Measurement differences between turbidity instruments, and their implications for suspended sediment concentration and load calculations: A sensor inter-comparison study.

The use of turbidity for indicating environmentally detrimental levels of suspended and colloidal matter in freshwater systems, and for defining acceptable water quality standards in national and European drinking water regulations, is well established. Turbidity is therefore frequently adopted as a surrogate for suspended sediment concentrations (SSC), or as a relative and objective measure of water clarity in monitoring programmes. Through systematic, controlled experimentation, we tested the response of 12 commercially available turbidity sensors, of various designs, to gauge their measurement consistency when benchmarked against pre-prepared sediment suspensions of known SSC. Results showed that despite calibration to a Formazin standard, sensor responses to identical SSC solutions (in the range of 20-1000 mg L-1) varied considerably. For a given SSC, up to five-fold differences in recorded turbidity were recorded across the tested instruments. Furthermore, inconsistent measurements were identified across instruments, regardless of whether they operated using backscatter or side-scatter optical principles. While the findings may have implications for compliance with turbidity-based water quality standards, they are less likely to be an issue when turbidity is being used as a surrogate for SSC, provided that instrument use remains constant and that instrument drift is not an issue. In this study, a field comparison of a subset of four study sensors showed that despite very different absolute turbidity readings for a given SSC, well correlated and reliable turbidity - SSC ratings were established (as evidenced by r2 coefficients from 0.92 to 0.98). This led to reasonably consistent suspended sediment load estimates of between 64.7 and 70.8 tonnes for a rainfall event analysed. This study highlights the potential for issues to arise when interpreting water turbidity datasets that are often assumed to be comparable, in that measurement inconsistency of the type reported here may remain unknown to water resource decision-makers and practitioners.

Enhanced wave overtopping simulation at vertical breakwaters using machine learning algorithms.

Accurate prediction of wave overtopping at sea defences remains central to the protection of lives, livelihoods, and infrastructural assets in coastal zones. In addressing the increased risks of rising sea levels and more frequent storm surges, robust assessment and prediction methods for overtopping prediction are increasingly important. Methods for predicting overtopping have typically relied on empirical relations based on physical modelling and numerical simulation data. In recent years, with advances in computational efficiency, data-driven techniques including advanced Machine Learning (ML) methods have become more readily applicable. However, the methodological appropriateness and performance evaluation of ML techniques for predicting wave overtopping at vertical seawalls has not been extensively studied. This study examines the predictive performance of four ML techniques, namely Random Forest (RF), Gradient Boosted Decision Trees (GBDT), Support Vector Machines-Regression (SVR), and Artificial Neural Network (ANN) for overtopping discharge at vertical seawalls. The ML models are developed using data from the EurOtop (2018) database. Hyperparameter tuning is performed to curtail algorithms to the intrinsic features of the dataset. Feature Transformation and advanced Feature Selection methods are adopted to reduce data redundancy and overfitting. Comprehensive statistical analysis shows superior performance of the RF method, followed in turn by the GBDT, SVR, and ANN models, respectively. In addition to this, Decision Tree (DT) based methods such as GBDT and RF are shown to be more computationally efficient than SVR and ANN, with GBDT performing simulations more rapidly that other methods. This study shows that ML approaches can be adopted as a reliable and computationally effective method for evaluating wave overtopping at vertical seawalls across a wide range of hydrodynamic and structural conditions.

New insights in the probability distributions of wave-by-wave overtopping volumes at vertical breakwaters.

Advances in the development of prediction tools for wave overtopping allow now for overtopping volumes to be estimated with good accuracy, with the combined use of mean overtopping rates and maximum wave by wave overtopping volumes in a sequence of wave overtopping events. While previous literature has tended to focus on mean overtopping rates at coastal structures, limited studies have investigated the wave by wave overtopping volumes at coastal sea defences; in particular, a paucity of studies have focussed on the prediction of the shape parameter in the Weibull distribution (i.e., Weibull b) of overtopping volumes. This study provides new insights on the probability distribution of individual wave overtopping volumes at plain vertical seawalls by analysing the measured Weibull b values derived from a series of laboratory experiments on seawalls performed on a wide range of wave conditions and crest freeboards. The influence of wave conditions (wave steepness, significant wave height), structural parameters (crest freeboard, toe water depth), impulsiveness, probability of overtopping waves, and overtopping discharge on Weibull b parameter were examined, and then compared with the well-established empirical formulae. For the conditions covered within this study, it was found that the probability distribution of wave-by-wave overtopping volumes follow a 2-parameter Weibull distribution. No apparent differences in Weibull b values were reported with the variation of incident wave steepness and impulsiveness parameter. Results of this study revealed that Weibull b values at vertical walls, subjected to non-impulsive wave conditions, can be predicted reasonably well using relative freeboard and relative overtopping rates. A new unified formula is proposed for the estimation of Weibull b values at vertical walls under impulsive and non-impulsive wave attack.

Enhancement of lobster growth.

Selected captive lobsters have been successfully mated at the Massachusetts Lobster Hatchery. Progeny raised in warm seawater grew at least four times as fast as lobsters grown at ambient ocean temperatures. These studies demonstrate that lobsters will reach sexual maturity (a weight of about 454 grams) in less than 2 years, compared to 8 years at ambient temperatures in Canadian waters. A further reduction in this time has been achieved by phenotypic selection for fast-growing lobsters. Our initial success in accelerating growth and in mating selected parents suggests that lobster farming may be possible.

The relationship between gestational age, systolic blood pressure and pulse pressure in children.

This cross-sectional study investigates the relationship between gestational age and systolic blood pressure and pulse pressure in childhood. Blood pressure was measured in 483 schoolchildren, free from cardiovascular disease, aged between 6 and 16 years. Pulse pressure was estimated as the difference between the 24-h mean systolic and diastolic blood pressure values. Linear regression showed an inverse relationship between gestational age and mean 24-h systolic blood pressure (adjusted regression coefficient mm Hg per week gestation -0.631, 95% confidence interval (CI) -1.21 to -0.04, P=0.036). Further, linear regression showed a significant negative association between gestational age and log-transformed pulse pressure (adjusted antilog regression coefficient mm Hg per week of gestation -1.39, 95% CI -2.96 to -0.3, P=0.013), which after gender-specific analyses was found to be restricted to the girls in the study. The results of the present study suggest that low gestational age is associated with elevated systolic blood pressure and pulse pressure in childhood, the latter particularly in girls. This observation provides some support for the developmental origins of adult disease hypothesis-that adverse events in early life may have long-term consequences for cardiovascular health. However, as gestational age itself is unlikely to be the causal event in determining blood pressure control, further investigation is required, particularly with regard to the nutritional, physiological and molecular mechanisms that explain such epidemiological observations.

Modelling spatial and temporal variations of annual suspended sediment yields from small agricultural catchments.

Estimates of sediment yield are important for ecological and geomorphological assessment of fluvial systems and for assessment of soil erosion within a catchment. Many regulatory frameworks, such as the Convention for the Protection of the Marine Environment of the North-East Atlantic, derived from the Oslo and Paris Commissions (OSPAR) require reporting of annual sediment fluxes. While they may be measured in large rivers, sediment flux is rarely measured in smaller rivers. Measurements of sediment transport at a national scale can be also challenging and therefore, sediment yield models are often utilised by water resource managers for the predictions of sediment yields in the ungauged catchments. Regression based models, calibrated to field measurements, can offer an advantage over complex and computational models due to their simplicity, easy access to input data and due to the additional insights into factors controlling sediment export in the study sites. While traditionally calibrated to long-term average values of sediment yields such predictions cannot represent temporal variations. This study addresses this issue in a novel way by taking account of the variation from year to year in hydrological variables in the developed models (using annual mean runoff, annual mean flow, flows exceeded in five percentage of the time (Q5) and seasonal rainfall estimated separately for each year of observations). Other parameters included in the models represent spatial differences influenced by factors such as soil properties (% poorly drained soils and % peaty soils), land-use (% pasture or % arable lands), channel slope (S1085) and drainage network properties (drainage density). Catchment descriptors together with year-specific hydrological variables can explain both spatial differences and inter-annual variability of suspended sediment yields. The methodology is demonstrated by deriving equations from Irish data-sets (compiled in this study) with the best model efficiency of 0.84 and best model fit of adjusted R2 of 0.82. Presented approach shows the potential for regression based models to model contemporary suspended sediment yields in small river systems.

The relationship between birth weight and pulse pressure in children: cross-sectional study.

This cross-sectional study investigates the relationship between birth weight and pulse pressure in childhood, after adjusting for mean blood pressure values and for potential confounding factors. Blood pressure was measured in 937 schoolchildren, free from cardiovascular disease, aged between 6 and 16 years. Pulse pressure was estimated as the difference between the 24 h mean systolic and diastolic blood pressure values. Linear regression showed a significant negative association between birth weight and log-transformed pulse pressure, which after gender-specific analyses was found to be restricted to the girls in the study (adjusted regression coefficient log mmHg per kg -0.06, 95% CI -0.09 to -0.03). A previous investigation of this cohort reported a significant negative association between birth weight and both systolic and diastolic blood pressure, again restricted to the girls in the cohort. The results of the present study provide limited support for the hypothesis that pulse pressure in childhood is determined in utero, particularly for female subjects. However, as little research has been published in this area, further investigation is required and in particular it would be important to assess whether such gender differences are apparent in other cohorts.

The impact of cattle access on ecological water quality in streams: Examples from agricultural catchments within Ireland.

Unrestricted cattle access to rivers and streams represent a potentially significant localised pressure on freshwater systems. However there is no consensus in the literature on the occurrence and extent of impact and limited research has examined the effects on aquatic biota in the humid temperate environment examined in the present study. Furthermore, this is one of the first times that research consider the potential for cattle access impacts in streams of varying water quality in Northern Europe. We investigated the effects of cattle access on macroinvertebrate communities and deposited fine sediment levels, in four rivers of high/good and four rivers of moderate water quality status which drain, low gradient, calcareous grassland catchments in Ireland. We assessed the temporal variability in macroinvertebrates communities across two seasons, spring and autumn. Site specific impacts were evident which appeared to be influenced by water quality status and season. All four high/good water status rivers revealed significant downstream changes in community structure and at least two univariate metrics (total richness and EPT richness together with taxon, E and EPT abundance). Two of the four moderate water status rivers showed significant changes in community structure, abundance and richness metrics and functional feeding groups driven in the main by downstream increases in collectors/gatherers, shredders and burrowing taxa. These two moderate water status rivers had high or prolonged livestock activity. In view of these findings, the potential for some of these sites to achieve at least high/good water quality status, as set out in the EU Water Framework Directive, may be compromised. The results presented highlight the need for additional research to further define the site specific factors and livestock management practices, under different discharge conditions, that increase the risk of impact on aquatic ecology due to these cattle-river interactions.

Evaluating the relationship between biotic and sediment metrics using mesocosms and field studies.

An ongoing research challenge is the detection of biological responses to elevated sediment and the identification of sediment-specific bioassessment metrics to evaluate these biological responses. Laboratory mesocosms and field observations in rivers in Ireland were used to evaluate the relationship between a range of biological and sediment metrics and to assess which biological metrics were best at discerning the effects of excess sediment on macroinvertebrates. Results from the mesocosm study indicated a marked decrease in the abundance of sensitive taxa with increasing sediment surface cover. % EPT (Ephemeroptera, Plecoptera, Trichoptera) and % E abundances exhibited the strongest negative correlation with sediment surface cover in the mesocosm study. The field study revealed that % EPT abundance was most closely correlated with % sediment surface cover, explaining 13% of the variance in the biological metric. Both studies revealed weaker relationships with a number of other taxonomy-based metrics including total taxon abundance, total taxon richness and moderate relationships with the Proportion of Sediment-sensitive Invertebrates metric (PSI). All trait-based metrics were poorly correlated with sediment surface cover in the field study. In terms of sediment metrics, % surface cover was more closely related to biological metrics than either re-suspendable sediment or turbidity. These results indicate that % sediment surface cover and % EPT abundance may be useful metrics for assessing the effect of excessive sediment on macroinvertebrates. However, EPT metrics may not be specific to sediment impact and therefore when applied to rivers with multiple pressures should be combined with observations on sediment cover.

Digoxin or flecainide for prophylaxis of supraventricular tachycardia in infants?

OBJECTIVES: This study compared the safety and efficacy of digoxin and flecainide in the prophylaxis of supraventricular tachycardia in infants. BACKGROUND: Recurrence of supraventricular tachycardia in infants is common. Digoxin is the conventional drug of first choice for prophylaxis, but its efficacy has not been tested in a controlled clinical trial, and there is no consensus on the drug of choice when digoxin is ineffective. METHODS: We reviewed retrospectively the records of all infants with supraventricular tachycardia due to atrioventricular (AV) reentry admitted to our hospital between January 1986 and December 1993. RESULTS: Thirty-nine infants presented with sustained AV reentrant tachycardia at age 1 to 330 days (median 12). Intravenous flecainide was required to maintain immediate control in six patients who were then treated with oral flecainide. The other 33 patients were treated with oral digoxin. There was no recurrence of tachycardia in 14 (42%) of the 33 patients (95% confidence interval [CI] 25% to 61%). In the other 19 patients (58%) (95% CI 39% to 75%), digoxin was replaced by oral flecainide because of multiple recurrence of tachycardia. Full control was achieved in all 19 of these patients (100%) (95% CI 82% to 100%) and in 5 of the 6 patients treated with both intravenous and oral flecainide. Thus, overall, flecainide was effective in 24 (96%) of 25 patients (95% CI 80% to 100%). CONCLUSIONS: Comparison with previous natural history studies suggests that digoxin is ineffective in the prophylaxis of supraventricular tachycardia. Oral flecainide was effective in a small number of infants, with no adverse effects (95% CI 0% to 12%), and may now be preferred as the primary prophylactic agent.

In-hospital prognosis of patients with fasting hyperglycemia after first myocardial infarction.

OBJECTIVE: To investigate the incidence and prognostic significance of fasting hyperglycemia in a large group of patients with a first myocardial infarction. RESEARCH DESIGN AND METHODS: Blood glucose was measured after an 8-h overnight fast in 752 patients with a first myocardial infarction. Three groups of patients were identified: patients with normal fasting blood glucose (92.5%), patients with fasting hyperglycemia but no prior history of glucose intolerance (3%), and patients previously known to have diabetes mellitus (4.5%). RESULTS: The fasting hyperglycemic patients were significantly older and had significantly more in-hospital complications than the normal blood glucose group. Previously known diabetic subjects tended to be older and had more mechanical complications postinfarction than the group with normal blood glucose but the difference did not reach statistical significance. There was no significant difference between the diabetic subjects and patients with fasting hyperglycemia in mean age and in-hospital prognosis. CONCLUSIONS: Fasting hyperglycemia detected after a first myocardial infarction is associated with a poor in-hospital prognosis that was not due to larger infarct size, as reflected in peak levels of cardiac enzymes. The measurement of a fasting blood glucose level provides additional information in identifying high-risk groups of patients postinfarction.

Tracking of 24-hour and casual blood pressure: a 1-year follow-up study in adolescents.

OBJECTIVE: Tracking of blood pressure begins in childhood but the relationship between casual blood pressure in childhood and adult levels is not strong enough to predict adult hypertension. The variability of blood pressure in children might suggest that 24 recordings would have less consistency than casual readings when repeated even a relatively short time later. This study compares the short-term tracking ability of casual versus 24-h blood pressure. DESIGN: An ambulatory blood pressure device was placed on 50 teenagers. Readings were taken at rest and the device was then worn for approximately 24 h, which included the schoolday. The protocol was repeated 1 year later. RESULTS: The correlation coefficient for systolic readings taken 1 year later were: 0.4 for casual, 0.6 for school, 0.6 for home, 0.5 for night-time and 0.8 for 24-h mean systolic blood pressures. When divided into upper and lower tertiles of systolic blood pressure the relationship between tertile ranking 1 year later was stronger for 24-h blood pressure than the casual readings. Casual diastolic pressure was more consistent than the 24-h mean diastolic measurement. CONCLUSIONS: In adolescents, in whom tracking of casual blood pressure has been shown to be poor, 24-h mean systolic blood pressure tracks better than any other time period and significantly better than the casual systolic readings. This study needs to be extended and the ability of 24-h blood pressure to track from childhood to adult life investigated.

High prevalence of anemia after cardiac transplantation in children.

BACKGROUND: Chronic anemia is common in adults after successful cardiac transplantation. However, the prevalence of anemia in children after cardiac transplantation is uncertain. The purpose of this study was to investigate the prevalence and causes of chronic anemia in well children after cardiac transplantation and in particular to define the role, if any, of iron deficiency, which is important and relatively common in normal children. METHODS: Twenty children (ages 7 months to 16 years) who were well 4 months to 6 years after cardiac transplantation were studied. Fourteen children (70%) were anemic and enrolled in a prospective trial of iron supplementation. RESULTS: In the majority of children, serum iron and erythropoietin levels were low, although serum ferritin and zinc protoporphyrin levels tended to be normal or high. Only one child demonstrated a definite response to iron supplementation, although the hemoglobin level remained low. CONCLUSIONS: Anemia is highly prevalent in this population, and, despite the presence of low serum iron and transferrin saturation, anemia is not usually due to iron deficiency. Although the diagnosis of iron deficiency in this group is difficult and must not be missed, inappropriate therapy should be avoided. In the majority of children, there appears to be an anemia of chronic disease which may be secondary to chronic inflammation or an effect of cyclosporine on erythropoietin production.

Hemolysis and suppression of neutrophil chemotaxis by a low molecular weight component of human burn patient sera.

During the past year, we have reported the isolation and characterization of a low molecular mass (less than 5000 Da) complex (SAP), having profound immunosuppressive activity, found in the plasma of patients with major thermal injuries. Our continued studies have revealed that non-cytotoxic inhibition of neutrophil chemotaxis by SAP is paralleled by erythrocyte hemolysis by the same compound. Both neutrophil inhibitory and hemolytic activities appear to be a function of the peptide portion of SAP (determined by sensitivity to trypsin and pronase), which is augmented by the presence of sialic acid in the complex (activity eliminated by the addition of neuraminidase). The lipid portion of SAP, which is critical to its neutrophil immunosuppressive activity, does not appear to participate in erythrocyte hemolysis. Hemolytic activity of SAP is not due to protease activity, and does not appear to be receptor dependent. However, it is completely dependent upon the presence of calcium. The hemolytic activity of SAP appears to be abrogated by the addition of cerium nitrate, leading to a hypothesized relationship of SAP to the immunological activity of "burn toxin", previously described in detail (Schoenenberger, G.A. (1975) Monogr. Allergy 9, 72-139).

Innate natural antibodies. Primary roles indicated by specific epitopes.

Two members of a unique class of natural antibodies have been identified in all of a large cohort of sera from clinically normal humans of broad age distribution. By means of a series of 10-12 mer peptides the epitope for each of those antibodies was characterized with regard to amino acid identity and conformation. Similar epitope specificity was revealed for the IgM isotopes of cord blood and early post natal sera and for IgM and IgG of adult sera, suggesting that the class of natural antibodies represented by the two identified in this study includes those genomically coded for at their effector level of maturation in the B cells of the neonate. Assay of series of specimens from each of four clinically normal adults revealed that those two natural antibodies are present at relatively constant titer, unique to each individual, over four to five and a half year periods. Those observations imply that the primary function of that class of natural antibodies may be related to maintenance of homeostasis and the molecular identity of each of the two epitopes suggests a role, for each, as monitor or control in intracellular traffic. The previous identification of those epitopes in a conserved protein of HIV also provides support for the proposition that a secondary function of natural antibodies, arising from fortuitous coincidence of the identity of the epitopes, may be that of early defense against infectious invaders.

The human uniqueness of HIV: innate immunity and the viral Tat protein.

We have previously reported, and confirm here, that the human innate system of natural antibodies includes two, each of which is reactive, presumably by happenstance, with a specific sequence of HIV Tat protein. Comparison of cohorts of HIV+ and normal (HIV-) sera indicate that, following a period of post-infection latency, the titers of those natural antibodies decline and other Tat reactive antibodies, as evidence of induced immune response, do not arise. That human-typical pattern of innate/adaptive reactivity with HIV Tat protein is shared by chimpanzees, but not by other mammals tested in this study, in which those natural antibodies are not present, and apparently induced Tat-reactive antibodies do arise. Evidence of a temporal relationship between the decline of the Tat reactive natural antibodies and progression of HIV pathogenesis, including demise of CD4+T cells, suggests a role for those antibodies in retardation of that pathoprogression. However, that providential arrest of Tat-related pathogenicity may be limited by the immune system recognition of the natural antibody-reactive sequences of Tat as "self" with consequent induction of tolerance and restriction of production of those antibodies. The limited occurrence of progression to AIDS in chimpanzees may reflect an additional innate characteristic, one of resistance to tolerance-based diminishment of the protective natural antibodies. Although not yet defined, that characteristic may be shared by the occasionally observed HIV+ humans known as LTNP (longterm-non-progressors).

Effect of pH and ammonium ions on mutagenic activity in cooked beef.

Controversy surrounding the extraction procedure commonly used for isolating and concentrating mutagens from foods has resulted in a need for the re-examination of the reported mutagenicity in fried hamburgers. Using a procedure in which Na2SO4 and NaOH are substituted for (NH4)2SO4 and NH4OH respectively, mutagenic activity in extracts of hamburgers fried for 5 min appeared to be unchanged. However, when organic extractions are performed at pH conditions more moderate than those generally employed to isolate mutagens from foods, a 30-50% decrease in mutagenicity is observed.

A source of error in mutagen testing of foods.

Mutagenic compounds reported to be present in foods may be forming during the extraction process rather than during cooking or baking. In this study, the formation of mutagenic substances in biscuits was examined using in the extraction procedure either ammonium sulfate and ammonium hydroxide or sodium sulfate and sodium hydroxide. Compounds producing high mutagenic activity in Salmonella strains 1538 and TA 98 obtained from aqueous biscuit extracts containing ammonium ions. No mutagenic activity was observed in extracts from aqueous biscuit extracts containing sodium ions until some ammonium ions (NH4OH) were added. We suggest that ammonium sulfate and ammonium hydroxide not be used in the extraction procedure of food when studying mutagen formation.

Long-term follow-up of pediatric cardiac transplant recipients on a steroid-free regime: the role of endomyocardial biopsy.

BACKGROUND: Endomyocardial biopsy is used in long-term follow-up of cardiac transplant recipients to detect sub-clinical rejection. The value of this for adults and children on triple-drug immunosuppression has been disputed. We investigated its value in children maintained on a steroid-free regime. METHODS: We used a retrospective review of annual surveillance biopsy results from children younger than 13 years at the time of cardiac transplant. RESULTS: In a series of 40 children older than 10 years, we found no evidence of rejection in 88/130 (67.7%) biopsies; 41/130 (31.5%) showed grade 1A rejection, and 1/130 (0.8%) showed grade 1B rejection. No grade 2, 3, or 4 biopsies were found. Nine patients with 1A rejection had subsequent grade 0 biopsies, without any adjustment in treatment. Seven children had treatment changes and repeat biopsies because of grade 1A biopsies. CONCLUSION: Significant late rejection is rare even in children on steroid-free maintenance. It is unlikely to be detected unexpectedly, and the practice of indefinite routine biopsy in children who are well is not justified. Future use should focus on individuals at higher risk of rejection.

Radioimmunoassay that measures serum vitamin B12.

AIMS: To develop a specific radioimmunoassay for the routine determination of serum vitamin B12. METHODS: Antisera were raised in rabbits by immunisation with the monocarboxylic acid derivative of cyanocobalamin coupled to human serum albumin. Antibody titres and affinities were determined and the antiserum giving the highest binding affinity constant, Ka, was used to develop the assay protocol. Donkey-anti-rabbit gamma globulin-coated magnetisable particles were used to separate the bound from free vitamin B12. The considerable cobalamin binding capacity of human serum was destroyed by autoclaving in acetate-cyanide buffer. Sixty samples were assayed by the radioimmunoassay (RIA) and the Lactobacillus leichmannii assay. Recovery and cross-reactivity experiments were performed. RESULTS: Final rabbit antibody titres varied from 1/20,000 to 1/188,000. Scatchard plots did not correlate with the antibody titres. The Ka values varied from 2.6 to 6.7 x 10(10) litres/mol. For maximum sensitivity the highest Ka (titre 1/66,000) was chosen. A tracer concentration of 22 pmol/l, an antiserum dilution of 1/100,000, and a sample volume of 0.1 ml were used. At an antiserum dilution of 1 in 100,000 the cyanocobalamin binding of the rabbit serum was diluted out. The assay showed excellent correlation with the microbiological assay, with 100% recovery of added vitamin B12. Levels of cross-reactivity for dicyanide cobinamide and hydroxocobalamin were 9.8 and 8.1%, respectively. CONCLUSIONS: The development of this immunoassay permits the measurement of serum vitamin B12 without important interference from cobalamin analogues, related corrinoids, and non-specific binders.