An Ecological Correlation Study of Late Age-Related Macular Degeneration and the Complement Factor H Y402H Polymorphism

PURPOSE:
To investigate whether variation in the distribution of the risk allele frequency of the Y402H single-nucleotide polymorphism (SNP) across various ethnicities and geographic regions reflects differences in the prevalence of late age-related macular degeneration (AMD) in those ethnicities.

METHODS:
Published data were obtained via a systematic search. Study samples were grouped into clusters by ethnicity and geographic location and the Spearman correlation coefficient of the prevalence of late AMD and risk allele frequencies was calculated across clusters.

RESULTS:
Across all ethnicities, AMD prevalence was seen to increase with age. Populations of European descent had both higher risk allele frequencies and prevalence of late AMD than did Japanese, Chinese, and Hispanic descendants. Results for African descendants were anomalous: although allele frequency was similar to that in European populations, the age-specific prevalence of late AMD was considerably lower. The correlation coefficient for the association between allele frequency and AMD prevalence was 0.40 (95% confidence interval [CI] = -0.36 to 0.84, P = 0.28) in all populations combined and 0.71 (95% CI = 0.02-0.94, P = 0.04) when people of African descent were excluded.

CONCLUSIONS:
Evidence was found at the population level to support a positive association between the Y204H risk allele and the prevalence of AMD after exclusion of studies undertaken on persons of African ancestry. Data in African, Middle Eastern, and South American populations are needed to provide a better understanding of the association of late AMD genetic risk across ethnicities.

Development and validation of an HPLC method for the rapid and simultaneous determination of 6-mercaptopurine and four of its metabolites in plasma and red blood cells

An HPLC method has been developed and validated for the rapid determination of mercaptopurine and four of its metabolites; thioguanine, thiouric acid, thioxanthine and methylmercaptopurine in plasma and red blood cells. The method involves a simple treatment procedure based on deproteinisation by perchloric acid followed by acid hydrolysis and heating for 45 min at 100 degrees C. The developed method was linear over the concentration range studied with a correlation coefficient >0.994 for all compounds in both plasma and erythrocytes. The lower limits of quantification were 13, 14, 3, 2, 95 pmol/8 x 101 RBCs and 2, 5, 2, 3, 20 ng/ml plasma for thioguanine, thiouric acid, mercaptopurine, thioxanthine and methylmercaptopurine, respectively. The method described is selective and sensitive enough to analyse the different metabolites in a single run under isocratic conditions. Furthermore, it has been shown to be applicable for monitoring these metabolites in paediatric patients due to the low volume requirement (200 mu l of plasma or erythrocytes) and has been successfully applied for investigating population pharmacokinetics, pharmacogenetics and non-adherence to therapy in these patients. (C) 2008 Elsevier B.V. All rights reserved.

Selection of an analytical method for evaluating bovine serum albumin concentrations in pharmaceutical polymeric formulations

Bovine serum albumin (BSA) is a commonly used model protein in the development of pharmaceutical formulations. In order to assay its release from various dosage forms, either the bicinchoninic acid (BCA) assay or a more specific size-exclusion high performance liquid chromatography (SE-HPLC) method are commonly employed. However, these can give erroneous results in the presence of some commonly-used pharmaceutical excipients. We therefore investigated the ability of these methods to accurately determine BSA concentrations in pharmaceutical formulations that also contained various polymers and compared them with a new and compared with a new reverse-phase (RP)–HPLC technique. We found that the RP-HPLC technique was the most suitable method. It gave a linear response in the range of 0.5 -100 µg/ml with a correlation coefficient of 0.9999, a limit of detection of 0.11 µg/ml and quantification of 0.33 µg/ml. The performed ‘t’ test for the estimated and theoretical concentration indicated no significant difference between them providing the accuracy. Low % relative standard deviation values (0.8-1.39%) indicate the precision of the method. Furthermore, the method was used to quantify in vitro BSA release from polymeric freeze-dried formulations.

Measurements, modeling and simulation of the off-body radio channel for the implementation of bodyworn antenna diversity at 868 MHz

This paper presents a systematic measurement campaign of diversity reception techniques for use in multiple-antenna wearable systems operating at 868 MHz. The experiments were performed using six time-synchronized bodyworn receivers and considered mobile off-body communications in an anechoic chamber, open office area and a hallway. The cross-correlation coefficient between the signal fading measured by bodyworn receivers was dependent upon the local environment and typically below 0.7. All received signal envelopes were combined in post-processing to study the potential benefits of implementing receiver diversity based upon selection combination, equal-gain and maximal-ratio combining. It is shown that, in an open office area, the 5.7 dB diversity gain obtained using a dual-branch bodyworn maximal-ratio diversity system may be further improved to 11.1 dB if a six-branch system was used. First-and second-order theoretical equations for diversity reception techniques operating in Nakagami fading conditions were used to model the postdetection combined envelopes. Maximum likelihood estimates of the Nakagami-parameter suggest that the fading conditions encountered in this study were generally less severe than Rayleigh. The paper also describes an algorithm that may be used to simulate the measured output of an M-branch diversity combiner operating in independent and identically-distributed Nakagami fading environments.

Channel characterization for single- and multiple-antenna wearable systems used for indoor body-to-body communications

In this paper, an analysis of radio channel characteristics for single- and multiple-antenna bodyworn systems for use in body-to-body communications is presented. The work was based on an extensive measurement campaign conducted at 2.45 GHz representative of an indoor sweep and search scenario for fire and rescue personnel. Using maximum-likelihood estimation in conjunction with the Akaike information criterion (AIC), five candidate probability distributions were investigated and from these the kappa - mu distribution was found to best describe small-scale fading observed in the body-to-body channels. Additional channel parameters such as autocorrelation and the cross-correlation coefficient between fading signal envelopes were also analyzed. Low cross correlation and small differences in mean signal levels between potential dual-branch diversity receivers suggested that the prospect of successfully implementing diversity in this type application is extremely good. Moreover, using selection combination, maximal ratio, and equal gain combining, up to 8.69-dB diversity gain can be made available when four spatially separated antennas are used at the receiver. Additional improvements in the combined envelopes through lower level crossing rates and fade durations at low signal levels were also observed.

Red-shifts and red herrings in geographical ecology

I draw attention to the need for ecologists to take spatial structure into account more seriously in hypothesis testing. If spatial autocorrelation is ignored, as it usually is, then analyses of ecological patterns in terms of environmental factors can produce very misleading results. This is demonstrated using synthetic but realistic spatial patterns with known spatial properties which are subjected to classical correlation and multiple regression analyses. Correlation between an autocorrelated response variable and each of a set of explanatory variables is strongly biased in favour of those explanatory variables that are highly autocorrelated - the expected magnitude of the correlation coefficient increases with autocorrelation even if the spatial patterns are completely independent. Similarly, multiple regression analysis finds highly autocorrelated explanatory variables "significant" much more frequently than it should. The chances of mistakenly identifying a "significant" slope across an autocorrelated pattern is very high if classical regression is used. Consequently, under these circumstances strongly autocorrelated environmental factors reported in the literature as associated with ecological patterns may not actually be significant. It is likely that these factors wrongly described as important constitute a red-shifted subset of the set of potential explanations, and that more spatially discontinuous factors (those with bluer spectra) are actually relatively more important than their present status suggests. There is much that ecologists can do to improve on this situation. I discuss various approaches to the problem of spatial autocorrelation from the literature and present a randomisation test for the association of two spatial patterns which has advantages over currently available methods.

Ca(2+) sparks promote myogenic tone in retinal arterioles

Background and Purpose: Ca(2+) imaging reveals subcellular Ca(2+) sparks and global Ca(2+) waves/oscillations in vascular smooth muscle. It is well established that Ca(2+) sparks can relax arteries, but we have previously reported that sparks can summate to generate Ca(2+) waves/oscillations in unpressurized retinal arterioles, leading to constriction. We have extended these studies to test the functional significance of Ca(2+) sparks in the generation of myogenic tone in pressurized arterioles.

Experimental Approach: Isolated retinal arterioles (25-40 μm external diameter) were pressurized to 70 mmHg, leading to active constriction. Ca(2+) signals were imaged from arteriolar smooth muscle in the same vessels using Fluo4 and confocal laser microscopy.

Key Results: Tone development was associated with an increased frequency of Ca(2+) sparks and oscillations. Vasomotion was observed in 40% of arterioles and was associated with synchronization of Ca(2+) oscillations, quantifiable as an increased cross-correlation coefficient. Inhibition of Ca(2+) sparks with ryanodine, tetracaine, cyclopiazonic acid or nimodipine, or following removal of extracellular Ca(2+) , resulted in arteriolar relaxation. Cyclopiazonic acid-induced dilatation was associated with decreased Ca(2+) sparks and oscillations but with a sustained rise in the mean global cytoplasmic [Ca(2+) ] ([Ca(2+) ]c ), as measured using Fura2 and microfluorimetry.

Conclusions and Implications: This study provides direct evidence that Ca(2+) sparks can play an excitatory role in pressurized arterioles, promoting myogenic tone. This contrasts with the generally accepted model in which sparks promote relaxation of vascular smooth muscle. Changes in vessel tone in the presence of cyclopiazonic acid correlated more closely with changes in spark and oscillation frequency than global [Ca(2+) ]c , underlining the importance of frequency-modulated signalling in vascular smooth muscle.

Do obesity and sleep problems cluster in the workplace?:A multivariate, multilevel study

OBJECTIVES: The aim of this study was to examine the co-occurrence of obesity and sleep problems among employees and workplaces. METHODS: We obtained data from 39 873 men and women working in 3040 workplaces in 2000-2002 (the Finnish Public Sector Study). Individual- and workplace-level characteristics were considered as correlates of obesity and sleep problems, which were modelled simultaneously using a multivariate, multilevel approach. RESULTS: Of the participants, 11% were obese and 23% reported sleep problems. We found a correlation between obesity and sleep problems at both the individual [correlation coefficient 0.048, covariance 0.047, standard error (SE) 0.005) and workplace (correlation coefficient 0.619, covariance 0.068, SE 0.011) level. The latter, but not the former, correlation remained after adjustment for individual- and workplace-level confounders, such as age, sex, socioeconomic status, shift work, alcohol consumption, job strain, and proportion of temporary employees and manual workers at the workplace. CONCLUSIONS: Obese employees and those with sleep problems tend to cluster in the same workplaces, suggesting that, in addition to targeting individuals at risk, interventions to reduce obesity and sleep problems might benefit from identifying "risky" workplaces.

Age-related changes in non-receptor dependent generation of reactive oxygen species from phagocytes of healthy adults

Several authors have shown that neutrophil generation of reactive oxygen species (ROS) declines with advancing age. Similar changes have also been suggested in monocytes. In both cases alterations in second messenger activity have been implicated as the most likely explanation for these observations. The aim of this study was to investigate the effect of age on phagocyte ROS generation, stimulated by the direct activation of protein kinase C (PKC). Venous blood was drawn from normal healthy subjects, cells were separated on a double density gradient into mononuclear and polymorphonuclear (pmn) cells. Phorbol myristate acetate (PMA) was employed as a cell stimulus. Superoxide generation was measured by cytochrome c reduction and myeloperoxidase (MPO) products by measurement of peak luminol chemiluminescence (CL). Fifty-eight subjects, 25 males and 33 females, were studied, median age 49 years (range 26-88 years). Polymorphonuclear cell superoxide generation was significantly higher in males and there was a trend towards higher pmn MPO product generation in males. Using Spearman's ranked correlation coefficient, monocyte superoxide generation was negatively correlated with age (r = -0.473, P <0.001). No changes in the generation of MPO products was found. There were also trends towards a negative correlation of pmn cytochrome c reduction and peak luminol CL with age in males but not females. Since PMA directly activates protein kinase C, reduced monocyte superoxide generation with increasing age appears to be related to alterations in the ROS generating system downstream of the cell receptor. Impaired monocyte superoxide generation may have implications for non-specific defence against certain infections and early tumour growth in the elderly. Factors underlying these changes in monocyte function therefore require further study.

Interobserver Reliability of Radiologists' Interpretations of Mobile Chest Radiographs for Nursing Home-Acquired Pneumonia

Objectives: To determine the interobserver reliability of radiologists' interpretations of mobile chest radiographs for nursing home-acquired pneumonia. Design: A cross-sectional reliability study. Setting: Nursing homes and an acute care hospital. Participants: Four radiologists reviewed 40 mobile chest radiographs obtained from residents of nursing homes who met a clinical definition of lower respiratory tract infections. Measurements: Radiologists were asked to interpret radiographs with respect to the film quality; presence, pattern, and extent of an infiltrate; and the presence of a pleural effusion or adenopathy. Interrater reliability was evaluated using the intraclass correlation coefficient derived from a 2-way random effects model. Results: On average the radiologists reported that 6 of the 40 films were of very good or excellent quality and 16 of the 40 were of fair or poor quality. When the finding of an infiltrate was dichotomized (0 = no; 1 = possible, probable, or definite) all 4 radiologists agreed on 21 of the 37 chest radiographs. The intraclass correlation coefficient for the presence or absence of infiltrates was 0.54 (95% confidence intervals [CI] 0.38 to 0.69). For the 14 radiographs where infiltrates were observed by all radiologists, intraclass correlation coefficients for the presence of pleural effusions was 0.08 (95% CI -0.10 to 0.41), hilar adenopathy 0.54 (95% CI 0.29 to 0.79), and mediastinal adenopathy 0.49 (95% CI 0.21 to 0.76). Conclusion: In conclusion, the interrater agreement among radiologists for mobile chest radiographs in establishing the presence or absence of an infiltrate can be judged to be "fair." Treatment decisions need to include clinical findings and should not be made based on radiographic findings alone. © 2006 American Medical Directors Association.

Quantification of interpoint topographic correlations of threshold values in glaucomatous visual fields

Purpose: The authors sought to quantify neighboring and distant interpoint correlations of threshold values within the visual field in patients with glaucoma. Methods: Visual fields of patients with confirmed or suspected glaucoma were analyzed (n = 255). One eye per patient was included. Patients were examined using the 32 program of the Octopus 1-2-3. Linear regression analysis among each of the locations and the rest of the points of the visual field was performed, and the correlation coefficient was calculated. The degree of correlation was categorized as high (r > 0.66), moderate (0.66 = r > 0.33), or low (r = 0.33). The standard error of threshold estimation was calculated. Results: Most locations of the visual field had high and moderate correlations with neighboring points and with distant locations corresponding to the same nerve fiber bundle. Locations of the visual field had low correlations with those of the opposite hemifield, with the exception of locations temporal to the blind spot. The standard error of threshold estimation increased from 0.6 to 0.9 dB with an r reduction of 0.1. Conclusion: Locations of the visual field have highest interpoint correlation with neighboring points and with distant points in areas corresponding to the distribution of the retinal nerve fiber layer. The quantification of interpoint correlations may be useful in the design and interpretation of visual field tests in patients with glaucoma.

Reproducibility of optic disk topographic measurements with the Topcon ImageNet and the Heidelberg Retina Tomograph

Objective: To compare the reproducibility of optic disk measurements provided by an image analyzer and a scanning laser tomograph. Methods: Ten images of the same eye of 10 normal volunteers were taken with the Heidelberg Retina Tomograph and with the Topcon ImageNet. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) were used to evaluate the reproducibility of the measurements. Results: Eleven parameters were analyzed with the Topcon ImageNet. Six parameters (55%) had ICC greater than 90%. Four parameters (36%) had CV less than 10%. Twelve parameters were evaluated with the Heidelberg Retina Tomograph. Nine parameters (75%) had ICC over 90%. Nine parameters (75%) had CV less than 10%. Conclusion: Both systems provided reproducible data. The optic disk parameters provided by the Heidelberg Retina Tomograph had a better reproducibility than those obtained from the Topcon ImageNet.

Comparison of two fast strategies, SITA fast and TOP, for the assessment of visual fields in glaucoma patients

Purpose: To compare two fast threshold strategies of visual field assessment; SITA Fast (HSF) and Tendency Orientated Perimetry (TOP), in detecting visual field loss in patients with glaucoma. Methods: Seventy-six glaucoma, ocular hypertensive and normal patients had HSF and TOP performed in random order. Quantitative comparisons for the global visual field indices - mean deviation and defect (MD) for HSF and TOP, and pattern standard deviation (PSD) for HSF and loss variance (LV) for TOP - were made using correlation coefficients. Humphrey global parameters were converted to Octopus equivalents, and method comparison analysis was used to determine agreement between the two strategies. Test duration times were compared using t-test. Sensitivity and specificity for these two algorithms were determined according to predetermined criteria. Results: High correlation coefficient values were obtained for MD measurements between HSF and TOP (r=-0.89, P

Fixed Bed Study of Ammonia Removal from Aqueous Solutions Using Natural Zeolite

Purpose
– The purpose of this paper is to investigate the performance of natural Jordanian zeolite tuff to remove ammonia from aqueous solutions using a laboratory batch method and fixed-bed column apparatus. Equilibrium data were fitted to Langmuir and Freundlich models.

Design/methodology/approach
– Column experiments were conducted in packed bed column. The used apparatus consisted of a bench-mounted glass column of 2.5 cm inside diameter and 100 cm height (column volume = 490 cm3). The column was packed with a certain amount of zeolite to give the desired bed height. The feeding solution was supplied from a 30 liter plastic container at the beginning of each experiment and fed to the column down-flow through a glass flow meter having a working range of 10-280ml/min.

Findings
– Ammonium ion exchange by natural Jordanian zeolite data were fitted by Langmuir and Freundlich isotherms. Continuous sorption of ammonium ions by natural Jordanian zeolite tuff has proven to be effective in decreasing concentrations ranging from 15-50 mg NH4-N/L down to levels below 1 mg/l. Breakthrough time increased by increasing the bed depth as well as decreasing zeolite particle size, solution flow-rate, initial NH4+ concentration and pH. Sorption of ammonium by the zeolite under the tested conditions gave the sorption capacity of 28 mg NH4-N/L at 20°C, and 32 mg NH4-N/L at 30°C.

Originality/value
– This research investigates the performance of natural Jordanian zeolite tuff to remove ammonia from aqueous solutions using a laboratory batch method and fixed-bed column apparatus. The equilibrium data of the sorption of Ammonia were plotted by using the Langmuir and Freundlich isotherms, then the experimental data were compared to the predictions of the above equilibrium isotherm models. It is clear that the NH4+ ion exchange data fitted better with Langmuir isotherm than with Freundlich model and gave an adequate correlation coefficient value.

Lung Clearance Index Is a Repeatable and Sensitive Indicator of Radiological Changes in Bronchiectasis

RATIONALE: In bronchiectasis there is a need for improved markers of lung function to determine disease severity and response to therapy.

OBJECTIVES: To assess whether the lung clearance index is a repeatable and more sensitive indicator of computed tomography (CT) scan abnormalities than spirometry in bronchiectasis.

METHODS: Thirty patients with stable bronchiectasis were recruited and lung clearance index, spirometry, and health-related quality of life measures were assessed on two occasions, 2 weeks apart when stable (study 1). A separate group of 60 patients with stable bronchiectasis was studied on a single visit with the same measurements and a CT scan (study 2).

MEASUREMENTS AND MAIN RESULTS: In study 1, the intervisit intraclass correlation coefficient for the lung clearance index was 0.94 (95% confidence interval, 0.89 to 0.97; P < 0.001). In study 2, the mean age was 62 (10) years, FEV1 76.5% predicted (18.9), lung clearance index 9.1 (2.0), and total CT score 14.1 (10.2)%. The lung clearance index was abnormal in 53 of 60 patients (88%) and FEV1 was abnormal in 37 of 60 patients (62%). FEV1 negatively correlated with the lung clearance index (r = -0.51, P < 0.0001). Across CT scores, there was a relationship with the lung clearance index, with little evidence of an effect of FEV1. There were no significant associations between the lung clearance index or FEV1 and health-related quality of life.

CONCLUSIONS: The lung clearance index is repeatable and a more sensitive measure than FEV1 in the detection of abnormalities demonstrated on CT scan. The lung clearance index has the potential to be a useful clinical and research tool in patients with bronchiectasis.