Unstructured numerical intensity scales: Models, protocols and errors.

A sample of 62 untrained subjects were assessed on their ability to use unstructured numerical 9-point and 30-point category scales along with an unstructured line scale, using both rank-rating and serial monadic protocols. Visual stimuli were used for convenience, the task being to rate the heights of 12 easily discriminable columns of mung beans held in transparent vertical cylinders. Such stimuli had no perceptual variance, which would otherwise have added uncontrolled variance to the subjects' performance. Two measures of performance were used for each of the 6 experimental conditions. First, mean number of 'scaling errors' made in each of the six experimental conditions was computed. In this experiment, a scaling error was defined as giving a taller column a score equal to or less than a shorter column. The lower the error count, the better the subjects' performance. The second measure was to match the subjects' rating scale pattern of scores to a 'true' pattern of scores, derived from the physical measurements of the 12 columns. For this, a 'dissimilarity score' was developed. This compared the sum of the Euclidean distances between standardized true scale ratings for each of the column's 12 true heights, with those obtained from each subject. This gave a measure of the mismatch between the subject's set of scores and the true set of scores. Both the scaling error counts and the dissimilarity measures, indicated that subjects performed significantly better using the rank-rating protocol than the serial monadic. This was because of the effects of forgetting the exact intensities of stimuli once they had been removed, removal of stimuli being a necessary part of the serial monadic protocol. Subjects were penalized when using the 9-point scales, because there were too few categories to represent the different heights of all 12 columns. This introduced the concept of 'sufficient space'. Using the rank-rating protocol, the 30-point and line scales, with no memory problems and sufficient space elicited the best performances; they were not significantly different.

Paired preference tests and placebo placement: 1. Should placebo pairs be placed before or after the target pair?

One type of paired preference test uses the 'target' pair of stimuli under consideration to record the measured preferences (prefer A, Prefer B, 'no preference') and a second putatively identical control pair, the 'placebo' pair (AA or BB) to indicate 'false' preferences, unrelated to the target pair, elicited by the effects of the testing situation. From the literature there is disagreement regarding whether it is important to place a placebo pair before or after its corresponding target pair, to elicit a greater proportion of 'no preference' responses. This is important, because the higher the frequency of 'no preference' responses in the placebo pair, the more powerful will be the chi-squared style analysis, which determines whether the target pair displays a significant preference or not. It has been hypothesized that placing the placebo pair after the target pair would elicit more 'no preference' responses in the placebo, because the consumers would have had a chance to experience the difference in sensory characteristics of the two stimuli in the target pair. Using a related samples design, the hypothesis was confirmed although the difference between placebos placed before and after the target was not always significant. It was hypothesized that this lack of significance was caused by greater variance among the items being assessed, making it more difficult to decide whether a putatively placebo pair, in the context of the experiment, was really 'identical'. Psychological adjustments in the consumers were discussed in terms of difference and preference tau criteria. A boost in the proportion of 'no preferences' was observed for the placebo pair built into the triadic preference test, this was explained by the experimenter gaining some control over the consumers' preference tau criteria.

Paired preference tests and placebo placement: 2. Unraveling the effects of stimulus variance.

From the literature on paired preference testing, there has been disagreement regarding whether a placebo pair would have a significantly higher frequency of 'no preference' responses if it were to be placed for assessment after its corresponding target pair rather than before. This can be important, because the higher the frequency of 'no preference' responses in the placebo pair, the more powerful will be any chi-squared related analysis, which determines whether the target pair indicates a significant preference or not. In the first paper in this series, it was shown, that indeed a placebo placed after the target pair induced a higher proportion of consumers to respond with a 'no preference'. However, the response was uneven. For some stimuli, the response was strong and significant, for others it was weaker and not significant. It was hypothesized that the weak response could be due to greater variance among the individual stimuli in the placebo sample to be tasted. The effect was confirmed using a priori chosen high and low variance stimuli. Further evidence was obtained from predictions for preference tau criterion levels and frequency of preference changes between two target pairs. All these indicated that the weaker response of some stimuli was due to a higher level of variance among the individual stimuli.

The 9-point hedonic scale: Using R-Index Preference Measurement to compute effect size and eliminate artifactual ties.

214 consumers used the verbal 9-point hedonic scale to assess 4 types of flavor coated peanuts and 4 types of flavored teas. They used the traditional ANOVA/LSD analysis to provide mean values derived from the 9-point hedonic scale along with measures of significant difference. However, these data did not provide effect sizes. They did not give direct measures of the strength of preference between the various products, which was the main interest. Accordingly, effect sizes were computed. For this, each consumer had also ranked their preferences as they made their ratings on the 9-point hedonic scale. From these, R-Index values were computed to provide the percentages of consumers, who preferred each product to every other product. These direct measures of effect size completed the analysis begun by the ANOVA analysis of the set of mean scores. Also, the measures were nonparametric and avoided issues of the validity of a parametric statistical analysis. They also avoided the problem with the traditional analysis when products in the same scale category are attributed the same scores, when they are not equally liked. Experiment 2, using 207 consumers indicated that this problem was only serious enough to reduce the power of the traditional analysis, compared with the R-Index Preference Measurement, when the number of products being tested approached a dozen say, for product optimization.

Knowledge and attitudes of Irish GPs towards abortion following its legalisation: a cross-sectional study.

BACKGROUND: In May 2018, the Irish Constitution was changed following a referendum allowing termination of pregnancy by abortion. It is envisaged that the majority of terminations will be by medical abortion and will take place in general practice before 12 weeks gestation. AIM: To elicit attitudes and level of preparedness of Irish GPs to provide medical abortion services. DESIGN & SETTING: Cross-sectional study of 222 GPs who were associated with the University of Limerick Graduate Entry Medical School (GEMS) and GP training programme. METHOD: An anonymous online questionnaire was distributed via email. Reminders were sent 2 and 4 weeks later. RESULTS: The response rate was 57.2% (n = 127/222). Of the responders, 105 (82.7%) had no training in this area, with only 4 (3.1%) indicating that they had sufficient training. Nearly all responders (n = 119, 93.7%) were willing to share abortion information with patients. Just under half of responders (n = 61, 48.0%) would be willing to prescribe abortion pills, with 47 (37.0%) unwilling to do so. Only 53 (41.7%) responders believed that provision of abortion services should be part of general practice, with 52 (40.9%) saying that it should not. As to whether doctors should be entitled to a conscientious objection but should also be obliged to refer the patient, 92 (72.4%) responders agreed. Over two-thirds of responders (n = 89, 70.1%) felt that necessary patient support services are not currently available. CONCLUSION: There is a lack of training and a considerable level of unwillingness to participate in this process among Irish GPs. There is also a perceived lack of patient support services for women experiencing unwanted pregnancy. It is incumbent upon state and professional bodies to address these issues.

Longitudinal Trends in Real-World Outcomes after Initiation of Ivacaftor. A Cohort Study from the Cystic Fibrosis Registry of Ireland.

RATIONALE: Patient registries have the potential to collect and analyze high-quality postauthorization data on new medicines. OBJECTIVES: We used cystic fibrosis (CF) registry data to assess outcomes after the initiation of ivacaftor, a CF transmembrane conductance regulator (CFTR) potentiator approved for the treatment of CF with a defective gating CFTR mutation. METHODS: Longitudinal trends were examined using mixed-effects regression analysis in 80 ivacaftor-treated patients with CF aged 6 to 56 years registered with the CF Registry of Ireland with at least 36 months of before and after commencement data. The effects of ivacaftor treatment on forced expiratory volume in 1 second (FEV1) % predicted, body mass index (BMI), hospitalization for pulmonary exacerbation, and oral and intravenous antibiotic use were assessed. RESULTS: In the 36 months after ivacaftor initiation, FEV1% predicted improved by 2.26% per annum (95% confidence interval [CI], 0.2 to 4.3) for patients aged younger than 12 years, remained unchanged for 12- to younger than 18-year-olds (95% CI, -1.9 to 2.9), and declined in adults by 1.74% per annum (95% CI, -3.1 to -0.4). BMI in adults increased 0.28 kg/m2 per annum (95% CI, 0.03 to 0.5), and there was no significant change in BMI z-score in children (95% CI, -0.01 to 0.1). In the year after ivacaftor initiation, intravenous antibiotic treatment reduced by 46% (95% CI, -62.5% to -23.3%, oral antibiotic treatment reduced by 49% (95% CI, -61.1% to -32.1%), and there was no significant reduction in hospitalization (95% CI, -59.2% to 9.7%). CONCLUSIONS: In this study of real-world CF registry data, clinical outcomes improved and healthcare resource utilization decreased after commencing ivacaftor.

A cross-cultural study of acceptability and food pairing for hot sauces.

This study was conducted to understand the acceptance levels of hot sauces among consumers from different culinary cultures. Two newly developed hot sauces [fermented red chili pepper with soybean-paste-based sauce(GS) and fermented red chili-pepper-based sauce(KS)] were compared with Tabasco sauce(TB) and Sriracha sauce(SR). Two separate cross-cultural home-use tests(HUTs) were conducted: pizza and cream soup were provided as food items in HUT 1, whereas grilled chicken wings and rice noodle soup were provided in HUT 2. Consumers residing in Denmark, South Korea, and US participated in each HUT (n≅100 per country). Acceptance levels and the reasons for (dis)liking particular hot sauces applied to food systems were assessed. The food items that paired well with different hot sauces when the sauces were applied freely to regular meals were also analyzed among the US and Korean subjects. When the hot-sauce samples were applied to pizza and cream soup, the preferred order of the samples exhibited a cross-cultural agreement (GS = KS > TB). In the case of grilled chicken and rice noodle soup, the acceptance rating was similar for the three types of hot sauces among Koreans, whereas the acceptance was higher for SR among the US subjects for both foodstuffs, while Danish subjects preferred GS and KS over SR. The US subjects did not like hot-sauce samples with sweet and weak spiciness, whereas the Korean and Danish subjects disliked the hot-sauce sample when it was too spicy and not sufficiently sweet. These findings indicate that the matching of particular sauces with specific food items is culture-dependent, and this needs to be considered when trying to export food products such as hot sauce to other countries.

Thermal processing of live bivalve molluscs for controlling viruses: On the need for a risk-based design.

Norovirus (NoV) and Hepatitis A virus (HAV) are the most important viral hazards associated with human illness following consumption of contaminated bivalve molluscs. The effectiveness of the current EU criteria for heat processing of bivalve molluscs (i.e. raising the temperature of the internal mollusc flesh to at least 90°C for a minimum of 90 seconds) was evaluated using predictive microbiology. A HAV thermal inactivation model was developed based on literature data in mollusc matrices during isothermal heat treatment. Application of the developed model demonstrated that the 90°C-90 s requirement may lead to significantly different virus inactivation depending on the commercial process design. This shows the need for the establishment of a Performance Criterion for bivalve molluscs heat processing which will assure a common specified level of consumer protection. A risk-based approach is described that allows for an effective processing design providing a more transparent and objective relation between the thermal processing targets and public health. Model simulations demonstrate that the F-value is a more appropriate Process Criterion than a single time-temperature combination since it enables the food business operators to design a process that is compliant with the safety requirements while at the same time achieving a desired product quality.

Patterns of Disease in Patients with Middle-Lobe Predominant Bronchiectasis.

BACKGROUND: Middle-lobe predominant bronchiectasis affecting the right middle-lobe and/or lingula (RMLP) is classically described in asthenic, elderly females with skeletal abnormalities or associated nontuberculous mycobacterial (NTM) infection. OBJECTIVES: We aimed to evaluate the frequency and clinical characteristics of patients with an RMLP phenotype in a cohort of newly diagnosed bronchiectasis patients and determine associations with disease severity. METHODS: A retrospective observational cross-sectional cohort study of consecutive bronchiectasis patients in our institution was performed. Data were collected on baseline variables, microbiology status, lung function, and radiology according to the modified Bhalla score. Disease severity was assessed using bronchiectasis severity index (BSI) and FACED severity scores. RESULTS: Of 81 patients (mean age [SD] 62.6 [12.4], females 55 [67.9%], BMI 26.9 [5.7%]), 20 (24.7%) had RMLP disease. These patients were significantly younger, female, and with lower BMIs than patients with the classical bronchiectasis phenotype (p = 0.03, 0.01, and p <0.01, respectively). Fewer symptoms of cough and daily sputum (p = 0.01 and <0.01), prior exacerbation frequency (p = 0.03), and higher baseline forced expiratory volume (p = 0.04) were noted. A higher incidence of NTM at diagnosis was demonstrated (p = 0.01). BSI and FACED severity scores in RMLP patients were significantly lower than their counterparts (both p < 0.001). CONCLUSIONS: The RMLP phenotype is associated with younger patients than classically described in the literature. An increased rate of NTM infection in this phenotype was noted, particularly in females, but much lower than previously described. Lung function and disease severity scores in this patient group are relatively normal, suggesting a milder phenotype in patients with this form of the disease.

Applying Disruptive Preference Test Protocols to Increase the Number of "No Preference" Responses in the Placebo Pair, Using Chinese Consumers.

One form of paired preference test protocol requires consumers to assess 2 pairs of products. One is the target pair under consideration, while the other is a putatively identical pair named the "placebo pair" which is also presented as a control. Counterintuitively, the majority of consumers report preferences when presented with the placebo pair. Their response frequencies are hypothesized to be those of consumers having "no preference" and are compared with the response frequencies elicited by a target pair, to determine whether the target pair elicits significant preferences. The primary goal of this paper was to study the robustness of 2 new so called disruptive protocols that reduced the proportion of consumers, who reported preferences when assessing a putatively identical pair of products. For this task, the tests were performed in a different language, in a different country, using different products from before. The results showed that the proportion of consumers reporting preferences for the placebo pair was reduced, confirming earlier work. Also, comparison of d' values showed a lack of significant overall differences between the placebo and target pairs, while chi-squared analyses indicated significant differences in the response frequencies. This indicated that the sample was segmented into 2 balanced groups with opposing preferences.

Paired preference testing: False preferences and disruptive protocols.

This review introduces recent changes regarding measurement of preferences brought about by the discovery of false preferences that occur with paired preference testing. Testing protocols are examined critically. False preferences result from a response bias elicited by factors distinct from sensory properties of products being tested that can distort results. Statistical approaches to circumventing this problem are examined. Alternative methods are being developed to eliminate false preferences based on understanding information processing in the brain. This has led to development of disruptive experimental preference testing protocols based on hypothesized use of processing subroutines in the brain to protect the central processing system from overload. These disruptive protocols suppress response bias. Paired preference testing is designed to predict consumer behavior. A paucity of studies addressing whether they do is put into perspective.

Identifying the drivers of liking by investigating the reasons for (dis)liking using CATA in cross-cultural context: a case study on barbecue sauce.

BACKGROUND: The present study cross-culturally investigated the drivers of liking for traditional and ethnic chicken marinades using descriptive analysis and consumer taste tests incorporating the check-all-that-apply (CATA) method. Seventy-three Koreans and 86 US consumers participated. The tested sauces comprised three tomato-based sauces, a teriyaki-based sauce and a Korean spicy seasoning-based sauce. Chicken breasts were marinated with each of the five barbecue sauces, grilled and served for evaluation. Descriptive analysis and consumer taste tests were conducted. Consumers rated the acceptance on a hedonic scale and checked the reasons for (dis)liking by the CATA method for each sauce. A general linear model, multiple factor analysis and chi-square analysis were conducted using the data. RESULTS: The results showed that the preference orders of the samples between Koreans and US consumers were strikingly similar to each other. However, the reasons for (dis)liking the samples differed cross-culturally. The drivers of liking of two sauces sharing relatively similar sensory profiles but differing significantly in hedonic ratings were effectively delineated by reasons of (dis)liking CATA results. CONCLUSION: Reasons for (dis)liking CATA proved to be a powerful supporting method to understand the internal drivers of liking which can be overlooked by generic descriptive analysis.

The 9-point hedonic scale and hedonic ranking in food science: some reappraisals and alternatives.

The 9-point hedonic scale has been used routinely in food science, the same way for 60 years. Now, with advances in technology, data from the scale are being used for more and more complex programs for statistical analysis and modeling. Accordingly, it is worth reconsidering the presentation protocols and the analyses associated with the scale, as well as some alternatives. How the brain generates numbers and the types of numbers it generates has relevance for the choice of measurement protocols. There are alternatives to the generally used serial monadic protocol, which can be more suitable. Traditionally, the 'words' on the 9-point hedonic scale are reassigned as 'numbers', while other '9-point hedonic scales' are purely numerical; the two are not interchangeable. Parametric statistical analysis of scaling data is examined critically and alternatives discussed. The potential of a promising alternative to scaling itself, simple ranking with a hedonic R-Index signal detection analysis, is explored in comparison with the 9-point hedonic scale.

Identification and genetic characterization of a novel picornavirus from chickens.

A novel picornavirus from commercial broiler chickens (Gallus gallus domesticus) has been identified and genetically characterized. The viral genome consists of a single-stranded, positive-sense RNA genome of >9243 nt excluding the poly(A) tail and as such represents one of the largest picornavirus genomes reported to date. The virus genome is GC-rich with a G+C content of 54.5 %. The genomic organization is similar to other picornaviruses: 5' UTR-L-VP0-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3' UTR. The partially characterized 5' UTR of >373 nt appears to possess a type II internal ribosomal entry site (IRES), which is also found in members of the genera Aphthovirus and Cardiovirus. This IRES exhibits significant sequence similarity to turkey 'gallivirus A'. The 3' UTR of 278 nt contains the conserved 48 nt 'barbell-like' structure identified in 'passerivirus', 'gallivirus', Avihepatovirus and some Kobuvirus genus members. A predicted large open reading frame (ORF) of 8592 nt encodes a potential polyprotein precursor of 2864 amino acids. In addition, the virus contains a predicted large L protein of 462 amino acids. Pairwise sequence comparisons, along with phylogenetic analysis revealed the highest percentage identity to 'Passerivirus A' (formerly called turdivirus 1), forming a monophyletic group across the P1, P2 and P3 regions, with <40, <40 and <50 % amino acid identity respectively. Reduced identity was observed against 'gallivirus A' and members of the Kobuvirus genus. Quantitative PCR analysis estimated a range of 4×10(5) to 5×10(8) viral genome copies g(-1) in 22 (73 %) of 30 PCR-positive faeces. Based on sequence and phylogenetic analysis, we propose that this virus is the first member of a potential novel genus within the family Picornaviridae. Further studies are required to investigate the pathogenic potential of this virus within the avian host.

Fertilisation and pesticides affect mandarin orange nutrient composition.

The effects of the application of foliar fertilisation and pesticide on nutritional quality of mandarin orange juices were evaluated using (1)H NMR metabolomics. Significant differences between the use of fertiliser and pesticides during fruit formation were observed, and included changes in sugar, amino acid and organic acid composition. To determine whether the difference in sugar concentration was enough for the consumer to detect, a sensory experiment was performed in which two orange juice samples were prepared to resemble the sweet/sour taste balance of juice from mandarin oranges in which foliar fertilisation was either applied or not. In a test using non-trained individuals, 68% could correctly identify which juice had a sourer, or less sweet, taste. The implications of this study could impact citrus growers, and ultimately aid in development of fruit with superior sensory quality.

Randomized trial: immunogenicity and safety of coadministered human papillomavirus-16/18 AS04-adjuvanted vaccine and combined hepatitis A and B vaccine in girls.

PURPOSE: This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone. METHODS: Healthy girls (9-15 years) were age-stratified (9, 10-12, and 13-15 years) and randomized to receive HPV (n = 270), HAB (n = 271), or HPV + HAB (n = 272). Vaccines were administered at months 0, 1, and 6. Immunogenicity was evaluated at months 0 and 7. RESULTS: The hepatitis A immune response was noninferior for HPV + HAB, versus HAB, for seroconversion rates (100% in each group) and geometric mean antibody titers (GMTs) (95% CI) (4,504.2 [3,993.0-5,080.8] and 5,288.4 [4,713.3-5,933.7] mIU/mL, respectively). The hepatitis B immune response was noninferior for HPV + HAB, versus HAB, for anti-HBs seroprotection rates (98.3% and 100%); GMTs were 3,136.5 [2,436.0-4,038.4] and 5,646.5 [4,481.3-7,114.6] mIU/mL, respectively. The HPV-16/18 immune response was noninferior for HPV + HAB, versus HPV, for seroconversion rates (99.6% and 100% for both antigens) and GMTs (22,993.5 [20,093.4-26,312.0] and 26,981.9 [23,909.5-30,449.1] EL.U/mL for HPV-16; 8,671.2 [7,651.7-9,826.6] and 11,182.7 [9,924.8-12,600.1] EL.U/mL for HPV-18, respectively). No subject withdrew because of adverse events. No vaccine-related serious adverse events were reported. Immune responses and reactogenicity were similar in girls aged 9 years compared with the entire study population. CONCLUSIONS: Results support coadministration of HPV-16/18 vaccine with HAB vaccine in girls aged 9-15 years. The HPV-16/18 vaccine was immunogenic and generally well tolerated in 9-year-old girls.

Safety and efficacy of low-dose esterified estrogens and methyltestosterone, alone or combined, for the treatment of hot flashes in menopausal women: a randomized, double-blind, placebo-controlled study.

This study evaluated safety and efficacy of esterified estrogens and methyltestosterone administered alone or in combination for the treatment of hot flashes in menopausal women. The 0.30-mg esterified estrogens and 0.30-mg methyltestosterone combination was the lowest effective dose, and our results are consistent with the known safety profile of estrogen and androgen combination products.

Threshold of biologic responses of the small airway epithelium to low levels of tobacco smoke.

RATIONALE: Epidemiologic data demonstrate that individuals exposed to low levels of tobacco smoke have decrements in lung function and higher risk for lung disease compared with unexposed individuals. Although this risk is small, low-level tobacco smoke exposure is so widespread, it is a significant public health concern. OBJECTIVES: To identify biologic correlates of this risk we hypothesized that, compared with unexposed individuals, individuals exposed to low levels of tobacco smoke have biologic changes in the small airway epithelium, the site of the first abnormalities associated with smoking. METHODS: Small airway epithelium was obtained by bronchoscopy from 121 individuals; microarrays were used to assess genome-wide gene expression; urine nicotine and cotinine were used to categorize subjects as "nonsmokers," "active smokers," and "low exposure." Gene expression data were used to determine the threshold and induction half maximal level (ID50) of urine nicotine and cotinine at which the small airway epithelium showed abnormal responses. MEASUREMENTS AND MAIN RESULTS: There was no threshold of urine nicotine without a small airway epithelial response, and only slightly above detectable urine cotinine threshold with a small airway epithelium response. The ID50 for nicotine was 25 ng/ml and for cotinine it was 104 ng/ml. CONCLUSIONS: The small airway epithelium detects and responds to low levels of tobacco smoke with transcriptome modifications. This provides biologic correlates of epidemiologic studies linking low-level tobacco smoke exposure to lung health risk, identifies the genes most sensitive to tobacco smoke, and defines thresholds at which the lung epithelium responds to low levels of tobacco smoke.

A transfer of technology from engineering: use of ROC curves from signal detection theory to investigate information processing in the brain during sensory difference testing.

This article reviews a beneficial effect of technology transfer from Electrical Engineering to Food Sensory Science. Specifically, it reviews the recent adoption in Food Sensory Science of the receiver operating characteristic (ROC) curve, a tool that is incorporated in the theory of signal detection. Its use allows the information processing that takes place in the brain during sensory difference testing to be studied and understood. The review deals with how Signal Detection Theory, also called Thurstonian modeling, led to the adoption of a more sophisticated way of analyzing the data from sensory difference tests, by introducing the signal-to-noise ratio, d', as a fundamental measure of perceived small sensory differences. Generally, the method of computation of d' is a simple matter for some of the better known difference tests like the triangle, duo-trio and 2-AFC. However, there are occasions when these tests are not appropriate and other tests like the same-different and the A Not-A test are more suitable. Yet, for these, it is necessary to understand how the brain processes information during the test before d' can be computed. It is for this task that the ROC curve has a particular use.

Smoking is associated with shortened airway cilia.

BACKGROUND: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exceed the 6-7 microm airway surface fluid depth to generate force in the mucus layer, we hypothesized that cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers. METHODOLOGY/PRINCIPAL FINDINGS: Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples were brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced by 15% compared to nonsmokers (p<0.05). In 39 air-dried samples of airway epithelial cells, smoker cilia length was reduced by 13% compared to nonsmokers (p<0.0001). Analysis of the length of individual, detached cilia in 27 samples showed that smoker cilia length was reduced by 9% compared to nonsmokers (p<0.05). Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05). Using genome-wide analysis of airway epithelial gene expression we identified 6 cilia-related genes whose expression levels were significantly reduced in healthy smokers compared to healthy nonsmokers. CONCLUSIONS/SIGNIFICANCE: Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia play a significant role in the pathogenesis of smoking-induced lung disease.