Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Control and management of multidrug resistant Acinetobacter baumannii: A review of the evidence and proposal of novel approaches.

Hospital-acquired infections are on the rise and are a substantial cause of clinical and financial burden for healthcare systems. While infection control plays a major role in curtailing the spread of outbreak organisms, it is not always successful. One organism of particular concern is Acinetobacter baumannii, due to both its persistence in the hospital setting and its ability to acquire antibiotic resistance. A. baumannii has emerged as a nosocomial pathogen that exhibits high levels of resistance to antibiotics, and remains resilient against traditional cleaning measures with resistance to Colistin increasingly reported. Given the magnitude and costs associated with hospital acquired infections, and the increase in multidrug-resistant organisms, it is worth re-evaluating our current approaches and looking for alternatives or adjuncts to traditional antibiotics therapies. The aims of this review are to look at how this organism is spread within the hospital setting, discuss current treatment modalities, and propose alternative methods of outbreak management.

Perceptions and Attitudes toward Data Sharing among Dental Researchers.

INTRODUCTION: Increasing attention is being given to the roles of data management and data sharing in the advancement of research. This study was undertaken to explore opinions and past experiences of established dental researchers as related to data sharing and data management. METHODS: Researchers were recruited from the International Association for Dental Research scientific groups to complete a survey consisting of Likert-type, multiple-choice, and open-ended questions. RESULTS: All 42 respondents indicated that data sharing should be promoted and facilitated, but many indicated reservations or concerns about the proper use of data and the protection of research subjects. Many had used data from data repositories and received requests for data originating from their studies. Opinions varied regarding restrictions such as requirements to share data and the time limits of investigator rights to keep data. Respondents also varied in their methods of data management and storage, with younger respondents and those with higher direct costs of their research tending to use dedicated experts to manage their data. DISCUSSION: The expressed respondent support for research data sharing, with the noted concerns, complements the idea of developing managed data clearinghouses capable of promoting, managing, and overseeing the data-sharing process. KNOWLEDGE TRANSFER STATEMENT: Researchers can use the results of this study to evaluate and improve management and sharing of research data. By encouraging and facilitating the data-sharing process, research can advance more efficiently, and research findings can be implemented into practice more rapidly to improve patient care and the overall oral health of populations.

Fatigue in systemic lupus: the role of disease activity and its correlates.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that leads to a variety of negative health outcomes resulting from inflammation in various organ systems. Although treatment continues to advance, fatigue remains one of the most salient, poorly understood and addressed patient complaints. Understanding the mechanisms of fatigue can help guide the development of interventions to improve health outcomes. The aim of this research was to evaluate the contribution of six variables (disease activity, insomnia, depression, stress, pain and physical health) to fatigue in SLE without concomitant fibromyalgia (FM). METHODS: A total of 116 ethnically diverse, primarily female participants (91%) with SLE, receiving care at university medical centers, completed assessments of disease activity and quality of life outcomes (FACIT-FT, Insomnia Severity Index, Perceived Stress Scale (PSS-4), Pain Inventory, Depression-PHQ-9, and LupusPRO-physical function). All patients met the American College of Rheumatology classification criteria for SLE and did not have a known diagnosis of FM. Multivariate linear and stepwise regression analyses were conducted with fatigue (FACIT-FT) as the dependent variable, and the above six variables as independent variables. RESULTS: Mean (SD) age was 39.80 (13.87) years; 50% were African American, 21% Caucasian, 13% Hispanic, 9% Asian and 8% other. Mean (SD) FACIT-FT was 20.09 (12.76). Collectively, these six variables explained 57% of the variance in fatigue. In the multivariate model, depression, stress and pain were significantly and independently associated with fatigue, but not disease activity, sleep or physical health. Stress had the largest effect on fatigue (ß 0.77, 95% CI 0.17-1.38, p = 0.01), followed by depression (ß 0.66, 95% CI 0.21-1.10, p = 0.005). On stepwise regression analysis, only stress, depression and pain were retained in the model, and collectively explained 56% of the variance in fatigue. All three remained independent correlates of fatigue, with the largest contribution being stress (ß 0.84, 95% CI 0.27-1.42, p = 0.005), followed by depression (ß 0.79, 95% CI 0.44-1.14, p < 0.001) with fatigue. CONCLUSION: Stress, depression and pain are the largest independent contributors to fatigue among patients with SLE, without concurrent FM. Disease activity, sleep and physical health were not associated with fatigue. The evaluation of stress, depression and pain needs to be incorporated during assessments and clinical trials of individuals with SLE, especially within fatigue. This stress-depression-fatigue model requires further validation in longitudinal studies and clinical trials. Significance and innovation: • Disease activity, sleep, pain, stress, depression, and physical health have been reported individually to be associated with fatigue in lupus. This analysis evaluated the role of each and all of these six variables collectively in fatigue among patients with SLE without a known diagnosis of FM. • Disease activity, sleep and physical health were not significantly related to fatigue, but depression, stress and pain were. • The results emphasize the need to evaluate and treat fatigue in individuals with SLE utilizing a biopsychosocial approach, particularly in the realm of clinical trials. Behavioral medicine interventions are shown to be most effective for the treatment of depression, stress and pain.

Seasonal variation of Pseudomonas aeruginosa in culture positive otitis externa in South East England.

Otitis externa is the inflammation of the external auditory canal. The disease is common and shows a seasonal variation with a greater incidence in warmer months. Pseudomonas aeruginosa is a common pathogen in otitis externa and in this retrospective study, we show a corresponding seasonal variation in the proportional incidence of P. aeruginosa isolates from otitis externa in South East England. In total 7770 patients were diagnosed with otitis externa over a period of 9 years from January 2008 to December 2016. P. aeruginosa was isolated from 2802 patients (proportional incidence of 36%). Incidence was higher in the months of August, September and October and in patients between 5 and 15 years of age. We postulate a combination of increased contact with water during warm weather in the holiday season and increased rainfall in the preceding season as a putative mechanism for the seasonal trends.

Validation of the LupusPRO version 1.8: an update to a disease-specific patient-reported outcome tool for systemic lupus erythematosus.

Objectives LupusPRO has shown good measurement properties as a disease-specific patient-reported outcome tool in systemic lupus erythematosus (SLE). For the purpose of clinical trials, the version 1.7 (v1.7) domain of Pain-Vitality was separated into distinct Pain, Vitality and Sleep domains in v1.8, and the psychometric properties examined. Methods A total of 131 consecutive SLE patients were self-administered surveys assessing fatigue (FACIT, SF-36), pain (Pain Inventory, SF-36), insomnia (Insomnia Severity Index), emotional health (PHQ-9, SF-36) and quality of life (SF-36, LupusPRO) at routine care visits. Internal consistency reliability (ICR) for each domain was obtained using Cronbach's alpha. The convergent construct validity of LupusPRO domains with corresponding SF-36 domains or tools were tested using Spearman correlation. Varimax rotations were conducted to assess factor structures of the LupusPRO v1.8. Results Mean (SD) age was 40.04 (14.10) years. Scores from the LupusPRO-Sleep domain strongly correlated with insomnia scores, while LupusPRO-Vitality correlated strongly with fatigue (FACIT) and SF-36 vitality. The LupusPRO-Pain domain correlated strongly with pain (SF36 Bodily-Pain, Pain Inventory) scores. Similarly, the LupusPRO domains of Physical and Emotional Health had significant correlations with corresponding SF-36 domains. The ICR for HRQoL and non-HRQoL were 0.96 and 0.81. LupusPRO (domains HRQoL and QoL) scores correlated with disease activity. Principal component analysis included seven factor loadings presenting for the HRQOL subscales (combined Sleep, Vitality, and Pain), and three factors for the NHRQoL (Combined Coping and Social Support). Conclusions LupusPRO v1.8 (including its Sleep, Vitality, and Pain domains) has acceptable reliability and validity. Use of LupusPRO as an outcome measure in clinical trials would facilitate responsiveness assessment.

Validation of the Vectra H1 portable three-dimensional photogrammetry system for facial imaging.

Three-dimensional (3D) surface imaging using stereophotogrammetry has become increasingly popular in clinical settings, offering advantages for surgical planning and outcome evaluation. The handheld Vectra H1 is a low-cost, highly portable system that offers several advantages over larger stationary cameras, but independent technical validation is currently lacking. In this study, 3D facial images of 26 adult participants were captured with the Vectra H1 system and the previously validated 3dMDface system. Using error magnitude statistics, 136 linear distances were compared between cameras. In addition, 3D facial surfaces from each system were registered, heat maps generated, and global root mean square (RMS) error calculated. The 136 distances were highly comparable across the two cameras, with an average technical error of measurement (TEM) value of 0.84mm (range 0.19-1.54mm). The average RMS value of the 26 surface-to-surface comparisons was 0.43mm (range 0.33-0.59mm). In each case, the vast majority of the facial surface differences were within a ±1mm threshold. Areas exceeding ±1mm were generally limited to facial regions containing hair or subject to facial microexpressions. These results indicate that 3D facial surface images acquired with the Vectra H1 system are sufficiently accurate for most clinical applications.

Ephaptic coupling rescues conduction failure in weakly coupled cardiac tissue with voltage-gated gap junctions.

Electrical conduction in cardiac tissue is usually considered to be primarily facilitated by gap junctions, providing a pathway between the intracellular spaces of neighboring cells. However, recent studies have highlighted the role of coupling via extracellular electric fields, also known as ephaptic coupling, particularly in the setting of reduced gap junction expression. Further, in the setting of reduced gap junctional coupling, voltage-dependent gating of gap junctions, an oft-neglected biophysical property in computational studies, produces a positive feedback that promotes conduction failure. We hypothesized that ephaptic coupling can break the positive feedback loop and rescue conduction failure in weakly coupled cardiac tissue. In a computational tissue model incorporating voltage-gated gap junctions and ephaptic coupling, we demonstrate that ephaptic coupling can rescue conduction failure in weakly coupled tissue. Further, ephaptic coupling increased conduction velocity in weakly coupled tissue, and importantly, reduced the minimum gap junctional coupling necessary for conduction, most prominently at fast pacing rates. Finally, we find that, although neglecting gap junction voltage-gating results in negligible differences in well coupled tissue, more significant differences occur in weakly coupled tissue, greatly underestimating the minimal gap junctional coupling that can maintain conduction. Our study suggests that ephaptic coupling plays a conduction-preserving role, particularly at rapid heart rates.

Memory in a fractional-order cardiomyocyte model alters properties of alternans and spontaneous activity.

Cardiac memory is the dependence of electrical activity on the prior history of one or more system state variables, including transmembrane potential (Vm), ionic current gating, and ion concentrations. While prior work has represented memory either phenomenologically or with biophysical detail, in this study, we consider an intermediate approach of a minimal three-variable cardiomyocyte model, modified with fractional-order dynamics, i.e., a differential equation of order between 0 and 1, to account for history-dependence. Memory is represented via both capacitive memory, due to fractional-order Vm dynamics, that arises due to non-ideal behavior of membrane capacitance; and ionic current gating memory, due to fractional-order gating variable dynamics, that arises due to gating history-dependence. We perform simulations for varying Vm and gating variable fractional-orders and pacing cycle length and measure action potential duration (APD) and incidence of alternans, loss of capture, and spontaneous activity. In the absence of ionic current gating memory, we find that capacitive memory, i.e., decreased Vm fractional-order, typically shortens APD, suppresses alternans, and decreases the minimum cycle length (MCL) for loss of capture. However, in the presence of ionic current gating memory, capacitive memory can prolong APD, promote alternans, and increase MCL. Further, we find that reduced Vm fractional order (typically less than 0.75) can drive phase 4 depolarizations that promote spontaneous activity. Collectively, our results demonstrate that memory reproduced by a fractional-order model can play a role in alternans formation and pacemaking, and in general, can greatly increase the range of electrophysiological characteristics exhibited by a minimal model.

Dental Decay Phenotype in Nonsyndromic Orofacial Clefting.

Although children with oral clefts have a higher risk for dental anomalies when compared with the general population, prior studies have shown conflicting results regarding their dental decay risk. Also, few studies have assessed dental decay risk in unaffected relatives of children with clefts. Thus, the question of increased risk of dental decay in individuals with oral clefts or their unaffected relatives is still open for empirical investigation. This study characterizes dental decay in the largest international cohort to date of children with nonsyndromic clefts and their relatives, as compared with controls, and it addresses whether families with oral clefts have a significantly increased risk for dental decay versus the general population. A total of 3,326 subjects were included: 639 case probands, 1,549 unaffected relatives, and 1,138 controls. Decay was identified from in-person dental examinations or intraoral photographs. Case-control differences were tested with regression analysis. No significant differences were shown in percentage decayed and filled teeth and decayed teeth in the primary dentition (dft, dt) and permanent dentition (DFT, DT) in cases versus controls. In the cleft region, no significant differences were seen in primary or permanent decay (dt, DT) when compared with controls. No difference was found with regard to cleft type and percentage dft, dt, DFT, and DT in case probands. Nonsignificant differences were found in unaffected siblings and parents versus controls (primary and permanent dentitions). Collectively, these findings indicate that individuals with nonsyndromic oral clefts and their families do not have a higher dental decay risk as compared with the general population. These results suggest that either genetic or environmental factors underlying a higher susceptibility for dental anomalies do not increase caries risk or that the seemingly higher risk for dental decay associated with increased dental anomalies in case probands may be superseded by possible greater access to dental care.

Spectrum of Dental Phenotypes in Nonsyndromic Orofacial Clefting.

Children with oral clefts show a wide range of dental anomalies, adding complexity to understanding the phenotypic spectrum of orofacial clefting. The evidence is mixed, however, on whether the prevalence of dental anomalies is elevated in unaffected relatives and is mostly based on small samples. In the largest international cohort to date of children with nonsyndromic clefts, their relatives, and controls, this study characterizes the spectrum of cleft-related dental anomalies and evaluates whether families with clefting have a significantly higher risk for such anomalies compared with the general population. A total of 3,811 individuals were included: 660 cases with clefts, 1,922 unaffected relatives, and 1,229 controls. Dental anomalies were identified from in-person dental exams or intraoral photographs, and case-control differences were tested using χ(2) statistics. Cases had higher rates of dental anomalies in the maxillary arch than did controls for primary (21% vs. 4%, P = 3 × 10(-8)) and permanent dentitions (51% vs. 8%, P = 4 × 10(-62)) but not in the mandible. Dental anomalies were more prevalent in cleft lip with cleft palate than other cleft types. More anomalies were seen in the ipsilateral side of the cleft. Agenesis and tooth displacements were the most common dental anomalies found in case probands for primary and permanent dentitions. Compared with controls, unaffected siblings (10% vs. 2%, P = 0.003) and parents (13% vs. 7%, P = 0.001) showed a trend for increased anomalies of the maxillary permanent dentition. Yet, these differences were nonsignificant after multiple-testing correction, suggesting genetic heterogeneity in some families carrying susceptibility to both overt clefts and dental anomalies. Collectively, the findings suggest that most affected families do not have higher genetic risk for dental anomalies than the general population and that the higher prevalence of anomalies in cases is primarily a physical consequence of the cleft and surgical interventions.

Prenatal sex hormones, digit ratio, and face shape in adult males.

OBJECTIVES: Several reports have demonstrated a relationship between second to fourth digit ratio (2D:4D) and facial shape, suggesting that prenatal sex hormones play a role in the development of the craniofacial complex. Using 3D surface imaging and geometric morphometrics, we test the hypothesis that decreased digit ratio (indicative of increased prenatal androgen exposure) is associated with a more masculine facial phenotype. METHODS: 3D facial surface images and digit measures were collected on a sample of 151 adult males. Facial landmarks collected from the images were aligned by Procrustes superimposition and the resulting shape coordinates regressed on 2D:4D. Variations in facial shape related to 2D:4D were visualized with deformable surface warps. RESULTS: A significant statistical relationship was observed between facial shape variation and 2D:4D (p = 0.0084). Lower 2D:4D ratio in adult males was associated with increased facial width relative to height, increased mandibular prognathism, greater nasal projection, and increased upper and lower lip projection. CONCLUSIONS: A statistical relationship between 2D:4D and facial shape in adult males was observed. Faces tended to look more masculine as 2D:4D decreased, suggesting a biologically plausible link between prenatal androgen exposure and the development of male facial characteristics.

The influence of integrated tuberculosis and human immunodeficiency virus service delivery on patient outcomes.

SETTING: Public health clinics in Cape Town, South Africa. OBJECTIVE: To examine the influence of integrated tuberculosis (TB) and human immunodeficiency virus (HIV) service delivery on mortality, TB cure and successful treatment completion and loss to follow-up of TB-HIV co-infected patients on concurrent anti-tuberculosis and antiretroviral treatment (ART). DESIGN: A survey instrument was used to measure the degree to which TB and HIV services were jointly delivered, and patient data were collected retrospectively from clinic sites and the Department of Health. Six domains measuring integrated TB and HIV service delivery were modelled to assess their relationship with patient outcomes. RESULTS: Two domains, integrated TB and ART service delivery and the delivery of TB and HIV care by one clinical team, were associated with lowered odds of death. Care by the same clinical team was also associated with reduced loss to follow-up. CONCLUSION: Overall, these findings show that the organization and delivery of health services are important factors that influence health outcomes. These findings strongly support efforts by local governments to integrate TB and ART services, and may help to alleviate concerns that restructuring of TB programs could have a negative impact on long-standing gains.

Face shape of unaffected parents with cleft affected offspring: combining three-dimensional surface imaging and geometric morphometrics.

OBJECTIVE: Various lines of evidence suggest that face shape may be a predisposing factor for non-syndromic cleft lip with or without cleft palate (CL/P). In the present study, 3D surface imaging and statistical shape analysis were used to evaluate face shape differences between the unaffected (non-cleft) parents of individuals with CL / P and unrelated controls. METHODS: Sixteen facial landmarks were collected from 3D captures of 80 unaffected parents and 80 matched controls. Prior to analysis, each unaffected parent was assigned to a subgroup on the basis of prior family history (positive or negative). A geometric morphometric approach was utilized to scale and superimpose the landmark coordinate data (Procrustes analysis), test for omnibus group differences in face shape, and uncover specific modes of shape variation capable of discriminating unaffected parents from controls. RESULTS: Significant disparity in face shape was observed between unaffected parents and controls (p < 0.01). Notably, these changes were specific to parents with a positive family history of CL/P. Shape changes associated with CL/P predisposition included marked flattening of the facial profile (midface retrusion), reduced upper facial height, increased lower facial height, and excess interorbital width. Additionally, a sex-specific pattern of parent-control difference was evident in the transverse dimensions of the nasolabial complex. CONCLUSIONS: The faces of unaffected parents from multiplex cleft families displayed meaningful shape differences compared with the general population. Quantitative assessment of the facial phenotype in cleft families may enhance efforts to discover the root causes of CL/P.

Parental craniofacial morphology in cleft lip with or without cleft palate as determined by cephalometry: a meta-analysis.

OBJECTIVE: To integrate findings from previous cephalometric studies comparing the craniofacial complex of unaffected parents with cleft lip with or without cleft palate (CL/P) children to controls with no history of the disease. DESIGN: Meta-analysis of case-control cephalometric data. INCLUSION CRITERIA: Studies were selected if the unaffected parents of children with CL/P were included and were not combined with parents of children with isolated CP; quantitative data were obtained through cephalometry; the cephalometric variables used were not unique to a study; a case-control design was used; and the means and standard deviations for all variables were reported or could be calculated for both the experimental and the control group. OUTCOME MEASURE: Using raw data obtained from nine studies, mean weighted effect sizes with 95% confidence intervals were calculated for 28 cephalometric variables (mothers and fathers combined) or 18 variables (mothers and fathers separately). Heterogeneity statistics for the effect sizes were also calculated. RESULTS: In general, unaffected parents of children with CL/P possessed significantly wider interorbital, nasal cavity and upper facial dimensions, narrower cranial vaults, longer cranial bases, longer and more protrusive mandibles, shorter upper faces and longer lower faces compared with controls. Increased width of the nasal cavity was the most robust finding. Significant effect size heterogeneity was observed in roughly half of the variables examined. CONCLUSION: Unaffected parents of children with CL/P are characterized by a suite of consistent, yet subtle, craniofacial differences, which could indicate an underlying genetic liability.

Low response rate schools in surveys of adolescent risk taking behaviours: possible biases, possible solutions.

STUDY OBJECTIVE: To examine the potential biases introduced when students in low response rate schools are dropped from classroom based surveys of adolescent risk taking behaviour. DESIGN: Self administered confidential surveys were conducted in classrooms, with follow up visits to each school to survey students absent during the initial survey administration. Data on students in schools that achieved a 70% response rate are compared with data on students in schools that did not achieve this level of response. SETTING: New York City, United States. PARTICIPANTS: 1854 10th graders in 13 public (state supported) high schools. MAIN RESULTS: Students in schools with low response rates resulting from high rates of absenteeism have different demographic characteristics and engage in more risk behaviours than students in schools with low absenteeism and high response rates. Excluding schools with low rates of response can have an effect on estimates of risk behaviour, even after data are weighted for individual absences. The potential for bias is greatest when, in sampling schools, the proportion of schools with low response rates is large, and when such schools represent a large share of the students in the area under study. CONCLUSIONS: Excluding schools with poor response rates from survey samples using a classroom based approach does not improve, and may, under some circumstances, underestimate risky behaviour among adolescent populations.

Cleft lip with or without cleft palate and dermatoglyphic asymmetry: evaluation of a Chinese population.

OBJECTIVE: To determine if Chinese individuals with non syndromic cleft lip with or without cleft palate (CL/P) display more dermatoglyphic asymmetry than unaffected relatives or controls. DESIGN: Case-control study with two control groups (genetically related and unrelated). SETTING AND SAMPLE POPULATION: A total of 500 CL/P probands from Shanghai, China, 421 unaffected relatives, and 66 controls of Chinese heritage. METHODS: Finger and palm prints were collected, and pattern frequencies, total ridge counts (TRC), and atd angles were calculated. Asymmetry scores between right and left hands were defined for each of the three dermatoglyphic measures. Probands' asymmetry scores were compared statistically with the scores of unaffected relatives and controls. RESULTS: In general, the probands' asymmetry scores for TRC and atd angle did not differ significantly from the scores of either unaffected relatives or controls. However, probands with a positive family history of clefting showed significantly more asymmetry in their pattern types than either probands without a family history, unaffected relatives or controls. CONCLUSION: These results suggest that a unique genetic mechanism of developmental instability may obtain in CL/P individuals with a positive family history of clefting.

Epidemiological and genetic study of 121 cases of oral clefts in Kuwait.

AIM: The aim of the study was to ascertain some epidemiological factors such as sex and consanguinity that may be associated with cleft lip with or without cleft palate (CL +/- CP) in Kuwait as well as to conduct genetic segregation analysis of these families. SETTING AND SAMPLE POPULATION: A total of 113 families ascertained through 121 CL +/- CP and CP surgical probands in Kuwait. The frequencies of cleft types and the epidemiological variables were calculated using SPSS version 5.0 software. Chi-square for goodness-of-fit test was used to test the significance of the associated epidemiological variables to facial clefts. Genetic segregation analysis was performed on 76 families with extended pedigrees and included only those with non-syndromic CL +/- CP (NS CL +/- CP). Major locus segregation analysis was used to fit models to the observed family patterns under Class A regressive models as implemented by REGD routine in S.A.G.E. release 4.0. A test for heterogeneity was also conducted to complete data set in addition to two subsets: Arabs and nomads. RESULTS: Of the 121 patients, 34(28.1%) had CP, 30(24.8%) had CL and 57 (47.1%) had CL + CP. The male to female ratio was 0.89 for CP, 1.14 for CL, 1.35 for CL + CP and 1.2 for all the clefts. The percentage of consanguineous families among those with a positive family history (60%) was not significantly different from that of the general population (54.3%), whereas for all the families with clefts the percent consanguineous was significantly lower (38%). No evidence of heterogeneity in the results between the Arab and nomad subsets was observed. The results for the major locus segregation analysis were inconclusive. CONCLUSION: No definite association was observed between consanguinity and the occurrence of facial clefts in Kuwait. General transmission models in the full data set showed no evidence of heterogeneity in the results between the Arab and nomad subsets.

Developmental screening of children diagnosed with congenital heart defects.

Children with congenital heart disease (CHD) are more likely than normal children to have developmental delays. The development of 64 children with CHD less than 6 years old was screened with the Denver II. Thirty-five of the 64 children had CHD that required surgical or catheter intervention. These 35 children were significantly less likely than other children with CHD to be normal on developmental screening (46% vs 86%, respectively). Thirty-four percent of children with more severe CHD were referred for early intervention. As research shows the efficacy of early intervention, results indicate the need for early developmental evaluation of children with CHD of hemodynamic significance.