Comparison of different objective functions for parameterization of simple respiration models

The eddy covariance measurements of carbon dioxide fluxes collected around the world offer a rich source for detailed data analysis. Simple, aggregated models are attractive tools for gap filling, budget calculation, and upscaling in space and time. Key in the application of these models is their parameterization and a robust estimate of the uncertainty and reliability of their predictions. In this study we compared the use of ordinary least squares (OLS) and weighted absolute deviations (WAD, which is the objective function yielding maximum likelihood parameter estimates with a double exponential error distribution) as objective functions within the annual parameterization of two respiration models: the Q10 model and the Lloyd and Taylor model. We introduce a new parameterization method based on two nonparametric tests in which model deviation (Wilcoxon test) and residual trend analyses (Spearman test) are combined. A data set of 9 years of flux measurements was used for this study. The analysis showed that the choice of the objective function is crucial, resulting in differences in the estimated annual respiration budget of up to 40%. The objective function should be tested thoroughly to determine whether it is appropriate for the application for which the model will be used. If simple models are used to estimate a respiration budget, a trend test is essential to achieve unbiased estimates over the year. The analyses also showed that the parameters of the Lloyd and Taylor model are highly correlated and difficult to determine precisely, thereby limiting the physiological interpretability of the parameter

TAUOLA the library for tau lepton decay, and KKMC/KORALB/KORALZ/... status report

The status of the Monte Carlo programs for the simulation of the $\tau$ lepton production in high energy accelerator experiments and decay is reviewed. In particular, the status of the following packages is discussed: (i) TAUOLA for tau-lepton decay, (ii) PHOTOS for radiative corrections in decays, (iii) KORALB, KORALZ, KKMC packages for tau-pair production in e+e- collisions and (iv) universal interface of TAUOLA for the decay of tau-leptons produced by``any'' generator. Special emphasis on requirements from new and future experiments is given. Some considerations about the software organization necessary to keep simultaneously distinct physics initializations for TAUOLA are also included.Comment: latex 7 pages, including 1 table and 5 figure files, all 6 in postscript format. Presented on 'Sixth international workshop on tau lepton physics', Victoria Canada, September 200

An Alternative Approach to the Calculation and Analysis of Connectivity in the World City Network

Empirical research on world cities often draws on Taylor's (2001) notion of an 'interlocking network model', in which office networks of globalized service firms are assumed to shape the spatialities of urban networks. In spite of its many merits, this approach is limited because the resultant adjacency matrices are not really fit for network-analytic calculations. We therefore propose a fresh analytical approach using a primary linkage algorithm that produces a one-mode directed graph based on Taylor's two-mode city/firm network data. The procedure has the advantage of creating less dense networks when compared to the interlocking network model, while nonetheless retaining the network structure apparent in the initial dataset. We randomize the empirical network with a bootstrapping simulation approach, and compare the simulated parameters of this null-model with our empirical network parameter (i.e. betweenness centrality). We find that our approach produces results that are comparable to those of the standard interlocking network model. However, because our approach is based on an actual graph representation and network analysis, we are able to assess cities' position in the network at large. For instance, we find that cities such as Tokyo, Sydney, Melbourne, Almaty and Karachi hold more strategic and valuable positions than suggested in the interlocking networks as they play a bridging role in connecting cities across regions. In general, we argue that our graph representation allows for further and deeper analysis of the original data, further extending world city network research into a theory-based empirical research approach.Comment: 18 pages, 9 figures, 2 table

Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group

BACKGROUND: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. PATIENTS AND METHODS: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m(2) alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. RESULTS: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). CONCLUSIONS: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance status

Peribiliary glands are key in regeneration of the human biliary epithelium after severe bile duct injury

Peribiliary glands (PBG) are a source of stem/progenitor cells organized in a cellular network encircling large bile ducts. Severe cholangiopathy with loss of luminal biliary epithelium has been proposed to activate PBG, resulting in cell proliferation and differentiation to restore biliary epithelial integrity. However, formal evidence for this concept in human livers is lacking. We, therefore, developed a novel ex vivo model using precision-cut slices of extrahepatic human bile ducts obtained from discarded donor livers, providing an intact anatomical organization of cell structures, to study spatiotemporal differentiation and migration of PBG cells after severe biliary injury. Post-ischemic bile duct slices were incubated in oxygenated culture medium for up to a week. At baseline, severe tissue injury was evident with loss of luminal epithelial lining and mural stroma necrosis. In contrast, PBG remained relatively well preserved and different reactions of PBG were noted, including PBG dilatation, cell proliferation and maturation. Proliferation of PBG cells increased after 24 h of oxygenated incubation, reaching a peak after 72 h. Proliferation of PBG cells was paralleled by a reduction in PBG apoptosis and differentiation from a primitive and pluripotent (Nanog+/Sox9+) to a mature (CFTR+/secretin receptor+) and activated phenotype (increased expression of HIF-1α, Glut-1, and VEGF-A). Migration of proliferating PBG cells in our ex vivo model was unorganized, but resulted in generation of epithelial monolayers at stromal surfaces. CONCLUSION: Human PBG contain biliary progenitor cells and are able to respond to bile duct epithelial loss with proliferation, differentiation, and maturation to restore epithelial integrity. The ex vivo spatiotemporal behaviour of human PBG cells provides evidence for a pivotal role of PBG in biliary regeneration after severe injury. This article is protected by copyright. All rights reserved

Staging clavicular development on MRI : pitfalls and suggestions for age estimation

Background MRI of the clavicle's sternal end has been studied for age estimation. Several pitfalls have been noted, but how they affect age estimation performance remains unclear. Purpose/Hypothesis To further study these pitfalls and to make suggestions for a proper use of clavicle MRI for forensic age estimation. Our hypotheses were that age estimation would benefit from 1) discarding stages 1 and 4/5; 2) including advanced substages 3aa, 3ab, and 3ac; 3) taking both clavicles into account; and 4) excluding morphological variants. Study Type Prospective cross-sectional. Population Healthy Caucasian volunteers between 11 and 30 years old (524; 277 females, 247 males). Field Strength/Sequence 3T, T-1-weighted gradient echo volumetric interpolated breath-hold examination (VIBE) MR-sequence. Assessment Four observers applied the most elaborate staging technique for long bone development that has been described in the current literature (including stages, substages, and advanced substages). One of the observers repeated a random selection of the assessments in 110 participants after a 2-week interval. Furthermore, all observers documented morphological variants. Statistical Tests Weighted kappa quantified reproducibility of staging. Bayes' rule was applied for age estimation with a continuation ratio model for the distribution of the stages. According to the hypotheses, different models were tested. Mean absolute error (MAE) differences between models were compared, as were MAEs between cases with and without morphological variants. Results Weighted kappa equaled 0.82 for intraobserver and ranged between 0.60 and 0.64 for interobserver agreement. Stages 1 and 4/5 were allocated interchangeably in 4.3% (54/1258). Age increased steadily in advanced substages of stage 3, but improvement in age estimation was not significant (right P = 0.596; left P = 0.313). The model that included both clavicles and discarded stages 1 and 4/5 yielded an MAE of 1.97 years, a root mean squared error of 2.60 years, and 69% correctly classified minors. Morphological variants rendered significantly higher MAEs (right 3.84 years, P = 0.015; left 2.93 years, P = 0.022). Data Conclusion Our results confirmed hypotheses 3) and 4), while hypotheses 1) and 2) remain to be investigated in larger studies. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019

Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy

Exome sequencing revealed a homozygous missense mutation (c.317C>G [p.Arg106Pro]) in POC1B, encoding POC1 centriolar protein B, in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy and compound-heterozygous POC1B mutations (c.199_201del [p.G1n67del] and c.810+1G>T) in an unrelated person with cone-rod dystrophy. Upon overexpression of POC1B in human TERT-immortalized retinal pigment epithelium 1 cells, the encoded wild-type protein localized to the basal body of the primary cilium, whereas this localization was lost for p.Arg106Pro and p.G1n67del variant forms of POC1B. Morpholino-oligonucleotide-induced knockdown of poc1b translation in zebrafish resulted in a dose-dependent small-eye phenotype, impaired optokinetic responses, and decreased length of photoreceptor outer segments. These ocular phenotypes could partially be rescued by wild-type human POC1B mRNA, but not by c.199_201del and c.317C>G mutant human POC1B mRNAs. Yeast two-hybrid screening of a human retinal cDNA library revealed FAM161A as a binary interaction partner of POC1B. This was confirmed in coimmunoprecipitation and colocalization assays, which both showed loss of FAM161A interaction with p.Arg106Pro and p.G1n67del variant forms of POC1B. FAM161A was previously implicated in autosomal-recessive retinitis pigmentosa and shown to be located at the base of the photoreceptor connecting cilium, where it interacts with several other ciliopathy-associated proteins. Altogether, this study demonstrates that POC1B mutations result in a defect of the photoreceptor sensory cilium and thus affect cone and rod photoreceptors