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While immune checkpoint blockade leads to potent antitumor efficacy, it also leads to immune-related adverse events in cancer patients. These toxicities stem from systemic immune activation resulting in inflammation of multiple organs, including the gastrointestinal tract, lung, and endocrine organs. We developed a dual variable domain immunoglobulin of anti-CTLA4 antibody (anti-CTLA4 DVD, where CTLA4 is defined as cytotoxic T lymphocyte–associated antigen-4) possessing an outer tumor-specific antigen-binding site engineered to shield the inner anti-CTLA4–binding domain. Upon reaching the tumor, the outer domain was cleaved by membrane type-serine protease 1 (MT-SP1) present in the tumor microenvironment, leading to enhanced localization of CTLA4 blockade. Anti-CTLA4 DVD markedly reduced multiorgan immune toxicity by preserving tissue-resident Tregs in Rag 1(–/–) mice that received naive donor CD4(+) T cells from WT C57BL/6j mice. Moreover, anti-CTLA4 DVD induced potent antitumor effects by decreasing tumor-infiltrating Tregs and increasing the infiltration of antigen-specific CD8(+) T lymphocytes in TRAMP-C2–bearing C57BL/6j mice. Treg depletion was mediated through the antibody-dependent cellular cytotoxicity (ADCC) mechanism, as anti-CTLA4 without the FcγR-binding portion (anti-CTLA4 DANA) spared Tregs, preventing treatment-induced toxicities. In summary, our results demonstrate an approach to anti-CTLA4 blockade that depletes tumor-infiltrating, but not tissue-resident, Tregs, preserving antitumor effects while minimizing toxicity. Thus, our tumor-conditional anti-CTLA4 DVD provides an avenue for uncoupling antitumor efficacy from immunotherapy-induced toxicities.

Objective To understand the impact of the coronavirus disease 2019 (COVID-19) pandemic on parental perceptions of health behaviors and food insecurity among children with overweight and obesity living in San Francisco and to assess the relationship between food insecurity and dietary intake during the pandemic. Methods Parents of children ages 4 to 12 in San Francisco with body mass index ≥85th percentile measured at a clinic visit at a Federally Qualified Health Center or academic practice from January 1st to March 15th, 2020 were eligible to participate. Parents completed a survey reporting on child health behaviors and household food insecurity prior to and since the start of the pandemic. Survey items were abstracted from validated surveys with adaptations. Regression models evaluated associations between food insecurity and dietary intake variables. Results Most participants (n = 145) were publicly insured (90%), Latino (77%), and spoke Spanish at home (70%). Parents perceived that child mean daily nonacademic screen time was higher during the pandemic compared to before (3.8 hours vs 1.6 hours). Mean daily physical activity was reported to be lower compared to prior to the pandemic (1 hour vs 1.8 hours). On average, reported bedtime shifted 1.6 hours later. Food insecurity increased significantly but was not associated with intake of fruits, vegetables, sugar-sweetened beverages, or foods with added sugar during the pandemic. Conclusions Parents of children with overweight or obesity in San Francisco perceive increased child screen time, decreased physical activity and later bedtimes during the COVID-19 pandemic. Findings suggest a need for policies that support healthy lifestyle behaviors among low-income children during the pandemic.

Know the risk factors, choose from among 3 validated screening tools, and use a trauma-informed approach with those likely involved in trafficking.

Non-syndromic orofacial clefts encompass a range of morphological changes affecting the oral cavity and the craniofacial skeleton, of which the genetic and epigenetic etiologic factors remain largely unknown. The objective of this study is to explore the contribution of underlying dentofacial deformities (also known as skeletal malocclusions) in the craniofacial morphology of non-syndromic cleft lip and palate patients (nsCLP). For that purpose, geometric morphometric analysis was performed using full skull cone beam computed tomography (CBCT) images of patients with nsCLP (n = 30), normocephalic controls (n = 60), as well as to sex- and ethnicity- matched patients with an equivalent dentofacial deformity (n = 30). Our outcome measures were shape differences among the groups quantified via principal component analysis and associated principal component loadings, as well as mean shape differences quantified via a Procrustes distance among groups. According to our results, despite the shape differences among all three groups, the nsCLP group shares many morphological similarities in the maxilla and mandible with the dentofacial deformity group. Therefore, the dentoskeletal phenotype in nsCLP could be the result of the cleft and the coexisting dentofacial deformity and not simply the impact of the cleft.

The regular collection of 3-dimensional (3D) imaging data is critical to the development and implementation of accurate predictive models of facial skeletal growth. However, repeated exposure to x-ray-based modalities such as cone-beam computed tomography has unknown risks that outweigh many potential benefits, especially in pediatric patients. One solution is to make inferences about the facial skeleton from external 3D surface morphology captured using safe nonionizing imaging modalities alone. However, the degree to which external 3D facial shape is an accurate proxy of skeletal morphology has not been previously quantified. As a first step in validating this approach, we tested the hypothesis that population-level variation in the 3D shape of the face and skeleton significantly covaries.We retrospectively analyzed 3D surface and skeletal morphology from a previously collected cross-sectional cone-beam computed tomography database of nonsurgical orthodontics patients and used geometric morphometrics and multivariate statistics to test the hypothesis that shape variation in external face and internal skeleton covaries.External facial morphology is highly predictive of variation in internal skeletal shape ([Rv] = 0.56, P0.0001; partial least squares [PLS] 1-13 = 98.7% covariance, P0.001) and asymmetry (Rv = 0.34, P0.0001; PLS 1-5 = 90.2% covariance, P0.001), whereas age-related (r(2) = 0.84, P0.001) and size-related (r(2) = 0.67, P0.001) shape variation was also highly correlated.Surface morphology is a reliable source of proxy data for the characterization of skeletal shape variation and thus is particularly valuable in research designs where reducing potential long-term risks associated with radiologic imaging methods is warranted. We propose that longitudinal surface morphology from early childhood through late adolescence can be a valuable source of data that will facilitate the development of personalized craniodental and treatment plans and reduce exposure levels to as low as reasonably achievable.

Purpose Orthognathic surgery can induce changes in airway volume. The aim of this study was to determine whether there is a correlation of surgical movement of the maxilla or mandible to airway volume changes. Materials and Methods This was a prospective cohort study and the sample was composed of patients undergoing single-jaw orthognathic procedures from 2004 through 2007. Cone-beam computed tomograms were obtained before surgery (T0), immediately after surgery (T1), and at least 6 months after surgery (T2). The airway was segmented from 3-dimensional images and identified as the whole airway, consisting of the naso-, oro-, and hypopharynx. The volumetric percentage of change of the airway between time points was compared and correlated to the surgical movements using paired t test and cubic regression analysis. The level of statistical significance was set at a P value less than or equal to .05. Results The sample was composed of 33 patients. Sixteen patients underwent maxillary advancement with mean advancement of 5.4 mm (3 to 8 mm), 13 underwent mandibular advancement with mean advancement of 8.0 mm (5 to 15 mm), and 4 underwent mandibular setback of 4.0 mm. For maxillary advancement at T1, volume percentages of change for the whole airway and the naso-, oro-, and hypopharynx were 18.4 ( P ≤ .05), 53.8 ( P ≤ .05), 26.3, and 5.5%, respectively, and at T2, the changes were 10.0, 46.7 ( P ≤ .05), 6.8, and 1.0%, respectively. For mandibular advancement at T1, volume percentages of change were 34.6 ( P ≤ .05), 26.1, 54.1 ( P ≤ .05), and 17.4%, respectively, and at T2, the changes were 15.0 ( P ≤ .05), −3.7, 23.5 ( P ≤ .05), and 12.1%, respectively. There were no meaningful long-term airway changes with mandibular setback. Conclusion The study results suggest that there might be an anatomic limit to pharyngeal airway expansion associated with single-jaw orthognathic surgery.

In der Praxis ist es eine der grosten Herausforderungen, einen kieferorthopadischen Fall einmal mit Brackets zu bekleben und dann samtliche Zahnwurzeln parallel zueinander auszurichten. Es ist beinahe immer erforderlich, nicht parallel zueinander stehende Zahnwurzeln zu erkennen und die Brackets neu zu positionieren. Stehen Zahnwurzeln zu eng beisammen, kann es zur Schadigung des interproximalen Knochens kommen. Im Rahmen der vorliegenden Studie wurde in einem ersten Schritt die Genauigkeit bei der Bestimmung der Angulation der Zahne mithilfe eines Typodont-Modells untersucht. Dazu wurde die Langsachse jedes Zahnes mit 2 radiopaken Markierungen gekennzeichnet. Anschliesend wurden von diesem Modell eine Panoramaschichtaufnahme und ein digitales Volumentomogramm angefertigt und vermessen. Im Vergleich zur Panoramaschichtaufnahme bildete die digi­tale Volumentomografie die mesiodistale Angulation der Zahne genauer ab. Im klinischen Teil der Studie wurden Panoramaschichtaufnahmen und digitale Volumentomogramme von 25 Patienten der Abteilung fur Kieferorthopadie der University of California in San Francisco ausgewertet. Insgesamt 56 Bilder (50 Originale und 6 Duplikate) wurden randomisiert und individuell von 10 Kieferorthopaden untersucht. Die Frage dabei lautete: „Welche Zahne mussen neu ausgerichtet werden, damit die Zahnwurzeln parallel zueinander stehen?“. Mit den beiden bildgebenden Verfahren wurden unterschiedliche Zahne, unterschiedliche Zahnstellungen und unterschiedliche Richtungen fur die Neuausrichtung ermittelt. Die grosten Unterschiede ergaben sich fur die oberen seitlichen Schneidezahne, die Eckzahne und die zweiten Pramolaren sowie die unteren ersten Pramolaren. Die Panoramaschichtaufnahme bildete die oberen seitlichen Schneidezahne und die Eckzahne zu weit mesial geneigt ab und legte damit eine Kippung der Wurzeln nach distal nahe. Die oberen Pramolaren und die unteren zweiten Pramolaren wurden demgegenuber zu weit distal geneigt abgebildet. In der Praxis kann die Verwendung von Panoramaschichtaufnahmen also dazu fuhren, dass die falschen Zahne neu ausgerichtet und andere Zahne ubersehen werden. Bei der Frage nach der diagnostischen Sicherheit bei den beiden bildgebenden Verfahren gab die Mehrheit der Bearbeiter an, sich bei ihren diagnostischen Entscheidungen mit der digitalen Volumentomografie sicherer zu fuhlen.

OBJECTIVE: To validate the accuracy of a cone-beam computed tomography (CBCT)–guided surgical stent for orthodontic mini-implant (OMI) placement by quantitatively evaluating the difference between CBCT-prescribed and actual position of mini-implants in preoperative and postoperative CBCT images. MATERIALS AND METHODS: A surgical stent was fabricated using Teflon-Perfluoroalkoxy, which has appropriate biological x-ray attenuation properties. Polyvinylsiloxane impression material was used to secure the custom-made surgical stent onto swine mandibles. CBCT scanning was done with the stent in place to virtually plan mini-implants using a three-dimensional (3D) software program. An appropriate insertion point was determined using 3D reconstruction data, and the vertical and horizontal angulations were determined using four prescribed angles. A custom-designed surveyor was used to drill a guide hole within the surgical stent as prescribed on the CBCT images for insertion of 32 OMIs. The mandibles with a surgical stent in place were rescanned with CBCT to measure the deviations between the virtual planning data and surgical results. RESULTS: The difference between the prescribed and actual vertical angle was 1.01 ± 7.25, and the horizontal difference was 1.16 ± 6.08. The correlation coefficient confirms that there was no intrarater variability in either the horizontal (R = .97) or vertical (R = .74) vectors. CONCLUSIONS: The surgical stent in this study guides mini-implants to the prescribed position as planned in CBCT. Since the statistical difference was not significant, the surgical stent can be considered to be an accurate guide tool for mini-implant placement in clinical use.

Introduction In this study, using a cone-beam computed tomography system, we evaluated the airways of 30 adults. Methods The shapes of the 3-dimensional volume of the airway were analyzed and compared among the subjects by using surface superimposition software techniques. Results The airway had the greatest variability in the hypopharynx, in the region below the epiglottis, and above the vocal folds. Moderate variation was apparent at the nares, behind the soft palate, and at the base of the tongue. Conservation of form was seen at the central portion of the nasal airway surrounding the inferior turbinate. Conclusions The potential for comparing the shape of the airway among subjects is possible.

Cone beam computed tomography (CBCT) provides a new method to evaluate the craniofacial region. The goal of our project was to introduce into the predoctoral dental curriculum a student-initiated, student-led introduction to CBCT and how to use it, with minimal expenditure of financial resources. A third-year student worked with two faculty members to design a course in which a small number of third-year students would lead a small group of second-year students. The first approach involved each small group of second-year dental students discussing one clinical case in which the patient’s CBCT record was included. Representatives of each of the ten small groups presented the patient and that patient’s clinical problem (e.g., an impacted tooth) to the entire class as well as demonstrating the superiority and limitations of using CBCT in clinical dentistry. The second approach also used small-group meetings led by third-year dental students, but paired two second-year dental students as a team to present the patient’s CBCT data in the small-group setting. There were five teams each presenting a different type of patient as assessed only from the CBCT data. The first model focused on the problem (e.g., an impacted tooth), while the second model focused on how to evaluate and use CBCT scans to determine the patient’s primary problem. Based on surveys conducted at the end of each course, the majority of students felt they had gained a better understanding of CBCT.

The purpose of this study was to quantify the consistency and precision of locating three-dimensional (3D) anatomic landmarks. The hypotheses tested are that these landmarks have characteristic and variable error patterns associated with their type and location. The consistency and precision of nine orthodontists identifying 32 landmarks of 19 patients were quantified. The cone beam computed tomography (CBCT) data were acquired using a Hitachi CB MercuRay system. Prior to the study, all examiners were calibrated with respect to the definitions of the landmarks and on the use of the software program (Dolphin) for identifying the landmarks. In addition, a reference guide was provided that had the definitions and sample images of the landmarks. Data were collected in spreadsheets as x, y, and z co-ordinates and statistically analysed to determine the mean and standard deviation (SD). The mean location for a given landmark on a given patient served as the reference point. The mean of the distances from the reference point was used as the consistency, while the SD of this mean was used as a measure of precision. The error in the x, y, and z planes was calculated in order to determine the specific characteristics of each landmark. The consistency in landmark location and precision did not differ significantly among the nine examiners. Sella turcica was the most consistently (0.50 mm) and most precisely (0.23 mm) identified anatomic landmark. The most inconsistent landmark was porion-right (2.72 mm) and the most imprecise landmark was orbitale-right (1.81 mm). Due to the lack of even distribution of the errors, careful use of these landmarks for analysis purposes is needed.

Orthodontic diagnosis is currently based primarily on two-dimensional (2D) measurements. The development of maxillofacial cone beam X-ray computed tomography (CBCT) has promoted the use of three-dimensional (3D) measurements for orthodontic diagnosis. This technology is also expected to generate new analytic methods aiming at establishing optimal occlusion according to the individual's maxillary shape and function. However, during the transitional stage from 2D to 3D measurements, it is necessary to relate 3D data to existing data analysis methods (e.g., lateral cephalogram) for the assessment of skeletal and dental relationship. Our objectives were to develop a new cephalometric analysis method based on 3D data obtained by CBCT from four aspects: (1) measurement of magnification of cephalogram, (2) assessment of the dimensional accuracy of CBCT images, (3) development of a method of cephalometric analysis using CBCT images and (4) comparison of cephalometric analytical values obtained from CBCT images with those obtained from existing cephalograms. The results demonstrated that our analytical method facilitated cephalometric analysis of CBCT images and therefore allowed direct comparison of CBCT images with existing cephalograms. Cephalometric analysis using CBCT images resulted in a smaller range of inter-operator measurement variability than that using conventional cephalograms.

Objective The goal of this project was to define and measure human airway space with radiographic volumetric 3-dimensional imaging and digital reconstruction of the pharynx using cone-beam computerized tomography. Study design This was a randomized retrospective study. Ten patient scans were selected randomly from a pool of 196 subjects seeking dental treatment at the University of California, San Francisco. Digital Imaging and Communications in Medicine–format volume images were captured using a low-radiation rapid-scanning cone-beam computerized tomography system (Hitachi MercuRay). Results Detailed progressive rostrocaudal cross-sectional area histograms indicated that 8 of the 10 subjects demonstrated a region of maximum constriction near the oropharynx level. The most restricted cross-sectional area varied from 90 mm2 to 360 mm2. Conclusions The maximum constriction of the airway in 10 subjects quietly breathing for 10 seconds indicated variation in the level of the pharynx and the extent of the rostrocaudal zone of restriction.

T cell activation following alloantigen recognition plays a critical role in the development of the rejection in all solid organ, tissue and cell transplantation. A recombinant molecule, cytotoxic T lymphocyte antigen 4 antibody (CTLA-4Ig), is known to induce to T-cell into “anergy” by blocking the costimulatory B7-CD28 interaction. Either systemic or localized administration of CTLA-Ig has been shown to prolong allograft survival and induce donor-specific tolerance in some transplant models. In this study, we characterized the expression and immunosuppressive effectiveness of adenoviral-mediated CTLA-4Ig gene transfer. We demonstrated transduction of the allografts with AdCTLA-4Ig resulted in localized expression, permanent graft survival and stable donor-specific tolerance. In addition, by performing simultaneous dual-organ transplantation, we targeted on immunosuppression through a local expression of CTLA-4Ig via adenoviral-mediated gene transfer into pancreatic allografts.

Purpose To examine and compare the skeletal and dental effects of surgically assisted rapid palatal expansion (SARPE) and multipiece Le Fort osteotomy using cone-beam computed tomography (CBCT). Materials and Methods This was a prospective cohort study. Patients underwent SARPE or multipiece Le Fort I osteotomy to address maxillary transverse deficiency. CBCT scans were taken preoperatively, immediately postoperatively or after retention, and at least 6 months postoperatively. Four landmark measurements and ratios of dental-to-skeletal change were used to follow skeletal and dental widths in the posterior and anterior maxillary regions. Wilcoxon signed-rank test and Wilcoxon 2-sample rank-sum test were used to compare the landmark measurements and the ratio of dental-to-skeletal change for the 2 surgeries. A P value less than .05 was statistically significant. Results Thirteen patients (mean, 28.3 yr old; 7 women) were enrolled: 9 were treated by multipiece Le Fort I osteotomy and 4 were treated by SARPE. The ratios of dental-to-skeletal expansion in the posterior maxilla for the Le Fort procedure and SARPE were 0.70 ± 0.41 and 25.20 ± 15.8, respectively, and the dental-to-skeletal relapses were 1.17 ± 0.80 and −3.63 ± 3.70, respectively. The ratios of dental-to-skeletal expansion in the anterior maxilla for the Le Fort procedure and SARPE were 0.58 ± 0.38 and 31.80 ± 59.4, respectively, and the dental-to-skeletal relapses were 2.25 ± 3.41 and 4.86 ± 8.10, respectively. Conclusion There was greater correlation between dental and skeletal changes in the multipiece Le Fort procedure, indicating bodily separation of the segments, whereas the SARPE showed noteworthy dental and skeletal tipping. Dental relapse was greater than skeletal relapse for these 2 procedures.

Cone beam computed tomography (CBCT) provides a new method to evaluate the craniofacial region. The goal of our project was to introduce into the predoctoral dental curriculum a student-initiated, student-led introduction to CBCT and how to use it, with minimal expenditure of financial resources. A third-year student worked with two faculty members to design a course in which a small number of third-year students would lead a small group of second-year students. The first approach involved each small group of second-year dental students discussing one clinical case in which the patient's CBCT record was included. Representatives of each of the ten small groups presented the patient and that patient's clinical problem (e.g., an impacted tooth) to the entire class as well as demonstrating the superiority and limitations of using CBCT in clinical dentistry. The second approach also used small-group meetings led by third-year dental students, but paired two second-year dental students as a team to present the patient's CBCT data in the small-group setting. There were five teams each presenting a different type of patient as assessed only from the CBCT data. The first model focused on the problem (e.g., an impacted tooth), while the second model focused on how to evaluate and use CBCT scans to determine the patient's primary problem. Based on surveys conducted at the end of each course, the majority of students felt they had gained a better understanding of CBCT.

Background Comprehensive visualization and records of the craniofacial complex have been goals in orthodontic imaging. These tasks have been performed by means of plaster, photographs and radiographs. These approaches have evolved across time, and cone-beam computed tomography (CBCT) has emerged as a comprehensive imaging modality for orthodontics. Methods The authors provide a practical guide for applying CBCT in orthodontics, with an emphasis on situations in which conventional imaging is limited. These situations include dental development, limits of tooth movement, airway assessment, craniofacial morphology and superimposition. Results Complexities of the craniofacial complex, dentition and airway present challenges in obtaining conventional images. CBCT has image-fidelity advantages over conventional imaging that can lead to improved visualization. Conclusions CBCT is changing orthodontics with respect to clinically assessing patients and is evolving with respect to diagnosis, clinical techniques and outcomes. Clinical Implications The clinical value proposition of CBCT is to describe craniofacial anatomy accurately and provide comprehensive information regarding anatomical relationships and individual patient findings for improved diagnosis, treatment planning and prognostication.

The purpose of the present prospective study was to develop a 3-dimensional analysis of the airway using cone-beam computed tomography (CBCT) and to determine whether changes in the airway before and after orthognathic surgery correlate on 2-dimensional lateral cephalogram and 3-dimensional CBCT images.Patients requiring orthognathic surgery during 2004 to 2005 were recruited for the present study. Lateral cephalograms and CBCT scans were obtained at 3 points: preoperatively, within 1 month postoperatively, and after 6 months postoperatively. The nasopharynx, oropharynx, and hypopharynx were segmented on both the radiograph and the CBCT scan for each patient in a repeatable manner at each point. For the lateral cephalogram, linear measurements in the middle of each of the 3 segments were obtained. For the CBCT, volumetric measurements of each of the 3 segments were obtained. The intrarater variability was assessed, and Pearson's correlation was used to compare the 2 imaging modalities.A total of 20 patients scheduled for orthognathic surgery were recruited for the present study. Of the 20 patients, 13 were female and 7 were male. The mean age at surgery was 23.85 years (range 14 to 43). Of the 20 patients, 6 underwent maxillary advancement only, 8 underwent mandibular advancement with or without genioplasty, and 6 underwent 2-jaw surgery or mandibular setback. We examined the entire cohort without separation into procedure or examination point and found a weak, but statistically significant, correlation between the linear and volume measurements in the nasopharyngeal and oropharyngeal regions but not in the hypopharyngeal region (r = 0.43, P.002; r = 0.49, P.0002; r = 0.16, P = .26, respectively). The maxillary advancement group (n = 6) demonstrated a correlation between the linear and volume measurements in the nasopharyngeal region (r = 0.53, P = .03). The mandibular advancement with or without genioplasty group (n = 8) showed a correlation in the nasopharyngeal and oropharyngeal regions (r = 0.55, P.02, and r = 0.46, P = .05, respectively). For the combination/setback procedures (n = 6), a correlation was found in the oropharyngeal region (r = 0.64, P.01). All other comparisons between the linear and volume measurements did not correlate. Additionally, no correlations were found between the linear and volumetric change in airway size between 6 months postoperatively and preoperatively, except for the oropharyngeal region (r = 0.67, P.01).We present a method of measuring the airway that could be used for both 2-dimensional and 3-dimensional images. It includes segmentation of the pharyngeal airway into its nasopharyngeal, oropharyngeal, and hypopharyngeal components. Correlations were found between the linear and volumetric measurements of the segmented airway in patients who had undergone orthognathic surgery; however, the correlations were generally weak.

Introduction The goal of this study was to look at mandibular cortical bone in live patients using cone-beam computed tomography (CBCT) to determine differences in cortical plate thicknesses and mandibular cross-sectional height and width in patients with different vertical facial dimensions. Methods A total of 111 scanned patients were used. Of these subjects, 43 were included in the average vertical facial dimension group (average face), 34 in the high vertical facial group (long face), and 34 in the low vertical facial group (square short face). Cross-sectional slices of the mandible were developed with the cone-beam scans to evaluate the cortical bone between the dentition at 13 locations. Each section was then measured at 8 sites, which included 1 height and 2 width measures of the cross-sectional area and 5 cortical plate thicknesses. An analysis of variance (ANOVA) with a posthoc Bonferroni statistical analysis was used with a significance level of P ≤0.0167. Results The long-face group had slightly more narrow cortical bone than the other 2 facial groups at a few selected sites of the mandible. The height of the cross-sectional area of the mandible in the long-face group was shorter posteriorly than in the other 2 groups and became greater toward the symphysis. Conclusions Mandibular height and width differed more than cortical bone thickness among the 3 types of subjects with different vertical facial dimensions, but statistically significant differences were evident is some sites for cortical bone thickness.

Introduction The purposes of this study were to evaluate the actual postplacement positions of orthodontic miniplate anchoring screws (MPAS) and to determine the risk factors for their failure and iatrogenic effects on the intraoral structures. Methods Three-dimensional cone-beam computed tomography images were generated to examine 31 orthodontic miniplates and their MPAS (diameter, 1.5 mm; length, 4 mm), which showed good clinical stability 6 months after placement in the posterior maxilla of 18 patients. The cone-beam computed tomography data were analyzed with analysis of variance (ANOVA) statistics to evaluate the difference of placement depth and vertical distance of the MPAS from the cementoenamel junction to the center of the screw. The Fisher exact test was used to determine differences in MPAS position, root proximity, and sinus penetration. Results The mean placement depth of the MPAS was 2.48 mm with no significant difference relative to their position. Twenty-six (of 74) MPAS were placed in the dentition area. Of these 26, 14 were placed in interdental spaces, and the other 12 followed the direction of the roots. Nine MPAS showed root proximity, and 7 MPAS had root penetration, all of which were placed in the central position of the miniplate. Thirty-nine MPAS penetrated the sinus, indicating a low interrelationship between placement depth and cortical bone thickness of the sinus. Conclusions Miniplates were successfully retained by MPAS even with less-than-ideal placement. Root contact and proximity of MPAS seem to have minimal effects on the successful stabilization of miniplates. Pertinent guidelines should, however, be followed during MPAS placement to minimize the risk of damage to adjacent roots.

Introduction In this prospective study, we compared differences in the diagnosis and treatment planning of impacted maxillary canines between 2 imaging modalities. Methods Twenty-five consecutive impacted maxillary canines were identified from the pool of patients seeking orthodontic treatment. The first set of radiographs consisted of traditional 2-dimensional (2D) images including panoramic, occlusal, and 2 periapical radiographs. The second set comprised prints of 3-dimensional (3D) volumetric dentition images obtained from a cone-beam computed tomography (CBCT) scan. Seven faculty member completed a questionnaire for every impacted canine and diagnostic radiographic modality (2D and 3D). Results The data show that the judges produced different decisions regarding localization depending on the x-ray method. There were 21% disagreement (or discordance) in the perceived mesiodistal cusp tip position and 16% difference in the perceived labiopalatal position. In the perception of root resorption of adjacent teeth, there was 36% lack of congruence. Twenty-seven percent of the teeth that were planned to be left, recovered, or extracted with the 2D radiographs had different treatment plans when the judges viewed the 3D CBCT images (McNemar test, chi-square, 4.45; P = 0.035). The clinicians' confidence of the accuracy of diagnosis and treatment plan was statistically higher for CBCT images (P Conclusions These results showed that 2D and 3D images of impacted maxillary canines can produce different diagnoses and treatment plans.

Introduction The purposes of this study were to determine factors favoring successful mini-implant placement and to evaluate root proximity as a possible risk factor for failure of osseointegration-based mini-implants during orthodontic treatment. Methods Three-dimensional cone-beam computed tomography images were used to examine 50 sandblasted, large-grit, and acid-etched surface-treated mini-implants (C-implant, Seoul, Korea) placed in 25 patients. The images were analyzed for 3-dimensional position of the mini-implant (placement angle and depth) and any contact with root surfaces or maxillary sinuses. Results There were no remarkable differences in horizontal placement angles in the axial plane and placement depths of the mini-implants, but the vertical placement angle was significantly higher on the left side (24.5° ± 11.0°) compared with the right side (11.8° ± 11.6°). The horizontal mini-implant placement angle had a greater inclination tendency toward the maxillary first molar, and 11 mini-implants with root proximity showed mesiobuccal contact with the maxillary first molar root. Only 1 failure in 15 mini-implants with root proximity and 1 failure in 35 without root proximity were observed on the images. Conclusions Root proximity alone was not considered a major risk factor for osseointegration-based mini-implant failure.

Purpose The purpose of this study is to assess cortical thickness, height, and width with cone-beam computed tomography (CBCT), and determine the relationship of these parameters with age. Patients and Methods A total of 113 subjects from the University of California at San Francisco Orthodontic Clinic with a CBCT scan were enrolled. Subjects were stratified by age in decades. Thickness of buccal and lingual cortices and mandibular height and width were evaluated in 5 regions (13 sites). A single factorial ANOVA was used to compare the parameters among age groups. P less than or equal to .05 was statistically significant. Results There were 44 (38.9%) males; 69 females. For all groups, the thickest to the least thick cortical plates were: base of the mandible, lower buccal one third, upper lingual one third, upper buccal one third, and lower lingual one third. In all groups, the mandible increased in height as the midline was approached, and the width of the upper third of the mandible decreased from the second molar to the symphysis whereas the reverse occurred in the lower third. Comparison of the age groups showed that subjects 10 to 19 years old had thinner cortical plates than other age groups ( P ≤ .05) with peak thickness in subjects 40 to 49 years old. The subjects 10 to 19 years old also had lower posterior mandibular height ( P ≤ .05). There was no statistical difference in width among the groups. Conclusions The mandibular cortical bone is thickest at the base, on the buccal side. Subjects who are 10 to 19 years old have thinner cortical bone and decreased mandibular height compared with all other age groups. The mandible continues to mature through 40 to 49 years of age and then decreases in thickness after this period.

Introduction Changes in the normal pattern of nasal respiration can profoundly affect the development of the craniofacial skeleton in both humans and experimental animals. The orthodontist is often the first clinician to notice that a child is breathing primarily through the mouth, either at the initial examination or later during treatment. The lateral headfilm, part of the patient's normal records, might show increased adenoid masses, suggesting that these could be part of the problem. Previous studies have, however, questioned the validity of the information from lateral headfilm. Methods Our aim was to compare imaging information about nasopharyngeal airway size between a lateral cephalometric headfilm and a 3-dimensional cone-beam computed tomography scan in adolescent subjects. The nasopharyngeal airway area and volume were measured in 35 subjects (8 boys, 27 girls; average age, 14 years). Results Volumetric measurement errors ranged from 0% to 5% compared with known physical airway phantoms used to calibrate. A moderately high (r = 0.75) correlation was found between airway area and volume; the larger the area, the larger the volume. However, there was considerable variability in the airway volumes of patients with relatively similar airways on the lateral headfilms. Nine of the 35 patients had over 25% of the potential nasopharyngeal airway volume occupied by inferior turbinate protuberances, leading to significant airway restriction in some patients. Conclusions The cone-beam 3-dimensional scan is a simple and effective method to accurately analyze the airway.

The problem of verifying multi-threaded execution against the memory consistency model of a processor is known to be an NP hard problem. However polynomial time algorithms exist that detect almost all failures in such execution. These are often used in practice for microprocessor verification. We present a low complexity and fully parallelized algorithm to check program execution against the processor consistency model. In addition our algorithm is general enough to support a number of consistency models without any degradation in performance. An implementation of this algorithm is currently used in practice to verify processors in the post silicon stage for multiple architectures.

RANKL and OPG gene expressions were measured with and without PTH at different stages of osteoblast development. Mouse stromal cells were cultured in osteoblast differentiating conditions, and RANKL, OPG, COL1, ALP, OC, and PTHRec genes were measured using qRT-PCR. OPG:RANKL ratios indicate that PTH may induce a possible switch in the regulatory mechanism of osteoclastogenesis where OPG is inhibited early and RANKL is increased at late stages of osteoblast differentiation. Introduction: RANKL is essential for osteoclastogenesis, and its decoy receptor osteoprotegerin (OPG) negatively regulates this process. Both genes are expressed in cells of the osteoblast lineage, but the precise relationship between the state of osteoblast differentiation and RANKL and OPG expression is not clearly defined. The goal of this project was to quantify changes in RANKL and OPG gene expression in response to parathyroid hormone (PTH) at different stages of osteoblast differentiation. In this study, mouse primary bone marrow stromal cells (BMSCs) were cultured for up to 28 days. At specific time-points of cell culture, cells were stimulated with bovine PTH peptide [bPTH (1–34)] for 2 h. Levels of RANKL, OPG, α-1 (type I) collagen (COL1), alkaline phosphatase (ALP), osteocalcin (OC), and PTH receptor (PTHRec) mRNA were assayed using quantitative real-time reverse-transcriptase-polymerase chain reaction (qRT-PCR). Materials and Methods: In control cells, there was a gradual increase of RANKL gene expression with murine osteoblastic stromal cell maturation to a 3-fold level at day 28. In contrast, OPG mRNA levels were maximal at day 14 of cell culture and decreased through the latter stages of osteoblast differentiation. Exposing the cells to 100 ng/ml of bPTH(1–34) induced minimal increases in RANKL mRNA levels from days 7 to 14 but elevated expression significantly at days 21 (2-fold) and 28 (3-fold). PTH inhibited OPG gene expression maximally at day 14, but continued to have inhibitory effects on cultured cells at days 21 and 28. Alterations of RANKL and OPG mRNA levels by PTH in day 14 osteoblasts were sufficient to sustain a 5.6-fold increase in the number of TRACP+ cells when cocultured with osteoclast precursor cells. Cells in culture after 28 days showed a 1.9-fold increase in TRACP+ cells after PTH treatment. Results and Conclusions: We conclude that (1) PTH significantly upregulates RANKL mRNA in primary bone marrow stromal osteoblasts with maximal sensitivity occurring late in osteoblast differentiation; (2) PTH inhibits OPG gene expression at all stages of osteoblast differentiation; and (3) changes in RANKL and OPG mRNA levels after exposure to PTH are associated with increased osteoclastogenesis as demonstrated by increased numbers of TRACP+ cells in cocultures. The results further suggest that the osteoclastogenic activity of PTH occurs primarily by suppression of OPG gene expression in early osteoblasts and elevation of RANKL gene expression in mature osteoblasts.

Ameloblastic tissue samples from unerupted bone molars were used to prepare subcellular enamel protein kinase preparations, nuclear + plasma membrane, cytosolic and microsomal, and used in in vitro phosphorylation of purified 20 kDa bovine amelogenin in the presence of 32P-ATP. Both cytosolic and microsomal preparations can phosphorylate purified native amelogenins, the addition of Ca2+ slightly increased the microsomal enzyme activity or at least did not inhibit the activity, whereas the presence of Ca2+ substantially decreased the cytosolic kinase activity towards phosphorylation of amelogenins. A comparative analysis using the enamel microsomal kinase against osteopontin, dephosphorylated casein and bone sialoprotein showed no phosphorylation of the first two proteins, and only minor phosphorylation of the bone sialoprotein. Overall, the present work demonstrates for the first time that the protein kinase responsible for the phosphorylation of amelogenins is a novel kinase, which is not inhibited by Ca2+, unlike the microsomal protein kinase (casein kinase type-II) of bone which phosphorylates secretory proteins osteopontin and bone sialoprotein and is strongly CaZ+ inhibited. The direct phosphoserine analysis on the purified bovine 20 kDa amelogenin indicated the presence of 0.8 moles of phosphoserine/mole protein naturally occurring, consistent with the quantitative analysis of 14C-radiolabeling of phosphoserines by conversion to dehydroalanine and in situ reaction with the thiol agent, 14C-mercaptoethanol, 0.64 moles 14C-incorporated/mole 20 kDa amelogenin. The purified low Mramelogenins 5.3 kDa E4 (TRAP) and 7.2 kDa E3 (LRAP), were also derivatized by 14C-mercaptoethanol, providing 0.46 and 0.88 moles 14C-incorporated/mole respectively. Further studies of the 14C-radiolabeled E4 amelogenin by sequence analysis confirmed one site of label to be at position 16 from the N-terminal and hence provided a direct evidence for the naturally occurring phosphoserine residue at this position.

Introduction The purposes of this study were to evaluate the actual postplacement positions of orthodontic miniplate anchoring screws (MPAS) and to determine the risk factors for their failure and iatrogenic effects on the intraoral structures. Methods Three-dimensional cone-beam computed tomography images were generated to examine 31 orthodontic miniplates and their MPAS (diameter, 1.5 mm; length, 4 mm), which showed good clinical stability 6 months after placement in the posterior maxilla of 18 patients. The cone-beam computed tomography data were analyzed with analysis of variance (ANOVA) statistics to evaluate the difference of placement depth and vertical distance of the MPAS from the cementoenamel junction to the center of the screw. The Fisher exact test was used to determine differences in MPAS position, root proximity, and sinus penetration. Results The mean placement depth of the MPAS was 2.48 mm with no significant difference relative to their position. Twenty-six (of 74) MPAS were placed in the dentition area. Of these 26, 14 were placed in interdental spaces, and the other 12 followed the direction of the roots. Nine MPAS showed root proximity, and 7 MPAS had root penetration, all of which were placed in the central position of the miniplate. Thirty-nine MPAS penetrated the sinus, indicating a low interrelationship between placement depth and cortical bone thickness of the sinus. Conclusions Miniplates were successfully retained by MPAS even with less-than-ideal placement. Root contact and proximity of MPAS seem to have minimal effects on the successful stabilization of miniplates. Pertinent guidelines should, however, be followed during MPAS placement to minimize the risk of damage to adjacent roots.

354 a Graduate Student, Department of Orthodontics, School of Dentistry, Seoul National University. Director, Department of Craniofacial Orthodontics, Childrens’ Hospital of Phildelphia. Associate Professor, Department of Prosthodontics, School of Dentistry, Seoul National University. d Graduate Student, g Associate Professor, Department of Orthodontics, School of Dentistry, Kyung Hee University. Clinical Fellow, Department of Restorative Dentistry, School of Dentistry, Kyung Hee University. Professor and Chairman, Department of Dentistry, School of Medicine, Ajou University. h Clinical Associate Professor, Division of Orthodontics, Department of Orofacial Science, University of California SanFrancisco. Corresponding author: Seong-Hun Kim. Department of Orthodontics, School of Dentistry, Kyung Hee University, 1 Hoeigi-dong, Dongdaemun-gu, Seoul 130-701, Korea. +82 2 958 9392; e-mail, bravortho@hanmail.net. Received May 30, 2011; Last Revision September 20, 2011; Accepted September 21, 2011. http://dx.doi.org/10.4041/kjod.2011.41.5.354 *Supported by a grant from Kyung Hee University in 2010 (KHU20100696). The effects of different pilot-drilling methods on the mechanical

γ-Sultines having an aryl substituent α to the oxygen atom have been shown to undergo photochemically induced loss of SO2, via radical intermediates. In the case of the monocyclic derivatives, arylcyclopropanes are formed in excellent yield. 3-Phenylbenz-2,1-thiole-2-oxides yield fluorene derivatives as the major photolysis product.

γ-Sultines having an aryl substituent α to the oxygen atom have been shown to undergo photochemically induced loss of SO2, via radical intermediates. In the case of the monocyclic derivatives, arylcyclopropanes are formed in excellent yield. 3-Phenylbenz-2,1-thiole-2-oxides yield fluorene derivatives as the major photolysis product.