Background noise levels measured in the NASA Lewis 9- by 15-foot low-speed wind tunnel

The acoustic capability of the NASA Lewis 9 by 15 Foot Low Speed Wind Tunnel has been significantly improved by reducing the background noise levels measured by in-flow microphones. This was accomplished by incorporating streamlined microphone holders having a profile developed by researchers at the NASA Ames Research Center. These new holders were fabricated for fixed mounting on the tunnel wall and for an axially traversing microphone probe which was mounted to the tunnel floor. Measured in-flow noise levels in the tunnel test section were reduced by about 10 dB with the new microphone holders compared with those measured with the older, less refined microphone holders. Wake interference patterns between fixed wall microphones were measured and resulted in preferred placement patterns for these microphones to minimize these effects. Acoustic data from a model turbofan operating in the tunnel test section showed that results for the fixed and translating microphones were equivalent for common azimuthal angles, suggesting that the translating microphone probe, with its significantly greater angular resolution, is preferred for sideline noise measurements. Fixed microphones can provide a local check on the traversing microphone data quality, and record acoustic performance at other azimuthal angles

Trial Protocol: Randomised controlled trial of the effects of very low calorie diet, modest dietary restriction, and sequential behavioural programme on hunger, urges to smoke, abstinence and weight gain in overweight smokers stopping smoking

Background\ud Weight gain accompanies smoking cessation, but dieting during quitting is controversial as hunger may increase urges to smoke. This is a feasibility trial for the investigation of a very low calorie diet (VLCD), individual modest energy restriction, and usual advice on hunger, ketosis, urges to smoke, abstinence and weight gain in overweight smokers trying to quit. \ud \ud Methods\ud This is a 3 armed, unblinded, randomized controlled trial in overweight (BMI > 25 kg/$m^2$), daily smokers (CO > 10 ppm); with at least 30 participants in each group. Each group receives identical behavioural support and NRT patches (25 mg(8 weeks),15 mg(2 weeks),10 mg(2 weeks)). The VLCD group receive a 429-559 kcal/day liquid formula beginning 1 week before quitting and continuing for 4 weeks afterwards. The modest energy restricted group (termed individual dietary and activity planning(IDAP)) engage in goal-setting and receive an energy prescription based on individual basal metabolic rate(BMR) aiming for daily reduction of 600 kcal. The control group receive usual dietary advice that accompanies smoking cessation i.e. avoiding feeling hungry but eating healthy snacks. After this, the VLCD participants receive IDAP to provide support for changing eating habits in the longer term; the IDAP group continues receiving this support. The control group receive IDAP 8 weeks after quitting. This allows us to compare IDAP following a successful quit attempt with dieting concurrently during quitting. It also aims to prevent attrition in the unblinded, control group by meeting their need for weight management. Follow-up occurs at 6 and 12 months. \ud \ud Outcome measures include participant acceptability, measured qualitatively by semi-structured interviewing and quantitatively by recruitment and attrition rates. Feasibility of running the trial within primary care is measured by interview and questionnaire of the treatment providers. Adherence to the VLCD is verified by the presence of urinary ketones measured weekly. Daily urges to smoke, hunger and withdrawal are measured using the Mood and Physical Symptoms Scale-Combined (MPSS-C) and a Hunger Craving Score (HCS). 24 hour, 7 day point prevalence and 4-week prolonged abstinence (Russell Standard) is confirmed by CO < 10 ppm. Weight, waist and hip circumference and percentage body fat are measured at each visit. \ud \ud Trial Registration\ud Current controlled trials ISRCTN83865809\ud \u

Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia.

The function of epithelial cell sheets depends on the integrity of specialized cell-cell junctions that connect neighbouring cells. We have characterized the novel coiled-coil protein AJM-1, which localizes to an apical junctional domain of Caenorhabditis elegans epithelia basal to the HMR-HMP (cadherin-catenin) complex. In the absence of AJM-1, the integrity of this domain is compromised. Proper AJM-1 localization requires LET-413 and DLG-1, homologues of the Drosophila tumour suppressors Scribble and Discs large, respectively. DLG-1 physically interacts with AJM-1 and is required for its normal apical distribution, and LET-413 mediates the rapid accumulation of both DLG-1 and AJM-1 in the apical domain. In the absence of both dlg-1 and let-413 function AJM-1 is almost completely lost from apical junctions in embryos, whereas HMP-1 (α α-catenin) localization is only mildly affected. We conclude that LET-413 and DLG-1 cooperatively control AJM-1 localization and that AJM-1 controls the integrity of a distinct apical junctional domain in C. elegans. D uring animal development, specialized junctional domains are crucial for the function of epithelial cell sheets. In both vertebrates and invertebrates, adherens junctions are thought to regulate cell-cell adhesion and dynamic changes in cell morphology Here we show that the novel coiled-coil protein AJM-1 (for &apos;apical junction molecule&apos;) is required for the integrity of epithelial junctions of C. elegans and that it localizes to an apical junctional domain. (AJM-1 was originally called JAM-1 (refs 13, 14) but has been renamed to avoid confusion with the vertebrate transmembrane tight junction protein, JAM-1.) This domain is basal to the HMR-HMP(cadherin-catenin) complex; on the basis of the localization of the Discs large homologue DLG-1 to the same domain, it might be required for maintaining a tight apical seal between epithelial cells at apical junctions. Furthermore, we show that AJM-1 directly binds DLG-1, which is required for the proper distribution of AJM-1 around the junctional belt but not for general cell polarity. In addition, we show that in embryos lacking LET-413 the patterns of both DLG-1 and AJM-1 are equally disrupted, including a delay in concentration of these proteins at a narrow apical domain. Almost complete loss of junctional AJM-1 is observed in the absence of both LET-413 and DLG-1, whereas HMP-1 (α-catenin) localization is reduced but junctional. We propose a model in which LET-413 and DLG-1 control the integrity of a distinct apical subdomain by cooperatively regulating the localization of AJM-1. Results AJM-1 encodes a novel coiled-coil protein localizing to C. elegans apical junctions. As an initial step in understanding the molecular composition of apical junctions in C. elegans, we characterized the antigen recognized by the MH27 antibody. The antibody had been previously shown to stain apical borders of C. elegans epitheli

Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia.

The function of epithelial cell sheets depends on the integrity of specialized cell-cell junctions that connect neighbouring cells. We have characterized the novel coiled-coil protein AJM-1, which localizes to an apical junctional domain of Caenorhabditis elegans epithelia basal to the HMR-HMP (cadherin-catenin) complex. In the absence of AJM-1, the integrity of this domain is compromised. Proper AJM-1 localization requires LET-413 and DLG-1, homologues of the Drosophila tumour suppressors Scribble and Discs large, respectively. DLG-1 physically interacts with AJM-1 and is required for its normal apical distribution, and LET-413 mediates the rapid accumulation of both DLG-1 and AJM-1 in the apical domain. In the absence of both dlg-1 and let-413 function AJM-1 is almost completely lost from apical junctions in embryos, whereas HMP-1 (α α-catenin) localization is only mildly affected. We conclude that LET-413 and DLG-1 cooperatively control AJM-1 localization and that AJM-1 controls the integrity of a distinct apical junctional domain in C. elegans. D uring animal development, specialized junctional domains are crucial for the function of epithelial cell sheets. In both vertebrates and invertebrates, adherens junctions are thought to regulate cell-cell adhesion and dynamic changes in cell morphology Here we show that the novel coiled-coil protein AJM-1 (for &apos;apical junction molecule&apos;) is required for the integrity of epithelial junctions of C. elegans and that it localizes to an apical junctional domain. (AJM-1 was originally called JAM-1 (refs 13, 14) but has been renamed to avoid confusion with the vertebrate transmembrane tight junction protein, JAM-1.) This domain is basal to the HMR-HMP(cadherin-catenin) complex; on the basis of the localization of the Discs large homologue DLG-1 to the same domain, it might be required for maintaining a tight apical seal between epithelial cells at apical junctions. Furthermore, we show that AJM-1 directly binds DLG-1, which is required for the proper distribution of AJM-1 around the junctional belt but not for general cell polarity. In addition, we show that in embryos lacking LET-413 the patterns of both DLG-1 and AJM-1 are equally disrupted, including a delay in concentration of these proteins at a narrow apical domain. Almost complete loss of junctional AJM-1 is observed in the absence of both LET-413 and DLG-1, whereas HMP-1 (α-catenin) localization is reduced but junctional. We propose a model in which LET-413 and DLG-1 control the integrity of a distinct apical subdomain by cooperatively regulating the localization of AJM-1. Results AJM-1 encodes a novel coiled-coil protein localizing to C. elegans apical junctions. As an initial step in understanding the molecular composition of apical junctions in C. elegans, we characterized the antigen recognized by the MH27 antibody. The antibody had been previously shown to stain apical borders of C. elegans epitheli

Computer-assisted assessment of the Human Epidermal Growth Factor Receptor 2 immunohistochemical assay in imaged histologic sections using a membrane isolation algorithm and quantitative analysis of positive controls

<p>Abstract</p> <p>Background</p> <p>Breast cancers that overexpress the human epidermal growth factor receptor 2 (HER2) are eligible for effective biologically targeted therapies, such as trastuzumab. However, accurately determining HER2 overexpression, especially in immunohistochemically equivocal cases, remains a challenge. Manual analysis of HER2 expression is dependent on the assessment of membrane staining as well as comparisons with positive controls. In spite of the strides that have been made to standardize the assessment process, intra- and inter-observer discrepancies in scoring is not uncommon. In this manuscript we describe a pathologist assisted, computer-based continuous scoring approach for increasing the precision and reproducibility of assessing imaged breast tissue specimens.</p> <p>Methods</p> <p>Computer-assisted analysis on HER2 IHC is compared with manual scoring and fluorescence in situ hybridization results on a test set of 99 digitally imaged breast cancer cases enriched with equivocally scored (2+) cases. Image features are generated based on the staining profile of the positive control tissue and pixels delineated by a newly developed Membrane Isolation Algorithm. Evaluation of results was performed using Receiver Operator Characteristic (ROC) analysis.</p> <p>Results</p> <p>A computer-aided diagnostic approach has been developed using a membrane isolation algorithm and quantitative use of positive immunostaining controls. By incorporating internal positive controls into feature analysis a greater Area Under the Curve (AUC) in ROC analysis was achieved than feature analysis without positive controls. Evaluation of HER2 immunostaining that utilized membrane pixels, controls, and percent area stained showed significantly greater AUC than manual scoring, and significantly less false positive rate when used to evaluate immunohistochemically equivocal cases.</p> <p>Conclusion</p> <p>It has been shown that by incorporating both a membrane isolation algorithm and analysis of known positive controls a computer-assisted diagnostic algorithm was developed that can reproducibly score HER2 status in IHC stained clinical breast cancer specimens. For equivocal scoring cases, this approach performed better than standard manual evaluation as assessed by ROC analysis in our test samples. Finally, there exists potential for utilizing image-analysis techniques for improving HER2 scoring at the immunohistochemically equivocal range.</p

Following the funding trail: Financing, nurses and teamwork in Australian general practice

Contains fulltext : 97927.pdf (publisher's version ) (Open Access)BACKGROUND: Across the globe the emphasis on roles and responsibilities of primary care teams is under scrutiny. This paper begins with a review of general practice financing in Australia, and how nurses are currently funded. We then examine the influence on funding structures on the role of the nurse. We set out three dilemmas for policy-makers in this area: lack of an evidence base for incentives, possible untoward impacts on interdisciplinary functioning, and the substitution/enhancement debate. METHODS: This three year, multimethod study undertook rapid appraisal of 25 general practices and year-long studies in seven practices where a change was introduced to the role of the nurse. Data collected included interviews with nurses (n = 36), doctors (n = 24), and managers (n = 22), structured observation of the practice nurse (51 hours of observation), and detailed case studies of the change process in the seven year-long studies. RESULTS: Despite specific fee-for-service funding being available, only 6% of nurse activities generated such a fee. Yet the influence of the funding was to focus nurse activity on areas that they perceived were peripheral to their roles within the practice. CONCLUSIONS: Interprofessional relationships and organisational climate in general practices are highly influential in terms of nursing role and the ability of practices to respond to and utilise funding mechanisms. These factors need to be considered, and the development of optimal teamwork supported in the design and implementation of further initiatives that financially support nursing in general practice

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

10Kin1day: a bottom-up neuroimaging initiative

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain

Association of Forced Vital Capacity with the Developmental Gene <i>NCOR2</i>

Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 chi