A Practical Assessment of Site Liquefaction Effects and Remediation Needs

This paper describes a case history where potential earthquake induced liquefaction is of concern at a site where a major housing development is planned. The site comprises inter-layer saturated loose to medium dense sandy silts, silty sands and soft clay layers to a depth of 35 ft. Liquefaction potential at the site was evaluated through the use of cone penetrometer test (CPT) logs and standard penetration test (SPT) data. Results of DESRA-2 effective stress site response analyses were also used to determine pore pressure response at the site for a given design earthquake, and are compared to liquefaction assessments conducted using the empirical SPT approach. Methods for determining post liquefaction settlement and potential surface manifestation of liquefaction are described along with the methods used to assess recommendations for site remediation

Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography

Objective We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS). Methods Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category. Results 49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS—comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged \u3c30 years vs \u3e80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p\u3c0.001). Conclusions New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance

Mild pulmonary hypertension and premature mortality among 154 956 men and women undergoing routine echocardiography

Background Although mild pulmonary hypertension is known to be associated with increased mortality, its impact on premature mortality is largely unknown. Methods We studied the distribution of estimated right ventricular systolic pressure (eRVSP) among a total of 154 956 adults with no evidence of left heart disease investigated with echocardiography. We then examined individually linked mortality, premature mortality and associated life-years lost (LYL) according to eRVSP levels. Results The cohort comprised 70 826 men and 84 130 women (aged 61.3±17.7 and 61.4±18.4 years, respectively). Overall, 85 173 (55.0%), 49 276 (31.8%), 13 060 (8.4%) and 7447 (4.8%) cases had eRVSP levels indicative of no (<30.0 mmHg), mild (30.0–39.9 mmHg), moderate (40.0–49.9 mmHg) or severe (≥50.0 mmHg) pulmonary hypertension, respectively. During a median (interquartile range) 5.7 (3.2–8.9) years of follow-up, 38 456/154 986 (24.8%) individuals died. Compared with eRVSP <30.0 mmHg, age and sex-adjusted hazard ratios for all-cause and cardiovascular-related mortality were 1.90 (95% CI 1.84–1.96) and 1.85 (95% CI 1.74–1.97), respectively, for eRVSP 35.0–39.9 mmHg. Overall, 6256 (54%) men and 7524 (55%) women died prematurely. As a proportion of all deaths, premature mortality rose from 46.7% to 79.2% among those with eRVSP <30.0 versus ≥60.0 mmHg with a mean of 5.1–11.4 LYL each time. However, due to more individuals affected overall, eRVSP 30.0–39.9 mmHg accounted for 58% and 53% of total LYL among men (40 606/70 019 LYL) and women (47 333/88 568 LYL), respectively. Conclusions These data confirm that elevated eRVSP levels indicative of mild pulmonary hypertension are associated with increased risk of death. Moreover, this results in a substantive component of premature mortality/LYL that requires more proactive clinical surveillance and management

Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography

Objective We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS). Methods Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category. Results 49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS—comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged 80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p<0.001). Conclusions New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance

Incident pulmonary hypertension in 13488 cases investigated with repeat echocardiography : A clinical cohort study

Background We addressed the paucity of data describing the characteristics and natural history of incident pulmonary hypertension. Methods Adults (n=13 448) undergoing routine echocardiography without initial evidence of pulmonary hypertension (estimated right ventricular systolic pressure, eRVSP <30.0 mmHg) or left heart disease were studied. Incident pulmonary hypertension (eRVSP ≥30.0 mmHg) was detected on repeat echocardiogram a median of 4.1 years apart. Mortality was examined according to increasing eRVSP levels (30.0–39.9, 40.0–49.9 and ≥50.0 mmHg) indicative of mild-to-severe pulmonary hypertension. Results A total of 6169 men (45.9%, aged 61.4±16.7 years) and 7279 women (60.8±16.9 years) without evidence of pulmonary hypertension were identified (first echocardiogram). Subsequently, 5412 (40.2%) developed evidence of pulmonary hypertension, comprising 4125 (30.7%), 928 (6.9%) and 359 (2.7%) cases with an eRVSP of 30.0–39.9 mmHg, 40.0–49.9 mmHg and ≥50.0 mmHg, respectively (incidence 94.0 and 90.9 cases per 1000 men and women, respectively, per year). Median (interquartile range) eRVSP increased by +0.0 (−2.27 to +2.67) mmHg and +30.68 (+26.03 to +37.31) mmHg among those with eRVSP <30.0 mmHg versus ≥50.0 mmHg. During a median 8.1 years of follow-up, 2776 (20.6%) died from all causes. Compared to those with eRVSP <30.0 mmHg, the adjusted risk of all-cause mortality was 1.30-fold higher in 30.0–39.9 mmHg, 1.82-fold higher in 40.0–49.9 mmHg and 2.11-fold higher in ≥50.0 mmHg groups (all p<0.001). Conclusions New-onset pulmonary hypertension, as indicated by elevated eRVSP, is a common finding among older patients without left heart disease followed-up with echocardiography. This phenomenon is associated with an increased morality risk even among those with mildly elevated eRVSP

Integrated Transcriptome and Binding Sites Analysis Implicates E2F in the Regulation of Self-Renewal in Human Pluripotent Stem Cells

Rapid cellular growth and multiplication, limited replicative senescence, calibrated sensitivity to apoptosis, and a capacity to differentiate into almost any cell type are major properties that underline the self-renewal capabilities of human pluripotent stem cells (hPSCs). We developed an integrated bioinformatics pipeline to understand the gene regulation and functions involved in maintaining such self-renewal properties of hPSCs compared to matched fibroblasts. An initial genome-wide screening of transcription factor activity using in silico binding-site and gene expression microarray data newly identified E2F as one of major candidate factors, revealing their significant regulation of the transcriptome. This is underscored by an elevated level of its transcription factor activity and expression in all tested pluripotent stem cell lines. Subsequent analysis of functional gene groups demonstrated the importance of the TFs to self-renewal in the pluripotency-coupled context; E2F directly targets the global signaling (e.g. self-renewal associated WNT and FGF pathways) and metabolic network (e.g. energy generation pathways, molecular transports and fatty acid metabolism) to promote its canonical functions that are driving the self-renewal of hPSCs. In addition, we proposed a core self-renewal module of regulatory interplay between E2F and, WNT and FGF pathways in these cells. Thus, we conclude that E2F plays a significant role in influencing the self-renewal capabilities of hPSCs