Query exhaustivity, relevance feedback and search success in automatic and interactive query expansion

This study explored how the expression of search facets and relevance feedback by users was related to search success in interactive and automatic query expansion in the course of the search process. Search success was measured both in the number of relevant documents retrieved and relevance scores of these items based on a four point scaling. Research design consisted of 26 users searching for four TREC topics in Okapi IR system, half using interactive and half automatic query expansion based on RF. The search logs were recorded, and the users filled in a questionnaire for each topic concerning various features of searching. The results showed that the exhaustivity of the query was the most significant predictor of search success, and that interactive expansion led to better search success than automatic one

Identifying the inheritable component of human thymic T cell repertoire generation in monozygous twins

We have analyzed T cell receptor repertoires in a unique set of thymus samples from a pair of monozygotic twins. While genetics affect the V(D)J rearrangement and generation of junctional sequences, the thymic selections seem largely stochastic and import no detectable inheritable effect at clonal level.Non peer reviewe

Uncertainty in maritime risk analysis: Extended case study on chemical tanker collisions

Uncertainty is inherent to risk analysis. Therefore, it is extremely important to properly address the issue of uncertainty. In the field of risk analysis for maritime transportation systems, the effect of uncertainty is rarely discussed or quantified. For this reason, this article discusses a case study dealing with risk analysis for a chemical spill in the Gulf of Finland and analyses the related uncertainties by adopting a systematic framework. Risk is assessed in terms of the expected spill frequency and spill volumes caused by collisions between ships and chemical tankers in the Gulf of Finland. This is done by applying a collision consequence with a novel approach-to-collision-speed linkage model and Gulf of Finland-specific causation factors, which are based on reanalysing accident data. This article also presents a metamodel for assessing collision probability with initial vessel speeds for any given scenario where a chemical tanker is about to be struck by another vessel. Even when conducting a risk analysis using state-of-the-art methods, there is still a medium-high degree of uncertainty in the model presented in this article, which only becomes apparent when conducting a systematic uncertainty assessment analysis. However, an uncertainty assessment is an important part of quantitative maritime risk analysis. For this purpose, a qualitative framework for uncertainty assessment analysis is introduced for general use in the field of maritime risk analysis.</p

Radium-223 dichloride treatment in metastatic castration-resistant prostate cancer in Finland: A real-world evidence multicenter study

Background: Radium-233 dichloride is an alpha emitter that specifically targets bone metastases in prostate cancer. Results of a previously reported phase III randomized trial showed survival benefit for radium-223 compared to best supportive care in castration-resistant prostate cancer (CRPC) with bone metastases. However, real-world data are also needed with wider inclusion criteria.Methods: We report results of a retrospective multicenter study including all patients with metastatic CRPC treated with radium-223 in all five university hospitals in Finland since the introduction of the treatment. We identified 160 patients who had received radium-223 in Finland in 2014-2019.Results: The median overall survival (OS) was 13.8 months (range 0.5-57 months), and the median real-world progression-free survival (rwPFS) was 4.9 months (range 0.5-29.8 months). Alkaline phosphatase (ALP) values within the normal range before and during the radium-223 treatment or the reduction of elevated ALP to normal range during treatment were associated with better OS when compared to elevated ALP values before and during treatment (p Conclusion: Radium-223 was well tolerated in routine clinical practice, and most patients achieved pain relief. Pain relief, ALP normalization, lower baseline PSA, and PSA decrease during radium-223 treatment were prognostic for better survival. The efficacy of radium-223 in mCRPC as estimated using OS was comparable to earlier randomized trial in this retrospective real-world study. Our results support using radium-223 for mCRPC patients with symptomatic bone metastases even in the era of new-generation androgen receptor-targeted agents.</p

Emissions from mechanically-biologically treated waste landfills at field scale

Modern waste management tends towards greater sustainability in landfilling, with the implementation of strategies such as the pretreatment of solid waste. This work assesses the behaviour of rejects from a refining stage of mechanically-biologically treated municipal solid waste at the landfill. The main results of 18 months' monitoring of an experimental pilot cell with waste from a full-scale plant are presented. This first stages are expected to be the most problematic period for this type of waste. The evolution of the temperature and the composition of leachate and gas at various points within the cell are included. During the first weeks, pollutant concentrations in the leachate exceeded the reference ranges in the literature, coinciding with a rapid onset of methanogenic conditions. However, there was a quick wash, reducing concentrations to below one third of the initial values before the first year. pH values influenced concentrations of some pollutants such as copper. These results indicate that, right from the beginning of disposal, such facilities should be prepared to treat a high pollution load in the leachate and install the gas emissions control elements due to the rapid onset of methanogenesis.This work is funded by the Spanish Ministry of Economics and Competitiveness through the CTM2012-35055 project. The project is financed jointly by the European Regional Development Fund, FEDER (operational period 2007-2013). The authors wish to thank the Government of Cantabria, through the public company MARE, and TirCantabria, the landfill operator company, for their collaboration

Collagen XIII secures pre- and postsynaptic integrity of the neuromuscular synapse

© The Author 2017. Published by Oxford University Press. All rights reserved. Both transmembrane and extracellular cues, one of which is collagen XIII, regulate the formation and function of the neuromuscular synapse, and their absence results in myasthenia. We show that the phenotypical changes in collagen XIII knock-out mice are milder than symptoms in human patients, but the Col13a1 -/- mice recapitulate major muscle findings of congenital myasthenic syndrome type 19 and serve as a disease model. In the lack of collagen XIII neuromuscular synapses do not reach full size, alignment, complexity and function resulting in reduced muscle strength. Collagen XIII is particularly important for the preterminal integrity, and when absent, destabilization of the motor nerves results in muscle regeneration and in atrophy especially in the case of slow muscle fibers. Collagen XIII was found to affect synaptic integrity through binding the ColQ tail of acetylcholine esterase. Although collagen XIII is a muscle-bound transmembrane molecule, it also undergoes ectodomain shedding to become a synaptic basal lamina component. We investigated the two forms' roles by novel Col13a1 tm/tm mice in which ectodomain shedding is impaired. While postsynaptic maturation, terminal branching and neurotransmission was exaggerated in the Col13a1 tm/tm mice, the transmembrane form's presence sufficed to prevent defects in transsynaptic adhesion, Schwann cell invagination/retraction, vesicle accumulation and acetylcholine receptor clustering and acetylcholinesterase dispersion seen in the Col13a1 -/- mice, pointing to the transmembrane form as the major conductor of collagen XIII effects. Altogether, collagen XIII secures postsynaptic, synaptic and presynaptic integrity, and it is required for gaining and maintaining normal size, complexity and functional capacity of the neuromuscular synapse

Activation Status of Wnt/ß-Catenin Signaling in Normal and Neoplastic Breast Tissues: Relationship to HER2/neu Expression in Human and Mouse

Wnt/ß-catenin signaling is strongly implicated in neoplasia, but the role of this pathway in human breast cancer has been controversial. Here, we examined Wnt/ß-catenin pathway activation as a function of breast cancer progression, and tested for a relationship with HER2/neu expression, using a human tissue microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS), and invasive carcinomas. Cores were scored for membranous ß-catenin, a key functional component of adherens junctions, and for nucleocytoplasmic ß-catenin, a hallmark of Wnt/ß-catenin pathway activation. Only 82% of benign samples exhibited membrane-associated ß-catenin, indicating a finite frequency of false-negative staining. The frequency of membrane positivity was similar in DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001), consistent with loss of adherens junctions during acquisition of invasiveness. Negative membrane status in cancers correlated with higher grade (P = 0.04) and estrogen receptor-negative status (P = 0.03), both indices of poor prognosis. Unexpectedly, a substantial frequency of nucleocytoplasmic ß-catenin was observed in benign breast tissues (36%), similar to that in carcinomas (35%). Positive-staining basal nuclei observed in benign breast may identify putative stem cells. An increased frequency of nucleocytoplasmic ß-catenin was observed in DCIS tumors (56%), suggesting that pathway activation may be an early event in human breast neoplasia. A correlation was observed between HER2/neu expression and nucleocytoplasmic ß-catenin in node-positive carcinomas (P = 0.02). Furthermore, cytoplasmic ß-catenin was detected in HER2/neu-induced mouse mammary tumors. The Axin2NLSlacZ mouse strain, a previously validated reporter of mammary Wnt/ß-catenin signaling, was utilized to define in vivo transcriptional consequences of HER2/neu-induced ß-catenin accumulation. Discrete hyperplastic foci observed in mammary glands from bigenic MMTV/neu, Axin2NLSlacZ mice, highlighted by robust ß-catenin/TCF signaling, likely represent the earliest stage of mammary intraepithelial neoplasia in MMTV/neu mice. Our study thus provides provocative evidence for Wnt/ß-catenin signaling as an early, HER2/neu-inducible event in breast neoplasia

Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life

Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness

Abstract: Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (N ROP = 79, N ROD = 30, N CHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (N ROP = 61, N ROD = 100, N CHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. Clinical trial registry name: German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/ . Clinical trial registry number: DRKS00005042