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Multi-analyte optimisation of uncertainty in infant food analysis.

The Optimised Uncertainty (OU) methodology has been developed to optimise multi-analyte situations. It has then been applied to a retail survey of infant food for trace elements, classifying the food as compliant or non-compliant with the regulatory thresholds or specification limits that are appropriate for each element. The large-scale survey of infant foods was successfully adapted to allow the estimation of uncertainties, from both primary sampling and chemical analysis, for elemental concentrations in infant formula (milk) and wet meals. The analytes included in this investigation comprised both contaminants (Pb and Cd) and elements essential for child development (Zn and Cu). Optimisation of the measurement process for a 'single analyte' demonstrated the potential financial benefits of optimising future surveys for a false compliance scenario. Uncertainty estimates for the measurement of elemental concentrations in infant formula were dominated by uncertainty from the analytical method. Large potential savings (up to pounds 575,000 per batch) are predicted for both Pb and Zn by increasing the expenditure on chemical analysis to the optimal level. In comparison the uncertainty estimates for elemental concentration in wet meals showed a dominance of sampling as a source of uncertainty for Cd and Cu due to the increased heterogeneity. The feasibility of 'multi-analyte' optimisation is demonstrated for the case study of infant milk. Single analyte optimisation of the four analytes for a false compliance scenario indicated a decrease in expectations of financial loss of between 99% and 8%. An overall decrease in the total expectation of financial loss of 99% is indicated following multi-analyte optimisation.

Child, Preschool↗

Ionic mechanism of acupuncture on improvement of learning and memory in aged mammals.

Memory impairment is one of the most frustrating problems for older people. Several acupoints were used for the treatment of memory loss in old rats, and the elemental mechanism of acupuncture therapy was studied with Inductively Coupled Plasma Spectroscopy. The result indicates that acupuncture improves learning and memory ability significantly in aged animals when compared with controls. This study demonstrated that elevations of eight essential elements (B, Ca, Cu, Fe, K, Mg, Na, and P) in the brain are the ionic basis for the therapeutic effect of acupuncture. A hypothetical model of the mechanism of acupuncture therapy is described.

Acupuncture Therapy↗

Assessment of essential and toxic elements in some kinds of vegetables.

Vegetables provide the human body with the essential bioavailable trace elements, and a constant supply of these various elements is necessary and highly recommended for daily life. Minor elements such as Ca, Fe, K, Mg, and Na as well as trace elements such as Cd, Co, Cu, Mn, Ni, Pb, and Zn were determined using an atomic absorption spectrophotometer in 12 different species of vegetables from Saudi Arabia (the Al-Taif district). These vegetables were cucumber, vegetable marrow, tomato, potato, green pepper, eggplant, carrots, parsley, lettuce, spinach, salq, onion, leek, watercress, and cabbage. The results reveal that the different element concentrations of each vegetable depend upon the selective uptake of the elements by the plant. Salq and watercress exhibited higher element concentrations than the other vegetables. Cluster analysis, principle component analysis, and transfer factor analysis of elements from soil to plant were applied to the elements database and produced good interpretations of the data. The element concentrations of these vegetables were within safety baseline levels for human consumption.

Biological Availability↗

Calcium-cadmium interaction on sugar absorption across the rabbit jejunum.

The element Cd is considered to have no biological function and is highly toxic to humans and animals. Toxic effects of this metal upon cell membrane structure and function have been shown. On the other hand, Ca is an essential element in a wide variety of cellular activities. The present study was initiated to research whether the interaction between Ca and Cd could affect D-galactose absorption across the rabbit jejunum in vitro. In media with Ca2+, when CdCl2 was present at 0.5 or 1 mM, Cd was found to significantly reduce the sugar absorption. In Ca2+ -free media, where CaCl2, was omitted and replaced isotonically with choline chloride, the sugar transport was not modified by Cd, but when CaCl2 was replaced isotonically with MgCl2, the inhibition is observed. Verapamil at 10(-6)M (blocking mainly Ca2+ transport) did not modify the inhibitory effect of cadmium on D-galactose transport. When 10(-6)M of A 23187 (Ca2+ specific ionophore) was added in media with/without Ca2+; CdCl2 produced no change in D-galactose transport. These results suggest that Ca and Cd could have affinity for the same chemical groups of enterocyte membrane, which would be related with the intestinal absorption of D-galactose.

Analysis of Variance↗

Minor and trace element content of two typical Italian sheep dairy products.

The concentration ranges in milk and cheese of a number of metallic elements relevant to the health of the consumer are dependent upon animal species, feeding, time of year, environmental conditions and manufacturing processes. We have measured the concentrations of selected trace elements--Al, Ba, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Pt, Sr and Zn--in raw ewes' milk and typical ewes' milk cheeses. Samples of milk, curd, whey, cheese after moulding, cheese after salting, commercial cheese (Pecorino), Ricotta, scotta and brine were analyzed for seven complete cycles of cheese production. Samples of curd, whey, brine and waste product (i.e. scotta) were collected and analysed in addition to the cheese and milk to assess the distribution of each element in the main product, by-products and waste products during cheesemaking. Quantitative determinations were performed mainly by inductively coupled plasma atomic emission spectrometry. There were considerable differences among the trace element contents of raw ewes' milk and related products, indicating that manufacturing processes play a key role in the distribution of minor and trace elements. Two different approaches were used to assess the dietary intake of these elements associated with the consumption of Pecorino and Ricotta, and whether this had any nutritional or toxicological implications. The results indicated no toxicological risk and showed that, on the contrary, Pecorino may be a good source of several essential elements.

Animal Feed↗

Outpatient intravenous antimicrobial therapy for the practicing orthopaedic surgeon.

The medical treatment of many musculoskeletal infections requires prolonged intravenous antimicrobial therapy, much of which is administered outside the hospital under the guidance of an infectious disease specialist. The essential elements of patient selection, antimicrobial administration, and clinical and laboratory monitoring of outpatient intravenous antimicrobial therapy for adult patients with musculoskeletal infection is described in the current study. Orthopaedists who treat patients with musculoskeletal infection should know the essential details of outpatient intravenous antimicrobial therapy to optimize the medical and surgical treatment of patients with these infections.

Adult↗

A minimal lentivirus Tat.

Transcriptional regulatory mechanisms found in lentiviruses employ RNA enhancer elements called trans-activation responsive (TAR) elements. These nascent RNA stem-loops are cis-acting targets of virally encoded Tat effectors. Interactions between Tat and TAR increase the processivity of transcription complexes and lead to efficient copying of viral genomes. To study essential elements of this trans activation, peptide motifs from Tats of two distantly related lentiviruses, equine infectious anemia virus (EIAV) and human immunodeficiency virus type 1 (HIV-1), were fused to the coat protein of bacteriophage R17 and tested on the long terminal repeat of EIAV, where TAR was replaced by the R17 operator, the target of the coat protein. This independent RNA-tethering mechanism mapped activation domains of Tats from HIV-1 and EIAV to 47 and 15 amino acids and RNA-binding domains to 10 and 26 amino acids, respectively. Thus, a minimal lentivirus Tat consists of 25 amino acids, of which 15 modify viral transcription and 10 bind to the target RNA stem-loop.

Amino Acid Sequence↗

Consent to electroconvulsive therapy: investigation of the validity of a competency questionnaire.

A valid consent is a necessary precondition to the administration of electroconvulsive therapy (ECT). However, the assessment of mental competence to consent may be both complicated and controversial because neither case law nor statutes provide a clear description of the necessary mental abilities. The closest approximation in the literature is that derived from judicial commentary on the relevant case law and summarized into four standards. We designed a 15-item questionnaire to define and test the content or essential elements of each of these standards, and surveyed lawyers and health care professionals with known expertise or interest in the field to investigate the content validity of the questionnaire. Of the 15 items, 12 were rated important or essential to the assessment of competence to consent to ECT by > or = 67% of the lawyers and 11 were so rated by > or = 67% of the health professionals. Ten items were rated as important or essential by > or = 67% of both groups. Only two items were not so endorsed by > or = 67% of one of the groups. We conclude that the questionnaire has a satisfactory content validity and may be considered a general guideline for assessing competence to consent to ECT.

Adult↗

Audit and summative assessment: a criterion-referenced marking schedule.

BACKGROUND: 1996 will see the introduction of summative assessment of general practitioner registrars (trainees). One part of this assessment is the written submission of practical work. In the west of Scotland, audit projects have been chosen as the format for practical work. A valid and reliable marking schedule for such projects is needed. AIM: A study was undertaken to develop a criterion-referenced marking schedule for assessing registrars' audit projects for summative assessment. METHOD: Medical and non-medical professionals, in a series of workshops, compiled a list of essential elements of good audit. These features were tested and refined using registrars' audit projects. All trainers in the west of Scotland were then sent a list of 14 criteria and asked to indicate whether each criterion was an essential or desirable component of a registrar's audit project for summative assessment. A final workshop was held to develop an audit marking schedule. RESULTS: Of 155 trainers in the west of Scotland, 135 replied to the list of criteria for registrar audit projects (87%). Ten criteria were deemed essential or desirable by 80% or more of the respondents. Participants in the final workshop selected five criteria which would form the audit project marking schedule for registrars undergoing summative assessment. These were: defined reason for choice of audit project, relevance of criteria chosen, appropriate preparation and planning, appropriate interpretation of relevant data and detailed proposals for change. For an audit project to pass assessment all five criteria must be present. CONCLUSION: A criterion-referenced approach to assessing registrars' audit projects, developed from their trainers' opinions of essential or desirable criteria for good audit, is described. Further evaluation of the criterion-referenced marking schedule is required.

Educational Measurement↗

Comparison of elements in bottlenose dolphins stranded on the beaches of Texas and Florida in the Gulf of Mexico over a one-year period.

We analyzed tissue samples from bottlenose dolphins (Tursiops truncatus) that had stranded on beaches in Texas and Florida over a 1-year period starting in September 1991. The concentrations of 10 elements plus methyl mercury (MeHg) were determined in brain, kidney, and liver, and we examined these results for differences based upon age, site, sex, and tissue type. A strong inverse relationship between total mercury (Hg) and the percentage that was MeHg was found in liver, kidney, and brain tissue, presumably due to demethylation of MeHg. A threshold concentration was found for total Hg in brain tissue, indicating that most Hg was present as MeHg up to about 8 years of age. Increases in total Hg after this age were accompanied by an increase in the ratio of total Hg to MeHg, indicating demethylation. Strong relationships were found between total Hg in liver and age and between total Hg and selenium in liver, which have been observed before in many fish- and squid-eating marine mammals. The only difference based on sex of the animals was observed for MeHg, which was higher in females and contrary to the pattern often observed for organic contaminants. Several elements (copper, Hg, lead, zinc) exhibited intersite differences, which were not consistent. Bottlenose dolphin from Florida exhibited the highest levels of MeHg and total Hg, while animals from Texas exhibited the highest levels of lead, copper, and zinc. The essential elements copper and zinc were expected to be the same for the Texas and Florida animals; however, observed differences may indicate population differences in basic physiological levels, dietary intake, or health status.

Animals↗

Mechanisms of noise-resistance in genetic oscillators.

A wide range of organisms use circadian clocks to keep internal sense of daily time and regulate their behavior accordingly. Most of these clocks use intracellular genetic networks based on positive and negative regulatory elements. The integration of these "circuits" at the cellular level imposes strong constraints on their functioning and design. Here, we study a recently proposed model [Barkai, N. & Leibler, S. (2000) Nature (London), 403, 267-268] that incorporates just the essential elements found experimentally. We show that this type of oscillator is driven mainly by two elements: the concentration of a repressor protein and the dynamics of an activator protein forming an inactive complex with the repressor. Thus, the clock does not need to rely on mRNA dynamics to oscillate, which makes it especially resistant to fluctuations. Oscillations can be present even when the time average of the number of mRNA molecules goes below one. Under some conditions, this oscillator is not only resistant to but, paradoxically, also enhanced by the intrinsic biochemical noise.

Algorithms↗

SILICON.

Silicon is present in plants in amounts equivalent to those of such macronutrient elements as calcium, magnesium, and phosphorus, and in grasses often at higher levels than any other inorganic constituent. Yet except for certain algae, including prominently the diatoms, and the Equisetaceae (horsetails or scouring rushes), it is not considered an essential element for plants. As a result it is routinely omitted from formulations of culture solutions and considered a nonentity in much of plant physiological research. But silicon-deprived plants grown in conventional nutrient solutions to which silicon has not been added are in many ways experimental artifacts. They are often structurally weaker than silicon-replete plants, abnormal in growth, development, viability, and reproduction, more susceptible to such abiotic stresses as metal toxicities, and easier prey to disease organisms and to herbivores ranging from phytophagous insects to mammals. Many of these same conditions afflict plants in silicon-poor soils-and there are such. Taken together, the evidence is overwhelming that silicon should be included among the elements having a major bearing on plant life.

Journal Article↗

[Cardiovascular risk and ambulatory blood pressure measurement of arterial pressure].

Many studies have demonstrated that elevation of blood pressure is proportional to the risk of developing cardiovascular accidents. The relationship between blood pressure and cardiovascular risk varies according to whether diastolic, systolic or pulse pressure is considered. Several other parameters are involved in the determinism of the blood pressure risk such as age, gender, ethnic group, etc. These elements emphasize the importance of considering the various blood pressures as well of the patient's risk factors and clinical characteristics for global evaluation of the cardiovascular risk. As blood pressure is an eminently variable parameter and as the essential element of evaluation of the blood pressure risk is based on its determination, it is important to measure blood pressure accurately and precisely. Clinical measurement of BP constitutes the reference method, but presents several limits and several causes of error which raise the problem of its validity to evaluate a given patient's mean blood pressure. Ambulatory blood pressure monitoring during 24 hours of usual activity appears to more accurately evaluate the blood pressure load likely to induce organic lesions, as several studies have demonstrated its superiority over occasional measurement to evaluate the risk and cardiovascular prognosis of HT. However, whether its application in the evaluation of the global cardiovascular risk and therapeutic management can improve the prevention strategy and long-term cardiovascular prognosis has yet to be determined.

Blood Pressure Monitoring, Ambulatory↗

Speciation of metallothionein-like proteins of the mussel Mytilus edulis at basal levels by chromatographic separations coupled to quadrupole and double-focusing magnetic sector ICPMS.

Characterization and partial purification of metallothionein-like proteins (MLPs) of the mussel Mytilus edulis from natural populations of three coastal regions in Spain were performed. Size exclusion chromatography (SEC) with quadrupole (Q-ICPMS) or double-focusing inductively coupled plasma mass spectrometry (DF-ICPMS) detection was used first for speciation of cadmium in such natural samples and those of mussels exposed to 500 mg x L(-1) Cd in an aquarium tank. SEC results showed always a single Cd-MLP peak (MLP fraction). The contents in Cd, Cu, and Zn of this MLP fraction, of the high molecular weight protein pool (HMW), and of the whole cytosol were then measured by DF-ICPMS. Then, a given aliquot (50 microL) of MLPs with the highest values for UV molecular absorption at 254 nm (also the maximum sulfur and Cd, Cu, or Zn contents) was used to further fractionation. Fast protein liquid chromatography "on line" with Q-ICPMS was used for the purpose. Two Cd-MLP isoforms (MLP-1, MLP-2), with retention times (tR) of 15.7 and 16.0 min, were then detected in cytosols of the mussel samples of aquarium tank and also of the industrial area and Galicia coast. Conversely, wild coast mussels did not show any Cd-MLP signals at all. Analysis of essential elements copper and zinc in such cytosols by FPLC-Q-ICPMS revealed that these two metals were associated just to MLP-1. These results tend to indicate a different role for the two MLP isoforms detected in mussels (i.e., essential metals' homeostasis role seems to be tied to the MLP-1 isoform only). They illustrate the fact that trace metal speciation of unknown species in biological materials is becoming a challenge and points to the use of several complementary analytical techniques to obtain the required speciation information.

Animals↗

P-type ATPase heavy metal transporters with roles in essential zinc homeostasis in Arabidopsis.

Arabidopsis thaliana has eight genes encoding members of the type 1(B) heavy metal-transporting subfamily of the P-type ATPases. Three of these transporters, HMA2, HMA3, and HMA4, are closely related to each other and are most similar in sequence to the divalent heavy metal cation transporters of prokaryotes. To determine the function of these transporters in metal homeostasis, we have identified and characterized mutants affected in each. Whereas the individual mutants exhibited no apparent phenotype, hma2 hma4 double mutants had a nutritional deficiency phenotype that could be compensated for by increasing the level of Zn, but not Cu or Co, in the growth medium. Levels of Zn, but not other essential elements, in the shoot tissues of a hma2 hma4 double mutant and, to a lesser extent, of a hma4 single mutant were decreased compared with the wild type. Together, these observations indicate a primary role for HMA2 and HMA4 in essential Zn homeostasis. HMA2promoter- and HMA4promoter-reporter gene constructs provide evidence that HMA2 and HMA4 expression is predominantly in the vascular tissues of roots, stems, and leaves. In addition, expression of the genes in developing anthers was confirmed by RT-PCR and was consistent with a male-sterile phenotype in the double mutant. HMA2 appears to be localized to the plasma membrane, as indicated by protein gel blot analysis of membrane fractions using isoform-specific antibodies and by the visualization of an HMA2-green fluorescent protein fusion by confocal microscopy. These observations are consistent with a role for HMA2 and HMA4 in Zn translocation. hma2 and hma4 mutations both conferred increased sensitivity to Cd in a phytochelatin-deficient mutant background, suggesting that they may also influence Cd detoxification.

Adenosine Triphosphatases↗

In vitro transcription of a Drosophila U1 small nuclear RNA gene requires TATA box-binding protein and two proximal cis-acting elements with stringent spacing requirements.

Transcription of a Drosophila U1 small nuclear RNA gene was functionally analyzed in cell extracts derived from 0- to 12-h embryos. Two promoter elements essential for efficient initiation of transcription in vitro by RNA polymerase II were identified. The first, termed PSEA, is located between positions -41 and -61 relative to the transcription start site, is crucial for promoter activity, and is the dominant element for specifying the transcription initiation site. PSEA thus appears to be functionally homologous to the proximal sequence element of vertebrate small nuclear RNA genes. The second element, termed PSEB, is located at positions -25 to -32 and is required for an efficient level of transcription initiation because mutation of PSEB, or alteration of the spacing between PSEA and PSEB, severely reduced transcriptional activity relative to that of the wild-type promoter. Although the PSEB sequence does not have any obvious sequence similarity to a TATA box, conversion of PSEB to the canonical TATA sequence dramatically increased the efficiency of the U1 promoter and simultaneously relieved the requirement for the upstream PSEA. Despite these effects, introduction of the TATA sequence into the U1 promoter had no effect on the choice of start site or on the RNA polymerase II specificity of the promoter. Finally, evidence is presented that the TATA box-binding protein is required for transcription from the wild-type U1 promoter as well as from the TATA-containing U1 promoter.

Animals↗

Tracking and follow-up of marginalized populations: a review.

Maintaining study cohorts is a key element of longitudinal research. Participant attrition introduces the possibility of bias and limits the generalizability of a study's findings, but with appropriate planning it is possible to sustain contact with even the most transient participants. This paper reviews the essential elements of tracking and follow-up of marginalized populations, which are (1) collection of contact information, (2) thorough organization of tracking efforts, (3) attention to staff training and support, (4) use of phone and mail follow-up, (5) use of incentives, (6) establishing rapport with participants, (7) assurance of confidentiality, (8) use of agency tracking, (9) use of field tracking, and (10) attention to safety concerns. Diligent application of these tracking strategies allows researchers to achieve follow-up rates of 75 percent to 97 percent with vulnerable populations such as homeless, mentally ill adults, injection drug users, and runaway youth.

Adolescent↗

Combined chelation therapy in reducing tissue lead concentrations in suckling rats.

The very young are more prone to lead poisoning than adults, and the treatment with chelating agents, either as monotherapy or combined treatment, is still a matter of dispute. The purpose of this work was to evaluate the efficiency of three chelating agents administered either as monotherapies or as combined treatments in sucklings. Lead acetate (5 mg Pb kg(-1) i.p.) was administered to the 7-day-old rat pups in eight litters on experimental day 1 and chelating agents on experimental days 2 and 3. Pups were divided into six groups: (1) untreated control; (2) EDTA (calcium disodium ethylendiaminetetraacetate, 0.3 mmol kg(-1) i.p. at 4 p.m.); (3) meso-DMSA (meso-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (4) rac-DMSA (racemic-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (5) EDTA+meso-DMSA; and (6) EDTA+rac-DMSA. Rats were killed on experimental day 5. Tissue element concentrations were analyzed by atomic absorption spectrometry. Treatment with EDTA did not affect tissue Pb, but it reduced Zn in the carcass and liver. Meso-DMSA reduced Pb in the kidneys and brain, and it did not affect organ essential elements. Rac-DMSA most efficiently reduced Pb concentrations in the carcass, kidneys and brain, but it also reduced Zn and Cu in the liver and Zn in the kidneys. Combined treatments with EDTA never improved the efficiency of either DMSA isoform in decreasing tissue Pb but they did reduce tissue Zn concentrations. All treatments caused the same decrease in the carcass Ca concentrations. The results do not support combined treatment in this age group, which is especially sensitive to trace element deficiencies, and suggest that meso-DMSA might be the treatment of choice in acute lead poisoning in infants.

Animals↗