Evidence of Linkage in a Hispanic Cohort with a Class III Dentofacial Phenotype

Despite the prevalence of craniofacial disorders, the genetic contribution remains poorly understood. Class III malocclusion represents a specific craniofacial problem that can be handicapping, both functionally and socially. We hypothesized that the Class III phenotype is genetically linked to specific loci that regulate maxillary or mandibular growth. To determine the region linked to the Class III phenotype in four Hispanic families, we performed a genome-wide scan and linkage analysis using 500 microsatellite markers. Pedigree and linkage analyses revealed that the Class III phenotype (primarily maxillary deficiency) segregates in an autosomal-dominant manner, and that 5 loci (1p22.1, 3q26.2, 11q22, 12q13.13, and 12q23) are suggestive of linkage. Candidate genes within the 12q23 region (ZLR = 2.93) include IGF1, HOXC, and COL2A1. Chromosome 1 results (ZLR = 2.92) were similar to those reported previously in an Asian cohort with mandibular prognathism, suggesting that a common upstream genetic element may be responsible for both mandibular prognathism and maxillary deficiency

Higher social tolerance is associated with more complex facial behavior in macaques

The social complexity hypothesis for communicative complexity posits that animal societies with more complex social systems require more complex communication systems. We tested the social complexity hypothesis on three macaque species that vary in their degree of social tolerance and complexity. We coded facial behavior in >3000 social interactions across three social contexts (aggressive, submissive, affiliative) in 389 animals, using the Facial Action Coding System for macaques (MaqFACS). We quantified communicative complexity using three measures of uncertainty: entropy, specificity, and prediction error. We found that the relative entropy of facial behavior was higher for the more tolerant crested macaques as compared to the less tolerant Barbary and rhesus macaques across all social contexts, indicating that crested macaques more frequently use a higher diversity of facial behavior. The context specificity of facial behavior was higher in rhesus as compared to Barbary and crested macaques, demonstrating that Barbary and crested macaques used facial behavior more flexibly across different social contexts. Finally, a random forest classifier predicted social context from facial behavior with highest accuracy for rhesus and lowest for crested, indicating there is higher uncertainty and complexity in the facial behavior of crested macaques. Overall, our results support the social complexity hypothesis

A new valuation school : Integrating diverse values of nature in resource and land use decisions

We are increasingly confronted with severe social and economic impacts of environmental degradation all over the world. From a valuation perspective, environmental problems and conflicts originate from trade-offs between values. The urgency and importance to integrate nature's diverse values in decisions and actions stand out more than ever. Valuation, in its broad sense of 'assigning importance', is inherently part of most decisions on natural resource and land use. Scholars from different traditions -while moving from heuristic interdisciplinary debate to applied transdisciplinary science- now acknowledge the need for combining multiple disciplines and methods to represent the diverse set of values of nature. This growing group of scientists and practitioners share the ambition to explore how combinations of ecological, socio-cultural and economic valuation tools can support real-life resource and land use decision-making. The current sustainability challenges and the ineffectiveness of single-value approaches to offer relief demonstrate that continuing along a single path is no option. We advocate for the adherence of a plural valuation culture and its establishment as a common practice, by contesting and complementing ineffective and discriminatory single-value approaches. In policy and decision contexts with a willingness to improve sustainability, integrated valuation approaches can be blended in existing processes, whereas in contexts of power asymmetries or environmental conflicts, integrated valuation can promote the inclusion of diverse values through action research and support the struggle for social and environmental justice. The special issue and this editorial synthesis paper bring together lessons from pioneer case studies and research papers, synthesizing main challenges and setting out priorities for the years to come for the field of integrated valuation.Peer reviewe

Preterm neonatal morbidity and mortality by gestational age: a contemporary cohort

Although preterm birth less than 37 weeks gestation is the leading cause of neonatal morbidity and mortality in the United States, the majority of data regarding preterm neonatal outcomes come from older studies, and many reports have been limited to only very preterm neonates. Delineation of neonatal outcomes by delivery gestational age is needed to further clarify the continuum of mortality and morbidity frequencies among preterm neonates

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Height, selected genetic markers and prostate cancer risk:Results from the PRACTICAL consortium

Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height 4180cm are at a 22% increased risk as compared to men with height o173cm (OR 1.22, 95% CI 1.01–1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.</p

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Although genome-wide association studies have identified over 100 risk loci that explain ~33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Although genome-wide association studies have identified over 100 risk loci that explain similar to 33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa