Heritability and genetic variance of dementia with Lewy bodies

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.Peer reviewe

Structure and genetic relationships between serrana de Teruel breed and other cattle breeds reared in Spain

In this work we analyze by microsatellite markers the genetic diversity, structure and relationships of the indigenous endangered Serrana de Teruel cattle breed with different breeds reared in Spain. All loci were polymorphic and a total of 198 alleles were observed across loci, with a mean of 6.79. Observed and expected heterozygosities values shown the high variability of Serrana de Teruel breed with values of 0.67 and 0.68 respectively. The neighbour net based on Reynolds distances shown the close genetic relationship among Serrana de Teruel and the mountain Parda de Montaña and Pirenaica breeds. STRUCTURE results showed a 47.5% of correctly assigned individuals to Serrana de Teruel breed using a q>0.8 threshold. The admixed animals shown a clear influence of Parda de Montaña breed.En este trabajo se analiza la variabilidad genética de la raza autóctona en peligro de extinción Serrana de Teruel, así como su relación con las ra-zas bovinas explotadas en España: Albera, Pajuna, Avileña-Negra Ibérica, Serrana Negra, Pirenaica y Parda de Montaña. La caracterización genética se ha realizado mediante marcadores microsatélites, todos han resultado polimórficos detectándose un total de 198 alelos con una media de 6,79 alelos por locus. Las heterocigosidades observadas y esperadas fueron altas y similares en el equilibrio, con valores de 0,67 y 0,68 respectivamente. A partir del estudio de las relaciones filogenéticas se ha podido observar la cercanía de la raza Serrana de Teruel con las razas de montaña Pirenaica y Parda de Montaña. Mediante el estudio de la estructura genética se observó que el porcentaje de animales correctamente asignados a la Serrana de Teruel para q>0,8 fue del 47,5%, apreciándose una clara influencia de la raza Parda de Montaña en los individuos mezclados

Uprobe 2008: an online resource for universal overgo hybridization-based probe retrieval and design†

Cross-species sequence comparisons are a prominent method for analyzing genomic DNA and an ever increasing number of species are being selected for whole-genome sequencing. Targeted comparative genomic sequencing is a complementary approach to whole-genome shotgun sequencing and can produce high-quality sequence assemblies of orthologous chromosomal regions of interest from multiple species. Genomic libraries necessary to support targeted mapping and sequencing projects are available for more than 90 vertebrates. An essential step for utilizing these and other genomic libraries for targeted mapping and sequencing is the development of the hybridization-based probes, which are necessary to screen a genomic library of interest. The Uprobe website (http://uprobe.genetics.emory.edu) provides a public online resource for identifying or designing ‘universal’ overgo-hybridization probes from conserved sequences that can be used to efficiently screen one or more genomic libraries from a designated group of species. Currently, Uprobe provides the ability to search or design probes for use in broad groups of species, including mammals and reptiles, as well as more specific clades, including marsupials, carnivores, rodents and nonhuman primates. In addition, Uprobe has the capability to design custom probes from multiple-species sequence alignments provided by the user, thus providing a general tool for targeted comparative physical mapping

Accelerated hot-carrier cooling in MAPbI3 perovskite by pressure-induced lattice compression

Hot-carrier cooling (HCC) in metal halide perovskites in the high-density regime is significantly slower compared to conventional semiconductors. This effect is commonly attributed to a hot-phonon bottleneck but the influence of the lattice properties on the HCC behaviour is poorly understood. Using pressure-dependent transient absorption spectroscopy (fs-TAS) we find that at an excitation density below Mott transition, pressure does not affect the HCC. On the contrary, above Mott transition, HCC in methylammonium lead iodide (MAPbI3) is around two times as fast at 0.3 GPa compared to ambient pressure. Our electron-phonon coupling calculations reveal about two times stronger electron-phonon coupling for the inorganic cage mode at 0.3 GPa. However, our experiments reveal that pressure promotes faster HCC only above Mott transition. Altogether, these findings suggest a change in the nature of excited carriers in the high-density regime, providing insights on the electronic behavior of devices operating at such high charge-carrier density

Combinations of School-Based Primary and Secondary Preventive Dental Programs in the United States and Other Countries

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65940/1/j.1752-7325.1979.tb02953.x.pd

Lattice compression increases the activation barrier for phase segregation in mixed-halide perovskites

The bandgap tunability of mixed-halide perovskites makes them promising candidates for light emitting diodes and tandem solar cells. However, illuminating mixed-halide perovskites results in the formation of segregated phases enriched in a single-halide. This segregation occurs through ion migration, which is also observed in single-halide compositions, and whose control is thus essential to enhance the lifetime and stability. Using pressure-dependent transient absorption spectroscopy, we find that the formation rates of both iodide- and bromide-rich phases in MAPb(BrxI1-x)3 reduce by two orders of magnitude on increasing the pressure to 0.3 GPa. We explain this reduction from a compression-induced increase of the activation energy for halide migration, which is supported by first-principle calculations. A similar mechanism occurs when the unit cell volume is reduced by incorporating a smaller cation. These findings reveal that stability with respect to halide segregation can be achieved either physically through compressive stress or chemically through compositional engineering

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity

ESMO-ESGO consensus conference recommendations on ovarian cancer: Pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically-relevant and evidence-based guidelines in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO-ESGO consensus conference on ovarian cancer was held on 12-14 April 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO-ESGO consensus conference, together with a summary of evidence supporting each recommendation

The prevalence of radiographic vertebral fractures in Mexican men

The prevalence of radiographically ascertained vertebral fractures in a random sample of 413 in Mexican men is 9.7% (95% CI 6.85–12.55). Increase of vertebral fracture rises with age from 2.0% in the youngest group (50–59 years) to 21.4% in the oldest group (80 years and over). This is the first population-based study of vertebral fractures in Mexican men using a standardized methodology reported in other studies. The presence of radiographic vertebral fractures increases with age. This same pattern was found in Mexican women with steady age increments, but the higher prevalence of fractures in women starts at age 70, whereas in men, the higher prevalence starts a decade later (80 years and over). The standardized prevalence per 1,000 men 50 years and over in the Mexican population for the year 2005 is 65.8 (95% CI 29.9–105.5), and it is 68.6 (95% CI 32.2–108.7) in the US population for the year 2000

Factors associated with the desire for orthodontic treatment among Brazilian adolescents and their parents

<p>Abstract</p> <p>Background</p> <p>In the period of adolescence physical appearance takes on significant importance in the construction of personal identity, including one's relationship with one's own body. A variety of social, cultural, psychological and personal factors influences the self-perception of dental appearance and the decision to undergo orthodontic treatment. Adolescents who seek orthodontic treatment are concerned with improving their appearance and social acceptance. The aim of the present study was to determine factors associated to the desire for orthodontic treatment among Brazilian adolescents and their parents.</p> <p>Methods</p> <p>The sample consisted of 403 subjects aged 14 to 18 years, selected randomly from a population of 182,291 schoolchildren in the same age group. The outcome variable "desire for orthodontic treatment" was assessed through a questionnaire. Self-perception of dental aesthetics was assessed using the Oral Aesthetic Subjective Impact Scale (OASIS) and the Dental Aesthetic Index (DAI) was used for clinical assessment. Statistical analysis involved the chi-square test as well as both simple and multiple logistic regression analyses.</p> <p>Results</p> <p>The majority (78%) of the Brazilian adolescents desired orthodontic treatment and 69% of the parents reported that their children were not in orthodontic treatment due to the high costs involved. There was significant association (p ≤ 0.05) between the desire for orthodontic treatment and most types of malocclusion. However, there was no significant association between the desire for orthodontic treatment and the variables gender and age.</p> <p>Conclusions</p> <p>The following were considered factors associated to the desire for treatment: upper anterior crowding ≥ 2 mm and parents' perception of their child's need for treatment.</p