Engineering a Model Cell for Rational Tuning of GPCR Signaling.

G protein-coupled receptor (GPCR) signaling is the primary method eukaryotes use to respond to specific cues in their environment. However, the relationship between stimulus and response for each GPCR is difficult to predict due to diversity in natural signal transduction architecture and expression. Using genome engineering in yeast, we constructed an insulated, modular GPCR signal transduction system to study how the response to stimuli can be predictably tuned using synthetic tools. We delineated the contributions of a minimal set of key components via computational and experimental refactoring, identifying simple design principles for rationally tuning the dose response. Using five different GPCRs, we demonstrate how this enables cells and consortia to be engineered to respond to desired concentrations of peptides, metabolites, and hormones relevant to human health. This work enables rational tuning of cell sensing while providing a framework to guide reprogramming of GPCR-based signaling in other systems.

Metformin inhibits digestive proteases and impairs protein digestion in mice.

Metformin is among the most prescribed medications worldwide and the first-line therapy for type 2 diabetes. However, gastrointestinal side effects are common and can be dose limiting. The total daily metformin dose frequently reaches several grams, and poor absorption results in high intestinal drug concentrations. Here, we report that metformin inhibits the activity of enteropeptidase and other digestive enzymes at drug concentrations predicted to occur in the human duodenum. Treatment of mouse gastrointestinal tissue with metformin reduces enteropeptidase activity; further, metformin-treated mice exhibit reduced enteropeptidase activity, reduced trypsin activity, and impaired protein digestion within the intestinal lumen. These results indicate that metformin-induced protein maldigestion could contribute to the gastrointestinal side effects and other impacts of this widely used drug.

The Job Demands and Accommodation Planning Tool (JDAPT): A Nine-Month Evaluation of Use, Changes in Self-efficacy, Presenteeism, and Absenteeism in Workers with Chronic and Episodic Disabilities.

PURPOSE: Enhancing workplace communication and support processes to enable individuals living with disabilities to sustain employment and return to work is a priority for workers, employers, and community stakeholders. The objective of this study was to evaluate a new resource that addresses support challenges, the Job Demands and Accommodation Planning Tool (JDAPT), and assess its use, relevance, and outcomes over a nine-month follow-up period. METHODS: Workers with physical and mental health/cognitive conditions causing limitations at work were recruited using purposive sampling. Online surveys were administered at baseline (prior to using the JDAPT), and at three and nine months post-baseline. Information was collected on demographics (e.g., age, gender) and work characteristics (e.g., job sector, organization size). Outcomes included assessing JDAPT use and relevance, and changes in self-efficacy, work productivity difficulties, employment concerns, difficulties with job demands, and absenteeism. RESULTS: Baseline participants were 269 workers (66% women; mean age 41 years) of whom 188 (69.9%) completed all three waves of data collection. Many workers reported using JDAPT strategies at and outside of work, and held positive perceptions of the tool's usability, relevance, and helpfulness. There were significant improvements (Time 1-2; Time 1-3) in self-efficacy, perceived work productivity, and absenteeism with moderate to large effect sizes in self-efficacy and productivity (0.46 to 0.78). Findings were consistent across gender, age, health condition, and work context variables. CONCLUSIONS: The JDAPT can enhance support provision and provide greater transparency and consistency to workplace disability practices, which is critical to creating more inclusive and accessible employment opportunities.

Gastrointestinal parasites in captive olive baboons in a UK safari park.

From the safety inside vehicles, Knowsley Safari offers visitors a close-up encounter with captive olive baboons. As exiting vehicles may be contaminated with baboon stool, a comprehensive coprological inspection was conducted to address public health concerns. Baboon stools were obtained from vehicles, and sleeping areas, inclusive of video analysis of baboon­vehicle interactions. A purposely selected 4-day sampling period enabled comparative inspections of 2662 vehicles, with a total of 669 baboon stools examined (371 from vehicles and 298 from sleeping areas). As informed by our pilot study, front-line diagnostic methods were: QUIK-CHEK rapid diagnostic test (RDT) (Giardia and Cryptosporidium), Kato­Katz coproscopy (Trichuris) and charcoal culture (Strongyloides). Some 13.9% of vehicles were contaminated with baboon stool. Prevalence of giardiasis was 37.4% while cryptosporidiosis was <0.01%, however, an absence of faecal cysts by quality control coproscopy, alongside lower than the expected levels of Giardia-specific DNA, judged RDT results as misleading, grossly overestimating prevalence. Prevalence of trichuriasis was 48.0% and strongyloidiasis was 13.7%, a first report of Strongyloides fuelleborni in UK. We advise regular blanket administration(s) of anthelminthics to the colony, exploring pour-on formulations, thereafter, smaller-scale indicator surveys would be adequate.

The Job Leeway Scale: Initial Evaluation of a Self-report Measure of Health-Related Flexibility and Latitude at Work.

Purpose Evidence suggests that workers manage health-related challenges at work, in part, by using available leeway to perform work differently. The purpose of this study was to evaluate the reliability and validity of the Job Leeway Scale (JLS), a new 18-item self-report questionnaire designed to assess worker perceptions of available flexibility and latitude to manage health-related challenges at work. Methods Workers seeking assistance for workplace difficulties due to chronic medical conditions (n = 119, 83% female, median age = 49) completed the JLS along with other workplace and health measures. Construct validity was assessed using exploratory factor analysis (EFA), and concurrent validity was assessed by associations with related measures. Results Mean item scores ranged from 2.13 to 4.16 within a possible range of 0-6. The EFA supported three underlying factors: organizational leeway (9 items), task leeway (6 items), and staffing leeway (3 items). Internal consistency (alpha) ranged from 0.78 to 0.91 for subscale scores and 0.94 for the total score. The JLS showed moderate correlations with other work outcome measures including work fatigue, self-efficacy, engagement, and productivity. Conclusion The JLS is a promising new measure with initial support for its reliability and validity to assess worker beliefs of available flexibility to manage health symptoms at work, and this construct may have organizational implications for worker support and accommodation.

Preventing Pain and Stress-Related Ill-Health in Employees: A 6-Months Follow-Up of a Psychosocial Program in a Cluster Randomized Controlled Trial.

Purpose Pain and stress-related ill-health are major causes of long-term disability and sick leave. This study evaluated the effects of a brief psychosocial program, which previously has been tested for an at-risk population of employees. Methods The Effective Communication within the Organization (ECO) program, where supervisors and employees were trained in communication and problem solving, was compared to an active control consisting of psychoeducative lectures (PE) about pain and stress in a cluster randomized controlled trial. First-line supervisors were randomized to ECO or PE, and a total of 191 mainly female employees with self-reported pain and/or stress-related ill-health were included. The hybrid format programs consisted of 2-3 group sessions. Sick leave data was collected from social insurance registers, before and 6-months after the program. Secondary outcomes (work ability, work limitations, pain-disability risk, exhaustion symptoms, perceived stress, perceived health, quality of life, perceived communication and support from supervisors) were assessed at baseline, post intervention, and at 6-months follow-up. Results No effects were observed on primary or secondary outcome variables. Pain symptoms were common (89%), however a lower proportion (30%) were identified as at risk for long-term pain disability, which might explain the lack of evident effects. The Covid-19 pandemic affected participation rates and delivery of intervention. Conclusion In this study, preventive effects of the ECO program were not supported. Altogether, the findings point at the importance of selecting participants for prevention based on screening of psychosocial risk. Further research on workplace communication and support, and impact on employee health is warranted.

A Sensibility Assessment of the Job Demands and Accommodation Planning Tool (JDAPT): A Tool to Help Workers with an Episodic Disability Plan Workplace Support.

Purpose Sensibility refers to a tool's comprehensiveness, understandability, relevance, feasibility, and length. It is used in the early development phase to begin assessing a new tool or intervention. This study examined the sensibility of the job demands and accommodation planning tool (JDAPT). The JDAPT identifies job demands related to physical, cognitive, interpersonal, and working conditions to better target strategies for workplace supports and accommodations aimed at assisting individuals with chronic health conditions. Methods Workers with a chronic health condition and workplace representatives were recruited from health charities, workplaces, and newsletters using convenience sampling. Cognitive interviews assessed the JDAPT's sensibility. A 70% endorsement rate was the minimum level of acceptability for sensibility concepts. A short screening tool also was administered, and answers compared to the complete JDAPT. Results Participants were 46 workers and 23 organizational representatives (n = 69). Endorsements highly exceeded the 70% cut-off for understandability, relevance, and length. Congruence between screening questions and the complete JDAPT suggested both workers and organizational representatives overlooked job demands when completing the screener. Participants provided additional examples and three new items to improve comprehensiveness. The JDAPT was rated highly relevant and useful, although not always easy to complete for someone with an episodic condition. Conclusions This study highlights the need for tools that facilitate accommodations for workers with episodic disabilities and provides early evidence for the sensibility of the JDAPT.

Early Secondary Alveolar Bone Grafting and Facial Growth of Patients with Complete Unilateral Cleft Lip and Palate.

OBJECTIVE: To investigate the craniofacial growth outcomes of early secondary alveolar bone grafting(ABG) around 6 years of age. DESIGN: Retrospective cohort study. SETTING: 1 North-American and 5 Northern-European cleft centers. SUBJECTS: 33 subjects with CUCLP consecutively treated with secondary ABG around 6 years of age were compared to 105 subjects from 4 centers treated with late secondary ABG and 19 subjects from 1 center with primary ABG. METHODS: Preorthodontic standardized lateral cephalometric radiographs taken after 12 years of age were traced and analyzed according to the Eurocleft Study protocol. Fourteen angular and two proportional measurements were performed. Measurement means from the Study Center(SC) were compared to 5 Northern-European centers using analysis of variance and Welch's modified t-tests, and P < .05 was considered statistically significant. RESULTS: For the SC, the mean age ± SD at the time of bone graft was 5.85 ± 0.71 years and the mean age at the time of the lateral cephalogram was 13.4 ± 1.8 years. The sagittal maxillary prominence of the SC was favorably comparable to the 5 Northern-European centers. The mean SNA (78.1 ± 4.3) for the SC was significantly higher compared to 4 of the 5 Northern-European centers(all P < .05), and the mean ANB angle was comparable to 4 of the 5 centers. Similarly, the mean soft tissue ANB angle was not significantly different to the 5 centers. The soft tissue vertical proportions compared favorably to all 5 Northern-European centers(all P < .01). CONCLUSIONS: Craniofacial growth outcomes of early secondary ABG around 6 years compare favorably to the outcomes of late secondary ABG.

Inter-rater reliability in classification of canonical babbling status based on canonical babbling ratio in infants with isolated cleft palate randomised to Timing of Primary Surgery for Cleft Palate (TOPS).

Canonical babbling (CB) is commonly defined as present when at least 15% of all syllables produced are canonical, in other words a canonical babbling ratio (CBR) ≥0.15. However, there is limited knowledge about inter-rater reliability in classification of CB status based on CBR and inter-rater differences in assessment of CBR. We investigated inter-rater reliability of experienced Speech Language Therapists (SLTs) on: classification of CB status based on CBR ≥ 0.15, CBRs and the total number of syllables per infant used to calculate CBR.Each infant (n = 484) was video-recorded at a clinical site in play interaction with their parent as part of the randomised controlled trial Timing of Primary Surgery for Cleft Palate. Each recording was subsequently assessed by three independent SLTs, from a pool of 29 SLTs. They assessed the recordings in real time.The three assessing SLTs agreed in classification of CB status in 423 (87.4%) infants, with higher complete agreement for canonical (91%; 326/358) than non-canonical (77%; 97/126). The average difference in CBR and total number of syllables identified between the SLT assessments of each infant was 0.12 and 95, respectively.This study provided new evidence that one trained SLT can reliably classify CB status (CBR ≥ 0.15) in real time when there is clear distinction between the observed CBR and the boundary (0.15); however, when the observed CBR approaches the boundary multiple SLT assessments are beneficial. Thus, we recommend to include assessment of inter-rater reliability, if the purpose is to compare CBR and total syllable count across infants or studies.Trial registration number here: www.clinicaltrials.gov, identifier NCT00993551.

Living materials with programmable functionalities grown from engineered microbial co-cultures.

Biological systems assemble living materials that are autonomously patterned, can self-repair and can sense and respond to their environment. The field of engineered living materials aims to create novel materials with properties similar to those of natural biomaterials using genetically engineered organisms. Here, we describe an approach to fabricating functional bacterial cellulose-based living materials using a stable co-culture of Saccharomyces cerevisiae yeast and bacterial cellulose-producing Komagataeibacter rhaeticus bacteria. Yeast strains can be engineered to secrete enzymes into bacterial cellulose, generating autonomously grown catalytic materials and enabling DNA-encoded modification of bacterial cellulose bulk properties. Alternatively, engineered yeast can be incorporated within the growing cellulose matrix, creating living materials that can sense and respond to chemical and optical stimuli. This symbiotic culture of bacteria and yeast is a flexible platform for the production of bacterial cellulose-based engineered living materials with potential applications in biosensing and biocatalysis.

Automatic contouring QA method using a deep learning-based autocontouring system.

PURPOSE: To determine the most accurate similarity metric when using an independent system to verify automatically generated contours. METHODS: A reference autocontouring system (primary system to create clinical contours) and a verification autocontouring system (secondary system to test the primary contours) were used to generate a pair of 6 female pelvic structures (UteroCervix [uterus + cervix], CTVn [nodal clinical target volume (CTV)], PAN [para-aortic lymph nodes], bladder, rectum, and kidneys) on 49 CT scans from our institution and 38 from other institutions. Additionally, clinically acceptable and unacceptable contours were manually generated using the 49 internal CT scans. Eleven similarity metrics (volumetric Dice similarity coefficient (DSC), Hausdorff distance, 95% Hausdorff distance, mean surface distance, and surface DSC with tolerances from 1 to 10 mm) were calculated between the reference and the verification autocontours, and between the manually generated and the verification autocontours. A support vector machine (SVM) was used to determine the threshold that separates clinically acceptable and unacceptable contours for each structure. The 11 metrics were investigated individually and in certain combinations. Linear, radial basis function, sigmoid, and polynomial kernels were tested using the combinations of metrics as inputs for the SVM. RESULTS: The highest contouring error detection accuracies were 0.91 for the UteroCervix, 0.90 for the CTVn, 0.89 for the PAN, 0.92 for the bladder, 0.95 for the rectum, and 0.97 for the kidneys and were achieved using surface DSCs with a thickness of 1, 2, or 3 mm. The linear kernel was the most accurate and consistent when a combination of metrics was used as an input for the SVM. However, the best model accuracy from the combinations of metrics was not better than the best model accuracy from a surface DSC as an input. CONCLUSIONS: We distinguished clinically acceptable contours from clinically unacceptable contours with an accuracy higher than 0.9 for the targets and critical structures in patients with cervical cancer; the most accurate similarity metric was surface DSC with a thickness of 1, 2, or 3 mm.

A Worksite Self-management Program for Workers with Chronic Health Conditions Improves Worker Engagement and Retention, but not Workplace Function.

Purpose An increasing number of workers in the US have chronic health conditions that limit their ability to work, and few worksite interventions have been tested to improve worker coping and problem solving at work. The purpose of this study was to evaluate a worksite-based health self-management program designed to improve workplace function among workers with chronic health conditions. Methods We conducted a randomized, controlled trial of a worksite self-management program ("Manage at Work") (clinicaltrials.gov #NCT01978392) for workers with chronic health conditions (N = 119; 82% female, ages 20-69). Most workers were recruited from the health care or light manufacturing industry sectors. Workers attended a 5-session, facilitated psychoeducational program using concepts of health self-management, self-efficacy, ergonomics, and communication. Changes on outcomes of work engagement, work limitation, job satisfaction, work fatigue, work self-efficacy, days absent, and turnover intention at 6-month follow-up were compared to wait-list controls. Results The most prevalent chronic health conditions were musculoskeletal pain, headaches, vision problems, gastrointestinal disorders, respiratory disorders, and mental health disorders. The self-management program showed greater improvement in work engagement and turnover intent at 6-month follow-up, but there was no evidence of a parallel reduction in perceived work limitation. Trends for improved outcomes of work self-efficacy, job satisfaction, and work fatigue in the intervention group did not reach statistical significance in a group x time interaction test. Conclusions Offering a worksite self-management program to workers with chronic health conditions may be a feasible and beneficial strategy to engage and retain skilled workers who are risking disability.Clinical trial registration: Clinicaltrials.gov #NCT01978392.

Expectations for Return to Work Predict Return to Work in Workers with Low Back Pain: An Individual Participant Data (IPD) Meta-Analysis.

Purpose Low back pain is associated with disability and lost productivity due to inability of workers to return to work. Personal recovery expectation beliefs may be associated with return to work outcomes in those with low back pain at high risk for chronic disability. We aimed to (1) assess whether workers' expectations for return to work, following a low back pain episode, are associated with subsequent return to work; and (2) explore the relationships between return to work expectations and other prognostic factors in their association with work outcomes.Methods We conducted an Individual Participant Data (IPD) meta-analysis using data from five prospective cohort studies identified by a Cochrane prognostic factor review. A one-stage IPD meta-analysis approach was applied. Multi-level mixed effects models were used to determine the unadjusted and adjusted associations between expectations and return to work (logistic regression) and time to return to work (parametric survival models with Weibull distribution).Results The final dataset included 2302 participants. Positive expectations for return to work were associated with return to work at follow-up in both unadjusted (Odds Ratio (OR) 2.95; 95% Confidence Interval (CI) 2.21, 3.95) (n = 2071) and comprehensively adjusted (OR 2.01; 95% CI 1.46, 2.77) (n = 1109) models. Similar findings were identified for shorter length of time to return to work in both unadjusted (HR 2.40; 95% CI 2.09, 2.75) (n = 1156) and minimally adjusted (HR 2.43; 95% CI 2.12, 2.79) (n = 1154) models.Conclusions Results suggest workers with low expectations for return to work are at increased risk for long-term work disability.

Does Sleep Position Influence Sleep-Disordered Breathing in Infants With Cleft Palate: A Feasibility Study?

OBJECTIVE: Cleft palate (CP) can affect breathing, leading to sleep-disordered breathing (SDB). Sleep position can affect SDB, but the optimum sleep position for infants with CP is unknown. We aimed to determine the design of a pragmatic study to investigate the effect of the 2 routinely advised sleep positions in infants with CP on oxygen saturations. DESIGN: A multicentered observational cohort. SETTING: Four UK-based cleft centers, 2 advising supine- and 2 side-lying sleep positions for infants with CP. PARTICIPANTS: Infants with isolated CP born July 1, 2015, and December 31, 2016. Of 48 eligible infants, 30 consented (17 side-lying; 13 supine). INTERVENTIONS: Oxygen saturation (SpO2) and end-tidal carbon dioxide (ETCO2) home monitoring at age 1 and 3 months. Qualitative interviews of parents. OUTCOME MEASURES: Willingness to participate, recruitment, retention, and acceptability/success (>90 minutes recording) of SpO2 and ETCO2 monitoring. RESULTS: SpO2 recordings were obtained during 50 sleep sessions on 24 babies (13 side-lying) at 1 month (34 sessions >90 minutes) and 50 sessions on 19 babies (10 side-lying) at 3 months (27 sessions >90 minutes). The ETCO2 monitoring was only achieved in 12 sessions at 1 month and 6 at 3 months; only 1 was >90 minutes long. The ETCO2 monitoring was reported by the majority as unacceptable. Parents consistently reported the topic of sleep position in CP to be of importance. CONCLUSIONS: This study has demonstrated that it is feasible to perform domiciliary oxygen saturation studies in a research setting and has suggested that there may be a difference in the effects of sleep position that requires further investigation. We propose a study with randomization is indicated, comparing side-lying with supine-lying sleep position, representing an important step toward better understanding of SDB in infants with CP.

Development of intra-oral automated landmark recognition (ALR) for dental and occlusal outcome measurements.

BACKGROUND: Previous studies embracing digital technology and automated methods of scoring dental arch relationships have shown that such technology is valid and accurate. To date, however there is no published literature on artificial intelligence and machine learning to completely automate the process of dental landmark recognition. OBJECTIVES: This study aimed to develop and evaluate a fully automated system and software tool for the identification of landmarks on human teeth using geometric computing, image segmenting, and machine learning technology. METHODS: Two hundred and thirty-nine digital models were used in the automated landmark recognition (ALR) validation phase, 161 of which were digital models from cleft palate subjects aged 5 years. These were manually annotated to facilitate qualitative validation. Additionally, landmarks were placed on 20 adult digital models manually by 3 independent observers. The same models were subjected to scoring using the ALR software and the differences (in mm) were calculated. All the teeth from the 239 models were evaluated for correct recognition by the ALR with a breakdown to find which stages of the process caused the errors. RESULTS: The results revealed that 1526 out of 1915 teeth (79.7%) were correctly identified, and the accuracy validation gave 95% confidence intervals for the geometric mean error of [0.285, 0.317] for the humans and [0.269, 0.325] for ALR-a negligible difference. CONCLUSIONS/IMPLICATIONS: It is anticipated that ALR software tool will have applications throughout clinical dentistry and anthropology, and in research will constitute an accurate and objective tool for handling large datasets without the need for time intensive employment of experts to place landmarks manually.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: comparison of dental arch relationships and dental indices at 5, 8, and 10 years.

BACKGROUND AND TRIAL DESIGN: The Scandcleft intercentre study evaluates the outcomes of four surgical protocols (common method Arm A, and methods B, C, and D) for treatment of children with unilateral cleft lip and palate (UCLP) in a set of three randomized trials of primary surgery (Trials 1, 2, and 3). OBJECTIVES: To evaluate and compare dental arch relationships of 5-, 8-, and 10-year-old children with UCLP after four different protocols of primary surgery and to compare three dental indices. The results are secondary outcomes of the overall trial. METHODS: Study models taken at the ages of 5 (n = 418), 8 (n = 411), and 10 years (n = 410) were analysed by a blinded panel of orthodontists using the Eurocran index, the 5-year-olds' (5YO) index, and the GOSLON Yardstick. Student's t-test, Pearson's correlation, chi-square test, and kappa statistics were used in statistical analyses. RESULTS: The reliability of the dental indices varied between moderate and very good, and those of the Eurocran palatal index varied between fair and very good. Significant correlations existed between the dental indices at all ages. No differences were found in the mean 5-, 8-, and 10-year index scores or their distributions within surgical trials. Comparisons between trials detected significantly better mean index scores in Trial 2 Arm C (at all ages) and in Trial 1 Arm B (at 5 and 10 years of age) than in Trial 3 Arm D. The mean Eurocran dental index scores of the total material at 5, 8, and 10 years of age were 2.50, 2.60, and 2.26, and those of the 5YO index and GOSLON Yardstick were 2.77, 2.90, and 2.54, respectively. At age 10 years, 75.8% of the patients had had orthodontic treatment. CONCLUSIONS: The results of these three trials do not provide evidence that one surgical method is superior to the others. The reliabilities of the dental indices were acceptable, and significant correlations existed between the indices at all ages. The reliability of the Eurocran palatal index was questionable. TRIAL REGISTRATION: ISRCTN29932826.

Disclosure, Privacy and Workplace Accommodation of Episodic Disabilities: Organizational Perspectives on Disability Communication-Support Processes to Sustain Employment.

Purpose Employers increasingly are asked to accommodate workers living with physical and mental health conditions that cause episodic disability, where periods of wellness are punctuated by intermittent and often unpredictable activity limitations (e.g., depression, anxiety, arthritis, colitis). Episodic disabilities may be challenging for workplaces which must comply with legislation protecting the privacy of health information while believing they would benefit from personal health details to meet a worker's accommodation needs. This research aimed to understand organizational perspectives on disability communication-support processes. Methods Twenty-seven participants from diverse employment sectors and who had responsibilities for supporting workers living with episodic disabilities (e.g., supervisors, disability managers, union representatives, occupational health representatives, labour lawyers) were interviewed. Five participants also had lived experience of a physical or mental health episodic disability. Participants were recruited through organizational associations, community networks and advertising. Semi-structured interviews and qualitative content analysis framed data collection and analyses, and mapped communication-support processes. Results Seven themes underpinned communication-support process: (1) similarities and differences among physical and mental health episodic disabilities; (2) cultures of workplace support, including contrasting medical and biopsychosocial perspectives; (3) misgivings about others and their role in communication-support processes; (4) that subjective perceptions matter; (5) the inherent complexity of the response process; (6) challenges arising when a worker denies a disability; and (7) casting disability as a performance problem. Conclusions This study identifies a conceptual framework and areas where workplace disability support processes could be enhanced to improve inclusion and the sustainability of employment among workers living with episodic disabilities.

The Effect of Earlier Bone Grafting, Prior to Orthodontic Treatment, on SWAG Ratings of Graft Outcomes.

OBJECTIVE: To compare the outcomes between 2 groups of patients with complete clefts treated with early secondary alveolar bone grafting (ABG) at 2 centers (5-7 years, before orthodontic intervention) and to a third group of patients treated at one of those centers (center 1) who had received later secondary ABG (8-10 years, after orthodontic intervention). DESIGN: Blind retrospective analysis of cleft site radiographs using Americleft Standardized Way to Assess Grafts (SWAG) scale. PATIENTS: A total of 99 patients with complete clefts from 2 North American cleft/craniofacial centers. INTERVENTIONS: Secondary ABG representing 2 protocols: early grafting at a mean age of 6.6 years prior to any orthodontic intervention, and later grafting at a mean age of 10.2 years following pregrafting orthodontic intervention. MAIN OUTCOME MEASURES: Using occlusal radiographs, the SWAG scale from 0 (failed graft) to 6 (ideal) was used. Six trained, calibrated raters scored each radiograph twice, with the average of the 2 ratings used as the final score. Reliability was assessed using the weighted κ statistic. The significance of differences between groups was determined using the Kruskal-Wallis test and Dunn test for pairwise comparisons. RESULTS: Inter-rater reliability of SWAG method was good (0.631). Intra-rater reliability was excellent (0.817). There was a tendency for improved total graft outcome in the early grafted group from center 1 compared to the later grafted group with improvement being significantly different in only the coronal third of the early, preorthodontic grafted group. However, the difference was not statistically significant for the graft overall.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: impact of maxillary dental agenesis on craniofacial growth and dental arch relationship in 8 year olds.

BACKGROUND: It is suggested that dental agenesis affects maxillary protrusion and dental arch relationship in children with unilateral cleft lip and palate (UCLP). In addition, an association between the need for orthognathic surgery and dental agenesis is reported. AIM: The aim was to study the impact of maxillary dental agenesis on craniofacial growth and dental arch relationship in 8-year-old children with UCLP. SUBJECTS AND METHODS: The sample consisted of individuals with UCLP from Scandcleft randomized trials. The participants had available data from diagnosis of maxillary dental agenesis as well as cephalometric measurements (n = 399) and GOSLON assessment (n = 408) at 8 years of age. RESULTS: A statistically significant difference was found for ANB between individuals with agenesis of two or more maxillary teeth (mean 1.52°) in comparison with those with no or only one missing maxillary tooth (mean 3.30° and 2.70°, respectively). Mean NSL/NL was lower among individuals with agenesis of two or more maxillary teeth (mean 9.90°), in comparison with individuals with no or one missing maxillary tooth (mean 11.46° and 11.45°, respectively). The number of individuals with GOSLON score 4-5 was 47.2% in the group with two or more missing maxillary teeth and 26.1% respectively 26.3% in the groups with no or one missing maxillary tooth. No statistically significant difference was found in the comparison between individuals with no agenesis or with agenesis solely of the cleft-side lateral. CONCLUSION: Maxillary dental agenesis impacts on craniofacial growth as well as dental arch relationship and should be considered in orthodontic treatment planning.

Scandcleft trial of primary surgery for unilateral cleft lip and palate: Craniofacial cephalometrics at 8 years.

BACKGROUND: The Scandcleft trial is a randomized controlled trial that includes children with unilateral cleft lip and palate where registrations are standardized and therefore provides the opportunity to describe craniofacial characteristics in a very large sample of patients. OBJECTIVES: The aim of this study was to describe craniofacial growth and morphology in a large study sample of 8-year-old children with unilateral cleft lip and palate (UCLP); before orthodontic treatment and before secondary alveolar bone grafting; and to compare the cephalometric values with age-matched non-cleft children from previous growth studies to identify the differences between untreated cleft- and non-cleft children. MATERIALS: There are 429 eight-year-old UCLP patients in the Scandcleft study group. A total of 408 lateral cephalograms with a mean age of 8.1 years were analysed. Cephalometric analyses were performed digitally. The results from three previously published growth studies on non-cleft children were used for comparison. RESULTS: Cephalometric analyses showed a large variation in craniofacial morphology among the UCLP group. In general, they present with significant maxillary retrusion and reduced intermaxillary relationships compared to the age-matched non-cleft children. In addition, the vertical jaw relationship was decreased, mainly due to decreased maxillary inclination. The upper and lower incisors were retroclined. It can be expected that these differences will increase in significance as the children age. CONCLUSION: Results from this study provide proposed norms for the young UCLP before any orthodontic treatment and can be valuable for the clinician in future treatment planning. TRIAL REGISTRATION: ISRCTN29932826.