bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing survival curves at a fixed point in time
Authors: Klein John P. , Logan Brent , Harhoff Mette , Andersen Per Kragh 
Published: March 2007

AbstractA common problem encountered in many medical applications is the comparison of survival curves. Often, rather than comparison of the entire survival curves, interest is focused on the comparison at a fixed point in time. In most cases, the naive test based on a difference in the estimates of survival is used for this comparison. In this note, we examine the performance of alternatives to the naive test. These include tests based on a number of transformations of the survival function and a test based on a generalized linear model for pseudo‐observations. The type I errors and power of these tests for a variety of sample sizes are compared by a Monte Carlo study. We also discuss how these tests may be extended to situations where the data are stratified. The pseudo‐value approach is also applicable in more detailed regression analysis of the survival probability at a fixed point in time. The methods are illustrated on a study comparing survival for autologous and allogeneic bone marrow transplants. Copyright © 2007 John Wiley & Sons, Ltd.
On robustness of marginal regression coefficient estimates and hazard functions in multivariate survival analysis of family data when the frailty distribution is mis‐specified
Authors: Hsu Li , Gorfine Malka , Malone Kathleen 
Published: March 2007

AbstractThe shared frailty model is an extension of the Cox model to correlated failure times and, essentially, a random effects model for failure time outcomes. In this model, the latent frailty shared by individual members in a cluster acts multiplicatively as a factor on the hazard function and is typically modelled parametrically. One commonly used distribution is gamma, where both shape and scale parameters are set to be the same to allow for unique identification of baseline hazard function. It is popular because it is a conjugate prior, and the posterior distribution possesses the same form as gamma. In addition, the parameter can be interpreted as a time‐independent cross‐ratio function, a natural extension of odds ratio to failure time outcomes. In this paper, we study the effect of frailty distribution mis‐specification on the marginal regression estimates and hazard functions under assumed gamma distribution with an application to family studies. The simulation results show that the biases are generally 10% and lower, even when the true frailty distribution deviates substantially from the assumed gamma distribution. This suggests that the gamma frailty model can be a practical choice in real data analyses if the regression parameters and marginal hazard function are of primary interest and individual cluster members are exchangeable with respect to their dependencies. Copyright © 2007 John Wiley & Sons, Ltd.
Role of Gts1p in regulation of energy‐metabolism oscillation in continuous cultures of the yeast Saccharomyces cerevisiae
Authors: Xu Zhaojun , Tsurugi Kunio 
Published: March 2007

AbstractEnergy‐metabolism oscillation (EMO) in an aerobic chemostat culture of yeast is basically regulated by a feedback loop of redox reactions in energy metabolism and modulated by metabolism of storage carbohydrates. In this study, we investigated the role of Gts1p in the stabilization of EMO, using the GTS1‐deleted transformant gts1Δ. We found that fluctuations in the redox state of the NAD co‐factor and levels of redox‐regulated metabolites in glycolysis, especially of ethanol, are markedly reduced in amplitude during EMO of gts1Δ, while respiration indicated by the oxygen uptake rate (OUR) and energy charge is not so affected throughout EMO in gts1Δ. Further, the transitions of the levels of OUR, NAD+ : NADH ratio and intracellular pH between the two phases were apparently retarded compared with those in the wild‐type, suggesting attenuation of EMO in gts1Δ. Furthermore, the mRNA levels of genes encoding enzymes for the synthesis of trehalose and glycogen are fairly reduced in gts1Δ, consistent with the decreased synthesis of storage carbohydrates. In addition, the level of inorganic phosphate, which is required for the reduction of NAD+ and mainly supplied from trehalose synthesis, was decreased in the early respiro‐fermentative phase in gts1Δ. Thus, we suggested that the deletion of GTS1 as a transcriptional co‐activator for these genes inhibited the metabolism of storage carbohydrates, which causes attenuation of the feedback loop of dehydrogenase reactions in glycolysis with the restricted fluctuation of ethanol as a main synchronizing agent for EMO in a cell population. Copyright © 2007 John Wiley & Sons, Ltd.
A practical approach to maternal phenylketonuria management
Authors: Maillot F. , Cook P. , Lilburn M. , Lee P. J. 
Published: March 2007

SummaryMore women with phenylketonuria are becoming pregnant and need appropriate management to avoid the effects of raised phenylalanine on the fetus: facial dysmorphism, microcephaly, growth retardation, developmental delay and congenital heart disease. Here we describe our experiences from a single centre gained over almost three decades. A series of six cases is presented to illustrate key points in management. Ideally, phenylalanine‐restricted diet is started before conception in a planned fashion, but some women present pregnant and blood phenylalanine must be lowered rapidly. The aims of management are to maintain blood phenylalanine concentration in the target range (100–250 μmol/L) before and throughout the pregnancy, and to ensure adequate maternal nutrition and appropriate weight gain. Blood phenylalanine is monitored twice, three times a week, before and after conception respectively. Weight is monitored on a weekly basis and key micronutrients are monitored every 6–8 weeks in clinic. From the second trimester onwards, dietary phenylalanine intake has to be promptly increased, as phenylalanine tolerance increases rapidly. Postnatal management includes a neurological assessment of the infant at 4–8 weeks and an echocardiogram for infants conceived off diet. Subsequently, offspring are seen at 1 year, 4 years, 8 years and 14 years for neuropsychometric evaluations. Regular follow‐up of the mother remains important whether on or off a phenylalanine‐restricted diet.
Response of the oxygen uptake efficiency slope to exercise training in patients with chronic heart failure
Authors: Van Laethem Christophe , Van De Veire Nico , De Backer Guy , Bihija Salhi , Seghers Tony , Cambier Dirk , Vanderheyden Marc , De Sutter Johan 
Published: March 2007

AbstractBackground:The oxygen uptake efficiency slope (OUES) is a new exercise parameter that provides prognostic power in patients with CHF. Little is known about the effects of exercise training (ET) on OUES.Aim:To describe the response of OUES to 6 months of ET in CHF patients and compare its evolution to that of other exercise variables.Methods:35 patients with CHF (NYHA II–III, age 54±9y, LVEF 31±10%) performed 3 maximal exercise tests, i.e. at the start, middle and end of a 6 month ET program. OUES, PeakVO2, ventilatory anaerobic threshold (VAT) and slope VE/VCO2 were determined.Results:OUES, peakVO2, VAT, slope VE/VCO2, peak Watt, 6MWT and NYHA‐class improved during the first part of the ET period (p<0.05). Only VAT, peak Watt and 6MWT continued to improve during the second part of the ET period (p>0.05) Improvements in OUES correlated better with improvements in peakVO2 (r=0.77, p<0.001), than changes in other prognostic variables.Discussion:OUES improves significantly after 6 months of ET. Changes in peakVO2 correlate best with changes in OUES. OUES is sensitive to ET and can be used to evaluate the progression of exercise capacity in CHF patients.
Effects of fructans-containing yacon (Smallanthus sonchifoliusPoepp & Endl.) flour on caecum mucosal morphometry, calcium and magnesium balance, and bone calcium retention in growing rats
Authors: Lobo Alexandre R. , Colli Célia , Alvares Eliana P. , Filisetti Tullia M. C. C. 
Published: March 2007

Yacon roots have been considered a functional food due to the high levels of fructans they contains. In the present study, Ca and Mg balance, bone mass and strength, and caecum mucosal morphometry were evaluated. Growing male Wistar rats (n24) were fedad libitumcontrol diets or diets supplemented with yacon flour (5 or 7·5 % fructooligosaccharides) for 27 d. Mineral balance was evaluated in three periods of 5 d (starting on the 4th, 10th and 16th days). After the rats were killled, the bones were removed and bone mineral density was measured. Ca analyses were performed on left femurs and tibias and biomechanical testing on right femurs. The caecum was removed and tissue samples were collected for histological analysis. Caecal histology changed noticeably in rats fed yacon flour: there was an increase in the depth and number of total and bifurcated crypts as well. Yacon flour consumption significantly (P < 0·05) resulted in a positive Ca and Mg balance, leading to higher values of bone mineral retention and biomechanical properties (peak load and stiffness) when compared to the control group. The positive effects on mineral intestinal absorption, bone mass and biomechanical properties showed an important role of yacon roots in the maintenance of healthy bones. The increased number of bifurcating crypts might be related to the higher mineral absorption caused by the enlargement of the absorbing surface in the large intestine of the animals.
Effect of meal composition and cooking duration on the fate of sulforaphane following consumption of broccoli by healthy human subjects
Authors: Rungapamestry Vanessa , Duncan Alan J. , Fuller Zoë , Ratcliffe Brian 
Published: March 2007

The isothiocyanate, sulforaphane, has been implicated in the cancer-protective effects of brassica vegetables. When broccoli is consumed, sulforaphane is released from hydrolysis of glucoraphanin by plant myrosinase and/or colonic microbiota. The influence of meal composition and broccoli-cooking duration on isothiocyanate uptake was investigated in a designed experiment. Volunteers (n 12) were each offered a meal, with or without beef, together with 150 g lightly cooked broccoli (microwaved 2·0 min) or fully cooked broccoli (microwaved 5·5 min), or a broccoli seed extract. They received 3 g mustard containing pre-formed allyl isothiocyanate (AITC) with each meal. Urinary output of allyl (AMA) and sulforaphane (SFMA) mercapturic acids, the biomarkers of production of AITC and sulforaphane respectively, were measured for 24 h after meal consumption. The estimated yield of sulforaphane in vivo was about 3-fold higher after consumption of lightly cooked broccoli than fully cooked broccoli. Absorption of AITC from mustard was about 1·3-fold higher following consumption of the meat-containing meal compared with the non meat-containing alternative. The meal matrix did not significantly influence the hydrolysis of glucoraphanin and its excretion as SFMA from broccoli. Isothiocyanates may interact with the meal matrix to a greater extent if they are ingested pre-formed rather than after their production from hydrolysis of glucosinolates in vivo. The main influence on the production of isothiocyanates in vivo is the way in which brassica vegetables are cooked, rather than the effect of the meal matrix.
Whole body and muscle energy metabolism in preruminant calves: effects of nutrient synchrony and physical activity
Authors: van den Borne Joost J. G. C. , Hocquette Jean-François , Verstegen Martin W. A. , Gerrits Walter J. J. 
Published: March 2007

The effects of asynchronous availability of amino acids and glucose on muscle composition and enzyme activities in skeletal muscle were studied in preruminant calves. It was hypothesized that decreased oxidative enzyme activities in muscle would explain a decreased whole body heat production with decreasing nutrient synchrony. Preruminant calves were assigned to one of six degrees of nutrient synchrony, step-wise separating the intake of protein and lactose over the two daily meals. Calves at the most synchronous treatment received two identical meals daily. At the most asynchronous treatment, 85 % of the daily protein and 20 % of the daily lactose supply were fed in one meal and the remainder in the other meal. Daily intakes of all dietary ingredients were identical for all treatments. Oxidative enzyme activities and fat content increased with decreasing nutrient synchrony inM. Rectus Abdominis(RA), but not inM. Semitendinosus. Cytochrome-c-oxidase activity was positively correlated with fat content in RA (r0·49;P < 0·01). Oxidative enzyme activities in both muscles were not correlated with average daily heat production, but citrate synthase activity in RA was positively correlated (P < 0·01) with the circadian amplitude (r0·53) and maximum (r0·61) of heat production associated with physical activity. In conclusion, this study indicates that muscle energy stores are regulated by nutrient synchrony. The lack of correlation between muscle oxidative enzyme activities and average daily heat production was in contrast with findings in human subjects. Therefore, oxidative enzyme activity in muscle should not be used as an indicator for whole body heat production in growing calves.
An NMR-based metabonomic investigation on effects of milk and meat protein diets given to 8-year-old boys
Authors: Bertram Hanne Christine , Hoppe Camilla , Petersen Bent O. , Duus Jens Ø. , Mølgaard Christian , Michaelsen Kim F. 
Published: March 2007

The objective of the study was to investigate the ability of an NMR-based metabonomic approach, applied to biofluids, to explore and identify overall exogenous and endogenous biochemical effects of a short-time high intake of milk protein or meat protein given to prepubertal children, the aim being to compare relative differences and not an absolute quantification. A total of twenty-four 8-year-old boys were asked to take 53 g protein as milk (n 12) or meat daily (n 12). At baseline and after 7 d, urine and serum samples were collected and high-resolution 1H NMR spectra were acquired on these using a 800 MHz spectrometer. The milk diet reduced the urinary excretion of hippurate, while the meat diet increased the urinary excretion of creatine, histidine and urea. The NMR measurements on serum revealed minor changes in the lipid profile, which most probably should be ascribed to an increase in the content of SCFA in the blood after consumption of the milk diet. The meat diet had no effect on the metabolic profile of serum. The study for the first time demonstrates the capability of proton NMR-based metabonomics to identify the overall biochemical effects of consumption of different animal proteins. The urine metabolite profile is more susceptible to perturbations as a result of short diet interventions than the serum metabolite profile. The milk diet-induced reduction in urinary excretion of hippurate suggests alterations in gut microflora, which may be useful information for further studies elucidating the effects of bioactive components in milk.
The glycaemic response to rolled oat is not influenced by the fat content
Authors: Tuomasjukka Saska , Viitanen Matti , Kallio Heikki 
Published: March 2007

Oat is promoted as a low-glycaemic index food. Our aim was to measure the effect of the fat content of oat in glycaemia and insulinaemia and compare it with the effect of wheat. The study design was a double-blind, randomised cross-over study with four treatment segments. Eight healthy males attended four study sessions in which porridge made from four different raw materials was consumed: rolled oat (O), defatted rolled oat (DO), rolled whole wheat (W) or rolled whole wheat with added oat fat (WF). Available carbohydrate content was analysed enzymatically, and was adjusted to 50 g in each test meal. Fat content per meal was either 6·1 g (O, WF) or approximately 1·9 g (W, DO). Venous plasma glucose, insulin and triacylglycerol concentrations were measured at 0, 30, 60, 90, 120 and 180 min. All products caused a rapid increase in glucose with a peak at 30 min, where W and WF were significantly higher than O (0 = 0·006). Also insulin peaked at 30 min (no differences). A 4·2 g difference in fat content between O and DO or W and WF did not result in any significant differences in their glycaemia or insulinaemia. W and O did not differ in their overall glycaemic or insulinaemic responses. The removal of two-thirds of oat fat did not affect the postprandial plasma triacylglycerol concentration. The present study shows that neither the glycaemic nor the insulinaemic response to rolled oat is affected by the fat content, and that rolled wheat differed from rolled oat in terms of peak glucose concentration only.
Microarray analysis of hepatic genes differentially expressed in the presence of the unsaponifiable fraction of olive oil in apolipoprotein E-deficient mice
Authors: Acín Sergio , Navarro María A. , Perona Javier S. , Surra Joaquín C. , Guillen Natalia , Arnal Carmen , Sarría Alfonso J. , Arbonés-Mainar José M. , Carnicer Ricardo , Ruiz-Gutiérrez Valentina , Osada Jesús 
Published: March 2007

The hypothesis that the unsaponifiable fraction of olive oil dramatically influences hepatic gene expression was tested in mice. Two olive oils, obtained from the same olive cultivar but by different technological procedures, were characterized to show that they differed mainly in terms of the composition/quantity of this unsaponifiable fraction. Using DNA microarrays, hepatic gene expression was analysed in apoE-deficient mice fed one of two isoenergetic, isonitrogenous diets containing either 10 % (w/w) olive oil or unsaponifiable fraction-enriched olive oil. To provide an initial screening of potential candidate genes involved in a differential response, only genes with remarkably modified expression (signal log2ratio >3 or < − 3) were further considered. The eleven genes fulfilling these prerequisites were confirmed by quantitative RT–PCR, and then analysed in apoE-deficient mice with a C57BL/6J genetic background.Orosomucoidandserum amyloid A2were upregulated (to variable extents depending on the genetic background) in the absence of hepatic steatosis and inflammation.Fabp5andMt2were also strongly upregulated. Several proteases were highly suppressed by the unsaponifiable-enriched olive diet, independent of the genetic background. The findings indicate that change in the expression of these genes is a good marker of the intake of the unsaponifiable fraction of olive oil. The results highlight the important biological effects of the unsaponifiable fraction of olive oil. The term ‘monounsaturated fatty acid-enriched oil’ no longer appears appropriate for describing all the oils to which it is currently applied since it does not adequately reflect that they have different biological effects.
Central adiposity in Brazilian schoolchildren aged 7–10 years
Authors: de Assis M. A. A. , Rolland-Cachera M. F. , de Vasconcelos F. A. G. , Bellisle F. , Conde W. , Calvo M. C. M. , Luna M. E. P. , Ireton M. J. , Grosseman S. 
Published: March 2007

Waist circumference (WC) is a measure of central adiposity related to elevated risk factor levels in children and adolescents. The aim of the present study was to describe WC percentiles in 7- to 10-year-old Brazilian children and to compare frequencies of obesity and overweight as defined by BMI and frequencies of excess and at risk of abdominal adiposity as defined by WC to the corresponding age and sex data from British references. A representative sample of 2919 schoolchildren of the city of Florianopolis (southern Brazil) was examined. Smoothed WC percentiles were derived using the least mean square method. Frequencies of overweight and obesity and of excess and at risk of abdominal adiposity were assessed using the 91st and 98th centiles of the British references as cut-off points. WC increased with age in both boys and girls, with higher values for boys at every age and percentile level. Nutritional status categories of children assessed by the 91st and 98th British BMI and WC centiles showed moderate agreement (weighted κ = 0·58). Overweight was more frequent in Brazilian than British children: 15·1 % of girls and 20·1 % of boys were above the 91st percentile of the 1990 BMI for age British references. About one-quarter (22·0 % of girls and 26·9 % of boys) exceeded the 91st percentile of WC British references. The present data could be used to compare WC in children in other populations and may serve as a baseline for future studies of temporal trends in WC in Brazil.
Dietary red palm oil reduces ischaemia–reperfusion injury in rats fed a hypercholesterolaemic diet
Authors: Kruger Maritza J. , Engelbrecht Anna-Mart , Esterhuyse Johan , du Toit Eugene F. , van Rooyen Jacques 
Published: March 2007

We have previously shown that dietary red palm oil (RPO) supplementation improves functional recovery in hearts subjected to ischaemia–reperfusion. However, little knowledge exists concerning the effects of RPO supplementation of a high-cholesterol diet on ischaemia–reperfusion injury. The signalling mechanisms responsible for RPO's effects in the presence of cholesterol also remain to be elucidated. Therefore, the aim of the present study was to examine the effects of RPO, given with a high-cholesterol diet, on mitogen-activated protein kinase (MAPK) phosphorylation and apoptosis. Long–Evans rats were fed a control diet, a control diet containing 2 % cholesterol, or a control diet containing 2 % cholesterol and 7 g RPO per kg (CRPO) for 5 weeks. Hearts were excised and mounted on an isolated working heart perfusion apparatus. Cardiac function was measured after which hearts were freeze-clamped and used to assess MAPK phosphorylation and to evaluate apoptosis. Cholesterol supplementation caused a poor aortic output (AO) recovery compared with the control group (35·5 (sem 6·2) v. 55·4 (sem 2·5) %), but when RPO was added, the percentage AO increased significantly. The cholesterol group's poor AO was associated with a significant increase in p38-MAPK phosphorylation, whereas the CRPO-supplemented group showed as significant reduction in p38-MAPK phosphorylation when compared with the cholesterol-supplemented group. This significant reduction in p38-MAPK was also associated with reduced apoptosis as indicated by significant reductions in caspase-3 and poly(ADP-ribose) polymerase cleavage.
HERMS, KOUROI AND THE POLITICAL ANATOMY OF ATHENS
Authors: QUINN JOSEPHINE CRAWLEY 
Published: March 2007

During preparations for the ill-fated Sicilian expedition in 415 BC, Thucydides tells us, the Athenians woke up one morning to find that:Of all the stone herms in the city of Athens (the square-cut type, which following local custom stand in great numbers in the doorways of private houses and shrines), most had their faces [προ´σωπα] mutilated during a single night. No one knew who the perpetrators were, but there was a search for them with large rewards out of public funds . . . They took the matter seriously; it looked like an omen for the voyage, and furthermore as though it had been done as part of a conspiracy for revolution and the overthrow of the democracy [δη´μου :kgr;αταλυ´σεωσ].Some accused the flamboyant politician and general Alcibiades, ‘adducing as evidence the undemocratic licentiousness of his conduct in general’. Andocides emphasizes how seriously the matter was taken by the city authorities:The boule, summoning the generals, ordered them to make an announcement that those of the Athenians who lived in the city should take their arms and go to the Agora, those within the Long Walls should go to the Theseion, those in Piraeus to the Hippodamian agora. As for the knights, a signal was to be given by trumpet before nightfall for them to go to the Anakeion; the boule was to go to the Acropolis and sleep there, the prytaneis in the Tholos.