International meta-analysis of stated preference studies of transportation noise nuisance

The final publication is available at Springer via http://dx.doi.org/10.1007/s11116-014-9527-4This paper reports the first meta-analysis and most extensive review of stated preference studies of transportation noise nuisance. The meta-analysis is based on a newly compiled data set of 258 values from 49 studies and 23 countries and spanning more than 40 years. Contrast this with the most extensive meta-analysis of the more conventional hedonic pricing approach which includes 53 noise valuations. Moreover, the sample compares favourably with the 444 observations from the very first meta-analysis of the value of travel time savings which is by far the most widely examined parameter in transport planning. A particularly significant finding of the study is that the intertemporal income elasticity is close to one, somewhat larger than the cross-sectional income elasticity typically obtained from individual studies. This demonstrates the importance of distinguishing the effects of 2 income variations that occur over time, which tend to drive policy, from variations across individuals at one point in time, and such findings are typical of those observed in other markets. Importantly, the values derived are transferable across countries and may be used to benchmark existing evidence and provide values in contexts where none exist. Other key results are that values for aircraft noise exceed those for other modes, whilst those exposed to higher noise levels and those who are highly annoyed also have higher values in line with expectations. A wide range of design effects were tested but few were significant and these included the consumer surplus measure, the representation of noise and the context

Spliceosome malfunction causes neurodevelopmental disorders with overlapping features

Pre-mRNA splicing is a highly coordinated process. While its dysregulation has been linked to neurological deficits, our understanding of the underlying molecular and cellular mechanisms remains limited. We implicated pathogenic variants in U2AF2 and PRPF19, encoding spliceosome subunits in neurodevelopmental disorders (NDDs), by identifying 46 unrelated individuals with 23 de novo U2AF2 missense variants (including 7 recurrent variants in 30 individuals) and 6 individuals with de novo PRPF19 variants. Eight U2AF2 variants dysregulated splicing of a model substrate. Neuritogenesis was reduced in human neurons differentiated from human pluripotent stem cells carrying two U2AF2 hyper-recurrent variants. Neural loss of function (LoF) of the Drosophila orthologs U2af50 and Prp19 led to lethality, abnormal mushroom body (MB) patterning, and social deficits, which were differentially rescued by wild-type and mutant U2AF2 or PRPF19. Transcriptome profiling revealed splicing substrates or effectors (including Rbfox1, a third splicing factor), which rescued MB defects in U2af50deficient flies. Upon reanalysis of negative clinical exomes followed by data sharing, we further identified 6 patients with NDD who carried RBFOX1 missense variants which, by in vitro testing, showed LoF. Our study implicates 3 splicing factors as NDD-causative genes and establishes a genetic network with hierarchy underlying human brain development and function

Metalation/De-metalation as a Post-Gelation Strategy to Tune the Mechanical Properties of Catenane-Crosslinked Gels

Mechanically interlocked molecules (MIMs) possess unique architectures and non-traditional degrees of freedom that arise from well-defined topologies that are achieved through precise mechanical bonding. Incorporation of MIMs into materials can thus provide an avenue to discover new and emergent macroscale properties. Here, the synthesis of a phenanthroline-based [2]catenane crosslinker and its incorporation into polyacrylate organogels is described. Specifically, Cu(I) metalation and de-metalation was used as a post-gelation strategy to tune the mechanical properties of a gel by controlling the conformational motions of integrated MIMs. The organogels were prepared via thermally initiated free radical polymerization, and Cu(I) metal was added in MeOH to pre-treated, swollen gels. De-metalation of the gels was achieved by adding cyanide salts and washing the gels. Changes in Young’s and shear moduli, as well as tensile strength, were quantified through oscillatory shear rheology and tensile testing. The reported approach provides a general method for post-gelation tuning of mechanical properties using metals and well-defined catenane topologies as part of a network architecture

Nonparametric Estimation of Dynamic Hedonic Price Models and the Construction of Residential Housing Price Indices

Parametric specifications for hedonic price equations are estimated using a data set from Alameda and San Francisco Counties and are compared to estimates using a nonparametric technique called locally weighted regression, LWR. LWR permits flexible estimation of the hedonic's curvature at median attributes and is less sensitive than standard regression techniques to the influence of unusual observations. The technique also avoids imposing a single functional form across time and municipalities. The LWR estimates of municipality-specific hedonics are then used to obtain implicit prices for housing attributes and to derive municipality-specific price indices. The results of extensive diagnostic checks of our technique are also reported. Copyright American Real Estate and Urban Economics Association.

Latino Men and Familial Risk Communication About Prostate Cancer

PURPOSE: This study investigated how familial communication about prostate cancer risk and screening affects sons of men with prostate cancer. It is important to engage Latino families shared decision making toward early detection because first degree relatives of men with PCa are at heightened risk and Latino men are diagnosed at more advanced stages of disease than Non-Hispanic White men. METHODS: The team conducted semi-structured interviews with seventeen sons of PCa survivors. Eight participants completed a follow up interview an average of seven months later. Therefore, our sample includes twenty-five transcripts. The sons are Latinos living in Southern California. Data were analyzed with a mix of a priori topical codes and grounded theory techniques. RESULTS: Sons were under informed about both familial risk and screening options. They became sensitized to PCa, desired information, and held protective intentions. Hopeful intentions came up against cultural taboos around sex, reproductive health, and intimacy that limited discussions between fathers and sons. Fathers were a valued source of information, but play various roles, which affect sons’ screening intentions. Open communication between father and son promoted awareness of screening and familial risk. DISCUSSION: Uncertainty about familial risk and screening options, especially early detection strategies, was exacerbated by cultural taboos around PCa. Fathers could have been primary and credible advocates for shared decision making, but sons found it difficult to learn from their fathers’ experience. NURSING IMPLICATIONS: Findings from our study can inform community based interventions with Latino families, help to culturally tailor health messaging, and sensitize clinicians to a group which needs concerted counseling about PCa risk and screening

The relevance of hedonic price indices

We argue that for the case of heterogeneous commodities with infrequent tradings, such as paintings, it is relevant to base a price index on hedonic regressions using all sales and not resales only. To support this conclusion we construct a price index for paintings by Impressionists and their followers and compare the various estimators using bootstrapping techniques. Copyright Kluwer Academic Publishers 1996price index, heterogeneous commodities, returns on art investment,

Discovery of <i>N</i>‑(4-Fluoro-3-methoxybenzyl)-6-(2-(((2<i>S</i>,5<i>R</i>)‑5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)‑2<i>H</i>‑tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A Highly Selective and Orally Bioavailable Matrix Metalloproteinase-13 Inhibitor for the Potential Treatment of Osteoarthritis

Matrix metalloproteinase-13 (MMP-13) is a zinc-dependent protease responsible for the cleavage of type II collagen, the major structural protein of articular cartilage. Degradation of this cartilage matrix leads to the development of osteoarthritis. We previously have described highly potent and selective carboxylic acid containing MMP-13 inhibitors; however, nephrotoxicity in preclinical toxicology species precluded development. The accumulation of compound in the kidneys mediated by human organic anion transporter 3 (hOAT3) was hypothesized as a contributing factor for the finding. Herein we report our efforts to optimize the MMP-13 potency and pharmacokinetic properties of non-carboxylic acid leads resulting in the identification of compound <b>43a</b> lacking the previously observed preclinical toxicology at comparable exposures