Minimal clinically important difference of the EORTC QLQ-CIPN20 for worsening peripheral neuropathy in patients receiving neurotoxic chemotherapy.

Context/objectivesThis is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy.MethodsCancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score.ResultsThere was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p < 0.001 and r = - 0.518, p < 0.001, respectively; T3: r = - 0.699; p < 0.001 and r = - 0.523, p < 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = - 0.354, p < 0.001; T3: r = 0.286, p < 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5-5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6-5.0 (8.1%-15.6% of the subdomain score).ConclusionThe MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5-5.9 for the sensory subscale and 2.6-5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention

An AUC-based Permutation Variable Importance Measure for Random Forests

The random forest (RF) method is a commonly used tool for classification with high dimensional data as well as for ranking candidate predictors based on the so-called random forest variable importance measures (VIMs). However the classification performance of RF is known to be suboptimal in case of strongly unbalanced data, i.e. data where response class sizes differ considerably. Suggestions were made to obtain better classification performance based either on sampling procedures or on cost sensitivity analyses. However to our knowledge the performance of the VIMs has not yet been examined in the case of unbalanced response classes. In this paper we explore the performance of the permutation VIM for unbalanced data settings and introduce an alternative permutation VIM based on the area under the curve (AUC) that is expected to be more robust towards class imbalance. We investigated the performance of the standard permutation VIM and of our novel AUC-based permutation VIM for different class imbalance levels using simulated data and real data. The results suggest that the standard permutation VIM loses its ability to discriminate between associated predictors and predictors not associated with the response for increasing class imbalance. It is outperformed by our new AUC-based permutation VIM for unbalanced data settings, while the performance of both VIMs is very similar in the case of balanced classes. The new AUC-based VIM is implemented in the R package party for the unbiased RF variant based on conditional inference trees. The codes implementing our study are available from the companion website: http://www.ibe.med.uni-muenchen.de/organisation/mitarbeiter/070_drittmittel/janitza/index.html

阿爾泰哈巴河群的沉積時代及其構造背景

Habahe Group mainly consists of elastic sediments, which widely distribute in the Chinese Altai and can provide important constraints on the tectonic evolution of the Central Asian Orogenic Belt (CAOB). However, there are different opinions about its deposition time and tectonic background. Previous studies suggested that the Habahe Group formed in Sinian to Mid-Ordovician or Mid- to Late Ordovician in a passive continental margin. On the other hand, recent geological investigations reveal a long lasting subduction-related setting in the Chinese Altai at least since Cambrian. The current geochronological study for detrital zircons from the Habahe Group reveals that the detrital zircons of individual samples, irrespective of their lithological and metamorphic differences, all show similar age patterns, with the early Paleozoic ( 206Pb/ 238U age = 463 ± 542Ma) grains predominating. The youngest detrital zircons from different samples display similar ages (ca. 470Ma), which may reflect the maximum deposition time of the Habahe Group. Dating of growth rim of detrital zircons from migmatite yielded a Mid-Devonian age (384 ± 6Ma), which was coeval with intrusion of Early to Mid-Devonian granitic plutons in the area and clearly indicates the minimum deposition time of the Hababe Group. Therefore, the deposition time of the Habahe Group can be constrained to be Mid-Ordovician to Early Devonian. Zircon U Pb dating results indicate that the detrital zircons of the Habahe Group are dominated by early Paleozoic grains, with small proportion formed in Precambrian. The early Paleozoic detrital zircons are mostly magmatic in origin, and their less rounded shapes indicate a limited transportation. The age and morphological characteristics of the detrital zircons are consistent with those of detrital zircons in active tectonic settings and indicate that the Chinese Altai was under an active continental margin environment during the Early Paleozoic. 北疆阿爾泰造山帶的哈巴河群變質碎屑巖分布廣泛,其沉積時代和構造環境對于認識中亞造山帶的演化歷史有重要意義。早期研究認為哈巴河群沉積于震旦紀—中奧陶世時期,形成于被動大陸邊緣構造環境。而最近有學者根據中亞造山帶的地質演化背景提出,阿爾泰形成于活動陸緣構造環境。對哈巴河群中碎屑鋯石的年代學研究表明,不同巖性或變質程度不同的樣品碎屑鋯石主要類群具有相似的年齡分布特征,其206Pb/238U 年齡主要介于463～542Ma 之間。在這些樣品中, 最年輕的碎屑鋯石年齡均集中于470Ma 左右,代表了碎屑沉積的時代下限。而哈巴河群混合巖樣品中碎屑鋯石增生邊形成于中泥盆世晚期（384±6Ma）,與侵入該群的早古生代花崗巖的年齡十分接近,大致反映了哈巴河群碎屑巖沉積時代的上限,因此哈巴河群的沉積時代應在早泥盆世—中奧陶世之間。鋯石的形態和內部結構特征顯示哈巴河群的年輕碎屑鋯石類群（463～542Ma）主要為巖漿鋯石,其磨圓度較差,而且在比例上遠高于前寒武紀碎屑鋯石。上述特點與活動大陸邊緣碎屑鋯石類群分布特征完全一致,反映阿爾泰在中奧陶世至早泥盆世可能處于活動大陸邊緣構造環境。postprin

Nodal dynamics, not degree distributions, determine the structural controllability of complex networks

Structural controllability has been proposed as an analytical framework for making predictions regarding the control of complex networks across myriad disciplines in the physical and life sciences (Liu et al., Nature:473(7346):167-173, 2011). Although the integration of control theory and network analysis is important, we argue that the application of the structural controllability framework to most if not all real-world networks leads to the conclusion that a single control input, applied to the power dominating set (PDS), is all that is needed for structural controllability. This result is consistent with the well-known fact that controllability and its dual observability are generic properties of systems. We argue that more important than issues of structural controllability are the questions of whether a system is almost uncontrollable, whether it is almost unobservable, and whether it possesses almost pole-zero cancellations.Comment: 1 Figures, 6 page

Impaired flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives: The effect of genetic loading

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia. © 2008 The Authors.published_or_final_versio

Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p> Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p> Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p> Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p&gt

Urban energy consumption and CO2 emissions in Beijing: current and future

This paper calculates the energy consumption and CO2 emissions of Beijing over 2005–2011 in light of the Beijing’s energy balance table and the carbon emission coefficients of IPCC. Furthermore, based on a series of energy conservation planning program issued in Beijing, the Long-range Energy Alternatives Planning System (LEAP)-BJ model is developed to study the energy consumption and CO2 emissions of Beijing’s six end-use sectors and the energy conversion sector over 2012–2030 under the BAU scenario and POL scenario. Some results are found in this research: (1) During 2005–2011, the energy consumption kept increasing, while the total CO2 emissions fluctuated obviously in 2008 and 2011. The energy structure and the industrial structure have been optimized to a certain extent. (2) If the policies are completely implemented, the POL scenario is projected to save 21.36 and 35.37 % of the total energy consumption and CO2 emissions than the BAU scenario during 2012 and 2030. (3) The POL scenario presents a more optimized energy structure compared with the BAU scenario, with the decrease of coal consumption and the increase of natural gas consumption. (4) The commerce and service sector and the energy conversion sector will become the largest contributor to energy consumption and CO2 emissions, respectively. The transport sector and the industrial sector are the two most potential sectors in energy savings and carbon reduction. In terms of subscenarios, the energy conservation in transport (TEC) is the most effective one. (5) The macroparameters, such as the GDP growth rate and the industrial structure, have great influence on the urban energy consumption and carbon emissions

Characteristics of transposable element exonization within human and mouse

Insertion of transposed elements within mammalian genes is thought to be an important contributor to mammalian evolution and speciation. Insertion of transposed elements into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Elucidation of the evolutionary constraints that have shaped fixation of transposed elements within human and mouse protein coding genes and subsequent exonization is important for understanding of how the exonization process has affected transcriptome and proteome complexities. Here we show that exonization of transposed elements is biased towards the beginning of the coding sequence in both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs) revealed that exonization of transposed elements can be population-specific, implying that exonizations may enhance divergence and lead to speciation. SNP density analysis revealed differences between Alu and other transposed elements. Finally, we identified cases of primate-specific Alu elements that depend on RNA editing for their exonization. These results shed light on TE fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure

A new concept for the combination of optical interferometers and high-resolution spectrographs

The combination of high spatial and spectral resolution in optical astronomy enables new observational approaches to many open problems in stellar and circumstellar astrophysics. However, constructing a high-resolution spectrograph for an interferometer is a costly and time-intensive undertaking. Our aim is to show that, by coupling existing high-resolution spectrographs to existing interferometers, one could observe in the domain of high spectral and spatial resolution, and avoid the construction of a new complex and expensive instrument. We investigate in this article the different challenges which arise from combining an interferometer with a high-resolution spectrograph. The requirements for the different sub-systems are determined, with special attention given to the problems of fringe tracking and dispersion. A concept study for the combination of the VLTI (Very Large Telescope Interferometer) with UVES (UV-Visual Echelle Spectrograph) is carried out, and several other specific instrument pairings are discussed. We show that the proposed combination of an interferometer with a high-resolution spectrograph is indeed feasible with current technology, for a fraction of the cost of building a whole new spectrograph. The impact on the existing instruments and their ongoing programs would be minimal.Comment: 27 pages, 9 figures, Experimental Astronomy; v2: accepted versio

Speech rhythm: a metaphor?

Is speech rhythmic? In the absence of evidence for a traditional view that languages strive to coordinate either syllables or stress-feet with regular time intervals, we consider the alternative that languages exhibit contrastive rhythm subsisting merely in the alternation of stronger and weaker elements. This is initially plausible, particularly for languages with a steep ‘prominence gradient’, i.e. a large disparity between stronger and weaker elements; but we point out that alternation is poorly achieved even by a ‘stress-timed’ language such as English, and, historically, languages have conspicuously failed to adopt simple phonological remedies that would ensure alternation. Languages seem more concerned to allow ‘syntagmatic contrast’ between successive units and to use durational effects to support linguistic functions than to facilitate rhythm. Furthermore, some languages (e.g. Tamil, Korean) lack the lexical prominence which would most straightforwardly underpin prominence alternation. We conclude that speech is not incontestibly rhythmic, and may even be antirhythmic. However, its linguistic structure and patterning allow the metaphorical extension of rhythm in varying degrees and in different ways depending on the language, and that it is this analogical process which allows speech to be matched to external rhythms