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Identifying new candidate colorectal cancer (CRC) genes and mutations are important for clinical cancer prevention as well as in cancer care. Genetic counseling is already implemented for known high-risk variants; however, the majority of CRC are of unknown causes. In our study, 110 CRC patients in 55 Swedish families with a strong history of CRC but unknown genetic causes were analyzed with the aim of identifying novel candidate CRC predisposing genes. Exome sequencing was used to identify rare and high-impact variants enriched in the families. No clear pathogenic variants were found in known CRC predisposing genes; however, potential pathogenic variants in novel CRC predisposing genes were identified. Over 3000 variants with minor allele frequency (MAF)0.01 and Combined Annotation Dependent Depletion (CADD) 20 were seen aggregating in the CRC families. Of those, 27 variants with MAF 0.001 and CADD25 were considered high-risk mutations. Interestingly, more than half of the high-risk variants were detected in three families, suggesting cumulating contribution of several variants to CRC. In summary, our study shows that despite a strong history of CRC within families, identifying pathogenic variants is challenging. In a small number of families, few rare mutations were shared by affected family members. This could indicate that in the absence of known CRC predisposing genes, a cumulating contribution of mutations leads to CRC observed in these families.

Summary Background and aims Systematic reviews (SRs) are considered to provide reliable estimates, but flaws in designs, methods of monitoring effects, and outcomes have the potential to bias results. There are several tools for assessing risk of bias (RoB), most of them designed for SRs of beneficial effects. To our knowledge, there is no tool that is adapted specifically to assess RoB in studies of adverse effects associated with orthodontic treatment. To address this, the aim of this study was first to introduce a tool for assessment of RoB in studies of adverse effects associated with orthodontic treatment and, second, to apply it in an SR of external root resorption (ERR) associated with orthodontic treatment with fixed appliance. Materials and methods The approach with domains supported by signalling questions was used for the tool. Domains and signalling questions were tailored to the review questions of the SR of studies of ERR after orthodontic treatment using periapical radiography or cone beam computed tomography. Duplicate study selection, data extraction, and RoB assessment using the tool, followed by meta-analyses, were performed. Results Using the tool for the assessment of RoB identified shortcomings and report deficiencies of primary studies concerning the presentation of orthodontic treatment, identification of ERR, and analysis of outcomes. RoB assessment resulted in 12 of 32 studies read in full text being included. Reported severe ERR varied across studies between 2 and 14 per cent for all incisors and 10 and 29 per cent for maxillary incisors. Results of ERR related to patients’ age and sex, orthodontic diagnosis, and treatment were contradictory. Quality of evidence evaluated by GRADE was low due to study limitations, imprecision, and inconsistency of study results. Conclusions As the tool and its application highlight important issues to consider when planning, conducting, and reporting research, the tool may have a valuable role for quality enhancement of future studies of outcomes of orthodontic treatment. The tool may also serve for authors when planning SRs. Our SR identified a need for studies that use rigorous methodology and transparent reporting. Registration PROSPERO (ID = CRD42018084725).

Craniosynostosis (CS), the premature closure of one or more cranial sutures, occurs both as part of a syndrome or in isolation (nonsyndromic form). Here, we have studied the prevalence and spectrum of genetic alterations associated with coronal suture closure in 100 Scandinavian patients treated at a single craniofacial unit. All patients were phenotypically assessed and analyzed with a custom-designed 63 gene NGS-panel. Most cases (78%) were syndromic forms of CS. Pathogenic and likely pathogenic variants explaining the phenotype were found in 80% of the families with syndromic CS and in 14% of those with nonsyndromic CS. Sixty-five percent of the families had mutations in the CS core genes FGFR2, TWIST1, FGFR3, TCF12, EFNB1, FGFR1, and POR. Five novel pathogenic/likely pathogenic variants in TWIST1, TCF12, and EFNB1 were identified. We also found novel variants in SPECC1L, IGF1R, and CYP26B1 with a possible modulator phenotypic effect. Our findings demonstrate that NGS targeted sequencing is a powerful tool to detect pathogenic mutations in patients with coronal CS and further emphasize the importance of thorough assessment of the patient's phenotype for reliable interpretation of the molecular findings. This is particularly important in patients with complex phenotypes and rare forms of CS.

Purpose: Some 10% of familial adenomatous polyposis (FAP) and 80% of attenuated polyposis (AFAP) cases remain molecularly unexplained. We scrutinized such cases by exome-wide and targeted methods to search for novel susceptibility genes. Methods: Exome sequencing was conducted on 40 unexplained (mainly sporadic) cases with FAP or AFAP from Finland. The DNA mismatch repair (MMR) gene MLH3 (MutL Homolog 3) was pinpointed and prompted a subsequent screen of similar to 1000 Swedish patients referred to clinical panel sequencing for colon tumor susceptibility. Results: Three homozygous carriers of a truncating variant in MLH3, c.3563C>G, p.Ser1188Ter, were identified among the index cases from the Finnish series. An additional biallelic carrier of the same variant was present in the Swedish series. All four patients shared a 0.8-Mb core haplotype around MLH3, suggesting a founder variant. Colorectal polyps from variant carriers showed no instability at mono-, di-, tri-, or tetranucleotide repeats, in agreement with previous findings of a minor role of MLH3 in MMR. Multiple loci were affected by loss of heterozygosity, suggesting chromosomal instability. Conclusion: Our results show that a biallelic nonsense variant of MLH3 underlies a novel syndrome with susceptibility to classical or attenuated adenomatous polyposis and possibly extracolonic tumors, including breast cancer.

Objectives: Direct cost for methods of prediction also named risk assessment in dentistry may be negligible compared with the cost of extensive constructions. On the other hand, as risk assessment is performed daily and for several patients in general dental practice, the costs may be considerable. The objective was to summarize evidence in studies of economic evaluation of prognostic prediction multivariable models and methods of caries and periodontitis and to identify knowledge gaps (PROSPERO registration number: CRD42020149763). Material and methods: Four electronic databases (PubMed, Web of Science, The Cochrane Library, NHS Economic Evaluation Database) and reference lists of included studies were searched. Titles and abstracts were screened by two reviewers in parallel. Full-text studies reporting resources used, costs and cost-effectiveness of prediction models and methods were selected and critically appraised using a protocol based on items from the CHEERS checklist for economic evaluations and the CHARMS checklist for evaluation of prediction studies. Results: From 38 selected studies, six studies on prediction fulfilled the eligibility criteria, four on caries and two on periodontitis. As the economic evaluations differed in method and perspective among the studies, the results could not be generalized. Our systematic review revealed methodological shortcomings regarding the description of predictive models and methods, and particularly of the economic evaluation. Conclusions: The systematic review highlighted a paucity of economic evaluations regarding methods or multivariable models for prediction of caries and periodontitis. Our results indicate that what we currently practice using models and methods to predict caries and periodontitis lacks evidence regarding cost-effectiveness. Funding Agencies|Malmo University

Immunotherapy with PD‐1 and PD‐L1 inhibitors has revolutionized the treatment for patients with NSCLC the last years with increased overall survival and in particular increased number of long‐time survivors in patients with metastatic disease. It is now a treatment of choice for patients with distant metastases (stage IV) and in conjunction with chemoradiotherapy for patients with limited spread confined to the chest (stage III). PD‐1 inhibition has been proven to be superior to standard chemotherapy, both as a single treatment and when combined with either chemotherapy or CTLA‐4 inhibition. Despite the success of immunotherapy, the majority of patients do not respond or relapse within a short time frame. Biomarkers that would help to properly select patients with a high likelihood of clinical response to PD‐1 and PD‐L1 inhibitors are scarce and far from optimal, and only one (PD‐L1 expression) has reached clinical practice. Thus for immunotherapy to be effective, the discovery and validation of additional biomarkers is critical for patient selection and prediction of clinical response. In this mini‐review, we give an overview of current clinical management of NSCLC including treatment landscape with regard to immunotherapy, as well as discuss the current genetic and immune cell biomarker studies and their potential for introduction into clinical practice.

Objectives: To apply the ROBIS tool for assessment of risk of bias (RoB) in systematic reviews (SRs) in a meta-review on effective doses (EDs) in dental and maxillofacial cone beam CT. Methods: Three electronic databases and reference lists of included SRs were searched. Eligible SRs were classified as having low, high or unclear RoB. Findings of SRs were synthesised and data from primary studies combined to relate ED to field of view (FOV) and operating potential (kV). Results: Seven SRs were included: three displayed low RoB, three high and one had unclear RoB. Only one SR related ED to image quality. Deficiencies in reporting of eligibility criteria, study selection and synthesis of results in SRs were identified. FOV height had a significant relationship with ED, explaining 27.2% of its variability. Median ED for three FOV categories differed significantly. Operating potential had a weak relationship with ED, with no significant difference in median ED between three operating potential groups. Conclusion: The ROBIS tool should have a role for meta-reviews of different aspects of radiology. The disappointing results for RoB might be remedied by developing standards to improve the quality of reporting of primary dosimetry studies and of SRs. Future dosimetry studies should always relate ED to image quality or diagnostic accuracy. Advances in knowledge: This meta-review is the first to implement ROBIS for SRs of ED and identified that trustworthiness of some SRs is questionable. The percentage change in average ED per cm increase in FOV height could be calculated, emphasizing the importance of FOV as a determinant of ED in CBCT.

Progressive tumor growth is associated with deficits in the immunity generated against tumor antigens. Vaccines targeting tumor neoepitopes have the potential to address qualitative defects; however, additional mechanisms of immune failure may underlie tumor progression. In such cases, patients would benefit from additional immune-oncology agents targeting potential mechanisms of immune failure. This study explores the identification of neoepitopes in the MC38 colon carcinoma model by comparison of tumor to normal DNA and tumor RNA sequencing technology, as well as neoepitope delivery by both peptide- and adenovirus-based vaccination strategies. To improve antitumor efficacies, we combined the vaccine with a group of rationally selected immune-oncology agents. We utilized an IL15 superagonist to enhance the development of antigen-specific immunity initiated by the neoepitope vaccine, PD-L1 blockade to reduce tumor immunosuppression, and a tumor-targeted IL12 molecule to facilitate T-cell function within the tumor microenvironment. Analysis of tumor-infiltrating leukocytes demonstrated this multifaceted treatment regimen was required to promote the influx of CD8+ T cells and enhance the expression of transcripts relating to T-cell activation/effector function. Tumor-targeted IL12 resulted in a marked increase in clonality of T-cell repertoire infiltrating the tumor, which when sculpted with the addition of either a peptide or adenoviral neoepitope vaccine promoted efficient tumor clearance. In addition, the neoepitope vaccine induced the spread of immunity to neoepitopes expressed by the tumor but not contained within the vaccine. These results demonstrate the importance of combining neoepitope-targeting vaccines with a multifaceted treatment regimen to generate effective antitumor immunity.

Objectives: To evaluate measurability and reliability of measurements of root length and marginal bone level in CBCT, periapical (PA) and bitewing (BW) radiographs. Methods: CBCT of both jaws, PA of maxillary incisors and posterior BW radiographs of 10 adolescents (mean age 13.4) were selected. The radiographs comprised part of the baseline examinations of a trial of orthodontic treatment. Six raters assessed measurability and measured root length and marginal bone level. Three raters repeated their assessments. Measurability was expressed as frequency of interpretable sites and reliability as intraclass correlation coefficient (ICC). Results: Measurability was 100 % in CBCT and 95 % in PA of maxillary incisors for root length measurements. For marginal bone level, measurability was 100 % in CBCT, 76 % in PA and 86 % in posterior BW. Mean ICC for interrater reliability for root length measurements in CBCT was 0.88 (range 0.27–0.96 among different teeth) and 0.69 in PA of maxillary incisors. For marginal bone level measurements, mean ICC was 0.4 in CBCT, 0.38 in PA of maxillary incisors and 0.4 in posterior BW. Intrarater reliability varied among methods, root length or marginal bone level and among raters, except for root length measurements in CBCT, which presented high reliability (above 0.8) for all raters. Conclusions: As measurability and reliability were high for root length measurements in CBCT, this may be the method of choice for scientific analyses in orthodontics. For clinical praxis, we recommend PA following the “as low as diagnostically acceptable” principle, as clinical decisions seem to be influenced only when severe root resorption occurs.

Objective: To evaluate effects of thresholds on estimates of predictive accuracy of methods for caries risk assessment. Material and methods: Adolescents, aged 12 visiting two dental clinics, were examined by visual/tactile examination and bitewing radiography at baseline and after one year. Three methods for caries risk assessment were applied: previous caries experience, dentists’ risk assessment according to set criteria (presence or absence of caries lesion) and acid tolerance of dental biofilm. The measure for validity (the reference standard) comprised caries lesion progression at 1 year. Predictive accuracy estimates were calculated for several thresholds. Results: Accuracy estimates changed with threshold values of the methods and the reference standard. Patient spectrum differed between the clinics, which resulted in different accuracy estimates for the two samples. Generally, negative predictive values were high while positive ones were low indicating that these methods were more efficient in finding individuals who are at low risk of developing caries lesions than those with increased risk. Conclusions: As thresholds and patient spectrum affected predictive accuracy, it may be difficult to design a universal model with set thresholds for caries risk assessment. Foremost, a model should consider the level of aspiration for prediction and clinical decisions that will be made based on the risk assessment in the actual clinical setting.

Hereditary syndromes causing colorectal cancer include both polyposis and non-polyposis syndromes. Overlapping phenotypes between the syndromes have been recognized and this make targeted molecular testing for single genes less favorable, instead there is a gaining interest for multi-gene panel-based approaches detecting both SNVs, indels and CNVs in the same assay. We applied a panel including 19 CRC susceptibility genes to 91 individuals of six phenotypic subgroups. Targeted NGS-based sequencing of the whole gene regions including introns of the 19 genes was used. The individuals had a family history of CRC or had a phenotype consistent with a known CRC syndrome. The purpose of the study was to demonstrate the diagnostic difficulties linked to genotype-phenotype diversity and the benefits of using a gene panel. Pathogenicity classification was carried out on 46 detected variants. In total we detected sixteen pathogenic or likely pathogenic variants and 30 variants of unknown clinical significance. Four of the pathogenic or likely pathogenic variants were found in BMPR1A in patients with unexplained familial adenomatous polyposis or atypical adenomatous polyposis, which extends the genotype-phenotype spectrum for this gene. Nine patients had more than one variant remaining after the filtration, including three with truncating mutations in BMPR1A, PMS2 and AXIN2. CNVs were found in three patients, in upstream regions of SMAD4, MSH3 and CTNNB1, and one additional individual harbored a 24.2 kb duplication in CDH1 intron1. Electronic supplementary material The online version of this article (doi:10.1007/s10689-016-9934-0) contains supplementary material, which is available to authorized users.

Lynch syndrome caused by constitutional mismatch-repair defects is one of the most common hereditary cancer syndromes with a high risk for colorectal, endometrial, ovarian and urothelial cancer. Lynch syndrome is caused by mutations in the mismatch repair (MMR) genes i.e., MLH1, MSH2, MSH6 and PMS2. After 20 years of genetic counseling and genetic testing for Lynch syndrome, we have compiled the mutation spectrum in Sweden with the aim to provide a population-based perspective on the contribution from the different MMR genes, the various types of mutations and the influence from founder mutations. Mutation data were collected on a national basis from all laboratories involved in genetic testing. Mutation analyses were performed using mainly Sanger sequencing and multiplex ligation-dependent probe amplification. A total of 201 unique disease-predisposing MMR gene mutations were identified in 369 Lynch syndrome families. These mutations affected MLH1 in 40%, MSH2 in 36%, MSH6 in 18% and PMS2 in 6% of the families. A large variety of mutations were identified with splice site mutations being the most common mutation type in MLH1 and frameshift mutations predominating in MSH2 and MSH6. Large deletions of one or several exons accounted for 21% of the mutations in MLH1 and MSH2 and 22% in PMS2, but were rare (4%) in MSH6. In 66% of the Lynch syndrome families the variants identified were private and the effect from founder mutations was limited and predominantly related to a Finnish founder mutation that accounted for 15% of the families with mutations in MLH1. In conclusion, the Swedish Lynch syndrome mutation spectrum is diverse with private MMR gene mutations in two-thirds of the families, has a significant contribution from internationally recognized mutations and a limited effect from founder mutations. Funding Agencies|Swedish Cancer Society

Objectives Resuscitation on in-hospital cardiac arrest (IHCA) is estimated to occur in 200,000 hospitalised patients annually in the US. The duration of the resuscitation attempt, measured as minutes of cardiopulmonary resuscitation (CPR), and its impact on survival remains unknown. Aim Investigate if there is a difference in 30-day survival among IHCA who experience return of spontaneous circulation (ROSC) depending on the duration of CPR. Material and methods All patients ≥18 years who experienced ROSC after an IHCA at Karolinska University Hospital between 2007 and 2017 were included. Data regarding the IHCA, patient characteristics, and death dates were obtained from medical records linked to Swedish national registries. Patients who experienced ROSC were stratified into quartiles depending on the length of CPR (in minutes). The difference in 30-day survival between the quartiles (Q) was assessed with adjusted logistic regression models and presented as odds ratios with 95% confidence intervals (OR 95% CI). Adjustments included sex, age, Charlson Comorbidity Index, first rhythm, ECG-surveillance, witnessed or not, time between CA and call, year of IHCA and location of the IHCA. Results In all, 1639 patients suffered an IHCA, of whom 840 (51%) experienced ROSC and 471 (29% of the total, 56% of those with ROSC) survived for at least 30 days. Among the 840 patients with ROSC, 768 (91%) had a documented duration of their CPR in their medical file with a median of 5 min (interquartile range 2–12 min). Among those with ROSC, the adjusted OR for 30-day survival was OR 0.69 (0.37–1.29) for Q2 (3–5 min), 0.35 (0.19–0.65) for Q3 (6–12 min) and 0.10 (0.05–0.20) Q4. A cut-off time of 15 min, 20 min and 60 min, respectively, captures 90%, 95% and 99% of the 30-day survivors. Conclusion Resuscitation attempts on IHCA are often short and duration of CPR is associated with 30-day survival among those with ROSC. Still, the 30-day survival is high enough to question the use of CPR duration as a prognostic marker in post-resuscitation care, and ideal duration of resuscitation should remain a bedside decision taking into consideration the whole clinical picture.

The videofluoroscopic swallowing study (VFSS) is commonly considered the gold standard for assessing a patient’s swallowing ability. Most dysphagic patients arrange food to make it thicker or softer and thus easier and safer to swallow. A popular point of discussion, even argument, about VFSS among clinicians is whether to use barium sulfate in isolation or in combination with real food. No firm answer has emerged from these discussions, and proponents of both perspectives have seemingly valid points. The aim of the present study was to review whether there were differences between the results using liquid or solid foods in VFSS. We performed a literature search and interpreted the data acquired according to a systematic method. After data extraction and interpretation, we were left with 14 publications that were considered relevant. Most of the research showed that the rate of aspiration was higher with liquids than with solid foods. According to the results of VFSS by using the various textured-foods, the aspiration risk was highest with two-phase food diet such as the mixtures of liquid and solid foods. However, descriptions of their results were often inadequate although many test foods were used for the VFSS. There were a few publications containing the detailed information of the food textures. As the VFSS images provide valuable data, the methods and the results should be described in as much detail as possible to help readers of the articles. Most patients make allowances for the differences in thin liquids, thick liquids, and solid foods. Hence, writing the details of test food textures would lead to improve the quality of the VFSS in the future.

To evaluate the accuracy of different methods used to identify individuals with increased risk of developing dental coronal caries.Studies on following methods were included: previous caries experience, tests using microbiota, buffering capacity, salivary flow rate, oral hygiene, dietary habits and sociodemographic variables. QUADAS-2 was used to assess risk of bias. Sensitivity, specificity, predictive values, and likelihood ratios (LR) were calculated. Quality of evidence based on ≥3 studies of a method was rated according to GRADE.PubMed, Cochrane Library, Web of Science and reference lists of included publications were searched up to January 2015.From 5776 identified articles, 18 were included. Assessment of study quality identified methodological limitations concerning study design, test technology and reporting. No study presented low risk of bias in all domains. Three or more studies were found only for previous caries experience and salivary mutans streptococci and quality of evidence for these methods was low. Evidence regarding other methods was lacking. For previous caries experience, sensitivity ranged between 0.21 and 0.94 and specificity between 0.20 and 1. Tests using salivary mutans streptococci resulted in low sensitivity and high specificity. For children with primary teeth at baseline, pooled LR for a positive test was 3 for previous caries experience and 4 for salivary mutans streptococci, given a threshold ≥10(5) CFU/ml.Evidence on the validity of analysed methods used for caries risk assessment is limited. As methodological quality was low, there is a need to improve study design.Low validity for the analysed methods may lead to patients with increased risk not being identified, whereas some are falsely identified as being at risk. As caries risk assessment guides individualized decisions on interventions and intervals for patient recall, improved performance based on best evidence is greatly needed.

Objectives To review the literature of economic evaluations regarding diagnostic methods used in dentistry. Data sources Four databases (MEDLINE, Web of Science, The Cochrane library, the NHS Economic Evaluation Database) were searched for studies, complemented by hand search, until February 2013. Study selection Two authors independently screened all titles or abstracts and then applied inclusion and exclusion criteria to select full-text publications published in English, which reported an economic evaluation comparing at least two alternative methods. Studies of diagnostic methods were assessed by four reviewers using a protocol based on the QUADAS tool regarding diagnostic methods and a check-list for economic evaluations. The results of the data extraction were summarized in a structured table and as a narrative description. Results From 476 identified full-text publications, 160 were considered to be economic evaluations. Only 12 studies (7%) were on diagnostic methods, whilst 78 studies (49%) were on prevention and 70 (40%) on treatment. Among studies on diagnostic methods, there was between-study heterogeneity methodologically, regarding the diagnostic method analysed and type of economic evaluation addressed. Generally, the choice of economic evaluation method was not justified and the perspective of the study not stated. Costing of diagnostic methods varied. Conclusions A small body of literature addresses economic evaluation of diagnostic methods in dentistry. Thus, there is a need for studies from various perspectives with well-defined research questions and measures of the cost and effectiveness. Clinical significance Economic resources in healthcare are finite. For diagnostic methods, an understanding of efficacy provides only part of the information needed for evidence-based practice. This study highlighted a paucity of economic evaluations of diagnostic methods used in dentistry, indicating that much of what we practise lacks sufficient evidence.

Syntrophus aciditrophicus is a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation by S. aciditrophicus. However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome of S. aciditrophicus leaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show that S. aciditrophicus uses AMP-forming, acetyl-CoA synthetase (Acs1) for ATP synthesis from acetyl-CoA. acs1 mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, of S. aciditrophicus grown in pure culture and coculture. Cell extracts of S. aciditrophicus had low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified from S. aciditrophicus and recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) in S. aciditrophicus cells support the operation of Acs1 in the acetate-forming direction. Thus, S. aciditrophicus has a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase., IMPORTANCE Bacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA. Syntrophus aciditrophicus apparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as its genome does not have homologs to the genes for phosphate acetyltransferase and acetate kinase. Here, we show that S. aciditrophicus uses an alternative approach, an AMP-forming, acetyl-CoA synthetase, to make ATP from acetyl-CoA. AMP-forming, acetyl-CoA synthetases were previously thought to function only in the activation of acetate to acetyl-CoA.

Familial adenomatous polyposis (FAP) is caused by germline mutations in the adenomatous polyposis coli (APC) gene. Two promoters, 1A and 1B, have been recognized in APC, and 1B is thought to have a minor role in the regulation of the gene. We have identified a novel deletion encompassing half of this promoter in the largest family (Family 1) of the Swedish Polyposis Registry. The mutation leads to an imbalance in allele-specific expression of APC, and transcription from promoter 1B was highly impaired in both normal colorectal mucosa and blood from mutation carriers. To establish the significance of promoter 1B in normal colorectal mucosa (from controls), expression levels of specific transcripts from each of the promoters, 1A and 1B, were examined, and the expression from 1B was significantly higher compared with 1A. Significant amounts of transcripts generated from promoter 1B were also determined in a panel of 20 various normal tissues examined. In FAP-related tumors, the APC germline mutation is proposed to dictate the second hit. Mutations leaving two or three out of seven 20-amino-acid repeats in the central domain of APC intact seem to be required for tumorigenesis. We examined adenomas from mutation carriers in Family 1 for second hits in the entire gene without any findings, however, loss of the residual expression of the deleterious allele was observed. Three major conclusions of significant importance in relation to the function of APC can be drawn from this study; (i) germline inactivation of promoter 1B is disease causing in FAP; (ii) expression of transcripts from promoter 1B is generated at considerable higher levels compared with 1A, demonstrating a hitherto unknown importance of 1B; (iii) adenoma formation in FAP, caused by impaired function of promoter 1B, does not require homozygous inactivation of APC allowing for alternative genetic models as basis for adenoma formation.

Aim: To determine the way in which Malmo University dental graduates perceive their problem-based dental education and evaluate their professional satisfaction. Method: The first five cohorts (graduating in years 1995–1999) of the problem-based curriculum were invited to participate. Of 166 graduates, 77% responded to a questionnaire comprising 20 questions on aspects of their dental education, professional situations and interest in postgraduate education. They were asked to rank their perception of their dental education and satisfaction with their professional situation on a visual analogue scale (VAS) with endpoints ranging from ‘Not at all’ (1) to ‘Very well’ (10). For other statements, the markings were made on a Likert scale from 1 (not important/not satisfied) to 5 (very important/very satisfied). There were also open-ended questions. Results: Most respondents perceived their education to prepare them well for a career in dentistry (median score VAS 8), and 90% rated above six on a VAS for their professional satisfaction as dentists. Importance and satisfaction were highly correlated with principles of the curriculum: holistic view, oral health, lifelong learning, integration between theory and clinic, and clinical competence. Forty-five per cent of the graduates noted the problem-based learning approach as the most valuable asset of their education, and 19% cited training in oral surgery as a deficit. Of the respondents, 77% expressed interest in specialist training and 55% in research education. Conclusion: Problem-based education was perceived to prepare graduates well for their profession, and their professional satisfaction was high.

Objectives: To survey definitions of bone tissue characteristics and methods of assessing them in studies of dental implant planning and placement. Material and methodology: Three databases were searched using specified indexing terms. Three reviewers selected from the titles and retrieved abstracts in accordance with inclusion and exclusion criteria. Descriptions of bone tissue characteristics (bone quality, density and quantity) used before or during dental implant placement were searched for and categorized. Results: The search yielded 488 titles. One hundred and fort-nine publications were selected and read in full text. One hundred and eight were considered relevant. There were many different definitions and classification systems for bone tissue characteristics and examination protocols. Approximately two-third of the included publications reported the Lekholm & Zarb classification system for bone quality and quantity. However, only four studies implemented the Lekholm & Zarb system as originally proposed. A few publications described bone quality in accordance with the Misch or Trisi and Rao classifications systems. Assessment methods were often described only briefly (or not at all in one-fifth of the publications). Only one study presented the diagnostic accuracy of the assessment method, while only two presented observer performance. Conclusion: The differing definitions and classification systems applied to dental implant planning and placement make it impossible to compare the results of various studies, particularly with respect to whether bone quality or quantity affect treatment outcomes. A consistent classification system for bone tissue characteristics is needed, as well as an appropriate description of bone tissue assessment methods, their diagnostic accuracy and observer performance.

An evidence-based (EB) approach has been a significant driver in reforming healthcare over the past two decades. This change has extended across a broad range of health professions, including oral healthcare. A key element in achieving an EB approach to oral healthcare is educating our practitioners, both current and future. This involves providing opportunities integrated within simulated and actual clinical settings for practitioners to learn and apply the principles and processes of evidence-based oral healthcare (EBOHC). Therefore, the focus of this discussion will be on ways in which EBOHC and associated research activities can be implemented into curricula, with the aim of improving patient care. This paper will initially define the scope of EBOHC and research, what these involve, why they are important, and issues that we need to manage when implementing EBOHC. This will be followed by a discussion of factors that enable successful implementation of EBOHC and research into curricula. The paper concludes with suggestions on the future of EBOHC and research in curricula.Key recommendations related to curricula include strengthening of the culture of a scientific approach to education and oral healthcare provision; complete integration of EBOHC into the curriculum at all levels; and faculty development to implement EBOHC based on their needs and evidence of effective approaches. Key recommendations to support implementation and maintenance of EBOHC include recognition and funding for high-quality systematic reviews and development of associated methodologies relevant for global environments; building global capacity of EBOHC researchers; research into improving translation of effective interventions into education and healthcare practice, including patient-reported outcomes, safety and harms, understanding and incorporation of patient values into EB decision-making, economic evaluation research specific to oral healthcare and effective methods for changing practitioner (faculty) behaviours; and extend access to synthesized research in 'user friendly' formats and languages tailored to meet users' needs. Realizing these recommendations may help to improve access to effective healthcare as a basic human right.

Biochemically, the syntrophic bacteria constitute the missing link in our understanding of anaerobic flow of carbon in the biosphere. The completed genome sequence of Syntrophus aciditrophicus SB, a model fatty acid- and aromatic acid-degrading syntrophic bacterium, provides a glimpse of the composition and architecture of the electron transfer and energy-transducing systems needed to exist on marginal energy economies of a syntrophic lifestyle. The genome contains 3,179,300 base pairs and 3,169 genes where 1,618 genes were assigned putative functions. Metabolic reconstruction of the gene inventory revealed that most biosynthetic pathways of a typical Gram-negative microbe were present. A distinctive feature of syntrophic metabolism is the need for reverse electron transport; the presence of a unique Rnf-type ion-translocating electron transfer complex, menaquinone, and membrane-bound Fe-S proteins with associated heterodisulfide reductase domains suggests mechanisms to accomplish this task. Previously undescribed approaches to degrade fatty and aromatic acids, including multiple AMP-forming CoA ligases and acyl-CoA synthetases seem to be present as ways to form and dissipate ion gradients by using a sodium-based energy strategy. Thus, S. aciditrophicus , although nutritionally self-sufficient, seems to be a syntrophic specialist with limited fermentative and respiratory metabolism. Genomic analysis confirms the S. aciditrophicus metabolic and regulatory commitment to a nonconventional mode of life compared with our prevailing understanding of microbiology.

To evaluate the influence of reimbursement system and organizational structure on oral rehabilitation of adult patients with tooth loss.Patient data were retrieved from the databases of the Swedish Social Insurance Agency. The data consisted of treatment records of patients aged 19 years and above claiming reimbursement for dental care from July 1, 2007 until June 30, 2009. Before July 1, 2008, a proportionately higher level of subsidy was available for dental care in patients 65 years and above, but thereafter the system was changed, so that the subsidy was the same, regardless of the patient's age. Prosthodontic treatment in patients 65 years and above was compared with that in younger patients before and after the change of the reimbursement system. Prosthodontic treatment carried out in the Public Dental Health Service and the private sector was also analyzed.Data were retrieved for 722,842 adult patients, covering a total of 1,339,915 reimbursed treatment items. After the change of the reimbursement system, there was a decrease in the proportion of items in patients 65 years and above in relation to those under 65. Overall, there was a minimal change in the proportion of treatment items provided by the private sector compared to the public sector following the change of the reimbursement system.Irrespective of service provider, private or public, financial incentive such as the reimbursement system may influence the provision of prosthodontic treatment, in terms of volume of treatment.

Aim To elucidate and compare patients' outcome preferences for removal and retention of mandibular third molars in Sweden and Wales. Subjects and method The subjects comprised patients referred and scheduled for removal of one or both mandibular third molars in Sweden and Wales. The multi-attribute utility (MAU) methodology was applied to study patients' preferences for outcomes of removal and retention of the mandibular third molar. Results Relative weighting of domains was similar in the two countries. 'Home and social life' received the highest relative weighting in Sweden and 'general health and wellbeing' in Wales. 'Your appearance' received the lowest relative weighting in both countries. In both Sweden and Wales operative jaw fracture was considered to be the outcome with most impact and dentigerous cyst and imbricated incisors the least impact. Outcome ranking was similar in both countries and operative outcomes were considered by patients to be more detrimental to health than retention outcomes. Conclusions This comparison showed that patients' preferences in Sweden and Wales were similar and that the outcomes of surgery were considered worse after third molar removal than retention. Patient-orientated treatment decisions were less subject to variation than clinician-orientated decisions.

it was concluded that there is little evidence for the effectiveness of CPD for the oral health team. The main recommendation from this study is that a systematic review of the effectiveness of CPD in improving the performance of the oral health team and patient based outcomes be undertaken. A range of other research questions was also identified including: how can CPD be best matched to clinicians’ needs rather than demands?

There appears to have been little previous research interest in continuing professional development* (CPD) of dentists and the oral health team. This paper presents data and information on the following aspects of CPD in 17 countries in Asia, Australasia, Europe and North America: availability of different types of CPD, its providers, data on uptake of CPD courses and activities, and funding of CPD. The results indicate that lectures and hands-on skills courses were held in all 17 countries but the use of the Internet to deliver CPD was by no means universal. CPD was funded from a variety of sources including universities, governments and commercial companies. However, the only universal source of funding for CPD was dentists themselves. Data on participation were available from only three countries. Research issues based on these results will be listed in a second paper.

To examine the strategies that general dental practitioners (GDPs) use to administer antibiotic prophylaxis and to study the agreement between the administration strategies of GDPs and local recommendations.Postal questionnaires in combination with telephone interviews were used. Two hundred GDPs in two Swedish counties, Skåne and Orebro, were asked to participate. The response rate was 51% (n = 101). The GDPs were presented with eight simulated cases of patients with different medical conditions for which antibiotic prophylaxis might be considered necessary when performing dental procedures (scaling, tooth removal, root canal treatment). The administration strategies of the GDPs were compared with local recommendations.In general, the variation in the administration strategies of the GDPs was large. For two medical conditions, type 1 diabetes that was not well controlled and hip prosthesis, significantly more GDPs in Skåne than in Orebro administered antibiotic prophylaxis for tooth removal. Agreement between the administration strategies of the GDPs and local recommendations was low. Differences between the two counties were non-significant. Furthermore, within Orebro, GDPs who did not have formal access to local recommendations did not differ in their administration strategies from those who did. The choice of substance was seldom in agreement with the substance recommended, while the majority followed the recommended duration of treatment.Although recommendations existed, their impact appeared to be limited. This is significant, since the implementation of recommendations is crucial in making clinical practice more effective and in promoting the health of patients.

The detection of postmenopausal women with low bone mineral density (BMD) is an important strategy to reduce the incidence of osteoporotic fracture. Recent studies suggested that incidental findings on dental panoramic radiographs may be used as a tool to detect women with low BMD. However, little is known whether this finding is sufficiently assessed by untrained general dental practitioners (GDPs). The purpose of this study was to investigate: (1) the observer agreement and (2) the diagnostic efficacy in detecting women with low BMD, when untrained GDPs assess the appearance (normal or eroded) of the mandibular inferior cortex on dental panoramic radiographs of postmenopausal women. Twenty-seven GDPs were asked to classify the appearance of the mandibular inferior cortex on dental panoramic radiographs of 100 postmenopausal women who had completed BMD assessments of the lumbar spine and of the femoral neck. Intra-and inter-observer agreements were analyzed with kappa statistics. The diagnostic efficacy (sensitivity, specificity and predictive values) was analyzed by comparing two groups classified by the mandibular inferior cortex (women with normal and women with eroded mandibular inferior cortex) with those classified by BMD (women with normal BMD and women with osteopenia or osteoporosis). The mean sensitivity and specificity were 77% and 40%, respectively, when BMD of the lumbar spine was used as standard and 75% and 39%, respectively, when BMD of the femoral neck comprised the standard. Nineteen untrained GDPs (70%) presented a moderate to almost perfect intra-observer agreement. We conclude that dental panoramic radiograph may be used in clinical dental practice to identify postmenopausal women who have undetected low BMD and should undergo further testing with bone densitometry.

An exploration is undertaken of the issues surrounding the assessment of attitudes in undergraduate dental programmes with a view to considering whether such an assessment is worthwhile. This paper addresses five questions: What are attitudes?; Why focus on them?; Can they be changed?; Can they be taught?; and How can they be assessed? The evidence and supporting arguments indicate that attitudes may be defined; there are cogent reasons for assessing them; they do change and they are taught; it is possible to assess them. The assessment of attitudes is not only worthwhile, it is essential.

To compare academic progress and performance of students admitted through two admission systems and to analyse the predictive power of different components in an alternative admission.The subjects were students admitted to the dental programme at Malmö University, Sweden. The grade admission group was admitted on grades from secondary school (n = 126) and the alternative admission group via an alternative admission procedure (n = 157). The alternative admission procedure consisted of the following components: problem-solving matrices, spatial capacity tested with folding and tin models, manual dexterity, capacity for empathy and interview. Comparisons were made for academic progress (dropouts from the programme and study rate) and academic performance (examinations failed and outcomes of a comprehensive clinical examination). Spearman correlation was calculated for each component of the alternative admission procedure and academic progress as well as academic performance. Multivariate analyses were also carried out.Compared to the grade admission group, the alternative admission group presented lower rate of dropouts (3% vs. 20%, P0.001) and a larger proportion graduated within the expected time (88% vs. 60%, P0.01). There was no difference between the groups concerning academic performance. Capacity of empathy was correlated with study rate and outcomes of the clinical examination. The matrices predicted low proportion failed examinations and high students' self-assessments in the clinical examination. Predictive power of folding was limited and so was that of the interview. Manual dexterity was not correlated with academic progress or performance.Results support further development of admission selection criteria, particularly emphatic capacity that predicts important student academic achievements.

Somatic mutations in the POLE gene encoding the catalytic subunit of DNA polymerase epsilon have been found in sporadic colorectal cancers (CRCs) and are most likely of importance in tumour development and/or progression. Recently, families with dominantly inherited colorectal adenomas and colorectal cancer were shown to have a causative heterozygous germline mutation in the proofreading exonuclease domain of POLE. The highly penetrant mutation was associated with predisposition to CRC only and no extra-colonic tumours were observed. We have identified a mutation in a large family in which the carriers not only developed CRC, they also demonstrate a highly penetrant predisposition to extra-intestinal tumours such as ovarian, endometrial and brain tumours. The mutation, NM_006231.2:c.1089C>A, p.Asn363Lys, also located in the proofreading exonuclease domain is directly involved in DNA binding. Theoretical prediction of the amino acid substitution suggests a profound effect of the substrate binding capability and a more severe impairment of the catalytic activity compared to the previously reported germline mutation. A possible genotype to phenotype correlation for deleterious mutations in POLE might exist that needs to be considered in the follow-up of mutation carriers.

Objectives In recent years, several critical outcome studies concerning the prophylactic removal of mandibular third molars have been published. These would appear to motivate a more restrictive approach today as compared with 10 years ago. The aim of the present study was to examine dentists' decisions on the prophylactic removal of impacted mandibular third molars over a 10-year period. Methods Thirty-six cases were selected so as to represent an equal distribution of males and females, ages, angular position and degree of impaction of the molar. Twenty-six general dental practitioners (GDPs) and 10 oral surgeons judged the same cases on two occasions 10 years apart. Results Calculated for each category of dentists, there was no significant difference in the mean number of molars designated for removal between the two occasions. Two GDPs and three oral surgeons presented a higher removal rate, whereas five GDPs presented a lower removal rate on the second occasion as compared to the first one. The dentists presented a considerable interindividual variation in removal rate, between 0 and 22 molars on the first occasion and between 0 and 25 molars on the second occasion. Conclusion In the decisions on prophylactic removal of mandibular third molars, there has been no change over the last 10 years towards a more noninterventionist attitude. Thus, the dentists seem not to have been influenced by the evidence that this intervention is not cost-effective.

The number of molars selected for prophylactic removal varies widely among general dental practitioners and oral surgeons. To understand the basis for such variations, we investigated two hypotheses: (1) Individual judgment strategies will differ concerning the use of cues (items of information), and (2) few dentists will integrate the cues according to evidence in the literature. To analyze 30 general dental practitioners' (GDPs) and 10 oral surgeons' use of cues in the judgment preceding the treatment decision, we used the Brunwik's lens as a conceptual model. The cues were the patient's age, and the angular position and the degree of impaction of the molar. The clinical situation was simulated by written case descriptions. The proportion of variation explained by the cues and their combinations (total model) varied between 61% and 100% and between 4% and 76% as main effects. Two GDPs and one oral surgeon integrated the cues additively, i.e., any of the cues is independent of the other cues in the judgment. In general, the dentists integrated the cues interactively, i.e., the impact of one cue depends on the levels of some other cues. Even though most variations in judgments were accounted for by the cues, the dentists did not integrate the cues according to evidence in the literature and lacked insight into their decision-making thought processes.

The aim was to study patients' preferences about outcomes of mandibular third molar removal and non-removal using multi-attribute utility (MAU) methodology. The study comprised three stages. Stage 1: Elicitation of domains, i.e. main areas of patients' lives which could be affected by third molar removal and non-removal. Stage 2a: Interdomain weighting was obtained by relative weighting of the domains elicited in Stage 1. Stage 2b: Intradomain weighting obtained by patients' designation of values for different health states of each domain. Stage 3: Rating of outcomes. The patients were asked to imagine experiencing a variety of outcomes of mandibular third molar removal and non-removal, described in 19 short vignettes. The numbers of patients interviewed for the three stages were 30, 78, and 55, respectively. Five domains were identified. The mean relative weightings were approximately equal for the domains "Home and social life" and "General health and well-being", followed in order of importance by 'Job and studies" and "Health and comfort of mouth, teeth and gums". "Your appearance" received the lowest mean relative weighting. The vignette, which described the presence of a fluid-filled sac and suggested that this tooth must be removed, received the highest mean preference (least effect on patients' lives). The lowest mean preference (most effect on patients' lives) was generated by the vignette, which stated that the jaw was broken and that the teeth must be wired together for 6 weeks. We conclude that, from the patient's perspective, outcomes of non-removal were preferable to outcomes of mandibular third molar removal.

Objectives: To review publications in dentistry of decision analyses during the last 30 years. Methods: A systematic review of the English literature from 1969 to 1998 was performed using specified indexing terms. The number of retrieved articles in dentistry was compared with the number of articles in medicine. The quality of articles in dentistry presenting a decision tree with utilities and a sensitivity analysis was judged using a published peer review process. We report weaknesses of the analyses together with selected applications. Results: Sixty-seven articles were published on decision analysis in dentistry. Whilst the number of articles published in medicine has accelerated there has been a decline in the last four years in dental publications. Only 22 of the articles in dentistry presented a decision analysis with utilities and a sensitivity analysis. Conclusions: Current weaknesses of the decision analyses reported were: opaque basic assumptions in the description of the analysis, lack of data on patient preferences and of reliable data on the chances of the long-term effects and side effects of intervention together with an absence of sensitivity analyses. The decision analysis approach complements that of “evidence-based health care” by enabling the best empirical evidence to be used in clinical practice. Formal methods such as decision analysis will promote the rational use of existing knowledge. For it to do this the quality of research data will have to improve in dentistry. Furthermore decision analysis is important in education to demonstrate explicitly how decisions might be arrived at and improved.

A new undergraduate dental curriculum was introduced in Malmö in 1990 which is based on problem-based learning (PBL). The principles of PBL are strongly influenced by evidence from cognitive psychology and they form the educational strategy throughout the whole curriculum. Two further essential principles underpin the curriculum: a holistic attitude to patient care, and the promotion of oral health. Basic sciences and clinical dentistry are integrated within a structure based on oral conditions prevalent in the community. Students are encouraged to build their new knowledge, understanding and skills into the context of what they have already learned. This approach is facilitated by the presentation of conceptual models, one of which, The Oral Ecosystem is described in detail. The educational programme also gives students opportunities to learn in the clinical context from an early stage, and we endeavour to promote a scientific attitude from the very beginning of the programme. This paper describes the curriculum at three organisational levels (whole curriculum, single course, individual week).

The purpose was to investigate if antigenic fragments of aggrecan and cartilage oligomeric matrix protein (COMP) are detectable by enzyme-linked immunosorbent assay in lavage fluids from the temporomandibular joint (TMJ) and to examine if the relative content of these cartilage markers changes during development of osteoarthrosis (OA) after diskectomy. Lavage fluid was obtained at surgery and 6 months postoperatively in 13 patients. Computed tomography or magnetic resonance imaging was without evidence of hard-tissue changes prior to surgery in all patients. In 9 of the patients, sufficient material for analysis was obtained at both examinations. Aggrecan and COMP were detectable in all but 2 fluids, in which the COMP levels were below detection limit. The aggrecan/COMP ratio increased in all 9 patients during the 6-month period, indicating increased release of aggrecan relative to COMP fragments. The changed aggrecan/COMP ratio possibly reflects increased cartilage turnover during development of OA. Changes compatible with OA were present on computed tomography in all cases at the 6-month follow-up. This study shows that the lavage procedure is feasible for obtaining synovial fluid from the TMJ for immunochemical analyses of tissue-derived macromolecules.

The aim was to compare the observer performance of direct digital radiography, with and without image processing, with that of conventional radiography, for the detection of periapical bone lesions. For 50 patients, a conventional periapical radiograph using E-speed film was taken. Then, a direct digital image of the same area was made. The images presenting the periapical bone tissue of 59 roots were assessed by seven observers using a 5-point confidence scale. The digital images were first presented as original images, with default contrast and brightness set by the computer system. Following this, the observers were allowed to use the processing facilities for greyscale treatment. The results for original and processed direct digital images and for conventional radiographs were compared by Receiver Operating Characteristic (ROC) analysis. The area under the ROC curve, calculated as P(A) value, was 0.88 for conventional film, 0.82 for original digital images and 0.78 for processed images. Corresponding Az values were slightly higher, 0.89, 0.84 and 0.81. Statistically significant differences between ROC areas calculated as P(A) values for the methods were found. Comparison between Az values showed no significant differences between conventional radiographs and original digital images, whereas the difference between Az values for original and processed digital images was still significant. It was concluded that conventional film radiography performed slightly better for the detection of periapical bone lesions than direct digital radiography and that image processing did not improve the observer performance.

Purpose: We have investigated the requirements, design, implementation, and operation of a computer-controlled medical accelerator with multileaf collimator (MLC), integrated with a radiation treatment-planning system (RTPS), and we report on the performance, benefits, and lessons learned from this experience. Methods and Materials: In 1984 the University of Washington installed a computer-controlled radiation therapy machine (the Clinical Neutron Therapy System, or CNTS) with a multileaf collimator. Since the beginning of operation the control system computer has been connected by commercially available network hardware and software to three generations of radiation treatment-planning systems. Semiautomated setup and completely computerized check and confirm were incorporated into the system from the beginning of clinical operation in 1984. The system cannot deliver a patient treatment without a computer-prepared treatment plan. Results: The CNTS has been in use for routine patient treatments for over 11 years. The cost of the network &%&ion and software was an insignificant fraction of the facility cost. Operation has been efficient and reliable. Of the 441 machine-related session reschedulings (out of 18,432 sessions total) during the past 9 years, only 20 were due to problems with data transfer between the RTPS and CNTS, associated primarily with two incidents. Close integration with the treatment-planning system allows complex treatments to be delivered. Dramatic evolution of the departmental treatment-planning system has not required any changes or redesign of either the accelerator control system or the network connection. Conclusions: Our experience shows that a large degree of automation is possible with reasonable effort, by using well-known software and hardware design strategies. The lessons we have learned from this can be carried over into photon therapy now that photon accelerators with MLC facilities are commercially available. 0 1997 Elsevier Science Inc.

OBJECTIVES To analyse the possible correlation between the trabecular bone pattern of the edentulous mandible visualized by panoramic radiography and the bone mineral density (BMD) measured by computed tomography (CT). METHODS Panoramic radiography and CT were performed on 28 patients with edentulous mandibles. The trabecular bone pattern of 47 regions on the panoramic radiographs was classified into one of five grades. BMD was measured within circular regions of interest on the axial CT images in the corresponding trabecular area. The gradings were correlated with the CT values using one-way analysis of variance. RESULTS There was a significant correlation between the grade of the trabecular bone pattern and the BMD (P < 0.0001). CONCLUSION The proposed classification for the trabecular bone pattern on panoramic radiographs might be a useful aid for the evaluation of the edentulous mandible prior to implant placement.

The aim was to develop a reproducible method for bone histomorphometry with the aid of a computerized image analysis program, and to examine the variation when assessing the total and the trabecular bone volume. Histologic sections of 18 temporomandibular joint autopsy specimens were read interactively using a cursor. The two parameters total bone volume and trabecular bone volume, of the condyle and the temporal component respectively, were estimated 2 x by 1 observer using 3 different threshold settings: an automatic, a semi-automatic and a manual technique. The threshold was based on the gray-scale distribution of the image. 2 observers read the same sections with the aid of the semi-automatic technique. The intra-observer variation expressed as coefficient of variation ranged between 1.9% and 7.1% for the different parameters, when the automatic threshold setting technique was employed, and between 2.8% and 8.7% with the semi-automatic technique. The manual technique resulted in a high intra-observer variation with a coefficient of variation between 5.2% and 19.9%. There was a systematic difference between the estimates of the 2 observers. In general, intra- and inter-observer variation was higher in the temporal component than in the condyle. The inter-section variation was moderate, the coefficient of variation ranging from 3.8% to 11.1%. The automatic and semi-automatic techniques resulted in comparable intra-observer variation, with a lower bias in the estimates of the semi-automatic technique. By letting one observer apply the semi-automatic technique, it was possible to achieve fast and reproducible analysis of the total and trabecular bone volume.

The aim was to study how three cues (patient's age and angular position and degree of impaction of the molar) were distributed among removed mandibular third molars associated with pathologic conditions and to compare these results with dentists' treatment decisions in another group of molars consisting of asymptomatic mandibular third molars, as mediated by the same cues. The overall agreement was fairly high between the dentists' treatment decisions and the removal rate among the molars subjected to removal. Thus, molars partially covered by soft tissue in patients aged 19 to 40 years had a high removal rate, and molars totally covered by bone tissue had the lowest removal rate in accordance with the dentists' treatment decisions. There were some exceptions. For example, molars partially covered by soft tissue in horizontal and mesioangular positions were rated higher by the dentists than the removal rates indicated. Distoangular molars in patients aged 26 to 40 years had the highest removal rate but a considerably lower order according to the dentists' decisions. Scientific evidence indicates that molars in mesioangular and horizontal positions present a low risk and molars in distoangular position present the highest risk of developing pathologic conditions, compared with other angular positions.

To elucidate the significance of the radiographic finding of a concavity of the posterior surface of the temporomandibular condyle.Three clinical cases with a concavity were followed up clinically and radiographically. A total of 39 temporomandibular joint (TMJ) autopsy specimens were examined by corrected sagittal tomography and seven condyles with a concavity of the posterior surface found. They were analysed microscopically together with three joints with a normal, rounded condyle.At follow-up tomography, two of the clinical cases revealed no change while the third patient had erosive changes after 7 months. The microscopic findings of the autopsy specimens varied. The articular cartilage in three of the seven joints with a concavity was similar to that in the normal condyles. The outer surface of the articular cartilage was sometimes uneven and the cartilage thickened, with an irregular junction between the articular cartilage and subchondral bone. In three joints the cartilage in the concavity had been replaced by granulation tissue. All seven joints had increased cellular activity in the concavity.The radiographic finding of a concavity in the posterior surface of the condyle is not specific. When small and well-defined it is indicative of remodelling and of osteoarthrosis when larger and with a diffuse outline.

Objectives. The diagnostic accuracy of direct digital radiography for the detection of small experimentally made periapical lesions was evaluated. A comparison was made between original digital images and images processed with different enhancement facilities of the digital system. Study design. Seven observers assessed the digital images in original mode and after individual image treatment. The diagnostic accuracy was calculated. The processing functions used by the observers were recorded, and the effect of processing was evaluated. Results. The overall diagnostic accuracy was not different for the two image modes. Neither were the individual results of the observers different. The image processing was most effective when alterings of contrast and brightness were used. More complicated processing procedures had less effect on the diagnostic accuracy. Conclusions. Image processing of direct digital images of high quality has a limited effect on the diagnostic accuracy. Basic processing functions, that is, alterings of contrast and brightness, were preferred for the detection of periapical lesions.

Objective To study the diagnostic outcome of periapical radiography in the assessment of the bone trabecular pattern of the mandible. Study Design Mandibular autopsy specimens were radiographed. Seven observers assessed the radiographs with the aid of a proposed classification with and without reference images and the classification presented by Lekholm and Zarb. Accuracy was estimated on the basis of morphometric measurements of trabecular bone volume. Observer agreement was calculated as the estimated probability of agreement between and within observers and as Kappa index. Results With the classification proposed by us, the overall accuracy was 58% with and 50% without reference images. The accuracy for assessing dense trabeculation was higher (78%) than that for sparse trabeculation (28%). The accuracy of the proposed classification by Lekholm and Zarb was not possible to evaluate. The interobserver agreement varied between 49% and 64% and the intraobserver agreement between 75% and 86%. Conclusions A new classification with reference images is recommended to assess the trabecular pattern in periapical radiographs before implant treatment.

Objective To measure the prevalence of disease of mandibular third molars referred for removal and to estimate the risk for development of pathoses for two cues. Study design A prospective cohort study on molars subjected to removal was performed. The prevalence of different diseases and the patient's age, angular position, and degree of impaction of the molars were registered. Odds ratio for molars with different positions and impaction states were estimated. Results Pericoronitis was found in 64% of cases, caries in the third molar in 31%, periodontitis in association with 8%, caries in the second molar in 5%, and root resorption of the second molar with 1% of the molars with pathoses. Odds ratio was highest for distoangular molars (5.8) and for molars partially covered by soft tissue (6.7). Conclusions The odds ratio is about 22 and 34 times higher for molars partially covered by soft tissue than for molars completely covered by soft or bone tissue. For distoangular molars the odds ratio is 5 to 12 times higher than for molars in other positions.