Using In Vitro High‐Throughput Screening Data for Predicting Benzo[k]Fluoranthene Human Health Hazards

Today there are more than 80,000 chemicals in commerce and the environment. The potential human health risks are unknown for the vast majority of these chemicals as they lack human health risk assessments, toxicity reference values, and risk screening values. We aim to use computational toxicology and quantitative high‐throughput screening (qHTS) technologies to fill these data gaps, and begin to prioritize these chemicals for additional assessment. In this pilot, we demonstrate how we were able to identify that benzo[k]fluoranthene may induce DNA damage and steatosis using qHTS data and two separate adverse outcome pathways (AOPs). We also demonstrate how bootstrap natural spline‐based meta‐regression can be used to integrate data across multiple assay replicates to generate a concentration–response curve. We used this analysis to calculate an in vitro point of departure of 0.751 μM and risk‐specific in vitro concentrations of 0.29 μM and 0.28 μM for 1:1,000 and 1:10,000 risk, respectively, for DNA damage. Based on the available evidence, and considering that only a single HSD17B4 assay is available, we have low overall confidence in the steatosis hazard identification. This case study suggests that coupling qHTS assays with AOPs and ontologies will facilitate hazard identification. Combining this with quantitative evidence integration methods, such as bootstrap meta‐regression, may allow risk assessors to identify points of departure and risk‐specific internal/in vitro concentrations. These results are sufficient to prioritize the chemicals; however, in the longer term we will need to estimate external doses for risk screening purposes, such as through margin of exposure methods.     

On the survival time of a repairable duplex system sustained by a cold standby unit subjected to a priority rule

We analyze the survival time of a general duplex system sustained by a cold standby unit subjected to a priority rule. The analysis is based on advanced complex function theory (sectionally holomorphic functions). As an example, we consider Weibull–Gnedenko and Erlang distributions for failure and repair. Several graphs are displaying the survival function.     

Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity,voiding function and prostate safety parameters

Whether testosterone replacement therapy (TRT) is a lifelong treatment for men with hypogonadism remains unknown. We investigated long-term TRT and TRT withdrawal on obesity and prostate-related parameters. Two hundred and sixty-two hypogonadal patients (mean age 59.5) received testosterone undecanoate in 12-week intervals for a maximum of 11 years. One hundred and forty-seven men had TRT interrupted for a mean of 16.9 months and resumed thereafter (Group A). The remaining 115 patients were treated continuously (Group B). Prostate volume, prostate-specific antigen (PSA), residual voiding volume, bladder wall thickness, C-reactive protein (CRP), aging male symptoms (AMS), International Index of erectile function – erectile function (IIEF-EF) and International Prostate Symptoms Scores (IPSS) were measured over the study period with anthropometric parameters of obesity, including weight, body mass index (BMI) and waist circumference. Prior to interruption, TRT resulted in improvements in residual voiding volume, bladder wall thickness, CRP, AMS, IIEF-EF, IPSS and obesity parameters while PSA and prostate volume increased. TRT interruption reduced total testosterone to hypogonadal levels in Group A and resulted in worsening of obesity parameters, AMS, IPSS, residual voiding volume and bladder wall thickness, IIEF-EF and PSA while CRP and prostate volume were unchanged until treatment resumed whereby these effects were reversed. TRT interruption results in worsening of symptoms. Hypogonadism may require lifelong TRT.     

Global employment and decent jobs, 2010–2030: The forces of demography and automation

Globally, an estimated 734 million jobs will be required between 2010 and 2030 to accommodate recent and ongoing demographic shifts, account for plausible changes in labour force participation rates, and achieve target unemployment rates of at or below 4 per cent for adults and at or below 8 per cent for youth. The facts that most new jobs will be required in countries where “decent” jobs are less prevalent and workers in many occupations are increasingly subject to risks of automation further compound the challenge of job creation, which is already quite sizable in historical perspective. Failure to create the jobs that are needed through 2030 would put currently operative social security systems under pressure and undermine efforts to guarantee the national social protection floors enshrined in the Sustainable Development Goals (SDGs).     

Romantic relationships,college student alcohol use,and negative consequences of drinking

This study examined whether being in a romantic relationship is associated with undergraduates’ alcohol use and negative consequences of drinking. Alcohol use was operationalized to include amount and frequency of drinking, binge drinking, and drunkenness. Negative consequences included: having a hangover, missing a class, getting behind in school work, doing something that was later regretted, forgetting where the student was or what they did, having unplanned sex, and getting hurt or injured. Data came from an online survey distributed to Midwestern undergraduate students (N = 572), with analyses conducted separately for men and women. Results indicated that being in a committed relationship generally served as a protective factor against drunkenness, but did not reduce frequency of drinking or binge drinking. Whereas romantically committed men were only less likely to report doing something that was later regretted, women in romantic relationships were less likely to experience all negative consequences of drinking considered here.     

Modeling the Adenoma and Serrated Pathway to Colorectal CAncer (ASCCA)

Several colorectal cancer (CRC) screening models have been developed describing the progression of adenomas to CRC. Currently, there is increasing evidence that serrated lesions can also develop into CRC. It is not clear whether screening tests have the same test characteristics for serrated lesions as for adenomas, but lower sensitivities have been suggested. Models that ignore this type of colorectal lesions may provide overly optimistic predictions of the screen‐induced reduction in CRC incidence. To address this issue, we have developed the Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model that includes the adenoma‐carcinoma pathway and the serrated pathway to CRC as well as characteristics of colorectal lesions. The model structure and the calibration procedure are described in detail. Calibration resulted in 19 parameter sets for the adenoma‐carcinoma pathway and 13 for the serrated pathway that match the age‐ and sex‐specific adenoma and serrated lesion prevalence in the COlonoscopy versus COlonography Screening (COCOS) trial, Dutch CRC incidence and mortality rates, and a number of other intermediate outcomes concerning characteristics of colorectal lesions. As an example, we simulated outcomes for a biennial fecal immunochemical test screening program and a hypothetical one‐time colonoscopy screening program. Inclusion of the serrated pathway influenced the predicted effectiveness of screening when serrated lesions are associated with lower screening test sensitivity or when they are not removed. To our knowledge, this is the first model that explicitly includes the serrated pathway and characteristics of colorectal lesions. It is suitable for the evaluation of the (cost)effectiveness of potential screening strategies for CRC.     

Popularity Contagion Among Adolescents

This study aimed to support the theory of popularity contagion, which posits that popularity spreads among friends spontaneously and regardless of behavioral changes. Peer nominations of status and behavior were collected annually between 6th and 12th grades from a total of 1062 adolescents. Longitudinal hypotheses were mostly supported using path analyses, showing (1) that individual popularity could be predicted by friends’ popularity levels over time, even when controlling for stability of individual popularity; (2) that this prediction was not accounted for by behavioral contagion of aggressive or prosocial behaviors; and (3) that individual social preference generally could not be predicted by friends’ preference levels over time. Implications, limitations, and directions for future research are discussed.     

Effects of Network Approval on Accounts of Commitment Trajectories in Intraracial and Interracial Relationships

The current study used dyadic data to investigate the impact of relationship type and social support on the retrospective accounts of commitment trajectories of romantic relationships. Past research suggests that social support is a positive contributor to relationship stability and commitment, which may be especially true for partners in interracial relationships who face broader societal opposition than intraracial couples. Using multilevel modeling, we investigated the effects of sex, relationship type, and social support on reports of commitment. Results showed differences in trajectories of commitment based on couple type (interracial vs. intraracial) for both men and women. Social support was found to have an especially strong impact for women in interracial relationships compared with women in intraracial relationships, but there was no differential impact among men.