Effect Modification of the Association between Short-term Meteorological Factors and Mortality by Urban Heat Islands in Hong Kong

Background Prior studies from around the world have indicated that very high temperatures tend to increase summertime mortality. However possible effect modification by urban micro heat islands has only been examined by a few studies in North America and Europe. This study examined whether daily mortality in micro heat island areas of Hong Kong was more sensitive to short term changes in meteorological conditions than in other areas. Method An urban heat island index (UHII) was calculated for each of Hong Kong’s 248 geographical tertiary planning units (TPU). Daily counts of all natural deaths among Hong Kong residents were stratified according to whether the place of residence of the decedent was in a TPU with high (above the median) or low UHII. Poisson Generalized Additive Models (GAMs) were used to estimate the association between meteorological variables and mortality while adjusting for trend, seasonality, pollutants and flu epidemics. Analyses were restricted to the hot season (June-September). Results Mean temperatures (lags 0–4) above 29°C and low mean wind speeds (lags 0–4) were significantly associated with higher daily mortality and these associations were stronger in areas with high UHII. A 1°C rise above 29°C was associated with a 4.1% (95% confidence interval (CI): 0.7%, 7.6%) increase in natural mortality in areas with high UHII but only a 0.7% (95% CI: −2.4%, 3.9%) increase in low UHII areas. Lower mean wind speeds (5th percentile vs. 95th percentile) were associated with a 5.7% (95% CI: 2.7, 8.9) mortality increase in high UHII areas vs. a −0.3% (95% CI: −3.2%, 2.6%) change in low UHII areas. Conclusion The results suggest that urban micro heat islands exacerbate the negative health consequences of high temperatures and low wind speeds. Urban planning measures designed to mitigate heat island effects may lessen the health effects of unfavorable summertime meteorological conditions

An integration of complementary strategies for gene-expression analysis to reveal novel therapeutic opportunities for breast cancer

INTRODUCTION. Perhaps the major challenge in developing more effective therapeutic strategies for the treatment of breast cancer patients is confronting the heterogeneity of the disease, recognizing that breast cancer is not one disease but multiple disorders with distinct underlying mechanisms. Gene-expression profiling studies have been used to dissect this complexity, and our previous studies identified a series of intrinsic subtypes of breast cancer that define distinct populations of patients with respect to survival. Additional work has also used signatures of oncogenic pathway deregulation to dissect breast cancer heterogeneity as well as to suggest therapeutic opportunities linked to pathway activation. METHODS. We used genomic analyses to identify relations between breast cancer subtypes, pathway deregulation, and drug sensitivity. For these studies, we use three independent breast cancer gene-expression data sets to measure an individual tumor phenotype. Correlation between pathway status and subtype are examined and linked to predictions for response to conventional chemotherapies. RESULTS. We reveal patterns of pathway activation characteristic of each molecular breast cancer subtype, including within the more aggressive subtypes in which novel therapeutic opportunities are critically needed. Whereas some oncogenic pathways have high correlations to breast cancer subtype (RAS, CTNNB1, p53, HER1), others have high variability of activity within a specific subtype (MYC, E2F3, SRC), reflecting biology independent of common clinical factors. Additionally, we combined these analyses with predictions of sensitivity to commonly used cytotoxic chemotherapies to provide additional opportunities for therapeutics specific to the intrinsic subtype that might be better aligned with the characteristics of the individual patient. CONCLUSIONS. Genomic analyses can be used to dissect the heterogeneity of breast cancer. We use an integrated analysis of breast cancer that combines independent methods of genomic analyses to highlight the complexity of signaling pathways underlying different breast cancer phenotypes and to identify optimal therapeutic opportunities.V Foundation for Cancer Research (Partners in Excellence grant

PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that strongly influence molecular signalling in normal and cancer cells. Although increasing evidence suggests a role of PPARs in skin carcinogenesis, only expression of PPARγ has been investigated in human melanoma tissues. Activation of PPARα has been shown to inhibit the metastatic potential, whereas stimulation of PPARγ decreased melanoma cell proliferation. We show here that the third member of the PPAR family, PPARβ/δ is expressed in human melanoma samples. Specific pharmacological activation of PPARβ using GW0742 or GW501516 in low concentrations inhibits proliferation of human and murine melanoma cells. Inhibition of proliferation is accompanied by decreased expression of the Wilms’ tumour suppressor 1 (WT1), which is implicated in melanoma proliferation. We demonstrate that PPARβ directly represses WT1 as (1) PPARβ activation represses WT1 promoter activity; (2) in chromatin immunoprecipitation and electrophoretic mobility shift assays, we identified a binding element for PPARβ in the WT1 promoter; (3) deletion of this binding element abolishes repression by PPARβ and (4) the WT1 downstream molecules nestin and zyxin are down-regulated upon PPARβ activation. Our findings elucidate a novel mechanism of signalling by ligands of PPARβ, which leads to suppression of melanoma cell growth through direct repression of WT1

The Maintenance of Traditions in Marmosets: Individual Habit, Not Social Conformity? A Field Experiment

Social conformity is a cornerstone of human culture because it accelerates and maintains the spread of behaviour within a group. Few empirical studies have investigated the role of social conformity in the maintenance of traditions despite an increasing body of literature on the formation of behavioural patterns in non-human animals. The current report presents a field experiment with free-ranging marmosets (Callithrix jacchus) which investigated whether social conformity is necessary for the maintenance of behavioural patterns within groups or whether individual effects such as habit formation would suffice.Using a two-action apparatus, we established alternative behavioural patterns in six family groups composed of 36 individuals. These groups experienced only one technique during a training phase and were thereafter tested with two techniques available. The monkeys reliably maintained the trained method over a period of three weeks, despite discovering the alternative technique. Three additional groups were given the same number of sessions, but those 21 individuals could freely choose the method to obtain a reward. In these control groups, an overall bias towards one of the two methods was observed, but animals with a different preference did not adjust towards the group norm. Thirteen of the fifteen animals that discovered both techniques remained with the action with which they were initially successful, independent of the group preference and the type of action (Binomial test: exp. proportion: 0.5, p<0.01).The results indicate that the maintenance of behavioural patterns within groups 1) could be explained by the first rewarded manipulation and subsequent habit formation and 2) do not require social conformity as a mechanism. After an initial spread of a behaviour throughout a group, this mechanism may lead to a superficial appearance of conformity without the involvement of such a socially and cognitively complex mechanism. This is the first time that such an experiment has been conducted with free-ranging primates

De jure determinants of new firm formation: how the pillars of constitutions influence entrepreneurship

This paper provides empirical evidence supporting the view that constitutions are the primary and fundamental institutional determinant of entrepreneurship. It shows that some of the provisions contained in national constitutions are positively and significantly associated with a standard measure of entrepreneurial dynamics, namely the rate of new business density. Using for 115 countries a novel dataset containing the characteristics of the constitutions enacted in the world, applying an IV-GMM treatment to deal with the endogeneity of constitutional rules, and controlling for de facto variables, the paper finds that provisions about the right to conduct/establish a business, the right to strike, consumer protection, anti-corruption, and compulsory education promote higher rates of new firm formation. Contrasting results are instead obtained for provisions concerning protection of intellectual property rights

Chimpanzees (Pan troglodytes) do not develop contingent reciprocity in an experimental task

Chimpanzees provide help to unrelated individuals in a broad range of situations. The pattern of helping within pairs suggests that contingent reciprocity may have been an important mechanism in the evolution of altruism in chimpanzees. However, correlational analyses of the cumulative pattern of interactions over time do not demonstrate that helping is contingent upon previous acts of altruism, as required by the theory of reciprocal altruism. Experimental studies provide a controlled approach to examine the importance of contingency in helping interactions. In this study, we evaluated whether chimpanzees would be more likely to provide food to a social partner from their home group if their partner had previously provided food for them. The chimpanzees manipulated a barpull apparatus in which actors could deliver rewards either to themselves and their partners or only to themselves. Our findings indicate that the chimpanzees’ responses were not consistently influenced by the behavior of their partners in previous rounds. Only one of the 11 dyads that we tested demonstrated positive reciprocity. We conclude that contingent reciprocity does not spontaneously arise in experimental settings, despite the fact that patterns of behavior in the field indicate that individuals cooperate preferentially with reciprocating partners

Meta-analysis of exome array data identifies six novel genetic loci for lung function

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease

Corporate boards and the performance of Asian firms: A meta-analysis

The prevalence of ownership concentration in Asian firms presents a challenge to the influential agency theory-based understanding of the role of corporate boards. In this paper we develop and test hypotheses about board attributes and firm performance that reflect Asian institutional conditions. We present the first meta-analysis of the relationship between board attributes and performance of Asian firms using a varied set of meta-analytical techniques on a database of 86 studies covering nine Asian countries. First, we find that board structure and composition preferences are influenced by the identity of the concentrated owner. Second, consistent with US data, we find very limited evidence of a direct relationship between board attributes and firm financial performance in the Asian context. Third, we find that the relationship between board structure and composition and firm performance is mediated by the revealed strategic preferences of Asian firms specifically by the level of R&D investment

To Each According to His Need? Variability in the Responses to Inequity in Nonhuman Primates

While it is well established that humans respond to inequity, it remains unclear the extent to which this behavior occurs in our nonhuman primate relatives. By comparing a variety of species, spanning from New World and Old World monkeys to great apes, scientists can begin to answer questions about how the response to inequity evolved, what the function of this response is, and why and how different contexts shape it. In particular, research across nonhuman primate species suggests that the response is quite variable across species, contexts and individuals. In this paper, we aim to review these differences in an attempt to identify and better understand the patterns that emerge from the existing data with the goal of developing directions for future research. To begin, we address the importance of considering socio-ecological factors in nonhuman primates in order to better understand and predict expected patterns of cooperation and aversion to inequity in different species, following which we provide a detailed analysis of the patterns uncovered by these comparisons. Ultimately, we use this synthesis to propose new ideas for research to better understand this response and, hence, the evolution of our own responses to inequity