Systematic review of preoperative mandibular canal position as it relates to postoperative neurosensory disturbance following the sagittal split ramus osteotomy

The purpose of this study was to review the current literature for the relationship between the preoperative position of the mandibular canal on three-dimensional (3D) radiographic imaging and postoperative neurosensory disturbance (NSD) following a sagittal split ramus osteotomy (SSRO). A literature search was conducted using PubMed, EMBASE, and the Cochrane Database for articles published from 1 January 2000 through 31 December 2013. Studies that included preoperative 3D imaging and assessment of NSD after surgery were reviewed. Study sample characteristics and results were extracted. Of the 69 articles identified, seven met the inclusion and exclusion criteria. There was no standardization for measuring the canal position or for evaluating NSD. General consensus was that the less space between the mandibular canal and the outer border of the buccal cortex the more frequent the occurrence of NSD. Increased bone density also appeared to contribute to a higher incidence of NSD. Utilization of 3D images to locate and measure the position of the mandibular canal is not standardized. Advances in 3D imaging and evaluation tools allow for new methodologies to be developed. Early attempts are informative, but additional studies are needed to verify the relationship between the location of the nerve and NSD following surgery

The sensitivity of BAO Dark Energy Constraints to General Isocurvature Perturbations

Baryon Acoustic Oscillation (BAO) surveys will be a leading method for addressing the dark energy challenge in the next decade. We explore in detail the effect of allowing for small amplitude admixtures of general isocurvature perturbations in addition to the dominant adiabatic mode. We find that non-adiabatic initial conditions leave the sound speed unchanged but instead excite different harmonics. These harmonics couple differently to Silk damping, altering the form and evolution of acoustic waves in the baryon-photon fluid prior to decoupling. This modifies not only the scale on which the sound waves imprint onto the baryon distribution, which is used as the standard ruler in BAO surveys, but also the shape, width and height of the BAO peak. We discuss these effects in detail and show how more general initial conditions impact our interpretation of cosmological data in dark energy studies. We find that the inclusion of these additional isocurvature modes leads to an increase in the Dark Energy Task Force Figure of merit by 140% and 60% for the BOSS and ADEPT experiments respectively when considered in conjunction with Planck data. We also show that the incorrect assumption of adiabaticity has the potential to bias our estimates of the dark energy parameters by $3\sigma$ ($1\sigma$) for a single correlated isocurvature mode, and up to $8\sigma$ ($3\sigma$) for three correlated isocurvature modes in the case of the BOSS (ADEPT) experiment. We find that the use of the large scale structure data in conjunction with CMB data improves our ability to measure the contributions of different modes to the initial conditions by as much as 100% for certain modes in the fully correlated case.Comment: 20 pages, 17 figure

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n = 109,122 individuals. We identified 59 sentinel variants (p &lt; 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that the independent signals colocalized with cell-type-specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes