The impact of the stone age diet on gingival conditions in the absence of oral hygiene

BACKGROUND: The objective of this study was to assess the oral microbiota and clinical data in subjects without access to traditional oral hygiene methods and who ate a diet available in the Stone Age. METHODS: Ten subjects living in an environment replicating the Stone Age for 4 weeks were enrolled in this study. Bleeding on probing (BOP), gingival and plaque indices, and probing depth (PD) were assessed at baseline and at 4 weeks. Microbiologic samples were collected at the mesio-buccal subgingival aspects of all teeth and from the dorsum of the tongue and were processed by checkerboard DNA-DNA hybridization methods. RESULTS: No subject had periodontitis. Mean BOP decreased from 34.8% to 12.6% (P <0.001). Mean gingival index scores changed from 0.38 to 0.43 (not statistically significant) and mean plaque scores increased from 0.68 to 1.47 (P <0.001). PD at sites of subgingival sampling decreased (mean difference: 0.2 mm; P <0.001). At week 4, the total bacterial count was higher (P <0.001) for 24 of 74 species, including Bacteroides ureolyticus, Eikenella corrodens, Lactobacillus acidophilus, Capnocytophaga ochracea, Escherichia coli, Fusobacterium nucleatum naviforme, Haemophilus influenzae, Helicobacter pylori, Porphyromonas endodontalis, Staphylococcus aureus (two strains), Streptococcus agalactiae, Streptococcus anginosis, and Streptococcus mitis. Bacterial counts from tongue samples were higher at baseline (P <0.001) for 20 species, including Tannerella forsythia (previously T. forsythensis), Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans; serotype a), and Streptococcus spp. CONCLUSIONS: The experimental gingivitis protocol is not applicable if the diet (e.g., Stone Age) does not include refined sugars. Although plaque levels increased, BOP and PD decreased. Subgingival bacterial counts increased for several species not linked to periodontitis, whereas tongue bacterial samples decreased during the study period.

Modeling of human P450 oxidoreductase structure by in silico mutagenesis and MD simulation

P450 oxidoreductase (POR) is the obligate electron donor for microsomal cytochrome P450s and mutations in POR cause several metabolic disorders. We have modeled the structure of human P450 oxidoreductase by in silico amino acid replacements in the rat POR crystal structure. The rat POR has 94% homology with human POR and 38 amino acids were replaced to make its sequence identical to human POR. Several rounds of molecular dynamic simulations refined the model and removed structural clashes from side chain alterations of replaced amino acids. This approach has the advantage of keeping the cofactor contacts and structural features of the core enzyme intact which could not be achieved by homology based approaches. The final model from our approach was of high quality and compared well with experimentally determined structures of other PORs. This model will be used for analyzing the structural implications of mutations and polymorphisms in human POR.

A comparative study on manual and automatic slice-to-volume registration of CT images

In order to assess the clinical relevance of a slice-to-volume registration algorithm, this technique was compared to manual registration. Reformatted images obtained from a diagnostic CT examination of the lower abdomen were reviewed and manually registered by 41 individuals. The results were refined by the algorithm. Furthermore, a fully automatic registration of the single slices to the whole CT examination, without manual initialization, was also performed. The manual registration error for rotation and translation was found to be 2.7+/-2.8 degrees and 4.0+/-2.5 mm. The automated registration algorithm significantly reduced the registration error to 1.6+/-2.6 degrees and 1.3+/-1.6 mm (p = 0.01). In 3 of 41 (7.3%) registration cases, the automated registration algorithm failed completely. On average, the time required for manual registration was 213+/-197 s; automatic registration took 82+/-15 s. Registration was also performed without any human interaction. The resulting registration error of the algorithm without manual pre-registration was found to be 2.9+/-2.9 degrees and 1.1+/-0.2 mm. Here, a registration took 91+/-6 s, on average. Overall, the automated registration algorithm improved the accuracy of manual registration by 59% in rotation and 325% in translation. The absolute values are well within a clinically relevant range.

Enriching Reverse Engineering with Annotations

Much of the knowledge about software systems is implicit, and therefore difficult to recover by purely automated techniques. Architectural layers and the externally visible features of software systems are two examples of information that can be difficult to detect from source code alone, and that would benefit from additional human knowledge. Typical approaches to reasoning about data involve encoding an explicit meta-model and expressing analyses at that level. Due to its informal nature, however, human knowledge can be difficult to characterize up-front and integrate into such a meta-model. We propose a generic, annotation-based approach to capture such knowledge during the reverse engineering process. Annotation types can be iteratively defined, refined and transformed, without requiring a fixed meta-model to be defined in advance. We show how our approach supports reverse engineering by implementing it in a tool called Metanool and by applying it to (i) analyzing architectural layering, (ii) tracking reengineering tasks, (iii) detecting design flaws, and (iv) analyzing features.

Does subjective burden of early breast cancer and its treatment affect immune measures during adjuvant therapy?

Psychosocial factors have been described as affecting cellular immune measures in healthy subjects. In patients with early breast cancer we explored bi-directional psycho-immune effects to determine whether subjective burden has an impact on immune measures, and vice versa. Patients (n = 239) operated for early breast cancer and randomized into International Breast Cancer Study Group (IBCSG) adjuvant clinical trials were assessed immediately before the beginning of adjuvant treatment (baseline) and 3 and 6 months thereafter, at the beginning of the corresponding treatment cycle. Cellular immune measures (leukocytes, lymphocytes, lymphocyte subset counts), markers of activation of the cellular immune system (beta2-microglobulin, soluble interleukin-2 receptor serum levels), and self-report subjective burden (global indicators of physical well-being, mood, coping effort) were assessed concurrently. The relationship between subjective burden and gradients of immune measures was investigated with regression analyses controlling for adjuvant treatment. There was a pattern of small negative associations between all variables assessing subjective burden before the beginning of adjuvant therapy with the gradients of the markers of activation of the cellular immune system and NK cell counts. In particular, better mood predicted a decline in the course of beta2-microglobulin and IL-2r at months 3 and 6. The gradient of beta2-microglobulin was associated with mood and coping effort at month 3. However, the effect sizes were very small. In conclusion, in this explorative investigation, there was an indication for subjective burden affecting and being affected by markers of activation of the cellular immune system during the first 3 and 6 months of adjuvant therapy. The question of clinical significance remains unanswered. These associations have to be investigated with refined assessment tools and schedules.

Arachnomelia in Brown Swiss cattle maps to chromosome 5

Arachnomelia in Brown Swiss cattle is a monogenic autosomal recessive inherited congenital disorder of the skeletal system giving affected calves a spidery look (OMIA ID 000059). Over a period of 20 years 15 cases were sampled in the Swiss and Italian Brown cattle population. Pedigree data revealed that all affected individuals trace back to a single acknowledged carrier founder sire. A genome scan using 240 microsatellites spanning the 29 bovine autosomes showed homozygosity at three adjacent microsatellite markers on bovine Chr 5 in all cases. Linkage analysis confirmed the localization of the arachnomelia mutation in the region of the marker ETH10. Fine-mapping and haplotype analysis using a total of 34 markers in this region refined the critical region of the arachnomelia locus to a 7.19-Mb interval on bovine Chr 5. The disease-associated IBD haplotype was shared by 36 proven carrier animals and allows marker-assisted selection. As the corresponding human and mouse chromosome segments do not contain any clear functional candidate genes for this disorder, the mutation causing arachnomelia in the Brown Swiss cattle might help to identify an unknown gene in bone development.

Genetic mapping of the belt pattern in Brown Swiss cattle to BTA3

The white belt pattern of Brown Swiss cattle is characterized by a lack of melanocytes in a stretch of skin around the midsection. This pattern is of variable width and sometimes the belt does not fully circle the body. To identify the gene responsible for this colour variation, we performed linkage mapping of the belted locus using six segregating half-sib families including 104 informative meioses for the belted character. The pedigree confirmed a monogenic autosomal dominant inheritance of the belted phenotype in Brown Swiss cattle. We performed a genome scan using 186 microsatellite markers in a subset of 88 animals of the six families. Linkage with the belt phenotype was detected at the telomeric region of BTA3. Fine-mapping and haplotype analysis using 19 additional markers in this region refined the critical region of the belted locus to a 922-kb interval on BTA3. As the corresponding human and mouse chromosome segments contain no obvious candidate gene for this coat colour trait, the mutation causing the belt pattern in the Brown Swiss cattle might help to identify an unknown gene influencing skin pigmentation.

Decreased functional connectivity of EEG theta-frequency activity in first-episode, neuroleptic-naïve patients with schizophrenia: preliminary results

We explored and refined the hypothesis that during a first episode of acute schizophrenia a disorganization of brain functioning is present. A novel EEG measure was introduced, Global Field Synchronization (GFS), that estimates functional connectivity of brain processes in different EEG frequency bands. The measure was applied to EEG's from 11 never-treated, first-episode, young patients with an acute, positive, schizophrenic symptomatology and from 19 controls, residing in Bern, Switzerland. In comparison to age- and sex- matched controls, patients had significantly decreased GFS in the theta EEG frequency band, indicating a loosened functional connectivity of processes in this frequency. The result was confirmed in an independent, comparable patient group from Osaka, Japan (9 patients and 9 controls), thus making a total of 20 analyzed patients. Previous EEG research in healthy, awake subjects indicated a positive correlation of theta activity with memory functions. Thus, our result suggests a loss of mutual interdependence of memory functions in patients with acute schizophrenia, which agrees well with previous reports of working memory dysfunction in schizophrenia.

Improving Management of Distributed Services Using Correlations and Predictions in SLA-Driven Cloud Computing Systems

Recent advancements in cloud computing have enabled the proliferation of distributed applications, which require management and control of multiple services. However, without an efficient mechanism for scaling services in response to changing environmental conditions and number of users, application performance might suffer, leading to Service Level Agreement (SLA) violations and inefficient use of hardware resources. We introduce a system for controlling the complexity of scaling applications composed of multiple services using mechanisms based on fulfillment of SLAs. We present how service monitoring information can be used in conjunction with service level objectives, predictions, and correlations between performance indicators for optimizing the allocation of services belonging to distributed applications. We validate our models using experiments and simulations involving a distributed enterprise information system. We show how discovering correlations between application performance indicators can be used as a basis for creating refined service level objectives, which can then be used for scaling the application and improving the overall application's performance under similar conditions.

Controversies of fetal cardiac intervention

Remarkable advances in ultrasound imaging technology have made it possible to diagnose fetal cardiovascular lesions as early as 12-14 weeks of gestation and to assess their physiological relevance by echocardiography. Moreover, invasive techniques have been developed and refined to relieve significant congenital heart disease (CHD), such as critical aortic and pulmonary stenoses in the pediatric population including neonates. Recognition of the fact that certain CHDs can evolve in utero, and early intervention may improve the outcome by altering the natural history of such conditions has led to the evolution of a new fetal therapy, i.e. fetal cardiac intervention. Two entities, pulmonary valvar atresia and intact ventricular septum (PA/IVS) and hypoplastic left heart syndrome (HLHS), are associated with significant morbidity and mortality even with postnatal surgical therapy. These cases are believed to occur due to restricted blood flow, leading to impaired growth and function of the right or left ventricle. Therefore, several centers started the approach of antenatal intervention with the primary goal of improving the blood flow through the stenotic/atretic valve orifices to allow growth of cardiac structures. Even though centers with a reasonable number of cases seem to have improved the technique and the immediate outcome of fetal interventions, the field is challenged by ethical issues as the intervention puts both the mother and the fetus at risk. Moreover, the perceived benefits of prenatal treatment have to be weighed against steadily improving postnatal surgical and hybrid procedures, which have been shown to reduce morbidity and mortality for these complex heart defects. This review is an attempt to provide a balanced opinion and an update on fetal cardiac intervention.

hp-dGFEM for Second-Order Elliptic Problems in Plyhedra I: Stability and Quasioptimality on Geometric Meshes

We introduce and analyze hp-version discontinuous Galerkin (dG) finite element methods for the numerical approximation of linear second-order elliptic boundary-value problems in three-dimensional polyhedral domains. To resolve possible corner-, edge- and corner-edge singularities, we consider hexahedral meshes that are geometrically and anisotropically refined toward the corresponding neighborhoods. Similarly, the local polynomial degrees are increased linearly and possibly anisotropically away from singularities. We design interior penalty hp-dG methods and prove that they are well-defined for problems with singular solutions and stable under the proposed hp-refinements. We establish (abstract) error bounds that will allow us to prove exponential rates of convergence in the second part of this work.

Handbook of LHC Higgs Cross Sections: 3. Higgs Properties. Report of the LHC Higgs Cross Section Working Group

This Report summarizes the results of the activities in 2012 and the first half of 2013 of the LHC Higgs Cross Section Working Group. The main goal of the working group was to present the state of the art of Higgs Physics at the LHC, integrating all new results that have appeared in the last few years. This report follows the first working group report Handbook of LHC Higgs Cross Sections: 1. Inclusive Observables (CERN-2011-002) and the second working group report Handbook of LHC Higgs Cross Sections: 2. Differential Distributions (CERN-2012-002). After the discovery of a Higgs boson at the LHC in mid-2012 this report focuses on refined prediction of Standard Model (SM) Higgs phenomenology around the experimentally observed value of 125-126 GeV, refined predictions for heavy SM-like Higgs bosons as well as predictions in the Minimal Supersymmetric Standard Model and first steps to go beyond these models. The other main focus is on the extraction of the characteristics and properties of the newly discovered particle such as couplings to SM particles, spin and CP-quantum numbers etc.

Validation of targeting the ventrointermediate thalamic nucleus using Q-ball calculation in deep brain stimulation for tremor

Objective: Identification of the ventrointermediate thalamic nucleus (Vim) in modern 3T high-field MRI for image-based targeting in deep brain stimulation (DBS) is still challenging. To evaluate the usefulness and reliability of analyzing the connectivity with the cerebellum using Q-ball-calculation we performed a retrospective analysis. Method: 5 patients who underwent bilateral implantation of electrodes in the Vim for treatment of Essential Tremor between 2011 and 2012 received additional preoperative Q-ball imaging. Targeting was performed according to atlas coordinates and standard MRI. Additionally we performed a retrospective identification of the Vim by analyzing the connectivity of the thalamus with the dentate nucleus. The exact position of the active stimulation contact in the postoperative CT was correlated with the Vim as it was identified by Q-ball calculation. Results: Localization of the Vim by analysis of the connectivity between thalamus and cerebellum was successful in all 5 patients on both sides. The average position of the active contacts was 14.6 mm (SD 1.24) lateral, 5.37 mm (SD 0.094 posterior and 2.21 mm (SD 0.69) cranial of MC. The cranial portion of the dentato-rubro-thalamic tract was localized an average of 3.38 mm (SD 1.57) lateral and 1.5 mm (SD 1.22) posterior of the active contact. Conclusions: Connectivity analysis by Q-ball calculation provided direct visualization of the Vim in all cases. Our preliminary results suggest, that the target determined by connectivity analysis is valid and could possibly be used in addition to or even instead of atlas based targeting. Larger prospective calculations are needed to determine the robustness of this method in providing refined information useful for neurosurgical treatment of tremor.

Detection of pulmonary amylase activity in exhaled breath condensate

Amylase activity in exhaled breath condensate (EBC) is usually interpreted as an indication of oropharyngeal contamination despite the fact that amylase can be found in pulmonary excretions. The aim of this study was to recruit and refine an amylase assay in order to detect amylase activity in any EBC sample and to develop a method to identify EBC samples containing amylase of pulmonary origin. EBC was collected from 40 volunteers with an EcoScreen condenser. Amylase assays and methods to discriminate between oropharyngeal and pulmonary proteins were tested and developed using matched EBC and saliva samples. Our refined 2-chloro-4-nitrophenyl-α-D-maltotriosid (CNP-G3) assay was 40-fold more sensitive than the most sensitive commercial assay and allowed detection of amylase activity in 30 µl of EBC. We developed a dot-blot assay which allowed detection of salivary protein in saliva diluted up to 150 000-fold. By plotting amylase activity against staining intensity we identified a few EBC samples with high amylase activity which were aligned with diluted saliva. We believe that EBC samples aligned with diluted saliva contain amylase activity introduced during EBC collection and that all other EBC samples contain amylase activity of pulmonary origin and are basically free of oropharyngeal protein contamination.

Kyzylkumite, Ti2V3+O5(OH): new structure type, modularity and revised formula

The crystal structure of kyzylkumite, ideally Ti2V3+O5(OH), from the Sludyanka complex in South Baikal, Russia was solved and refined (including the hydrogen atom position) to an agreement index, R1, of 2.34 using X-ray diffraction data collected on a twinned crystal. Kyzylkumite crystallizes in space group P21/c, with a = 8.4787(1), b = 4.5624(1), c = 10.0330(1) Å, β = 93.174(1)°, V = 387.51(1) Å3 and Z = 4. Tivanite, TiV3+O3OH, and kyzylkumite have modular structures based on hexagonal close packing of oxygen, which are made up of rutile TiO2 and montroseite V3+O(OH) slices. In tivanite the rutile:montroseite ratio is 1:1, in kyzylkumite the ratio is 2:1. The montroseite module may be replaced by the isotypic paramontroseite V4+O2 module, which produces a phase with the formula Ti2V4+O6. In the metamorphic rocks of the Sludyanka complex, vanadium can be present as V4+ and V3+ within the same mineral (e.g. in batisivite, schreyerite and berdesinskiite). Kyzylkumite has a flexible composition with respect to the M4+/M3+ ratio. The relationship between kyzylkumite and a closely related Be-bearing kyzylkumite-like mineral with an orthorhombic norbergite-type structure from Byrud mine, Norway is discussed. Both minerals have similar X-ray powder diffraction patterns.