A cone-beam computed tomography study of canalis sinuosus and its accessory canals in a South African population.

OBJECTIVES: Canalis sinuosus (CS) is a clinically relevant structure in the anterior maxilla. The present study aimed to determine the prevalence and distribution of CS and its accessory canals (ACs) in the South African population and describe its anatomical variations. METHODS: In total, 500 cone-beam computed tomography (CBCT) scans of the anterior maxilla were assessed for prevalence, sidedness, diameter, and distribution of CS. The frequency, number, diameter, configuration, and point of termination of ACs were also recorded. Statistical analysis was performed using analysis of variance, Kruskal-Wallis, chi-squared, and Fisher Exact tests with P < 0.05. RESULTS: CS was present in most cases (99.6%), and commonly occurred bilaterally (98.8%). The mean diameter of CS was 1.08 mm (range: 0.50 mm-2.39 mm). Sex, population group, and age had no significant effect on the prevalence or sidedness of CS. Additionally, 535 ACs were observed in 58.8% of the sample, with 42.9% of ACs found bilaterally and 57.1% unilaterally. The mean diameter of the ACs was 0.86 mm on the left and 0.87 mm on the right (range; 0.50 mm-1.52 mm). The majority of ACs maintained a straight vertical configuration (72.3%). ACs most commonly terminated in the anterior palatal region of the maxilla (57.2%). No significant differences were found in any groups mentioned (P > 0.05). CONCLUSIONS: A high prevalence of CS as well as ACs were observed in the sample population. Due to their clinical significance, surgical planning with the aid of high quality CBCT scans of the anterior maxilla is advisable.

Tropical decadal variability in nutrient supply and phytoplankton community in the Central Equatorial Pacific during the late Holocene.

We have reconstructed baseline δ15N and δ13C of export production at Kingman Reef in the Central Equatorial Pacific (CEP) at sub-decadal resolution, nearly continuously over the last 2000 years. The changes in δ15N reflects the strength of the North Equatorial Counter Current (NECC) relative to the South Equatorial Current (SEC), and to a lesser extent, the North Equatorial Current (NEC). Seasonal to multi-decadal variation in the strength of these currents, through the redistribution of heat, have global climate impacts and influence marine and terrestrial ecosystems. We use modern El Niño-La Nina dynamics and the Tropical Pacific Decadal Variability (TPDV) pattern, which is defined in the CEP, as a framework for analyzing the isotopic data. The CEP δ15N and δ13C records exhibit multi-decadal (50-60 year) variability consistent with TPDV. A large multi-centennial feature in the CEP δ15N data, within age-model uncertainties, is consistent with one of the prolonged dry-pluvial sequences in the American west at the end of the Medieval Climate Anomaly, where low TPDV is correlated with drier conditions. This unique record shows that the strength of the NECC, as reflected in baseline δ15N and δ13C, has at quasi-predictable intervals throughout the late Holocene, toggled the phytoplankton community between prokaryotes and picoplankton versus eukaryotes.

Investigation of mandibular second molar root and canal morphology in a Black South African population using cone-beam computed tomography and two classification systems.

PURPOSE: To investigate the root and canal morphology of mandibular second molars, including anatomical variations, in a Black South African population using two classification systems. METHODS: Cone-beam computed tomography images of 386 teeth were evaluated. The number of roots and canal configurations were categorized using the classifications of Vertucci (with modifications by Sert and Bayirli) and Ahmed et al. (including the modified Melton classification). Relationships between variables were assessed using Fisher's exact test (P < 0.05). RESULTS: Mandibular second molars were predominantly two-rooted (91.7%). The majority of teeth had three canals including Type IV mesial (41.2%) and Type I (75.1%) distal (Ahmed et al. configuration: 2MDM M2 D1). Three or more canals were present in almost one-fifth of mesial (n = 72/386, 18.6%) and a small number of distal (n = 21/386, 5.4%) roots. Males displayed additional canals more frequently in the distal root (P = 0.02). C-shaped anatomy was found in 5.7%. Among the C-shapes, the most common was Melton's Type III in the coronal (50%), middle (81%) and apical (72%) thirds. CONCLUSION: In this population, mandibular second molar teeth exhibited diverse morphology, which would have clinical significance for endodontic practitioners. The Ahmed et al. classification provided a better description than the Vertucci classification.

In vitro comparison of the physical and mechanical properties of an ormocer with an ormocer-based composite and a nanocomposite restorative material.

OBJECTIVES: To compare an ormocer with a first generation ormocer-based composite and a nanocomposite in terms of surface roughness, surface hardness, and microleakage. MATERIALS AND METHODS: An ormocer (Admira Fusion), a first generation ormocer-based composite (Admira) and a nanocomposite (Filtek Z350 XT) were prepared strictly in accordance with the manufacturer's instruction and recommendation to provide optimal material properties. Twelve disk samples of each material were evaluated to assess both surface roughness and surface hardness. For surface roughness, all samples were finished, polished, and Ra values measured with a profilometer. For surface hardness, samples were stored in an incubator, polished and a Vickers diamond indenter was used to record values. For microleakage, 36 standardized, Class V cavities were prepared and randomly divided into three groups. Restored teeth were thermally fatigued, immersed in 2% methylene blue solution for 48 h, sectioned, and scored for occlusal and gingival microleakage. RESULTS: Statistical significance was set at p < .05. The one-way analysis of variance identified no significant difference in terms of surface roughness between the three material groups (p > .05). A significantly higher surface hardness was identified for the nanocomposite compared to both the ormocer (p < .001) and ormocer-based composite (p < .001). Fisher's exact test identified no significant difference in terms of occlusal microleakage (p = .534) and gingival microleakage (p = .093) between the three material groups. CONCLUSIONS: No significant differences in terms of surface roughness or microleakage were noted. The nanocomposite was significantly harder than the ormocer materials.

A study of mandibular premolar root and canal morphology in a Black South African population using cone-beam computed tomography and two classification systems.

PURPOSE: An investigation of the configurations of mandibular premolar roots and canals in a population of Black South Africans. METHODS: Cone-beam computed tomography analysis of 772 mandibular premolars was performed, and the premolars were classified according to the systems proposed by Vertucci and Ahmed et al. Root number, canal morphology, age, and sex were recorded. Fisher's exact test was used to determine relationships based on age and sex (P < 0.05). RESULTS: Single roots were seen in the majority of mandibular premolars (97.1%). Single canal configurations (i.e., Vertucci Type 1/Ahmed et al. 1MP1) were observed in 48.5% of first and 81.3% of second mandibular premolars. Mandibular first premolars demonstrated multiple canals in more than half of the sample (51.5%), and C-shaped morphology in more than one-tenth (11.1%). A relationship between sex and the presence of radicular grooves was demonstrated (P = 0.049), males being more likely to demonstrate this feature (P = 0.051). Multiple canals in mandibular first premolars also showed a relationship with sex (P = 0.005), a male predilection being evident (P = 0.007). The Ahmed et al. system proved superior to the Vertucci classification for reporting complex configurations and anatomical variations, although a greater number of unique categories were created. CONCLUSION: Diverse mandibular premolar root and canal morphology was observed in the studied population. Clinicians must be aware of common morphological features as well as possible anatomical variations in mandibular premolars, as failure to treat complete root canal systems may negatively impact endodontic treatment outcomes.

Root and canal morphology of the permanent anterior dentition in a Black South African population using cone-beam computed tomography and two classification systems.

PURPOSE: This study investigated the root and canal morphology of the permanent anterior dentition in a Black South African population. METHODS: In total 2,343 permanent anterior teeth were evaluated using cone-beam computed tomography images and described according to the Vertucci and Ahmed et al. classifications. Demographic information, root number and internal canal morphology were recorded. Age and sex associations were made using Fisher's exact test (P < 0.05). RESULTS: All anterior teeth were single-rooted (100%). The most frequent configuration in maxillary anteriors was a single canal (Vertucci Type I/1MXA1). In mandibular anteriors, single canal configurations (Type I/1MDA1) predominated, however 36.6% of mandibular central and 33.9% of lateral incisors displayed two canals. Older subjects (>40 years) demonstrated single canals more than younger subjects (P = 0.0004). Females displayed variations more compared to males (P = 0.002). The two classifications were found to be comparable for evaluation of permanent anterior teeth. Complex configurations were better described using the newer system. CONCLUSION: The permanent anterior teeth of this population exhibited exclusively single roots and diverse internal characteristics. Clinicians should be aware of anatomical variations, particularly in mandibular incisors, as these may result in adverse endodontic outcomes if not taken into consideration by the treating practitioner.

Root and canal configurations of mandibular first molars in a South African subpopulation.

PURPOSE: This study investigated root number and canal configurations, including morphological variations, of mandibular first molars in a subpopulation of South Africans. METHODS: Two calibrated examiners retrospectively evaluated 371 mandibular first molars by using high-resolution cone-beam CT images and the Vertucci classification system with the additions of Sert and Bayirli. Internal and external configurations were recorded, and correlations of sex and age with root number and canal configuration were determined with the chi-square and Fisher exact tests (P < 0.05). RESULTS: Among mandibular first molars, 0.3% were single-rooted, 98.7% were two-rooted, and 1% were three-rooted. The most frequent configuration was Vertucci Type IV in mesial roots and Vertucci Type I in distal roots. Middle mesial canals were found in 20% and middle-distal canals in 7% of samples. The prevalence of third canals increased in mesial and distal roots as age increased (P > 0.05). Canal configuration and sex were not correlated (P > 0.05). CONCLUSION: Mandibular first molars exhibited diverse anatomic characteristics in this subpopulation. Clinicians should be aware of the possibility of additional canals in mandibular first molars, as treatment outcomes may be worse if canals are left untreated.

Visible light-mediated Smiles rearrangements and annulations of non-activated aromatics.

We report the first examples of radical cation Smiles rearrangements. A series of aryloxy alkylamines underwent spontaneous reaction, with the amino group displacing the ipso-alkoxy group through substitution, at ambient temperature and under photoactivation by visible light in the presence of an acridinium catalyst (5 mol%). The study was extended to 3-(2-methoxyphenyl)propan-1-amine derivatives, which lack an appropriate ipso leaving group. Here, efficient cyclisations resulted in displacement of the methoxy group and formation of tetrahydroquinolines.

A Scalable Metal-, Azide-, and Halogen-Free Method for the Preparation of Triazoles.

A scalable metal-, azide-, and halogen-free method for the synthesis of substituted 1,2,3-triazoles has been developed. The reaction proceeds through a 3-component coupling of α-ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional-group tolerance with respect to both the α-ketoacetal and amine coupling partners, providing access to 4-, 1,4-, 1,5-, and 1,4,5-substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3-triazoles that remain challenging to prepare by azide-alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation.

Root and canal configurations of maxillary premolars in a South African subpopulation using cone beam computed tomography and two classification systems.

This cone beam computed tomography (CBCT) study aimed to describe the maxillary premolar anatomy of a South African subpopulation using two classification systems. A total of 601 premolars were evaluated. For each tooth, the root number and canal configurations were described using the classification systems devised by Vertucci (1984) and Ahmed et al. (2017). Correlations between root number and sex were determined using the chi-squared test (P = 0.05). Two roots were present in approximately half of all maxillary first premolars (54.1%, n = 171/316). The majority of maxillary second premolars displayed one root (78.2%, n = 223/285). Single-rooted maxillary second premolars were more common in females (P < 0.05). The Vertucci type IV configuration was most prevalent in the maxillary first premolars. In contrast, maxillary second premolars showed a greater tendency toward Vertucci's type I configuration. The classification proposed by Ahmed et al. indicated the most prevalent maxillary first premolar configuration to be 2MP B1P1. The most common configuration among the maxillary second premolars was 1 MP1. Diverse root and canal anatomical presentations were found in this subpopulation. Both classification systems adequately describe maxillary premolar anatomy; however, the system proposed by Ahmed et al. may more accurately describe complex teeth.

Copper-catalysed C-H functionalisation gives access to 2-aminobenzimidazoles.

This paper describes the development, optimisation and exemplification of a copper-catalysed C-H functionalisation to form pharmaceutically relevant 2-aminobenzimidazoles from aryl-guanidines. High throughput screening was used as a tool to identify a catalytically active copper source, DoE was used for reaction optimisation and a range of aryl-guanidines were prepared and exposed to the optimum conditions to afford a range of 2-aminobenzimidazoles in moderate to good yields. The methodology has been applied to the synthesis of Emedastine, a marketed anti-histamine pharmaceutical compound, with the key cyclisation step performed on a gram-scale.

Liquid-Phase Synthesis of 2'-Methyl-RNA on a Homostar Support through Organic-Solvent Nanofiltration.

Due to the discovery of RNAi, oligonucleotides (oligos) have re-emerged as a major pharmaceutical target that may soon be required in ton quantities. However, it is questionable whether solid-phase oligo synthesis (SPOS) methods can provide a scalable synthesis. Liquid-phase oligo synthesis (LPOS) is intrinsically scalable and amenable to standard industrial batch synthesis techniques. However, most reported LPOS strategies rely upon at least one precipitation per chain extension cycle to separate the growing oligonucleotide from reaction debris. Precipitation can be difficult to develop and control on an industrial scale and, because many precipitations would be required to prepare a therapeutic oligonucleotide, we contend that this approach is not viable for large-scale industrial preparation. We are developing an LPOS synthetic strategy for 2'-methyl RNA phosphorothioate that is more amenable to standard batch production techniques, using organic solvent nanofiltration (OSN) as the critical scalable separation technology. We report the first LPOS-OSN preparation of a 2'-Me RNA phosphorothioate 9-mer, using commercial phosphoramidite monomers, and monitoring all reactions by HPLC, (31)P NMR spectroscopy and MS.

Knowledge and attitudes of anesthesia providers about noncardiac surgery in adults with congenital heart disease.

OBJECTIVE: To examine the knowledge and attitudes of anesthesia providers in relation to the care of adult congenital heart disease (ACHD) patients presenting for noncardiac surgery. DESIGN/SETTING: A novel survey was designed and administered to 168 anesthesiologists across a single academic department in a range of practice environments. INTERVENTIONS: None. OUTCOME MEASURES: Survey responses, including true/false, multiple choice, and Likert scale questions. RESULTS: A total of 118 anesthesiologists (response rate = 70%) completed the survey. Knowledge scores ranged from 0 to 19 (median [interquartile range] = 7 [5-13]) out of a possible maximum of 20. Total knowledge scores differed significantly by fellowship background (P = .004), with higher scores in those with cardiac (11 [7-15], P = .005) and pediatric (12 [6-15], P = .001) fellowship training, but not in those with critical care, obstetric, regional, or pain management training. Scores also differed by frequency of providing care for cardiopulmonary bypass cases and frequency of providing care for patients under 2 years of age (P < .001 for both), but not by gender or years removed from residency. Respondents reported only moderate levels of comfort with a range of questions about providing perioperative or obstetric care to ACHD patients, with decreasing levels of comfort reported in patients with more complex lesions. CONCLUSIONS: Within the context of the limitations of a single-institution survey design, the low levels of knowledge and comfort we observed suggest that providers may benefit from improved training and protocols for ensuring adequate preparedness for the care of ACHD patients.

Vertical Integration in Teaching And Learning (VITAL): an approach to medical education in general practice.

There is increasing demand to provide clinical and teaching experiences in the general practice setting. Vertical integration in teaching and learning, whereby teaching and learning roles are shared across all learner stages, has the potential to decrease time demands and stress on general practitioners, to provide teaching skills and experience to GP registrars, and to improve the learning experience for medical students, and may also help meet the increased demand for teaching in general practice. We consider potential advantages and barriers to vertical integration of teaching in general practice, and provide results of focus group discussions with general practice principals and registrars about vertical integration. We recommend further research into the feasibility of using vertical integration to enhance the capacity to teach medical students in general practice.

Enhanced decision support for policy makers using a web interface to health-economic models--illustrated with a cost-effectiveness analysis of nation-wide infant vaccination with the 7-valent pneumococcal conjugate vaccine in the Netherlands.

We have developed a web-based user-interface (web interface) to enhance the usefulness of health-economic evaluations to support decision making (http://pcv.healtheconomics.nl). It allows the user to interact with a health-economic model to evaluate predefined and customized scenarios and perform sensitivity analysis. To explore its usefulness, it was applied to an evaluation of cost-effectiveness of nation-wide infant vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7), that was used to support a policy decision on the inclusion of PCV7 in the national vaccination program (NVP) of the Netherlands. We used a decision-tree analytic model to project the impact of infant vaccination with four doses of PCV7 on an annual cohort of infants born in the Netherlands. The base-case analysis includes the beneficial effects on unvaccinated individuals (herd protection). Additional scenarios varying the number of doses, discount rate for effects and the number of serotypes in the vaccine were evaluated and can be analysed on the web. Our model projects a base-case incremental cost-effectiveness ratio (iCER) of euro14,000 (95% uncertainty interval (UI): 9,800-20,200) per quality adjusted life year (QALY) or euro15,600 (95% UI: 11,100-23,900) per life year gained (LYG).

One-pot formation of nitrogen-containing heterocyclic ring systems using a deprotection-cyclisation-asymmetric reduction sequence.

A one-pot sequence of amine deprotection, intramolecular C=N bond formation and subsequent asymmetric reduction may be promoted by a ruthenium catalyst.

A one-pot process for the enantioselective synthesis of amines via reductive amination under transfer hydrogenation conditions.

[reaction: see text]. Cyclic amines may be prepared via a sequence of deprotection followed by intramolecular reductive amination of t-Boc-protected amino ketones under asymmetric transfer hydrogenation conditions. In cases where the corresponding imine reaction proceeds with high enantioselectivity, this is reflected in the one-step process.

Reimbursement for new health technologies. Breakthrough pharmaceuticals as a 20th century challenge.

The regulation of pricing and trade for in-patent medicines within the European pharmaceutical sector presents a major challenge. In conditions of large sunk costs and consumers with differential willingness to pay--between different Member States--an efficient way of pricing in-patent medicines is through price discrimination, by which more is charged in markets that can bear it and re-exports are prevented from undercutting this strategy. Parallel trade and the use of international price comparisons by government regulators can result in pressure for price convergence with consequent delays in launching products in certain markets. Imposing free movement of pharmaceuticals may particularly harm patients in lower income Member States, who may find pharmaceuticals more expensive or unavailable. Data on first consumption of important new pharmaceuticals show long delays for patients in certain Member States.