Stochastic and epistemic uncertainty propagation in LCA

Purpose: When performing uncertainty propagation, most LCA practitioners choose to represent uncertainties by single probability distributions and to propagate them using stochastic methods. However the selection of single probability distributions appears often arbitrary when faced with scarce information or expert judgement (epistemic uncertainty). Possibility theory has been developed over the last decades to address this problem. The objective of this study is to present a methodology that combines probability and possibility theories to represent stochastic and epistemic uncertainties in a consistent manner and apply it to LCA. A case study is used to show the uncertainty propagation performed with the proposed method and compare it to propagation performed using probability and possibility theories alone. Methods: Basic knowledge on the probability theory is first recalled, followed by a detailed description of hal-00811827, version 1- 11 Apr 2013 epistemic uncertainty representation using fuzzy intervals. The propagation methods used are the Monte Carlo analysis for probability distribution and an optimisation on alpha-cuts for fuzzy intervals. The proposed method (noted IRS) generalizes the process of random sampling to probability distributions as well as fuzzy intervals, thus making the simultaneous use of both representations possible

Nicotine replacement therapy for agitation and delirium management in the intensive care unit: a systematic review of the literature.

BACKGROUND: Active smokers are prevalent within the intensive care setting and place a significant burden on healthcare systems. Nicotine withdrawal due to forced abstinence on admission may contribute to increased agitation and delirium in this patient group. The aim of this systematic review was to determine whether management of nicotine withdrawal, with nicotine replacement therapy (NRT), reduces agitation and delirium in critically ill patients admitted to the intensive care unit (ICU). METHODS: The following sources were used in this review: MEDLINE, EMBASE, and CINAHL Plus databases. Included studies reported delirium or agitation outcomes in current smokers, where NRT was used as management of nicotine withdrawal, in the intensive care setting. Studies were included regardless of design or number of participants. Data were extracted on ICU classification; study design; population baseline characteristics; allocation and dose of NRT; agitation and delirium assessment methods; and the frequency of agitation, delirium, and psychotropic medication use. RESULTS: Six studies were included. NRT was mostly prescribed for smokers with heavier smoking histories. Three studies reported an association between increased agitation or delirium and NRT use; one study could not find any significant benefit or harm from NRT use; and two described a reduction of symptomatic nicotine withdrawal. A lack of consistent and validated assessment measures, combined with limitations in the quality of reported data, contribute to conflicting results. CONCLUSIONS: Current evidence for the use of NRT in agitation and delirium management in the ICU is inconclusive. An evaluation of risk versus benefit on an individual patient basis should be considered when prescribing NRT. Further studies that consider prognostic balance, adjust for confounders, and employ validated assessment tools are urgently needed

Species differential regulation of COX2 can be described by an NFκB-dependent logic AND gate

Cyclooxygenase 2 (COX2), a key regulatory enzyme of the prostaglandin/eicosanoid pathway, is an important target for anti-inflammatory therapy. It is highly induced by pro-inflammatory cytokines in a Nuclear factor kappa B (NFκB)-dependent manner. However, the mechanisms determining the amplitude and dynamics of this important pro-inflammatory event are poorly understood. Furthermore, there is significant difference between human and mouse COX2 expression in response to the inflammatory stimulus tumor necrosis factor alpha (TNFα). Here, we report the presence of a molecular logic AND gate composed of two NFκB response elements (NREs) which controls the expression of human COX2 in a switch-like manner. Combining quantitative kinetic modeling and thermostatistical analysis followed by experimental validation in iterative cycles, we show that the human COX2 expression machinery regulated by NFκB displays features of a logic AND gate. We propose that this provides a digital, noise-filtering mechanism for a tighter control of expression in response to TNFα, such that a threshold level of NFκB activation is required before the promoter becomes active and initiates transcription. This NFκB-regulated AND gate is absent in the mouse COX2 promoter, most likely contributing to its differential graded response in promoter activity and protein expression to TNFα. Our data suggest that the NFκB-regulated AND gate acts as a novel mechanism for controlling the expression of human COX2 to TNFα, and its absence in the mouse COX2 provides the foundation for further studies on understanding species-specific differential gene regulation

Timeless standards for species delimitation

published_or_final_versio

Disparities in diabetes care: role of the patient's socio-demographic characteristics

<p>Abstract</p> <p>Background</p> <p>The commitment to promoting equity in health is derived from the notion that all human beings have the right to the best attainable health. However, disparities in health care are well-documented. The objectives were to explore disparities in diabetes prevalence, care and control among diabetic patients. The study was conducted by Maccabi Healthcare Services (MHS), an Israeli HMO (health care plan).</p> <p>Methods</p> <p>Retrospective study. The dependent variables were diabetes prevalence, uptake of follow-up examinations, and disease control. The independent variables were socio-economic rank (SER), ethnicity (Arab vs non Arab), supplementary voluntary health insurance (SVHI), and immigration from Former Soviet Union (FSU) countries. Chi Square and Logistic Regression Models were estimated.</p> <p>Results</p> <p>We analyzed 74,953 diabetes patients. Diabetes was more prevalent in males, lower SER patients, Arabs, immigrants and owners of SVHI. Optimal follow up was more frequent among females, lower SERs patients, non Arabs, immigrants and SVHI owners. Patients who were female, had higher SERs, non Arabs, immigrants and SVHI owners achieved better control of the disease. The multivariate analysis revealed significant associations between <it>optimal follow up </it>and age, gender (males), SER (Ranks 1-10), Arabs and SVHI (OR 1.02, 0.95, 1.15, 0.85 and 1.31, respectively); <it>poor diabetes control </it>(HbA1C > 9 gr%) was significantly associated with age, gender (males), Arabs, immigrants, SER (Ranks1-10) and SVHI (OR 0.96, 1.26, 1.38, 0.72, 1.37 and 0.57, respectively); significant associations with <it>LDL control </it>(< 100 gr%) were revealed for age, gender (males) and SVHI (OR 1.02, 1.30 and 1.44, respectively).</p> <p>Conclusion</p> <p>Disparities in diabetes prevalence, care and control were revealed according to population sub-group. MHS has recently established a comprehensive strategy and action plan, aimed to reduce disparities among members of low socioeconomic rank and Arab ethnicity, sub-groups identified in our study as being at risk for less favorable health outcomes.</p

Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer

BACKGROUND: Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial. METHODS: Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured. RESULTS: Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers. CONCLUSION: This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study

Purpose Recalibration and determining discriminative power, internationally, of the existing delirium prediction model (PRE-DELIRIC) for intensive care patients. Methods A prospective multicenter cohort study was performed in eight intensive care units (ICUs) in six countries. The ten predictors (age, APACHE-II, urgent and admission category, infection, coma, sedation, morphine use, urea level, metabolic acidosis) were collected within 24 h after ICU admission. The confusion assessment method for the intensive care unit (CAM-ICU) was used to identify ICU delirium. CAM-ICU screening compliance and inter-rater reliability measurements were used to secure the quality of the data. Results A total of 2,852 adult ICU patients were screened of which 1,824 (64 %) were eligible for the study. Main reasons for exclusion were length of stay <1 day (19.1 %) and sustained coma (4.1 %). CAM-ICU compliance was mean (SD) 82 ± 16 % and inter-rater reliability 0.87 ± 0.17. The median delirium incidence was 22.5 % (IQR 12.8–36.6 %). Although the incidence of all ten predictors differed significantly between centers, the area under the receiver operating characteristic (AUROC) curve of the eight participating centers remained good: 0.77 (95 % CI 0.74–0.79). The linear predictor and intercept of the prediction rule were adjusted and resulted in improved re-calibration of the PRE-DELIRIC model. Conclusions In this multinational study, we recalibrated the PRE-DELIRIC model. Despite differences in the incidence of predictors between the centers in the different countries, the performance of the PRE-DELIRIC-model remained good. Following validation of the PRE-DELIRIC model, it may facilitate implementation of strategies to prevent delirium and aid improvements in delirium management of ICU patients

Enhancement of stress tolerance in transgenic tobacco plants constitutively expressing AtIpk2β, an inositol polyphosphate 6-/3-kinase from Arabidopsis thaliana

Inositol phosphates (IPs) and their turnover products have been implicated to play important roles in stress signaling in eukaryotic cells. In higher plants genes encoding inositol polyphosphate kinases have been identified previously, but their physiological functions have not been fully resolved. Here we expressed Arabidopsis inositol polyphosphate 6-/3-kinase (AtIpk2β) in two heterologous systems, i.e. the yeast Saccharomycescerevisiae and in tobacco (Nicotiana tabacum), and tested the effect on abiotic stress tolerance. Expression of AtIpk2β rescued the salt-, osmotic- and temperature-sensitive growth defects of a yeast mutant strain (arg82Δ) that lacks inositol polyphosphate multikinase activity encoded by the ARG82/IPK2 gene. Transgenic tobacco plants constitutively expressing AtIpk2β under the control of the Cauliflower Mosaic Virus 35S promoter were generated and found to exhibit improved tolerance to diverse abiotic stresses when compared to wild type plants. Expression patterns of various stress responsive genes were enhanced, and the activities of anti-oxidative enzymes were elevated in transgenic plants, suggesting a possible involvement of AtIpk2β in plant stress responses

Natural course of behavioral addictions: A 5-year longitudinal study

BACKGROUND: Resolving the theoretical controversy on the labeling of an increasing number of excessive behaviors as behavioral addictions may also be facilitated by more empirical data on these behavioral problems. For instance, an essential issue to the classification of psychiatric disorders is information on their natural course. However, longitudinal research on the chronic vs. episodic nature of behavioral addictions is scarce. The aim of the present study, therefore, was to provide data on prevalence, substance use comorbidity, and five-year trajectories of six excessive behaviors—namely exercising, sexual behavior, shopping, online chatting, video gaming, and eating. METHODS: Analyses were based on the data of the Quinte Longitudinal Study, where a cohort of 4,121 adults from Ontario, Canada was followed for 5 years (2006 to 2011). The response rate was 21.3%, while retention rate was 93.9%. To assess the occurrence of each problem behavior, a single self-diagnostic question asked people whether their over-involvement in the behavior had caused significant problems for them in the past 12 months. To assess the severity of each problem behavior reported, the Behavioral Addiction Measure was administered. A mixed design ANOVA was used to investigate symptom trajectories over time for each problem behavior and whether these symptom trajectories varied as a function of sex. RESULTS: The large majority of people reported having problematic over-involvement for just one of these behaviors and just in a single time period. A main effect of time was found for each problem behavior, indicating a moderately strong decrease in symptom severity across time. The time x sex interaction was insignificant in each model indicating that the decreasing trend is similar for males and females. The data also showed that help seeking was very low in the case of excessive sexual behavior, shopping, online chatting, and video gaming but substantially more prevalent in the case of excessive eating and exercising. CONCLUSIONS: The present results indicate that self-identified excessive exercising, sexual behavior, shopping, online chatting, video gaming, and/or eating tend to be fairly transient for most people. This aspect of the results is inconsistent with conceptualizations of addictions as progressive in nature, unless treated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-015-0383-3) contains supplementary material, which is available to authorized users