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Simulation ist eine etablierte Methode bei der Entwicklung von technischen Systemen. Allerdings erfordert sie meist spezielle Kenntnisse sowie zusätzliche Aufwände bei der Erzeugung der Modelle und zur Ausführung der Simulationen. Mit dem Trend der Digitalisierung und der Technologie des „Digitalen Zwillings“ verstärkt sich der Impuls, ihren Einsatz und ihre durchgängige Verwendung in allen Lebenszyklusphasen eines Systems zu ermöglichen. Der vorliegende Beitrag diskutiert die damit mögliche, veränderte Rolle der Simulation und die sich ergebenden Chancen für virtuelle Inbetriebnahme-Modelle und beschreibt entsprechende technologische Aspekte zur Weiterentwicklung der Simulation.

Die Bewertung der Qualität von Simulationsmodellen bildet nach wie vor eine grundsätzliche Herausforderung in allen Phasen des Anlagen- und Produktlebenszyklus. Gleichzeitig wird eine objektive und möglichst breit einsetzbare Qualitätsmetrik dann notwendig, wenn ein Simulationsmodell ein Teil der Lieferung einer Anlage oder ihrer Komponenten wird und als wesentlicher Bestandteil des Digitalen Zwillings über den gesamten Lebenszyklus weiterentwickelt wird. Im ersten Teil dieses Beitrages „Identifikation und Clustering von Qualitätskriterien“ (atp magazin 6/7-2020) wurden Attribute identifiziert, welche als maßgebliche Grundlage für die Bewertung der Qualität von Simulationsmodellen dienen. In diesem zweiten Beitragsteil werden unterschiedliche Bewertungsmechanismen eingeführt, mit deren Hilfe eine quantifizierte Einordnung in unterschiedliche Qualitätsniveaus möglich wird. Darüber hinaus beschreibt der Beitrag die aus der Validierung der komplettierten Metrik gewonnenen Erkenntnisse und zeigt den weiteren Entwicklungs- und Diskussionsbedarf auf.

Zunehmend suchen Komponentenhersteller nach Lösungen zur Bereitstellung von digitalen Abbildern ihrer realen Komponenten. Ziel ist es, dass Kunden damit ihre Automatisierungskonzepte virtuell validieren und Steuerungssysteme im Entwicklungsprozess anhand einer virtuellen Inbetriebnahme eingehend testen und optimieren können. Simulationswerkzeuge für die virtuelleInbetriebnahme bieten mittlerweile vielfältige Schnittstellen zur Einbindung bestehender Teilmodelle bei der Modellierung eines digitalen Zwillings einer Maschine oder Anlage. In diesem Beitrag wird die Online-Plattform „TwinStore“ für den Austausch von Simulationsmodellen zur virtuellen Inbetriebnahme vorgestellt.

Dieser Beitrag stellt die Mixed-Reality-in-the-Loop Simulation (MRiLS) zur Schulung technischer Fachkräfte im Maschinen- und Anlagenbau vor. Die MRiLS koppelt die aus dem Engineering bereits vorhandenen Modelle der Hardware-in-the-Loop Simulation (HiLS) mit Visualisierungs- und Interaktionsmethoden der Mixed Reality (MR) und integriert dadurch den Nutzenden und dessen Verhalten sowie die reale Umgebung vollständig in den Simulationskreislauf. Der Beitrag thematisiert neben der notwendigen Middleware zur Kopplung der HiLS mit der MR-Umgebung auch die Steuerungsbelastung durch Multiuser-Zugriffe. Die Funktionsfähigkeit des vorgestellten Konzepts wird anhand eines ausgewählten beispielhaften Automatisierungssystems belegt. Für das Automatisierungssystem wird der Aufbau der MRiLS sowie das Konzept für den Ablauf einer Schulung mittels MRiLS vorgestellt.

A hardware-in-the-loop simulation has to use the control cycle as simulation clock. This time-deterministic clocking can be difficult to meet for complex behavior models in a real-time simulation. To accelerate a real-time simulation, the calculation can be parallelized by co-simulation whereby multiple, differently detailed behavior models can be simulated parallelly. In these multi-scale models, a slower, detailed model guides a fast, abstract model. In this work, a Kalman filter is examined as a multi-rate method to predict the signals of a physical-based model for a material flow simulation in real-time. To improve the results, smoothing and boundary conditions are added.

Der X-in-the-Loop Entwicklungsprozess nimmt einen großen Stellenwert in der heutigen Entwicklung und Inbetriebnahme von Produktionssystemen im Maschinenbau ein. In Zukunft wird die Bedeutung der Aus- und Weiterbildung technischer Fachkräfte z.B. für den Betrieb der Anlagen weiter zunehmen. Zu diesem Zweck werden bislang im Engineering entstehende virtuelle Anlagenmodelle in Kombination mit modernen Visualisierungstechnologien nur vereinzelt eingesetzt. Dies ist neben dem großen Erstellungsaufwand auch auf die fehlende Konsistenz der Modelle zurückzuführen. Der Beitrag stellt dazu einen Lösungsansatz zur Verknüpfung von Hardware-in-the-Loop Simulationen mit modernen Visualisierungsmethoden zu einer Mixed-Reality-in-the-Loop Simulation vor. Die Funktionsfähigkeit des Konzepts wird an einem ausgewählten Produktionssystem nachgewiesen.

Bei der Entwicklung von Produkten und im Engineerung von Maschinen und Anlagen kommen heute Modellierung und Simulation zum Einsatz. Durch die Struktur der betrachteten Systeme und das verteilte Arbeiten entstehen häufig einzelne Simulationsmodelle, die für viele Anwendungen kombiniert werden müssen. Eine simulationstechnische Lösung stellt die Co-Simulation dar. Mit dem zunehmenden Einsatz der Simulation in Betrieb und Service steigt zusätzlich der Bedarf an leistungsfähigen Co-Simulationstechniken an, um kooperativ arbeitende digitale Zwillinge zu realiseren. Der Beitrag gibt einen Überblick zu bestehenden Umsetzungen mit dem Schwerpunkt für die virtuelle Inbetriebnahme des Automatisierungssystems.

During virtual commissioning, the real control technology is put into operation in advance using a model-based digital twin of the production system. The growing demands on the significance of digital twins result in the need for higher model depths and model scopes of the behavior models used. However, new approaches to enhance the usable computing power in a real-time simulation are required. This paper presents a real-time co-simulation platform for virtual commissioning. The platform includes the integration of powerful technology-specific simulation solutions based on integration interfaces and a real-time co-simulation architecture based on partitioning, parallelization, synchronization and data exchange mechanisms.

Bei der virtuellen Planung, Auslegung und Inbetriebnahme steigen die Anforderungen an die Aussagekraft Digitaler Zwillinge zur umfassenden Abbildung der Interaktionen zwischen Prozess, Maschine, Steuerungssystem und Bediener. Die Zunahme der Modellkomplexität eines Digitalen Zwillings stellt die Echtzeitsimulation vor neue Herausforderungen. Dieser Beitrag stellt eine Echtzeit-Co-Simulations Plattform für die Virtuelle Inbetriebnahme mit Hilfe eines Digitalen Zwillings vor. Diese umfasst (i) die Integration leistungsfähiger technologiespezifischer Simulationsmodelle durch Ansätze zur Modellintegration und (ii) die Echtzeit-Co-Simulation auf Basis von Separations-, Parallelisierungs-, Synchronisations- und Datenaustauschmechanismen.

Model-Based Systems Engineering (MBSE) has been known in aerospace and automotive industries for more than a decade and is based on a model-driven approach to integrate all engineering disciplines. This paper shows a promising approach to meet the ongoing challenges in the development of production systems. First, the current sequential, mechatronic engineering process of production systems is summarized and deficits are pointed out. Then, the paper outlines a roadmap with necessary steps to adapt the MBSE approach to the engineering of production systems, called Model-Based Production Engineering (MBPE). This roadmap includes the definition of a design language for production systems.

Beim „Griff in die Kiste“ kommen Robotersysteme mit intelligenten Algorithmen für die Objekterkennung, Bewegungsplanung und Bewegungssteuerung zum Einsatz. Auf dem Markt gibt es derzeit verschiedene Softwaretools, die sich mit der Steuerung solcher Systeme beschäftigen. Um die steigende Komplexität zu beherrschen und die Auslegung der Systeme zu optimieren, wird ein simulationsgestütztes Werkzeug zur simulationsbasierten Inbetriebnahme benötigt. Dieser Beitrag stellt ein Konzept für eine umfassende virtuelle Absicherung des industriellen „Griffs in die Kiste“ vor. Robotic systems with intelligent algorithms for object detection, motion planning and motion control are used in bin picking. Various software tools which deal with the control of such systems, are available on the market. To manage the increasing complexity and to optimize the design of the systems, a simulation-based tool is required for simulation-based commissioning. This paper presents a concept for a comprehensive virtual security solution for industrial bin picking.

Bei einer Hardware-in-the-Loop (HiL)-Simulation wird die reale Steuerungstechnik mit einer experimentierfähigen Maschinensimulation verbunden. Soll das Bewegungsverhalten des Materialflusses in der Maschinensimulation zur Generierung von Steuerungssignalen berechnet werden, so müssen die harten Echtzeitanforderungen einer HiL-Simulation eingehalten werden. Dieser Beitrag betrachtet verschiedene Materialflussmodelle und gibt das Ziel eines mehrskaligen Simulationsmodells für die HiL-Simulation vor. A Hardware-in-the-Loop (HiL) simulation couples real control technology with an experimental machine simulation. When computing the movement behavior of a material flow in the machine simulation to generate control signals, the hard real-time requirements of a HiL-simulation must be considered. This article checks different material flow models and defines the objective of a multi-scale material flow model for HiL-Simulation.

In this paper a solution is presented, which extends the network of non-real-time-capable ROS nodes (Robot Operating System) by a modular network of configurable and real-time-capable blocks with control and path planning functionalities. By means of this solution, ROS can be coupled with real-time algorithms from the field of industrial path planning controls, such as spline interpolation (e.g. Akima, B-spline). Furthermore, the real-time network can communicate directly with industrial hardware via real-time bus protocols established in the industrial automation technology. The available engineering-tool allows to model the real-time network in a user-friendly way. Custom real-time blocks can be generated from C++ code.

Currently, the gold standard for dental imaging is projection radiography or cone-beam computed tomography (CBCT). These methods are fast and cost-efficient, but exhibit poor soft tissue contrast and expose the patient to ionizing radiation (X-rays). The need for an alternative imaging modality e.g. for soft tissue management has stimulated a rising interest in dental magnetic resonance imaging (MRI) which provides superior soft tissue contrast. Compared to X-ray imaging, however, so far the spatial resolution of MRI is lower and the scan time is longer. In this contribution, we describe wireless, inductively-coupled intraoral coils whose local sensitivity enables high resolution MRI of dental soft tissue. In comparison to CBCT, a similar image quality with complementary contrast was obtained ex vivo. In-vivo, a voxel size of the order of 250∙250∙500 μm3 was achieved in 4 min only. Compared to dental MRI acquired with clinical equipment, the quality of the images was superior in the sensitive volume of the coils and is expected to improve the planning of interventions and monitoring thereafter. This method may enable a more accurate dental diagnosis and avoid unnecessary interventions, improving patient welfare and bringing MRI a step closer to becoming a radiation-free alternative for dental imaging.

Summary Mandibular reconstruction is still a challenge for surgeons. Distraction osteogenesis (DO) might contribute in certain instances to solve this problem. A principal advantage of DO is the expansion of the surrounding soft tissues that accompanies the bony regeneration. In addition there is no donor site morbidity when compared with reconstruction by autologous bone grafting. However its application may be limited by the thinness of the mandible and the attendant fracture risk. This article describes a technique that combines stable internal fixation with vertical distraction of the alveolar ridge in six patients with critical mandibular thickness after ablative surgery for cancer of the oral cavity. Prior to implant insertion for further prosthodontic restoration stable vertical mandibular distraction produced an additional 11–20 mm. Improvement of the surrounding soft tissues, especially intraorally was achieved and dental implants were inserted after bony consolidation. This method can be a useful salvage technique for the augmentation of the atrophic mandible in patients who are not able or willing to undergo the risks and disadvantages of established methods such as free autologous bone transfer or microsurgical techniques.

Background: Dental mutilations (DM) were and are still common among people in Africa. The purpose of this study was to examine DM in 33 skulls from Cameroon, which have been collected around the turn of the 20th century (anthropological collection, Berlin Museum of Medical History). Materials and methods: From the files of the museum, locations and/or tribal origin were recorded. DM classification described by De Almeida was used (1957). Results: DM of the inverted V-shaped type was most common (30.3%). Pulp exposure was seen in 10 cases (30.3%). Periapical ostitis/radicular cysts were seen in nine cases (27.3%). General loss of alveolar bone was seen in all cases with a marked loss of the maxillary anterior labial alveolar bone plate in six cases (18.2%). Conclusions: DM may result in alveolar bone pathology characterised by inflammatory changes such as periapical ostitis or formation of radicular cysts.

A Mecanum-wheeled robot benefits from great omni-direction maneuverability. However it suffers from random slippage and high-speed vibration, which creates electric power safety, uncertain position errors and energy waste problems for heavy-duty tasks. A lack of Mecanum research on heavy-duty autonomous navigation demands a robot platform to conduct experiments in the future. This paper introduces AuckBot, a heavy-duty omni-directional Mecanum robot platform developed at the University of Auckland, including its hardware overview, the control system architecture and the simulation design. In particular the control system, synergistically combining the Beckhoff system as the Controller-PC to serve low-level motion execution and ROS as the Navigation-PC to accomplish highlevel intelligent navigation tasks, is developed. In addition, a computer virtual simulation based on ISG-virtuos for virtual AuckBot has been validated. The present status and future work of AuckBot are described at the end.

The purpose of this study was to evaluate the incidence and basic characteristics of oral, pharyngeal, and laryngeal squamous cell carcinomas (OPLC) in a single-centre series of liver transplantations (LT). The medical records of 1515 LT cases with a median follow-up of 6 years were analysed retrospectively for incident cases of OPLC. Incidence rates for the oral cavity and pharynx (ICD-9: 141-149), and larynx (ICD-9: 161) were assessed separately. OPLC cases and non-cases were evaluated with regard to end-stage alcoholic liver disease (ALD) as LT indication, smoking, and immunosuppression. The cumulative incidence of 13 cases with OPLC was 0.86% in total (n=1515). For 11 cases of OPLC in 307 patients with LT for ALD, it was 3.58%. The estimates for the annual incidence of OPLC (ICD-9: 141-149) were 121.79 for females and 111.65 for males (/100.000 patient-years). For OPLC (ICD-9: 161), the estimate was 37.21 for males, respectively (no female cases). ALD (84.6%) and pre-LT smoking (92.3%) were significantly overrepresented in OPLC cases (p0.001). Age and gender distribution were comparable to non-cases. The 5-year survival rate after OPLC was 41.5%. OPLC were demonstrated as a late-onset complication of LT with poor prognosis. The impact of pre-, post-LT smoking, and, in particular, ALD as a confounder of OPLC deserves further investigation.

In this study, we compared 103 OralCDx results with the histological findings of 96 clinical sites in 80 patients (33 females; 64.3+/-13.7 years and 47 males; 53.2+/-11.5 years). The histological findings were classified as follows: compatible with oral leukoplakia (OL; n = 60) or oral lichen planus (OLP; n = 17), both without dysplasia; dysplasia in OL or OLP (n = 9); and oral squamous cell carcinoma (OSCC; n = 17). There were seven (6.8%) specimens with an inadequate cell count. Overall, the sensitivity of the OralCDx technique to detect dysplasia and OSCC was 92.3% (95% CI: 74.9-99.1%), and the specificity was 94.3% (95% CI: 86.0-98.4%). The positive likelihood ratio (LR+) was 16.2 (95% CI: 6.2-42.1) and the negative likelihood ratio (LR-) was 0.08 (95% CI: 0.02-0.31). In conclusion, these figures are in agreement with previously published data and support the use of OralCDx as a screening tool of oral lesions, but further trials are still necessary.

Studies on the risk factors of oral leukoplakia (OL) are relatively scarce. The objectives of this paper are to assess the clinical risk factors of OL in a representative sample of the US population. Data from the oral mucosal tissue assessment and some other covariates of 15,811 participants in the US National Health and Nutrition Examination Survey (NHANES III) were included. The clinical definition of OL was applied according to the WHO criteria. Tobacco smoking was found as the strongest independent risk factor. The OR were 3.00 (0.77–11.8) for ⩽10 cigarettes/day up to 6.01 (2.4–15.0) for >20 cigarettes/day. Diabetes, age and socio-economic status were found as independent predictors of OL. Alcohol consumption, race/ethnicity, years of education and BMI showed no independent association with OL. Females with a history of estrogen use were less likely to have OL with an OR of 0.34 (0.11–1.07). In conclusion, the role of diabetes and estrogen in the pathogenesis of OL should be further investigated.

Communication between the surgeon, the pathologist and the radiation oncologist is improved by a virtual model of the final resection combining 3D imaging with computer aided navigation. The pathologist localises any questionable margins and the oncologist plans focussed delivery of radiation to native tissue in an area of complex anatomy.

Over the last decade tissue engineering has emerged as a key factor in bone regeneration within the field of cranio-maxillofacial surgery. Despite this in vivo analysis of tissue-engineered-constructs to monitor bone rehabilitation are difficult to conduct. Novel high-resolving flat-panel based volume CTs (fp-VCT) are increasingly used for imaging bone structures. This study compares the potential value of novel fp-VCT with conventional multidetector CT (MDCT) based on a sheep sinus floor elevation model. Calcium-hydroxyapatite reinforced collagen scaffolds were populated with autologous osteoblasts and implanted into sheep maxillary sinus. After 8, 16 and 24 weeks MDCT and fp-VCT scans were performed to investigate the volume of the augmented area; densities of cancellous and compact bone were assessed as comparative values. fp-VCT imaging resulted in higher spatial resolution, which was advantageous when separating closely related anatomical structures (i.e. trabecular and compact bone, biomaterials). Fp-VCT facilitated imaging of alterations occurring in test specimens over time. fp-VCTs therefore displayed high volume coverage, dynamic imaging potential and superior performance when investigating superfine bone structures and bone remodelling of biomaterials. Thus, fp-VCTs may be a suitable instrument for intraoperative imaging and future in vivo tissue-engineering studies.

Purpose: To evaluate the ability of conventional and ultra-short or zero echo time MRI for imaging of soft and solid dental components in and ex vivo. Materials and Methods: Turbo spin echo (TSE), ultra-short echo time (UTE), and zero echo time (ZTE) MRI were performed on extracted (human and equine) teeth and in vivo using whole-body and small-bore MR systems at 3 T, 7T, and 9.4T, respectively. Results: At an isotropic resolution of (600 μm)3, strong signal of soft-tissue, e.g., mucosa and nerves with excellent contrast was achieved using TSE at 3T in vivo. No signal, though, was obtained from solid components, e.g., teeth (due to short T2). In contrast, dentin, cementum as well as enamel of extracted teeth were readily depicted using UTE and ZTE at a resolution of ≈ (150 μm)3 at 7T and 9.4T. In particular, ZTE provided higher signal in enamel. Conclusion: As an alternative to X-ray based methods like cone-beam computed tomography (CT) or conventional CT, the presented results demonstrate the potential of ZTE and UTE MRI as a radiation-free imaging modality, delivering contrast of soft and solid components at the same time. J. Magn. Reson. Imaging 2012;36:841–846. © 2012 Wiley Periodicals, Inc.

Dental mutilations (DM) were and are still common among people in Africa. The purpose of this study was to examine DM in 33 skulls from Cameroon, which have been collected around the turn of the 20th century (anthropological collection, Berlin Museum of Medical History).From the files of the museum, locations and/or tribal origin were recorded. DM classification described by De Almeida was used (1957).DM of the inverted V-shaped type was most common (30.3%). Pulp exposure was seen in 10 cases (30.3%). Periapical ostitis/radicular cysts were seen in nine cases (27.3%). General loss of alveolar bone was seen in all cases with a marked loss of the maxillary anterior labial alveolar bone plate in six cases (18.2%).DM may result in alveolar bone pathology characterised by inflammatory changes such as periapical ostitis or formation of radicular cysts.

This report describes the 'Skull from Bangkok', collected by Rudolf Virchow (Berlin, Germany) in the late 19th century. The skull is part of an extensive anthropological collection of skeletons and skulls from all over the world. The skull was probably brought to Berlin during the years 1882-1883. An inscription on the frontal bone gives the name of the skull: 'Skull from Bangkok'. The few remaining teeth of the maxilla show brown black stains because of betel quid chewing. In the collection, there is an extensive number of skulls from South- and Southeast Asia with similar betel stains. Virchow himself was aware of this habit and has described some of the skulls in detail often mentioning the black stains because of betel quid chewing. The Skull from Bangkok is a proof that betel quid chewing was prevalent in Siam of the late 19th century.

Summary The purpose of this study was to assess the prevalence of oral precancerous lesions and squamous cell carcinoma (OSCC) in Yemeni users of shammah , a traditional smokeless tobacco habit known in the Arabian Peninsula. The study group comprised 199 male and one female shammah users who were interviewed via a standardised questionnaire and clinically examined in 48 Yemeni villages and cities. Cases with oral leukoplakia (OL) or mucosal burns (MB) were compared with users without any lesion. MB were detected in 31%, of which 46.8% were located on the tongue or floor of the mouth, and OL in 27%, of which 59.2% were located in the same region. In addition, two cases (1%) of apparent OSCC were identified. Statistically significant increased OR (95% CI) of OL were (a) 6.91 (2.66–17.95) for an average duration of the respective shammah application >5 min.; (b) 4.90 (1.99–12.08) for a daily frequency of those applications >10; and (c) 4.22 (1.43–12.43) for a daily duration >6 h of chewing qat, also a traditional habit in Yemen. Likewise, decreased OR were (a) 0.39 (0.18–0.85) for rinsing the mouth after the shammah application; (b) 0.36 (0.17–0.78) for successful attempts to stop the use in the past; and (c) 0.26 (0.09–0.72) for existing knowledge about the carcinogenicity of shammah that was present in only 19% overall. In conclusion, evidence was shown for a significant association between the prevalence of OL and the daily duration of shammah application in a dose-dependent manner. An appropriate public health program might help to reduce this potential OSCC burden in shammah users.

Recent studies reported a tendency towards a lower prevalence of oral leukoplakia (OL), compared with the past. To assess the prevalence of OL in a representative sample of the US population, data from the oral mucosal tissue assessment and some other covariates of 16128 participants in the US National Health and Nutrition Examination Survey (NHANES III) were included. The clinical definition of OL was applied according to the WHO criteria. The weighted prevalence estimates of OL were 0.66+/-0.14% in males, 0.21+/-0.05% in females and 0.42+/-0.08% in total. The age peaks were at 40-49 years in males and at >or=70 years in females. The prevalence estimates were 0.37% for homogeneous OL and 0.06% for non-homogeneous OL. Gingiva (38.8%) and buccal mucosa (30.9%) were the most frequent locations. Compared to previous studies in the USA, a substantial decline of the prevalence of OL was shown.

Recent reviews described a cumulative risk of 0-38% of oral leukoplakias (OL) to transform into oral squamous cell carcinoma (OSCC). The annual transformation rate (ATR) of OL into OSCC amounted up to 6.3%. To elucidate epidemiological consequences of varying ATR. Variations of the prevalence (1-2%) and ATR (0.5-4%) of OL were used to compute the proportional incidences of OSCC developing in OL. These were compared to the actual incidences of OSCC excerpted from European cancer registries. A ratio50% of predicted to actual incidence overall indicated a plausible ATR. With an ATRor=3%, the predicted incidences of OSCC would exceed the reported incidences in all countries. With an ATRor=1%, the ratio of OSCC developed in OL to OSCC overall would be always lower than 50%. Based on present data, it was concluded that the ATR of OL into OSCC should not exceed 1%.

Data sources Searches were made of Medline, Cancerlit, the Institute for Scientific Information (ISI) databases of SCI-expanded and Social Sciences Citation Index (SciSearch), and of Embase (1980–present) and the International Bibliography of the Social Sciences both via BIDS. Relevant journals and indices were searched by hand. Study selection Only English-language articles published between 1957 and 2000 were included. Articles that did not include studies of squamous cell carcinoma or describing cancer of upper aerodigestive tract, oesophagus or larynx were excluded. Data abstraction and synthesis A qualitative synthesis of the studies included was carried out. Results A total of 46 articles exclusively considering young adults were identified, of which 28 examined potential risk factors. About 4–6% of oral cancers occur in people aged under 40 years. The usual male dominance does not appear to hold for younger patients. There are inconsistencies in the survival rates of younger patients compared with older patients but this may be due to small sample sizes and differences in treatment type and duration. Several studies suggest that many younger patients have never used tobacco or consumed alcohol or the duration of exposure is too short for malignant transformation too occur. There is insufficient research on association with occupation, immune defence, viral infections, diets low in fruit and vegetables or genetic factors. Conclusions There is mixed evidence regarding the role of alcohol and tobacco as risk factors in young people. There is limited research on other risk factors.