Ticagrelor or clopidogrel dual antiplatelet therapy following a pharmacoinvasive strategy in ST-segment elevation myocardial infarction.

OBJECTIVES: To describe and evaluate outcomes in STEMI patients sustained on clopidogrel compared to those switched to ticagrelor following fibrinolysis. BACKGROUND: World-wide, many STEMI patients cannot achieve timely PCI and therefore require fibrinolysis. Although comparable 30-day and 1-year safety was shown with clopidogrel or ticagrelor in the TREAT study, there is paucity of long-term outcomes in pharmacoinvasive treated STEMI. METHODS: We conducted an observational cohort study evaluating consecutive pharmacoinvasive STEMI patients treated in a network, comparing those switched to ticagrelor to those sustained on clopidogrel. The primary efficacy composite was one-year all-cause death, recurrent myocardial infarction, and stroke with major bleeding and intracranial hemorrhage (ICH) as the safety outcomes. Multivariable Cox regression model was used to examine the association between P2Y12 inhibitor and outcomes with inverse probability weighting. RESULTS: Of 1426 pharmacoinvasive STEMI patients, 28% (n = 396) were converted to ticagrelor at a mean of 9.9 h after fibrinolysis with comparable GRACE Risk Scores (median; 158 vs 157, p0.352). The primary composite occurred in 3.5% of ticagrelor and 7.0% of clopidogrel treated patients (p0.014). Following adjustment, ticagrelor was associated with a 54% lower composite outcome (adjusted HR 0.46, 95% confidence interval 0.26-0.84). Major bleeding 6.3% vs 6.1% (NS) and ICH 0.0% vs 0.2% (NS) were similar. CONCLUSIONS: In a prospective STEMI cohort, switching to ticagrelor compared with sustaining clopidogrel following fibrinolysis pharmacoinvasive reperfusion reduced recurrent ischemic events at 1-year with no differences in major bleeding or ICH. Aligned with randomized data, these findings provide support to switch pharmaco-invasively treated STEMI patients.

Null association between serum 25-hydroxyvitamin D levels with allergic rhinitis, allergic sensitization and non-allergic rhinitis: A Mendelian randomization study.

BACKGROUND: Previous observational studies have not found a conclusive association between serum 25-hydroxyvitamin D (25(OH)D) levels and allergic rhinitis (AR) or allergic sensitization (AS). OBJECTIVE: To investigate a causal association between 25(OH)D levels with risk of AR and AS, using a two-sample Mendelian randomization (MR) approach. METHODS: Seven single nucleotide polymorphisms (SNPs), previously shown to be associated with serum 25(OH)D levels, were identified as instrumental variables. The primary outcome was AR, and the secondary outcomes were AS and non-allergic rhinitis (NAR). The genome-wide association (GWA) summary statistics of the outcomes were obtained from two cohort studies (EAGLE Consortium and UK Biobank). An MR analysis with random-effects inverse-variance weighted method was performed as the primary analysis to estimate overall effect size (odds ratio [OR] and 95% confidence interval [CI]). Sensitivity analysis using weighted median method and MR-Egger regression method was conducted. A subgroup analysis based on 25(OH)D synthesis-related SNPs was further applied. RESULTS: Serum 25(OH)D levels were not causally associated with risk of AR (OR: 0.960; 95% CI: 0.779-1.184), AS (OR: 1.059; 95% CI: 0.686 to 1.634) or NAR (OR: 0.937; 95% CI: 0.588-1.491). Subgroup analysis also showed null association between 25(OH)D synthesis-related SNPs and the outcomes. Sensitivity analyses yielded similar results. CONCLUSIONS AND CLINICAL RELEVANCE: This MR study found no evidence supporting a causal association between serum 25(OH)D levels and risk of AR, AS and NAR in European-ancestry population. This argues against the previous postulation that vitamin D supplementation is effective in prevention of allergic diseases.

Serum metabolomic profiling and its association with 25-hydroxyvitamin D.

INTRODUCTION: The beneficial effect of vitamin D on the risk of non-musculoskeletal diseases has been investigated in observational studies and randomized clinical trials, but the findings were inconsistent. Identification of the metabolomic profile associated with vitamin D helps to identify novel biomarkers and increase the understanding of the biochemical and physiological role of vitamin D in different health conditions. METHOD: Serum metabolomic profiling was performed using liquid chromatography/tandem mass spectrometry [LC/MS] and their association with serum 25(OH)D was evaluated using multivariable linear regression in the baseline cohort of 316 participants (aged 20 or above; 92 men, 224 women; mean age±SD: 48.1 ± 15.8 years) and in the follow-up cohort of 275 participants (aged 20 or above; 12 men, 263 women; mean age: 56.2 ± 9.6) of the Hong Kong Osteoporosis Study. We discovered and validated potential metabolites; and by meta-analysis of these associations in two cohorts, we identified metabolites that were significantly associated with serum 25(OH)D levels. RESULTS: Among 835 known metabolites, 102 metabolites showed significant correlation with 25(OH)D levels at baseline visit. Of these metabolites, 27 were validated in the follow-up visit. In meta-analysis of data from these two visits, 13 metabolites were highly correlated with 25(OH)D. The majority of metabolites identified were lipid in nature. Docosahexaenoylcarnitine and eicosapentaenoylcholine had the highest correlations, with effect estimates 0.2554 (p = 9.60 × 10-9) and 0.1682 (p = 4.94 × 10-7) respectively. CONCLUSION: In Hong Kong Chinese at least, serum vitamin D level is closely related to lipid metabolism. Our finding highlights an important new direction in the study of vitamin D in different health conditions.

25-Hydroxyvitamin D and the risk of incident diabetes in Hong Kong Chinese.

OBJECTIVE: To investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) and risk of incident diabetes in Hong Kong Chinese, after accounting for the effect of multiple bone- and mineral-related markers. DESIGN: We conducted a retrospective study on the Hong Kong Osteoporosis Study cohort. Incident diabetes was ascertained using electronic medical records. Serum 25(OH)D was measured at baseline and its association with incident diabetes was evaluated using multivariable Cox proportional-hazard regression. PARTICIPANTS: Individuals (n 4342) aged 20 years or above (1395 men, 2947 women; mean age 54·3 (sd 16·5) years) from the Hong Kong Osteoporosis Study, who were free of diabetes at baseline, were included. RESULTS: During 40 124·7 person-years of follow-up (a median of 9·2 years), 443 participants developed diabetes. Mean 25(OH)D was 63·34 (sd 13·07) nmol/l. Age-, sex- and BMI-adjusted Cox proportional-hazard regression showed no significant difference in the risk of incident diabetes between the lowest and the highest quintiles of 25(OH)D. In the analysis of the interaction effect between 25(OH)D and serum Ca, the interaction term did not affect the risk of incident diabetes significantly (P = 0·694). Similarly, there was no significant interaction of different subgroups (age, sex, BMI, femoral-neck T-score, serum Ca levels) with serum 25(OH)D. CONCLUSIONS: The present study finds that serum vitamin D level is not associated with the risk of incident diabetes in Hong Kong Chinese and this relationship is not modified by serum Ca level.

Pharmacoinvasive Strategy Versus Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction in Clinical Practice: Insights From the Vital Heart Response Registry.

BACKGROUND: Recent clinical trial data support a pharmacoinvasive strategy as an alternative to primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction. We evaluated whether this is true in a real-world prehospital ST-segment elevation myocardial infarction network using ECG assessment of reperfusion coupled with clinical outcomes within 1 year. METHODS: Of the 5583 ST-segment elevation myocardial infarction patients in the Alberta Vital Heart Response Program (Cohort 1 [2006-2011]: n=3593; Cohort 2 [2013-2016]: n=1990), we studied 3287 patients who received a pharmacoinvasive strategy with tenecteplase (April 2013: half-dose tenecteplase was employed in prehospital patients ≥75 years) or pPCI. ECGs were analyzed within a core laboratory; sum ST-segment deviation resolution ≥50% was defined as successful reperfusion. The primary composite was all-cause death, congestive heart failure, cardiogenic shock, and recurrent myocardial infarction within 1 year. RESULTS: The pharmacoinvasive approach was administered in 1805 patients (54.9%), (493 [27.3%] underwent rescue/urgent percutaneous coronary intervention and 1312 [72.7%] had scheduled angiography); pPCI was performed in 1482 patients (45.1%). There was greater ST-segment resolution post-catheterization/percutaneous coronary intervention with a pharmacoinvasive strategy versus pPCI (75.8% versus 64.3%, IP-weighted odds ratio, 1.59; 95% CI, 1.33-1.90; P<0.001). The primary composite was significantly lower with a pharmacoinvasive approach (16.3% versus 23.1%, IP-weighted hazard ratio, 0.84; 95% CI, 0.72-0.99; P=0.033). Major bleeding and intracranial hemorrhage were similar between a pharmacoinvasive strategy and pPCI (7.6% versus 7.5%, P=0.867; 0.6% versus 0.6%; P=0.841, respectively). In the 82 patients ≥75 years with a prehospital pharmacoinvasive strategy, similar ST-segment resolution and rescue rates were observed with full-dose versus half-dose tenecteplase (75.8% versus 88.9%, P=0.259; 31.0% versus 29.2%, P=0.867) with no difference in the primary composite (31.0% versus 25.0%, P=0.585). CONCLUSIONS: In this large Canadian ST-segment elevation myocardial infarction registry, a pharmacoinvasive strategy was associated with improved ST-segment resolution and enhanced outcomes within 1 year compared with pPCI. Our findings support the application of a selective pharmacoinvasive reperfusion strategy when delay to pPCI exists.

What are patients' knowledge, expectation and experience of radial extracorporeal shockwave therapy for the treatment of their tendinopathies? A qualitative study.

BACKGROUND: Extracorporeal shockwave therapy (ESWT) is used to manage different tendinopathies and appears to be effective in some tendinopathies but not others. The reasons for this are unclear. There is evidence that patient outcomes can be influenced by a patient-centred approach. There is therefore a need to qualitatively evaluate patient experiences for a treatment like ESWT where uncertainties exist. The aim of this study was to understand patients' overall perspective of ESWT to manage their tendinopathy. METHODS: A qualitative semi-structured face-to-face interview study design was used and the data was analysed thematically using 'Framework Analysis'. RESULTS: Eleven participants that have had radial ESWT (rESWT) to treat a range of tendinopathies were recruited from a private London sports clinic and interviewed in person or via Skype™. Four main themes and 16 subthemes were identified. Subthemes included previous failed treatment, clinician factors, mechanisms of ESWT, positive aspects, negative aspects, responsibility over own health and perceived outcomes. CONCLUSION: The participants understood the procedural aspects of rESWT, but were largely unaware of its mechanism of action and whether it was found to be effective for their condition or not. The participants felt that self-management measures were equally or more important than rESWT to help treat their tendinopathies. Recommendations would be for rESWT providers to offer patients written information, maintain continuity of care, address patients' expectations, feedback on progress, and encourage self-management measures such as activity modification.

An uncommon chronic osteochondral defect in the lateral tibial plateau detected after a separate injury.

Osteochondral defects (OCD) are rare conditions that usually present in young adolescents. The causes include trauma, inflammation, ischaemia, genetics and changes at secondary ossification centres. The case report presents a 27-year-old man with chronic intermittent left knee pain for about 3 years. He typically develops the symptom after prolonged standing or when rising from a prolonged seated position. An initial MRI scan in 2014 did not identify and report an OCD that was present in his left lateral tibial plateau. It was only after an accidental tibial fracture injury this year that the defect was incidentally detected on a scan. OCD can be staged based on MRI and/or arthroscopic findings. The treatment can be either non-operative or operative, but this largely depends on the age of the patient, the severity of symptoms and the staging of the defect.

Optimal vitamin D status and its relationship with bone and mineral metabolism in Hong Kong Chinese.

BACKGROUND: Although 25-hydroxyvitamin D (25[OH]D) is commonly used to define vitamin D status, there is no consensus on the cutoff levels for vitamin D deficiency and insufficiency. In this study, we aimed to identify the 25(OH)D threshold that maximally suppressed parathyroid hormone (PTH) in Hong Kong Chinese population. METHODS: The study included 5276 participants (70% female) of the Hong Kong Osteoporosis Study aged 20 or above who had total 25(OH)D measured. Three-phase segmented regression was used to identify the optimal break-point between 25(OH)D and PTH. RESULTS: The prevalence of vitamin D deficiency observed was 43.8% and the prevalence of insufficient (<75nmol/L) or deficient (<50nmol/L) vitamin D levels was 90.1% in our study population. Using unadjusted three-phase segmented regression, the estimated first and second break-point of 25(OH)D on PTH suppression were 32nmol/L (95% CI: 29-35) and 89nmol/L (95% CI: 77-101) with an r2 of 0.048, whereas the estimated first and second break-point of 25(OH)D were 27nmol/L (95% CI: 24-30) and 47nmol/L (95% CI: 37-56) after adjusting for factors affecting bone and mineral metabolism. In addition, the relationship between 25(OH)D and PTH significantly differed by sex and age. CONCLUSION: The threshold for 25OHD at the point of maximal suppression of PTH estimated in this study was lower than the suggested threshold of vitamin D deficiency in the literature, perhaps due to race or assay differences, and the relationship between vitamin D and PTH changed with sex and age. Standardization in the methodology of searching for the optimal break-point is desirable so that a consensus on cutoff points can be obtained.

Serum 25-hydroxyvitamin D and the risk of stroke in Hong Kong Chinese.

Low vitamin D levels have been associated with various cardiovascular diseases; however, whether it is associated with stroke remains inconclusive. We aimed to evaluate the association between serum 25-hydroxyvitamin D and risk of stroke. We conducted a cohort study consisting of 3,458 participants from the Hong Kong Osteoporosis Study aged ≥45 at baseline, examined between 1995 and 2010 and followed up using electronic medical records. Ischaemic and haemorrhagic stroke were defined using the ICD-9 code. In multivariable Cox-proportional hazard regression, quintiles 1 and 4 were significantly associated with increased risk of stroke when compared to the highest quintile (Quintile 1: HR, 1.78; 95 % CI, 1.16-2.74 and quintile 4: HR, 1.61; 95 % CI, 1.07-2.43). A similar association was observed in both men and women. In subgroup analysis, the association was specifically observed for ischaemic stroke, but not haemorrhagic stroke. Using a penalized regression spline, the association between vitamin D and risk of stroke was in a reverse J-shape, with the lowest risk of stroke being observed at 25(OH)D levels between 70 and 80 nmol/l. In conclusion, a low vitamin D level is associated with increased risk of ischaemic stroke; however, whether high vitamin D level is also associated with increased risk of stroke requires further study.

Myocardial blush and microvascular reperfusion following manual thrombectomy during percutaneous coronary intervention for ST elevation myocardial infarction: insights from the TOTAL trial.

AIMS: Thrombectomy during primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI) has been thought to be an effective therapy to prevent distal embolization and improve microvascular perfusion. The TOTAL trial (N = 10 732), a randomized trial of routine manual thrombectomy vs. PCI alone in STEMI, showed no difference in the primary efficacy outcome. This angiographic sub-study was performed to determine if thrombectomy improved microvascular perfusion as measured by myocardial blush grade (MBG). METHODS AND RESULTS: Of the 10 732 patients randomized, 1610 randomly selected angiograms were analysable by the angiographic core laboratory. Primary outcomes included MBG and post-PCI thrombolysis in myocardial infarction (TIMI) flow grade. Secondary outcomes included distal embolization, PPCI complications, and each component of the complications. The primary end point of final myocardial blush (221 [28%] 0/1 for thrombectomy vs. 246 {30%} 0/1 for PCI alone group, P = 0.38) and TIMI flow (712 [90%] TIMI 3 for thrombectomy vs. 733 [89.5%] TIMI 3 for PCI alone arm, P = 0.73) was similar in the two groups. Thrombectomy was associated with a significantly reduced incidence of distal embolization compared with PCI alone (56 [7.1%] vs. 87 [10.7%], P = 0.01). In multivariable analysis, distal embolization was an independent predictor of mortality (HR 3.00, 95% CI 1.19-7.58) while MBG was not (HR 2.73, 95% CI 0.94-5.3). CONCLUSIONS: Routine thrombectomy during PPCI did not result in improved MBG or post-PCI TIMI flow grade but did reduce distal embolization compared with PCI alone. Distal embolization and not blush grade is independently associated with mortality.

Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial.

BACKGROUND: Two large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice. METHODS: The trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10,732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear. In this longer-term follow-up of the TOTAL study, we report the results on the primary outcome (cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure) and secondary outcomes at 1 year. Analyses of the primary outcome were by modified intention to treat and only included patients who underwent index PCI. This trial is registered with ClinicalTrials.gov, number NCT01149044. FINDINGS: Between Aug 5, 2010, and July 25, 2014, 10,732 eligible patients were enrolled and randomly assigned to thrombectomy followed by PCI (n=5372) or to PCI alone (n=5360). After exclusions of patients who did not undergo PCI in each group (337 in the PCI and thrombectomy group and 331 in the PCI alone group), the final study population comprised 10,064 patients (5035 thrombectomy and 5029 PCI alone). The primary outcome at 1 year occurred in 395 (8%) of 5035 patients in the thrombectomy group compared with 394 (8%) of 5029 in the PCI alone group (hazard ratio [HR] 1·00 [95% CI 0·87-1·15], p=0·99). Cardiovascular death within 1 year occurred in 179 (4%) of the thrombectomy group and in 192 (4%) of 5029 in the PCI alone group (HR 0·93 [95% CI 0·76-1·14], p=0·48). The key safety outcome, stroke within 1 year, occurred in 60 patients (1·2%) in the thrombectomy group compared with 36 (0·7%) in the PCI alone group (HR 1·66 [95% CI 1·10-2·51], p=0·015). INTERPRETATION: Routine thrombus aspiration during PCI for STEMI did not reduce longer-term clinical outcomes and might be associated with an increase in stroke. As a result, thrombus aspiration can no longer be recommended as a routine strategy in STEMI. FUNDING: Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic Inc.

Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial

BackgroundTwo large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice.MethodsThe trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10 732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear...

Stroke in the TOTAL trial: a randomized trial of routine thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction.

AIMS: TOTAL (N = 10 732), a randomized trial of routine manual thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction, showed no difference in the primary efficacy outcome but a significant increase in stroke. We sought to understand these findings. METHODS AND RESULTS: A detailed analysis of stroke timing, stroke severity, and stroke subtype was performed. Strokes were adjudicated by neurologists blinded to treatment assignment. Stroke within 30 days, the primary safety outcome, was increased [33 (0.7%) vs. 16 (0.3%), hazard ratio (HR) 2.06; 95% confidence interval (CI) 1.13-3.75]. The difference in stroke was apparent within 48 h [15 (0.3%) vs. 5 (0.1%), HR 3.00; 95% CI 1.09-8.25]. There was an increase in strokes within 180 days with minor or no disability (Rankin 0-2) [18 (0.4%) vs. 13 (0.3%) HR 1.38; 95% CI 0.68-2.82] and in strokes with major disability or fatal (Rankin 3-6) [35 (0.7%) vs. 13 (0.3%), HR 2.69; 95% CI 1.42-5.08]. Most of the absolute difference was due to an increase in ischaemic strokes within 180 days [37 (0.7%) vs. 21 (0.4%), HR 1.71; 95% CI 1.03-3.00], but there was also an increase in haemorrhagic strokes [10 (0.2%) vs. 2 (0.04%), HR 4.98; 95% CI 1.09-22.7]. Patients that had a stroke had a mortality of 30.8% within 180 days vs. 3.4% without a stroke (P < 0.001). A meta-analysis of randomized trials (N = 21 173) showed an increase in risk of stroke (odds ratio 1.59; 95% CI 1.11-2.27) but a trend towards reduction in mortality odds ratio (odds ratio 0.87; 95% CI 0.76-1.00). CONCLUSION: Thrombectomy was associated with a significant increase in stroke. Based on these findings, future trials must carefully collect stroke to determine safety in addition to efficacy.

Fatal Fusarium solani species complex infections in elasmobranchs: the first case report for black spotted stingray (Taeniura melanopsila) and a literature review.

Fusarium species are environmental saprophytic fungi. Among the many Fusarium species, members of the Fusarium solani species complex (FSSC) are the most prevalent and virulent in causing human and animal infections. In this study, we describe the first case of fatal FSSC infection in a black spotted stingray and three concomitant infections in scalloped hammerhead sharks. In the stingray, cutaneous lesions were characterised by ulcers and haemorrhage of the ventral pectoral fin, or 'ray', especially around the head; while cutaneous lesions in the sharks were characterised by ulcers, haemorrhage, as well as white and purulent exudates at the cephalic canals of the cephalofoil and lateral line. Histological sections of the cutaneous lesions revealed slender (1-4 µm in diameter), branching, septate fungal hyphae. Internal transcribed spacer region and 28S nrDNA sequencing of the fungal isolates from the fish showed two isolates were F. keratoplasticum (FSSC 2) and the other two were FSSC 12. Environmental investigation revealed the FSSC strains isolated from water and biofilms in tanks that housed the elasmobranchs were also F. keratoplasticum and FSSC 12. Fusarium is associated with major infections in elasmobranchs and FSSC 12 is an emerging cause of infections in marine animals. DNA sequencing is so far the most reliable method for accurate identification of Fusarium species.

Near field stacking of zone plates for reduction of their effective zone period.

Here we analyze the potential of a new fabrication method for high resolution zone plates with high aspect ratios based on near field stacking of frequency doubled atomic layer deposited (ALD) zone plates. The proposed method enables reduction of the effective zone period by a factor of four with two zone plate layers compared to the initial e-beam lithography exposed outermost zone period. It also overcomes the problem that very small zone widths with high aspect ratios have to be fabricated for high-resolution hard X-ray microscopy. Using rigorous coupled wave theory, we have analyzed the diffraction behavior of these near field stacked zone plates and investigated strategies to optimize fabrication parameters to compensate for separation of stacked zone plates. The calculations performed for 8 keV photon energy and effective outermost zone widths of 28 nm and 15 nm predict diffraction efficiencies ≥ 20% suggesting that such optics could find widespread practical applications.

Plasma level of adrenomedullin is influenced by a single nucleotide polymorphism in the adiponectin gene.

OBJECTIVE: Adrenomedullin (ADM) and adiponectin are both involved in inflammation and cardiovascular diseases. The plasma levels of these peptides are influenced by single nucleotide polymorphisms (SNPs) in the ADM and ADIPOQ genes respectively. There is some evidence that ADM may regulate adiponectin gene expression, but whether adiponectin can regulate ADM expression is unclear, and was therefore investigated. METHODS: Plasma ADM level was measured in 476 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2). We genotyped them for 2 ADIPOQ SNPs that are known to be associated with plasma adiponectin level. RESULTS: The minor allele frequencies of ADIPOQ SNPs rs182052 and rs12495941 were 40.6% and 42.2% respectively. Plasma ADM level was significantly associated with rs182052 after adjusting for age and sex (ß=0.104, P=0.023) but not with rs12495941 (ß=0.071, P=0.120). In multivariate analysis, plasma ADM level increased with the number of minor alleles of rs182052 (P=0.013). Compared to subjects with GG genotype, subjects with AA genotype had 17.7% higher plasma ADM level (95% CI: 3.6%-33.7%). Subgroup analysis revealed that the association was significant in diabetic patients (ß=0.344, P=0.001) but not in non-diabetic subjects. CONCLUSION: Plasma ADM level is related to SNP rs182052 in the ADIPOQ gene. Our findings provide new evidence of the interplay between these two important peptides in cardiovascular disease and diabetes. Knowing the genotype may help to refine the interpretation of these biomarkers.

Instituting a smoke-free policy for city recreation centers and playgrounds, Philadelphia, Pennsylvania, 2010.

BACKGROUND: In the United States, more than 600 municipalities have smoke-free parks, and more than 100 have smoke-free beaches. Nevertheless, adoption of outdoor smoke-free policies has been slow in certain regions. Critical to widespread adoption is the sharing of knowledge about the policy development and implementation process. In this article, we describe our experience in making City of Philadelphia recreation centers and playgrounds smoke-free. COMMUNITY CONTEXT: Of the 10 largest US cities, Philadelphia has among the highest rates of adult and youth smoking. Our objectives for an outdoor smoke-free policy included protecting against secondhand smoke, supporting a normative message that smoking is harmful, motivating smokers to quit, and mitigating tobacco-related sanitation costs. METHODS: The Philadelphia Department of Public Health and the Department of Parks and Recreation engaged civic leaders, agency staff, and community stakeholders in the following steps: 1) making the policy case, 2) vetting policy options and engaging stakeholders, and 3) implementing policy. Near-term policy impacts were assessed through available data sources. OUTCOME: More than 220 recreation centers, playgrounds, and outdoor pools became smoke-free through a combined mayoral executive order and agency regulation. Support for the policy was high. Estimates suggest a policy reach of 3.6 million annual visitors and almost 850 acres of new smoke-free municipal property. INTERPRETATION: Localities can successfully implement outdoor smoke-free policies with careful planning and execution. Such policies hold great potential for reducing exposure to secondhand smoke, promoting nonsmoking norms, and providing additional motivation for residents to quit smoking.