Cleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The ...other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized. To identify such risk factors, we performed a genome-wide association study of this disorder. We discovered a genome-wide significant association with a missense variant in GRHL3 (p.Thr454Met c.1361C>T; rs41268753; p = 4.08 × 10−9) and replicated the result in an independent sample of case and control subjects. In both the discovery and replication samples, rs41268753 conferred increased risk for CP (OR = 8.3, 95% CI 4.1–16.8; OR = 2.16, 95% CI 1.43–3.27, respectively). In luciferase transactivation assays, p.Thr454Met had about one-third of the activity of wild-type GRHL3, and in zebrafish embryos, perturbed periderm development. We conclude that this mutation is an etiologic variant for nonsyndromic CP and is one of few functional variants identified to date for nonsyndromic orofacial clefting. This finding advances our understanding of the genetic basis of craniofacial development and might ultimately lead to improvements in recurrence risk prediction, treatment, and prognosis.
Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P ...is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case-parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 × 10
), and 19q13 near RHPN2, a gene involved in organizing the actin cytoskeleton (P = 4.17 × 10
). Other regions reaching genome-wide significance were 1p36 (PAX7), 1p22 (ARHGAP29), 1q32 (IRF6), 8q24 and 17p13 (NTN1), all reported in previous GWASs. Stratification by ancestry group revealed a novel association with a region on 17q23 (P = 2.92 × 10
) among individuals with European ancestry. This region included several promising candidates including TANC2, an oncogene required for development, and DCAF7, a scaffolding protein required for craniofacial development. In the Central and South American ancestry group, significant associations with loci previously identified in Asian or European ancestry groups reflected their admixed ancestry. In summary, we have identified novel CL/P risk loci and suggest new genes involved in craniofacial development, confirming the highly heterogeneous etiology of OFCs.
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.
Abstract
Background
Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of ...the 90–90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact.
Methods
A scoping review was done following Arksey & O′Malley’s methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles.
Results
Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures.
Conclusions
This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied.
We have undertaken a thorough dynamical investigation of five extrasolar planetary systems using extensive numerical experiments. The systems Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208 were ...examined concerning the question of whether they could host terrestrial-like planets in their habitable zones (HZ). First we investigated the mean motion resonances between fictitious terrestrial planets and the existing gas giants in these five extrasolar systems. Then a fine grid of initial conditions for a potential terrestrial planet within the HZ was chosen for each system, from which the stability of orbits was then assessed by direct integrations over a time interval of 1 million years. For each of the five systems the 2-dimensional grid of initial conditions contained 80 eccentricity points for the Jovian planet and up to 160 semimajor axis points for the fictitious planet. The computations were carried out using a Lie-series integration method with an adaptive step size control. This integration method achieves machine precision accuracy in a highly efficient and robust way, requiring no special adjustments when the orbits have large eccentricities. The stability of orbits was examined with a determination of the Rényi entropy, estimated from recurrence plots, and with a more straightforward method based on the maximum eccentricity achieved by the planet over the 1 million year integration. Additionally, the eccentricity is an indication of the habitability of a terrestrial planet in the HZ; any value of $e>0.2$ produces a significant temperature difference on a planet's surface between apoapse and periapse. The results for possible stable orbits for terrestrial planets in habitable zones for the five systems are: for Gl 777 A nearly the entire HZ is stable, for 47 Uma, HD 72659 and HD 4208 terrestrial planets can survive for a sufficiently long time, while for Gl 614 our results exclude terrestrial planets moving in stable orbits within the HZ. Studies such as this one are of primary interest to future space missions dedicated to finding habitable terrestrial planets in other stellar systems. Assessing the likelihood of other habitable planets, and more generally the possibility of other life, is the central question of astrobiology today. Our investigation indicates that, from the dynamical point of view, habitable terrestrial planets seem to be compatible with many of the currently discovered extrasolar systems.
Liquid-free cryogenic devices are acquiring importance in basic science and engineering. But they can also lead to improvements in teaching low temperature and solid-state physics to graduate ...students and specialists. Most of the devices are relatively expensive, but small-sized equipment is slowly becoming available. Here, we have designed several simple experiments which can be performed using a small Stirling refrigerator. We discuss the measurement of the critical current and temperature of a bulk YBasubscript 2Cusubscript 3Osubscript 7 - delta (YBCO) sample, the observation of the levitation of a magnet over a YBCO disc when cooled below the critical temperature and the observation of a phase transition using ac calorimetry. The equipment can be easily handled by students and also used to teach the principles of liquid-free cooling. (Contains 10 figures and 8 footnotes.)
Liquid free cryogenic devices are acquiring importance in basic science and engineering. But they can also lead to improvements in teaching low temperature an solid state physics to graduate students ...and specialists. Most of the devices are relatively expensive, but small sized equipment is slowly becoming available. Here, we have designed several simple experiments which can be performed using a small Stirling refrigerator. We discuss the measurement of the critical current and temperature of a bulk YBa2Cu3O(7-d) (YBCO) sample, the observation of the levitation of a magnet over a YBCO disk when cooled below the critical temperature and the observation of a phase transition using ac calorimetry. The equipment can be easily handled by students, and also used to teach the principles of liquid free cooling.
PDF
