Immunogenicity and safety of AZD2816, a beta (B.1.351) variant COVID-19 vaccine, and AZD1222 (ChAdOx1 nCoV-19) as third-dose boosters for previously vaccinated adults: a multicentre, randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study in the UK and Poland.

BACKGROUND: This study aimed to evaluate AZD2816, a variant-updated COVID-19 vaccine expressing the full-length SARS-CoV-2 beta (B.1.351) variant spike protein that is otherwise similar to AZD1222 (ChAdOx1 nCoV-19), and AZD1222 as third-dose boosters. METHODS: This phase 2/3, partly double-blinded, randomised, active-controlled study was done at 19 sites in the UK and four in Poland. Adult participants who had received a two-dose AZD1222 or mRNA vaccine primary series were randomly assigned by means of an Interactive Response Technology-Randomisation and Trial Supply Management system (1:1 within each primary-series cohort, stratified by age, sex, and comorbidities) to receive AZD1222 or AZD2816 (intramuscular injection; 5 × 1010 viral particles). Participants, investigators, and all sponsor staff members involved in study conduct were masked to randomisation. AZD1222 and AZD2816 doses were prepared by unmasked study staff members. The primary objectives were to evaluate safety and humoral immunogenicity (non-inferiority of day-29 pseudovirus neutralising antibody geometric mean titre [GMT] against ancestral SARS-CoV-2: AZD1222 booster vs AZD1222 primary series [historical controls]; margin 0·67; SARS-CoV-2-seronegative participants). This study is registered with ClinicalTrials.gov, NCT04973449, and is completed. FINDINGS: Between June 27 and Sept 30, 2021, 1394 participants of the 1741 screened were randomly assigned to AZD1222 or AZD2816 following an AZD1222 (n=373, n=377) or mRNA vaccine (n=322, n=322) primary series. In SARS-CoV-2-seronegative participants receiving AZD1222 or AZD2816, 78% and 80% (AZD1222 primary series) and 90% and 93%, respectively (mRNA vaccine primary series) reported solicited adverse events to the end of day 8; 2%, 2%, 1%, and 1% had serious adverse events and 12%, 12%, 10%, and 11% had adverse events of special interest, respectively, to the end of day 180. The primary immunogenicity non-inferiority endpoint was met: day-29 neutralising antibody GMT ratios (ancestral SARS-CoV-2) were 1·02 (95% CI 0·90-1·14) and 3·47 (3·09-3·89) with AZD1222 booster versus historical controls (AZD1222 and mRNA vaccine primary series, respectively). Responses against beta were greater with AZD2816 versus AZD1222 (GMT ratios, AZD1222, mRNA vaccine primary series 1·84 [1·63-2·08], 2·22 [1·99-2·47]). INTERPRETATION: Both boosters were well tolerated, with immunogenicity against ancestral SARS-CoV-2 similar to AZD1222 primary-series vaccination. AZD2816 gave greater immune responses against beta versus AZD1222. FUNDING: AstraZeneca.

The course and distribution of the buccal nerve: clinical relevance in dentistry.

BACKGROUND: The buccal branch of the mandibular division of the trigeminal nerve is commonly anaesthetized for dental procedures and may be damaged during surgery. Descriptions of the distribution of the buccal nerve (BN) in anatomical texts are generally lacking in detail and do not provide information about the extent of its variation between individuals. There are also commonly-held clinical beliefs about the BN that lack support from anatomical dissections. METHODS: Detailed dissections of the course and distribution of the BN were performed in a sample of 12 hemi-heads from 11 edentulous and partially dentate human adult cadavers. RESULTS: A broader distribution of the BN was found than described previously, with innervation extending to the lips in all cases. Approximately half of the lateral sides of the lips were innervated by the BN in two cases and approximately one-third of their lateral sides in the other 10 cases. Distribution of the BN to the lower lips was wider than to the upper lips. CONCLUSIONS: Our findings provide a stronger anatomical basis to underpin clinical procedures involving the BN and indicate that some commonly-held clinical views about this nerve are not supported by anatomical evidence.

Evaluating brain-computer interface performance using color in the P300 checkerboard speller.

OBJECTIVE: Current Brain-Computer Interface (BCI) systems typically flash an array of items from grey to white (GW). The objective of this study was to evaluate BCI performance using uniquely colored stimuli. METHODS: In addition to the GW stimuli, the current study tested two types of color stimuli (grey to color [GC] and color intensification [CI]). The main hypotheses were that in a checkboard paradigm, unique color stimuli will: (1) increase BCI performance over the standard GW paradigm; (2) elicit larger event-related potentials (ERPs); and, (3) improve offline performance with an electrode selection algorithm (i.e., Jumpwise). RESULTS: Online results (n=36) showed that GC provides higher accuracy and information transfer rate than the CI and GW conditions. Waveform analysis showed that GC produced higher amplitude ERPs than CI and GW. Information transfer rate was improved by the Jumpwise-selected channel locations in all conditions. CONCLUSIONS: Unique color stimuli (GC) improved BCI performance and enhanced ERPs. Jumpwise-selected electrode locations improved offline performance. SIGNIFICANCE: These results show that in a checkerboard paradigm, unique color stimuli increase BCI performance, are preferred by participants, and are important to the design of end-user applications; thus, could lead to an increase in end-user performance and acceptance of BCI technology.

The human medial pterygoid muscle: Attachments and distribution of muscle spindles.

Published descriptions about the sites of origin of the human medial pterygoid muscle vary and there are few reports on the distribution and density of muscle spindles in this muscle. We aimed to: (1) determine the extent of anatomical variability in the origins and insertions of the superficial and deep heads of the human medial pterygoid muscle and (2) determine the extent of variation in the distribution of spindles in the two heads of the muscle. Thirty-nine human cadaver hemi-heads were dissected and the attachments of the medial pterygoid muscle examined. The whole muscle was removed, weighed, cut into segments and embedded in wax for light microscopy. Sections were stained with Weigert-Van Gieson stain and scanned into digital images. Spindles were manually counted. In seven specimens, the deep head of the muscle arose from the medial surface of the lateral pterygoid plate and the pterygoid fossa. In 28 specimens, the origin extended onto the lateral surface of the medial pterygoid plate. There were abundant muscle spindles in the middle of the muscle, slightly fewer 1 cm toward the insertion, significantly fewer 1 cm toward the origin, and few or no spindles near the origins of the superficial and deep heads or near their insertion. In conclusion, firstly, this study shows that in 72% of the specimens examined, the origin of the medial pterygoid is wider than conventionally described in anatomical textbooks. Secondly, the segmental distribution of muscle spindles is described for the first time. Clin. Anat. 30:1064-1071, 2017. © 2017 Wiley Periodicals, Inc.

Alterations in mandibular morphology associated with glypican 1 and glypican 3 gene mutations.

OBJECTIVES: Glypican 1 (GPC1) and glypican 3 (GPC3) are bone co-regulators that act downstream in many of the signalling pathways associated with craniosynostosis. Morphometric data from GPC-knockout mice were analysed to determine whether elimination of GPC1 and GPC3 genes would alter mandibular morphology. SETTING AND SAMPLE POPULATION: The murine model included five male and five female mandibles in each of GPC1-knockout, GPC1/GPC3-knockout and wild-type (control) groups. Female GPC3-knockout mice had a very high rate of perinatal lethality, and therefore, only five males were included in this group. METHODS: The mandibular morphology of GPC1-knockout (n=10), GPC3-knockout (n=5), GPC1/GPC3-knockout (n=10) and wild-type (n=10) mice was compared by analysing five landmark-based linear dimensions: anterior and posterior lengths, as well as ascending, descending and posterior heights. Measurements were recorded on three-dimensional micro-CT reconstructions. RESULTS: GPC3-knockout mandibles were larger than wild-type mandibles for all dimensions (P<.05). Mandibular heights were more affected than lengths. A decreasing trend of mandibular dimensions across the mouse groups (GPC3-knockout>GPC1/GPC3-knockout>GPC1-knockout=wild-type) (P<.05) indicated that an increase in mandibular size was associated with increased GPC3 expression, but not GPC1. CONCLUSIONS: Alterations in GPC3 expression are likely to mediate changes to mandibular size in craniosynostosis. These findings have potential future applications in the prevention and treatment of craniosynostosis and associated craniofacial dysmorphology.

Surface-Sensitive Microwear Texture Analysis of Attrition and Erosion.

Scale-sensitive fractal analysis of high-resolution 3-dimensional surface reconstructions of wear patterns has advanced our knowledge in evolutionary biology, and has opened up opportunities for translatory applications in clinical practice. To elucidate the microwear characteristics of attrition and erosion in worn natural teeth, we scanned 50 extracted human teeth using a confocal profiler at a high optical resolution (X-Y, 0.17 µm; Z < 3 nm). Our hypothesis was that microwear complexity would be greater in erosion and that anisotropy would be greater in attrition. The teeth were divided into 4 groups, including 2 wear types (attrition and erosion) and 2 locations (anterior and posterior teeth; n = 12 for each anterior group, n = 13 for each posterior group) for 2 tissue types (enamel and dentine). The raw 3-dimensional data cloud was subjected to a newly developed rigorous standardization technique to reduce interscanner variability as well as to filter anomalous scanning data. Linear mixed effects (regression) analyses conducted separately for the dependent variables, complexity and anisotropy, showed the following effects of the independent variables: significant interactions between wear type and tissue type ( P = 0.0157 and P = 0.0003, respectively) and significant effects of location ( P < 0.0001 and P = 0.0035, respectively). There were significant associations between complexity and anisotropy when the dependent variable was either complexity ( P = 0.0003) or anisotropy ( P = 0.0014). Our findings of greater complexity in erosion and greater anisotropy in attrition confirm our hypothesis. The greatest geometric means were noted in dentine erosion for complexity and dentine attrition for anisotropy. Dentine also exhibited microwear characteristics that were more consistent with wear types than enamel. Overall, our findings could complement macrowear assessment in dental clinical practice and research and could assist in the early detection and management of pathologic tooth wear.

Pushing the P300-based brain-computer interface beyond 100 bpm: extending performance guided constraints into the temporal domain.

OBJECTIVE: A new presentation paradigm for the P300-based brain-computer interface (BCI) referred to as the 'asynchronous paradigm' (ASP) is introduced and studied. It is based on the principle of performance guided constraints (Townsend et al 2012 Neurosci. Lett. 531 63-8) extended from the spatial domain into the temporal domain. The traditional constraint of flashing targets in predefined constant epochs of time is eliminated and targets flash asynchronously with timing based instead on constraints intended to improve performance. APPROACH: We propose appropriate temporal constraints to derive the ASP and compare its performance to that of the 'checkerboard paradigm' (CBP), which has previously been shown to be superior to the standard 'row/column paradigm' introduced by Farwell and Donchin (1988 Electroencephalogr. Clin. Neurophysiol. 70 510-23). Ten participants were tested in the ASP and CBP conditions both with traditional flashing items and with flashing faces in place of the targets (see Zhang et al 2012 J. Neural Eng. 9 026018; Kaufmann and Kübler 2014 J. Neural Eng. 11 ; Chen et al 2015 J. Neurosci. Methods 239 18-27). Eleven minutes of calibration data were used as input to a stepwise linear discriminant analysis to derive classification coefficients used for online classification. MAIN RESULTS: Accuracy was consistently high for both paradigms (87% and 93%) while information transfer rate was 45% higher for the ASP than the CBP. In a free spelling task, one subject spelled a 66 character sentence (from a 72 item matrix) with 100% accuracy in 3 min and 24 s demonstrating a practical throughput of 120 bits per minute (bpm) with a theoretical upper bound of 258 bpm. The subject repeated the task three times in a row without error. SIGNIFICANCE: This work represents an advance in P300 speller technology and raises the ceiling that was being reached on P300-based BCIs. Most importantly, the research presented here is a novel and effective general strategy for organising timing for flashing items. The ASP is only one possible implementation of this work since in general it can be used to describe all previous existing presentation paradigms as well as any possible new ones. This may be especially important for people with neuromuscular disabilities.

Effects of non-carious cervical lesion size, occlusal loading and restoration on biomechanical behaviour of premolar teeth.

BACKGROUND: Information on fracture biomechanics has implications in materials research and clinical practice. The aim of this study was to analyse the influence of non-carious cervical lesion (NCCL) size, restorative status and direction of occlusal loading on the biomechanical behaviour of mandibular premolars, using finite element analysis (FEA), strain gauge tests and fracture resistance tests. METHODS: Ten buccal cusps were loaded on the outer and inner slopes to calculate the strain generated cervically. Data were collected for healthy teeth at baseline and progressively at three lesion depths (0.5 mm, 1.0 mm and 1.5 mm), followed by restoration with resin composite. The magnitude and distribution of von Mises stress and maximum principal stress were simulated at all stages using FEA, and fracture strength was also determined (n = 7 per group). RESULTS: There were significant effects of the lesion size and loading directions on stress, strain and fracture resistance (p < 0.05). Fracture resistance values decreased with increase in lesion size, but returned to baseline with restorations. CONCLUSIONS: Combined assessment of computer-based and experimental techniques provide an holistic approach to characterize the biomechanical behaviour of teeth with both unrestored and restored NCCLs.

An unusual ocular complication following dental anaesthesia: case report.

Used routinely by dental practitioners, local anaesthetics are generally a safe and effective means of achieving pain control during invasive dental procedures. Delivery, however, is technique sensitive and the potential for patient complication exists. Although reasonably rare, ocular complications have occurred, often leaving the patient and the clinician in distress. Such reported events have almost always involved tissue responses ipsilateral to the injection site. The current case report presents an unusual event involving involuntary fasciculation or hemifacial spasm and eventual eyelid closure on the contralateral side following a routine inferior alveolar nerve block. Aspects including the patient's history, the observed response, a pathophysiological hypothesis and patient management are discussed.

Prevalence of infraocclusion of primary molars determined using a new 2D image analysis methodology.

BACKGROUND: The reported prevalence of infraocclusion varies widely, reflecting differences in definitions and measurement/scoring approaches. This study aimed to quantify the prevalence and extent of infraocclusion in singletons and twins during the late mixed dentition stage of dental development using a new diagnostic imaging method and objective criteria. The study also aimed to determine any associations between infraocclusion and gender, arch type, arch side and tooth type. METHODS: Two samples were analysed, 1454 panoramic radiographs of singletons and 270 dental models of twins. Both samples ranged in age from 8 to 11 years. Adobe Photoshop CS5 was used to measure the extent of infraocclusion. Repeatability tests showed systematic and random errors were small. RESULTS: The prevalence in the maxilla was low (<1%), whereas the prevalence in the mandible was 22% in the singleton sample and 32% in the twin sample. The primary mandibular first molar was affected more often than the second molar. There was no significant difference in the expression between genders or sides. CONCLUSIONS: A new technique for measuring infraocclusion has been developed with high intra- and interoperator reproducibility. This method should enhance early diagnosis of tooth developmental abnormalities and treatment planning during the late mixed dentition stage of development.

Nanoscratch testing for the assessment of enamel demineralization under conditions simulating wine erosion.

BACKGROUND: Erosive tooth wear and dentinal hypersensitivity are common problems affecting professional wine tasters. By using nanoscratch testing, the aim of this in vitro study was to assess enamel softening under conditions simulating 10 one-minute episodes of wine erosion. METHODS: Ten enamel specimens were bathed in artificial saliva for 2 hours before being eroded for 10 episodes, with each episode comprising one minute of wine erosion followed by one minute of remineralization in artificial saliva. Nanoscratches were placed with a spherical tip (20 µm radius) in a nanoindenter under a load of 100 mN at baseline (stage 1), after a one-erosion episode (stage 2) and after 10-erosion episodes (stage 3). RESULTS: There were significant effects of erosion stages on both scratch depth (p<0.001) and surface roughness (p<0.001). Post hoc tests showed significant differences in both scratch depths and surface roughness between stages 1 and 3 (p<0.001), and between stages 2 and 3 (p<0.01). CONCLUSIONS: Enamel softening occurs at an early stage of wine tasting, emphasizing the need to implement early preventive strategies in professional wine tasters. Further research elucidating the fundamental mechanisms involved in early stages of erosion has the potential to lead to development of more effective preventive strategies.

Features of an effective operative dentistry learning environment: students' perceptions and relationship with performance.

OBJECTIVE: Students' perceptions of their learning environment influence the quality of outcomes they achieve. Learning dental operative techniques in a simulated clinic environment is characterised by reciprocal interactions between skills training, staff- and student-related factors. However, few studies have examined how students perceive their operative learning environments and whether there is a relationship between their perceptions and subsequent performance. Therefore, this study aimed to clarify which learning activities and interactions students perceived as supporting their operative skills learning and to examine relationships with their outcomes. METHODS: Longitudinal data about examples of operative laboratory sessions that were perceived as effective or ineffective for learning were collected twice a semester, using written critical incidents and interviews. Emergent themes from these data were identified using thematic analysis. Associations between perceptions of learning effectiveness and performance were analysed using chi-square tests. RESULTS: Students indicated that an effective learning environment involved interactions with tutors and peers. This included tutors arranging group discussions to clarify processes and outcomes, providing demonstrations and constructive feedback. Feedback focused on mistakes, and not improvement, was reported as being ineffective for learning. However, there was no significant association between students' perceptions of the effectiveness of their learning experiences and subsequent performance. CONCLUSIONS: It was clear that learning in an operative technique setting involved various factors related not only to social interactions and observational aspects of learning but also to cognitive, motivational and affective processes. Consistent with studies that have demonstrated complex interactions between students, their learning environment and outcomes, other factors need investigation.

Under your nose: a rare finding during dissection provides insights into maxillary supernumerary teeth.

BACKGROUND: A supernumerary tooth was found during anatomical dissection. The position of this tooth, still impacted in the maxilla, and the associated pathology make this a rare case. METHODS: During dissection by dental students of the sagittally-sectioned head of a cadaver, a supernumerary tooth was identified in the mid-palatal area. Further dissection revealed a swelling with a thin bony covering related to the crown of the tooth. The maxilla was removed en bloc and radiographic examination, CT scanning, electron microscopy and histology were undertaken. RESULTS: The tooth had a crenulated occlusal surface and a single root. It was 25 mm posterior to the root apex of the permanent upper central incisor. The swelling, confirmed by radiographs and CT imaging to be associated with the crown, occupied approximately one-third of the maxillary sinus. The 3D shape of the cystic lesion was visualized by a composite digital movie. CONCLUSIONS: The crown form, position of the tooth and the associated dentigerous cyst suggested it was a palatally developing supernumerary premolar which had been displaced to the palatal midline by the expanding cyst. This rare case highlights the learning and teaching opportunities available during dissection, showing important variations in both development and clinical anatomy.

Variation in natural head position and establishing corrected head position.

Corrected head position (CHP) has been simulated by using the Frankfurt horizontal (FH) for over 100 years but FH varies between individuals. Because CHP is biologically relevant for orthodontic diagnosis and treatment planning, orthognathic surgical planning, and art, this study examined relationships between head position and selected cephalometric planes. Natural head position cephalograms of Aboriginal Australians and two contemporary samples from private orthodontic practices were analysed. Each sample comprised 40 individuals (20 males and 20 females). The Aboriginal Australian sample comprised longitudinal data (T1 early adolescent, T2 late adolescent, and T3 adult), enabling examination of natural head position (NHP) reproducibility over a period of approximately 8 years. Results of reproducibility differences revealed an absolute mean=2.9°, range=-7.9° to 8.2°, and standard deviation=3.6°. Stable basicranial line (SBL), neutral horizontal axis (NHA), FH, palatal plane (P plane), and Krogman-Walker plane (KW plane) demonstrated near parallelism and their mean angulations from the true horizontal (HOR) ranged between -4.6° and 2.4°. While NHP is not consistently reproducible at the individual level, the combined use of multiple planes such as SBL, P plane, and KW plane enables a more consistent CHP to be achieved.

General and craniofacial development are complex adaptive processes influenced by diversity.

Complex systems are present in such diverse areas as social systems, economies, ecosystems and biology and, therefore, are highly relevant to dental research, education and practice. A Complex Adaptive System in biological development is a dynamic process in which, from interacting components at a lower level, higher level phenomena and structures emerge. Diversity makes substantial contributions to the performance of complex adaptive systems. It enhances the robustness of the process, allowing multiple responses to external stimuli as well as internal changes. From diversity comes variation in outcome and the possibility of major change; outliers in the distribution enhance the tipping points. The development of the dentition is a valuable, accessible model with extensive and reliable databases for investigating the role of complex adaptive systems in craniofacial and general development. The general characteristics of such systems are seen during tooth development: self-organization; bottom-up emergence; multitasking; self-adaptation; variation; tipping points; critical phases; and robustness. Dental findings are compatible with the Random Network Model, the Threshold Model and also with the Scale Free Network Model which has a Power Law distribution. In addition, dental development shows the characteristics of Modularity and Clustering to form Hierarchical Networks. The interactions between the genes (nodes) demonstrate Small World phenomena, Subgraph Motifs and Gene Regulatory Networks. Genetic mechanisms are involved in the creation and evolution of variation during development. The genetic factors interact with epigenetic and environmental factors at the molecular level and form complex networks within the cells. From these interactions emerge the higher level tissues, tooth germs and mineralized teeth. Approaching development in this way allows investigation of why there can be variations in phenotypes from identical genotypes; the phenotype is the outcome of perturbations in the cellular systems and networks, as well as of the genotype. Understanding and applying complexity theory will bring about substantial advances not only in dental research and education but also in the organization and delivery of oral health care.

Epigenetics: a new frontier in dentistry.

In 2007, only four years after the completion of the Human Genome Project, the journal Science announced that epigenetics was the 'breakthrough of the year'. Time magazine placed it second in the top 10 discoveries of 2009. While our genetic code (i.e. our DNA) contains all of the information to produce the elements we require to function, our epigenetic code determines when and where genes in the genetic code are expressed. Without the epigenetic code, the genetic code is like an orchestra without a conductor. Although there is now a substantial amount of published research on epigenetics in medicine and biology, epigenetics in dental research is in its infancy. However, epigenetics promises to become increasingly relevant to dentistry because of the role it plays in gene expression during development and subsequently potentially influencing oral disease susceptibility. This paper provides a review of the field of epigenetics aimed specifically at oral health professionals. It defines epigenetics, addresses the underlying concepts and provides details about specific epigenetic molecular mechanisms. Further, we discuss some of the key areas where epigenetics is implicated, and review the literature on epigenetics research in dentistry, including its relevance to clinical disciplines. This review considers some implications of epigenetics for the future of dental practice, including a 'personalized medicine' approach to the management of common oral diseases.

Dental phenomics: advancing genotype to phenotype correlations in craniofacial research.

The field of dental phenomics provides many opportunities to elucidate the roles of genetic, epigenetic and environmental factors in craniofacial development. To date, research findings have helped to clarify the pathogenesis of many conditions, aiding diagnosis and clinical management. This paper provides an overview of dental phenomics research in some commonly encountered oral diseases in everyday clinical practice, as well as research relating to craniofacial growth and development. Clinically, advances in cariology and periodontology have led to better diagnostic capabilities and treatment provision. In the study of growth and development, important information regarding the varying clinical presentation and pathogenesis of many disorders is now apparent through the accurate quantification of phenotypes. Improvements in two-dimensional (2D) and three-dimensional (3D) imaging and analytical techniques have allowed for accurate dental phenotyping, and efforts are ongoing to apply these in vitro techniques to the in vivo setting. The field of dental phenomics represents an exciting avenue that links research findings to practical application, and collaboration between researcher and clinicians will help advance the field further.

The face, the future, and dental practice: how research in craniofacial biology will influence patient care.

It has been a privilege to assemble a group of Australian and international researchers to produce a special issue of the Australian Dental Journal that reflects the cutting edge of research in different aspects of craniofacial biology, and also considers how these advances will influence future education and practice within dentistry. The aim of this special issue is to provide a collection of concept papers and critical reviews on key topics that cover both fundamental and applied research in craniofacial biology and to consider the clinical implications. To do this, four questions have been addressed that lead to the four sections of this issue. These are: How have we come to the present exciting position in craniofacial biology with breakthroughs over the past 50 years? What are current fundamental research topics that are helping us to understand more about craniofacial and general development, possibly leading to future clinical developments? What are the current applied research topics that will influence future clinical practice? Looking forward, what new developments in craniofacial biology may come about that will change the face of dental education and practice? The refereed papers in this special issue are grouped into the four sections that seek to respond to these demanding questions.

The dentition: the outcomes of morphogenesis leading to variations of tooth number, size and shape.

The clinical importance of variations of tooth number, size and shape is seen in many dental disciplines. Early diagnosis allows optimal patient management and treatment planning, with intervention at an appropriate time to prevent complications in development and so reduce later treatment need. Understanding the process of dental morphogenesis and the variations in outcomes is an important contribution to the multidisciplinary clinical team approach to treatment. Tooth number, size and shape are determined during the initiation and morphogenetic stages of odontogenesis. The molecular evidence of repetitive signalling throughout initiation and morphogenesis is reflected clinically in the association of anomalies of number, size and shape. This association has been statistically modelled from epidemiological evidence and confirmed by 2D and 3D measurement of human dental study casts. In individuals with hypodontia, the teeth that are formed are smaller than the population mean and often show reduced and simplified shape. In contrast, in individuals with supernumerary teeth, the other teeth are larger than average and may show an enhanced shape. Clinical observations in humans and studies of laboratory animals gave rise to the concept of morphogenetic fields within the dentition. The findings, which can also be considered as reflecting gene expression territories, have been developed to incorporate field, clone and homeobox theories. The clinical distribution of developmental anomalies tends to follow the pattern of these fields or territories. Improved care for patients with these anomalies will come not only from utilizing a multidisciplinary clinical team but also by expanding the approach to include other relevant scientific disciplines.

Functional dental occlusion: an anthropological perspective and implications for practice.

Physiologic changes occur in dental occlusion throughout life, resulting from the interplay between functional demands and reciprocating adaptive responses. These changes have been reported in the anthropological literature and they reflect evolutionary changes in the human stomatognathic system during the Paleolithic, hunter-gatherer period. Specific occlusal changes occur in response to different environments, leading to extensive variation within and between extinct and extant human populations. For example, functional demands can cause occlusal and interproximal tooth wear, resulting in shortening of the dental arch, continual tooth eruption and changes in masticatory patterns. Since the advent of farming through to our current industrialized culture, functional demands on the human masticatory system, and its adaptive responses to these demands, have been reduced considerably. Indeed, it is only occasionally that functional demands are severe enough to lead to obvious pathology in the modern human dentition. In contrast to normal masticatory activity, 'modern-day conditions' such as dental caries, periodontal disease and erosion, can lead to significant changes in dental occlusion that are pathological and need to be treated. The masticatory system is a dynamic, functional unit that displays considerable change over a lifetime. In this concept paper, it is proposed that modern human populations living in industrialized environments display dental occlusions that can be considered to be 'neotenous'; that is, our dentitions tend to reflect an unworn stage of our ancestors that was only seen in infants, juveniles and young adults. Clinicians can draw on both phylogenetic and ontogenetic perspectives of 'functional dental occlusion' to differentiate continual physiological changes occurring over time that require ongoing review, from pathological responses that require intervention.