Weight loss, bariatric surgery, and novel antidiabetic drugs effects on diabetic retinopathy: a review.

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is a leading cause of visual impairment, and the increasing prevalence of diabetes and obesity will impact rates of visual impairment moving forward. Our review aims to synthesize the current body of evidence regarding the impact of lifestyle interventions, such as weight loss, bariatric surgery, and novel antidiabetic drugs, on DR. RECENT FINDINGS: Literature review revealed insufficient evidence regarding the impact of weight loss on DR. Preoperative DR patients undergoing bariatric surgery were found to have similar short-term chances of improvement or worsening DR. Progression of DR with glucagon-like peptide 1 receptor agonists treatments appears unrelated to specific drugs and was also observed with traditional antidiabetic medications. SUMMARY: Rapidly correcting HbA1c levels (≥2%) can paradoxically lead to early worsening DR. Patients considering weight loss, bariatric surgery, and novel antidiabetic drugs should be aware of the potential for DR progression, but they should not be discouraged, as achieving glycemic control is essential for reducing long-term morbidity and mortality from other diabetes-related complications. It is advisable to conduct a baseline retinal examination before treatment and continue monitoring during therapy. Further research is needed to understand the long-term effects of these treatments on DR.

Collision tumor: Multinodular and vacuolating neuronal tumor with isocitrate dehydrogenase-mutant diffuse astrocytoma.

Herein, we report a case of a collision tumor involving a multinodular and vacuolating neuronal tumor (MVNT) and a diffuse astrocytoma. A collision tumor between these two entities has not previously been reported. The patient is a 35-year-old woman who presented with new-onset hearing loss and ringing in her right ear. Magnetic resonance imaging identified a non-enhancing mass involving the gray matter and subcortical white matter of the left middle frontal gyrus. Additionally, tiny clustered nodules were noted along the underlying subcortical ribbon and superficial subcortical white matter of the left superior frontal gyrus. The patient underwent a left frontal craniotomy and complete resection of the mass. Histologic examination of the resected specimen demonstrated a collision tumor consisting of a diffuse astrocytoma (isocitrate dehydrogenase [IDH] mutant, central nervous system [CNS] World Health Organization [WHO] grade 2) and an MVNT, with the latter demonstrating characteristic morphologic and immunohistochemical features.

Citrobacter freundii-associated lesions in stranded loggerhead sea turtles (Caretta caretta).

Citrobacter freundii, an opportunistic bacterial pathogen belonging to the family Enterobacteriaceae, has been sporadically reported in sea turtles. Here, the authors describe 3 unusual lesions associated with C. freundii infection in 3 loggerhead sea turtles stranded on the coast of Gran Canaria Island, Spain. It is possible that these 3 distinct lesions played a major role in the death of these turtles. The first turtle had caseous cholecystitis, a lesion not previously described in sea turtles. The second turtle had large intestinal diverticulitis, a rare condition in loggerheads. The third turtle had bilateral caseous salt gland adenitis. Histologically, numerous gram-negative bacilli were observed at the deepest edge of inflammation in all cases. Pure cultures of C. freundii were obtained from these 3 lesions. Molecular detection of C. freundii DNA in formalin-fixed paraffin-embedded samples from the lesions of the 3 turtles confirmed the microbiological isolation. These cases, in addition to expanding the limited body of knowledge on bacterial infections in sea turtles, highlight the potential pathogenic role of C. freundii in loggerhead turtles.

Advanced Machine Learning Techniques for Corrosion Rate Estimation and Prediction in Industrial Cooling Water Pipelines.

This paper presents the results of a study on data preprocessing and modeling for predicting corrosion in water pipelines of a steel industrial plant. The use case is a cooling circuit consisting of both direct and indirect cooling. In the direct cooling circuit, water comes into direct contact with the product, whereas in the indirect one, it does not. In this study, advanced machine learning techniques, such as extreme gradient boosting and deep neural networks, have been employed for two distinct applications. Firstly, a virtual sensor was created to estimate the corrosion rate based on influencing process variables, such as pH and temperature. Secondly, a predictive tool was designed to foresee the future evolution of the corrosion rate, considering past values of both influencing variables and the corrosion rate. The results show that the most suitable algorithm for the virtual sensor approach is the dense neural network, with MAPE values of (25 ± 4)% and (11 ± 4)% for the direct and indirect circuits, respectively. In contrast, different results are obtained for the two circuits when following the predictive tool approach. For the primary circuit, the convolutional neural network yields the best results, with MAPE = 4% on the testing set, whereas for the secondary circuit, the LSTM recurrent network shows the highest prediction accuracy, with MAPE = 9%. In general, models employing temporal windows have emerged as more suitable for corrosion prediction, with model performance significantly improving with a larger dataset.

Economic evaluation of adjuvant therapy with osimertinib in patients with early-stage non-small cell lung cancer and mutated EGFR.

PURPOSE: The ADAURA trial demonstrated the superiority of osimertinib over a placebo with regard to disease-free survival, showing it to be indicated as an adjuvant therapy for treatment of non-small cell lung cancer with mutated epidermal growth factor receptor (EGFR). The aim of the present study was to conduct a cost-utility analysis and an analysis of the budgetary impact of adjuvant therapy with osimertinib in patients with non-small cell lung cancer with mutated EGFR who had undergone resection surgery with curative intent. METHODS: Analyses were based on the outcomes of the ADAURA clinical trial and were conducted through a Spanish National Health Service perspective. The outcome measures used were quality-adjusted life years (QALY). RESULTS: The average overall cost of adjuvant treatment with osimertinib over a period of 100 months in the overall sample of trial patients (stages IB-IIIA) was 220,961 €, compared with 197,849 € in the placebo group. Effectiveness, estimated according to QALY, was 6.26 years in the osimertinib group and 5.96 years in the placebo group, with the incremental cost-utility ratio being 77,040 €/QALY. With regard to the budgetary impact, it was estimated that, in 2021, approximately 1130 patients would be subsidiaries to receive osimertinib. This pertains to a difference of 17,375,330 € over 100 months to fund this treatment relative to no treatment. CONCLUSION: Taking into account a Spanish threshold of 24,000 €/QALY, the reduction in the acquisition cost of osimertinib will have to be greater than 10%, to obtain a cost-effective alternative.

Influence of brushing motions on the shaping of oval canals by rotary and reciprocating instruments.

OBJECTIVE: The effects of brushing on shaping with three different instruments were assessed in oval canals. DESIGN: Mandibular incisors were assigned to 6 groups (n = 12/group) according to the system, each one with or without brushing: Reciproc Blue, VDW.Rotate, and Race EVO. Micro-computed tomography was performed before and after preparation. RESULTS: Brushing strokes caused no increase in canal volume, surface area, and structure model index independently of the system (p > 0.05), except for RaCe EVO in the full canal surface area (p < 0.05). Brushing did not increase the prepared areas (p > 0.05), except for Reciproc in the apical canal (p < 0.05). Reciproc with no brushing exhibited less pericervical dentin than with brushing (p < 0.05), while RaCe EVO with brushing resulted in less remaining dentin (p < 0.05). CONCLUSIONS: The brushing motion had no effects on the overall shaping performance of the 3 instruments tested. An exception was the increase in prepared surface area in the apical canal segment when the Reciproc instrument was used with brushing strokes.

Freight Wagon Digitalization for Condition Monitoring and Advanced Operation.

Traditionally, freight wagon technology has lacked digitalization and advanced monitoring capabilities. This article presents recent advancements in freight wagon digitalization, covering the system's definition, development, and field tests on a commercial line in Sweden. A number of components and systems were installed on board on the freight wagon, leading to the intelligent freight wagon. The digitalization includes the integration of sensors for different functions such as train composition, train integrity, asset monitoring and continuous wagon positioning. Communication capabilities enable data exchange between components, securely stored and transferred to a remote server for access and visualization. Three digitalized freight wagons operated on the Nässjo-Falköping line, equipped with strategically placed monitoring sensors to collect valuable data on wagon performance and railway infrastructure. The field tests showcase the system's potential for detecting faults and anomalies, signifying a significant advancement in freight wagon technology, and contributing to an improvement in freight wagon digitalization and monitoring. The gathered insights demonstrate the system's effectiveness, setting the stage for a comprehensive monitoring solution for railway infrastructures. These advancements promise real-time analysis, anomaly detection, and proactive maintenance, fostering improved efficiency and safety in the domain of freight transportation, while contributing to the enhancement of freight wagon digitalization and supervision.

Discreteness Unravels the Black Hole Information Puzzle: Insights from a Quantum Gravity Toy Model.

The black hole information puzzle can be resolved if two conditions are met. The first is that the information about what falls inside a black hole remains encoded in degrees of freedom that persist after the black hole completely evaporates. These degrees of freedom should be capable of purifying the information. The second is if these purifying degrees of freedom do not significantly contribute to the system's energy, as the macroscopic mass of the initial black hole has been radiated away as Hawking radiation to infinity. The presence of microscopic degrees of freedom at the Planck scale provides a natural mechanism for achieving these two conditions without running into the problem of the large pair-creation probabilities of standard remnant scenarios. In the context of Hawking radiation, the first condition implies that correlations between the in and out Hawking partner particles need to be transferred to correlations between the microscopic degrees of freedom and the out partners in the radiation. This transfer occurs dynamically when the in partners reach the singularity inside the black hole, entering the UV regime of quantum gravity where the interaction with the microscopic degrees of freedom becomes strong. The second condition suggests that the conventional notion of the vacuum's uniqueness in quantum field theory should fail when considering the full quantum gravity degrees of freedom. In this paper, we demonstrate both key aspects of this mechanism using a solvable toy model of a quantum black hole inspired by loop quantum gravity.

A novel homozygous ZNF469 variant causing brittle cornea syndrome is associated with corneal ectasias in heterozygous carriers.

AIM: To describe a family segregating a novel truncating ZNF469 homozygous mutation causing brittle cornea syndrome type 1 in a male patient and associated with corneal ectasia in his two heterozygous young children. METHODS: A 49-year-old affected male and his 12- and 8-year-old, apparently healthy, siblings underwent phenotypic and genetic assessment. An Oculus Pentacam Scheimpflug topographer system was employed for keratometries and central corneal thickness measurements. Exome sequencing was performed in DNA from the index case with subsequent Sanger sequencing confirmation of the ZNF469 gene causal variant in his relatives. RESULTS: The index case had a history of bilateral keratoglobus, corneal perforations, bilateral hypoacusia, and skeletal anomalies. His two children exhibited topographic anomalies compatible with keratoconus suspects as well as mild skeletal anomalies. Genetic analysis identified a novel homozygous c.2340delC variant in the ZNF469 gene, which predicts a p.(Arg781Glufs*19) truncated protein. Sanger sequencing identified heterozygosity for the c.2340delC variant in DNA from both siblings. CONCLUSION: Our results expand the mutational spectrum associated with brittle cornea syndrome and provide the first demonstration of early corneal anomalies in subjects carrying monoallelic ZNF469 variants.

Unified Coding of Spectral and Temporal Phonetic Cues: Electrophysiological Evidence for Abstract Phonological Features.

Spoken word recognition models and phonological theory propose that abstract features play a central role in speech processing. It remains unknown, however, whether auditory cortex encodes linguistic features in a manner beyond the phonetic properties of the speech sounds themselves. We took advantage of the fact that English phonology functionally codes stops and fricatives as voiced or voiceless with two distinct phonetic cues: Fricatives use a spectral cue, whereas stops use a temporal cue. Evidence that these cues can be grouped together would indicate the disjunctive coding of distinct phonetic cues into a functionally defined abstract phonological feature. In English, the voicing feature, which distinguishes the consonants [s] and [t] from [z] and [d], respectively, is hypothesized to be specified only for voiceless consonants (e.g., [s t]). Here, participants listened to syllables in a many-to-one oddball design, while their EEG was recorded. In one block, both voiceless stops and fricatives were the standards. In the other block, both voiced stops and fricatives were the standards. A critical design element was the presence of intercategory variation within the standards. Therefore, a many-to-one relationship, which is necessary to elicit an MMN, existed only if the stop and fricative standards were grouped together. In addition to the ERPs, event-related spectral power was also analyzed. Results showed an MMN effect in the voiceless standards block-an asymmetric MMN-in a time window consistent with processing in auditory cortex, as well as increased prestimulus beta-band oscillatory power to voiceless standards. These findings suggest that (i) there is an auditory memory trace of the standards based on the shared [voiceless] feature, which is only functionally defined; (ii) voiced consonants are underspecified; and (iii) features can serve as a basis for predictive processing. Taken together, these results point toward auditory cortex's ability to functionally code distinct phonetic cues together and suggest that abstract features can be used to parse the continuous acoustic signal.

Automating Case Reporting of Chlamydia and Gonorrhea to Public Health Authorities in Oregon Clinics.

BACKGROUND: Optimizing sexually transmitted disease (STD) reporting to state public health authorities is important to reduce incidence and manage outbreaks of STDs. Electronic laboratory reporting (ELR) is the standard through which local clinics report STDs to state public health authority. Electronic case reporting (eCR) is an alternative approach which automates transmission of case reports to public health jurisdictions using electronic health record (EHR) data. METHODS: Working with 3 community health centers in Oregon between February 3, 2020 and May 15, 2020, we piloted an automated eCR approach for gonorrhea (GC) and chlamydia (CT) from these clinics to the Oregon Health Authority. We compared the eCR approach to the existing ELR approach to determine completeness of case reporting for GC/CT. RESULTS: A total of 365 eCRs from 206 unique patients were generated. Among 154 instances where the case detection logic was satisfied for CT, 37% (54 instances) were based on the presence of a diagnosis and 63% (97 instances) were based on laboratory data. Among 232 instances where logic was satisfied for GC, 44% (102 instances) reflected a diagnosis and 56% (130 instances) reflected laboratory results. Data completeness was uniformly equal or higher for eCRs versus ELRs. CONCLUSIONS: The eCR approach was successful in identifying CT and GC cases and provided a more complete set of information to assist public health authorities when compared with ELRs. Electronic case reporting has the potential to automate and relieve staff burden on an important reporting requirement for clinical providers.

Do rates of dental wear in extant African great apes inform the time of weaning?

Reconstructing the life histories of extinct hominins remains one of the main foci of paleoanthropological inquiry, as an extended juvenile period impacts the social and cognitive development of species. However, the paucity of hominin remains, the lack of comparative hominoid data, and the destructive nature of many life history approaches have limited our understanding of the relationship between dental development (eruption) and weaning in primates. Alternatively, the rate of dental wear in early-forming teeth has been suggested a good proxy for the timing of weaning. Here we test this hypothesis on an ontogenetic series of Gorilla gorilla gorilla and Pan troglodytes troglodytes, using geographic information systems-based shape descriptors of M1s in relation to the nitrogen (δ15N) and carbon (δ13C) isotope composition of their associated hair. Results show that Gorilla g. gorilla are fully weaned considerably later than Pan t. troglodytes, that is, after M1s had been in full functional occlusion for some time. Yet, throughout ontogeny, gorilla dental wear rates are greater than they are in chimpanzees. This refutes the hypothesis that the rates of wear of early-forming teeth inform the time of weaning (i.e., nutritional independence). Instead, dietary breadth and seasonal variation in resource availability are implicated. This finding has implications for interpreting the hominin fossil record and raises questions about the triggers for, and the mechanisms of, life history change in hominin evolution. As a case in point, commonalities in life history patterns between early hominins and Western lowland gorillas seem to be a means to mitigate the effects of recurrent (i.e., seasonal) resource limitations and-conceivably-to prevent high infant mortality rates. Taken further, difference between hominid life histories are likely to be of degree, not kind.

The Evolving Classification of Diffuse Gliomas: World Health Organization Updates for 2021.

PURPOSE OF REVIEW: The upcoming 2021 World Health Organization (WHO) Classification of Tumours of the Central Nervous System will feature numerous changes in classification, diagnostic criteria, nomenclature, and grading of diffuse gliomas. This article reviews these changes and the clinical and molecular findings underlying them. RECENT FINDINGS: Since the publication of the 2016 World Health Organization (WHO) Classification of Tumours of the Central Nervous System, research has led to new insights into how molecular changes impact both the classification and grading of CNS tumors. The continued integration of molecular and histopathological features has led to changes in diagnostic criteria and grading for various tumors. In the new 2021 WHO CNS tumor classification scheme, diffuse gliomas will be classified as either adult-type diffuse gliomas, pediatric-type diffuse high-grade gliomas, or pediatric-type diffuse low-grade gliomas. The upcoming changes in the classification of adult-type and pediatric-type diffuse gliomas allow for more effective communication of both diagnostic and prognostic information, and-particularly in the case of pediatric-type diffuse gliomas-may suggest possible targeted strategies for therapeutic intervention.

Mapping IPF helps identify geographic regions at higher risk for disease development and potential triggers.

BACKGROUND AND OBJECTIVE: The relationship between IPF development and environmental factors has not been completely elucidated. Analysing geographic regions of idiopathic pulmonary fibrosis (IPF) cases could help identify those areas with higher aggregation and investigate potential triggers. We hypothesize that cross-analysing location of IPF cases and areas of consistently high air pollution concentration could lead to recognition of environmental risk factors for IPF development. METHODS: This retrospective study analysed epidemiological and clinical data from 503 patients registered in the Observatory IPF.cat from January 2017 to June 2019. Incident and prevalent IPF cases from the Catalan region of Spain were graphed based on their postal address. We generated maps of the most relevant air pollutant PM2.5 from the last 10 years using data from the CALIOPE air quality forecast system and observational data. RESULTS: In 2018, the prevalence of IPF differed across provinces; from 8.1 cases per 100 000 habitants in Barcelona to 2.0 cases per 100 000 in Girona. The ratio of IPF was higher in some areas. Mapping PM2.5 levels illustrated that certain areas with more industry, traffic and shipping maintained markedly higher PM2.5 concentrations. Most of these locations correlated with higher aggregation of IPF cases. Compared with other risk factors, PM2.5 exposure was the most frequent. CONCLUSION: In this retrospective study, prevalence of IPF is higher in areas of elevated PM2.5 concentration. Prospective studies with targeted pollution mapping need to be done in specific geographies to compile a broader profile of environmental factors involved in the development of pulmonary fibrosis.

Training strategies to minimize interchannel interference effects using supervised learning in gridless Nyquist-WDM systems.

The dynamism envisioned in future high-capacity gridless optical networks requires facing several challenges in distortion mitigation, such as the mitigation of interchannel interference (ICI) effects in any optical channel without information of their adjacent channels. Machine learning (ML)-based techniques have been proposed in recent works to estimate and mitigate different optical impairments with promising results. We propose and evaluate two training strategies for supervised learning algorithms with the aim to minimize ICI effects in a gridless 3×16-Gbaud 16-quadrature amplitude modulation (QAM) Nyquist-wavelength-division multiplexing (WDM) system. One strategy, called updating strategy, is based on symbol training sequence, and the other one, called characterization strategy, is based on an offline training using a previous system characterization. Artificial neural networks (ANN), support vector machine (SVM), K-nearest neighbors (KNN), and extreme learning machine (ELM) algorithms are explored for both training strategies. Experimental results showed a bit error rate (BER) improvement at low training lengths for both training strategies, for instance, gains up to ∼4dB in terms of optical signal-to-noise ratio were achieved in a back-to-back scenario. Besides, the KNN and ELM algorithms showed significant BER reduction in transmission over 250 km optical fiber. Additionally, we carried out a brief computational complexity analysis where ELM presented only 1.9% of ANN processing time. Hence, the use of ML-based techniques could enhance the optical gridless networks performance and consequently fulfill future traffic demands.

Morphology of Shear-Induced Colloidal Aggregates in Porous Media: Consequences for Transport, Deposition, and Re-entrainment.

Colloid deposition in granular media is relevant to numerous environmental problems. Classic filtration models assume a homogeneous pore space and largely ignore colloid aggregation. However, substantial evidence exists on the ubiquity of aggregation within porous media, suggesting that deposition is enhanced by it. This work studies the deposition process in relation to aggregate size and structure. We demonstrate that aggregation is induced at typical groundwater velocities by comparing the repulsive DLVO force between particle pairs to the hydrodynamic shear force opposing it. Column experiments imaged with high-resolution X-ray computed tomography are used to measure aggregate structure and describe their morphology probability distribution and spatial distribution. Aggregate volume and surface area are found to be power-law distributed, while Feret diameter is exponentially distributed with some flow rate dependencies caused by erosion and restructuring by the fluid shear. Furthermore, size and shape of aggregates are heterogeneous in depth, where a small number of large aggregates control the concentration versus depth profile shape. The range of aggregate fractal dimensions found (2.22-2.42) implies a high potential for restructuring or breaking during transport. Shear-induced aggregation is not currently considered in macroscopic models for particle filtration, yet is critical to consider in the processes that control deposition.

Rituximab effect in severe progressive connective tissue disease-related lung disease: preliminary data.

Progressive connective tissue disease (CTD)-related lung disease is a challenging condition that requires lung transplantation in some patients. Treatment with rituximab may improve lung function. To evaluate the effect of rituximab in patients with progressive CTD-related lung disease who met criteria for inclusion in waiting list for a lung transplant. Retrospective study of patients with progressive CTD-related lung disease with criteria for lung transplant (FVC < 60% and/or DLCO < 40%) that started treatment with rituximab because of disease progression. Clinical variables, pulmonary function tests and chest computed tomography were used to monitor the effect of rituximab. The cohort included 18 patients; systemic sclerosis (7), rheumatoid arthritis (5), systemic lupus erythematosus (4), Sjögren syndrome (1) and antisynthetase syndrome (1). The radiologic patterns observed were: usual interstitial pneumonia (1), non-specific interstitial pneumonia (9), lymphoid interstitial pneumonia (1), emphysema-usual interstitial pneumonia (1), shrinking lung syndrome (3) and undetermined pattern (3). Over the previous year to rituximab initiation a decline in FVC (- 3.8%, p = 0.095) and DLCO (- 8.4%, p = 0.004) was observed. After 2 years of treatment, DLCO significantly improved (+ 12.4%, p < 0.001 at 1 year and + 15.3%, p = 0.001 at 2 years). Six patients (33.3%) presented adverse events related to rituximab. No patient required lung transplant or died during the study period. Rituximab is an effective treatment for patients with severe and progressive CTD-related lung disease, which allows to delay lung transplantation in some cases.

Conjunctival Melanoma: Features and Outcomes Based on the Fitzpatrick Skin Type in 540 Patients at a Single Ocular Oncology Center.

PURPOSE: To determine the association of Fitzpatrick skin type (FST) with conjunctival melanoma. METHODS: Retrospective case series of 540 patients with conjunctival melanoma to assess clinical features and outcomes per FST. RESULTS: The FST was Type I (n = 126, 23%), II (n = 337, 62%), III (n = 56, 10%), IV (n = 8, 2%), V (n = 12, 2%), and VI (n = 1, <1%). A comparison (FST I vs. II vs. III, IV, V, and VI) revealed Types I and II associated with older mean patient age (63.9 vs. 60.7 vs. 51.1 years, p < 0.001), greater percentage of female patients (68% vs. 44% vs. 42%, p < 0.001), lower frequency of complexion associated melanosis (1% vs. 2% vs. 13%, p < 0.001), smaller tumor thickness (2.1 vs. 2.8 vs. 3.6 mm, p = 0.01), and less eyelid involvement (13% vs. 13% vs. 28%, p = 0.02). Kaplan-Meier estimates for 5-year risk showed no difference by Types for visual acuity loss ≥3 lines, local tumor recurrence, exenteration, metastasis, or death. CONCLUSION AND RELEVANCE: Most patients with conjunctival melanoma show FST I or II, and this demonstrated no association with 5-year rate of vision loss, tumor recurrence, exenteration, metastasis, or death.

Distribution of sodium hypochlorite throughout the mesial root canal system of mandibular molars after adjunctive irrigant activation procedures: a micro-computed tomographic study.

OBJECTIVES: To evaluate and compare irrigant distribution throughout the root canal system of mesial roots of mandibular molars after application of distinct adjunctive irrigant activation procedures. MATERIALS AND METHODS: Fifteen extracted mandibular molars presenting Fan's type II, III, or IV isthmus configurations were selected. The canals were initially enlarged and cleaned. The same specimens were subjected to conventional positive pressure irrigation (PPI) followed by adjunctive irrigation approaches: passive ultrasonic irrigation (PUI), mechanical activation with the XP-endo Finisher instrument, and a control group in which the irrigant remained in the canal with no activation. Retention time for the irrigant was the same for all groups. Sodium hypochlorite mixed with a contrast medium (Omnipaque 300) was used as the irrigant. Before and immediately after the adjunctive irrigation, micro-computed tomographic (micro-CT) scans were taken to evaluate the volume of the entire root canal system that was filled by the irrigant. An exclusive analysis was also done for the isthmus area. RESULTS: Analysis of the entire root canal system showed that the XP-endo Finisher instrument promoted better distribution of the irrigant than PUI and the control group (p < 0.01). PUI was not significantly different from the control group (p > 0.05). A separate analysis of the isthmus area showed no significant difference between the adjunctive irrigation methods and the control (p > 0.05). CONCLUSIONS: The XP-endo Finisher instrument promoted better distribution of irrigant throughout the root canal system, especially in the apical canal segment, when compared to PUI. However, the tested approaches did not differ as to the ability to drive irrigants into the isthmus area. CLINICAL RELEVANCE: This study highlighted that the XP-endo Finisher instrument presented a better performance to distribute irrigant throughout the root canal system, especially in the apical canal segment compared to positive pressure irrigation and PUI.

Dark Energy from Quantum Gravity Discreteness.

We argue that discreteness at the Planck scale (naturally expected to arise from quantum gravity) might manifest in the form of minute violations of energy-momentum conservation of the matter degrees of freedom when described in terms of (idealized) smooth fields on a smooth spacetime. In the context of applications to cosmology, such "energy diffusion" from the low energy matter degrees of freedom to the discrete structures underlying spacetime would lead to the emergence of an effective dark energy term in Einstein's equations. We estimate this effect using a (relational) hypothesis about the materialization of discreteness in quantum gravity which is motivated by the strict observational constraints supporting the validity of Lorentz invariance at low energies. Arguments based on a simple dimensional analysis lead to an estimate of an effective cosmological constant agreeing in order of magnitude with its observed value. If correct, this would constitute remarkable empirical evidence for a Planckian granular aspect of spacetime.