Colonization in the rectum and uterine cervix with group B streptococci may induce specific antibody responses in cervical secretions of pregnant women.

We have studied the relationships between genital or rectal carriage of group B streptococci (GBS) with the levels of systemic and mucosal antibodies to GBS in 200 women at about week 17 of pregnancy. Secretions from the uterine cervix were collected with absorbent cylindrical wicks for quantification of antibody levels with whole cell enzyme-linked immunosorbent assay. GBS were cultured from the cervix (with or without concomitant rectal colonization) of 13.5%, from the rectum (with or without concomitant cervical colonization) of 12%, and from both culture sites of 8.5% of the women. Serotypes Ia, II, and III were predominant. Compared with culture-negative women, the group of women colonized rectally had markedly elevated levels of both immunoglobulin A (IgA) and IgG antibodies to GBS in cervical secretions and also had a moderate but significant elevation of IgA antibodies in sera. Women colonized only in the cervix had increases of specific IgA and IgG antibodies in cervical secretions, but their serum antibody levels were not elevated. In cervical secretions, the increase in antibody levels in the groups of colonized women was most pronounced for the IgG isotype, indicating a mucosal immune response involving IgG as well as IgA. A close correlation was found among the levels of antibodies to each of the three GBS serotypes tested. Evidence for such cross-reacting antibodies to different serotypes of GBS, as well as to group A streptococci, was also obtained from absorption experiments. Altogether, our results show that undiluted secretions for antibody determination can be easily collected from the uterine cervix with absorbent wicks and demonstrate that colonization of GBS in the rectum and the uterine cervix may induce a systemic as well as a pronounced local immune response in the female genital tract. The findings may have implications for the development of a mucosal vaccine against GBS disease.     

Simulation of clinical fractures for three different all‐ceramic crowns

Comparison of fracture strength and fracture modes of different all‐ceramic crown systems is not straightforward. Established methods for reliable testing of all‐ceramic crowns are not currently available. Published in‐vitro tests rarely simulate clinical failure modes and are therefore unsuited to distinguish between the materials. The in‐vivo trials usually lack assessment of failure modes. Fractographic analyses show that clinical crowns usually fail from cracks initiating in the cervical margins, whereas in‐vitro specimens fail from contact damage at the occlusal loading point. The aim of this study was to compare three all‐ceramic systems using a clinically relevant test method that is able to simulate clinical failure modes. Ten incisor crowns of three types of all‐ceramic systems were exposed to soft loading until fracture. The initiation and propagation of cracks in these crowns were compared with those of a reference group of crowns that failed during clinical use. All crowns fractured in a manner similar to fracture of the clinical reference crowns. The zirconia crowns fractured at statistically significantly higher loads than alumina and glass‐ceramic crowns. Fracture initiation was in the core material, cervically in the approximal areas.     

Induction of oxidative DNA base damage in human skin cells by UV and near visible radiation

The premutagenic oxidative DNA base damage, 7,8-dihydro-8-oxoguanine, is induced in human skin fibroblasts by monochromatic radiation ranging from a UVB wavelength (312 nm) up to wavelengths in the near visible (434 nm). The oxidative damage is not generated by absorption of radiation in DNA but rather by activation of photosensitizers generating genotoxic singlet oxygen species. The spectrum for the yield of the oxidative damage in confluent, non-growing, primary skin fibroblasts shows that it is UVA (above 334 nm) and near visible radiations which cause almost all of this guanine oxidation by natural sunlight in the fibroblast model. We estimate that the total amount of oxidation of guanine induced by sunlight in fibroblasts in the epidermis of the skin equals or exceeds the amount of the major type of direct DNA damage, cyclobutane pyrimidine dimers. In rapidly dividing lymphoblastoid cells, no oxidative guanine damage was induced. However, in melanoma cells almost as much damage as in non-growing fibroblasts (1.1 per 10(4) guanine bases after 1200 kJ/m2 UVA) was found. We conclude that oxidative DNA base damage can probably contribute to the induction of both non-melanoma and melanoma skin cancer by sunlight.      

Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis

To demonstrate that the lipid volume fraction In liver steatosis can be accurately estimated with in vivo hydrogen-1 magnetic resonance (MR) spectroscopy, the authors developed a calibration procedure based on in vitro MR spectroscopy of lipid extracts from steatotlc liver specimens. The lipid volume fractions determined with the calibration procedure were compared with the results of histomorphometry and with calibrated computed tomographic (CT) data. The volume fraction of fat determined with MR spectroscopy was in good agreement with the CT results, whereas histomorphometry underestimated the amount of hepatic fat. The results indicate that determination of the fat volume fraction in steatotic liver can be achieved noninvasively with MR spectroscopy.     

Cancer in the Norwegian printing industry

OBJECTIVES: The aim of this study was to investigate cancer risk among Norwegian workers in the printing industry, particularly lung and bladder cancer. METHODS: Cancer incidence was investigated from 1953 through 1998 in a cohort of 10 549 male members of a trade union in the printing industry in Oslo and nearby areas. Rates from the region, were used to calculate standardized incidence ratios (SIR) separately for the skilled and unskilled workers. Smoking data from a sample of the cohort were utilized for evaluating the risk estimates of smoking-related cancers. Specific exposure data were not available. RESULTS: Among the skilled workers, significantly elevated risks of cancer of the urinary bladder [standardized incidence ratio (SIR) 1.47, 95% confidence interval (95% CI) 1.19-1.79], liver (SIR 1.92, 95% CI 1.15-2.99), pancreas (SIR 1.46, 95% CI 1.07-1.94) and colon (SIR 1.27, 95% CI 1.05-1.55) were observed, whereas an increased risk of lung cancer in this group was confined to those born before 1910. Among the unskilled workers, there were significantly increased risks of cancer of the mouth, esophagus, stomach, larynx, lung, and all sites. CONCLUSIONS: The study showed that workers in the printing industry were at increased risk of several types of cancer. In particular the increased risk of bladder cancer among the skilled workers is suggestive of an occupational cause. However, no specific agent could be identified as an occupational carcinogen. The results did not support the hypothesis of a generally increased risk of lung cancer. The risk pattern for unskilled workers may reflect confounding by nonoccupational factors.     

Fracture toughness measurements of some dental core ceramics: a methodologic study.

Fracture toughness is regarded as an important property of dental ceramics. The most widely used methods for fracture toughness (KIc) determination are based on assessment of cracks created by hardness indentations. Different formulas have been developed for KIc calculations and all these methods and formulas include empirical factors based on pure ceramics, i.e. non-composite ceramics. These factors may, however, vary for a specified method for materials with different and complex structure. An important question is whether the various proposed methods and formulas lead to approximately the same numerical KIc values or at least to the same ranking of materials. The aim of this work was to compare two indentation methods and various formulas for calculation of KIc values when used on four commercial composite dental ceramics. The two applied methods and the different formulas showed substantial differences in the obtained values for one and the same material and a different ranking of various materials. It is unknown which method gives the most correct KIc values for these ceramic materials.     

The iron regulatory protein can determine the effectiveness of 5-aminolevulinic acid in inducing protoporphyrin IX in human primary skin fibroblasts

The level of endogenous photosensitiser, protoporphyrin IX (PPIX), can be enhanced in the cells by 5-aminolevulinic acid (ALA). We investigated the effect of critical parameters such as growth state of the cells and availability of intracellular iron in modulating the level of PPIX, in human primary cultured skin fibroblasts (FEK4) maintained either in exponentially growing or growth-arrested phase, following treatment with ALA. The addition of ALA to exponentially growing cells increased the level of PPIX 6-fold relative to control cells; however, in growth-arrested cells the same treatment increased the level of PPIX up to 34-fold. The simultaneous addition of the hydrophilic iron-chelator Desferal with ALA, boosted the level of PPIX up to 47-fold in growing cells and up to 42-fold in growth-arrested cells, suggesting that iron is limiting under the latter conditions. The strict dependence of PPIX enhancement on free available iron levels was examined by the level of activation of iron regulatory protein in band shift assays. This analysis revealed that the basal level of iron regulatory protein in growth-arrested cells was 6-fold higher than in growing cells, reflecting the influence of the free available iron pool in exponentially growing cells. Interestingly, the same ratio was found between the basal level concentration of PPIX in growing and growth-arrested cells. We propose that iron regulatory protein activation could serve as a marker for developing photodynamic therapy protocols because it identifies cells and tissues with a propensity to accumulate PPIX and it is therefore likely to predict the effectiveness of such therapies.     

Fracture toughness determination of ceramic and resin-based dental composites.

A new method has been developed for Klc determinations of brittle materials with precracks introduced by indentations. A reference glass, five ceramic materials, and one resin-based composite were tested. Knoop hardness indentations were made with a load of 49 N in a line from edge to edge vertical to the long axis on one surface of four-point flexure bars, to make a continuous crack under the indentations. Five specimens of each material were fractured in a four-point bend test with the line of indentations placed in the zone of constant and maximum tensile stress. Separate unfractured specimens were ground and polished to expose and measure the preformed continuous crack. The mean of six crack-depth measurements was used together with the fracture load and the dimensions of the bend specimens to calculate the fracture toughness, Klc of each material. The determined Klc value (x +/- SD) for the reference glass was 0.81 +/- .24 MPa m1/2 and corresponds to previous studies. The resin-based composite material, Silux Plus, had a value of 1.04 +/- 0.14 MPa m1/2. The Klc values (MPa m1/2) were 0.94 +/- 0.31 for Dicor, 1.41 +/- 0.18 for Cerestore, 1.50 +/- 0.29 for NBK-1000, 1.60 +/- 0.17 for Vitadur-N and 2.14 +/- 0.14 for Hi-Ceram. Hi-Ceram had significantly higher Klc values than the other materials. The new method seemed to be of value in determining the fracture toughness of non-metallic dental materials.     

Interference effects of choice on confidence: Quantum characteristics of evidence accumulation

Decision-making relies on a process of evidence accumulation which generates support for possible hypotheses. Models of this process derived from classical stochastic theories assume that information accumulates by moving across definite levels of evidence, carving out a single trajectory across these levels over time. In contrast, quantum decision models assume that evidence develops over time in a superposition state analogous to a wavelike pattern and that judgments and decisions are constructed by a measurement process by which a definite state of evidence is created from this indefinite state. This constructive process implies that interference effects should arise when multiple responses (measurements) are elicited over time. We report such an interference effect during a motion direction discrimination task. Decisions during the task interfered with subsequent confidence judgments, resulting in less extreme and more accurate judgments than when no decision was elicited. These results provide qualitative and quantitative support for a quantum random walk model of evidence accumulation over the popular Markov random walk model. We discuss the cognitive and neural implications of modeling evidence accumulation as a quantum dynamic system.Decisions in a wide range of tasks (e.g., inferring the presence or absence of a disease, the guilt or innocence of a suspect, and the left or right direction of enemy movement) require evidence to be accumulated in support of different hypotheses. Arguably, the most successful theory of evidence accumulation in humans and other animals is Markov random walk (MRW) theory (and diffusion models, their continuous space extensions) (1, 2). MRWs can be viewed as psychological implementations of a first-order Bayesian inference process that assigns a posterior probability to each hypothesis (3). MRWs can account for choices, response times, and confidence for a variety of different decision types (2, 4). Moreover, these models of the accumulation process have been connected to neural activity during decision-making (5, 6).According to MRW models, when deciding between two hypotheses, the cumulative evidence for or against each hypothesis realizes different levels at different times to generate a single particle-like trajectory of evidence levels across time (Fig. 1). At any point in time, the decision-maker has a definite level of evidence, and choices are made by comparing the existing level of evidence against a criterion. Evidence above the criterion favors one option, and evidence below it favors the alternative. Other responses are modeled in a similar manner; for example, confidence ratings are modeled by mapping evidence states onto one or more ratings (4). However, this idea that judgments and decisions are simply read out from the existing level of evidence—henceforth referred to as the “read-out” assumption—is inconsistent with the well-established idea that preferences and beliefs are constructed rather than revealed by judgments and decisions (7).Open in a separate windowFig. 1.Diagram of a state representation of a Markov and a quantum random walk model. In the Markov model, evidence (shaded state) evolves over time by moving from state to state, occupying one definite evidence level at any given time. In the quantum model the decision-maker is in an indefinite evidence state, with each evidence level having a probability amplitude (shadings) at each point in time.We present an alternative model of choice and judgment based on quantum random walk (QRW) theory (8–11), which posits that preferences and beliefs are constructed when a judgment or decision is made. Note that this work does not make the assumption that the brain is a quantum computer; instead, we simply use the mathematics of quantum theory to explain and predict human behavior. According to QRW theory, at any point in time before a decision, the decision-maker is in a superposition state that is not located at a single level of evidence. Instead, each level of evidence has a potential to be expressed, formalized as a probability amplitude (Fig. 1). New information changes the amplitudes, producing a wavelike process that moves the amplitude distribution across time.In some ways the QRW is like a second-order Bayesian model (12). According to the latter, the decision-maker assigns a probability (rather than an amplitude) to each level of evidence for each hypothesis. However, like the MRW model, second-order Bayesian models are perfectly compatible with the read-out assumption, and as an optimal model, this would suggest that a decision should not change the probability assigned to each evidence level. In contrast, a QRW, like all quantum models of cognition (13), treats a judgment or decision as a measurement process that constructs a definite state from an indefinite (superposition) state. When a decision is made, the indefinite state collapses onto a set of evidence levels that correspond to the observed choice, producing a definite choice state. Confidence ratings work similarly, with the indefinite state collapsing onto a more specific set of levels corresponding to the observed rating.These different theories of choice and judgment have strong implications for sequences of responses. Consider the situation when decision-makers have to make a choice (e.g., decide that hypothesis A or B is true) and later rate their confidence that a given (usually the chosen) hypothesis is true. According to the read-out assumption, a choice is reported on the basis of existing evidence that does not change the internal state of evidence itself. This applies to the MRW, a second-order Bayesian model, and many other accumulation models as well. Thus, after pooling across a person’s choices, the distribution of confidence ratings should be identical to conditions in which the person makes no choice at all. By contrast, the state of the system in a QRW is changed when a choice creates a definite state. Subsequent processing starts from the definite state, and the amplitudes spread out again. Thus, if information processing continues after the initial stage, the QRW predicts an interference effect where the marginal distribution of confidence judgments following a choice will differ from a condition in which no choice is made.A proof of the predicted interference effect for QRWs is in SI Appendix. The proof shows that the interference effect of choice on confidence is the result of the interaction between the creation of a definite state and subsequent evidence accumulation after making a choice. Subsequent or second-stage processing is a necessary condition for the effect. Critically, second-stage processing occurs when people are asked to report a confidence rating following a choice, giving rise to response reversals (14) and other properties (15). We also provide a proof that MRWs predict no difference between the marginal distributions of confidence ratings (i.e., no interference) regardless of the presence of second-stage processing. This proof holds for a large range of MRWs, including ones with decay (16), leakage of evidence (17), and trial-by-trial variability in the decision process (18).     

Flecainide pharmacokinetics after multiple dosing in patients with impaired renal function

Study objective: To determine the pharmacokinetics of oral flecainide acetate after single and multiple doses in patients with impaired renal function. Design: Paired study of single followed by multiple oral doses. Setting: Patients enrolled in a Veterans Administration Hospital renal subspecialty clinic and dialysis unit. Patients: Twenty men and one woman between the ages of 33 and 74 years with impaired renal function including ten patients with end-stage renal disease receiving maintenance hemodialysis. Interventions: All patients received a single, oral, 200-mg dose of flecainide acetate followed by sequential venous blood sampling. Seven to 14 days after the single-dose study, each patient received 100 mg of flecainide acetate by mouth every 12 hours or every 24 hours for 10 days. Venous blood samples were drawn periodically during multiple dosing and sequentially after the last dose. Measurements and primary results: Peak flecainide acetate concentrations (micrograms/L) were 330 +/- 104 micrograms/L (mean +/- SD) after the single dose and 687 +/- 505 micrograms/L after multiple doses. Time to peak occurred at 3.3 +/- 2.3 hours and 2.7 +/- 1.2 hours after single and multiple doses, respectively. The apparent volume of distribution was 8.2 +/- 2.9 L/kg and 9.2 +/- 5 L/kg after single and multiple dose studies, respectively. Plasma elimination half-life after the single dose (20.4 +/- 9.0 hours) was significantly shorter (P less than .001) than after multiple doses (37.8 +/- 39.7 hours), as was total body clearance: 391 +/- 154 mL/min versus 302 +/- 194 mL/min. There were no statistically significant differences between pharmacokinetic measurements determined for patients on chronic hemodialysis when compared with nondialysis patients during the multiple-dose study.(ABSTRACT TRUNCATED AT 250 WORDS)