[Show abstract][Hide abstract] ABSTRACT: Background
Sarcosine has been investigated as a prostate cancer biomarker with mixed results concerning its predictive power. We performed a case–control evaluation of the predictive value of serum sarcosine for early detection in a population-based cohort of men undergoing prostate-specific antigen (PSA) screening.
For analysis we used 251 cancer cases and 246 age-matched non-cancer cases from the San Antonio Biomarkers Of Risk (SABOR) screening study. For cancer cases, pre-diagnostic serum was utilized for sarcosine measurement. Controls were defined as men who had been followed at least for 5 years on study with no prostate cancer diagnosis; sarcosine was measured on the initial baseline serum. HPLC-electrospray ionization mass spectrometry was used for serum sarcosine quantification. The association of sarcosine with prostate cancer was assessed using area underneath the receiver-operating characteristic curve (AUC), and logistic regression adjusting for PSA, digital rectal exam, family history, age, race, and history of a prior negative biopsy. Among cancer cases, nominal logistic regression was used for the association of sarcosine with Gleason grade.
Sarcosine levels were overlapping between the prostate cancer cases (median 15.8 uM, range 6.2 to 42.5 uM) and controls (median 16.2 uM, range 6.4 to 53.6 uM). The AUC of sarcosine was not statistically different from random chance either for participants with any PSA value (52.2 %) or those with PSA values in the range of 2 to 10 ng/mL (54.3 %). Sarcosine was not predictive of Gleason score and added no independent predictive power to standard prostate cancer risk factors for detection of prostate cancer (all p-values > 0.05).
Serum sarcosine should not be pursued further as a marker for the early detection of prostate cancer.
[Show abstract][Hide abstract] ABSTRACT: Key message: Daily stem growth was reduced by drought with high significance, but not affected by ozone uptake or drought–ozone interaction. Increasing air temperature showed capacity of compensating negative drought effects. Abstract: Future increases in stress on forest trees due to rising ozone deposition and/or exacerbating drought are one of many contemporary climate change concerns. European beech (Fagus sylvatica L.) is known to be sensitive to both stressors. To date, there is limited evidence concerning the impact of ozone uptake, or its combined effect with drought, on the growth of forest trees. This study emanated from the hypothesis that high daily ozone influx potentially limits daily radial stem increment. A secondary hypothesis intimated that not only prolonged, but also short-term water limitation has the capacity for reducing intra-annual growth performance. To address these hypotheses, the concerted impacts of drought and O3 on radial stem growth were analyzed as components of multi-factorial field scenarios comprising gradients in altitude, temperature, precipitation and ozone exposure. Linear mixed models, adjusting for meteorological factors and nutrition, were fit to daily growth measurements in nine beech forest sites across Bavaria/Germany during three consecutive growing seasons. During individual years, daily ozone influx did not statistically significantly limit daily stem growth. However, short-term drought was associated with statistically significant, but minor and reversible limitations of intra-annual radial stem growth. Distinctive levels of plant-available soil water and soil water potential limited growth. Increases in air temperature were conducive to beech stem growth across the study region, apparently offering the capacity for buffering drought impact on the stem growth of beech.
[Show abstract][Hide abstract] ABSTRACT: While the rise in global mean temperature over the past several decades is now widely acknowledged, the issue as to whether and to what extent temperature variability is changing continues to undergo debate. Here, variability refers to the spread of the temperature distribution. Much attention has been given to the effects that changes in mean temperature have on extremes, but these changes are accompanied by changes in variability, and it is actually the two together, in addition to all aspects of a changing climate pattern, that influence extremes. Since extremes have some of the largest impacts on society and ecology, changing temperature variability must be considered in tandem with a gradually increasing temperature mean. Previous studies of trends in temperature variability have produced conflicting results. Here we investigated ten long-term instrumental records in Europe of minimum, mean and maximum temperatures, looking for trends in seasonal, annual and decadal measures of variability (standard deviation and various quantile ranges) as well as asymmetries in the trends of extreme versus mean temperatures via quantile regression. We found consistent and accelerating mean warming during 1864–2012. In the last 40 years (1973–2012) trends for Tmax were higher than for Tmin, reaching up to 0.8 °C per 10a in spring. On the other hand, variability trends were not as uniform: significant changes occurred in opposing directions depending on the season, as well as when comparing 1864–2012 trends to those of 1973–2012. Moreover, if variability changed, then it changed asymmetrically, that is only in the part above or below the median. Consequently, trends in the extreme high and low quantiles differed. Regional differences indicated that in winter, high-alpine stations had increasing variability trends for Tmax especially at the upper tail compared to no changes or decreasing variability at low altitude stations. In contrast, summer variability increased at all stations studied.
Full-text · Article · Apr 2015 · International Journal of Climatology
[Show abstract][Hide abstract] ABSTRACT: Process-orientated, unmanaged forest remnants are not sufficient for halting the loss of forest biodiversity. Thus, integrated biodiversity-promoting management for forest inhabitants is needed. Microhabitats, such as tree cavities or bark pockets, are essential for the preservation of saproxylic species and of critical importance for endangered ones. This study investigates (1) which factors trigger the formation of microhabitats at both the individual tree and aggregated plot level, and (2) whether the co-occurrence of microhabitats differs between managed (=logged) and unmanaged forests. Relationships between the occurrence of 17 microhabitat types and individual tree features (e.g. light availability, and tree vitality) and plot characteristics (e.g. stand density index and stand age) in 398 plots dominated by Fagus sylvatica or Pseudotsuga menziesii in Germany and the USA were studied using random-effects logistic and normal regression modelling. Separate analyses were performed for German beech forests, German Douglas-fir forests, and the US Douglas-fir forests. Our results show that (1) tree diameter in breast height (DBH), tree vitality and branchiness or epicormic branches are highly related with the occurrence of one or more microhabitats on individual trees in managed and unmanaged beech and US Douglas-fir forests. In managed German Douglas-fir forests, vitality is not a predictor for the occurrence of microhabitats on a tree, but tree density and the maximum age of trees in a stand in addition to DBH and branchiness have an effect. Time since last management is not a statistically significant predictor for the presence of microhabitats at the tree level, but it is for German beech at the plot level. In Douglas-fir-dominated forests both in Germany and in the USA, the stand density index was the only common predictor at the plot level. (2) Unmanaged German beech and Douglas-fir forests exhibit more statistically significant and positive correlations with microhabitat groups than managed stands, implying that the presence of one microhabitat group on a tree is associated with the presence of other microhabitat groups. We finally conclude that measures for supporting microhabitat inhabitants in managed forests are scale and species dependent (tree versus plot level; beech versus Douglas-fir-dominated forests). Trees that carry microhabitats seem to have similar features independently of forest management. At the plot level, density management may trigger the accumulation of microhabitats. Our results indicate that in forest management, it is possible to consider the factors influencing the formation of microhabitats and implement adequate forest practices to advance their formation.
Full-text · Article · Dec 2014 · European Journal of Forest Research
[Show abstract][Hide abstract] ABSTRACT: Purpose:
A detailed family history provides an inexpensive alternative to genetic profiling for individual risk assessment. We updated the PCPT Risk Calculator to include detailed family histories.
Materials and methods:
The study included 55,168 prostate cancer cases and 638,218 controls from the Swedish Family Cancer Database who were 55 years old or older in 1999 and had at least 1 male first-degree relative 40 years old or older and 1 female first-degree relative 30 years old or older. Likelihood ratios, calculated as the ratio of risk of observing a specific family history pattern in a prostate cancer case compared to a control, were used to update the PCPT Risk Calculator.
Having at least 1 relative with prostate cancer increased the risk of prostate cancer. The likelihood ratio was 1.63 for 1 first-degree relative 60 years old or older at diagnosis (10.1% of cancer cases vs 6.2% of controls), 2.47 if the relative was younger than 60 years (1.5% vs 0.6%), 3.46 for 2 or more relatives 60 years old or older (1.2% vs 0.3%) and 5.68 for 2 or more relatives younger than 60 years (0.05% vs 0.009%). Among men with no diagnosed first-degree relatives the likelihood ratio was 1.09 for 1 or more second-degree relatives diagnosed with prostate cancer (12.7% vs 11.7%). Additional first-degree relatives with breast cancer, or first-degree or second-degree relatives with prostate cancer compounded these risks.
A detailed family history is an independent predictor of prostate cancer compared to commonly used risk factors. It should be incorporated into decision making for biopsy. Compared with other costly biomarkers it is inexpensive and universally available.
Full-text · Article · Sep 2014 · The Journal of Urology
[Show abstract][Hide abstract] ABSTRACT: Individual tree mortality prediction is a key component of single tree-based stand simulators. However, accurate modeling of long-term research plot data is hampered by rare events, variable lengths of observation, and multiple sources of heterogeneity. This study makes use of a result
from medicine that demonstrates the equivalence of logistic and Cox proportional hazards regression for modeling survival data in the case of large sample sizes, rare events, and variable interval periods of observation. Pooled logistic regression models are used to model tree mortality across
multiple observation periods with random effects to account for heterogeneity due to plots and calendar year. The models are applied to data from 21,051 observation periods (each approximately 5 years) from 9,292 beech trees in a Bavarian long-term forest research plot network. Among the observation
periods studied, 604 (2.9%) resulted in a mortality. Indices measuring competition from light, trees of the same species, conifer trees, and shading are significantly associated with mortality, whereas other variables, including dbh, fail to add additional predictive value. Analytic equations
for predicting mortality in new trees are provided and yield an area underneath the receiver operating characteristic curve of 91.5%.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) as potential surrogate endpoints (SEP) for overall survival (OS) in second-line treatment for metastatic colorectal cancer (mCRC).
A systematic literature search of randomised trials of second-line chemotherapy for mCRC reported from January 2000 to July 2013 was performed. Correlation coefficients weighted by number of patients in the treatment arms between median PFS, ORR and DCR with median OS were estimated.
Twenty-three trials reflecting 10 800 patients met the inclusion criteria. Median PFS and OS across all trials were 4.5 months and 11.5 months and median ORR and DCR were 11.4% and 65%, respectively. PFS showed moderate correlation with OS [RPFS = 0.73; 95% confidence interval (CI) 0.61-0.82]. In contrast, ORR only weakly correlated with OS (RORR = 0.58; 95% CI 0.38-0.72, n = 22). Despite a small number of studies (n = 10) reporting on DCR, moderate correlation with OS was observed (RDCR = 0.74; 95% CI 0.56-0.86).
Based on the available trial-level data, PFS may serve as an appropriate SEP in second-line chemotherapy for mCRC. A small number of studies revealed moderate correlation of DCR with OS that justifies further investigation.