Celiac disease (CD) is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8) and the environmental trigger (gluten) are known and necessary but not sufficient for its development. Other ...environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late) on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to deciphering the role of the gut microbiota on CD onset.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The stability of the surface of in situ cleaved black phosphorus crystals upon exposure to atmosphere is investigated with synchrotron-based photoelectron spectroscopy. After 2 days atmosphere ...exposure a stable subnanometer layer of primarily P2O5 forms at the surface. The work function increases by 0.1 eV from 3.9 eV for as-cleaved black phosphorus to 4.0 eV after formation of the 0.4 nm thick oxide, with phosphorus core levels shifting by <0.1 eV. The results indicate minimal charge transfer, suggesting that the oxide layer is suitable for passivation or as an interface layer for further dielectric deposition.
Vaginal microbiome of reproductive-age women Ravel, Jacques; Gajer, Pawel; Abdo, Zaid ...
Proceedings of the National Academy of Sciences - PNAS,
03/2011, Letnik:
108, Številka:
Supplement 1
Journal Article
Recenzirano
Odprti dostop
The means by which vaginal microbiomes help prevent urogenital diseases in women and maintain health are poorly understood. To gain insight into this, the vaginal bacterial communities of 396 ...asymptomatic North American women who represented four ethnic groups (white, black, Hispanic, and Asian) were sampled and the species composition characterized by pyrosequencing of barcoded 16S rRNA genes. The communities clustered into five groups: four were dominated by Lactobacillus iners, L. crispatus, L. gasseri, or L. jensenii, whereas the fifth had lower proportions of lactic acid bacteria and higher proportions of strictly anaerobic organisms, indicating that a potential key ecological function, the production of lactic acid, seems to be conserved in all communities. The proportions of each community group varied among the four ethnic groups, and these differences were statistically significant ϲ(10) = 36.8, P < 0.0001. Moreover, the vaginal pH of women in different ethnic groups also differed and was higher in Hispanic (pH 5.0 ± 0.59) and black (pH 4.7 ± 1.04) women as compared with Asian (pH 4.4 ± 0.59) and white (pH 4.2 ± 0.3) women. Phylotypes with correlated relative abundances were found in all communities, and these patterns were associated with either high or low Nugent scores, which are used as a factor for the diagnosis of bacterial vaginosis. The inherent differences within and between women in different ethnic groups strongly argues for a more refined definition of the kinds of bacterial communities normally found in healthy women and the need to appreciate differences between individuals so they can be taken into account in risk assessment and disease diagnosis.
In communications, the frequency range 0.1-30 THz is essentially terra incognita. Recently, research has focused on this terahertz gap, because the high carrier frequencies promise unprecedented ...channel capacities. Indeed, data rates of 100 Gbit s-1 were predicted for 2015. Here, we present, for the first time, a single-input and single-output wireless communication system at 237.5 GHz for transmitting data over 20 m at a data rate of 100 Gbit s-1 . This breakthrough results from combining terahertz photonics and electronics, whereby a narrow-band terahertz carrier is photonically generated by mixing comb lines of a mode-locked laser in a uni-travelling-carrier photodiode. The uni-travelling-carrier photodiode output is then radiated over a beam-focusing antenna. The signal is received by a millimetre-wave monolithic integrated circuit comprising novel terahertz mixers and amplifiers. We believe that this approach provides a path to scale wireless communications to Tbit s-1 rates over distances of >1 km.
Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal ...dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analysis revealed the dynamics of five major classes of bacterial communities and showed that some communities change markedly over short time periods, whereas others are relatively stable. Modeling community stability using new quantitative measures indicates that deviation from stability correlates with time in the menstrual cycle, bacterial community composition, and sexual activity. The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis.
Mobile robots often operate in domains that are only incompletely known, for example, when they have to move from given start coordinates to given goal coordinates in unknown terrain. In this case, ...they need to be able to replan quickly as their knowledge of the terrain changes. Stentz' Focussed Dynamic A/sup */ (D/sup */) is a heuristic search method that repeatedly determines a shortest path from the current robot coordinates to the goal coordinates while the robot moves along the path. It is able to replan faster than planning from scratch since it modifies its previous search results locally. Consequently, it has been extensively used in mobile robotics. In this article, we introduce an alternative to D/sup */ that determines the same paths and thus moves the robot in the same way but is algorithmically different. D/sup */ Lite is simple, can be rigorously analyzed, extendible in multiple ways, and is at least as efficient as D/sup */. We believe that our results will make D/sup */-like replanning methods even more popular and enable robotics researchers to adapt them to additional applications.
Theta: Any-Angle Path Planning on Grids Daniel, K.; Nash, A.; Koenig, S. ...
The Journal of artificial intelligence research,
01/2010, Letnik:
39
Journal Article
Recenzirano
Odprti dostop
Grids with blocked and unblocked cells are often used to represent terrain in robotics and video games. However, paths formed by grid edges can be longer than true shortest paths in the terrain since ...their headings are artificially constrained. We present two new correct and complete any-angle path-planning algorithms that avoid this shortcoming. Basic Theta* and Angle-Propagation Theta* are both variants of A* that propagate information along grid edges without constraining paths to grid edges. Basic Theta* is simple to understand and implement, fast and finds short paths. However, it is not guaranteed to find true shortest paths. Angle-Propagation Theta* achieves a better worst-case complexity per vertex expansion than Basic Theta* by propagating angle ranges when it expands vertices, but is more complex, not as fast and finds slightly longer paths. We refer to Basic Theta* and Angle-Propagation Theta* collectively as Theta*. Theta* has unique properties, which we analyze in detail. We show experimentally that it finds shorter paths than both A* with post-smoothed paths and Field D* (the only other version of A* we know of that propagates information along grid edges without constraining paths to grid edges) with a runtime comparable to that of A* on grids. Finally, we extend Theta* to grids that contain unblocked cells with non-uniform traversal costs and introduce variants of Theta* which provide different tradeoffs between path length and runtime.
Summary Background Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis. The aim of the combination of methotrexate and etanercept in active early ...rheumatoid arthritis (COMET) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept. Methods 542 outpatients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3–24 months were randomly assigned to receive either methotrexate alone titrated up from 7·5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate (same titration) plus etanercept 50 mg a week. Coprimary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints (DAS28) and radiographic non-progression measured with modified total Sharp score. Treatment was allocated with a computerised randomisation and enrolment system, which masked both participants and carers. Analysis was done by modified intention to treat with last observation carried forward for missing data. This study is registered with ClinicalTrials.gov , number NCT00195494 ). Findings 274 participants were randomly assigned to receive combined treatment and 268 methotrexate alone. 132 of 265 (50%, 95% CI 44–56%) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 (28%, 23–33%) taking methotrexate alone (effect difference 22·05%, 95%CI 13·96–30·15%, p<0·0001). 487 evaluable patients had severe disease (DAS28>5·1). 196 of 246 (80%, 75–85%) and 135 of 230 (59%, 53–65%), respectively, achieved radiographic non-progression (20·98%, 12·97–29·09%, p<0·0001). Serious adverse events were similar between groups. Interpretation Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate. Funding Wyeth Research.
Objective
To assess the efficacy of etanercept in the treatment of early active nonsteroidal antiinflammatory drug (NSAID)–refractory nonradiographic axial spondyloarthritis (SpA).
Methods
The study ...population consisted of patients who met the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA but not the modified New York radiographic criteria for ankylosing spondylitis (as assessed by a radiologist at the central trial site), had a symptom duration of >3 months but <5 years, had a score of ≥4 on the Bath Ankylosing Spondylitis Disease Activity Index, and had been treated unsuccessfully with ≥2 NSAIDs. Patients were randomized to receive etanercept 50 mg/week or placebo and continued background NSAID treatment for 12 weeks (double‐blind study); during the subsequent open‐label period, all patients received etanercept 50 mg/week. The primary study end point was meeting the ASAS criteria for 40% improvement (ASAS40) at week 12. Magnetic resonance imaging (MRI) of the sacroiliac joints and spine was performed at baseline and week 12.
Results
One hundred six patients were randomized to the etanercept group and 109 to the placebo group. Of the 215 patients, the mean ± SD age at baseline was 32.0 ± 7.8 years, 154 (72%) were HLA–B27 positive, and 174 (81%) had MRI‐confirmed sacroiliitis. At 12 weeks, the proportion of patients with improvement according to the ASAS40 was significantly higher in the etanercept group than in the placebo group (34 of 105 32% versus 17 of 108 16%; P = 0.006). Patients who received etanercept exhibited a greater reduction in MRI‐based scores for sacroiliac joint inflammation (−46.9% versus −10.9%; P < 0.001) and spinal inflammation (−45.4% versus −33.4%; P = 0.04) compared with placebo‐treated patients at week 12. Post hoc analyses suggested a possible association between higher baseline C‐reactive protein levels or MRI sacroiliac joint inflammation scores and higher rates of ASAS40 response to etanercept. At week 24, patients in the placebo group who had switched to etanercept at 12 weeks exhibited improvement similar to that observed in patients who had received etanercept for 24 weeks.
Conclusion
In patients with nonradiographic axial SpA, etanercept treatment was associated with rapid, significant improvement in symptomatic disease activity, function, and systemic and skeletal inflammation over 12 weeks; clinical/functional improvement was sustained over 24 weeks.
Summary Background Clinical remission and low disease activity are essential treatment targets in patients with rheumatoid arthritis. Although moderately active rheumatoid arthritis is common, ...treatment effects in moderate disease have not been well studied. Additionally, optimum use of biologics needs further investigation, including the use of induction, maintenance, and withdrawal treatment strategies. The aim of the PRESERVE trial was to assess whether low disease activity would be sustained with reduced doses or withdrawal of etanercept in patients with moderately active disease. Methods In a randomised controlled trial, patients aged between 18 and 70 years with moderately active rheumatoid arthritis (disease activity score in 28 joints DAS28 >3·2 and ≤5·1) despite treatment with methotrexate were enrolled at 80 centres in Europe, Latin America, Asia, and Australia between March 6, 2008, and Sept 9, 2009. To be eligible, patients had to have been receiving 15–25 mg of methotrexate every week for at least 8 weeks. In an open-label period of 36 weeks, all patients were given 50 mg etanercept plus methotrexate every week. To be eligible for a subsequent double-blind period of 52 weeks, participants had to have achieved sustained low disease activity. These patients were randomly assigned (1:1:1) by an interactive voice-response system to one of three treatment groups: 50 mg etanercept plus methotrexate, 25 mg etanercept plus methotrexate, or placebo plus methotrexate. Patients were stratified in blocks of three by DAS28 response (low disease activity or remission) at week 36. Patients, investigators, data analysts, and study staff were all masked to treatment allocation. The primary endpoint was the proportion of patients with low disease activity at week 88 in the groups given 50 mg etanercept or placebo in the double-blind period. A conditional primary endpoint was the proportion of patients receiving 25 mg etanercept who achieved low disease activity. Modified intention-to-treat populations were used for analyses. This trial is registered with ClinicalTrials.gov , number NCT00565409. Findings 604 (72·4%) of 834 enrolled patients were eligible for the double-blind period, of whom 202 were assigned to 50 mg etanercept plus methotrexate, 202 to 25 mg etanercept plus methotrexate, and 200 to placebo plus methotrexate. At week 88, 166 (82·6%) of 201 patients who had received at least one dose of 50 mg etanercept and one or more DAS28 evaluations had low disease activity, compared with 84 (42·6%) of 197 who had received placebo (mean difference 40·8%, 95% CI 32·5–49·1%; p<0·0001). Additionally, 159 (79·1%) of 201 patients given 25 mg etanercept had low disease activity at week 88 (mean difference from placebo 35·9%, 27·0–44·8%; p<0·0001). Interpretation Conventional or reduced doses of etanercept with methotrexate in patients with moderately active rheumatoid arthritis more effectively maintain low disease activity than does methotrexate alone after withdrawal of etanercept. Funding Pfizer.
PDF
