An economic way of reducing health, environmental, and other pressures of urban traffic: a decision analysis on trip aggregation

BACKGROUND: Traffic congestion is rapidly becoming the most important obstacle to urban development. In addition, traffic creates major health, environmental, and economical problems. Nonetheless, automobiles are crucial for the functions of the modern society. Most proposals for sustainable traffic solutions face major political opposition, economical consequences, or technical problems. METHODS: We performed a decision analysis in a poorly studied area, trip aggregation, and studied decisions from the perspective of two different stakeholders, the passenger and society. We modelled the impact and potential of composite traffic, a hypothetical large-scale demand-responsive public transport system for the Helsinki metropolitan area, where a centralised system would collect the information on all trip demands online, would merge the trips with the same origin and destination into public vehicles with eight or four seats, and then would transmit the trip instructions to the passengers' mobile phones. RESULTS: We show here that in an urban area with one million inhabitants, trip aggregation could reduce the health, environmental, and other detrimental impacts of car traffic typically by 50–70%, and if implemented could attract about half of the car passengers, and within a broad operational range would require no public subsidies. CONCLUSION: Composite traffic provides new degrees of freedom in urban decision-making in identifying novel solutions to the problems of urban traffic

Are all ‘research fields’ equal? Rethinking practice for the use of data from crowd-sourcing market places

New technologies like large-scale social media sides (e.g., Facebook and Twitter) and crowdsourcing services (e.g., Amazon Mechanical Turk, Crowdflower, Clickworker) impact social science research and provide many new and interesting avenues for research. The use of these new technologies for research has not been without challenges and a recently published psychological study on Facebook led to a widespread discussion on the ethics of conducting large-scale experiments online. Surprisingly little has been said about the ethics of conducting research using commercial crowdsourcing market places. In this paper, I want to focus on the question of which ethical questions are raised by data collection with crowdsourcing tools. I briefly draw on implications of internet research more generally and then focus on the specific challenges that research with crowdsourcing tools faces. I identify fair-pay and related issues of respect for autonomy as well as problems with power dynamics between researcher and participant, which has implications for ‘withdrawal-withoutprejudice’, as the major ethical challenges with crowdsourced data. Further, I will to draw attention on how we can develop a ‘best practice’ for researchers using crowdsourcing tools

NSC23925, Identified in a High-Throughput Cell-Based Screen, Reverses Multidrug Resistance

Multidrug resistance (MDR) is a major factor which contributes to the failure of cancer chemotherapy, and numerous efforts have been attempted to overcome MDR. To date, none of these attempts have yielded a tolerable and effective therapy to reverse MDR; thus, identification of new agents would be useful both clinically and scientifically.To identify small molecule compounds that can reverse chemoresistance, we developed a 96-well plate high-throughput cell-based screening assay in a paclitaxel resistant ovarian cancer cell line. Coincubating cells with a sublethal concentration of paclitaxel in combination with each of 2,000 small molecule compounds from the National Cancer Institute Diversity Set Library, we identified a previously uncharacterized molecule, NSC23925, that inhibits Pgp1 and reverses MDR1 (Pgp1) but does not inhibit MRP or BCRP-mediated MDR. The cytotoxic activity of NSC23925 was further evaluated using a panel of cancer cell lines expressing Pgp1, MRP, and BCRP. We found that at a concentration of >10 microM NSC23925 moderately inhibits the proliferation of both sensitive and resistant cell lines with almost equal activity, but its inhibitory effect was not altered by co-incubation with the Pgp1 inhibitor, verapamil, suggesting that NSC23925 itself is not a substrate of Pgp1. Additionally, NSC23925 increases the intracellular accumulation of Pgp1 substrates: calcein AM, Rhodamine-123, paclitaxel, mitoxantrone, and doxorubicin. Interestingly, we further observed that, although NSC23925 directly inhibits the function of Pgp1 in a dose-dependent manner without altering the total expression level of Pgp1, NSC23925 actually stimulates ATPase activity of Pgp, a phenomenon seen in other Pgp inhibitors.The ability of NSC23925 to restore sensitivity to the cytotoxic effects of chemotherapy or to prevent resistance could significantly benefit cancer patients

Genetic Variations and Haplotype Diversity of the UGT1 Gene Cluster in the Chinese Population

Vertebrates require tremendous molecular diversity to defend against numerous small hydrophobic chemicals. UDP-glucuronosyltransferases (UGTs) are a large family of detoxification enzymes that glucuronidate xenobiotics and endobiotics, facilitating their excretion from the body. The UGT1 gene cluster contains a tandem array of variable first exons, each preceded by a specific promoter, and a common set of downstream constant exons, similar to the genomic organization of the protocadherin (Pcdh), immunoglobulin, and T-cell receptor gene clusters. To assist pharmacogenomics studies in Chinese, we sequenced nine first exons, promoter and intronic regions, and five common exons of the UGT1 gene cluster in a population sample of 253 unrelated Chinese individuals. We identified 101 polymorphisms and found 15 novel SNPs. We then computed allele frequencies for each polymorphism and reconstructed their linkage disequilibrium (LD) map. The UGT1 cluster can be divided into five linkage blocks: Block 9 (UGT1A9), Block 9/7/6 (UGT1A9, UGT1A7, and UGT1A6), Block 5 (UGT1A5), Block 4/3 (UGT1A4 and UGT1A3), and Block 3′ UTR. Furthermore, we inferred haplotypes and selected their tagSNPs. Finally, comparing our data with those of three other populations of the HapMap project revealed ethnic specificity of the UGT1 genetic diversity in Chinese. These findings have important implications for future molecular genetic studies of the UGT1 gene cluster as well as for personalized medical therapies in Chinese

Inequalities in the commuting burden: Institutional constraints and job-housing relationships in Tianjin, China

Encouraging transport equality is vital in order to create a liveable city. However, the burden of commuting has become a key concern in urban areas, particularly in developing countries. Inequalities in the commuting burden are accompanied by inequalities in housing and employment, because these institutions have a significant impact on individuals' choices of accommodation and jobs, thus shaping commuting behaviour and causing imbalances in job-housing relationships. Therefore, this paper aims to analyse the role of employment and housing system constraints in the unequal commuting burden by using Tianjin as a case study. The results of the study show that the effects of institutional factors, such as Hukou and the Danwei system, help to explain imbalances in the job-housing relationship and the unequal commuting burden. Some commuters are employed by Danweis or have Tianjin Hukou, and can, therefore, live in Danwei housing, which means that Danweis provide effective solutions for some people in terms of their accommodation, enabling them to significantly decrease the time they spend commuting. Moreover, our study provides new evidence that institutional barriers constrain the job-housing balance in the case of high-skilled immigrants, while local residents and low-skilled immigrants can avoid institutional barriers by returning to Danwei housing and choosing to live in informal housing. In terms of suggesting measures for improving commuting inequalities, commuters generally wanted to eliminate the housing benefits resulting from the legacy of the Danwei system and for equal housing subsidies to be implemented. At the same time, they appealed for improvements to be made in terms of housing benefits, the quality of public transport and mixed housing-workplace planning. This study finds that institutional discrimination causes social inequalities in relation to the commuting burden, which could continue to worsen unless the influence of institutional factors is eliminated. The findings could be used to assist planners and decision makers in developing effective strategies to promote sustainable urban development

Inequitable walking conditions among older people: examining the interrelationship of neighbourhood socio-economic status and urban form using a comparative case study

<p>Abstract</p> <p>Background</p> <p>Supportive neighbourhood walking conditions are particularly important for older people as they age and who, as a group, prefer walking as a form of physical activity. Urban form and socio-economic status (SES) can influence neighbourhood walking behaviour. The objectives of this study were: a) to examine how urban form and neighbourhood SES inter-relate to affect the experiences of older people who walk in their neighbourhoods; b) to examine differences among neighbourhood stakeholder key informant perspectives on socio-political processes that shape the walkability of neighbourhood environments.</p> <p>Methods</p> <p>An embedded comparative case study examined differences among four Ottawa neighbourhoods that were purposefully selected to provide contrasts on urban form (inner-urban versus suburban) and SES (higher versus lower). Qualitative data collected from 75 older walkers and 19 neighbourhood key informants, as well as quantitative indicators were compared on the two axes of urban form and SES among the four neighbourhoods.</p> <p>Results and discussion</p> <p>Examining the inter-relationship of neighbourhood SES and urban form characteristics on older people's walking experiences indicated that urban form differences were accentuated positively in higher SES neighbourhoods and negatively in lower SES neighbourhoods. Older people in lower SES neighbourhoods were more affected by traffic hazards and more reliant on public transit compared to their higher SES counterparts. In higher SES neighbourhoods the disadvantages of traffic in the inner-urban neighbourhood and lack of commercial destinations in the suburban neighbourhood were partially offset by other factors including neighbourhood aesthetics. Key informant descriptions of the socio-political process highlighted how lower SES neighbourhoods may face greater challenges in creating walkable places. These differences pertained to the size of neighbourhood associations, relationships with political representatives, accessing information and salient neighbourhood association issues. Findings provide evidence of inequitable walking environments.</p> <p>Conclusion</p> <p>Future research on walking must consider urban form-SES inter-relationships and further examine the equitable distribution of walking conditions as well as the socio-political processes driving these conditions. There is a need for municipal governments to monitor differences in walking conditions among higher and lower SES neighbourhoods, to be receptive to the needs of lower SES neighbourhood and to ensure that policy decisions are taken to address inequitable walking conditions.</p

Lipid Composition of the Human Eye: Are Red Blood Cells a Good Mirror of Retinal and Optic Nerve Fatty Acids?

International audienceBACKGROUND: The assessment of blood lipids is very frequent in clinical research as it is assumed to reflect the lipid composition of peripheral tissues. Even well accepted such relationships have never been clearly established. This is particularly true in ophthalmology where the use of blood lipids has become very common following recent data linking lipid intake to ocular health and disease. In the present study, we wanted to determine in humans whether a lipidomic approach based on red blood cells could reveal associations between circulating and tissue lipid profiles. To check if the analytical sensitivity may be of importance in such analyses, we have used a double approach for lipidomics. METHODOLOGY AND PRINCIPAL FINDINGS: Red blood cells, retinas and optic nerves were collected from 9 human donors. The lipidomic analyses on tissues consisted in gas chromatography and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS). Gas chromatography did not reveal any relevant association between circulating and ocular fatty acids except for arachidonic acid whose circulating amounts were positively associated with its levels in the retina and in the optic nerve. In contrast, several significant associations emerged from LC-ESI-MS analyses. Particularly, lipid entities in red blood cells were positively or negatively associated with representative pools of retinal docosahexaenoic acid (DHA), retinal very-long chain polyunsaturated fatty acids (VLC-PUFA) or optic nerve plasmalogens. CONCLUSIONS AND SIGNIFICANCE: LC-ESI-MS is more appropriate than gas chromatography for lipidomics on red blood cells, and further extrapolation to ocular lipids. The several individual lipid species we have identified are good candidates to represent circulating biomarkers of ocular lipids. However, further investigation is needed before considering them as indexes of disease risk and before using them in clinical studies on optic nerve neuropathies or retinal diseases displaying photoreceptors degeneration

Why Pleiotropic Interventions are Needed for Alzheimer's Disease

Alzheimer's disease (AD) involves a complex pathological cascade thought to be initially triggered by the accumulation of β-amyloid (Aβ) peptide aggregates or aberrant amyloid precursor protein (APP) processing. Much is known of the factors initiating the disease process decades prior to the onset of cognitive deficits, but an unclear understanding of events immediately preceding and precipitating cognitive decline is a major factor limiting the rapid development of adequate prevention and treatment strategies. Multiple pathways are known to contribute to cognitive deficits by disruption of neuronal signal transduction pathways involved in memory. These pathways are altered by aberrant signaling, inflammation, oxidative damage, tau pathology, neuron loss, and synapse loss. We need to develop stage-specific interventions that not only block causal events in pathogenesis (aberrant tau phosphorylation, Aβ production and accumulation, and oxidative damage), but also address damage from these pathways that will not be reversed by targeting prodromal pathways. This approach would not only focus on blocking early events in pathogenesis, but also adequately correct for loss of synapses, substrates for neuroprotective pathways (e.g., docosahexaenoic acid), defects in energy metabolism, and adverse consequences of inappropriate compensatory responses (aberrant sprouting). Monotherapy targeting early single steps in this complicated cascade may explain disappointments in trials with agents inhibiting production, clearance, or aggregation of the initiating Aβ peptide or its aggregates. Both plaque and tangle pathogenesis have already reached AD levels in the more vulnerable brain regions during the “prodromal” period prior to conversion to “mild cognitive impairment (MCI).” Furthermore, many of the pathological events are no longer proceeding in series, but are going on in parallel. By the MCI stage, we stand a greater chance of success by considering pleiotropic drugs or cocktails that can independently limit the parallel steps of the AD cascade at all stages, but that do not completely inhibit the constitutive normal functions of these pathways. Based on this hypothesis, efforts in our laboratories have focused on the pleiotropic activities of omega-3 fatty acids and the anti-inflammatory, antioxidant, and anti-amyloid activity of curcumin in multiple models that cover many steps of the AD pathogenic cascade (Cole and Frautschy, Alzheimers Dement 2:284–286, 2006)