Timing Metabolic Depression: Predicting Thermal Stress in Extreme Intertidal Environments.

AbstractAnticipatory changes in organismal responses, triggered by reliable environmental cues for future conditions, are key to species' persistence in temporally variable environments. Such responses were tested by measuring the physiological performance of a tropical high-shore oyster in tandem with the temporal predictability of environmental temperature. Heart rate of the oyster increased with environmental temperatures until body temperature reached ∼37°C, when a substantial depression occurred (∼60%) before recovery between ∼42° and 47°C, after which cardiac function collapsed. The sequential increase, depression, and recovery in cardiac performance aligned with temporal patterns in rock surface temperatures, where the risk of reaching temperatures close to the oysters' lethal limit accelerates if the rock heats up beyond ∼37°C, coinciding closely with the body temperature at which the oysters initiate metabolic depression. The increase in body temperature over a critical threshold serves as an early-warning cue to initiate anticipatory shifts in physiology and energy conservation before severe thermal stress occurs on the shore. Cross-correlating the onset of physiological mechanisms and temporal structures in environmental temperatures, therefore, reveals the potential role of reliable real-time environmental cues for future conditions in driving the evolution of anticipatory responses.

The COMPARE Data Hubs.

Data sharing enables research communities to exchange findings and build upon the knowledge that arises from their discoveries. Areas of public and animal health as well as food safety would benefit from rapid data sharing when it comes to emergencies. However, ethical, regulatory and institutional challenges, as well as lack of suitable platforms which provide an infrastructure for data sharing in structured formats, often lead to data not being shared or at most shared in form of supplementary materials in journal publications. Here, we describe an informatics platform that includes workflows for structured data storage, managing and pre-publication sharing of pathogen sequencing data and its analysis interpretations with relevant stakeholders.

Combined effects of thermal conditions and food availability on thermal tolerance of the marine bivalve, Perna viridis.

Organisms can mitigate the effects of long term variation in environmental conditions through acclimation, which involves changes in various physiological responses. To elucidate the possible effects of temperature and food concentrations on acclimation capacity, physiological responses of the mussel, Perna viridis, were measured after individuals were held for six weeks under varying temperatures and food availability. Warm-acclimated mussels experiencing higher food levels had significantly greater upper thermal limits than those maintained on lower food levels. In contrast, the upper thermal limits of cold-acclimated mussels were not affected by food levels. For warm-acclimated mussels, differences in upper thermal limits were likely due to rapid depletion of energy storage as predicted by Dynamic Energy Budget model simulations for P. viridis exposed to lower food levels. Clearance rates of cold-acclimated mussels were significantly lower than warm-acclimated mussels, regardless of food availability. The impacts of lower food acquisition on energy storage, however, could be compensated by lower metabolic rates of the cold-acclimated mussels. The availability and the ability to acquire food are not, therefore, the main drivers differentiating between the upper thermal tolerances of cold- and warm-acclimated mussels, but these differences are driven by the past thermal history the mussels experienced. The temperature tolerance range of P. viridis showed a positive shift to tolerate higher temperatures after acclimation. Such flexibility in thermal tolerance implies P. viridis has high capacity to acclimate to novel environments, which will enhance its future success given its commercial importance as an aquaculture species.

Development of a Web Tool for Escherichia coli Subtyping Based on fimH Alleles.

The aim of this study was to construct a valid publicly available method for in silico fimH subtyping of Escherichia coli particularly suitable for differentiation of fine-resolution subgroups within clonal groups defined by standard multilocus sequence typing (MLST). FimTyper was constructed as a FASTA database containing all currently known fimH alleles. The software source code is publicly available at https://bitbucket.org/genomicepidemiology/fimtyper, the database is freely available at https://bitbucket.org/genomicepidemiology/fimtyper_db, and a service implementing the software is available at https://cge.cbs.dtu.dk/services/FimTyper FimTyper was validated on three data sets: one containing Sanger sequences of fimH alleles of 42 E. coli isolates generated prior to the current study (data set 1), one containing whole-genome sequence (WGS) data of 243 third-generation-cephalosporin-resistant E. coli isolates (data set 2), and one containing a randomly chosen subset of 40 E. coli isolates from data set 2 that were subjected to conventional fimH subtyping (data set 3). The combination of the three data sets enabled an evaluation and comparison of FimTyper on both Sanger sequences and WGS data. FimTyper correctly predicted all 42 fimH subtypes from the Sanger sequences from data set 1 and successfully analyzed all 243 draft genomes from data set 2. FimTyper subtyping of the Sanger sequences and WGS data from data set 3 were in complete agreement. Additionally, fimH subtyping was evaluated on a phylogenetic network of 122 sequence type 131 (ST131) E. coli isolates. There was perfect concordance between the typology and fimH-based subclones within ST131, with accurate identification of the pandemic multidrug-resistant clonal subgroup ST131-H30. FimTyper provides a standardized tool, as a rapid alternative to conventional fimH subtyping, highly suitable for surveillance and outbreak detection.

CO2 adsorption using TiO2 composite polymeric membranes: A kinetic study.

CO2 is the main greenhouse gas which causes global climatic changes on larger scale. Many techniques have been utilised to capture CO2. Membrane gas separation is a fast growing CO2 capture technique, particularly gas separation by composite membranes. The separation of CO2 by a membrane is not just a process to physically sieve out of CO2 through the controlled membrane pore size. It mainly depends upon diffusion and solubility of gases, particularly for composite dense membranes. The blended components in composite membranes have a high capability to adsorb CO2. The adsorption kinetics of the gases may directly affect diffusion and solubility. In this study, we have investigated the adsorption behaviour of CO2 in pure and composite membranes to explore the complete understanding of diffusion and solubility of CO2 through membranes. Pure cellulose acetate (CA) and cellulose acetate-titania nanoparticle (CA-TiO2) composite membranes were fabricated and characterised using SEM and FTIR analysis. The results indicated that the blended CA-TiO2 membrane adsorbed more quantity of CO2 gas as compared to pure CA membrane. The high CO2 adsorption capacity may enhance the diffusion and solubility of CO2 in the CA-TiO2 composite membrane, which results in a better CO2 separation. The experimental data was modelled by Pseudo first-order, pseudo second order and intra particle diffusion models. According to correlation factor R(2), the Pseudo second order model was fitted well with experimental data. The intra particle diffusion model revealed that adsorption in dense membranes was not solely consisting of intra particle diffusion.

Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn's disease.

BACKGROUND: Azathioprine (AZA), a pro-drug metabolised to the active metabolites 6-tioguanine nucleotides (6TGN), is a steroid-sparing therapy for Crohn's disease (CD). AIM: To investigate whether AZA therapy is optimised by individualised dosing based on thiopurine methyltransferase (TPMT) activity and 6TGN concentrations. METHODS: This multicentre, double-blind, randomised controlled trial compared the efficacy and safety of weight-based vs. individualised AZA dosing in inducing and maintaining remission in adults and children with steroid-treated CD. The primary outcome was clinical remission (CR) at 16 weeks. In the weight-based arm, subjects received 2.5 mg/kg/day. In the individualised dosing arm, the initial AZA dose was 1.0 mg/kg/day (if intermediate TPMT) or 2.5 mg/kg/day (if normal TPMT). Starting at week 5, the dose was adjusted to target 6TGN concentrations of 250-400 pmol/8 × 10(8) red blood cells (RBC), or to a maximal dose of 4 mg/kg/day. RESULTS: After randomising 50 subjects, the trial was stopped prematurely due to insufficient enrolment. In intention-to-treat analysis, CR rates at week 16 were 40% in the individualised arm vs. 16% in the weight-based arm (P = 0.11). In per-protocol (PP) analysis, week 16 CR rates were 60% in the individualised arm and 25% in the weight-based arm (P = 0.12). At week 16, median 6TGN concentrations in PP remitters and nonremitters were 216 and 149 pmol/8 × 10(8) RBC respectively (P = 0.07). CONCLUSIONS: Despite trends favouring individualised over weight-based AZA dosing, there were no statistically significant differences in efficacy, likely due to low statistical power and inability to achieve the target 6TGN concentrations in the individualised arm. [Clinicaltrials.Gov Identifier Nct00113503].

Heterocyclic amines, meat intake, and association with colon cancer in a population-based study.

The authors examined the association between colon cancer and meat intake categorized by level of doneness, cooking method, and estimated levels of heterocyclic amines (HCAs), benzo[a]pyrene, and mutagenicity. Data were collected as part of a population-based, case-control study of colon cancer in North Carolina between 1996 and 2000 that included 701 African-American (274 cases, 427 controls) and 957 White (346 cases, 611 controls) participants. Odds ratios were calculated by using unconditional logistic regression, comparing the fifth to the first quintile levels of intake or exposure. Intake of red meat was positively associated with colon cancer (odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.3, 3.2). Associations with meat intake by cooking method were strongest for pan-fried red meat (OR = 2.0, 95% CI: 1.4, 3.0). Associations with meat intake by doneness were strongest for well-/very well done red meat (OR = 1.7, 95% CI: 1.2, 2.5). The strongest association for individual HCAs was reported for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) across all levels of exposure, with odds ratios of 1.8-2.0. Overall, sophisticated exposure measures were used to report modest, positive associations between red meat intake and colon cancer consistent with the hypothesis that HCAs may be among the etiologically relevant compounds in red meat.

Effects of short interpregnancy intervals on small-for-gestational age and preterm births.

We examined the effects of short interpregnancy intervals on small-for-gestational age and preterm births in a biracial population using North Carolina birth certificate data from 1988 to 1994. We defined small-for-gestational age birth as being below the 10th percentile on a race-, sex-, and parity-specific growth curve after a gestation of 37-42 weeks. We defined preterm birth as a gestation of less than 37 weeks. We analyzed birth records from all eligible singleton births to black or white women ages 15-45 years after an interpregnancy interval of 0-3 months (N = 11,451) and a random sample of singleton births after an interval of 4-24 months (N = 23,118). We defined interpregnancy interval exposure categories as 0-3, 4-12, and 13-24 months. The multivariate adjusted odds ratio for small-for-gestational age births after interpregnancy intervals of 0-3 months compared with 13-24-month intervals was 1.6 (95% confidence interval = 1.4-1.8). The odds ratio for preterm birth after interpregnancy intervals of 0-3 months was 1.2 (95% confidence interval = 1.1-1.3). Odds ratios did not vary substantially by race for either outcome.

The appropriateness of early discharge of hospitalized children with suspected sepsis.

BACKGROUND: Febrile children with suspected sepsis are often hospitalized and empirically treated with parenteral antibiotics pending results of bacterial cultures. The question of just how long such children should be observed and treated following initial negative culture reports has not been adequately addressed. This study was designed to determine the appropriateness of discharging hospitalized culture-negative children with suspected sepsis at the end of 48 hours. METHODS: All children admitted with a diagnosis of "suspected sepsis" over an 8-month period were prospectively evaluated. Based on initial culture data, children were divided into two groups: group A with positive bacterial cultures and group B with negative bacterial cultures. Clinical assessment and review of cerebrospinal fluid, blood, and urine culture data were made at 24 hours, 48 hours, and until discharge, and at 2 weeks following discharge of all group B patients. RESULTS: Of the 83 children enrolled in the study, 8 (9.5%) patients had a culture positive for bacterial infection (group A): meningitis in two, bacteremia in six, and urinary tract infection in two. All cultures were positive within 48 hours. Cultures were negative at 48 hours in the remaining 75 (90.4%) children (group B), and remained negative until discharge and at 2-week follow-up. Eight (10.6%) patients had received antibiotics prior to admission. After the workup, 37 of 73 (50.6%) children received antibiotics for less than 48 hours, while 36 (49.4%) children did so for more than 48 hours. Clinical assessment was normal at 48 hours in 71 of the 75 children. Sixty-three (84%) children available for follow-up continued to do well after discharge. No statistical distinction could be made between those children who remained hospitalized after 48 hours and those children who were dismissed at 48 hours. CONCLUSIONS: Although our study data suggest that culture-negative children hospitalized for suspected sepsis who meet the criteria for normal clinical assessment can be safely discharged at 48 hours, a stronger statistical validation of this approach can be made if a larger sample size is studied.

The prevention of coronary artery aneurysm in Kawasaki disease: a meta-analysis on the efficacy of aspirin and immunoglobulin treatment.

OBJECTIVE: Varying observations have been made concerning the use of aspirin (ASA) and/or intravenous immunoglobulin (IVIG) in the prevention of coronary artery aneurysm (CAA) in children with Kawasaki disease. A meta-analysis of published articles on the subject was conducted to evaluate the reported efficacy of these therapies. METHODS: All published studies in all languages from 1967 through 1993 obtained from MEDLINE and EMBASE were considered, and a defined set of inclusion and exclusion criteria selected the studies for analysis. These studies were grouped based on whether the children in the studies received: (1) ASA alone, (2) low IVIG (< or = 1 g/kg) and ASA, (3) high IVIG (> 1 g/kg) and ASA, (4) single IVIG (> 1 g/kg) and ASA, (5) high IVIG and low ASA (< or = 80 mg/kg), or (6) high IVIG and high ASA (> 80 mg/kg). Studies that satisfied the test for homogeneity were subjected to further analysis. The best estimate of the true proportion of CAA as well as the 95% confidence interval for each group were calculated at 30 and 60 days. Hypothesis testing was conducted to determine the statistical significance of the calculated difference in each compared treatment group. RESULTS: The best estimate of true proportion of CAA and the 95% confidence interval in each group at 30 and 60 days were: (1) ASA group, 30 days, 22.8% (20.6%, 25%); 60 days, 17.1% (13.6%, 20.7%); (2) low-IVIG group, 30 days, 17.3% (14.3%, 20.2%); 60 days, 11.1% (8.7%, 13.6%); (3) high-IVIG group, 30 days, 10.3% (8.3%, 12.3%); 60 days, 4.4% (2.8%, 6%); (4) single-IVIG group, 30 days, 2.3% (0.5%, 4.2%); 60 days, 2.4% (0.5%, 4.2%); (5) high-IVIG-low-ASA group, 30 days, 13% (9%, 17%); 60 days, 4.8% (2.3%, 7.4%); and (6) high-IVIG-high-ASA group, 30 days, 9.1% (6.9%, 11.4%); 60 days, 4% (2%, 6.1%). CONCLUSION: The incidence of CAA both at 30 and 60 days was significantly lower in low-IVIG than in ASA and in high-IVIG than in low-IVIG groups. Also, the incidence was lower in the single-IVIG than in the high-IVIG group, but this was noted at 30 days and not at 60 days. There was no statistically significant difference in the incidence of CAA both at 30 and 60 days between the high-IVIG-low-ASA and high-IVIG-high-ASA groups.

Analysis of a measles epidemic.

In January, February and March of 1989 an epidemic of rubeola occurred on the campus of Texas Tech University. A vaccination programme was initiated as soon as the epidemic was confirmed. Extensive case histories of all confirmed cases were collected by the Lubbock City Health Department and given an exhaustive statistical analysis by a group from the Department of Mathematics at Texas Tech University. The data and statistical analysis were used to formulate stochastic and deterministic models of the measles epidemic based on the standard SEIR model. The analysis and the simulations indicate that in order to prevent a measles outbreak on a university campus a high rate of immunity may be required (> 98 per cent). The assumptions in the models raise some interesting questions regarding social contacts which require further investigation.

A model study of instability of the inverse problem in electrocardiography.

The inverse problem in electrocardiography is studied analytically using a concentric spheres model with no symmetry assumptions on the potential distribution. The mathematical formulation is presented, and existence and uniqueness of the solution are briefly discussed. Solution to the inverse problem is inherently very unstable. The magnitude of this instability is demonstrated using the derived analytical inverse solution for the spherical model. Regularization methods used to date are based on a regularization parameter that does not relate to any measurable physiological parameters. This paper presents a regularization method that is based on a parameter in the form of an a priori bound on the L2 norm of the inverse solution. Such a bound can be obtained from the theoretical estimates based on the measured values of the body surface potentials together with experimental knowledge about the magnitudes of the epicardial potentials. Based on the presented regularization, an exact form of the regularized solution and estimates of its accuracy are derived.

[Prevalence of the Epstein-Barr virus among different populations in the central area]. / Prevalencia del virus de Epstein-Barr en diferentes poblaciones de la zona centro.

In order to estimate the seroprevalence of the Epstein-Barr virus in the centre area, a serological study is carried out using the indirect immunofluorescence technique on 759 supposed healthy people, from both sexes and with ages between 6 months and 50 years, 565 from which were living in urban areas (Madrid and Guadalajara city) and 194 in rural areas (Arganda del Rey, Madrid) and Chiloeches (Guadalajara). Global seroprevalence was of 81% in Madrid city, 90% in Guadalajara city and 85% in both rural populations. Comparing groups of the same age, we have not found any statistically significant differences between the urban (86%) and the rural (85%) areas. Neither we have found any relation between seropositivity and sex (74.7% for women and 81% for men). On the other hand, we observed that in our study group, seroprevalence was related to socioeconomic status--the higher the antibody percentages, the lower the socioeconomic status, both in the rural and in the urban areas (p less than 0.001)-- and age antibody percentages increased with age, with p less than 0.025 for urban areas and p less than 0.05 for rural areas.

Cell cycle-dependent expression of CD4 antigen in a monocytoid cell line.

The CD4 molecule has several biological functions, physiologically as a receptor for major histocompatibility complex class II molecules on antigen-presenting cells, and pathologically as a receptor for human immunodeficiency virus (HIV) by its binding to the HIV envelope glycoprotein gp 120. The frequency of CD4+ cells has been shown to correlate positively with both susceptibility and cytopathogenic effect by HIV. To determine if CD4 expression varied during the cell cycle, a CD4-expressing monocytoid cell line, U 937 clone 16, was synchronized with regard to cell growth. The CD4 antigen was analysed with regard to expression, density and rate of reappearance after treatment with trypsin, during the different phases of the cell cycle. The CD4 reappearance rate was found to be maximal during the S phase. This was followed by an increased expression and density in the late S/G2 phase. Thus a cell cycle-dependent expression of CD4 molecules on the cell surface was observed.

A discrete-time model with vaccination for a measles epidemic.

A discrete-time, age-independent SIR-type epidemic model is formulated and analyzed. The effects of vaccination are also included in the model. Three mathematically important properties are verified for the model: solutions are nonnegative, the population size is time-invariant, and the epidemic concludes with all individuals either remaining susceptible or becoming immune (a property typical of SIR models). The model is applied to a measles epidemic on a university campus. The simulated results are in good agreement with the actual data if it is assumed that the population mixes nonhomogeneously. The results of the simulations indicate that a rate of immunity greater than 98% may be required to prevent an epidemic in a university population. The model has applications to other contagious diseases of SIR type. Furthermore, the simulated results of the model can easily be compared to data, and the effects of a vaccination program can be examined.

In vitro correlation between force and energy metabolism in porcine malignant hyperthermic muscle studied by 31P NMR.

A comparative study of mechanical and energetic parameters of superfused muscle strips from normal pigs and malignant hyperthermia susceptible (MHS) pigs has been conducted. Phosphorus nuclear magnetic resonance spectroscopy at 80.9 MHz and mechanical measurements were used to assess muscle metabolic state. At rest, biceps femoris biopsies of MHS pigs displayed reduced phosphocreatine level, higher inorganic phosphate, and a more acidic internal pH. In normal stimulated fibers, caffeine infusion (8 or 16 mM) induced twitch potentiation and contracture while twitch tension was reduced and contracture more pronounced in malignant fibers. In normal and malignant fibers, calcium ionophore A23187 produced effects similar to those of caffeine, with the exception of twitch potentiation, which was not observed. With caffeine or A23187, the ATP level remained constant throughout the rest-stimulation-recovery protocol for normal and malignant fibers but phosphocreatine dropped to undetectable levels upon stimulation of malignant fibers. In both treatments some heterogeneity in the resonances of inorganic phosphate was observed in malignant fibers together with a more severe acidosis which might play a role in the impairment of the excitation-contraction process.

Production of monoclonal antibodies specific for Haemophilus ducreyi: a screening method to discriminate specific and cross-reacting antibodies.

Haemophilus ducreyi is the etiological agent of chancroid. The organism shares extensive immunological cross-reactivity with other Haemophilus species. This presents substantial difficulties for the production of specific monoclonal antibodies (MAbs). A competition ELISA was devised for hybridoma screening which allowed the detection of H. ducreyi-specific antibody-producing hybridoma cultures during the initial screening process. With this screening method, seven MAbs specific for H. ducreyi were obtained in a single cell fusion exercise. The specificities of the 7 MAbs were demonstrated by direct ELISA and dot immunobinding assays against several strains each of H. influenzae, H. parainfluenzae and Neisseria gonorrhoeae. Five of the MAbs reacted against all ten strains of H. ducreyi. These MAbs may permit the development of rapid and efficient immunodiagnostics for chancroid. The principle of the competition ELISA for hybridoma screening should be widely applicable to the development of specific MAbs to other organisms in which immunological cross-reactivity is an impediment to hybridoma screening by conventional methods.

Changes in host cell membrane activities in response to adhesion of Neisseria gonorrhoeae.

Physiological changes in host cell model membranes (intact human erythrocytes and ghosts) as a consequence of bacterial adhesion were studied with special reference to Neisseria gonorrhoeae. Membrane activities examined were transport of K+, Cl- ions, pyruvate kinase, Na-K-dependent ATPase, and cAMP. We found that K+ and Cl- transport were affected, more so in membranes with attached pilated (P+) organisms than in those with apilated (P-) isogenic strains. In N. gonorrhoeae and in several other species of gram-negative bacteria studied, hemagglutination titres were directly correlated with effects on anion transport, suggesting that perturbations in anion transport are an immediate result of adhesion. Of three P+ gonococcus strains tested, two depressed Na-K-ATPase activity in the membrane, indicating a possible effect on the Na-K pump. Pyruvate kinase activity associated with the membrane appeared to be stimulated by attached gonococci, again by P+ strains to higher levels than P- organisms. Clearly, some enzyme properties of host membranes are intrinsically affected by bacterial adhesion. Human polymorphonuclear neutrophils were also investigated, and with some exceptions, changes observed in leukocyte enzyme activities tended to parallel those in erythrocytes. Since hypochlorous acid production is considered to be an important microbicidal mechanism in neutrophils, interference with Cl- transport could jeopardize their role in host defense.