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BACKGROUND: Hypertension is the biggest contributor to the global cardiovascular burden with evidence for ethnic differences in treatment response and outcomes. Under-representation of ethnic minorities in clinical research is well known, and despite wide-ranging public engagement events by the Glasgow Blood Pressure Clinic team, there was a lack of participation of ethnic minorities in both engagement activities and clinical trials conducted by them. This study aims to explore the awareness and knowledge of hypertension and the facilitators and barriers to participation in hypertension clinical research among South Asian (SA) and African (AFR) communities in Glasgow. METHODS: A survey questionnaire was co-developed with representatives from South Asian (SA) and African (AFR) patients and community members in Glasgow to understand awareness and knowledge of hypertension and enablers and barriers to participation in clinical research. The survey was distributed to adults (aged > 18) years of SA or AFR ancestry at public engagement events at venues that were frequently visited by these two communities in Glasgow. RESULTS: The survey response rate was 337 (67.4%) consisting of 242 (71.8%) South Asian (SA) and 56 (16.9%) African (AFR) respondents. Thirty-nine questionnaires were excluded because of incompletion. Most of the respondents were not born in the UK and were in the 35-53-year group (AFR 29 (51%), SA 113 (47%)). The proportion living in the most deprived (SIMD 1) and least deprived (SIMD 5) was respectively 26 (12.4%) and 34 (16.2%) for SA and 20 (42.6%) and 2 (4.3%) for AFR. There was a considerable recognition that treatment needs to be ethnicity-specific (SA/AFR = 107 (48%)/23 (45.1%)) and that current cardiovascular disease treatment guidelines were not tailored for different ethnicities 84 (38.5%)/23 (45.1%). The key enablers encouraging research participation are enhanced health information, conducting aspects of their clinical research visits/appointment

©2019. American Geophysical Union. All Rights Reserved. The expansion of globally consistent satellite-radar imagery presents new opportunities to measure Earth-surface displacements on intercontinental scales. Yet global applications, including a complete assessment of the land contribution to relative sea-level rise, first demand new solutions to unify relative satellite-radar observations in a geocentric reference frame. The international network of Very Long Baseline Interferometry telescopes provides an existing, yet unexploited, link to unify satellite-radar measurements on a global scale. Proof-of-concept experiments reveal the suitability of these instruments as high-amplitude reflectors for satellite radar and thus provide direct connections to a globally consistent reference frame. Automated tracking of radar satellites is easily integrated into telescope operations alongside ongoing schedules for geodesy and astrometry. Utilizing existing telescopes in this way completely avoids the need for additional geodetic infrastructure or ground surveys and is ready to implement immediately across the telescope network as a first step toward using satellite radar on a global scale.

Background: Most studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia's national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births. Methods: Births records for 2001–2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children <2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 − adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children. Results: Following introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9–98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5–94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4–90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children. Conclusion: Our population-based cohort study demonstrates that >90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The si

Background: Most studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccinationprograms afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia’s national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births. Methods: Births records for 2001–2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children <2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 − adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children. Results: Following introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9–98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5–94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4–90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children. Conclusion: Our population-based cohort study demonstrates that >90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The siz

INTRODUCTION: Several countries have developed national immunisation registers, but only the Nordic countries have linked their registers to other health data in order to comprehensively evaluate the `real world' effectiveness of vaccines. Nordic countries can link datasets deterministically using the national person identifier, but most countries, including Australia, don't have such an identifier to enable this type of linkage. OBJECTIVES: To describe the process for assembling a linked study cohort that will enable the conduct of population-based studies related to immunisation and immunisation policy. METHODS: National death and immunisation databases along with state health data (notifications of vaccine preventable diseases, perinatal data, hospital admissions and emergency department presentations) up until December 2013 were probabilistically linked (using demographic details) for children born between 1996 and 2012 in two states: Western Australia and New South Wales (42% of Australia's population, combined). RESULTS: After exclusions there were 1.95 million children in the study cohort (live born children with both a birth and perinatal record which represents 97.5% of all live births in the state perinatal data collections - our source population) and 18.0 million person years of follow up (mean: 9.2 years per child). The characteristics of children in the cohort were generally similar to those only included in state perinatal databases and outcome measures were in keeping with expected figures from unlinked data sources. However, the lack of a dynamic national population register meant immigrants could not be included. CONCLUSIONS: We have been able to develop a similarly comprehensive system to the Nordic countries based on probabilistic linkage methods. Our experience should provide encouragement to other countries with national immunisation registers looking to establish similar systems.

Background and Purpose— The characteristics of intracerebral hemorrhage (ICH) may vary by ICH location because of differences in the distribution of underlying cerebral small vessel diseases. Therefore, we investigated the incidence, characteristics, and outcome of lobar and nonlobar ICH. Methods— In a population-based, prospective inception cohort study of ICH, we used multiple overlapping sources of case ascertainment and follow-up to identify and validate ICH diagnoses in 2010 to 2011 in an adult population of 695 335. Results— There were 128 participants with first-ever primary ICH. The overall incidence of lobar ICH was similar to nonlobar ICH (9.8 [95% confidence interval, 7.7–12.4] versus 8.6 [95% confidence interval, 6.7–11.1] per 100 000 adults/y). At baseline, adults with lobar ICH were more likely to have preceding dementia (21% versus 5%; P=0.01), lower Glasgow Coma Scale scores (median, 13 versus 14; P=0.03), larger ICHs (median, 38 versus 11 mL; P<0.001), subarachnoid extension (57% versus 5%; P<0.001), and subdural extension (15% versus 3%; P=0.02) than those with nonlobar ICH. One-year case fatality was lower after lobar ICH than after nonlobar ICH (adjusted odds ratio for death at 1 year: lobar versus nonlobar ICH 0.21; 95% confidence interval, 0.07–0.63; P=0.006, after adjustment for known predictors of outcome). There were 4 recurrent ICHs, which occurred exclusively in survivors of lobar ICH (annual risk of recurrent ICH after lobar ICH, 11.8%; 95% confidence interval, 4.6%–28.5% versus 0% after nonlobar ICH; log-rank P=0.04). Conclusions— The baseline characteristics and outcome of lobar ICH differ from other locations.

Background and Purpose— The characteristics of intracerebral hemorrhage (ICH) may vary by ICH location because of differences in the distribution of underlying cerebral small vessel diseases. Therefore, we investigated the incidence, characteristics, and outcome of lobar and nonlobar ICH. Methods— In a population-based, prospective inception cohort study of ICH, we used multiple overlapping sources of case ascertainment and follow-up to identify and validate ICH diagnoses in 2010 to 2011 in an adult population of 695 335. Results— There were 128 participants with first-ever primary ICH. The overall incidence of lobar ICH was similar to nonlobar ICH (9.8 [95% confidence interval, 7.7–12.4] versus 8.6 [95% confidence interval, 6.7–11.1] per 100 000 adults/y). At baseline, adults with lobar ICH were more likely to have preceding dementia (21% versus 5%; P=0.01), lower Glasgow Coma Scale scores (median, 13 versus 14; P=0.03), larger ICHs (median, 38 versus 11 mL; P<0.001), subarachnoid extension (57% versus 5%; P<0.001), and subdural extension (15% versus 3%; P=0.02) than those with nonlobar ICH. One-year case fatality was lower after lobar ICH than after nonlobar ICH (adjusted odds ratio for death at 1 year: lobar versus nonlobar ICH 0.21; 95% confidence interval, 0.07–0.63; P=0.006, after adjustment for known predictors of outcome). There were 4 recurrent ICHs, which occurred exclusively in survivors of lobar ICH (annual risk of recurrent ICH after lobar ICH, 11.8%; 95% confidence interval, 4.6%–28.5% versus 0% after nonlobar ICH; log-rank P=0.04). Conclusions— The baseline characteristics and outcome of lobar ICH differ from other locations.

FK506 binding protein-like (FKBPL) and its peptide derivatives exert potent anti-angiogenic activity in vitro and in vivo and control tumour growth in xenograft models, when administered exogenously. However, the role of endogenous FKBPL in angiogenesis is not well characterised. Here we investigated the molecular effects of the endogenous protein and its peptide derivative, AD-01, leading to their anti-migratory activity. Inhibition of secreted FKBPL using a blocking antibody or siRNA-mediated knockdown of FKBPL accelerated the migration of human microvascular endothelial cells (HMEC-1). Furthermore, MDA-MB-231 tumour cells stably overexpressing FKBPL inhibited tumour vascular development in vivo suggesting that FKBPL secreted from tumour cells could inhibit angiogenesis. Whilst FKBPL and AD-01 target CD44, the nature of this interaction is not known and here we have further interrogated this aspect. We have demonstrated that FKBPL and AD-01 bind to the CD44 receptor and inhibit tumour cell migration in a CD44 dependant manner; CD44 knockdown abrogated AD-01 binding as well as its anti-migratory activity. Interestingly, FKBPL overexpression and knockdown or treatment with AD-01, regulated CD44 expression, suggesting a co-regulatory pathway for these two proteins. Downstream of CD44, alterations in the actin cytoskeleton, indicated by intense cortical actin staining and a lack of cell spreading and communication were observed following treatment with AD-01, explaining the anti-migratory phenotype. Concomitantly, AD-01 inhibited Rac-1 activity, up-regulated RhoA and the actin binding proteins, profilin and vinculin. Thus the anti-angiogenic protein, FKBPL, and AD-01, offer a promising and alternative approach for targeting both CD44 positive tumours and vasculature networks. © 2013 Yakkundi et al.

FK506 binding protein-like (FKBPL) and its peptide derivatives exert potent anti-angiogenic activity in vitro and in vivo and control tumour growth in xenograft models, when administered exogenously. However, the role of endogenous FKBPL in angiogenesis is not well characterised. Here we investigated the molecular effects of the endogenous protein and its peptide derivative, AD-01, leading to their anti-migratory activity. Inhibition of secreted FKBPL using a blocking antibody or siRNA-mediated knockdown of FKBPL accelerated the migration of human microvascular endothelial cells (HMEC-1). Furthermore, MDA-MB-231 tumour cells stably overexpressing FKBPL inhibited tumour vascular development in vivo suggesting that FKBPL secreted from tumour cells could inhibit angiogenesis. Whilst FKBPL and AD-01 target CD44, the nature of this interaction is not known and here we have further interrogated this aspect. We have demonstrated that FKBPL and AD-01 bind to the CD44 receptor and inhibit tumour cell migration in a CD44 dependant manner; CD44 knockdown abrogated AD-01 binding as well as its anti-migratory activity. Interestingly, FKBPL overexpression and knockdown or treatment with AD-01, regulated CD44 expression, suggesting a co-regulatory pathway for these two proteins. Downstream of CD44, alterations in the actin cytoskeleton, indicated by intense cortical actin staining and a lack of cell spreading and communication were observed following treatment with AD-01, explaining the anti-migratory phenotype. Concomitantly, AD-01 inhibited Rac-1 activity, up-regulated RhoA and the actin binding proteins, profilin and vinculin. Thus the anti-angiogenic protein, FKBPL, and AD-01, offer a promising and alternative approach for targeting both CD44 positive tumours and vasculature networks. © 2013 Yakkundi et al.

Migraine is a common, genetically influenced neurovascular disorder. The dopamine transporter gene is a candidate for migraine association studies. This study tested a functionally linked variable number tandem repeat (VNTR) in intron 8 of the dopamine transporter gene (DATInt8) in 550 migraine cases (401 with aura, 149 without aura) and 550 non-migraine controls. Chi-squared analysis of the DATInt8 revealed that the allele and genotype frequency distributions for migraine cases (including subtype analysis) and controls were not different (P > 0.1). These findings offer no evidence for an association of the DATInt8 with migraine with and without aura and therefore do not implicate the dopamine transporter gene as a modifier of migraine risk.