Observation of Radar Echoes from High-Energy Particle Cascades.

We report the observation of radar echoes from the ionization trails of high-energy particle cascades. Data were taken at the SLAC National Accelerator Laboratory, where the full electron beam (∼10^{9} e^{-} at ∼10 GeV/e^{-}) was directed into a plastic target to simulate an ultrahigh-energy neutrino interaction. The target was interrogated with radio waves, and coherent radio reflections from the cascades were detected with properties consistent with theoretical expectations. This is the first definitive observation of radar echoes from high-energy particle cascades, which may lead to a viable neutrino detection technology for energies ≳10^{16} eV.

Dynamic wetting of imidazolium-based ionic liquids on gold and glass.

Many of the applications of ionic liquids rely on their bulk properties or their solvation abilities. However, it is their interactions with solid surfaces that underpin many of their potential applications in advanced technologies. Whether it is as lubricants for wind turbines or as electrolytes in supercapacitors, there are many areas where ionic liquids can provide an improvement in performance relative to more commonplace liquids. However, there are some barriers to their implementation in such applications. Foremost of these is the lack of systematic studies of their interactions with solid surfaces as well as neglecting the effect of the absorbed water on wetting. The present study explores the dynamic wetting of three ionic liquids (with a different length of hydrocarbon chain in the cation) on gold and glass substrates, both of which are relevant for nano- and micromechanical machine applications, under well-controlled environmental conditions. The form of data capture (Wilhelmy plate) allows for a direct analysis using analytical expressions for the two dominant approaches for dynamic wetting: the hydrodynamic and molecular kinetic models. All ionic liquids yield data that are described best by the molecular kinetic model. Substrate-ionic liquid and water-ionic liquid interactions contribute to the mechanisms involved in the wetting process.

Provider perceptions of the value of same-day, electronic patient-reported measures for use in clinical HIV care.

Strong evidence suggests that patient-reported outcomes (PROs) aid in managing chronic conditions, reduce omissions in care, and improve patient-provider communication. However, provider acceptability of PROs and their use in clinical HIV care is not well known. We interviewed providers (n = 27) from four geographically diverse HIV and community care clinics in the US that have integrated PROs into routine HIV care, querying perceived value, challenges, and use of PRO data. Perceived benefits included the ability of PROs to identify less-observable behaviors and conditions, particularly suicidal ideation, depression, and substance use; usefulness in agenda setting prior to a visit; and reduction of social desirability bias in patient-provider communication. Challenges included initial flow integration issues and ease of interpretation of PRO feedback. Providers value same-day, electronic patient-reported measures for use in clinical HIV care with the condition that PROs are (1) tailored to be the most clinically relevant to their population; (2) well integrated into clinic flow; and (3) easy to interpret, highlighting chief patient concerns and changes over time.

Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network.

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.

The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI): 1.2-1.4), P=1.0 × 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01-1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01-1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15-1.32), P=1.9 × 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.

Dynamics of capillary-driven liquid-liquid displacement in open microchannels.

The dynamics of the spontaneous spreading of a liquid droplet along an open hydrophilic microchannel filled with another immiscible liquid is primarily determined by the competition between the capillary driving force and the viscous drag. While the former force depends on the channel cross-section and dimensions, interfacial tension between two liquids and the contact angle formed between the channel's wall and the two liquids, the latter arises from the motion of fluid molecules in the two bulk liquids. This paper focuses on the influence of the outer (displaced) phase viscosity. In general, as the viscosity of the displaced phase increases relative to the viscosity of the displacing phase, the velocity of the liquid-liquid meniscus decreases. The experiments were interpreted by extending a previously established correlation for liquid-vapour systems (J. Phys. Chem. C, 2011, 115(38), 18761-18769) in open microchannels of the same geometry. The relationship between the liquid-liquid flow dynamics and the properties of the liquids (e.g. viscosities) is still unclear. Nonetheless, by taking a self-consistent empirical approach to estimate the influence of the viscosities on the flow kinetics for a given system, it is possible to obtain a reasonable theoretical description for the experimental system over a specific range of viscosity ratios.

Design and anticipated outcomes of the eMERGE-PGx project: a multicenter pilot for preemptive pharmacogenomics in electronic health record systems.

We describe here the design and initial implementation of the eMERGE-PGx project. eMERGE-PGx, a partnership of the Electronic Medical Records and Genomics Network and the Pharmacogenomics Research Network, has three objectives: (i) to deploy PGRNseq, a next-generation sequencing platform assessing sequence variation in 84 proposed pharmacogenes, in nearly 9,000 patients likely to be prescribed drugs of interest in a 1- to 3-year time frame across several clinical sites; (ii) to integrate well-established clinically validated pharmacogenetic genotypes into the electronic health record with associated clinical decision support and to assess process and clinical outcomes of implementation; and (iii) to develop a repository of pharmacogenetic variants of unknown significance linked to a repository of electronic health record-based clinical phenotype data for ongoing pharmacogenomics discovery. We describe site-specific project implementation and anticipated products, including genetic variant and phenotype data repositories, novel variant association studies, clinical decision support modules, clinical and process outcomes, approaches to managing incidental findings, and patient and clinician education methods.

Home blood pressure monitoring, secure electronic messaging and medication intensification for improving hypertension control: a mediation analysis.

OBJECTIVE: We evaluated the role of home monitoring, communication with pharmacists, medication intensification, medication adherence and lifestyle factors in contributing to the effectiveness of an intervention to improve blood pressure control in patients with uncontrolled essential hypertension. METHODS: We performed a mediation analysis of a published randomized trial based on the Chronic Care Model delivered over a secure patient website from June 2005 to December 2007. Study arms analyzed included usual care with a home blood pressure monitor and usual care with home blood pressure monitor and web-based pharmacist care. Mediator measures included secure messaging and telephone encounters; home blood pressure monitoring; medications intensification and adherence and lifestyle factors. Overall fidelity to the Chronic Care Model was assessed with the Patient Assessment of Chronic Care (PACIC) instrument. The primary outcome was percent of participants with blood pressure (BP) <140/90 mm Hg. RESULTS: At 12 months follow-up, patients in the web-based pharmacist care group were more likely to have BP <140/90 mm Hg (55%) compared to patients in the group with home blood pressure monitors only (37%) (p = 0.001). Home blood pressure monitoring accounted for 30.3% of the intervention effect, secure electronic messaging accounted for 96%, and medication intensification for 29.3%. Medication adherence and self-report of fruit and vegetable intake and weight change were not different between the two study groups. The PACIC score accounted for 22.0 % of the main intervention effect. CONCLUSIONS: The effect of web-based pharmacist care on improved blood pressure control was explained in part through a combination of home blood pressure monitoring, secure messaging, and antihypertensive medication intensification.

Inhibition of stearoyl-CoA desaturase-1 in differentiating 3T3-L1 preadipocytes upregulates elongase 6 and downregulates genes affecting triacylglycerol synthesis.

BACKGROUND: Stearoyl-CoA desaturase-1 (SCD1) is rate limiting for the conversion of saturated fatty acids palmitate (16:0) and stearate (18:0) to monounsaturated fatty acids palmitoleate (16:1n7) and oleate (18:1n9), respectively. Given that reduced SCD1 activity is associated with improved insulin sensitivity and decreased body weight, there is considerable interest to elucidate the role of this enzyme in adipocytes. During adipogenesis, SCD1 levels increase concomitantly with the accumulation of triacylglycerol (TG); however, the extent to which reduced SCD1 activity can influence TG synthesis and metabolic pathways in differentiating adipocytes remains relatively unexplored. OBJECTIVE: The aim of this work was to delineate how reduced SCD1 activity affects gene expression, protein content and cellular fatty acids in differentiating murine preadipocytes. METHODS: 3T3-L1 preadipocytes were treated with an SCD1 inhibitor (10 nM) throughout differentiation. After 7 days, global gene expression, protein content and fatty acid profiles were examined using microarrays, western blotting and gas chromatography, respectively. RESULTS: SCD1 inhibition increased the abundance of 16:0 and 18:0 (45% and 194%, respectively) and decreased 16:1n7 and 18:1n7 (61% and 35%, respectively) in differentiated preadipocytes. Interestingly, 18:1n9 levels increased by 61%. The augmented 18:0 suggested a possible increase in elongase activity. Elongase 6 (Elovl6) gene expression was increased 2.8-fold (P = 0.04); however, changes were not detected for ELOVL6 protein content. Microarray analysis revealed that genes affecting TG synthesis were downregulated with SCD1 inhibition, which coincided with a 33% decrease in cellular TG content. CONCLUSION: These results provide new mechanistic insight into the role of SCD1 as a regulator of fatty acid profiles and TG synthesis in adipocytes, and reinforce that modulating SCD1 activity may help reduce the risk of obesity-related complications.

Capillary rise dynamics of aqueous glycerol solutions in glass capillaries: a critical examination of the Washburn equation.

The classic description of capillary rise given by the Washburn equation was recently questioned in the light of experimental evidence for a velocity dependent dynamic contact angle at a moving contact line. We present a systematic investigation of the capillary rise dynamics of glycerol and aqueous glycerol solutions in vertical glass capillaries of various radii. For pure glycerol, the results of our experiments are in almost perfect agreement with the predictions of the Washburn equation using independently measured values for the liquid and capillary parameters. For aqueous glycerol solutions we observe discrepancies between the theoretical expectations and the experimental results, which are increasing with the water content of the solution. A thorough analysis, combined with scaling arguments, allows us to conclude that dynamic contact angle effects alone cannot provide a consistent explanation for these discrepancies. Rather, they can be perfectly accounted for if the mixture flowing in the capillary would have an effective, increased viscosity (in respect to the nominal value). We suggest and briefly discuss various mechanisms that could contribute to this observed behavior.

The analytical model of nanoparticle recovery by microflotation.

A model of collision and collection of Brownian submicron particles based on the creation of a convective-diffusion layer near a bubble surface and overcoming the energy barrier created by particle/bubble interaction is developed. Simple analytical expressions describing the rate of collision and collection efficiency are obtained. The collision and collection minimums and the limits of theory applicability are analysed.

Premedication with meloxicam exacerbates intracranial haemorrhage in an immature swine model of non-impact inertial head injury.

Meloxicam is a cyclo-oxygenase-2 (COX-2) preferential non-steroidal anti-inflammatory drug with very effective analgesic and anti-inflammatory effects in swine. Previous reports in piglets have demonstrated that meloxicam also inhibits COX-1 and reduces production of thromboxane significantly. We use preinjury analgesia in our immature swine (3-5-day-old piglets) model of brain injury using rapid head rotations without impact. In 23 consecutive subjects we found that premedication with meloxicam (n = 6) produced a significantly higher mortality rate (5/6 or 83%) than buprenorphine (n = 17, 1/17 or 6%, P < 0.02). On gross neuropathological examination of the meloxicam-treated swine, we observed massive subdural and subarachnoid bleeding which were not present in buprenorphine-premedicated animals. To our knowledge there are no previous reports in swine of increased bleeding or platelet inhibition associated with meloxicam administration and further research is needed to define mechanisms of action in piglets. We caution the use of meloxicam in swine when inhibition of platelet aggregation might adversely affect refinement of experimental research protocols, such as in stroke, trauma and cardiac arrest models.

Integrating a web-based, patient-administered assessment into primary care for HIV-infected adults.

Providers routinely under diagnose at risk behaviors and outcomes, including depression, suicidal ideation, substance abuse, and poor medication adherence. To address this, we developed a web-based, self-administered patient-reported assessment tool and integrated it into routine primary care for HIV-infected adults. Printed results were delivered to providers and social workers immediately prior to patient appointments. The assessment included brief, validated instruments measuring clinically relevant domains including depression, substance use, medication adherence, and HIV transmission risk behaviors. Utilizing the Institute for Healthcare Improvement's Plan-Do-Study-Act (PDSA) approach to quality improvement, we addressed issues with clinic flow, technology, scheduling, and delivery of assessment results with the support of all levels of clinic staff. We found web-based patient-reported assessments to be a feasible tool that can be integrated into a busy multi-provider HIV primary care clinic. These assessments may improve provider recognition of key patient behaviors and outcomes. Critical factors for successful integration of such assessments into clinical care include: strong top-level /ort from clinic management, provider understanding of patient-reported assessments as a valuable clinical tool, tailoring the assessment to meet provider needs, communication among clinic staff to address flow issues, timeliness of delivery, and sound technological resources.

Genotyping assay for the identification of 2009-2010 pandemic and seasonal H1N1 influenza virus reassortants.

New Zealand identified its first pandemic H1N1 influenza cases in late April 2009, immediately prior to the historical start of the New Zealand influenza season. Both pandemic and oseltamivir-resistant seasonal H1N1 viruses cocirculated in the population for a period of time. Thus, concerns were raised about the possibility of reassortment events between the two strains. An RT-PCR-based genotyping assay was developed so that H1N1 influenza coinfections and reassortants could be detected quickly. The assay differentiated effectively the seasonal and pandemic strains. It also confirmed the identification of the first reported coinfection of pandemic and seasonal H1N1 strains during the 2009 Southern Hemisphere influenza season in New Zealand.

Phoretic motion of spheroidal particles due to self-generated solute gradients.

We study theoretically the phoretic motion of a spheroidal particle, which generates solute gradients in the surrounding unbounded solvent via chemical reactions active on its surface in a cap-like region centered at one of the poles of the particle. We derive, within the constraints of the mapping to classical diffusio-phoresis, an analytical expression for the phoretic velocity of such an object. This allows us to analyze in detail the dependence of the velocity on the aspect ratio of the polar and the equatorial diameters of the particle and on the fraction of the particle surface contributing to the chemical reaction. The particular cases of a sphere and of an approximation for a needle-like particle, which are the most common shapes employed in experimental realizations of such self-propelled objects, are obtained from the general solution in the limits that the aspect ratio approaches one or becomes very large, respectively.

Pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir.

New Zealand, like other southern hemisphere countries with a temperate climate, has been in the winter period with seasonal influenza activity. New Zealand has also experienced a dramatic increase in the number of cases of pandemic influenza A(H1N1)v virus. Early reports from the northern hemisphere at the beginning of the pandemic showed that the virus was sensitive to the antiviral drug oseltamivir. In this study we report that pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir, but seasonal influenza A(H1N1) viruses - the co-circulating predominant seasonal strain, is resistant to oseltamivir.

Capillary rise with velocity-dependent dynamic contact angle.

The classic description of the rate of capillary rise given by the Washburn equation, which assumes that the contact angle preserves the equilibrium value at all times, has been recently questioned in the light of the known experimental dependence of the dynamic contact angle on the velocity of the contact line. For a number of such proposed functions of velocity for the dynamic contact angle, we analyze the resulting dependences of the contact angle and of the time of rise, respectively, on the height of the capillary rise. By applying our results to the particular cases of a high-viscosity silicone oil and water, respectively, in a glass capillary, we show that, in general, strong similarities arise between the various approaches and the classic theory in what concerns the time dependence of the capillary rise, which explains the lack of consistent experimental evidence for deviations in the rate of capillary rise from the Washburn equation. However, for a strong dependency of the contact angle on the velocity in the range of small velocities, as in the case of water on glass, one of the models predicts significant deviations even for the time dependence of the capillary rise. Moreover, our results show that the time or height dependence of the contact angle during the capillary rise can clearly discriminate between the various models.