Street imagery is a promising and growing big data source providing current and historical images in more than 100 countries. Studies have reported using this data to audit road infrastructure and ...other built environment features. Here we explore a novel application, using Google Street View (GSV) to predict travel patterns at the city level.
We sampled 34 cities in Great Britain. In each city, we accessed 2000 GSV images from 1000 random locations. We selected archived images from time periods overlapping with the 2011 Census and the 2011-2013 Active People Survey (APS). We manually annotated the images into seven categories of road users. We developed regression models with the counts of images of road users as predictors. The outcomes included Census-reported commute shares of four modes (combined walking plus public transport, cycling, motorcycle, and car), as well as APS-reported past-month participation in walking and cycling.
We found high correlations between GSV counts of cyclists ('GSV-cyclists') and cycle commute mode share (r = 0.92)/past-month cycling (r = 0.90). Likewise, GSV-pedestrians was moderately correlated with past-month walking for transport (r = 0.46), GSV-motorcycles was moderately correlated with commute share of motorcycles (r = 0.44), and GSV-buses was highly correlated with commute share of walking plus public transport (r = 0.81). GSV-car was not correlated with car commute mode share (r = -0.12). However, in multivariable regression models, all outcomes were predicted well, except past-month walking. The prediction performance was measured using cross-validation analyses. GSV-buses and GSV-cyclists are the strongest predictors for most outcomes.
GSV images are a promising new big data source to predict urban mobility patterns. Predictive power was the greatest for those modes that varied the most (cycle and bus). With its ability to identify mode of travel and capture street activity often excluded in routinely carried out surveys, GSV has the potential to be complementary to new and traditional data. With half the world's population covered by street imagery, and with up to 10 years historical data available in GSV, further testing across multiple settings is warranted both for cross-sectional and longitudinal assessments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Air pollution (AP) and physical activity (PA) are important health risk factors;•We reviewed current evidence of AP and PA interactions for health;•PA behaviour and health effects might be moderated ...by AP exposure;•Epidemiological studies provide mixed results on AP and PA interaction;•More research collaboration is needed to study AP and PA relations.
Exposure to air pollution and physical inactivity are both significant risk factors for non-communicable diseases (NCDs). These risk factors are also linked so that the change in exposure in one will impact risks and benefits of the other. These links are well captured in the active transport (walking, cycling) health impact models, in which the increases in active transport leading to increased inhaled dose of air pollution. However, these links are more complex and go beyond the active transport research field. Hence, in this study, we aimed to summarize the empirical evidence on the links between air pollution and physical activity, and their combined effect on individual and population health.
We conducted a non-systematic mapping review of empirical and modelling evidence of the possible links between exposure to air pollution and physical activity published until Autumn 2019. We reviewed empirical evidence for the (i) impact of exposure to air pollution on physical activity behaviour, (ii) exposure to air pollution while engaged in physical activity and (iii) the short-term and (iv) long-term health effects of air pollution exposure on people engaged in physical activity. In addition, we reviewed (v) public health modelling studies that have quantified the combined effect of air pollution and physical activity. These broad research areas were identified through expert discussions, including two public events performed in health-related conferences.
The current literature suggests that air pollution may decrease physical activity levels during high air pollution episodes or may prevent people from engaging in physical activity overall in highly polluted environments. Several studies have estimated fine particulate matter (PM2.5) exposure in active transport environment in Europe and North-America, but the concentration in other regions, places for physical activity and for other air pollutants are poorly understood. Observational epidemiological studies provide some evidence for a possible interaction between air pollution and physical activity for acute health outcomes, while results for long-term effects are mixed with several studies suggesting small diminishing health gains from physical activity due to exposure to air pollution for long-term outcomes. Public health modelling studies have estimated that in most situations benefits of physical activity outweigh the risks of air pollution, at least in the active transport environment. However, overall evidence on all examined links is weak for low- and middle-income countries, for sensitive subpopulations (children, elderly, pregnant women, people with pre-existing conditions), and for indoor air pollution.
Physical activity and air pollution are linked through multiple mechanisms, and these relations could have important implications for public health, especially in locations with high air pollution concentrations. Overall, this review calls for international collaboration between air pollution and physical activity research fields to strengthen the evidence base on the links between both and on how policy options could potentially reduce risks and maximise health benefits.
Logistics and transport increasingly play a pivotal role in international trade relations. The Logistics Performance Index (LPI) analyses differences between countries in terms of customs procedures, ...logistics costs and the quality of the infrastructure for overland and maritime transport. The aim of this article is to analyse the impact that each of these components has on trade in emerging economies using a gravity model. Furthermore, the study also attempts to detect possible advances in logistics in developing countries, which are grouped into five regions (Africa, South America, Far East, Middle East and Eastern Europe) by comparing the first LPI data published in 2007 with the most recent data, released in 2012. The results obtained reveal that improvements in any of the components of the LPI can lead to significant growth in a country's trade flows. Specifically, LPI components are becoming increasingly important for international trade in many countries in Africa, South America and Eastern Europe.
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We ...sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Mammalian target of rapamycin (mTOR) is a central regulator of mammalian metabolism and physiology. Aberrant hyperactivation of the mTOR pathway promotes tumor growth and metastasis, and can also ...promote tumor resistance to chemotherapy and cancer drugs; this makes mTOR an attractive cancer therapeutic target. mTOR inhibitors have been approved to treat cancer; however, the mechanisms underlying drug sensitivity remain poorly understood. Here, whole exome sequencing of three chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed that all three patients shared somatic mutations in the deubiquitinase gene USP9X. The clonal characteristics of the mutations, which were amassed by studying multiple patients' primary and metastatic samples from various years, together with the low USP9X mutation rate in unselected chRCC series, reinforced a causal link between USP9X and mTOR inhibitor sensitivity. Rapamycin treatment of USP9X-depleted HeLa and renal cancer 786-O cells, along with the pharmacological inhibition of USP9X, confirmed that this protein plays a role in patients' sensitivity to mTOR inhibitors. USP9X was not found to exert a direct effect on mTORC1, but subsequent ubiquitylome analyses identified p62 as a direct USP9X target. Increased p62 ubiquitination and the augmented rapamycin effect upon bortezomib treatment, together with the results of p62 and LC3 immunofluorescence assays, suggested that dysregulated autophagy in USP9X-depleted cells can have a synergistic effect with mTOR inhibitors. In summary, we show that USP9X constitutes a potential novel marker of sensitivity to mTOR inhibitors in chRCC patients, and represents a clinical strategy for increasing the sensitivity to these drugs.
Paclitaxel, a widely used chemotherapeutic drug, can cause peripheral neuropathies leading to dose reductions and treatment suspensions and decreasing the quality of life of patients. It has been ...suggested that genetic variants altering paclitaxel pharmacokinetics increase neuropathy risk, but the major causes of interindividual differences in susceptibility to paclitaxel toxicity remain unexplained. We carried out a whole-exome sequencing (WES) study to identify genetic susceptibility variants associated with paclitaxel neuropathy.
Blood samples from 8 patients with severe paclitaxel-induced peripheral neuropathy were selected for WES. An independent cohort of 228 cancer patients with complete paclitaxel neuropathy data was used for variant screening by DHPLC and association analysis. HEK293 cells were used for heterologous expression and characterization of two novel CYP3A4 enzymes.
WES revealed 2 patients with rare CYP3A4 variants, a premature stop codon (CYP3A4*20 allele) and a novel missense variant (CYP3A4*25, p.P389S) causing reduced enzyme expression. Screening for CYP3A4 variants in the independent cohort revealed three additional CYP3A4*20 carriers, and two patients with missense variants exhibiting diminished enzyme activity (CYP3A4*8 and the novel CYP3A4*27 allele, p.L475V). Relative to CYP3A4 wild-type patients, those carrying CYP3A4 defective variants had more severe neuropathy (2- and 1.3-fold higher risk of neuropathy for loss-of-function and missense variants, respectively, P = 0.045) and higher probability of neuropathy-induced paclitaxel treatment modifications (7- and 3-fold higher risk for loss-of-function and missense variants, respectively, P = 5.9 × 10(-5)).
This is the first description of a genetic marker associated with paclitaxel treatment modifications caused by neuropathy. CYP3A4 defective variants may provide a basis for paclitaxel treatment individualization.
Summary Background Sunitinib is a tyrosine kinase inhibitor with proven efficacy in renal-cell carcinoma, but some patients do not respond or need dose reductions due to toxicity. Because there are ...no validated molecular predictors of response or toxicity to sunitinib, we aimed to identify genetic markers predictive of outcome and toxic effects. Methods In our observational, prospective study we enrolled previously untreated adults (≥18 years) with clear-cell renal-cell carcinoma at 15 institutions in the Spanish Oncology Genitourinary Group in Spain. Patients received sunitinib according to local practice guidelines. We assessed RECIST response, progression-free survival (PFS), overall survival, and toxicity of sunitinib with 16 key polymorphisms in nine genes: VEGFR2 (rs2305948 and rs1870377), VEGFR3 (rs307826, rs448012, and rs307821), PDGFR -α (rs35597368), VEGF-A (rs2010963, rs699947, and rs1570360), IL8 (rs1126647), CYP3A4 (rs2740574), CYP3A5 (rs776746), ABCB1 (rs1045642, rs1128503, and rs2032582), and ABCB2 (rs2231142). We assessed associations with efficacy and toxicity by use of univariable and multivariable analyses (with clinical factors associated with outcomes as covariates). We adjusted for multiplicity using the Bonferroni method; p values of less than 0·0031 before adjustment were deemed to still be significant after adjustment. Findings We enrolled 101 patients between Oct 10, 2007, and Dec 13, 2010. 95 of these patients were included in toxicity analyses and 89 in the efficacy analyses. Two VEGFR3 missense polymorphisms were associated with reduced PFS with sunitinib on multivariable analysis: rs307826 (hazard ratio HR per allele 3·57, 1·75–7·30; punadjusted =0·00049, padjusted =0·0079) and rs307821 (3·31, 1·64–6·68; punadjusted =0·00085, padjusted =0·014). The CYP3A5*1 (rs776746) high metabolising allele was associated in a multivariable analysis with an increased risk of dose reductions due to toxicity (HR per allele 3·75, 1·67–8·41; punadjusted =0·0014, padjusted =0·022). No other SNPs were associated with sunitinib response or toxicity. Interpretation Polymorphisms in VEGFR3 and CYP3A5*1 might be able to define a subset of patients with renal-cell carcinoma with decreased sunitinib response and tolerability. If confirmed, these results should promote interventional studies testing alternative therapeutic approaches for patients with such variants. Funding Pfizer.
To compare the country-level absolute and relative contributions of physical activity at work and in the household, for travel, and during leisure-time to total moderate-to-vigorous physical activity ...(MVPA).
We used data collected between 2002 and 2019 from 327 789 participants across 104 countries and territories (n=24 low, n=34 lower-middle, n=30 upper-middle, n=16 high-income) from all six World Health Organization (WHO) regions. We calculated mean min/week of work/household, travel and leisure MVPA and compared their relative contributions to total MVPA using Global Physical Activity Questionnaire data. We compared patterns by country, sex and age group (25-44 and 45-64 years).
Mean MVPA in work/household, travel and leisure domains across the 104 countries was 950 (IQR 618-1198), 327 (190-405) and 104 (51-131) min/week, respectively. Corresponding relative contributions to total MVPA were 52% (IQR 44%-63%), 36% (25%-45%) and 12% (4%-15%), respectively. Work/household was the highest contributor in 80 countries; travel in 23; leisure in just one. In both absolute and relative terms, low-income countries tended to show higher work/household (1233 min/week, 57%) and lower leisure MVPA levels (72 min/week, 4%). Travel MVPA duration was higher in low-income countries but there was no obvious pattern in the relative contributions. Women tended to have relatively less work/household and more travel MVPA; age groups were generally similar.
In the largest domain-specific physical activity study to date, we found considerable country-level variation in how MVPA is accumulated. Such information is essential to inform national and global policy and future investments to provide opportunities to be active, accounting for country context.
Abstract
Differentiated thyroid cancers (DTCs) are primarily initiated by mutations that activate the MAPK signaling cascade, typically at BRAF or RAS oncoproteins. DTCs can evolve to more aggressive ...forms, specifically, poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), by acquiring additional genetic alterations which deregulate key pathways. In this review, we focused on bona fide mutations involved in thyroid cancer progression for which consistent mechanistic data exist. Here we summarized the relevant literature, spanning approximately 2 decades, highlighting genetic alterations that are unquestionably enriched in PDTC/ATC. We describe the relevant functional data obtained in multiple in vitro and in vivo thyroid cancer models employed to study genetic alterations in the following genes and functional groups: TP53, effectors of the PI3K/AKT pathway, TERT promoter, members of the SWI/SNF chromatin remodeling complex, NF2, and EIF1AX. In addition, we briefly discuss other genetic alterations that are selected in aggressive thyroid tumors but for which mechanistic data is still either limited or nonexistent. Overall, we argue for the importance conveyed by preclinical studies for the clinical translation of genomic knowledge of thyroid cancers.
Background:
We explore frequentist operating characteristics of a Bayesian adaptive design that allows continuous early stopping for futility. In particular, we focus on the power versus sample size ...relationship when more patients are accrued than originally planned.
Methods:
We consider the case of a phase II single-arm study and a Bayesian phase II outcome-adaptive randomization design. For the former, analytical calculations are possible; for the latter, simulations are conducted.
Results:
Results for both cases show a decrease in power with an increasing sample size. It appears that this effect is due to the increasing cumulative probability of incorrectly stopping for futility.
Conclusion:
The increase in cumulative probability of incorrectly stopping for futility is related to the continuous nature of the early stopping, which increases the number of interim analyses with accrual. The issue can be addressed by, for instance, delaying the start of testing for futility, reducing the number of futility tests to be performed or by setting stricter criteria for concluding futility.
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