Flow cytometer for a dilution-free measurement approach with sample recollection.

Blood testing using flow cytometry is a common and rapid method for the initial screening and diagnosis of patients. Measurements are often combined with other scientific techniques, and analyzed samples are commonly diluted and discarded afterward. When the sample is recollected instead, sample dilution is a challenge when the sample is intended or needed for additional measurements. Therefore, it is advantageous to recollect the undiluted sample. In order to enable measurements of the same undiluted sample aliquot, we designed and constructed a purpose-built flow cytometer. Our instrument employs syringes, acoustic focusing, and an open fluidics system to recollect and reuse the unadulterated sample. The cytometer is compact, which reduces sample consumption. It acquires forward, sideward, and fluorescence signals, offering opportunities for diverse measurement approaches. In particular, our cytometer has been designed to be ready for additional downstream analysis of cells, e.g., applying mass spectrometry, magnetic resonance spectroscopy, or other analytical tools. This study presents results on instrument performance, a comparison with a cytometer that uses standard hydrodynamic focusing, and a proof of concept for multiple measurements.

Split-bolus single-phase versus single-bolus split-phase CT acquisition protocols for staging in patients with testicular cancer: A retrospective study.

INTRODUCTION: Computed tomography (CT) imaging has become indispensable in the management of medical oncology patients. Risks associated with high cumulative effective dose (CED) are relevant in testicular cancer patients. Split-bolus protocols, whereby the contrast medium injection is divided into two, followed by combining the required phase images in a single scan acquisition has been shown to provide images of comparable image quality and less radiation dose compared to single-bolus split-phase CT for various indications. We retrospectively evaluated the performance of split-bolus and single-bolus protocols in patients having follow-up CT imaging for testicular cancer surveillance. METHODS: 45 patients with testicular cancer undergoing surveillance CT imaging of the thorax, abdomen, and pelvis who underwent split-bolus and single-bolus protocols were included. Quantitative image quality analysis was conducted by placing region of interests in pre-defined anatomical sub-structures within the abdominal cavity. The signal-to-noise ratio (SNR) and radiation dose in the form of dose length product (DLP) and effective dose (ED) were recorded. RESULTS: The DLP and ED for the single-bolus, split-phase acquisition was 506 ± 89 mGy cm and 7.59 ± 1.3 mSv, respectively. For the split-bolus, single-phase acquisition, 397 ± 94 mGy∗cm and 5.95 ± 1.4 mSv, respectively (p < 0.000). This represented a 21.5 % reduction in radiation dose exposure. The SNR for liver, muscle and fat for the single-bolus were 7.4, 4.7 and 8, respectively, compared to 5.5, 3.8 and 7.4 in the split-bolus protocol (p < 0.001). CONCLUSION: In a testicular cancer patient cohort undergoing surveillance CT imaging, utilization of a split-bolus single-phase acquisition CT protocol enabled a significant reduction in radiation dose whilst maintaining subjective diagnostic acceptability. IMPLICATIONS FOR PRACTICE: Use of split-bolus, single-phase acquisition has the potential to reduce CED in surveillance of testicular cancer patients.

Effect of oral nutritional supplements on outcomes in children presenting with, or at risk of, faltering growth in clinical settings: A systematic review and meta-analysis.

This systematic review summarises evidence regarding oral nutritional supplement (ONS) use in children with, or at risk of, faltering growth (FG). Ten randomised controlled trials (RCTs), compared changes in outcomes amongst children receiving ONS versus control were included. Overall, 1116 children (weighted mean (WM) age 5 years; n658 (59%) male) were recruited, of which 585 (52%) received ONS (WM intake contribution 412 kcal, 16.3 g protein, 395 ml) for 116 days (WM). ONS use was associated with significantly greater gains in weight (mean difference (MD) 0.4 kg, 95% CI [0.36, 0.44]) and height (MD 0.3 cm, 95% CI [0.03, 0.57]), likely related to improvements in nutritional intake. Mean compliance to prescribed dose was 98%. Data suggested an association between ONS use and reduced infections. Further research is warranted to establish ONS dosage and effects upon other outcomes. This review provides evidence to support use of ONS in the management of children with, or at risk of, FG.

An Anaesthesiology and Emergency Medicine Multidisciplinary Simulation-Based Bootcamp

Aim The fundamental concept of multidisciplinary education is a shared mental model that leads to better interdependent collaboration. The aim of this bootcamp was to create a sustainable induction curriculum for Anaesthesiology and Emergency Medicine trainees and nurses through training in a simulated multidisciplinary environment. Methods The two-day bootcamp consisted of lectures, equipment demonstration, workshops, and high-fidelity simulated scenarios. A pre- and post-course MCQ test was used for assessment of knowledge acquisition. Pre and post confidence scores were used to evaluate procedural skill confidence level. A 5-point Likert scale was used to evaluate qualitative feedback from participants. Results Seven anaesthesiology trainees, two anaesthetic nurses, six emergency medicine trainees and three emergency medicine nurses were enrolled. There was a statistically significant increase (p-value<0.01) in post-MCQ scores, portraying significant knowledge acquisition. The total procedural confidence scores increased from 375 (±9.15) to 550 (±8.43), (p < 0.01). All participants agreed that the stated educational objectives were met and relevant to their clinical practice, and strongly commended team training exercises. Conclusion Multidisciplinary simulation-based training improves team performance as well as transfer of knowledge across two or more disciplines. Overlapped training between Anaesthesiology and Emergency Medicine created an opportunity for sharing of educational resources in the current time-based speciality training system.

A Novel method for the identification and quantification of weight faltering.

OBJECTIVE: We describe a new method for identifying and quantifying the magnitude and rate of short-term weight faltering episodes, and assess how (a) these episodes relate to broader growth outcomes, and (b) different data collection intervals influence the quantification of weight faltering. MATERIALS AND METHODS: We apply this method to longitudinal growth data collected every other day across the first year of life in Gambian infants (n = 124, males = 65, females = 59). Weight faltering episodes are identified from velocity peaks and troughs. Rate of weight loss and regain, maximum weight loss, and duration of each episode were calculated. We systematically reduced our dataset to mimic various potential measurement intervals, to assess how these intervals affect the ability to derive information about short-term weight faltering episodes. We fit linear models to test whether metrics associated with growth faltering were associated with growth outcomes at 1 year, and generalized additive mixed models to determine whether different collection intervals influence episode identification and metrics. RESULTS: Three hundred weight faltering episodes from 119 individuals were identified. The number and magnitude of episodes negatively impacted growth outcomes at 1 year. As data collection interval increases, weight faltering episodes are missed and the duration of episodes is overestimated, resulting in the rate of weight loss and regain being underestimated. CONCLUSIONS: This method identifies and quantifies short-term weight faltering episodes, that are in turn negatively associated with growth outcomes. This approach offers a tool for investigators interested in understanding how short-term weight faltering relates to longer-term outcomes.

Location-specific reflex epilepsy: a novel reflex epilepsy phenotype.

Reflex epilepsies are rare syndromes where seizures are triggered by particular stimuli or activities that may be motor, sensory or cognitive in nature. Triggers are diverse, may be extrinsic or intrinsic in nature and heterogeneous phenotypes have been described over the years. We give an account of a case of location-specific reflex epilepsy which we suggest is a novel reflex epilepsy phenotype relating to higher cortical function (HCF), and review the literature in relation to features of HCF reflex epilepsies described to date.

Timing of the Infancy-Childhood Growth Transition in Rural Gambia.

The Karlberg model of human growth describes the infancy, childhood, and puberty (ICP) stages as continuous and overlapping, and defined by transitions driven by sequential additional effects of several endocrine factors that shape the growth trajectory and resultant adult size. Previous research has suggested that a delayed transition from the infancy to the childhood growth stage contributes to sub-optimal growth outcomes. A new method developed to analyze the structure of centile crossing in early life has emerged as a potential tool for identifying the infancy-childhood transition (ICT), through quantifying patterns of adjacent monthly weight-for-age z-score (WAZ) deviation correlations. Using this method, the infancy-childhood transition was identified as taking place at around 12 months of age in two cohorts of UK infants. Here, we apply this method to data collected as part of a longitudinal growth study in rural Gambia [the Hormonal and Epigenetic Regulators of Growth, or HERO-G study, N = 212 (F = 99, M = 113)], in order to identify the ICT and assess whether timing of this transition differs across groups based on sex or birth seasonality. We calculated Pearson correlation coefficients for adjacent monthly WAZ score deviations. Based on the patterns of change in the correlation structure over time, our results suggest that the infancy-childhood transition occurs at around 9 months of age in rural Gambian infants. This points to an accelerated ICT compared to UK infants, rather than a delayed ICT. A comparatively later transition, seen in UK infants, allows maximal extension of the high rates of growth during the infancy stage; an earlier transition as seen in Gambian infants cuts short this period of rapid growth, potentially impacting on growth outcomes in childhood while diverting energy into other processes critical to responses to acute infectious challenges. Growth in later developmental stages in this population offers an extended window for catch-up.

Assessment of RAdiopaque Patient IDentification Stickers (RAPIDS) for patient-scan correlation in a mass casualty incident.

PURPOSE: To qualitatively assess the legibility of radiopaque patient identification stickers and their effect on image quality. These stickers are intended for use as a part of a patient registration and identification pack utilized in a mass casualty incident (MCI), to prevent errors in correlating patients with their diagnostic imaging and reports. METHODS: Four different prototype designs of stickers with radiopaque identification numbers which are legible on radiographs and CT were created. These were affixed to head and thorax phantoms and scanned using standard imaging protocols. Images were reviewed qualitatively for legibility and the presence of image degradation due to the radiopaque sticker materials using Likert scales by four radiologists and four emergency physicians. RESULTS: All four prototypes were confidently legible on forehead, shoulder and sternum on CT on topogram and reconstructed images. Sticker positioning over the temple resulted in unreliable legibility on topogram. All prototypes were confidently legible on shoulder and sternum on CT and radiographs. Significant image degradation was reported on radiographs with sticker position over the sternum. The preferred anatomic position was the forehead. CONCLUSION: In a mass casualty incident, radiopaque patient identification stickers affixed to injured patients may help to ensure confidence in the correlation between patients and their imaging. Tested prototypes were found to be easily legible without substantial degradation of image quality. Preferred anatomical position and construction material was established. Consideration should be given to addition of such radiographic identity aides to MCI patient registration packs.

Influence of select bioenergy by-products on soil carbon and microbial activity: A laboratory study.

Concerns about the negative impacts of crop biomass removal on soil ecological functions have led to questioning the long-term sustainability of bioenergy production. To offset this potential negative impact, use of organic C rich by-products from the bioenergy industries have been proposed as a means to replenish soil C in degraded soils. However, the impact of these by-products application on soil carbon dynamics is not fully understood. We measured biogeochemical changes in soil organic C following a three-year field application of two by-products, biochar (BC) and fermentation-by product (FBP), of bioenergy industry processes in an elephant grass [Pennisetum purpureum (L.) Schum.] field. There was a significant increase in overall soil organic C (SOC) observed in BC (270%) treated plots, however the higher labile SOC (51%) content was present in FBP treated plots. Solid-state 13C NMR spectroscopy further revealed increased aromatic and alkyl groups in BC amended soils which lend to its significantly higher hydrophobicity index, HI (2.13) compared with FBP amended soils (HI = 0.8). Initial biogeochemical responses of amended soils to drought conditions were also investigated during a short-term experiment with drying and rewetting of soils. Increased concentrations of extractable C and higher stimulation of microbial activities (respiration and enzyme activities) in FBP amended soils were measured. Overall, our results reveal different impacts of the two soil amendments, where FBP soil application can affect the labile SOC availability, and stimulate rapid microbial response in drought affected soils, and biochar soil application lowers the labile SOC and microbial stimulation facilitating C sequestration over time.

Grey-scale silicon diffractive optics for selective laser ablation of thin conductive films.

Laser beam shaping can play a crucial role in improving many laser processes, especially in selective laser patterning of thin films for display devices and solar cells. Typical Gaussian spatial energy distributions can increase damage to the substrate and lead to large crater edge ridges, which are sub-optimal for typical industrial thin film processes. We report on the design, fabrication, and testing of reflective silicon diffractive optics developed for spatial beam shaping at a wavelength of 355 nm. The application of the elements for laser-selective removal of 20 nm indium tin oxide thin films on glass substrates is demonstrated. The design of the phase profile is first generated using the numerical method of computer-generated holography. The phase profiles are realized on a silicon substrate using a novel two-step fabrication technique consisting of a calibrated focused ion beam and an inductively coupled plasma etch. This results in truly grey-scale, blazed diffractive optics, which were analyzed using white light interferometry and atomic force microscopy. Using the diffractive elements with 355 nm nanosecond pulses shows excellent focused spot profiles with a good reproduction of the intended design with a first-order off-axis diffractive efficiency of approximately 80% at a 45 deg angle of incidence.

Activating KIR Haplotype Influences Clinical Outcome Following HLA-Matched Sibling Hematopoietic Stem Cell Transplantation.

Natural killer cells are thought to influence the outcome of hematopoietic stem cell transplant (HSCT), impacting on relapse, overall survival, graft versus host disease and the control of infection, in part through the complex interplay between the large and genetically diverse killer immunoglobulin-like receptor (KIR) family and their ligands. This study examined the relationship between KIR gene content and clinical outcomes including the control of opportunistic infections such as cytomegalovirus in the setting of human leucocyte antigen (HLA)-matched sibling HSCT in an Australian cohort. The presence of the KIR B haplotype which contain more activating receptors in the donor, in particular centromeric B haplotype genes (Cen-B), was associated with improved overall survival of patients with acute myeloid leukemia (AML) undergoing sibling HSCT and receiving myeloablative conditioning. Donor Cen-B haplotype was also associated with reduced acute graft versus host disease grades II-IV whereas donor telomeric-B haplotype was associated with decreased incidence of CMV reactivation. In contrast, we were not able to demonstrate a reduced rate of relapse when the donor had KIR Cen-B, however relapse with a donor Cen-A haplotype was a competing risk factor to poor overall survival. Here we show that the presence of donor activating KIR led to improved outcome for the patient, potentially through reduced relapse rates and decreased incidence of acute GvHD translating to improved overall survival. This article is protected by copyright. All rights reserved.

Patient acceptability and experiences of therapeutic switching of proton pump inhibitors within the National Preferred Drugs initiative in Ireland.

INTRODUCTION: A 'Preferred Drugs' initiative was introduced into Ireland in 2013. This identified a single recommended drug to be prescribed to patients requiring treatment from a particular class of drugs. AIMS: This study investigates how patients on established proton pump inhibitor (PPI) therapy experienced the therapeutic switching of their medication to the 'preferred drug', and the extent to which they regarded it as an acceptable practice. METHODS: The experiences of 61 patients on established proton pump inhibitor (PPI) therapy were sought before and after their drug was switched to the 'preferred drug'. RESULTS: Eighty per cent of patients were happy to switch medications. When asked for their opinions on medications in general, 71% felt doctors should prescribe the least expensive medication, 84% agreed that all licensed medications were safe while 67% felt their GP changing medication for cost reasons was safe. After 8 weeks, 20% of patients had switched back to their old PPI. When asked how they felt about their medication change, 74% felt happy or pleased. CONCLUSIONS: The majority of patients in our study were satisfied to have their medication switched. However, prescribers should be mindful that 1 in 5 patients encountered problems as a result of the switching process.

Assessment of plant availability and environmental risk of biosolids-phosphorus in a U.S. Midwest Corn-Belt Soil.

A field experiment was conducted from 2005 to 2008 in Fulton County, Western Illinois with biosolids from conventional wastewater treatment applied as corn fertilizer in a series of P rates (0, 163, 325, 488, 650 kg P ha(-1)) along with commercial P fertilizer - triple superphosphate P (TSP) as reference to assess biosolids-P plant availability and potential loss to waterbodies through runoff. Air-dried biosolids and TSP were incorporated into surface soil at end of 2005, and corn (Zea mays) was planted for three consecutive years (2006-2008). Concentrations of soil extractable P except for Mehlich-3 P were always lower in the biosolids than TSP treatments at the same P rates. The soil potentially available P in water extractable P (WEP) and Olsen P derived from biosolids-P estimated by the exponential depletion model was 2-4% and 15-24% of total P in the applied biosolids, respectively. The residence time of biosolids-induced WEP and Olsen P in Midwest soil under annual corn cropping was 5 and 2 years, respectively. Corn tissue analysis showed lower increase in P concentration by biosolids-P than TSP. The elevation rate of soluble reactive P (SRP) concentration in simulated runoff was less by biosolids than TSP. Based on the data in this study, the plant availability and environmental risk of biosolids-P are lower than those of TSP in the Midwest soil, thus use of biosolids as P nutrient for corn would not cause a major impairment to water sources even P applied through biosolids was not completely used by annual crop.

Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells.

Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR-HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self-limited viral infections. During our investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56(dim) NK cells, which are known to express KIRs. Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA-B57(+) subjects with acute DENV infection revealed marked activation of NS1 tetramer-binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR-HLA interactions in the modulation of disease outcomes.

The effect of "Jelly" CdTe QD uptake on RAW264.7 monocytes: immune responses and cell fate study.

Encapsulation of Quantum Dots (QDs) has become an essential factor which regulates particles cytotoxicity, as well as physical and chemical stability. Negatively charged cellular membranes have a great affinity to nanoparticles with surface molecules carrying positive charge, hence creating perfect conditions for fast and aggressive intracellular penetration. The preference for non-charged outer shells is topical in QD design and various applications. In the current paper we develop gelatination as a prominent coating approach to create neutrally passivated QDs with improved biocompatibility. We have revealed the trends in particle's uptake, accumulation, intracellular localisation and retaining time as well as RAW264.7 monocyte cell fate and immune responses. Also the difference in particle endocytosis kinetics and dynamics has been shown to depend on the QD core size. The intracellular QD content along with cell responses at the population level was quantified by flow cytometry.

Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study.

BACKGROUND: Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults. METHODS: We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts. RESULTS: We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P=0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P=0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P<0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P=0.09). CONCLUSIONS: Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.

Characterization of a weakly expressed KIR2DL1 variant reveals a novel upstream promoter that controls KIR expression.

Members of the human KIR (killer cell immunoglobulin-like receptor) class I major histocompatibility complex receptor gene family contain multiple promoters that determine the variegated expression of KIR on natural killer cells. In order to identify novel genetic alterations associated with decreased KIR expression, a group of donors was characterized for KIR gene content, transcripts and protein expression. An individual with a single copy of the KIR2DL1 gene but a very low level of gene expression was identified. The low expression phenotype was associated with a single-nucleotide polymorphism (SNP) that created a binding site for the inhibitory ZEB1 (Zinc finger E-box-binding homeobox 1) transcription factor adjacent to a c-Myc binding site previously implicated in distal promoter activity. Individuals possessing this SNP had a substantial decrease in distal KIR2DL1 transcripts initiating from a novel intermediate promoter located 230 bp upstream of the proximal promoter start site. Surprisingly, there was no decrease in transcription from the KIR2DL1 proximal promoter. Reduced intermediate promoter activity revealed the existence of alternatively spliced KIR2DL1 transcripts containing premature termination codons that initiated from the proximal KIR2DL1 promoter. Altogether, these results indicate that distal transcripts are necessary for KIR2DL1 protein expression and are required for proper processing of sense transcripts from the bidirectional proximal promoter.

Circulating TSLP associates with decreased wheezing in non-atopic preschool children: data from the URECA birth cohort.

BACKGROUND: Mouse models of atopic march suggest that systemic, skin-derived thymic stromal lymphopoietin (TSLP) mediates progression from eczema to asthma. OBJECTIVE: We investigated whether circulating TSLP is associated with eczema, allergic sensitization, or recurrent wheezing in young children. METHODS: A prospective analysis of the relationship between plasma levels of TSLP to allergic sensitization and recurrent wheezing was conducted in the birth cohort from the Urban Environment and Childhood Asthma (URECA) study. Plasma TSLP levels were measured at 1, 2, and 3 years of age and analysed for correlation with clinical parameters in each of the three years. Only those children with consecutive samples for all three years were included in this analysis. RESULTS: We detected TSLP in 33% of 236 children for whom plasma samples were available for all three years. Overall, a consistently significant association was not found between TSLP and eczema or allergic sensitization. With regard to recurrent wheezing, children with detectable TSLP at one year of age were significantly less likely to experience recurrent wheezing by 3 years compared with those children without detectable TSLP, but this was only seen in children without aeroallergen sensitization at 3 years (P < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to our expectations, circulating TSLP was not significantly associated with eczema, allergen sensitization, or recurrent wheezing during the first three years of life. Early presence of circulating TSLP was significantly associated with reduced incidence of recurrent wheeze in those children not sensitized to aeroallergen. These findings suggest a possible underlying distinction between pathogenesis of developing atopic vs. non-atopic recurrent wheeze.

Reflections on mental capacity assessments in general hospitals.

Research suggests that a significant proportion of inpatients in general medical wards may lack capacity to make treatment decisions, a situation that often goes unrecognised by clinicians. We would like to briefly discuss two cases from a non-psychiatric setting, where a mental disorder served to inhibit the individual's ability to weigh-up associated risks when deciding to refuse potentially life-sustaining healthcare interventions. In both cases the history of mental disorder was well established yet, for markedly different reasons, the respective presentation was such that the influence of the disorder on decision-making was not evident to the treating teams.

Adhesion molecules, endothelin-1 and lung function in seven population-based cohorts.

CONTEXT: Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown. OBJECTIVE: Test associations of endothelial biomarkers with FEV1 using instrumental variables. METHODS: Among 26 907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets. RESULTS: ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative. CONCLUSION: Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal.