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Identifying high yield sources of patients with coronary artery disease for clinical trials: lessons from the Asymptomatic Cardiac Ischemia Pilot (ACIP) experience. The ACIP Study Group.

BACKGROUND AND HYPOTHESIS: Successful recruitment strategies for ischemic heart disease (IHD) clinical trials must identify high yield sources and efficient methods for selecting patients likely to have coronary artery disease (CAD) and ischemia, but such information is lacking. METHODS: Data from the recently completed Asymptomatic Cardiac Ischemia Pilot (ACIP) Trial were used as a model contemporary CAD/IHD trial to determine the relative patient yields, within a specific time frame, for various recruitment sources. RESULTS: Over 15 months, a total of 88,881 patient records was screened at 10 sites. The highest yield source was found by screening records of patients directly referred by a physician for possible study entry. This source accounted for 595 of 814 or 73% of potential patients and for 30% of patients eventually randomized. The largest volume of potential patients was observed from coronary angiographic laboratory record screening, and this source accounted for 39% (n = 7.542) of potential patients and for 24% of those randomized. The exercise electrocardiography (ECG) laboratory patient records yielded only 16% (5,340/33,784) of potential patients and 35% of patients randomized, but this source required considerably more time and resources for screening. CONCLUSION: Considering that time and resources for screening are fixed by budget in any trial, there is a need to balance high volume-moderate yield sources with low volume-high yield sources in order to optimize recruitment in future larger scale trials, and these data provide information and direction to focus such screening efforts.

Coronary Disease↗

On the possibility of long-wavelength long-lifetime high-quantum-yield luminophores.

We describe an approach to creating a new class of luminophores which display both long wavelength emissions exceeding 600 nm and long lifetimes. These luminophores are based on resonance energy transfer (RET) from a long lifetime donor to a short lifetime but long wavelength acceptor. We demonstrated the possibility of obtaining these desirable spectral properties using donors and acceptors noncovalently bound to DNA. The donor was a ruthenium (Ru) metal-ligand complex in which one of the diimine ligands intercalated into double-helix DNA. The acceptors were either nile blue, TOTO-3, or TO-PRO-3. Upon binding of the acceptor to donor-labeled DNA, we found that the acceptor quantum yield was remarkably enhanced so that the wavelength-integrated intensities of the donor and acceptor bound to DNA were many-fold greater than the intensity of the donor and acceptor alone when separately bound to DNA. The origin of this effect is efficient energy transfer from the donor. Under these conditions the effective overall quantum yield approaches that of the acceptor. Importantly, the increased quantum yield can be obtained while maintaining usefully long apparent acceptor lifetimes of 30 to 80 ns. The effect of an increased quantum yield from a low quantum yield donor may find use in assays to detect macromolecular binding interactions. These results suggest the synthesis of covalently linked donor-acceptor pairs with the desirable spectral properties of long wavelength emission, high quantum yield, and moderately long lifetimes for gated detection.

Acridine Orange↗

High yield hepatocyte isolation from pig livers for investigation of hybrid liver support systems: influence of collagenase concentration and body weight.

Cultured hepatocytes would be required in large quantities if a hybrid liver support system became available. We have therefore performed a study of larger scale enzymatic hepatocyte isolation on whole pig livers. A new method of open-loop and recirculating perfusion in five steps using both the portal venous and the hepatic arterial vascular systems has been developed. In a study of the yield and cell viability of hepatocytes afer isolation, the collagenase concentration of the perfusate was investigated over a range of 0.02 to 0.15%. The effect of animal weight on yield and cell viability was determined within the body weight range of 6 to 40 kg. At collagenase concentrations of less than 0.08%, yield and viability declined. As collagenase concentration increased, the yield continuously increased while the viability peaked at 0.1%. There was a decline of viability and yield with rising body weight. Optimal results were obtained with the lowest body weight (6 kg) which gave a yield of 95% (g wet weight) and a viability of 98% (trypan blue). This novel five-step collagenase perfusion technique with arterial perfusion appears to be reproducible and safe. Application of this method enables the large scale investigations to be undertaken towards the development of hybrid liver support.

Animals↗

Smoke yield of cigarettes and puffing behavior in men and women.

Puffing behavior (number of puffs, puff interval, puff duration, peak pressure, latency to peak pressure, average and total puff volume) was measured in 67 dependent male and 43 dependent female smokers when they smoked two cigarettes of their habitual brand under laboratory conditions. Test-retest reliability for the two cigarettes was high, and factor analysis showed that puff shape, puff volume, and puff frequency accounted for about 50% of variation obtained with the different puffing variables. Expiratory tidal CO levels increased with the number of cigarettes smoked before the tests and with the intensity of the smoking habit, but pre- to postsmoking delta tidal CO differences were similar for smokers of all types of cigarettes (0.1 - 1.7 mg standard machine smoking nicotine yield). Volume compensation for differences of smoke yield of the cigarettes was generally more pronounced in women than in men and, additionally, it was more pronounced for cigarettes with standard smoke nicotine yield below 0.9 mg than for cigarettes with standard smoke nicotine yield above 0.9 mg for both sexes. Only for women, partial correlation procedures suggested that nicotine might be more important in determining puffing behavior than CO and condensate yield, but there were also no women smoking the strongest cigarettes (1.3 - 1.7 mg nicotine yield). For both sexes, no compensation by adjusting the number of cigarettes smoked daily was obtained. Personality ratings, pulmonary functions, and cardiovascular functions were not, or only inconsistently, correlated with puffing behavior or type of cigarette.

Adolescent↗

Long-term effects of switching to cigarettes with lower tar and nicotine yields.

On switching to cigarettes with lower tar and nicotine yields, most individuals smoke more intensively, but it is not clear if this effect persists over a long period. Smoking behaviour was monitored in 10 male and 18 female volunteers at five monthly visits, smoking commercially available cigarettes (tar yield greater than 10 mg), then for six more visits at 6-week intervals after switching (mean reduction of 5.9 mg tar and 0.45 mg nicotine). Puffing behaviour was monitored with a flow sensing holder, and measurements were made before and after smoking of plasma cotinine, carboxyhaemglobin and alveolar carbon monoxide. After switching, cotinine levels only fell 40% of that predicted from the fall in nicotine yields, and there were no systematic trends for the rest of the study. Puff volumes rose (reflecting perhaps the reduced draw resistance of the lower yield cigarettes), and remained higher thereafter. The number of puffs per cigarette appeared to rise on switching, but then decreased again. In conclusion, most effects of switching to lower yield cigarettes appeared to persist for at least 36 weeks, suggesting that the strategy of reducing exposure to cigarette smoke by lowering tar and nicotine yields may be of limited value.

Adolescent↗

Energy yields for hydrogen cyanide and formaldehyde syntheses: the HCN and amino acid concentrations in the primitive ocean.

Prebiotic electric discharge and ultraviolet light experiments are usually reported in terms of carbon yields and involve a large input of energy to maximize yields. Experiments using lower energy inputs are more realistic prebiotic models and give energy yields which can be used to estimate the relative importance of the different energy sources on the primitive earth. Simulated prebiotic atmospheres containing either CH4, CO or CO2 with N2, H2O and variable amounts of H2 were subjected to the spark from a high frequency Tesla coil. The energy yields for the synthesis of HCN and H2CO were estimated. CH4 mixtures give the highest yields of HCN while H2CO is most efficiently produced with the CO mixtures. These results are a model for atmospheric corona discharges, which are more abundant than lightning and different in character. Preliminary experiments using artificial lightning are also reported. The energy yields from these experiments combined with the corona discharge available on the earth, allows a yearly production rate to be estimated. These are compared with other experiments and model calculations. From these production rates of HCN (e.g. 100 nmoles cm-2 yr-1) and the experimental hydrolysis rates, the steady state concentration in the primitive ocean can be calculated (e.g., 4 X 10(-6) M at pH 8 and 0 degrees). A steady state amino acid concentration of 3 X 10(-4) M is estimated from the HCN production rate and the rate of decomposition of the amino acids by passage through the submarine vents.

Amino Acids↗

Yield of fluorescence from indocyanine green in plasma and flowing blood.

The purpose of this work was to obtain more quantitative knowledge about the yield of fluorescence from retinal vessels during indocyanine green angiography (ICG). The yield of fluorescence from blood was investigated for various shear rates, concentrations of ICG, and layer thicknesses. Measurements were performed in vitro on samples of human blood in a cone-plate shear chamber using frontal illumination as in scanning laser angiography. In blood and in plasma, the yield of fluorescence of ICG increased with concentration up to 0.05 and 0.1 mg/ml, respectively. At higher concentrations, the yield decreased for all layer thicknesses. For increasing layer thicknesses, both in plasma and in blood, the yield of ICG fluorescence increased nonlinearly for concentrations higher than 0.012 mg/ml. Saturation occurred for layers thicker than 200 microns in combination with ICG concentrations of 0.4 mg/ml and higher. Application of shear rates within the physiological range of the microcirculation (88/sec and 528/sec) increased the yield of fluorescence from the blood sample compared with stasis. The high transparency of blood for the excitation and emission light of ICG that was demonstrated will lead to superposition of fluorescence from superficial and deeper layers. This superposition precludes quantitative indocyanine angiography of ocular vessels.

Biomechanical Phenomena↗

Diagnostic yield of gastroscopy in a general surgical unit.

Gastroscopy is the gold standard for investigating upper gastrointestinal complaints. Open access gastroscopy has advantages, but may not always be feasible in a small unit. Our 2-consultant general surgical unit provides gastroscopy on demand for medical and surgical patients. We audited the 499 gastroscopies carried out in our unit in 1997 to assess yield and diagnostic trends. The overall diagnostic yield of 69 per cent was comparable with published data from centres in Ireland and overseas. Diagnostic yield in our series was significantly lower for medical patients (59 per cent) than for surgical patients (72 per cent) (p < 0.05). Yield also varied considerably according to indication for referral. Patients referred with anaemia had a low yield (41 per cent). The indications associated with high yields were haematemesis (95 per cent), dysphagia (91 per cent), and persistent vomiting (85 per cent).

Adolescent↗

Grain yield responses to moisture regimes in a rice population: association among traits and genetic markers.

Drought is a major constraint to rice (Oryza sativa L.) production in rainfed and poorly irrigated environments. Identifying genomic regions influencing the response of yield and its components to water deficits will aid our understanding of the genetic mechanism of drought tolerance (DT) of rice and the development of DT varieties. Grain yield (GY) and its components of a recombinant inbred population developed from a lowland rice and an upland rice were investigated under different water levels in 2003 and 2004 in a rainout DT screening facility. Correlation and path analysis indicated that spikelet fertility (SF) was particularly important for grain yield with direct effect (P=0.60) under drought stress, while spikelet number per panicle (SN) contributed the most to grain yield (P=0.41) under well-watered condition. A total of 32 quantitative trait loci (QTLs) for grain yield and its components were identified. The phenotypic variation explained by individual QTLs varied from 1.29% to 14.76%. Several main effect QTLs affecting SF, 1,000-grain weight (TGW), panicle number (PN), and SN were mapped to the same regions on chromosome 4 and 8. These QTLs were detected consistently across 2 years and under both water levels in this study. Several digenic interactions among yield components were also detected. The identification of genomic regions associated with GY and its components under stress will be useful to improve drought tolerance of rice by marker-aided approaches.

Chromosome Mapping↗

Quantitative trait analysis of seed yield and other complex traits in hybrid spring rapeseed (Brassica napus L.): 1. Identification of genomic regions from winter germplasm.

The introgression of winter germplasm into spring canola (Brassica napus L.) represents a novel approach to improve seed yield of hybrid spring canola. In this study, quantitative trait loci (QTL) for seed yield and other traits were genetically mapped to determine the effects of genomic regions introgressed from winter germplasm into spring canola. Plant materials used comprised of two populations of doubled haploid (DH) lines having winter germplasm introgression from two related French winter cultivars and their testcrosses with a spring line used in commercial hybrids. These populations were evaluated for 2 years at two locations (Wisconsin, USA and Saskatchewan, Canada). Genetic linkage maps based on RFLP loci were constructed for each DH population. Six QTL were detected in the testcross populations for which the winter alleles increased seed yield. One of these QTL explained 11 and 19% of the phenotypic variation in the two Canadian environments. The winter allele for another QTL that increased seed yield was linked in coupling to a QTL allele for high glucosinolate content, suggesting that the transition of rapeseed into canola could have resulted in the loss of favorable seed yield alleles. Most QTL for which the introgressed allele decreased seed yield of hybrids mapped to genomic regions having homoeologous non-reciprocal transpositions. This suggests that allelic configurations created by these rearrangements might make an important contribution to genetic variation for complex traits in oilseed B. napus and could account for a portion of the heterotic effects in hybrids.

Alleles↗

Genome-wide transcript analysis of maize hybrids: allelic additive gene expression and yield heterosis.

Heterosis, or hybrid vigor, has been widely exploited in plant breeding for many decades, but the molecular mechanisms underlying the phenomenon remain unknown. In this study, we applied genome-wide transcript profiling to gain a global picture of the ways in which a large proportion of genes are expressed in the immature ear tissues of a series of 16 maize hybrids that vary in their degree of heterosis. Key observations include: (1) the proportion of allelic additively expressed genes is positively associated with hybrid yield and heterosis; (2) the proportion of genes that exhibit a bias towards the expression level of the paternal parent is negatively correlated with hybrid yield and heterosis; and (3) there is no correlation between the over- or under-expression of specific genes in maize hybrids with either yield or heterosis. The relationship of the expression patterns with hybrid performance is substantiated by analysis of a genetically improved modern hybrid (Pioneer hybrid 3394) versus a less improved older hybrid (Pioneer hybrid 3306) grown at different levels of plant density stress. The proportion of allelic additively expressed genes is positively associated with the modern high yielding hybrid, heterosis and high yielding environments, whereas the converse is true for the paternally biased gene expression. The dynamic changes of gene expression in hybrids responding to genotype and environment may result from differential regulation of the two parental alleles. Our findings suggest that differential allele regulation may play an important role in hybrid yield or heterosis, and provide a new insight to the molecular understanding of the underlying mechanisms of heterosis.

Alleles↗

Quantitative trait loci associated with traits determining grain and stover yield in pearl millet under terminal drought-stress conditions.

Drought stress during the reproductive stage is one of the most important environmental factors reducing the grain yield and yield stability of pearl millet. A QTL mapping approach has been used in this study to understand the genetic and physiological basis of drought tolerance in pearl millet and to provide a more-targeted approach to improving the drought tolerance and yield of this crop in water-limited environments. The aim was to identify specific genomic regions associated with the enhanced tolerance of pearl millet to drought stress during the flowering and grain-filling stages. Testcrosses of a set of mapping-population progenies, derived from a cross of two inbred pollinators that differed in their response to drought, were evaluated in a range of managed terminal drought-stress environments. A number of genomic regions were associated with drought tolerance in terms of both grain yield and its components. For example, a QTL associated with grain yield per se and for the drought tolerance of grain yield mapped on linkage group 2 and explained up to 23% of the phenotypic variation. Some of these QTLs were common across stress environments whereas others were specific to only a particular stress environment. All the QTLs that contributed to increased drought tolerance did so either through better than average maintenance (compared to non-stress environments) of harvest index, or harvest index and biomass productivity. It is concluded that there is considerable potential for marker-assisted backcross transfer of selected QTLs to the elite parent of the mapping population and for their general use in the improvement of pearl millet productivity in water-limited environments.

Journal Article↗

A further study of FTC yield and nicotine absorption in smokers.

The relationship between nicotine yield as determined by the FTC method and nicotine absorption was examined in 72 smokers in a more rigorous repetition of a previous study of 33 smokers. For this study, 113 smokers evenly distributed across four FTC "tar" yield ranges were recruited, only 72 demonstrated reasonable compliance with the study criteria with regard to sample collections and cigarette brand style consistency. Subjects recorded the number of cigarettes smoked daily and collected a 24-h urine sample and a saliva sample on 3 consecutive days. Nicotine absorption was determined by monitoring urinary excretion of nicotine and its metabolites. In addition, saliva samples were monitored for cotinine using radioimmunoassay (RIA). The correlation of the relationship for nicotine absorbed per cigarette was positive and significant (r = 0.31, P = 0.008) but weaker than in the previous study. Only smokers in the highest yield range showed any statistical difference from smokers in the lower ranges. Our results suggest that FTC nicotine yield is weakly related to nicotine absorption and that smoker-controlled factors exert a great influence on the amount of nicotine absorbed by smokers. Compensation is substantial but incomplete for the minority (by market share) of smokers at the low end of the yield scale. It is uncertain how well any alternative set of machine parameters would predict nicotine absorption for the majority of smokers, even if it were more predictive for the small number of smokers at the lower yield part of the range.

Adult↗

The concept of constant emission yield in GDOES.

This review paper describes the evolution of the quantification procedure for compositional depth profiling (CDP) in glow discharge optical emission spectrometry (GD-OES), based on the constant emission yield concept. The concept of emission yield (EY) is defined and ways of measuring it experimentally are discussed. The history of the development of quantitative CDP is reviewed, which shows that all of the different approaches depend on the assumption that the EY is essentially a matrix-independent quantity. Particular emphasis is placed on the dependence of the EY on the plasma parameters of current, voltage, power and pressure. In short, impedance changes (current voltage) can significantly affect the emission yield and should either be corrected mathematically or the impedance should be kept constant by pressure regulation in order to obtain reliable results from GDOES CDP. On the other hand, the effect of varying the pressure on the emission yield can be considered to be minor within the limits of practical operating conditions for most CDP applications. It is worth, however, bearing in mind that varying the discharge pressure has a significant effect on the plasma processes, and does affect the emission yield when these variations are large. The experimental results obtained for the emission yield are related to the results from theoretical model calculations published on the subject.

Journal Article↗

Glycolytic pathway and hydrogen yield studies of the extreme thermophile Caldicellulosiruptor saccharolyticus.

NMR analysis of (13)C-labelling patterns showed that the Embden-Meyerhof (EM) pathway is the main route for glycolysis in the extreme thermophile Caldicellulosiruptor saccharolyticus. Glucose fermentation via the EM pathway to acetate results in a theoretical yield of 4 mol of hydrogen and 2 mol of acetate per mole of glucose. Previously, approximately 70% of the theoretical maximum hydrogen yield has been reached in batch fermentations. In this study, hydrogen and acetate yields have been determined at different dilution rates during continuous cultivation. The yields were dependent on the growth rate. The highest hydrogen yields of 82 to 90% of theoretical maximum (3.3 to 3.6 mol H(2) per mol glucose) were obtained at low growth rates when a relatively larger part of the consumed glucose is used for maintenance. The hydrogen productivity showed the opposite effect. Both the specific and the volumetric hydrogen production rates were highest at the higher growth rates, reaching values of respectively 30 mmol g(-1) h(-1) and 20 mmol l(-1) h(-1). An industrial process for biohydrogen production will require a bioreactor design, which enables an optimal mix of high productivity and high yield.

Acetates↗

Some factors affecting variation in milk yield in crossbred dairy cows on smallholder farms in north-east Tanzania.

A 2-year longitudinal survey was carried out to investigate factors affecting milk yield in crossbred cows on smallholder farms in and around an urban centre. Sixty farms were visited at approximately 2-week intervals and details of milk yield, body condition score (BCS) and heart girth measurements were collected. Fifteen farms were within the town (U), 23 farms were approximately 5 km from town (SU), and 22 farms approximately 10 km from town (PU). Sources of variation in milk yield were investigated using a general linear model by a stepwise forward selection and backward elimination approach to judge important independent variables. Factors considered for the first step of formulation of the model included location (PU, SU and U), calving season, BCS at calving, at 3 months postpartum and at 6 months postpartum, calving year, herd size category, source of labour (hired and family labour), calf rearing method (bucket and partial suckling) and parity number of the cow. Daily milk yield (including milk sucked by calves) was determined by calving year (p < 0.0001), calf rearing method (p = 0.044) and BCS at calving (p < 0.0001). Only BCS at calving contributed to variation in volume of milk sucked by the calf, lactation length and lactation milk yield. BCS at 3 months after calving was improved on farms where labour was hired (p = 0.041) and BCS change from calving to 6 months was more than twice as likely to be negative on U than SU and PU farms. It was concluded that milk production was predominantly associated with BCS at calving, lactation milk yield increasing quadratically from score 1 to 3. BCS at calving may provide a simple, single indicator of the nutritional status of a cow population.

Animal Husbandry↗

Parameters affecting the yield of DNA from human blood.

An examination of variables affecting the yield of DNA from blood was undertaken in order to improve sample processing and to evaluate alternative methods of mailing blood samples for DNA analysis. A rapid, high-yield method was developed for the isolation of high-molecular-weight DNA from fresh and frozen blood. In addition, the following observations were made: (1) Of the anticoagulants examined, acid citrate dextrose (ACD) solution B was found to be superior to EDTA and heparin for preserving yields of DNA during incubation at room temperature. If DNA is isolated from frozen blood, high yields of undegraded DNA are achieved after incubation at 23 degrees C for 5 days with ACD solution B. (2) High yields of undegraded DNA are obtained from blood stored with ACD solution B for at least 1 day at 42 degrees C, 5 days at 0 degrees C, or 1 month at -20 degrees C. (3) Three cycles of freezing and thawing may have little if any affect on the yield of DNA. The results indicate that blood for DNA extraction may be mailed in an ambient temperature container and, in many cases, sent by first-class mail rather than by overnight delivery services.

Anticoagulants↗

The emission yields of delayed and prompt fluorescence from chloroplasts.

1. The decay of delayed fluorescence from chloroplasts blocked with 3-(3,4-dichlorophenyl)-1,1-dimethylurea and uncoupled with gramicidin has been measured in the time range 0.75--45 ms by use of a laser phosphoroscope. 2. The decays have been analysed as the sum of three first-order components of approximate half-lives 0.2, 2.5 and 300 ms by a computer-assisted least-squares fit procedure. 3. The prompt fluorescence yield of the chloroplasts was manipulated by changing the cation concentration of the chloroplast-suspending medium. 4. Analysis of the concentration dependence of the components of the delayed fluorescence decay and of the prompt fluorescence inductions indicates that the emission yield of the intermediate (tau approximately 2.5 ms) component of the decay is equal to the fluorescence yield of a Photosystem II photosynthetic unit with an open trap, and that for the slow (tau approximately 300 ms) component the emission yield is equal to the total Photosystem II prompt fluorescence yield. 5. It is concluded that the delayed fluorescence yield in the time range studied is a complex function of time, which may be due to there being different mechanisms leading to delayed fluorescence production at short and long times after cessation of illumination.

Chloroplasts↗