Exposure to low-level ambient air pollution and the relationship with lung and bladder cancer in older men, in Perth, Western Australia

Background: Air pollution is a cause of lung cancer and is associated with bladder cancer. However, the relationship between air pollution and these cancers in regions of low pollution is unclear. We investigated associations between fine particulate matter (PM2.5), nitrogen dioxide, and black carbon (BC), and both these cancers in a low-pollution city. Methods: A cohort of 11,679 men ≥65 years old in Perth (Western Australia) were followed from 1996–1999 until 2018. Pollutant concentrations, as a time-varying variable, were estimated at participants’ residential addresses using land use regression models. Incident lung and bladder cancer were identified through the Western Australian Cancer Registry. Risks were estimated using Cox proportional-hazard models (age as the timescale), adjusting for smoking, socioeconomic status, and co-pollutants. Results: Lung cancer was associated with PM2.5 and BC in the adjusted single-pollutant models. A weak positive association was observed between ambient air pollution and squamous cell lung carcinoma but not lung adenocarcinoma. Positive associations were observed with bladder cancer, although these were not statistically significant. Associations were attenuated in two-pollutant models. Conclusion: Low-level ambient air pollution is associated with lung, and possibly bladder, cancer among older men, suggesting there is no known safe level for air pollution as a carcinogen

Arterial spin labeling using spatio-temporal encoding readout for robust perfusion imaging in inhomogenous magnetic fields

Purpose: To evaluate the feasibility of spatio-temporal encoding (SPEN) readout for pseudo-continuous ASL (pCASL) in brain, and its robustness to susceptibility artifacts as introduced by aneurysm clips. Methods: A 2D self-refocused T 2*-compensated hybrid SPEN scheme, with super-resolution reconstruction was implemented on a 1.5T Philips system. Q (=BW chirp*T chirp) was varied and, the aneurysm clip-induced artifact was evaluated in phantom (label-images) as well as in vivo (perfusion-weighted signal (PWS)-maps and temporal SNR (tSNR)). In vivo results were compared to gradient-echo EPI (GE-EPI) and spin-echo EPI (SE-EPI). The dependence of tSNR on TR was evaluated separately for SPEN and SE-EPI. SPEN with Q ˜ 75 encodes with the same off-resonance robustness as EPI. Results: The clip-induced artifact with SPEN decreased with increase in Q, and was smaller compared to SE-EPI and GE-EPI in vivo. tSNR decreased with Q and the tSNR of GE-EPI and SE-EPI corresponded to SPEN with a Q-value of approximately ˜85 and ˜108, respectively. In addition, SPEN perfusion images showed a higher tSNR (p  75) compared to SE-EPI and GE-EPI. However, the SPEN chirp-pulse saturates incoming blood, thereby reducing pCASL labeling efficiency of the next acquisition for short TRs. Future developments are needed to enable 3D scanning

Multiparametric Renal MRI: An Intrasubject Test-Retest Repeatability Study

BACKGROUND: Renal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease. PURPOSE: To determine intrasubject test-retest repeatability of renal MRI measurements. STUDY TYPE: Prospective. POPULATION: Nineteen healthy subjects aged over 40 years. FIELD STRENGTH/SEQUENCES: T1 and T2 mapping, R2 * mapping or blood oxygenation level-dependent (BOLD) MRI, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI), 2D phase contrast, arterial spin labelling (ASL), dynamic contrast enhanced (DCE) MRI, and quantitative Dixon for fat quantification at 3T. ASSESSMENT: Subjects were scanned twice with ~1 week between visits. Total scan time was ~1 hour. Postprocessing included motion correction, semiautomated segmentation of cortex and medulla, and fitting of the appropriate signal model. STATISTICAL TEST: To assess the repeatability, a Bland-Altman analysis was performed and coefficients of variation (CoVs), repeatability coefficients, and intraclass correlation coefficients were calculated. RESULTS: CoVs for relaxometry (T1 , T2 , R2 */BOLD) were below 6.1%, with the lowest CoVs for T2 maps and highest for R2 */BOLD. CoVs for all diffusion analyses were below 7.2%, except for perfusion fraction (FP ), with CoVs ranging from 18-24%. The CoV for renal sinus fat volume and percentage were both around 9%. Perfusion measurements were most repeatable with ASL (cortical perfusion only) and 2D phase contrast with CoVs of 10% and 13%, respectively. DCE perfusion had a CoV of 16%, while single kidney glomerular filtration rate (GFR) had a CoV of 13%. Repeatability coefficients (RCs) ranged from 7.7-87% (lowest/highest values for medullary mean diffusivity and cortical FP , respectively) and intraclass correlation coefficients (ICCs) ranged from -0.01 to 0.98 (lowest/highest values for cortical FP and renal sinus fat volume, respectively). DATA CONCLUSION: CoVs of most MRI measures of renal function and structure (with the exception of FP and perfusion as measured by DCE) were below 13%, which is comparable to standard clinical tests in nephrology. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1

Exploring label dynamics of velocity-selective arterial spin labeling in the kidney

Purpose: Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR). Methods: Arterial spin labeling data were acquired in 7 subjects, using free-breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior–posterior velocity-encoding direction. Cortical perfusion-weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported. Results: In contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was ≤ 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 ± 79 ms, P .05) with good correlations on subject level. Conclusion: Velocity-selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time-efficient, single-time-point, free-breathing renal perfusion measurements, despite lower tSNR than FAIR

The global burden of injury: Incidence, mortality, disability-adjusted life years and time trends from the global burden of disease study 2013

Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disabilityadjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for illdefined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made

The burden of unintentional drowning : global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study

Background Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017. Methods Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning. Results Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes. Conclusions There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.Peer reviewe

Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions

Over 90% of all cancers are carcinomas, malignancies derived from cells of epithelial origin. As carcinomas progress, these tumors may lose epithelial morphology and acquire mesenchymal characteristics which contribute to metastatic potential. An epithelial-to-mesenchymal transition (EMT) similar to the process critical for embryonic development is thought to be an important mechanism for promoting cancer invasion and metastasis. Epithelial-to-mesenchymal transitions have been induced in vitro by transient or unregulated activation of receptor tyrosine kinase signaling pathways, oncogene signaling and disruption of homotypic cell adhesion. These cellular models attempt to mimic the complexity of human carcinomas which respond to autocrine and paracrine signals from both the tumor and its microenvironment. Activation of the epidermal growth factor receptor (EGFR) has been implicated in the neoplastic transformation of solid tumors and overexpression of EGFR has been shown to correlate with poor survival. Notably, epithelial tumor cells have been shown to be significantly more sensitive to EGFR inhibitors than tumor cells which have undergone an EMT-like transition and acquired mesenchymal characteristics, including non-small cell lung (NSCLC), head and neck (HN), bladder, colorectal, pancreas and breast carcinomas. EGFR blockade has also been shown to inhibit cellular migration, suggesting a role for EGFR inhibitors in the control of metastasis. The interaction between EGFR and the multiple signaling nodes which regulate EMT suggest that the combination of an EGFR inhibitor and other molecular targeted agents may offer a novel approach to controlling metastasis

Burden of injury along the development spectrum: associations between the Socio-demographic Index and disability-adjusted life year estimates from the Global Burden of Disease Study 2017

Background The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. Methods Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm-the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. results For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. Conclusions The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum

The burden of unintentional drowning: Global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study

__Background:__ Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017. __Methods:__ Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning. __Results:__ Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes. __Conclusions:__ There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low-and middle-income countries