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BACKGROUND: While genome-wide association studies (GWAS) have identified germline variants influencing the risk of developing colorectal cancer (CRC), there has been limited examination of the possible role of inherited variation as a determinant of patient outcome. PATIENTS AND METHODS: We performed a GWAS for overall survival (OS) in 1926 patients with advanced CRC from the COIN and COIN-B clinical trials. For single nucleotide polymorphisms (SNPs) showing an association with OS (P < 1.0 × 10(−5)), we conducted sensitivity analyses based on the time from diagnosis to death and sought independent replications in 5675 patients from the Study of Colorectal Cancer in Scotland (SOCCS) and 16,964 patients from the International Survival Analysis in Colorectal cancer Consortium (ISACC). We analysed the Human Protein Atlas to determine if ERBB4 expression was associated with survival in 438 patients with colon adenocarcinomas. RESULTS: The most significant SNP associated with OS was rs79612564 in ERBB4 (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 1.16–1.32, P = 1.9 × 10(−7)). SNPs at 17 loci had suggestive associations for OS and all had similar effects on the time from diagnosis to death. No lead SNPs were independently replicated in the meta-analysis of all patients from SOCCS and ISACC. However, rs79612564 was significant in stage-IV patients from SOCCS (P = 2.1 × 10(−2)) but not ISACC (P = 0.89) and SOCCS combined with COIN and COIN-B attained genome-wide significance (P = 1.7 × 10(−8)). Patients with high ERBB4 expression in their colon adenocarcinomas had worse survival (HR = 1.50, 95% CI = 1.1–1.9, P = 4.6 × 10(−2)). CONCLUSIONS: Genetic and expression data support a potential role for rs79612564 in the receptor tyrosine kinase ERBB4 as a predictive biomarker of survival.

Background: Pharmacotherapy provides an option for overweight and obese adults to reduce their body weight if lifestyle modification fails. This systematic review summarises latest and likely practice-changing evidence for the benefits and harms of weight-lowering drugs. Methods: The network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) for randomised controlled trials of weight-lowering drugs in overweight and obese adults. We performed a frequentist random-effect network meta-analysis to summarise the evidence and applied GRADE frameworks to rate the certainty of the evidence, calculate the absolute effects, categorise interventions and present the findings. Findings: The 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered body weight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification alone. High to moderate certainty evidence established phentermine/topiramate (odds ratio [OR] of ≥5% weight reduction: 8·00, 95% confidence interval [CI]: 5·19 to 12·34; mean difference [MD] of percent body weight change: −7·97%, 95%CI: −9·28 to −6·66%) and glucagon-like peptide-1 (GLP-1) receptor agonists (OR: 6·20, 95% CI: 4·88 to 7·89; MD: −5·75%, 95%CI: −6·30 to −5·20%) were among the most effective in lowering weight. Naltrexone/bupropion (OR: 2·68, 95% CI: 2·06 to 3·49), phentermine/topiramate (OR, 2·36, 95% CI: 1·60 to 3·46), GLP-1 receptor agonists (OR: 2·16, 95% CI: 1·68 to 2·78), and orlistat (OR: 1·68, 95% CI: 1·38 to 2·05) increase any adverse event leading to drug discontinuation. In a post hoc analysis, semaglutide, one of the GLP-1 receptor agonists, demonstrated for both likelihood of ≥5% weight loss (OR: 9·81, 95% CI: 7·06 to 13·63) and percent body weight change (MD: −11.41%, 95%CI: −12.54 to −10.27%) and substantially larger than any other drugs with an increased risk of adverse events leading to discontinuation (OR: 1·98; 95% CI: 1·33 to 2·96). Interpretation: In overweight and obese adults, phentermine/topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide may be the most effective. Funding: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (grant numbers ZYGD18022 and 2020HXF011). Declaration of Interest: We declare no competing interests.

Chinese Abstract: 在社区公益活动中，我们观察到对自身经济状况不满意的人群更有可能被投资机构的推广信息所影响，出现较高的P2P网贷投资意愿。虽然该现象非常普遍，然而这其中的机制却缺乏研究。在本研究中，我们通过稀缺思维理论 (Shah, Shafir, & Mullainathan, 2015) 和错误管理理论 (Haselton & Buss, 2009) 对这一现象的形成机制进行了分析。通过两个实验，我们取得了三项研究发现。首先，经济状况满意程度对P2P网贷投资意愿有着显著影响，对自身经济状况不满意的个体表现出了显著更高的P2P网贷投资意愿。其次，这一现象的形成原因是因为对自身经济状况不满意的个体会显著高估P2P网贷中的投资利益，显著低估投资中的风险，使得其在面对P2P网贷投资产品时更倾向于选择II类错误（即冒着风险进行投资的取伪错误）。最后，鼓励网贷投资的推广信息在经济状况满意程度对P2P网贷投资意愿的影响中起了显著的正向调节作用，暴露于网贷投资推广信息增强了对自身经济状况不满意的个体在面对P2P网贷投资时的感知利益上升、感知风险下降和投资意愿升高的倾向。基于这些发现，我们一方面建议未来的互联网金融投资应该设立一定的投资门槛以防范盲目投资，另一方面建议应该加强对网贷投资推广信息的监管。 English Abstract: In our community charity activities, we observed that people who are dissatisfied with their financial situation are more likely to be affected by the promotion information from online investment institutions, resulting in higher P2P lending investment intention. Although this phenomenon is very common, the mechanism is lacking in research. In this study, we explored the mechanism of this phenomenon through scarcity mind-set theory (Shah, Shafir, & Mullainathan, 2015) and error management theory (Haselton & Buss, 2009). Through two experiments, we have made three research findings. Firstly, the degree of financial satisfaction has a significant impact on P2P lending investment intention. Individuals who are relatively financial dissatisfied have shown a significantly higher intention in investing in P2P lending. Secondly, the mechanism of the above phenomenon is that individuals in financial dissatisfaction were significantly overestimated the investment benefits in P2P lending, and significantly underestimated the risks in that investment, making them more inclined to choose a type II error (the false negative error, i.e., investing in risk) in P2P lending investment. Finally, the promotion information which encouraging online investment has played as a significant positive moderator between financial dissatisfaction and P2P lending investment intention. After being exposed to investment promotion information, individuals in financial dissatisfaction shown an increasing tendency in overestimate investment benefits and underestimate investment risks, and the intention to invest in P2P lending were much stronger. Based on these findings, we suggest that online financial investment firms should set a certain investment threshold to prevent irrational investment. Moreover, we suggest strengthening the supervision of online investment promotion information.

While shareholder proposals related to ES issues nearly always fail, we show that investors’ support for these proposals contains information regarding future risks that firms face. Support levels are informative regarding the probability of negative tail returns that stem from future ES incidents. Examining the economic channels underlying this finding, we find that agency frictions contribute to proposal failure, leading to predictable tail events. Contrasting ES versus non-ES failed proposals within the same firm, we find that predictability is unique to ES initiatives; this is consistent with higher uncertainty regarding the value of ES initiatives exacerbating agency frictions.

Introduction The plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism was considered to be associated with risk of venous thromboembolism (VTE), while evidence remains inadequate. To provide a more accurate estimation of this relationship, we performed an updated meta-analysis of all eligible studies. Materials and Methods A systematical search was performed in PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure (CNKI) and Cqvip databases to identify relevant studies published before March 6th 2014. The odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using the fixed/random-effects model using Review Manager 5.1 and STATA 12.0. Results A total of 34 studies with 3561 cases and 5693 controls were analyzed. Overall, significant association between the PAI-1 4G/5G variant and VTE risk in total population (dominant model: OR = 1.32, 95%CI: 1.13-1.54) was observed. And this variant was also related to the deep vein thrombosis risk (dominant model: OR = 1.60, 95%CI: 1.24-2.06, P = 0.0003). In the subgroup analyses on ethnicity, significant results were obtained in both Asians (dominant model: OR = 2.08, 95%CI: 1.29-3.35, P = 0.003) and Caucasians (dominant model: OR = 1.31, 95%CI: 1.10-1.56, P = 0.003). However, no significant association was found in patients with provoked VTE. In terms of subgroup analyses on co-existence of other thrombotic risk factors, the PAI-1 4G/5G polymorphism was significantly associated with VTE risk in patients with factor V Leiden mutation (dominant model: OR = 1.72, 95%CI: 1.17-2.53), but not in patients with cancer or surgery. Conclusion Our findings demonstrate the role of PAI-1 4G/5G polymorphism being a risk candidate locus for VTE susceptibility, especially in patients with other genetic thrombophilic disorders.

The effect of gender on outcomes after lower extremity revascularization is controversial. The aim of our systemic review and meta-analysis was to evaluate the gender-related outcomes after peripheral vascular interventions.We systematically searched MEDLINE, Embase, Cochrane Database, and Scopus to identify studies comparing outcomes after revascularization according to gender. A random-effects model was used to pool outcomes. Time-to-event data were reported using hazard ratios (HRs) and dichotomous data were presented using odds ratios (ORs).Included were 40 studies. Pooling of short-term outcomes after intervention showed that women had significantly increased risks of 30-day mortality (OR, 1.31; 95% confidence interval [CI], 1.11-1.55; P = .001), amputation (OR, 1.07; 95% CI, 1.02-1.12; P = .002), early graft thrombosis (OR, 1.56; 95% CI, 1.28-1.90; P .0001), embolization (OR, 1.64; 95% CI, 1.24-2.17; P = .0005), incisional site complication (OR, 1.56; 95% CI, 1.34-1.80; P .0001), cardiac events (OR, 1.21; 95% CI, 1.16-1.26; P .0001), stroke (OR, 1.35; 95% CI, 1.19-1.53; P .0001), and pulmonary complication (OR, 1.07; 95% CI, 1.03-1.12; P = .0006). No significant differences were found between women and men for short-term reinterventions (OR, 1.06; 95% CI, 0.73-1.54; P = .74) and renal complications (OR, 1.03; 95% CI, 0.76-1.39; P = .86). No significant differences in long-term outcomes between women and men were found, with similar rates of cumulative survival (HR, 1.10; 95% CI, 0.97-1.24; P = .12), primary patency (HR, 1.14; 95% CI, 1.00-1.30; P = .06), secondary patency (HR, 1.07; 95% CI, 0.86-1.34; P = .54), and limb salvage (HR, 0.93; 95% CI, 0.70-1.24; P = .63). However, in the open surgery subgroup, women had significantly reduced survival compared with men (HR, 1.21; 95% CI, 1.01-1.44; P = .04).Women have inferior short-term outcomes but similar long-term outcomes compared with men after lower limb revascularization. A higher treatment threshold may be warranted when considering intervening on women with symptomatic peripheral arterial disease owing to the increased risks of postprocedural mortality and complications.