Extensive collection of femtoliter pad secretion droplets in beetle Leptinotarsa decemlineata allows nanoliter microrheology

Pads of beetles are covered with long, deformable setae, each ending in a micrometric terminal plate coated with secretory fluid. It was recently shown that the layer of the pad secretion covering the terminal plates is responsible for the generation of strong attractive forces. However, less is known about the fluid itself because it is produced in extremely small quantity. We here present a first experimental investigation of the rheological properties of the pad secretion in the Colorado potato beetle {\it Leptinotarsa decemlineata}. Because the secretion is produced in an extremely small amount at the level of the terminal plate, we first develop a procedure based on capillary effects to collect the secretion. We then manage to incorporate micrometric beads, initially in the form of a dry powder, and record their thermal motion to determine the mechanical properties of the surrounding medium. We achieve such a quantitative measurement within the collected volume, much smaller than the $1 {\rm \mu}$l sample volume usually required for this technique. Surprisingly, the beetle secretion was found to behave as a purely viscous liquid, of high viscosity. This suggests that no specific complex fluid behaviour is needed during beetle locomotion. We build a scenario for the contact formation between the spatula at the setal tip and a substrate, during the insect walk. We show that the attachment dynamics of the insect pad computed from the high measured viscosity is in good agreement with observed insect pace. We finally discuss the consequences of the secretion viscosity on the insect adhesion

Characterizing temporary hydrological regimes at a European scale

Monthly duration curves have been constructed from climate data across Europe to help address the relative frequency of ecologically critical low flow stages in temporary rivers, when flow persists only in disconnected pools in the river bed. The hydrological model is 5 based on a partitioning of precipitation to estimate water available for evapotranspiration and plant growth and for residual runoff. The duration curve for monthly flows has then been analysed to give an estimate of bankfull flow based on recurrence interval. The corresponding frequency for pools is then based on the ratio of bank full discharge to pool flow, arguing from observed ratios of cross-sectional areas at flood 10 and low flows to estimate pool flow as 0.1% of bankfull flow, and so estimate the frequency of the pool conditions that constrain survival of river-dwelling arthropods and fish. The methodology has been applied across Europe at 15 km resolution, and can equally be applied under future climatic scenarios

Diabetes status modifies the long-term effect of lipoprotein-associated phospholipase A2 on major coronary events

AIMS/HYPOTHESIS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has an independent prognostic association with major coronary events (MCE). However, no study has investigated whether type 2 diabetes status modifies the effect of Lp-PLA2 activity or inhibition on the risk of MCE. We investigate the interaction between diabetes status and Lp-PLA2 activity with risk of MCE. Subsequently, we test the resulting hypothesis that diabetes status will play a role in modifying the efficacy of an Lp-PLA2 inhibitor. METHODS: A retrospective cohort study design was utilised in two study populations. Discovery analyses were performed in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) cohort based in Scotland, UK. Participants were categorised by type 2 diabetes control status: poorly controlled (HbA1c ≥ 48 mmol/mol or ≥6.5%) and well-controlled (HbA1c < 48 mmol/mol or <6.5%) diabetes (n = 7420). In a secondary analysis of the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial of Lp-PLA2 inhibitor (darapladib) efficacy, 15,828 participants were stratified post hoc by type 2 diabetes diagnosis status (diabetes or no diabetes) at time of recruitment. Lp-PLA2 activity was then divided into population-specific quartiles. MCE were determined from linked medical records in GoDARTS and trial records in STABILITY. First, the interaction between diabetes control status and Lp-PLA2 activity on the outcome of MCE was explored in GoDARTS. The effect was replicated in the placebo arm of STABILITY. The effect of Lp-PLA2 on MCE was then examined in models stratified by diabetes status. This helped determine participants at higher risk. Finally, the effect of Lp-PLA2 inhibition was assessed in STABILITY in the higher risk group. Cox proportional hazards models adjusted for confounders were used to assess associations. RESULTS: In GoDARTS, a significant interaction between increased Lp-PLA2 activity (continuous and quartile divided) and diabetes control status was observed in the prediction of MCE (p < 0.0001). These effects were replicated in the placebo arm of STABILITY (p < 0.0001). In GoDARTS, stratified analyses showed that, among individuals with poorly controlled diabetes, the hazards of MCE for those with high (Q4) Lp-PLA2 activity was 1.19 compared with individuals with lower (Q1-3) Lp-PLA2 activity (95% CI 1.11, 1.38; p < 0.0001) and 1.35 (95% CI 1.16, 1.57; p < 0.0001) when compared with those with the lowest activity (Q1). Those in the higher risk group were identified as individuals with the highest Lp-PLA2 activity (Q4) and poorly controlled diabetes or diabetes. Based on these observations in untreated populations, we hypothesised that the Lp-PLA2 inhibitor would have more benefit in this higher risk group. In this risk group, Lp-PLA2 inhibitor use was associated with a 33% reduction in MCE compared with placebo (HR 0.67 [95% CI 0.50, 0.90]; p = 0.008). In contrast, Lp-PLA2 inhibitor showed no efficacy in individuals with low activity, regardless of diabetes status, or among those with no baseline diabetes and high Lp-PLA2 activity. CONCLUSIONS/INTERPRETATION: These results support the hypothesis that diabetes status modifies the association between Lp-PLA2 activity and MCE. These results suggest that cardiovascular morbidity and mortality associated with Lp-PLA2 activity is especially important in patients with type 2 diabetes, particularly those with worse glycaemic control. Further investigation of the effects of Lp-PLA2 inhibition in diabetes appears warranted. DATA AVAILABILITY: STABILITY trial data are available from clinicaltrials.gov repository through the GlaxoSmithKline clinical study register https://clinicaltrials.gov/ct2/show/NCT00799903 . GoDARTS datasets generated during and/or analysed during the current study are available following request to the GoDARTS Access Managements Group https://godarts.org/scientific-community/

Bragg coherent x-ray diffractive imaging of a single indium phosphide nanowire

Three-dimensional (3D) Bragg coherent x-ray diffractive imaging (CXDI) with a nanofocused beam was applied to quantitatively map the internal strain field of a single indium phosphide nanowire. The quantitative values of the strain were obtained by pre-characterization of the beam profile with transmission ptychography on a test sample. Our measurements revealed the 3D strain distribution in a region of 150 nm below the catalyst Au particle. We observed a slight gradient of the strain in the range of ±0.6% along the [111] growth direction of the nanowire. We also determined the spatial resolution in our measurements to be about 10 nm in the direction perpendicular to the facets of the nanowire. The CXDI measurements were compared with the finite element method simulations and show a good agreement with our experimental results. The proposed approach can become an effective tool for in operando studies of the nanowires

ProteinSeq: High-Performance Proteomic Analyses by Proximity Ligation and Next Generation Sequencing

Despite intense interest, methods that provide enhanced sensitivity and specificity in parallel measurements of candidate protein biomarkers in numerous samples have been lacking. We present herein a multiplex proximity ligation assay with readout via realtime PCR or DNA sequencing (ProteinSeq). We demonstrate improved sensitivity over conventional sandwich assays for simultaneous analysis of sets of 35 proteins in 5 µl of blood plasma. Importantly, we observe a minimal tendency to increased background with multiplexing, compared to a sandwich assay, suggesting that higher levels of multiplexing are possible. We used ProteinSeq to analyze proteins in plasma samples from cardiovascular disease (CVD) patient cohorts and matched controls. Three proteins, namely P-selectin, Cystatin-B and Kallikrein-6, were identified as putative diagnostic biomarkers for CVD. The latter two have not been previously reported in the literature and their potential roles must be validated in larger patient cohorts. We conclude that ProteinSeq is promising for screening large numbers of proteins and samples while the technology can provide a much-needed platform for validation of diagnostic markers in biobank samples and in clinical use

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Impact of on-site cardiac catheterization on resource utilization and fatal and non-fatal outcomes after acute myocardial infarction

BACKGROUND: Patterns of care for acute myocardial infarction (AMI) strongly depend on the availability of on-site cardiac catheterization facilities. Although the management found at hospitals without on-site catheterization does not lead to increased mortality, little it known about its impact on resource utilization and non-fatal outcomes. METHODS: We identified all patients (n = 35,289) admitted with a first AMI in the province of Quebec between January 1, 1996 and March 31, 1999 using population-based administrative databases. Medical resource utilization and non-fatal and fatal outcomes were compared among patients admitted to hospitals with and without on-site cardiac catheterization facilities. RESULTS: Cardiac catheterization and PCI were more frequently performed among patients admitted to hospitals with catheterization facilities. However, non-invasive procedures were not used more frequently at hospitals without catheterization facilities. To the contrary, echocardiography [odds ratio (OR), 2.04; 95% confidence interval (CI), 1.93–2.16] and multi-gated acquisition imaging (OR, 1.24; 95% CI, 1.17–1.32) were used more frequently at hospitals with catheterization, and exercise treadmill testing (OR, 1.02; 95% CI, 0.91–1.15) and Sestamibi/Thallium imaging (OR, 0.93; 95% CI, 0.88–0.98) were used similarly at hospitals with and without catheterization. Use of anti-ischemic medications and frequency of emergency room and physician visits, were similar at both types of institutions. Readmission rates for AMI-related cardiac complications and mortality were also similar [adjusted hazard ratio, recurrent AMI: 1.02, 95% CI, 0.89–1.16; congestive heart failure: 1.02; 95% CI, 0.90–1.15; unstable angina: 0.93; 95% CI, 0.85–1.02; mortality: 0.99; 95% CI, 0.93–1.05)]. CONCLUSION: Although on-site availability of cardiac catheterization facilities is associated with greater use of invasive cardiac procedures, non-availability of catheterization did not translate into a higher use of non-invasive tests or have an impact on the fatal and non-fatal outcomes available for study in our administrative database