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Since the accessory dwelling unit (ADU) has emerged as a policy alternative to increase housing stock and provide affordable options for areas impacted by housing shortages, many local governments recently adopted ADU policies that promote the construction of ADUs. Taking the City of Los Angeles as the study area, this paper examines how the city's ADU ordinance impacts the relationship of the characteristics of the properties and neighborhoods with ADU development by constructing multilevel logistic regression models. The outputs of the models suggest that the ordinance contributes to diversifying the types and locations of the properties and neighborhoods where ADUs are built. The influence of the property characteristics associated with ADU development before the implementation of the ordinance significantly diminished after the ordinance. The outputs also indicate that the ordinance probably attracted ADU developments in the areas with higher accessibility to bus transit. These findings will help planners take appropriate actions and policies that support ADU developments. [ABSTRACT FROM AUTHOR]

Although vaccines against antigenically evolving pathogens such as seasonal influenza ; and are designed to protect against circulating strains by affecting the emergence and transmission of antigenically divergent strains, they might in theory also be able to change the rate of antigenic evolution. Vaccination might slow antigenic evolution by increasing immunity, reducing the overall prevalence or population size of the pathogen. This reduction could decrease the supply and growth rates of mutants and might thereby slow adaptation. But vaccination might accelerate antigenic evolution by increasing the transmission advantage of more antigenically diverged strains relative to less diverged strains (i.e., by positive selection). Such evolutionary effects could affect vaccination's direct benefits to individuals and indirect benefits to the host population (i.e., the private and social benefits). To investigate these potential impacts, we simulated vaccination against a continuously circulating influenza-like pathogen in a simple population. On average, more vaccination decreased the incidence of infection. Notably, this decrease was driven partly by a vaccine-induced decline in the rate of antigenic evolution. To understand how the evolutionary effects of vaccines might affect their social and private benefits, we fitted linear panel models to simulated data. By slowing evolution, vaccination increased the social benefit and decreased the private benefit. Thus, vaccination's potential social and private benefits may differ from current theory, which omits evolutionary effects. These results suggest that conventional vaccines against influenza and other antigenically evolving pathogens, if protective against transmission and given to the appropriate populations, could further reduce disease burden by slowing antigenic evolution. [ABSTRACT FROM AUTHOR]

This study focused on the development of Bayesian bivariate semiparametric models for ozone and PM2.5 emissions. The semiparametric models rely on a Dirichlet mixture, which accounts for unobserved heterogeneity by employing random distribution for the intercept of each entity. The models with and without spatially structured random effects were also evaluated. Overall, four models were developed: three semiparametric with a flexible intercept and one parametric to serve as a reference. The significance of simultaneous estimation of PM2.5 and ozone was demonstrated by selection of common contributing factors as well as the statistically significant bivariate error term. In terms of relationship between dependent and independent variables, the areas with higher population and poverty, along with lesser educated residents, were observed to experience higher ozone and PM2.5 concentration. Also, the entities with higher vehicular traffic density and larger geographic areas were observed to be positively correlated with ozone and PM2.5 concentration. The underlying influential factor for both such variables may be the vehicular emissions, which is directly associated with traffic density and indirectly with land area as larger entities may tend to have higher traffic activity. The superiority of the semiparametric models, compared with parametric, signified the advantage associated with the flexible Dirichlet approach. The models with and without spatial correlation structures illustrated the mixed performance across the cases of parametric and semiparametric bivariate ones. The lack of consistent advantages associated with the inclusion of spatial effects may be due to the fact that the spatial correlation was not observed to be significant for the current dataset. Other spatial structure specifications may lead to different performance results. [ABSTRACT FROM AUTHOR]

Vaccination could be an evolutionary pressure on seasonal influenza if vaccines reduce the transmission rates of some ("targeted") strains more than others. In theory, more vaccinated populations should have a lower prevalence of targeted strains compared to less vaccinated populations. We tested for vaccine-induced selection in influenza by comparing strain frequencies between more and less vaccinated human populations. We defined strains in three ways: first as influenza types and subtypes, next as lineages of type B, and finally as clades of influenza A/H3N2. We detected spatial differences partially consistent with vaccine use in the frequencies of subtypes and types and between the lineages of influenza B, suggesting that vaccines do not select strongly among all these phylogenetic groups at regional scales. We did detect a significantly greater frequency of an H3N2 clade with known vaccine escape mutations in more vaccinated countries during the 2014-2015 season, which is consistent with vaccine-driven selection within the H3N2 subtype. Overall, we find more support for vaccine-driven selection when large differences in vaccine effectiveness suggest a strong effect size. Variation in surveillance practices across countries could obscure signals of selection, especially when strain-specific differences in vaccine effectiveness are small. Further examination of the influenza vaccine's evolutionary effects would benefit from improvements in epidemiological surveillance and reporting. [ABSTRACT FROM AUTHOR]

This study investigates the effects of the urban spatial structure on the excess commuting rate (ECR) by comparing commuting patterns in two cities having distinctive urban forms, Seoul, Korea and Los Angeles, California, USA. A major difference was found in that commuters working closer to employment centres, or living in single-family detached housing in LA, are likely to have lower ECR, but not in Seoul. Employment suburbanisation, strict zoning separating residence and workplace and single-family housing-dominant low-density suburbs in LA are regarded as the reasons for their lower ECRs, which, by definition, imply relatively shorter actual commute duration and/or longer minimum time. Seoul can learn a lesson from LA for employment decentralisation in order to reduce actual commute time, while land use patterns in Seoul such as high level of mixed land use and compact development can provide policy implications for LA for improving commuters’ accessibility and reducing minimum time. [ABSTRACT FROM AUTHOR]

Most antigenically novel and evolutionarily successful strains of seasonal influenza A (H3N2) originate in East, South and Southeast Asia. To understand this pattern, we simulated the ecological and evolutionary dynamics of influenza in a host metapopulation representing the temperate north, tropics and temperate south. Although seasonality and air traffic are frequently used to explain global migratory patterns of influenza, we find that other factors may have a comparable or greater impact. Notably, a region’s basic reproductive number (R0) strongly affects the antigenic evolution of its viral population and the probability that its strains will spread and fix globally: a 17–28% higher R0 in one region can explain the observed patterns. Seasonality, in contrast, increases the probability that a tropical (less seasonal) population will export evolutionarily successful strains but alone does not predict that these strains will be antigenically advanced. The relative sizes of different host populations, their birth and death rates, and the region in which H3N2 first appears affect influenza’s phylogeography in different but relatively minor ways. These results suggest general principles that dictate the spatial dynamics of antigenically evolving pathogens and offer predictions for how changes in human ecology might affect influenza evolution. [ABSTRACT FROM AUTHOR]

We conducted a systematic analysis to determine the reason for the apparent disparity of success of immunotherapy between clinical and experimental cancers. To do this, we performed a search of PubMed using the keywords "immunotherapy" AND "cancer" for the years of 1980 and 2010. The midspread of experimental tumors used in all the relevant literature published in 2010 were between 0.5-121 mm³ in volume or had grown for four to eight days. Few studies reported large tumors that could be considered representative of clinical tumors, in terms of size and duration of growth. The predominant effect of cancer immunotherapies was slowed or delayed outgrowth. Regression of tumors larger than 200 mm³ was observed only after passive antibody or adoptive T cell therapy. The effectiveness of other types of immunotherapy was generally scattered. By comparison, very few publications retrieved by the 1980 search could meet our selection criteria; all of these used tumors smaller than 100 mm³, and none reported regression. In the entire year of 2010, only 13 used tumors larger than 400 mm³, and nine of these reported tumor regression. Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth. Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy. For the future, we aspire to witness the increased use of experimental studies treating tumors that model clinical cancers in terms of size and duration of growth. [ABSTRACT FROM AUTHOR]

Macropinocytosis is essential for myeloid cells to survey their environment and for growth of RAS-transformed cancer cells. Several growth factors and inflammatory stimuli are known to induce macropinocytosis, but its endogenous inhibitors have remained elusive. Stimulation of Roundabout receptors by Slit ligands inhibits directional migration of many cell types, including immune cells and cancer cells. We report that SLIT2 inhibits macropinocytosis in vitro and in vivo by inducing cytoskeletal changes in macrophages. In mice, SLIT2 attenuates the uptake of muramyl dipeptide, thereby preventing NOD2-dependent activation of NF-κB and consequent secretion of pro-inflammatory chemokine, CXCL1. Conversely, blocking the action of endogenous SLIT2 enhances CXCL1 secretion. SLIT2 also inhibits macropinocytosis in RAS-transformed cancer cells, thereby decreasing their survival in nutrient-deficient conditions which resemble tumor microenvironment. Our results identify SLIT2 as a physiological inhibitor of macropinocytosis and challenge the conventional notion that signals that enhance macropinocytosis negatively regulate cell migration, and vice versa. Macrophages survey their surroundings using macropinocytosis, but its regulation is unclear. Here, the authors report that SLIT2, a known inhibitor of Rac GTPases, is an endogenous inhibitor of macropinocytosis, and that SLIT2 limits the uptake of NOD2 ligands into immune cells and subsequent release of the inflammatory chemokine, CXCL1, in vivo. [ABSTRACT FROM AUTHOR]

We recently reported that therapeutic vaccination with live tumor antigen-producingSalmonella typhimuriumrescues dysfunctional endogenous T cell responses and eradicates long-established tumors refractory to αCTLA-4 and αPD-L1 checkpoint inhibitor blockade. Here, we show that live intravenously injected or heat-killed (HK) intratumorally injectedSalmonella typhimurium, even when not producing tumor antigen, synergize with adoptive T cell therapy to eradicate tumors. These data demonstrate that the combination of adoptive T cell transfer with the injection of live or deadSalmonella typhimuriumis a promising approach for cancer treatment. [ABSTRACT FROM AUTHOR]