The Stabilized Poincare-Heisenberg algebra: a Clifford algebra viewpoint

The stabilized Poincare-Heisenberg algebra (SPHA) is the Lie algebra of quantum relativistic kinematics generated by fifteen generators. It is obtained from imposing stability conditions after attempting to combine the Lie algebras of quantum mechanics and relativity which by themselves are stable, however not when combined. In this paper we show how the sixteen dimensional Clifford algebra CL(1,3) can be used to generate the SPHA. The Clifford algebra path to the SPHA avoids the traditional stability considerations, relying instead on the fact that CL(1,3) is a semi-simple algebra and therefore stable. It is therefore conceptually easier and more straightforward to work with a Clifford algebra. The Clifford algebra path suggests the next evolutionary step toward a theory of physics at the interface of GR and QM might be to depart from working in space-time and instead to work in space-time-momentum.Comment: 14 page

Integrated transcriptomic and proteomic analyses ofP. falciparumgametocytes: molecular insight into sex-specific processes and translational repression

Sexual differentiation of malaria parasites into gametocytes in the vertebrate host and subsequent gamete fertilization in mosquitoes is essential for the spreading of the disease. The molecular processes orchestrating these transitions are far from fully understood. Here, we report the first transcriptome analysis of male and female Plasmodium falciparum gametocytes coupled with a comprehensive proteome analysis. In male gametocytes there is an enrichment of proteins involved in the formation of flagellated gametes; proteins involved in DNA replication, chromatin organization and axoneme formation. On the other hand, female gametocytes are enriched in proteins required for zygote formation and functions after fertilization; protein-, lipid- and energy-metabolism. Integration of transcriptome and proteome data revealed 512 highly expressed maternal transcripts without corresponding protein expression indicating large scale translational repression in P. falciparum female gametocytes for the first time. Despite a high degree of conservation between Plasmodium species, 260 of these 'repressed transcripts' have not been previously described. Moreover, for some of these genes, protein expression is only reported in oocysts and sporozoites indicating that repressed transcripts can be partitioned into short- and long-term storage. Finally, these data sets provide an essential resource for identification of vaccine/drug targets and for further mechanistic studies

Influence of Deep Margin Elevation and preparation design on the fracture strength of indirectly restored molars

The objectives of this in-vitro study were to investigate the influence of Deep Margin Elevation (DME) and the preparation design (cusp coverage) on the fracture strength and repairability of CAD/CAM manufactured lithium disilicate (LS2) restorations on molars. Sound extracted human molars (n = 60) were randomly divided into 4 groups (n = 15) (inlay without DME (InoD); inlay with DME (IWD); onlay without DME (OnoD); onlay with DME (OnWD)). All samples were aged (1.2 × 106 cycles of 50N, 8000 cycles of 5–55 °C) followed by oblique static loading until fracture. Fracture strength was measured in Newton and the fracture analysis was performed using a (scanning electron) microscope. Data was statistically analyzed using two-way ANOVA and contingency tables. DME did not affect the fracture strength of LS2 restorations to a statistically significant level (p =.15). Onlays were stronger compared to inlays (p =.00). DME and preparation design did not interact (p =.97). However, onlays with DME were significantly stronger than inlays without DME (p =.00). More repairable fractures were observed among inlays (p =.00). Catastrophic, crown-root fractures were more prevalent in onlays (p =.00). DME did not influence repairability of fractures or fracture types to a statistically significant level (p &gt;.05). Within the limitations of this in-vitro study, DME did not statistical significantly affect the fracture strength, nor the fracture type or repairability of LS2 restorations in molars. Cusp coverage did increase the fracture strength. However, oblique forces necessary to fracture both inlays and onlays, either with or without DME, by far exceeded the bite forces that can be expected under physiological clinical conditions. Hence, both inlays and onlays are likely to be fracture resistant during clinical service.</p

Randomized clinical trial on the survival of lithium disilicate posterior partial restorations bonded using immediate or delayed dentin sealing after 3 years of function

Objectives: The survival and success rate and the quality of survival of partial ceramic restorations bonded employing Immediate (IDS) or Delayed Dentin Sealing (DDS) in vital molar teeth were evaluated in a randomized clinical trial with within-subject comparison study.Materials and methods: 30 patients received two lithium disilicate ceramic (IPS-e.max press, Ivoclar Vivadent) partial restorations on vital first or second molar teeth (N = 60). The two teeth randomly received either IDS (test group, n = 30) or DDS (control group, n = 30). Partial ceramic restorations were luted (Variolink Ultra, Ivoclar Vivadent) two weeks after preparation. Evaluations were performed at 1 week, 12 months and 36 months post-operatively, using qualitative (FDI) criteria. Representative failures were evaluated microscopically (SEM) and by means of simplified qualitative fractography analysis.Results: One absolute failure occurred in the DDS group due to (secondary) caries. The overall survival rate according to Kaplan-Meier after 3 years was 98.3% (FDI criteria score 1-4, n = 59) and the overall success rate was 85% (FDI criteria score 1-3, n = 51), with no significant difference between restorations in the IDS and DDS group (p = 0.32; Kaplan-Meier, Log Rank (Mantel-Cox), CI = 95%). For the quality of the survival, no statistically significant differences were found between IDS and DDS (p = 0.7; Kaplan-Meier, Log Rank (Mantel-Cox), CI = 95%) restorations on any follow-up timepoints for any of the FDI criteria (Wilcoxon, McNemar, p &gt; 0.05).Conclusion: Adhesively luted partial ceramic restorations in vital molar teeth have a good prognosis, however IDS did not show any differences in success and survival rates after 3 years of function.</p

8-year multicenter retrospective study on partial laminate veneers

Purpose: This retrospective study aimed to evaluate the survival and success rates of ceramic partial laminate veneers. Scanning electron microscopy was used to evaluate fractures and marginal defects. Methods: In total, 31 patients received 79 partial laminate veneers on the maxillary anterior teeth. After adhesive luting, restorations were evaluated by calibrated clinicians for up to eight years using modified United States Public Health Service (USPHS) criteria. In addition, epoxy resin replicas were fabricated from silicone impressions and analyzed using scanning electron microscopy. Survival analyses were performed using the Kaplan-Meier and log-rank tests (α = 0.05). Success was analyzed in percentages by comparing the baseline and last follow-up. Results: The cumulative survival rates were 100% after 1 year; 95.9% (SE 2.8%) after 5 years; and 61.4% (SE 25.3%) after 8 years. No significant differences (P &gt; 0.05) were observed between functional and non-functional restorations. Changes in the USPHS criteria evaluation were only observed for adaptation: 12.5% (SE 4.7%), marginal discoloration: 4.2% (SE 3.0%), color match: 4.2% (SE 3.0%), and fractures: 16.7% (SE 5.3%). Scanning electron microscopy evaluations revealed undetected initial cracks and deficiencies in the restorations. Conclusions: Partial laminate veneers displayed good survival rates during the long-term follow-up. The main problems observed were related to the quality of the margins, color mismatch, and restoration integrity. However, in most cases, restoration replacement was not required.</p

Clinical longevity of intracoronal restorations made of gold, lithium disilicate, leucite, and indirect resin composite:a systematic review and meta-analysis

OBJECTIVES: The aim of this systematic review and meta-analysis is to assess the comparative clinical success and survival of intracoronal indirect restorations using gold, lithium disilicate, leucite, and indirect composite materials.MATERIAL AND METHODS: This systematic review and meta-analysis were conducted following the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. The protocol for this study was registered in PROSPERO (registration number: CRD42021233185). A comprehensive literature search was conducted across various databases and sources, including PubMed/Medline, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and gray literature. A total of 7826 articles were screened on title and abstract. Articles were not excluded based on the vitality of teeth, the language of the study, or the observation period. The risk difference was utilized for the analyses, and a random-effects model was applied. All analyses were conducted with a 95% confidence interval (95% CI). The calculated risk differences were derived from the combined data on restoration survival and failures obtained from each individual article. The presence of heterogeneity was assessed using the I2 statistic, and if present, the heterogeneity of the data in the articles was evaluated using the non-parametric chi-squared statistic (p &lt; 0.05).RESULTS: A total of 12 eligible studies were selected, which included 946 restorations evaluated over a minimum observation period of 1 year and a maximum observation period of 7 years. Results of the meta-analysis indicated that intracoronal indirect resin composite restorations have an 18% higher rate of failure when compared to intracoronal gold restorations over 5-7 years of clinical service (risk difference =  - 0.18 [95% CI: - 0.27, - 0.09]; p = .0002; I2 = 0%). The meta-analysis examining the disparity in survival rates between intracoronal gold and leucite restorations could not be carried out due to methodological differences in the studies.CONCLUSIONS: According to the currently available evidence, medium-quality data indicates that lithium disilicate and indirect composite materials demonstrate comparable survival rates in short-term follow-up. Furthermore, intracoronal gold restorations showed significantly higher survival rates, making them a preferred option over intracoronal indirect resin-composite restorations. Besides that, the analysis revealed no statistically significant difference in survival rates between leucite and indirect composite restorations. The short observation period, limited number of eligible articles, and low sample size of the included studies were significant limitations.CLINICAL SIGNIFICANCE: Bearing in mind the limitations of the reviewed literature, this systematic review and meta-analysis help clinicians make evidence-based decisions on how to restore biomechanically compromised posterior teeth.</p

Genetic deficiency of NOD2 confers resistance to invasive aspergillosis

Invasive aspergillosis (IA) is a severe infection that can occur in severely immunocompromised patients. Efficient immune recognition of Aspergillus is crucial to protect against infection, and previous studies suggested a role for NOD2 in this process. However, thorough investigation of the impact of NOD2 on susceptibility to aspergillosis is lacking. Common genetic variations in NOD2 has been associated with Crohn's disease and here we investigated the influence of these  genetic variations on the anti-Aspergillus host response. A NOD2 polymorphism reduced the risk of IA after hematopoietic stem-cell transplantation. Mechanistically, absence of NOD2 in monocytes and macrophages increases phagocytosis leading to enhanced fungal killing, conversely, NOD2 activation reduces the antifungal potential of these cells. Crucially, Nod2 deficiency results in resistance to Aspergillus infection in an in vivo model of pulmonary aspergillosis. Collectively, our data demonstrate that genetic deficiency of NOD2 plays a protective role during Aspergillus infection.We thank C. Wertz and M. Fanton D'Andon for providing Nod2-deficient mice, M. Schlotter for organizing patient inclusion, B. Rosler for assistance with flowcytometry. We also thank the NOD2-deficient patients for contributing to our study by providing blood samples. M.S.G. was supported by the Erasmus lifelong learning program. F.L.v.d.V. was supported by the E-rare project EURO-CMC. M.O. was supported by the NWO, 016.176.006). A.C. and C.C. were supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundacao para a Ciencia e Tecnologia (FCT) (IF/00735/2014 to A.C. and SFRH/BPD/96176/2013 to C. C.)

General practice activity in Australia 2012-13

Patients with chronic granulomatous disease (CGD) have a mutated NADPH complex resulting in defective production of reactive oxygen species; these patients can develop severe colitis and are highly susceptible to invasive fungal infection. In NADPH oxidase-deficient mice, autophagy is defective but inflammasome activation is present despite lack of reactive oxygen species production. However, whether these processes are mutually regulated in CGD and whether defective autophagy is clinically relevant in patients with CGD is unknown. Here, we demonstrate that macrophages from CGD mice and blood monocytes from CGD patients display minimal recruitment of microtubule-associated protein 1 light chain 3 (LC3) to phagosomes. This defect in autophagy results in increased IL-1β release. Blocking IL-1 with the receptor antagonist (anakinra) decreases neutrophil recruitment and T helper 17 responses and protects CGD mice from colitis and also from invasive aspergillosis. In addition to decreased inflammasome activation, anakinra restored autophagy in CGD mice in vivo, with increased Aspergillus-induced LC3 recruitment and increased expression of autophagy genes. Anakinra also increased Aspergillus-induced LC3 recruitment from 23\% to 51\% (P < 0.01) in vitro in monocytes from CGD patients. The clinical relevance of these findings was assessed by treating CGD patients who had severe colitis with IL-1 receptor blockade using anakinra. Anakinra treatment resulted in a rapid and sustained improvement in colitis. Thus, inflammation in CGD is due to IL-1-dependent mechanisms, such as decreased autophagy and increased inflammasome activation, which are linked pathological conditions in CGD that can be restored by IL-1 receptor blockade

Clinical survival and performance of premolars restored with direct or indirect cusp-replacing resin composite restorations with a mean follow-up of 14 years

Objectives: The objective is to evaluate the long-term clinical survival and performance of direct and indirect resin composite restorations replacing cusps in vital upper premolars. Methods: Between 2001 and 2007, 176 upper premolars in 157 patients were restored with 92 direct and 84 indirect resin composite restorations as part of an RCT. Inclusion criteria were fracture of the buccal or palatal cusp of vital upper premolars along with a class II cavity or restoration in the same tooth. Results: Forty patients having 23 direct and 22 indirect composite restorations respectively, were lost to follow-up (25.6%). The cumulative Kaplan-Meier survival rates were 63.6% (mean observation time: 15.3 years, SE 5.6%) with an AFR of 2.4% for direct restorations and 54.5% (mean observation time: 13.9 years, SE: 6.4%) with an AFR of 3.3% for indirect restorations. The Cox regression analysis revealed a statistically significant influence of the patient's age at placement on the survival of the restoration (HR 1.036, p = 0.024), the variables gender, type of upper premolar, type of restoration, and which cusp involved in the restoration had no statistically significant influence. Direct composite restorations failed predominantly due to tooth fracture, indirect restorations primarily by adhesive failure (p < 0.05). Significance: There was no statistically significant difference in survival rates between direct and indirect composite cusp-replacing restorations. Both direct and indirect resin composite cusp-replacing restorations are suitable options to restore compromised premolars. The longer treatment time and higher costs for the indirect restoration argue in favor of the direct technique