The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology ...designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.
Living up to the expectations of the JIBS Decade Award, Goerzen, Asmussen, and Nielsen’s 2013 paper not only introduced the literature on global cities to the international business (IB) community ...but continues to be generative. In their “Retrospective and a Looking Forward” paper 10 years later, the authors highlight megatrends about people, places and things, and new contexts and alternative perspectives, and they encourage further new ways of thinking about global cities and IB. This commentary expands upon their framework of three overlapping circles of global issues, global organizations, and global locations, by drawing especially from recent experiences in the U.S. and research in economic geography and allied fields. Facing global issues of climate change, human rights, health, housing, and the impacts of digital technologies on work, cities offer prospects of responding to these challenges, a context for multinational enterprises (MNEs) to consider. Against the backdrop of large-scale global migrations of unskilled, mostly contract, workers to global cities in developed economies, recruitment agencies and advocacy groups for migrants are global organizations as important as MNEs. Finally, the fluidity of physical boundaries, as illustrated by city-regions, world regions beyond traditional Western-centric perspectives, and intra-national variations, is key to analyzing global locations.
How does political decentralization affect the frequency and costliness of bribe extraction by corrupt officials? Previous empirical studies, using subjective indexes of perceived corruption and ...mostly fiscal indicators of decentralization, have suggested conflicting conclusions. In search of more precise findings, we combine and explore two new data sources—an original cross-national data set on particular types of decentralization and the results of a firm level survey conducted in 80 countries about firms' concrete experiences with bribery. In countries with a larger number of government or administrative tiers and (given local revenues) a larger number of local public employees, reported bribery was more frequent. When local—or central—governments received a larger share of GDP in revenue, bribery was less frequent. Overall, the results suggest the danger of uncoordinated rent-seeking as government structures become more complex.
Summary
Background
Cirrhotic patients admitted to intensive care units (ICUs) have high mortality rates. The Chronic Liver Failure–Sequential Organ Failure Assessment (CLIF‐SOFA) score, a modified ...Sequential Organ Failure Assessment (SOFA) score, is a newly developed scoring system exclusively for patients with end‐stage liver disease.
Aim
To externally validate the efficacy of the CLIF‐SOFA score and evaluate other scoring systems for 6‐month mortality in critically ill cirrhotic patients.
Methods
This study prospectively recorded and analysed the data for 30 demographical parameters and some clinical characteristic variables on day 1 of 250 cirrhotic patients admitted to a 10‐bed specialised hepatogastroenterology ICU in a 2000‐bed tertiary care referral hospital during the period from September 2010 to August 2013.
Results
The overall in‐hospital and 6‐month mortality rate were 58.8% (147/250) and 78.0% (195/250), respectively. Liver diseases were mostly attributed to hepatitis B virus infection (32%). Multiple Cox logistic regression hazard analysis revealed that Glasgow coma scale, both the CLIF‐SOFA and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of ICU admission were independent predictors of 6‐month mortality. Analysis of the area under the receiver operating characteristic curve revealed that the CLIF‐SOFA score had the best discriminatory power (0.900 ± 0.020). Moreover, the cumulative 6‐month survival rates differed significantly for patients with a CLIF‐SOFA score ≤11 and those with a CLIF‐SOFA score >11 on the ICU admission day.
Conclusion
Both CLIF‐SOFA and APACHE III scores are excellent prognosis evaluation tools for critically ill cirrhotic patients.
Despite the fact that urban hukou is understood to be far superior to rural hukou and that rural migrants have strong intention to stay in cities for many years, responses to hukou reforms that ...increase opportunities to obtain urban hukou have been less than enthusiastic. This article addresses this puzzle by showing how the respective values of rural hukou and urban hukou have changed in recent decades. The access and benefits that are tied to rural hukou-including farming and housing land, compensation for land requisition, and more relaxed birth control-are considered increasingly valuable. Thus, many migrants are opting to straddle and circulate between the city and countryside rather than giving up their rural hukou. Meanwhile, the competitive advantage of urban hukou has declined as China seeks to expand basic public services to all and as the market's role in distri-buting food, housing, and other needs increases. The mismatch between rural migrants' preference for large cities and hukou reforms' focus on medium-sized and small cities and towns also undermines the reforms' effectiveness. From a policy point of view, this article's findings suggest that China's urbanization strategy should take multilocality seriously and should focus on rural migrants' livelihood and well-being in cities, rather than on hukou conversion alone.
Given the central role of households in motivating and implementing migration, this paper argues that the “householding” and split-household approaches are fundamental and essential for migration ...research, by drawing from original research on rural-urban migrants in China and four published studies on Asian migrants. Translocality and household-splitting that enable the earning of remittances or help meet other family goals such as children's education, set in motion processes of gender and intergenerational divisions of labor that involve both the migrants and the left-behind, and have implications for urban development in large cities as well as cities near rural areas. Hundreds of millions of rural migrants in China circulate between their home villages and host cities, and large numbers of women from Southeast Asia work overseas. Likewise, skilled migrants from South Asia and East Asia maintain transnational households that straddle their home and host countries. Household biographies and interviewees' narratives from these examples highlight two strategies of migrants and their family members: their flexibility and frequent changes of location, work, activity, and household arrangement; and their reinventing women's and men's responsibilities without challenging traditional gender ideology. These stories underscore the importance of householding and split-households for informing contemporary migration theories and research.
•Both international and internal migrants pursue “householding” and split-household strategies.•Both migrants to cities and the left-behind contribute to sustaining and maintaining the split households.•Members of split households change frequently their location, work, and household arrangement.•Migrants and the left-behind reinvent their family responsibilities vis-à-vis gender norms.•Experiences of Asian migrants to cities are important for migration theories and research.
The concept of integration is central for understanding the experiences of groups in marginalized positions in contemporary urban societies. Research on integration has primarily focused on ...international migrants, especially immigrants. Yet internal migrants like rural-urban migrant workers in China also face formidable institutional, economic, cultural, and social barriers in the host society. Informed by integration theory, and drawing on a questionnaire survey of 1,100 migrants conducted in Wuhan, this research effort examines how institutional barriers intersect with economic, social/cultural, and identity integration to explain the experiences of rural migrant workers in Chinese cities. The authors' analysis, based on OLS and logit regressions, shows that the hukou system is a persistent barrier to migrant workers, despite improvement over time of their economic, social/cultural, and identity integration into urban society. Their findings also indicate that human capital is important for migrants' economic and identity integration. Moreover, migrant workers who are socially and culturally adapted, speak the dialect of the host society, and have the financial resources to be self-employed (or buy an apartment in the city) are more likely to develop a sense of belonging in the city than other migrants.
Toll-like receptors (TLRs) are a family of pattern recognition receptors involved in cardiovascular diseases. Notably, numerous studies have demonstrated that TLR4 activates the expression of several ...of pro-inflammatory cytokine genes that play pivotal roles in myocardial inflammation, particularly myocarditis, myocardial infarction, ischemia-reperfusion injury, and heart failure. In addition, TLR4 is an emerging target for anti-inflammatory therapies. Given the significance of TLR4, it would be useful to summarize the current literature on the molecular mechanisms and roles of TLR4 in myocardial inflammation. Thus, in this review, we first introduce the basic knowledge of the TLR4 gene and describe the activation and signaling pathways of TLR4 in myocardial inflammation. Moreover, we highlight the recent progress of research on the involvement of TLR4 in myocardial inflammation. The information reviewed here may be useful to further experimental research and to increase the potential of TLR4 as a therapeutic target.
Summary
Background
Hepatitis C virus (HCV) infection has been linked to an increased risk of insulin resistance and carotid atherosclerosis.
Aim
To investigate the association between HCV infection ...and stroke, and the effect of interferon‐based therapy (IBT) on stroke risk in chronic hepatitis C (CHC) patients.
Methods
We conducted a retrospective cohort study that followed up 3113 subjects with a newly detected HCV infection and 12 452 age‐ and gender‐matched subjects without HCV infection selected from a random sample of 106 beneficiaries from the Taiwan National Health Insurance Program up to 5 years. Use of IBT was defined as treatment with interferon alpha, pegylated interferon alpha‐2a or pegylated interferon alpha‐2b for at least 3 months. The hazard ratio (HR) for newly detected stroke was calculated for subjects with HCV compared to those without HCV, and for IBT‐treated HCV patients compared to non‐IBT‐treated HCV patients while adjusting for possible confounding factors.
Results
The overall person‐years of follow‐up were 8624.11 in patients with HCV, 54 533.69 in patients without HCV, 666.65 in IBT‐treated patients, and 7886.49 in nontreated patients. The multivariable‐adjusted hazard ratio (HR) for newly detected stroke was 1.23 for subjects with HCV compared to the age‐ and sex‐matched subjects without HCV (adjusted HR = 1.23, 95% CI = 1.06–1.42, P = 0.008). Moreover, use of IBT significantly reduced the risk of stroke in HCV patients (adjusted HR = 0.39, 95% CI = 0.16–0.95, P = 0.039) after adjusting for known prognostic factors.
Conclusions
Interferon‐based therapy may reduce the long‐term risk of stroke in patients with chronic HCV infection.
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