stunting and wasting, and the mechanisms underlying growth faltering are poorly understood. There is a clear need to distinguish populations of children most likely to benefit from any given intervention and to develop tools to monitor response to therapy prior to the development of morbid sequelae. In resource-limited settings, environmental enteric dysfunction (EED) is common among children, contributing to malnutrition and increasing childhood morbidity and mortality risk. In addition to EED, early alterations in the gut microbiota can adversely affect growth through nutrient malabsorption, altered metabolism, gut inflammation, and dysregulation of the growth hormone axis. We examined the evidence linking EED and the gut microbiome to growth faltering and explored novel biomarkers to identify subgroups of children at risk of malnutrition due to underlying pathology. These and other biomarkers could be used to identify specific groups of children at risk of malnutrition and monitor response to targeted interventions.

Fecal Markers of Environmental Enteropathy and Subsequent Growth in Bangladeshi Children.

Environmental enteropathy (EE), a subclinical intestinal disorder characterized by mucosal inflammation, reduced barrier integrity, and malabsorption, appears to be associated with increased risk of stunting in children in low- and middle-income countries. Fecal biomarkers indicative of EE (neopterin [NEO], myeloperoxidase [MPO], and alpha-1-antitrypsin [AAT]) have been negatively associated with 6-month linear growth. Associations between fecal markers (NEO, MPO, and AAT) and short-term linear growth were examined in a birth cohort of 246 children in Bangladesh. Marker concentrations were categorized in stool samples based on their distribution (< first quartile, interquartile range, > third quartile), and a 10-point composite EE score was calculated. Piecewise linear mixed-effects models were used to examine the association between markers measured quarterly (in months 3-21, 3-9, and 12-21) and 3-month change in length-for-age z-score (ΔLAZ). Children with high MPO levels at quarterly time points lost significantly more LAZ per 3-month period during the second year of life than those with low MPO (ΔLAZ = -0.100; 95% confidence interval = -0.167 to -0.032). AAT and NEO were not associated with growth; however, composite EE score was negatively associated with subsequent 3-month growth. In this cohort of children from an urban setting in Bangladesh, elevated MPO levels, but not NEO or AAT levels, were associated with decreases in short-term linear growth during the second year of life, supporting previous data suggesting the relevance of MPO as a marker of EE.

Estimating the burden of paratyphoid a in Asia and Africa.

Despite the increasing availability of typhoid vaccine in many regions, global estimates of mortality attributable to enteric fever appear stable. While both Salmonella enterica serovar Typhi (S. Typhi) and serovar Paratyphi (S. Paratyphi) cause enteric fever, limited data exist estimating the burden of S. Paratyphi, particularly in Asia and Africa. We performed a systematic review of both English and Chinese-language databases to estimate the regional burden of paratyphoid within Africa and Asia. Distinct from previous reviews of the topic, we have presented two separate measures of burden; both incidence and proportion of enteric fever attributable to paratyphoid. Included articles reported laboratory-confirmed Salmonella serovar classification, provided clear methods on sampling strategy, defined the age range of participants, and specified the time period of the study. A total of 64 full-text articles satisfied inclusion criteria and were included in the qualitative synthesis. Paratyphoid A was commonly identified as a cause of enteric fever throughout Asia. The highest incidence estimates in Asia came from China; four studies estimated incidence rates of over 150 cases/100,000 person-years. Paratyphoid A burden estimates from Africa were extremely limited and with the exception of Nigeria, few population or hospital-based studies from Africa reported significant Paratyphoid A burden. While significant gaps exist in the existing population-level estimates of paratyphoid burden in Asia and Africa, available data suggest that paratyphoid A is a significant cause of enteric fever in Asia. The high variability in documented incidence and proportion estimates of paratyphoid suggest considerable geospatial variability in the burden of paratyphoid fever. Additional efforts to monitor enteric fever at the population level will be necessary in order to accurately quantify the public health threat posed by S. Paratyphi A, and to improve the prevention and treatment of enteric fever.

Impact of helminth diagnostic test performance on estimation of risk factors and outcomes in HIV-positive adults.

BACKGROUND: Traditional methods using microscopy for the detection of helminth infections have limited sensitivity. Polymerase chain reaction (PCR) assays enhance detection of helminths, particularly low burden infections. However, differences in test performance may modify the ability to detect associations between helminth infection, risk factors, and sequelae. We compared these associations using microscopy and PCR. METHODS: This cross-sectional study was nested within a randomized clinical trial conducted at 3 sites in Kenya. We performed microscopy and real-time multiplex PCR for the stool detection and quantification of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Strongyloides stercoralis, and Schistosoma species. We utilized regression to evaluate associations between potential risk factors or outcomes and infection as detected by either method. RESULTS: Of 153 HIV-positive adults surveyed, 55(36.0%) and 20(13.1%) were positive for one or more helminth species by PCR and microscopy, respectively (p<0.001). PCR-detected infections were associated with farming (Prevalence Ratio 1.57, 95% CI: 1.02, 2.40), communal water source (PR 3.80, 95% CI: 1.01, 14.27), and no primary education (PR 1.54, 95% CI: 1.14, 2.33), whereas microscopy-detected infections were not associated with any risk factors under investigation. Microscopy-detected infections were associated with significantly lower hematocrit and hemoglobin (means of -3.56% and -0.77 g/dl) and a 48% higher risk of anemia (PR 1.48, 95% CI: 1.17, 1.88) compared to uninfected. Such associations were absent for PCR-detected infections unless infection intensity was considered, Infections diagnosed with either method were associated with increased risk of eosinophilia (PCR PR 2.42, 95% CI: 1.02, 5.76; microscopy PR 2.92, 95% CI: 1.29, 6.60). CONCLUSION: Newer diagnostic methods, including PCR, improve the detection of helminth infections. This heightened sensitivity may improve the identification of risk factors for infection while reducing ability to discriminate infections associated with adverse clinical outcomes. Quantitative assays can be used to differentiate infection loads and discriminate infections associated with sequelae.

Autoantibodies against thyroid hormones and their influence on thyroxine determination with chemiluminescence immunoassay in dogs.

Autoantibodies against thyroxin (T4AA) and triiodothyronine (T3AA) are present in dogs with autoimmune thyroiditis and have been reported to interfere with immunoassays. The objectives of this study were to determine the frequency of autoantibodies and to determine whether interference occurs by T4AA, using a non-immunological method (high performance liquid chromatography, HPLC) for thyroxin (T4) measurement. Based on clinical symptoms, T4 and thyroid stimulating hormone (TSH) concentration, 1,339 dogs were divided into six groups: Group 1: hypothyroid (n = 149); Group 2: subclinical thyroiditis (n = 110); Group 3: suspicious for non thyroidal illness (n = 691); Group 4: biochemical euthyroid (n = 138); Group 5: hypothyroid dogs under substitution therapy (n = 141); Group 6: healthy dogs (n = 110). The incidence of T4AA and T3AA, determined using radiometric assay, was low (0.5% and 3.8%) and higher in hypothyroid dogs compared to dogs suspicious for hypothyroidism (Group 2-4) (p < 0.05). T4AA was not detected in dogs with normal T4 and elevated TSH. T4 concentrations of T4AA positive samples determined using HPLC were comparable to results obtained by chemiluminescence immunoassay. These findings indicate that the probability of interference of T4AA leading to falsely elevated T4 concentration in the T4 assay seems to be low.

An experimental analysis of the contribution of 210Po and of 210Po produced by 210Pb decay to the gross alpha-particle activity of water samples.

The contribution of 210Po and of 210Po produced by 210Pb decay to the gross alpha-particle activity of water samples by U.S. Environmental Protection Agency Method 900.0 is investigated as a function of residue mass and geometry and time between sample collection and analysis. It is shown that these factors can cause the contribution to gross alpha-particle activity of 210Po to be up to 2.0 and 1.1 times the initial 210Po activity for grab and quarterly composite samples, respectively, and can cause the contribution to gross alpha-particle activity of 210Po from 210Pb decay to be up to 1.1 times and 1.5 times the 210Pb activity for grab and quarterly composite samples, respectively. It is also shown qualitatively that at least for some residues, there is a loss of polonium due to volatilization when the sample is heated over a flame.

An experimental analysis of the contribution of 228Ra progeny to the gross alpha-particle activity of water samples.

The contribution of 228Ra progeny to the gross alpha-particle activity of water samples by EPA Method 900.0 is investigated as a function of residue mass and geometry and time between sample collection and analysis. It is shown that these factors can cause the contribution of 228Ra progeny to gross alpha-particle activity to be up to 2.2 times the initial 228Ra activity for grab samples and up to 3.5 times the initial 228Ra activity for quarterly composite samples when samples are held for the maximum 6-mo holding time. Thus, under some conditions, 228Ra, by itself, can cause a gross alpha-particle violation (>0.55 Bq L(-1)). Since 228Ra activity is already regulated, a gross alpha-particle activity violation that only exists because of the presence of 228Ra can be considered to be a false positive violation.

An experimental analysis of the contribution of 224Ra and 226Ra and progeny to the gross alpha-particle activity of water samples.

The gross alpha-particle activity of water samples analyzed by EPA Method 900.0 is investigated as a function of residue mass and geometry, time between sample collection and analysis, and time between sample preparation and analysis for samples containing 224Ra, 212Pb, and 226Ra. It is shown that the gross alpha-particle activity due to 224Ra and its progeny can be up to 10 times the 224Ra activity at collection time and that due to 212Pb progeny can be up to 3 times the 212Pb activity at collection time. In samples with roughly equal activities of 224Ra and 226Ra analyzed soon after collection, it is shown that the gross alpha-particle activity is approximately constant with time because the decay of 224Ra and its progeny is offset by the ingrowth of 226Ra progeny.

Multiple model approach to modelling of Escherichia coli fed-batch cultivation extracellular production of bacterial phytase

The paper presents the implementation of multiple model approach to modelling of Escherichia coli BL21(DE3)pPhyt109 fed-batch cultivation processes for an extracellular production of bacterial phytase. Due to the complex metabolic pathways of microorganisms, the accurate modelling of bioprocesses is rather difficult. Multiple model approach is an alternative concept which helps in modelling and control of complex processes. The main idea is the development of a model based on simple submodels for the purposes of further high quality process control. The presented simulations of E. coli fed-batch cultivation show how the process could be divided into different functional states and how the model parameters could be obtained easily using genetic algorithms. The obtained results and model verification demonstrate the effectiveness of the applied concept of multiple model approach and of the proposed identification scheme.

Characterization of ethyl chloroformate derivative of beta-methylamino-L-alanine.

Beta-methylamino-L-alanine (BMAA) is a neurotoxic amino acid that can be produced by cyanobacteria in aqueous environments. To analyze this compound by gas chromatography/mass spectrometry (GC/MS), BMAA must be derivatized to a nonpolar, volatile compound. This can be accomplished by reacting BMAA with ethyl chloroformate. While carrying out electron ionization (EI) mass spectrometric analysis on the (13)C-labeled derivative, it was discovered that the formation of an ion with a peak at m/z 245.12 is the result of [CH(3)CH(2)O.] loss from the amino groups resulting from alpha-cleavage. This differs from previous reports that attributed this peak to alpha-cleavage of the carboxylic ester portion of the BMAA derivative. This finding is important for understanding BMAA derivative mass spectrometric fragmentation patterns and ultimately to properly identifying and quantifying BMAA. Fragmentation pathways for the formation of other major peaks observed in the EI mass spectra are also proposed.