The formal foundation of an evolutionary theory of reinforcement.

Reinforcement learning is often described by analogy to natural selection. However, there is no coherent theory relating reinforcement learning to evolution within a single formal model of selection. This paper provides the formal foundation of such a unified theory. The model is based on the most general description of natural selection as given by the Price equation. We extend the Price equation to cover reinforcement learning as the result of a behavioral selection process within individuals and relate it to the principle of natural selection via the concept of statistical fitness predictors by means of a multilevel model of behavioral selection. The main result is the covariance-based law of effect, which describes reinforcement learning on a molar level by means of the covariance between behavioral allocation and a statistical fitness predictor. We further demonstrate how this abstract principle can be applied to derive theoretical explanations of various empirical findings, like conditioned reinforcement, blocking, matching and response deprivation. Our model is the first to apply the abstract principle of selection to derive a unified description of reinforcement learning and natural selection within a single model. It provides a general analytical tool for behavioral psychology in a similar way that the theory of natural selection does for evolutionary biology. We thus lay the formal foundation of a general theory of reinforcement as the result of behavioral selection on multiple levels.

The Canadian Core Cariology Curriculum: Outcomes of a national symposium.

Despite the efforts that have been made in dental education and clinical practice to adopt the evidence-informed, risk-based, nonsurgical caries management approach, the surgical treatment approach continues to prevail. There is an urgent need to understand resistance to such a paradigm shift and establish a coordinated evidence-based Cariology teaching approach in Canadian dental schools so trainees are equipped to implement caries management in their practice. To work towards this goal, a two-day interinstitutional symposium was organized in Montreal, QC, bringing together clinical and research experts in cariology and dental education from all 10 Canadian dental schools to develop a consensus on an evidence-informed Core Cariology Curriculum, and strategies for its implementation. Through consensus, participants produced the Core Cariology Curriculum for Canadian dental schools and articulated the challenges and solutions for its implementation. Future work will include working collaboratively on the curriculum integration and evaluation.

Biology of teeth and implants: Host factors - pathology, regeneration, and the role of stem cells.

In chronic periodontitis and peri-implantitis, cells of the innate and adaptive immune systems are involved directly in the lesions within the tissues of the patient. Absence of a periodontal ligament around implants does not prevent a biologic process similar to that of periodontitis from affecting osseointegration. Our first focus is on factors in the biology of individuals that are responsible for the susceptibility of such individuals to chronic periodontitis and to peri-implantitis. Genetic factors are of significant importance in susceptibility to these diseases. Genetic factors of the host affect the composition of the oral microbiome in the same manner that they influence other microbiomes, such as those of the intestines and of the lungs. Our second focus is on the central role of stem cells in tissue regeneration, in the functioning of innate and adaptive immune systems, and in metabolism of bone. Epithelial cell rests of Malassez (ERM) are stem cells of epithelial origin that maintain the periodontal ligament as well as the cementum and alveolar bone associated with the ligament. The tissue niche within which ERM are found extends into the supracrestal areas of collagen fiber-containing tissues of the gingivae above the bony alveolar crest. Maintenance and regeneration of all periodontal tissues involves the activity of a variety of stem cells. The success of dental implants indicates that important groups of stem cells in the periodontium are active to enable that biologic success. Successful replantation of avulsed teeth and auto-transplantation of teeth is comparable to placing dental implants, and so must also involve periodontal stem cells. Biology of teeth and biology of implants represents the biology of the various stem cells that inhabit specialized niches within the periodontal tissues. Diverse biologic processes must function together successfully to maintain periodontal health. Osseointegration of dental implants does not involve formation of cementum or collagen fibers inserted into cementum - indicating that some stem cells are not active around dental implants or their niches are not available. Investigation of these similarities and differences between teeth and implants will help to develop a better understanding of the biology and physiologic functioning of the periodontium.

Biology of teeth and implants: The external environment, biology of structures, and clinical aspects.

For the past several thousand years, until development of the titanium dental implant, only a few missing teeth were replaced successfully in a very small number of individuals. Nowadays, placement of dental implants has become sufficiently commonplace that there is a need to interchange information between what we know about periodontal health and disease and what we know about health and disease involving dental implants. This review discusses the similarities and differences between teeth and dental implants with regards to anatomy, biology, physiology, and pathologic processes. The concept of biologic width is discussed in the context of interaction of periodontal and peri-implant tissues with microbial products produced by periodontal biofilms. The periodontal microbiome is discussed as networks of organisms interacting not only with periodontal and peri-implant tissues, but also with each other as networks of competing organisms. Overall, the transfer of biologic knowledge from what we know about peri-implantitis and what we know about periodontitis should help to develop new directions for biologic understanding about both health and disease of teeth and dental implants.

A cyclopropene-modified nucleotide for site-specific RNA labeling using genetic alphabet expansion transcription.

Site-specific RNA modification with methyl cyclopropene moieties is performed by T7 in vitro transcription. An existing unnatural base is functionalized with a cyclopropene moiety and used in transcription reactions to produce site-specifically cyclopropene-modified RNA molecules. The posttranscriptional inverse electron demand Diels-Alder cycloaddition reaction with a selected tetrazine-fluorophore conjugate is demonstrated.

Effect of chronic coffee consumption on weight gain and glycaemia in a mouse model of obesity and type 2 diabetes.

OBJECTIVE: Epidemiological evidence shows that chronic coffee consumption in humans is correlated with a lower incidence of type 2 diabetes mellitus. For the experimental exploration of the underlying mechanisms, this effect needs to be replicated in an animal model of type 2 diabetes with a short lifespan. DESIGN: Male C57BL/6 mice consumed regular coffee or water ad libitum and the development of obesity and diabetes caused by high-fat diet (55% lipids, HFD) was observed from week 10 on for 35 weeks in comparison with mice feeding on a defined normal diet (9% lipids, ND). RESULTS: The massive weight gain in HFD mice was dose-dependently retarded (P=0.034), the moderate weight gain in ND mice was abolished (P<0.001) by coffee consumption, probably because of a lower feeding efficiency. The consumption of fluid (water or coffee) was significantly diminished by HFD (P<0.001), resulting in a higher coffee exposure of ND mice. On week 21 intraperitoneal glucose tolerance tests (IPGTT) showed a dose-dependent faster decline of elevated glucose levels in coffee-consuming HFD mice (P=0.016), but not in ND mice. Remarkably, a spontaneous decrease in non-fasting glycaemia occurred after week 21 in all treatment groups (P<0.001). On week 39 the IPGTT showed diminished peak of glucose levels in coffee-consuming HFD mice (P<0.05). HFD mice were hyperinsulinaemic and had significantly (P<0.001) enlarged islets. Coffee consumption did not affect islet size or parameters of beta-cell apoptosis, proliferation and insulin granule content. CONCLUSION: Coffee consumption retarded weight gain and improved glucose tolerance in a mouse model of type 2 diabetes and corresponding controls. This gives rise to the expectation that further insight into the mechanism of the diabetes-preventive effect of coffee consumption in humans may be gained by this approach.

Performance of a commercial immunoassay for detection and differentiation of periodontal marker bacteria: analysis of immunochemical performance with clinical samples.

BACKGROUND: We employed a commercial immunoassay for simultaneous detection and differentiation of marker bacteria Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia and reassessed the immunochemical performance of the assay. METHODS: We compared the analytical performance of the immunoassay in our study of clinical samples from 249 periodontal patients in 2 private periodontal practices with the previously reported analytical performance of the same immunoassay. We also compared immunoassay measurements of the marker bacteria in clinical samples with values obtained in other studies by direct culture of the same organisms. RESULTS: The assay produced 3 times more high-end readings than reported previously. We also reassessed and revised previously published calibration curves for the immunoassay. The immunoassay provided measurements of the marker bacteria in clinical samples from our patients that were comparable to and consistent with measurements of the same bacteria by direct culture in other studies. CONCLUSIONS: We ascribe the increased sensitivity of the immunoassay in our study to: 1) a more standardized and vigorous sample dispersion that improves release of particulate and soluble antigens from dental plaque biofilm, and 2) better visualization of the reaction product of the enzyme-linked immunoassay. High-technology assays, such as diagnostic immunoassays, have a significant potential for future development in dental diagnosis, because they simplify detection and measurement of biologically important markers such as specific bacteria in clinical samples. Commercial assays also have an important potential for standardization of clinical measurements of biological markers.

Effects of smoking and treatment status on periodontal bacteria: evidence that smoking influences control of periodontal bacteria at the mucosal surface of the gingival crevice.

BACKGROUND: We examined whether smoking status could influence growth of potentially pathogenic bacteria in the periodontal environment of treated and untreated periodontal patients. METHODS: We have previously reported effects of treatment status on marker bacteria in our patients. We established a history of any smoking during 6 months prior to microbiological sampling (F-ME, 16 smokers out of 64; MHM, 70 smokers out of 185). We used a commercial immunoassay to quantitate Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans in paper point samples from periodontal sites. RESULTS: Logistic regression showed that in smokers, neither P. gingivalis nor A. actinomycetemcomitans was quantitatively increased, while P intermedia was somewhat increased. Multiple regression demonstrated that smoking disrupts the positive relationship between increasing probing depth and increasing bacterial growth that is found in non-smokers. In smokers, growth of marker bacteria at shallow sites (< or =5 mm) was significantly increased to the levels found at deeper sites (>5 mm) in both smokers and non-smokers. Supragingival plaque biofilm was identified as a reservoir for marker bacteria; smokers and nonsmokers had equal ranges of oral cleanliness. CONCLUSIONS: Smoking-associated periodontitis is not simply a reflection of oral cleanliness. Smoking extends a favorable habitat for bacteria such as P. gingivalis, P. intermedia, and A. actinomycetemcomitans to shallow sites (< or =5 mm). Molecular byproducts of smoking interfere with mechanisms that normally contain growth of damaging bacteria at the surface of the oral mucosa in gingival crevices. In this way, smoking can promote early development of periodontal lesions.

In vitro investigation of the liberation of fluoride ions from toothpaste compounds in a permeation model.

The most important requirement for effective topical fluoride prophylaxis from toothpaste containing fluoride is that the active fluoride agent must be chemically free, and the rapid spread of the dissolved fluoride ions over the tooth surface. Abrasive compounds in the toothpastes and the brief residence time at the site of action, the oral cavity and tooth surface must not prevent the liberation. Using a two-chamber diffusion cell and an ion-selective fluoride electrode, the content of fluoride ions in five different fluoride-containing toothpastes was determined by direct potentiometry as a function of time and the different abrasive compounds employed. The investigation has demonstrated that a reduction of the release rate of fluoride ions by nearly 50% is seen when calcium carbonate and calcium hydrogen phosphate dihydrate are used as abrasive compounds and combined with sodium fluoride.

Antimicrobial resistance: dentistry's role.

The resistance of bacteria, fungi and viruses to antimicrobials is increasing rapidly, with deleterious consequences. Dentistry's role in this development is unclear, because the necessary information has not yet been collected. Nevertheless, dentists should recognize that it is essential to use antimicrobials in an appropriate and responsible manner, both to treat infection effectively, and to minimize the likelihood that the bacteria in the general population will develop resistance to antimicrobials. The purpose of this article is to make dentists aware of the concerns raised by antimicrobial resistance, and how it can be avoided.

Pathophysiologically correlated deficits of information processing in obstructive sleep apnea patients.

In obstructive sleep apnea patients, who intermittently stop breathing at night for some seconds, functions of vigilance and attention seem to be impaired. The aim of our study was to investigate if nocturnal hypoxia as one possible detrimental factor is associated with the degree of modality shift effect expressing attention function at a very basic level of information processing. For the first time an experimental approach was applied to examine attention deficits in sleep apnea patients. Correlation analyses between pathophysiological parameters and attention function revealed a stronger association for the modality shift effect than for simple reaction times.

Diagnostic utility of specific microbiological markers for periodontal diseases.

Specific detection of marker organisms Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans with an immunoassay provided 2 types of useful information directly into private clinical practice: 1) persistence of P. gingivalis in patients undergoing regular treatment allowed rapid identification of pockets requiring further treatment without waiting for measurable progression of lesions and 2) presence of A. actinomycetemcomitans in adults at any stage of diagnosis or treatment identified patients who may prove to have difficult-to-manage periodontitis. We made these findings in 253 patients (234 in specialist periodontal practices [F-ME 55; MHM 179] and 19 in general dental practice [EWM]). The search for useful diagnostic markers overlaps only partly with the search for periodontal pathogens. The P. gingivalis marker and the A. actinomycetemcomitans marker identify 2 different patterns of infection that appear to reflect 2 different underlying problems. Demonstration of pocket-dependent infection with P. gingivalis in treated patients provides an outcome marker for sites not converting to marker-negative sites at detection levels of the immunoassay. This information facilitates selection of sites and patients requiring adjustment of treatment regimens. Detection of A. actinomycetemcomitans in adult patients is significantly associated with periodontitis characterized as refractory. Positive identification of A. actinomycetemcomitans with the immunoassay supports clinical decision-making by drawing attention to adult patients who require closer monitoring and intensive persistent treatment. Successful application of immunoassay detection of microbiological markers is based on continuous patient monitoring to support clinical decisions; it does not replace careful clinical judgment.

Periodontitis-associated marker bacteria in an urban North American patient population: application of a commercial immunoassay.

We used an immunoassay to demonstrate marker organisms (Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans) in 3 private practice populations (F-ME periodontist, 55 patients; MHM periodontist, 179 patients; and EWM general dentist, 19 patients). Occurrence of the marker organisms involves the whole oral environment, not just individual sites, as shown by close correlation between presence of the marker organisms in 2 independent sites/samples within a single mouth. Presence of the marker P. gingivalis (and P. intermedia) relates closely to periodontal pocketing while presence of A. actinomycetemcomitans does not have this pocket-associated characteristic. There was no significant relationship between presence of the marker organisms and the number of teeth in a mouth, and in the periodontal practice patients there was no significant effect of gender on occurrence of the marker organisms. A. actinomycetemcomitans and the other 2 markers were found over the entire age range (12 to 75) of our patients. Regular periodontal treatment reduced occurrence of all marker organisms and increased the frequency of marker-negative patients and sites. Occurrence of the marker organisms above immunoassay threshold levels appears to represent how receptive a patient is to each individual organism. Most patients appear receptive to the presence of P. intermedia whether treated or not. Significantly fewer patients who underwent regular treatment show the presence of P. gingivalis or A. actinomycetemcomitans when compared to untreated patients. Diagnostic application of microbial markers requires ongoing clinical assessment of patients and careful clinical judgment. 1391.

High-Resolution X-ray Spectroscopy Close to Room Temperature.

: Originally designed as position-sensitive detectors for particle tracking, silicon drift detectors (SDDs) are now used for high-count rate X-ray spectroscopy, operating close to room temperature. Their low-capacitance read-node concept places them among the fastest high-resolution detector systems. They have been used in a new spectrum of experiments in the wide field of X-ray spectroscopy: fluorescent analysis, diffractometry, materials analysis, and synchrotron experiments such as X-ray holography and element imaging in scanning electron microscopes. The fact that the detector system can be used at room temperature with good spectroscopic performance and at -10 degrees C with excellent energy resolution, avoiding liquid nitrogen for cooling and high-quality vacuum, guarantees a large variety of new applications, independent of the laboratory environment. A brief description of the device principles is followed by basics on low noise amplification. The performance results of a complete detector system are presented as well as some dedicated applications already realized, including use in a surface mapping instrument and use of a "mini-spectrometer" for the analysis of works of art. Fully depleted pn-charge-coupled devices (pn-CCDs) have been fabricated for the European X-ray Multi-Mirror mission (XMM) and the German X-ray satellite ABRIXAS, enabling high-speed, low-noise, position-resolving X-ray spectroscopy. The detector was designed and fabricated with a homogeneously sensitive area of 36 cm2. At -70 degrees C it has a noise of 4 e- rms, with a readout time of the total focal plane array of 4 msec. The maximum count rate for single photon counting was 10(5) cps under flat field conditions. In the integration mode, more than 10(9) cps can be detected at 6 keV. Its position resolution is on the order of 100 µm. The quantum efficiency is higher than 90%, ranging from carbon K X-rays (277 eV) up to 10 keV.

Olfactory cues associated with the major histocompatibility complex.

Besides its immunological function of self/non-self discrimination the major histocompatibility complex (MHC) has been recognized as a possible source of individual specific body odors. Dating back to speculations on the role of the extraordinary polymorphism of the MHC as background of an individual chemosensory identity and to early observations of MHC-dependent mate choice in inbred strains of mice, systematic experimental studies revealed a first evidence for H-2 related body odors in this species. Meanwhile a large number of animal studies with rodents and a series of field studies and experiments with humans have extended our knowledge of MHC-related odor signals and substantiated the hypothesis of immunogenetic associated odor types. These results suggest that the most prominent feature of the MHC, its extraordinary genetic diversity, seems in part to be selectively maintained by behavioral mechanisms which operate in contemporary natural populations. The high degree of heterozygosity found in natural populations of most species seems to be promoted by non-disease-based selection such as mating preferences and selective block of pregnancy.

The major histocompatibility complex and the chemosensory signalling of individuality in humans.

The chemosensory identity of mice and rats is determined partly by polymorphic genes of the major histocompatibility complex (MHC). In inbred strains of mice, as well as in seminatural populations, MHC-associated mating preferences selectively influence reproductive success, thus serving to promote heterozygocity in the MHC. In order to determine whether MHC-associated chemosignals are present in humans, two studies were conducted. In a first study, olfactory identification of MHC-associated chemosignals was conducted on 12 trained rats' responses to the urine odors of humans. In a second study, MHC-associated olfactory cues in humans were analyzed by means of gas chromatography. The results indicate that the urine odors of humans are associated with the MHC and demonstrate that the profile of volatile components in the urine odors shows some association with the MHC. Furthermore, results show that a profile of some specific components, as well as a few ubiquitous volatiles, constitutes MHC-associated odor signals in humans.

Molecular forms of soluble HLA in body fluids: potential determinants of body odor cues.

The major histocompatibility complex (MHC) has been linked to encoding for individual olfactory identity. Experiments in mice and rats proved that behavior and mating were, at least in part, determined by genes within the MHC. This study was aimed at investigating whether sHLA are excreted in human urine, saliva and sweat. In particular examination of the molecular forms in these fluids would give clues to whether break down forms of soluble MHC molecules might participate in shaping behavior. Major bands of 45, 40, and 23 kD were detectable. Increased levels of sHLA were measured using a quantitative ELISA in urine shortly before ovulation decreasing to normal levels thereafter. In animal models strain specific MHC-linked odor cues have been detected in urine. Thus, excretion of sHLA in urine might indicate a similar role for these molecules in humans.

Fractionation and bioassay of human odor types.

Human urine samples were fractionated to examine the contribution of volatiles to the individual body odor. The samples were obtained from 4 male donors and fractionated using a vacuum technique. The volatiles from the chemical fractions were analyzed using the CLSA technique and gas chromatography. Thereafter, these fractions were tested in a computer-controlled olfactometer by trained rats. Although the rats were able to discriminate the distillation residue, they could not recognize the urine odor in the distilled fraction. The results of gas chromatography indicate a continuous release of volatile constituents in the distillation residue.