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The common law on vicarious liability is unsatisfactory because the doctrine is couched at such a high level of generality that it cannot yield predictable results when applied to a given fact situation. This paper is an attempt to inject some precision into the doctrine. It examines and rejects three justifications for the doctrine: effective compensation/risk spreading, deterrence and certain theories related to quid pro quo. It then proposes the most suitable justification for the doctrine: vicarious liability is imposed because and when the defendant, by placing the tortfeasor in the position in its organisation that it did with that position's accompanying privileges and demands, had created or significantly enhanced the risk of the claimant’s injury. Three implications follow from this justification: (1) there is no vicarious liability for the wrongful acts of independent contractors; (2) agency reasoning should be rejected; and (3) we should stop using the phrase ‘enterprise-risk approach’.

SummaryRelationships between the genome, transcriptome, and metabolome underlie all evolved phenotypes. However, it has proved difficult to elucidate these relationships because of the high number of variables measured. A recently developed data analytic method for characterizing the transcriptome can simplify interpretation by grouping genes into independently modulated sets (iModulons). Here, we demonstrate how iModulons reveal deep understanding of the effects of causal mutations and metabolic rewiring. We use adaptive laboratory evolution to generateE. colistrains that tolerate high levels of the redox cycling compound paraquat, which produces reactive oxygen species (ROS). We combine resequencing, iModulons, and metabolic models to elucidate six interacting stress tolerance mechanisms: 1) modification of transport, 2) activation of ROS stress responses, 3) use of ROS-sensitive iron regulation, 4) motility, 5) broad transcriptional reallocation toward growth, and 6) metabolic rewiring to decrease NADH production. This work thus reveals the genome-scale systems biology of ROS tolerance.Graphical Abstract

In recent years, there is a large increase in structural diversity of novel psychoactive substances (NPS), exacerbating drug abuse issues as these variants evade classical detection methods such as spectral library matching. Gas chromatography mass spectrometry (GC-MS) is commonly used to identify these NPS. To tackle this issue, machine learning models are developed to address the analytical challenge of identifying unknown NPS, using only GC-MS data. 891 GC-MS spectra are used to train and evaluate multiple supervised machine learning classifiers, namely artificial neural network (ANN), convolutional neural network (CNN) and balanced random forest (BRF). 7 classes, comprising 6 NPS classes (cathinone, cannabinoids, phenethylamine, piperazine, tryptamines and fentanyl) and other unrelated compounds can be effectively classified with a macro-F1 score ~ 0.9, averaged across all cross-validation folds. These results indicate that machine learning models are a promising complement as an effective NPS detection tool.

By introducing diversity of ownership interests via “mixed-ownership reform”, China seeks to alleviate internal governance problems in state-owned enterprises (SOEs), enhancing their efficiency and competitiveness. Private strategic partners invest for a large minority stake, with government typically retaining a majority share and influence. Resulting questions related to strategic leadership and corporate governance, addressed in this paper from the perspective of principal-agent theory, include: To what extent do the board chairs of SOEs affect their financial performance? How is this relationship impacted by the institutional changes induced by mixed-ownership reform? Do these effects vary between SOEs operating in competitive and monopolistic industries? Analyzing data on Shanghai- and Shenzhen-listed SOEs from 2008 to 2017 using the multilevel linear model (MLM) method, we determine that board chairs have a noticeable effect on financial performance, varying by type of SOE, and that mixed-ownership reform reduces their impact.

Can state governance spur firm innovation in an emerging economy and transform state-owned enterprises (SOEs) from “dying dinosaurs” to “dynamic dynamos”? We seek an answer to this question by investigating the innovative performance of restructured SOEs in China’s high-speed train sector. We expect that SOE restructuration will improve firm innovation, but that the degree of improvement will depend on how the state conducts firm governance. Building on institutional theory, we distinguish state governance via equity ownership and administrative affiliation in an emerging economy with market-hierarchy institutional conflicts. Under such conflicts, restructured SOEs experience institutional logic dissonance, which hinders organizational change for technological innovation. We hypothesize that state ownership exacerbates institutional logic dissonance at a restructured SOE, thus limiting innovation improvement from restructuration; in contrast, state affiliation mitigates firm dissonance and hence augments such improvement. We find empirical evidence for these hypotheses in a comprehensive panel of high-speed train manufacturers in China between 1989 and 2015. This study contributes to the institution-based theory of technological innovation in emerging economies. On the practical front, our findings suggest that emerging states may adopt arms-length governance to spur SOE innovation and unleash these dynamic dynamos to fuel sustainable economic growth.

Background Adaptive Laboratory Evolution (ALE) has emerged as an experimental approach to discover mutations that confer phenotypic functions of interest. However, the task of finding and understanding all beneficial mutations of an ALE experiment remains an open challenge for the field. To provide for better results than traditional methods of ALE mutation analysis, this work applied enrichment methods to mutations described by a multiscale annotation framework and a consolidated set of ALE experiment conditions. A total of 25,321 unique genome annotations from various sources were leveraged to describe multiple scales of mutated features in a set of 35 Escherichia coli based ALE experiments. These experiments totalled 208 independent evolutions and 2641 mutations. Additionally, mutated features were statistically associated across a total of 43 unique experimental conditions to aid in deconvoluting mutation selection pressures. Results Identifying potentially beneficial, or key, mutations was enhanced by seeking coding and non-coding genome features significantly enriched by mutations across multiple ALE replicates and scales of genome annotations. The median proportion of ALE experiment key mutations increased from 62%, with only small coding and non-coding features, to 71% with larger aggregate features. Understanding key mutations was enhanced by considering the functions of broader annotation types and the significantly associated conditions for key mutated features. The approaches developed here were used to find and characterize novel key mutations in two ALE experiments: one previously unpublished with Escherichia coli grown on glycerol as a carbon source and one previously published with Escherichia coli tolerized to high concentrations of L-serine. Conclusions The emergent adaptive strategies represented by sets of ALE mutations became more clear upon observing the aggregation of mutated features across small to large scale genome annotations. The clarification of mutation selection pressures among the many experimental conditions also helped bring these strategies to light. This work demonstrates how multiscale genome annotation frameworks and data-driven methods can help better characterize ALE mutations, and thus help elucidate the genotype-to-phenotype relationship of the studied organism.

PURPOSE: Despite the increasing use of GnRHa to trigger final oocyte maturation in segmented IVF cycles, the effects of trigger modality on chromosomal competence and embryo quality remain controversial. Hence, the purpose of this study was to compare euploidy rates and pregnancy outcomes among hyper-responding women using hCG versus GnRHa trigger. METHODS: This retrospective study included 333 hyper-responders, defined as >15 oocytes retrieved, who underwent preimplantation genetic testing (PGT-A) in segmented IVF cycles using either GnRHa or urinary hCG trigger. Live birth rate (LBR) was the primary outcome of interest. Implantation rate (IR), clinical pregnancy rate (CPR), and euploidy rate were secondary outcomes. RESULTS: GnRH triggering was associated with improved IR (70.5 vs. 53.2%, p = 0.0475), LBR (51.3 vs. 33.8%, p = 0.0170) compared to hCG. A greater number of oocytes were retrieved (21.9 vs 18.4%, p

Universities in China have increased their entrepreneurship significantly, yet a good understanding of the specific characteristics of university-based technology transfers remains missing. This study focuses on a special type of university spinoffs in China, University-Run Enterprises (UREs), and examines how URE eminence contributes to a university's technology transfer performance, using panel data covering 195 universities over the five years from 2002 to 2006. The findings reveal that URE eminence not only signifies a university's strong entrepreneurial culture, but also signals commercial values and quality of the university research. It moderates the contribution of university scientists from the supply side and that of sourcing firms from the demand side.

What is the impact of noncavity-distorting intramural fibroids on live birth rates in in vitro fertilization (IVF) cycles? We searched Embase, MEDLINE, Google Scholar, Cochrane Library, and PUBMED ...

Although it is well recognized that environmental labeling certification (ELC) is becoming an increasingly important voluntary environmental regulation worldwide, the evidence regarding its role in environmental innovation remains unknown. This study examines the impact of ELC on corporate environmental innovation (CEI) from both external and internal perspectives via the combination of legitimacy theory and the resource management perspective. Based on panel data of listed Chinese manufacturing firms from 2008 to 2014, it is found that ELC improves CEI. However, this relationship is also regulated by two contextual factors: the positive impact of ELC on CEI is found to be stronger for non-state-owned enterprises (non-SOEs) than for state-owned enterprises (SOEs), and it is stronger for firms in regions with a low degree of local government intervention than for firms in regions with a high degree of local government intervention. This study makes important theoretical contributions and has extensive practical value.

PurposeThe literature on how emerging market multinational enterprises (EMNEs) overcome the liability of emergingness/origin has sidestepped a prerequisite for any efforts to overcome liability, namely, corporate compliance. The authors argue that EMNEs build corporate compliance capability as a knowledge-based firm-specific advantage (FSA) to adapt to institutional norms in advanced economies. In this study, the authors empirically examine the intricate relationships between corporate compliance capability and performance in the US subsidiaries of Chinese firms.Design/methodology/approachIn this study, the authors use survey data to empirically examine the intricate relationships between corporate compliance capability and performance in the US subsidiaries of Chinese firms.FindingsThe findings reveal a positive relationship between corporate compliance capability and subsidiary performance, as mediated by local financing.Originality/valueThe study suggests that corporate compliance capability helps a subsidiary gain legitimacy, which leads to local resource acquisition and utilization. Corporate compliance capability thus serves as a source of a knowledge-based FSA for EMNEs in developed economies.

OBJECTIVES: Complete deficiency of the serine protease inhibitor gene, SERPINB6, is responsible for autosomal-recessive, nonsyndromic sensorineural hearing loss in humans. A mouse model of this deafness gene identifies Serpinb6a expression in the neurosensory epithelium and fibrocytes of the cochlea. Homozygous Serpinb6a mutant mice display an exaggerated hearing loss after exposure to moderate acoustic trauma. It is unknown if and how heterozygous Serpinb6a mice show increased vulnerability to acoustic trauma. METHODS: We exposed Serpinb6a+/- and Serpinb6a+/+ mice to acoustic trauma and measured their hearing function prior to, 3 and 14 days postexposure, analysing shifts in hearing threshold and amplitudes of Wave I and II of the auditory brainstem-evoked response (ABR) to 4, 8, 16 and 32 kHz tones. RESULTS: Shifts in hearing threshold and Wave I amplitude of Serpinb6a+/- mice were not significantly different from Serpinb6a+/+ mice at both time points and all frequencies tested (P > 0.05, Mann-Whitney test). However, Wave II amplitudes at 16 and 32 kHz tones, were more severely diminished in Serpinb6a+/- mice (P

The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, Brachydactyly B and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of receptor action. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr alter ROR2 function. Moreover, we demonstrated that the activity of the ROR2 CRD requires Frizzled receptors. Thus, ROR2 acts via its CRD to potentiate the function of a receptor supercomplex that includes Frizzleds to transduce WNT5A signals.

The purpose of this review is to summarize and highlight recent critical advances in the diagnosis, classification, and management of adenomyosis.Recent studies have clarified the specific mechanism through which adenomyotic lesions invade the underlying myometrium by epithelial-mesenchymal transition. Correlation studies using diagnostic MRI also strongly support the hypothesis of a different pathogenesis between the inner and outer myometrium forms of adenomyosis. Given advances in diagnostic imaging, several international organizations have also highlighted the importance of classification systems for adenomyosis. Finally, selective progesterone receptor modulators and gonadotropin-releasing hormone antagonists have demonstrated significant promise for treating pelvic pain and bleeding associated with adenomyosis, whereas novel fertility-preserving surgical techniques have been introduced to excise diffuse adenomyotic pathology while maintaining adequate uterine integrity.Recent attempts at a uniform and reproducible classification system likely represent the first step for the development of a staging system for adenomyosis that can be correlated with the severity of clinical symptoms and promote an individualized therapeutic approach. Simultaneously, further insights into the etiology and pathogenesis as outlined in this review may also help in the development of targeted medical therapies.

Catalysis using iron–sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can prevent cell growth and survival when unmanaged, thus eliciting an essential stress response that is universal and fundamental in biology. Here we develop a computable multiscale description of the ROS stress response in Escherichia coli , called OxidizeME. We use OxidizeME to explain four key responses to oxidative stress: 1) ROS-induced auxotrophy for branched-chain, aromatic, and sulfurous amino acids; 2) nutrient-dependent sensitivity of growth rate to ROS; 3) ROS-specific differential gene expression separate from global growth-associated differential expression; and 4) coordinated expression of iron–sulfur cluster (ISC) and sulfur assimilation (SUF) systems for iron–sulfur cluster biosynthesis. These results show that we can now develop fundamental and quantitative genotype–phenotype relationships for stress responses on a genome-wide basis.

Endometriosis and atherosclerotic cardiovascular disease (ASCVD) are both essentially diseases of inflammation. It is well established that inflammation is the leading mechanism in the initiation and maintenance of vascular injury and in the development and progression of atherosclerosis. Thus, if women with endometriosis do indeed have increased general inflammation, they are at increased risk of developing microvascular dysfunction and atherosclerosis. Currently available evidence suggests that young female patients with proven endometriosis may be at a higher lifetime risk of developing cardiovascular disease; this may be unrecognized due to the relatively young age of women found to have endometriosis. Other mechanisms proposed to explain the link between endometriosis and ASCVD include similarities in the genetic underpinnings of each condition, including microRNA dysfunction and the association between endometriosis and early menopause, a risk for developing ASCVD. Although physicians today primarily focus on traditional risk factors when evaluating an individual female patient's risk of developing ASCVD, we believe that a history of endometriosis should be included as a possible risk factor and needs further exploration. A better understanding of the mechanisms linking endometriosis with ASCVD will hopefully guide the implementation of new therapies to mitigate the increased cardiovascular disease burden that patients with endometriosis might face.

Sperm DNA fragmentation (sDF) has emerged as a valuable tool for evaluating male fertility, yet the relationship between DNA fragmentation in the male gamete and idiopathic recurrent pregnancy loss (RPL) remains a topic of ongoing debate. Hence, a meta-analysis was conducted of 12 prospective and 2 retrospective studies involving 530 men with a history of RPL who underwent sDF testing compared with 639 fertile control participants. The main outcome measures were sDF measured by comet assay, TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL), sperm chromatin dispersion (SCD) or sperm chromatin structure assay. Overall, couples with a history of idiopathic RPL demonstrated higher levels of sDF than fertile couples (average mean difference 11.98, P 0.001). Subgroup analysis demonstrated a similar average mean difference between the RPL and control groups using SCD compared with TUNEL, while mean paternal age and mean sperm motility in the RPL groups tested by meta-regression demonstrated no significant effect on the mean differences in sDF (P 0.10). These results support the diagnostic value of sDF over standard semen analysis, as well as a possible paternally derived genetic origin of unexplained RPL. Further prospective studies are required to further assess the predictive utility of sDF for assessing couples with unexplained RPL.

This study examines the varying roles of power, status, and national culture in unethical decision-making. Most research on unethical behavior in organizations is grounded in Western societies; empirical comparative studies of the antecedents of unethical behavior across nations are rare. The authors conduct this comparative study using scenario studies with four conditions (high power vs. low power × high status vs. low status) in both China and Canada. The results demonstrate that power is positively related to unethical decision-making in both countries. Status has a positive effect on unethical decision-making and facilitates the unethical decisions of Canadian participants who have high power but not Chinese participants who have high power. To explicate participants’ unethical decision-making rationales, the authors ask participants to justify their unethical decisions; the results reveal that Chinese participants are more likely to cite position differences, whereas Canadian participants are more likely to cite work effort and personal abilities. These findings expand theoretical research on the relationship between social hierarchy and unethical decision-making and provide practical insights on unethical behavior in organizations.

Glucocorticoids have direct anti-inflammatory, anti-oxidant and anti-apoptotic effects on cochlear hair cells. Cochlear glucocorticoid therapy has gained particular attention for its ability to enhance the protection of residual hearing following hearing preservation cochlear implantation. Local drug delivery methods achieve high drug concentrations within the inner ear fluids but are reliant upon diffusion across the round window membrane. Diffusion has been shown to demonstrate large individual variability. This study explores the role of "adjuvant agents", which when administered with glucocorticoids, enhance inner ear absorption and distribution. Guinea pig cochleae were administered either dexamethasone alone or in combination with hyaluronic acid, histamine, or combination histamine and hyaluronic acid, targeted at the round window membrane. Control subjects received saline. Perilymph was sampled from the cochlear apex, and basal to apical dexamethasone concentrations recorded with mass spectroscopy. Cochleae were harvested, and immunohistochemistry employed to explore dexamethasone tissue penetration and distribution. Basal to apical gradients were observed along the scala tympani, with higher dexamethasone concentrations observed at the cochlear base. Gradients were more pronounced and uniform when administered on a hyaluronic acid sponge, while histamine increased absolute concentrations reaching the inner ear. Tissue penetration correlated with perilymph concentration. Our results demonstrate that adjuvant agents can be employed to enhance dexamethasone absorption and distribution in the inner ear, thus proposing therapeutic strategies that may enhance steroid facilitated hearing protection.