A proposed psychological model of driving automation

This paper considers psychological variables pertinent to driver automation. It is anticipated that driving with automated systems is likely to have a major impact on the drivers and a multiplicity of factors needs to be taken into account. A systems analysis of the driver, vehicle and automation served as the basis for eliciting psychological factors. The main variables to be considered were: feed-back, locus of control, mental workload, driver stress, situational awareness and mental representations. It is expected that anticipating the effects on the driver brought about by vehicle automation could lead to improved design strategies. Based on research evidence in the literature, the psychological factors were assembled into a model for further investigation

The "Artificial Mathematician" Objection: Exploring the (Im)possibility of Automating Mathematical Understanding

Reuben Hersh confided to us that, about forty years ago, the late Paul Cohen predicted to him that at some unspecified point in the future, mathematicians would be replaced by computers. Rather than focus on computers replacing mathematicians, however, our aim is to consider the (im)possibility of human mathematicians being joined by “artificial mathematicians” in the proving practice—not just as a method of inquiry but as a fellow inquirer

Network meta-analysis on the log-hazard scale, combining count and hazard ratio statistics accounting for multi-arm trials: a tutorial.

BACKGROUND: Data on survival endpoints are usually summarised using either hazard ratio, cumulative number of events, or median survival statistics. Network meta-analysis, an extension of traditional pairwise meta-analysis, is typically based on a single statistic. In this case, studies which do not report the chosen statistic are excluded from the analysis which may introduce bias. METHODS: In this paper we present a tutorial illustrating how network meta-analyses of survival endpoints can combine count and hazard ratio statistics in a single analysis on the hazard ratio scale. We also describe methods for accounting for the correlations in relative treatment effects (such as hazard ratios) that arise in trials with more than two arms. Combination of count and hazard ratio data in a single analysis is achieved by estimating the cumulative hazard for each trial arm reporting count data. Correlation in relative treatment effects in multi-arm trials is preserved by converting the relative treatment effect estimates (the hazard ratios) to arm-specific outcomes (hazards). RESULTS: A worked example of an analysis of mortality data in chronic obstructive pulmonary disease (COPD) is used to illustrate the methods. The data set and WinBUGS code for fixed and random effects models are provided. CONCLUSIONS: By incorporating all data presentations in a single analysis, we avoid the potential selection bias associated with conducting an analysis for a single statistic and the potential difficulties of interpretation, misleading results and loss of available treatment comparisons associated with conducting separate analyses for different summary statistics

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

CT pulmonary angiography: an over-utilized imaging modality in hospitalized patients with suspected pulmonary embolism

Aims: To determine if computed tomographic pulmonary angiography (CTPA) was overemployed in the evaluation of hospitalized patients with suspected acute pulmonary embolism (PE). Methods: Data were gathered retrospectively on hospitalized patients (n=185) who had CTPA for suspected PE between June and August 2009 at our institution. Results: CTPA was done in 185 hospitalized patients to diagnose acute PE based on clinical suspicion. Of these, 30 (16.2%) patients were tested positive for acute PE on CTPA. The Well's pretest probability for PE was low, moderate, and high in 77 (41.6%), 83 (44.9%), and 25 (13.5%) patients, respectively. Out of the 30 PE-positive patients, pretest probability was low in 2 (6.6%), moderate in 20 (66.7%), and high in 8 (26.6%) (p=0.003). Modified Well's criteria applied to all patients in our study revealed 113 (61%) with low and 72 (39%) with high clinical pretest probability. When modified Well's criteria was applied to 30 PE-positive patients, 10 (33.3%) and 20 (66.6%) were found to have low and high pretest probability, respectively (p=0.006). D-dimer assay was done in 30 (16.2%) of the inpatients with suspected PE and all of them were found to have elevated levels. A lower extremity duplex ultrasound confirmed deep venous thrombosis in 17 (9.1%) of the patients with suspected PE, at least 1 week prior to having CTPA. Conclusion: Understanding the recommended guidelines, evidence-based literature, and current concepts in evaluation of patients with suspected acute PE will reduce unnecessary CTPA examinations

An experimental model of rhinovirus induced chronic obstructive pulmonary disease exacerbations: a pilot study

BACKGROUND: Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation. Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood. Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists. METHODS: We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients. We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II). Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage. RESULTS: All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage. These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV(1). There were no severe exacerbations or other adverse events. CONCLUSION: Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation

A critical base pair in k-turns that confers folding characteristics and correlates with biological function

Kink turns (k-turns) are widespread elements in RNA that mediate tertiary contacts by kinking the helical axis. We have found that the ability of k-turns to undergo ion-induced folding is conferred by a single base pair that follows the conserved A·G pairs, that is, the 3b·3n position. A Watson–Crick pair leads to an inability to fold in metal ions alone, while 3n=G or 3b=C (but not both) permits folding. Crystallographic study reveals two hydrated metal ions coordinated to O6 of G3n and G2n of Kt-7. Removal of either atom impairs Mg(2+)-induced folding in solution. While SAM-I riboswitches have 3b·3n sequences that would predispose them to ion-induced folding, U4 snRNA are strongly biased to an inability to such folding. Thus riboswitch sequences allow folding to occur independently of protein binding, while U4 should remain unfolded until bound by protein. The empirical rules deduced for k-turn folding have strong predictive value

Ki67 proliferation in core biopsies versus surgical samples - a model for neo-adjuvant breast cancer studies

Background: An increasing number of neo-adjuvant breast cancer studies are being conducted and a novel model for tumor biological studies, the "window-of-opportunity" model, has revealed several advantages. Change in tumor cell proliferation, estimated by Ki67-expression in pre-therapeutic core biopsies versus post-therapeutic surgical samples is often the primary end-point. The aim of the present study was to investigate potential differences in proliferation scores between core biopsies and surgical samples when patients have not received any intervening anti-cancer treatment. Also, a lack of consensus concerning Ki67 assessment may raise problems in the comparison of neo-adjuvant studies. Thus, the secondary aim was to present a novel model for Ki67 assessment. Methods: Fifty consecutive breast cancer cases with both a core biopsy and a surgical sample available, without intervening neo-adjuvant therapy, were collected and tumor proliferation (Ki67, MIB1 antibody) was assessed immunohistochemically. A theoretical model for the assessment of Ki67 was constructed based on sequential testing of the null hypothesis 20% Ki67-positive cells versus the two-sided alternative more or less than 20% positive cells.. Results: Assessment of Ki67 in 200 tumor cells showed an absolute average proliferation difference of 3.9% between core biopsies and surgical samples (p = 0.046, paired t-test) with the core biopsies being the more proliferative sample type. A corresponding analysis on the log-scale showed the average relative decrease from the biopsy to the surgical specimen to be 19% (p = 0.063, paired t-test on the log-scale). The difference was significant when using the more robust Wilcoxon matched-pairs signed-ranks test (p = 0.029). After dichotomization at 20%, 12 of the 50 sample pairs had discrepant proliferation status, 10 showed high Ki67 in the core biopsy compared to two in the surgical specimen (p = 0.039, McNemar's test). None of the corresponding results for 1000 tumor cells were significant - average absolute difference 2.2% and geometric mean of the ratios 0.85 (p = 0.19 and p = 0.18, respectively, paired t-tests, p = 0.057, Wilcoxon's test) and an equal number of discordant cases after dichotomization. Comparing proliferation values for the initial 200 versus the final 800 cancer cells showed significant absolute differences for both core biopsies and surgical samples 5.3% and 3.2%, respectively (p < 0.0001, paired t-test). Conclusions: A significant difference between core biopsy and surgical sample proliferation values was observed despite no intervening therapy. Future neo-adjuvant breast cancer studies may have to take this into consideration

Occupation, smoking, and chronic obstructive respiratory disorders: a cross sectional study in an industrial area of Catalonia, Spain

BACKGROUND: Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction. We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain. METHODS: We interviewed 576 subjects of both sexes aged 20–70 years (response rate 80%) randomly selected from census rolls, using the ATS questionnaire. Forced spirometry was performed by 497 subjects according to ATS normative. RESULTS: Lifetime occupational exposure to dust, gases or fumes was reported by 52% of the subjects (63% in men, 41% in women). Textile industry was the most frequently reported job in relation to these exposures (39%). Chronic cough, expectoration and wheeze were more prevalent in exposed subjects with odds ratios ranging from 1.7 to 2.0 being highest among never-smokers (2.1 to 4.3). Lung function differences between exposed and unexposed subjects were dependent on duration of exposure, but not on smoking habits. Subjects exposed more than 15 years to dusts, gases or fumes had lower lung function values (FEV(1 )-80 ml, 95% confidence interval (CI) -186 to 26; MMEF -163 ml, CI -397 to 71; FEV(1)/FVC ratio -1.7%, CI -3.3 to -0.2) than non-exposed. CONCLUSION: Chronic bronchitis symptoms and airflow obstruction are associated with occupational exposures in a population with a high employment in the textile industry. Lung function impairment was related to the duration of occupational exposure, being independent of the effect of smoking

Molecular diversity of phospholipase D in angiosperms

BACKGROUND: The phospholipase D (PLD) family has been identified in plants by recent molecular studies, fostered by the emerging importance of plant PLDs in stress physiology and signal transduction. However, the presence of multiple isoforms limits the power of conventional biochemical and pharmacological approaches, and calls for a wider application of genetic methodology. RESULTS: Taking advantage of sequence data available in public databases, we attempted to provide a prerequisite for such an approach. We made a complete inventory of the Arabidopsis thaliana PLD family, which was found to comprise 12 distinct genes. The current nomenclature of Arabidopsis PLDs was refined and expanded to include five newly described genes. To assess the degree of plant PLD diversity beyond Arabidopsis we explored data from rice (including the genome draft by Monsanto) as well as cDNA and EST sequences from several other plants. Our analysis revealed two major PLD subfamilies in plants. The first, designated C2-PLD, is characterised by presence of the C2 domain and comprises previously known plant PLDs as well as new isoforms with possibly unusual features-catalytically inactive or independent on Ca(2+). The second subfamily (denoted PXPH-PLD) is novel in plants but is related to animal and fungal enzymes possessing the PX and PH domains. CONCLUSIONS: The evolutionary dynamics, and inter-specific diversity, of plant PLDs inferred from our phylogenetic analysis, call for more plant species to be employed in PLD research. This will enable us to obtain generally valid conclusions