Relationship between atorvastatin dose and the harm caused by torcetrapib

Development of the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib, was halted after the ILLUMINATE trial revealed an increase in both all-cause mortality (ACM) and major cardiovascular events (MCVEs) associated with its use. We now report that the harm caused by torcetrapib was confined to those in the 10 mg atorvastatin subgroup for both ACM [hazard ratio (HR) = 2.68, 95% CI (1.58, 4.54), P < 0.0001] and MCVEs [HR = 1.41, 95% CI (1.14, 1.74), P = 0.002], with no evidence of harm when torcetrapib was coadministered with higher doses of atorvastatin. In the atorvastatin 10 mg subgroup, age, prior heart failure and stroke were significantly associated with ACM, independent of torcetrapib treatment, whereas low apoA-I, smoking, hypertension, heart failure, myocardial infarction, and stroke were independently associated with MCVEs. After adjusting for these factors, the HR associated with torcetrapib treatment in the 10 mg atorvastatin subgroup remained elevated for both ACM [HR = 2.67, 95% CI (1.57, 4.54), P < 0.001] and MCVE [HR = 1.36, 95% CI (1.10, 1.69), P = 0.005]. Thus, the harm caused by torcetrapib was confined to individuals taking atorvastatin 10 mg. The harm could not be explained by torcetrapib-induced changes in lipid levels, blood pressure, or electrolytes. It is conceivable that higher doses of atorvastatin protected against the harm caused by torcetrapib.     

Relation between Water Balance and Climatic Variables Associated with the Geographical Distribution of Anurans

Amphibian species richness increases toward the equator, particularly in humid tropical forests. This relation between amphibian species richness and environmental water availability has been proposed to be a consequence of their high rates of evaporative water loss. In this way, traits that estimate water balance are expected to covary with climate and constrain a species’ geographic distribution. Furthermore, we predicted that coexisting species of anurans would have traits that are adapted to local hydric conditions. We compared the traits that describe water balance in 17 species of anurans that occur in the mesic Atlantic Forest and xeric Cerrado (savannah) habitats of Brazil. We predicted that species found in the warmer and dryer areas would show a lower sensitivity of locomotor performance to dehydration (SLPD), increased resistance to evaporative water loss (REWL) and higher rates of water uptake (RWU) than species restricted to the more mesic areas. We estimated the allometric relations between the hydric traits and body mass using phylogenetic generalized least squares. These regressions showed that REWL scaled negatively with body mass, whereas RWU scaled positively with body mass. Additionally, species inhabiting areas characterized by higher and more seasonally uniform temperatures, and lower and more seasonally concentrated precipitation, such as the Cerrado, had higher RWU and SLPD than species with geographical distributions more restricted to mesic environments, such as the Atlantic Forest. These results support the hypothesis that the interspecific variation of physiological traits shows an adaptation pattern to abiotic environmental traits.     

Relationship between Sevoflurane Plasma Concentration,Clinical Variables and Bispectral Index Values during Cardiopulmonary Bypass

Background

Anesthetic administration is increasingly guided by electroencephalography (EEG)-based monitoring, such as the bispectral index (BIS). However, during cardiopulmonary bypass (CPB), factors other than the administered hypnotic agents may influence EEG signals, and their effects on BIS values are unknown.

Methods

This report is a secondary analysis of data from a prospective, controlled interventional study comparing the effect of sevoflurane administration guided by BIS monitoring (group Sevo_BIS) and constant administration of sevoflurane (group Sevo_1.8Vol%) during CPB. Sevoflurane plasma concentration (SPC) was measured using gas chromatography. The relationships of BIS to SPC, CPB pump flow, arterial pressure, hematocrit, temperature, time on CPB, and patient characteristics were analysed.

Results

No association was observed between BIS values and SPC in group Sevo_BIS. In group Sevo_1.8Vol%, a 40 μg ml^-1 increase in SPC, which encompassed the entire range of observed values of the SPC in this analysis, was associated with a decrease of 3.6 (95% confidence interval (CI): 1.1–6.1) in BIS values (p = 0.005). Each increase in CPB time of 10 minutes was associated with an increase in BIS values of 0.25 (95%CI: 0.11–0.39, p<0.001). Path analysis revealed that the BIS values of Sevo_BIS patients were 5.3 (95%CI: 3.2–7.5) units higher than those of Sevo_1.8Vol% patients (p<0.001), which was the strongest effect on BIS values. Path analysis revealed a slope of 0.5 (95%CI: 0.3–0.7) BIS units per 1°C body temperature (p<0.001).

Conclusion

BIS monitoring is insensitive to clinically relevant changes in SPC in individual patients during CPB.     

Changes in Pollen Viability and Concomitant Increase in the Incidence of Sorghum Ergot with Flowering Date and Implications in Selection for Escape Resistance

Pollen viability and ergot severity were monitored in a line evaluation nursery at Potchefstroom and Bethlehem (South Africa). Percentage grain fill was also evaluated at the latter locality. Changes in pollen viability with flowering date were closely correlated with changes in ergot severity (r = 0.91 and r = 0.81 at Potchefstroom and Bethlehem, respectively). Pollen viability was significantly reduced by pre-flowering daily minimum temperatures < 16°C at both localities during the period 23–27 days before flowering. The concomitant increase in ergot severity closely mirrored changes in pollen viability. Lines differed in their ability to tolerate low pre-flowering minimum temperature. Lines with pollen viabilities > 60% despite pre-flowering minimum temperature <14°C were observed. A number of lines with inherent low pollen viability, despite minimum temperatures >17°C were also found. Avoiding these in favour of vigourous pollen producers may contribute towards enhancing escape resistance in sorghum to ergot.     

Incidence of Hemorrhagic Disease in White-Tailed Deer Is Associated with Winter and Summer Climatic Conditions

Hemorrhagic disease (HD) is an important vector-borne disease of white-tailed deer (Odocoileus virginianus). The objective of this study was to determine whether temperature and precipitation were associated with a measure of annual incidence of HD in white-tailed deer from Virginia. The annual percentages of deer with hoof wall growth interruptions (a clinical sign of HD) from four climate divisions in the HD endemic area of Virginia recorded during 1993–2006 were used as indicators of annual HD incidence. Pearson’s correlation coefficients between these indicators of incidence and average temperature (°F) or total precipitation (in.) for each month, as well as for winter (January–February), early summer (June–July), and late summer/fall (August–September–October) seasons were calculated. Strong direct correlations between the measure of annual HD incidence and average temperature for winter (r = 0.39, P = 0.003, n = 57), early summer (r = 0.51, P < 0.0001, n = 57), and late summer/fall (r = 0.42, P = 0.001, n = 57) were evident. There also was a strong inverse correlation between the measured annual HD incidence and June precipitation (r = −0.44, P = 0.0006, n = 57). Poisson regression models of seasonal temperatures and June precipitation to annual percentage of deer with hoof wall growth interruptions were developed. Based on Akaike’s Information Criterion with small sample size correction (AICc), the global model was selected as the top model. Higher winter and summer temperatures may increase vector capacity and competence, and lower precipitation in June may create favorable breeding sites for midges.     

Linear Relations between Carbon Dioxide Concentration and Rate of Development Towards Flowering in Sorghum, Cowpea and Soyabean

Negative linear relations were detected (P < 0·005)between the rate of progress from sowing to panicle initiationand CO₂ concentration (210-720 µmol CO₂ mol^-1 air) fortwo genotypes of sorghum [Sorghum bicolor (L.) Moench]. Relationsbetween CO₂ concentration and the rate of progress from sowingto first flowering were also negative in soyabean [Glycine max(L.) Merrill] (P < 0·025), but positive in cowpea[Vigna unguiculata (L.) Walp.] (P < 0·025), albeitthat in both grain legumes sensitivity was much less than insorghum. Thus CO₂ elevation does not delay flowering in allshort-day species. The considerable effect of CO₂ concentrationon times to panicle initiation resulted in large differencesamong the sorghum plants at this developmental stage; with increasein CO₂ concentration, plants were taller with slightly moreleaves and more pronounced apical extension. At the same timeafter sowing however, sorghum plants were heavier (P < 0·05)at 210 than at 360 µmol CO₂ mol^-1 air. In contrast, relationsbetween the dry masses of the soyabean and cowpea plants andCO₂ concentration were positive and curvilinear (P < 0·05).It is suggested that the impact of global environmental changecould be severe for sorghum production in the semi-arid tropics.Copyright1995, 1999 Academic Press Sorghum bicolor (L.) Moench., sorghum, Glycine max (L.) Merrill, soyabean, Vigna unguiculata (L.) Walp., cowpea, development, flowering, CO₂, dry matter accumulation, environmental change     

The Effects of Landscape Variables on the Species-Area Relationship during Late-Stage Habitat Fragmentation

Few studies have focused explicitly on the later stages of the fragmentation process, or "late-stage fragmentation", during which habitat area and patch number decrease simultaneously. This lack of attention is despite the fact that many of the anthropogenically fragmented habitats around the world are, or soon will be, in late-stage fragmentation. Understanding the ecological processes and patterns that occur in late-stage fragmentation is critical to protect the species richness in these fragments. We investigated plant species composition on 152 islands in the Thousand Island Lake, China. A random sampling method was used to create simulated fragmented landscapes with different total habitat areas and numbers of patches mimicking the process of late-stage fragmentation. The response of the landscape-scale species-area relationship (LSAR) to fragmentation per se was investigated, and the contribution of inter-specific differences in the responses to late-stage fragmentation was tested. We found that the loss of species at small areas was compensated for by the effects of fragmentation per se, i.e., there were weak area effects on species richness in landscapes due to many patches with irregular shapes and high variation in size. The study also illustrated the importance of inter-specific differences for responses to fragmentation in that the LSARs of rare and common species were differently influenced by the effects of fragmentation per se. In conclusion, our analyses at the landscape scale demonstrate the significant influences of fragmentation per se on area effects and the importance of inter-specific differences for responses to fragmentation in late-stage fragmentation. These findings add to our understanding of the effects of habitat fragmentation on species diversity.     

铁破锣花序的开花特性与昆虫传粉的相互关系研究

为了揭示植物花的空间布局与开花动态的调节机制以及避免同株异花传粉的生态学策略,该研究对铁破锣［Beesia calthifolia (Maxim.) Ulbr.］花序形态结构、开花动态和传粉生物学进行了观察分析。结果表明：（1）铁破锣花序结构设计巧妙,由3朵花组成一个聚伞花序单元并依次排列在主花序轴上,且花序轴上聚伞花序之间距离较远。（2）铁破锣通过单个聚伞花序顶花先开,通常只有6～8朵聚伞花序的顶花同时开放,而且总状花序从基部到顶部逐次开放,从而使得大量聚集单花的花序达到尽量少开花。（3）铁破锣花白色,花粉是访花昆虫的仅有诱物,纤细巴蚜蝇（Baccha maculata）是铁破锣的主要传粉昆虫,这种昆虫能够以花丝为着力点取食花粉,通常在一个花序上取食一朵单花后很快飞向另外一个花序的花。研究认为,铁破锣花序的空间设计和开花的时间序列动态减少了昆虫访问同株异花的可能性。     

A Meta-Analysis of the Relationship between Cigarette Smoking and Incidence of Myelodysplastic Syndromes

Background

In recent years, epidemiologic studies have reported controversial results relating cigarette smoking to myelodysplastic syndromes (MDS) risk. A meta-analysis was performed to assess such potential relationship between cigarette smoking and incidence of MDS.

Methods

A search of literature published before October 2012 for observational studies evaluating the association between cigarette smoking and MDS, returned 123 articles and of these, 14 were selected for this study. The outcomes from these studies were calculated and reported as odds ratios (OR). Quality assessments were performed with the Newcastle-Ottawa Scale. Heterogeneity was evaluated by the I² index and source of heterogeneity was detected by sensitivity analyses. Finally, publication bias was assessed through visual inspection of funnel plots and Egger’s test.

Results

The pooled OR of developing MDS in ever-smokers was 1.45 (95% CI, 1.25 to 1.68) versus non-smokers. Current and former smokers had increased risks of MDS, with ORs of 1.81 (95% CI, 1.24 to 2.66) and 1.67 (95% CI, 1.42 to 1.96), respectively. In subset analyses, ever-smokers had increased risks of developing MDS if they were living in the United States, or in Europe, female in gender, had refractory anemia (RA)/RA with ringed sideroblasts (RARS) or RA with excess blasts (RAEB)/RAEB in transformation (RAEBt), respectively. Our results demonstrated that the association was stronger in individuals who smoked ≥20 cigarettes/day (OR, 1.62; 95% CI, 1.03 to 2.55) versus those who smoked <20 cigarettes/day (OR, 1.36; 95% CI, 1.13 to 1.64). Moreover, individuals who smoked more than 20 pack-years had increased MDS risk (OR, 1.94; 95% CI, 1.29 to 2.92).

Conclusion

Our outcomes show that smoking increases the risk of developing MDS in ever-smokers who are current or former smokers. We also demonstrate here that positive association between cigarette smoking and risk of MDS exists, and occurs in a dose-dependent manner.     

Practical Implications of the Non-Linear Relationship between the Test Positivity Rate and Malaria Incidence

Background

The test positivity rate (TPR), defined as the number of laboratory-confirmed malaria tests per 100 suspected cases examined, is widely used by malaria surveillance programs as one of several key indicators of temporal trends in malaria incidence. However, there have been few studies using empiric data to examine the quantitative nature of this relationship.

Methods

To characterize the relationship between the test positivity rate and the incidence of malaria, we fit regression models using the confirmed malaria case rate as the outcome of interest and TPR as the predictor of interest. We varied the relationship between the two by alternating linear and polynomial terms for TPR, and compared the goodness of fit of each model.

Results

A total of 7,668 encounters for malaria diagnostic testing were recorded over the study period within a catchment area of 25,617 persons. The semi-annual TPR ranged from 4.5% to 59% and the case rates ranged from 0.5 to 560 per 1,000 persons. The best fitting model was an exponential growth model (R² = 0.80, AIC = 637). At low transmission levels (TPR<10%), the correlation between TPR and CMCR was poor, with large reductions in the TPR, for example from 10% to 1%, was associated with a minimal change in the CMCR (3.9 to 1.7 cases per 1,000 persons). At higher transmission levels, the exponential relationship made relatively small changes in TPR suggestive of sizeable change in estimated malaria incidence, suggesting that TPR remains a valuable surveillance indicator in such settings.

Conclusions

The TPR and the confirmed malaria case rate have a non-linear relationship, which is likely to have important implications for malaria surveillance programs, especially at the extremes of transmission.     

Relationship between ammonium accumulation and senescence of detached rice leaves caused by excess copper

The possibility that ammonium (NH ₄ ⁺ ) accumulation is linked to the senescence of detached rice (Oryza sativa) leaves induced by copper (Cu) was investigated. CuSO₄ was effective in promoting senescence of detached rice leaves. Both CuSO₄ and CuCl₂ induced NH ₄ ⁺ accumulation in detached rice leaves, indicating that NH ₄ ⁺ accumulation is induced by copper. Sulfate salts of Mg, Mn, Zn, and Fe were ineffective in inducing NH ₄ ⁺ accumulation in detached rice leaves. The senescence of detached rice leaves induced by Cu was found to be prior to NH ₄ ⁺ accumulation. Free radical scavengers, such as glutathione and thiourea, inhibited senescence caused by Cu and at the same time inhibited Cu-induced NH ₄ ⁺ accumulation. The current results suggest that NH ₄ ⁺ accumulation is not associated with senescence induced by Cu, but is part of the overall expression of oxidative damage caused by an excess of Cu. Evidence was presented to show that copper-induced ammonium accumulation in detached rice leaves is attributed to a decrease in glutamine synthetase activity and an increase in reduction of nitrate.     

Plants under Climatic Stress: V. Chilling and Light Effects on Radiocarbon Exchange between Photosynthetic Intermediates of Sorghum

Patterns of radiocarbon exchange between photosynthetic intermediates of the chilling sensitive Sorghum bicolor were modified by exposure to a combined environmental stress of low temperature (10 C) and moderate light levels (170 w·m⁻², visible). Pulse chase experiments with¹⁴CO₂ showed that this stress initially slowed the release of photosynthetically absorbed radiocarbon from malate. Further exposure caused an increased proportion of the radiocarbon to accumulate in aspartate. This trend continued, so that after 30 hours, some 80% of absorbed radiocarbon remained in aspartate after 1 minute of chasing and subsequent release of carbon into the C₃ cycle was very slow. In Sorghum, chilling combined with light seemed to cause a restriction in an early step of the C₄ pathway before ultrastructural changes could be detected in the mesophyll chloroplasts.     

Fatiguing Exercise Intensity Influences the Relationship between Parameters Reflecting Neuromuscular Function and Postural Control Variables

The purpose of this study was to investigate the influence of fatiguing exercise intensity on the nature and extent of fatigue-induced changes in neuromuscular function and postural stability in quiet standing. We also explored the contribution of selected neuromuscular mechanisms involved in force production to postural stability impairment observed following fatigue using an approach based on multivariate regressions. Eighteen young subjects performed 30-s postural trials on one leg with their eyes closed. Postural trials were performed before and after fatiguing exercises of different intensities: 25, 50 and 75% of maximal isometric plantarflexor torque. Fatiguing exercises consisted of sustaining a plantarflexor isometric contraction at the target intensity until task failure. Maximal isometric plantarflexor torque, electromyographic activity of plantarflexor and dorsiflexor muscles, activation level (twitch interpolation technique) and twitch contractile properties of plantarflexors were used to characterize neuromuscular function. The 25% exercise was associated with greater central fatigue whereas the 50 and 75% exercises involved mostly peripheral fatigue. However, all fatiguing exercises induced similar alterations in postural stability, which was unexpected considering previous literature. Stepwise multiple regression analyses showed that fatigue-related changes in selected parameters related to neuromuscular function could explain more than half (0.51≤R²≤0.82) of the changes in postural variables for the 25% exercise. On the other hand, regression models were less predictive (0.17≤R²≤0.73) for the 50 and 75% exercises. This study suggests that fatiguing exercise intensity does not influence the extent of postural stability impairment, but does influence the type of fatigue induced and the neuromuscular function predictors explaining changes in postural variables.     

Incidence and identification of Cassava tuber rot caused by Phytophthora palmivora

The occurrence of Cassava tuber rot in regions of Kolli hills, Kollam, and Kottayam of South India, causes major economic loss up to 70% in Cassava production. The disease tuber is characterised by brown watery lesions with foul smell, making it unfit for further use. The sporangia of the pathogen were oval and ellipsoid with a short pedicle. Identification of the isolate from these regions was also confirmed by ribosomal internal transcribed spacer (ITS) of rDNA region. The pathogen was highly aggressive when pathogenicity was tested. Based on morphological, pathogenicity and ITS sequences, the pathogen was identified as Phytophthora palmivora. Development of integrated disease management practices is essential to combat the disease. This is the first report recording the spread of Cassava tuber rot disease in regions of Kolli hills of Tamil Nadu and Kollam and Kottayam, of Kerala.     

高丹草杂种和亲本叶片基因差异表达研究

以4份高粱不育系和5种类型苏丹草为亲本,按照NCⅡ设计配制成20个杂交组合,分析各组合及亲本的表型值和中亲及超亲优势并筛选出8个优势强的组合为试材,利用cDNA-AFLP技术,分析杂种与亲本苗期叶片基因差异表达类型与主要产量性状的杂种表现及杂种优势的关系。研究表明:(1)12对引物共扩增出315条TDFs,杂种与亲本间基因表达类型有:单亲表达一致一型(P1F1型)和二型(P2F1型)、杂种特异表达类型(F1型)、单亲表达沉默一型(P1型)和二型(P2型)、双亲共沉默类型(P1P2型)和杂种亲本表达一致型(P1F1P2型)7种。(2)在差异展示类型与产量构成因素的相关分析中,有效分蘖数与P1F1型(0.726**)呈极显著正相关,单株鲜重与P1P2型(0.659*)、叶长与P2型(0.647*)呈显著正相关,成株期叶片数与F1型(-0.81**)呈极显著负相关。在与中亲优势相关分析中发现,单株鲜重与P1(0.695*)、P2(0.637*)呈显著正相关,单株鲜重与P1F1P2型(0.743**)呈极显著正相关,叶宽与P1P2型(-0.619*)呈显著负相关。在与超亲优势进行相关分析后发现,穗长与P2F1型(0.732**)呈极显著正相关,叶宽与P2F1型(-0.731**)以及P1P2型(-0.731**)呈极显著负相关。(3)差异展示类型P1F1、P2F1、P1和P2是显性效应类型,共占总检测的91.4%。差异展示类型F1和P1P2表现超显性,共占总检测的4.8%,说明各个性状的杂种表现主要受到的是(超)显性效应影响。(4)对8个与高丹草杂种优势相关的TDFs进行回收及BLAST分析均得到同源核苷酸,并且找到7个同源蛋白,这些蛋白质在控制植物生长发育方面具有重要作用。(5)将克隆测序获得差异片段的核苷酸序列,采用半定量RT-PCR进行了验证。本研究为进一步揭示高丹草杂种优势的分子机制和提高高丹草强优势组合的筛选效率以及种质资源的创建提供依据。     

Relationship between the induction of swelling and the inhibition of elongation caused by oryzalin and colchicine in corn roots

In corn seedling roots, colchicine and the dinitroaniline herbicideoryzalin cause swelling and inhibition of elongation which seemto be interconnected responses, yet they can be separated. First,both colchicine (10^–3 M) and oryzalin (10^–6 M) affectelongation (2–4 hr) well before swelling (8–10 hr).Second, a short (4 hr) oryzalin treatment produces maximal inhibitionof elongation but not maximal swelling. Third, a combinationof colchicine and oryzalin (at concentrations which give maximalor saturating effects on swelling and elongation when appliedsingly) produces a greater effect on swelling (but not elongation)than either alone. Thus swelling and inhibition of elongationare not related in a simple reciprocal relationship and maybe, at least in part, separate responses, and colchicine andoryzalin may not act in completely identical ways. (Received June 14, 1977; )