Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Higher low-density lipoprotein cholesterol levels are associated with decreased mortality in patients with intracerebral hemorrhage

Background and aims: The relationship between lipoprotein levels, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and clinical outcome after intracerebral hemorrhage (ICH) remains controversial. We sought to evaluate the association of lipoprotein cholesterol levels and statin dosage with clinical and neuroimaging outcomes in patients with ICH. Methods: Data on consecutive patients hospitalized with spontaneous acute ICH was prospectively collected over a 5-year period and retrospectively analyzed. Demographic characteristics, clinical severity documented by NIHSS-score and ICH-score, neuroimaging parameters, pre-hospital statin use and doses, and LDL-C and HDL-C levels were recorded. Outcome events characterized were hematoma volume, hematoma expansion, in-hospital functional outcome, and in-hospital mortality. Results: A total of 672 patients with acute ICH [(mean age 61.6±14.0 years, 43.6% women, median ICH score 1 (IQR: 0-2)] were evaluated. Statin pretreatment was not associated with neuroimaging or clinical outcomes. Higher LDL-C levels were associated with several markers of poor clinical outcome and in-hospital mortality. LDL-C levels were independently and negatively associated with the cubed root of hematoma volume (linear regression coefficient - 0.021, 95% CI: -0.042−-0.001; p=0.049) on multiple linear regression models. Higher admission LDL-C (OR 0.88, 95% CI 0.77 – 0.99; p= 0.048) was also an independent predictor for decreased hematoma expansion. Higher admission LDL-C levels were independently (p <0.001) associated with lower likelihood of in-hospital mortality (OR per 10mg/dL increase 0.68, 95% CI: 0.57– 0.80) in multivariable logistic regression models.Conclusions: Higher LDL-C levels at hospital admission were an independent predictor for lower likelihood of hematoma expansion and decreased in-hospital mortality in patients with acute spontaneous ICH. This association requires independent confirmation

Elevated pulse pressure levels are associated with increased in-hospital mortality in acute spontaneous intracerebral hemorrhage

Objectives: Clinical outcome after intracerebral hemorrhage (ICH) remains poor. Definitive phase-3 trials in ICH have failed to demonstrate improved outcomes with intensive systolic blood pressure (SBP) lowering. We sought to determine whether other BP parameters—diastolic BP (DBP), pulse pressure (PP), and mean arterial pressure (MAP)—showed an association with clinical outcome in ICH. Methods: We retrospectively analyzed a prospective cohort of 672 patients with spontaneous ICH and documented demographic characteristics, stroke severity, and neuroimaging parameters. Consecutive hourly BP recordings allowed for computation of SBP, DBP, PP, and MAP. Threshold BP values that transitioned patients from survival to death were determined from ROC curves. Using in-hospital mortality as outcome, BP parameters were evaluated with multivariable logistic regression analysis. Results: Patients who died during hospitalization had higher mean PP compared to survivors (68.5 ± 16.4 mm Hg vs. 65.4 ± 12.4 mm Hg; P = 0.032). The following admission variables were associated with significantly higher in-hospital mortality (P < 0.001): poorer admission clinical condition, intraventricular hemorrhage, and increased admission normalized hematoma volume. ROC analysis showed that mean PP dichotomized at 72.17 mm Hg, provided a transition point that maximized sensitivity and specific for mortality. The association of this increased dichotomized PP with higher in-hospital mortality was maintained in multivariable logistic regression analysis (odds ratio, 3.0; 95% confidence interval, 1.7–5.3; P < 0.001) adjusting for potential confounders. Conclusion: Widened PP may be an independent predictor for higher mortality in ICH. This association requires further study