Inference of the genetic architecture underlying BMI and height with the use of 20,240 sibling pairs

Evidence that complex traits are highly polygenic has been presented by population-based genome-wide association studies (GWASs) through the identification of many significant variants, as well as by family-based de novo sequencing studies indicating that several traits have a large mutational target size. Here, using a third study design, we show results consistent with extreme polygenicity for body mass index (BMI) and height. On a sample of 20,240 siblings (from 9,570 nuclear families), we used a within-family method to obtain narrow-sense heritability estimates of 0.42 (SE = 0.17, p = 0.01) and 0.69 (SE = 0.14, p = 6 x 10(-)(7)) for BMI and height, respectively, after adjusting for covariates. The genomic inflation factors from locus-specific linkage analysis were 1.69 (SE = 0.21, p = 0.04) for BMI and 2.18 (SE = 0.21, p = 2 x 10(-10)) for height. This inflation is free of confounding and congruent with polygenicity, consistent with observations of ever-increasing genomic-inflation factors from GWASs with large sample sizes, implying that those signals are due to true genetic signals across the genome rather than population stratification. We also demonstrate that the distribution of the observed test statistics is consistent with both rare and common variants underlying a polygenic architecture and that previous reports of linkage signals in complex traits are probably a consequence of polygenic architecture rather than the segregation of variants with large effects. The convergent empirical evidence from GWASs, de novo studies, and within-family segregation implies that family-based sequencing studies for complex traits require very large sample sizes because the effects of causal variants are small on average.

Procurement-related critical factors for briefing in public-private partnership projects: Case of Hong Kong

Public private partnerships (PPP) are widely used for construction project procurement. However, the briefing stage of PPP projects has been largely overlooked, although it has a far-reaching influence throughout the project life cycle. In response, we rectify this by exploring the critical factors involved. A set of 15 procurement-related factors are first identified from the existing literature. Then the effects of four background variables on the factors are tested with Hong Kong government data by an exploratory factor analysis extracting four major dimensions. The relationships between these dimensions and background variables indicate the need to take the background variables into account when ranking the factors. The ranking of the factors is then obtained by considering their weighted importance. Finally, the final practical value of the results is discussed.

Dynamics of nitrate-nitrogen removal in experimental stormwater biofilters under intermittent wetting and drying

High concentrations of nitrate-nitrogen degrade the quality of aquatic environments. The primary mechanism by which nitrate-nitrogen is removed (denitrification) requires anoxic conditions and electron donors. While removal of total and ammonium-nitrogen is often high in stormwater biofilters, poor removal or even the release of nitrate-nitrogen in the outflow has often been observed. Five Perspex biofilter columns (94 mm internal diameter) were fabricated with a filter layer that contained 8% organic material. Columns were operated at 875  mm/h 875  mm/h and fed with simulated stormwater with different antecedent dry days (ADDs) and concentrations of nitrate-nitrogen. Samples were collected from the outflow at different time intervals between 2 and 150 min and were tested for nitrate-nitrogen. The removal of nitrate-nitrogen varied during an event from a high removal percentage (60–90%) in the initial outflow that gradually decreased in the first 30 min and settled at 0–15% removal thereafter. This remained consistent during all simulated events independent of the number of ADDs or inflow concentrations. ADDs and previous event feed concentrations affected the outflow nitrate-nitrogen concentration in the first 30 min of the current event. Therefore, from this study it is concluded that denitrification within stormwater biofilters occurs mainly during drying periods rather than wetting periods.

A closed-form optimal tuning of mass dampers for one degree-of-freedom systems under rotating unbalance forcing

This paper is focused on the study of a vibrating system forced by a rotating unbalance and coupled to a tuned mass damper (TMD). The analysis of the dynamic response of the entire system is used to define the parameters of such device in order to achieve optimal damping properties. The inertial forcing due to the rotating unbalance depends quadratically on the forcing frequency and it leads to optimal tuning parameters that differ from classical values obtained for pure harmonic forcing. Analytical results demonstrate that frequency and damping ratios, as a function of the mass parameter, should be higher than classical optimal parameters. The analytical study is carried out for the undamped primary system, and numerically investigated for the damped primary system. We show that, for practical applications, proper TMD tuning allows to achieve a reduction in the steady-state response of about 20% with respect to the response achieved with a classically tuned damper. Copyright © 2015 by ASME.

Experimental studies of lipped channel beams subject to web crippling under two-flange load cases

Lipped channel beams (LCBs) are commonly used as flexural members such as floor joists and bearers in the construction 6 industry. These thin-walled LCBs are subjected to specific buckling and failure modes, one of them being web crippling. Despite considerable 7 research in this area, some recent studies have shown that the current web crippling design rules are unable to predict the test capacities under 8 end-two-flange (ETF) and interior-two-flange (ITF) load conditions. In many instances, web crippling predictions by the available design 9 standards such as AISI S100, AS/NZS 4600 and Eurocode 3 Part 1-3 are inconsistent, i.e., unconservative in some cases, although they 10 are conservative in other cases. Hence, experimental studies consisting of 36 tests were conducted in this research to assess the web crippling 11 behavior and capacities of high-strength LCBs under two-flange load cases (ETF and ITF). Experimental results were then compared with the 12 predictions from current design rules. Comparison of the ultimate web crippling capacities from tests showed that the design equations are 13 very unconservative for LCB sections under the ETF load case and are conservative for the ITF load case. Hence, improved equations were 14 proposed to determine the web crippling capacities of LCBs based on the experimental results from this study. Current design equations do 15 not provide the direct strength method (DSM) provisions for web crippling. Hence, suitable design rules were also developed under the DSM 16 format using the test results and buckling analyses using finite-element analyses.

Field performance of in-service cast iron gas reticulation pipe buried in reactive clay

Field instrumentation of an in-service cast iron gas pipe buried in a residential area is detailed in this paper. The aim of the study was to monitor the long-term pipe behavior to understand the mechanisms of pipe bending in relation to ground movement as a result of seasonal fluctuation of soil moisture content. Field data showed that variation of soil temperature, suction, and moisture content are closely related to the prevailing climate. Change of soil temperature is generally related to the ambient air temperature, with a variation of approximately −3°C −3°C per meter depth from the ground surface in summer (decrease with depth) and winter (increase with depth). Seasonal cyclic variation in moisture content was observed with maxima in February and March, and a minimum around September. The pipe top was under tensile strain during summer and subsequently subjected to compressive strain as soil swelling occurred as a result of increase in moisture content. The study suggests that downward pipe bending occurs in summer because of soil shrinkage, while upward pipe bending occurs in winter when the soil swells.

Clinician perspective on molecular profiling of non-small-cell lung cancer

The article by Meric-Bernstam et al1 that was recently published in Journal of Clinical Oncology raises important questions about the clinical application of large-scale genomic testing. We congratulate the authors for this ambitious study, which successfully profiled 2,000 consecutive patients with advanced cancer. The next-generation sequencing (NGS) platform was used for 1,749 of 2,000 patients (87.5%). Of 789 patients with potentially actionable mutations, 83 (11%, or 4% of screened population) were enrolled in a genomically matched clinical study. As the editorial2 accompanying the article by Meric-Bernstam et al1 pointed out, the 4% figure, albeit disappointing, may be an underestimate because cancers such as lung adenocarcinoma and melanoma, for which ≥ 50% of patients have actionable mutations, were under-represented. ...

Detection of recently discovered human polyomaviruses in a longitudinal kidney transplant cohort

A large number of human polyomaviruses have been discovered in the last 7 years. However, little is known about the clinical impact on vulnerable immunosuppressed patient populations. Blood, urine, and respiratory swabs collected from a prospective, longitudinal adult kidney transplant cohort (n = 167) generally pre-operatively, at day 4, months 1, 3, and 6 posttransplant, and at BK viremic episodes within the first year were screened for 12 human polyomaviruses using real-time polymerase chain reaction. Newly discovered polyomaviruses were most commonly detected in the respiratory tract, with persistent shedding seen for up to 6 months posttransplant. Merkel cell polyomavirus was the most common detection, but was not associated with clinical symptoms or subsequent development of skin cancer or other skin abnormalities. In contrast, KI polyomavirus was associated with respiratory disease in a subset of patients. Human polyomavirus 9, Malawi polyomavirus, and human polyomavirus 12 were not detected in any patient samples.

Strategies for improving safety and health of ethnic minority construction workers

The construction industries of developed countries are faced with an aging workforce and a shortage of recruits. It is common for migrant workers/ethnic minorities (EMs) who are already part of the society to join the construction industry. With increasing involvement of EMs in the construction industry, effective strategies for improving their safety and health are urgently needed. The existing body of knowledge is mainly derived from research conducted in English-speaking countries with Western cultures. Research on safety of migrant/EM construction workers in multidialect Asian countries with Eastern cultures has been lacking. This study aimed to identify various strategies for improving the safety and health of EM construction workers from the Asian perspective. Twenty-two face-to-face semistructured interviews were performed with safety professionals in Hong Kong followed by two rounds of Delphi survey with 18 safety experts to verify the interview findings and rank the relative importance of the strategies. The study unveiled 14 strategies for improving the safety performance of EM workers. The three most important ones identified were: (1) to provide safety training in EM native languages; (2) that government and industry associations should play an active role in promoting health and safety awareness of EM workers, and; (3) to encourage EM workers to learn the local language. This study contributes to filling the research gap by evaluating the strategies for improving safety of migrant/EM construction workers in Asian countries with Eastern cultures in which English is not the first language. Research findings would assist occupational health and safety experts and relevant stakeholders in designing strategies for improving the safety and health of EM workers, which will ultimately improve overall safety performance of the construction industry.