Representing Polar Questions

Although the linguistic properties of polar questions have been extensively studied, comparatively little is known about how polar questions are processed in real time. In this paper, we report on three eye-tracking experiments on the processing of positive and negative polar questions in English and French. Our results show that in the early stages, participants pay attention to both positive and negative states of affairs for both positive and negative questions. In the late stages, positive and certain negative polar questions were associated with a bias for the positive state, and this bias appears to be pragmatic in nature. We suggest that different biases in mental representations reflect the hearer’s reasoning about the speaker’s purposes of enquiry

Strategic Deception in Adults with Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is often associated with impaired perspective-taking skills. Deception is an important indicator of perspective-taking, and therefore may be thought to pose difficulties to people with ASD (e.g., Baron-Cohen in J Child Psychol Psychiatry 3:1141–1155, 1992). To test this hypothesis, we asked participants with and without ASD to play a computerised deception game. We found that participants with ASD were equally likely—and in complex cases of deception even more likely—to deceive and detect deception, and learned deception at a faster rate. However, participants with ASD initially deceived less frequently, and were slower at detecting deception. These results suggest that people with ASD readily engage in deception but may do so through conscious and effortful reasoning about other people’s perspective

Nitric oxide synthase inhibition results in synergistic anti-tumour activity with melphalan and tumour necrosis factor alpha-based isolated limb perfusions

Nitric oxide (NO) is an important molecule in regulating tumour blood flow and stimulating tumour angiogenesis. Inhibition of NO synthase by L-NAME might induce an anti-tumour effect by limiting nutrients and oxygen to reach tumour tissue or affecting vascular growth. The anti-tumour effect of L-NAME after systemic administration was studied in a renal subcapsular CC531 adenocarcinoma model in rats. Moreover, regional administration of L-NAME, in combination with TNF and melphalan, was studied in an isolated limb perfusion (ILP) model using BN175 soft-tissue sarcomas. Systemic treatment with L-NAME inhibited growth of adenocarcinoma significantly but was accompanied by impaired renal function. In ILP, reduced tumour growth was observed when L-NAME was used alone. In combination with TNF or melphalan, L-NAME increased response rates significantly compared to perfusions without L-NAME (0–64% and 0–63% respectively). An additional anti-tumour effect was demonstrated when L-NAME was added to the synergistic combination of melphalan and TNF (responses increased from 70 to 100%). Inhibition of NO synthase reduces tumour growth both after systemic and regional (ILP) treatment. A synergistic anti-tumour effect of L-NAME is observed in combination with melphalan and/or TNF using ILP. These results indicate a possible role of L-NAME for the treatment of solid tumours in a systemic or regional setting. © 2000 Cancer Research Campaig

Methods for calculating nonconcave entropies

Five different methods which can be used to analytically calculate entropies that are nonconcave as functions of the energy in the thermodynamic limit are discussed and compared. The five methods are based on the following ideas and techniques: i) microcanonical contraction, ii) metastable branches of the free energy, iii) generalized canonical ensembles with specific illustrations involving the so-called Gaussian and Betrag ensembles, iv) restricted canonical ensemble, and v) inverse Laplace transform. A simple long-range spin model having a nonconcave entropy is used to illustrate each method.Comment: v1: 22 pages, IOP style, 7 color figures, contribution for the JSTAT special issue on Long-range interacting systems. v2: Open problem and references added, minor typos corrected, close to published versio

TNF- α augments intratumoural concentrations of doxorubicin in TNF- α -based isolated limb perfusion in rat sarcoma models and enhances anti-tumour effects

We have shown previously that isolated limb perfusion (ILP) in sarcoma-bearing rats results in high response rates when melphalan is used in combination with tumour necrosis factor alpha (TNF-α). This is in line with observations in patients. Here we show that ILP with doxorubicin in combination with TNF-α has comparable effects in two different rat sarcoma tumour models. The addition of TNF-α exhibits a synergistic anti-tumour effect, resulting in regression of the tumour in 54% and 100% of the cases for the BN175-fibrosarcoma and the ROS-1 osteosarcoma respectively. The combination is shown to be mandatory for optimal tumour response. The effect of high dose TNF-α on the activity of cytotoxic agents in ILP is still unclear. We investigated possible modes by which TNF-α could modulate the activity of doxorubicin. In both tumour models increased accumulation of doxorubicin in tumour tissue was found: 3.1-fold in the BN175 and 1.8-fold in the ROS-1 sarcoma after ILP with doxorubicin combined with TNF-α in comparison with an ILP with doxorubicin alone. This increase in local drug concentration may explain the synergistic anti-tumour responses after ILP with the combination. In vitro TNF-α fails to augment drug uptake in tumour cells or to increase cytotoxicity of the drug. These findings make it unlikely that TNF-α directly modulates the activity of doxorubicin in vivo. As TNF-α by itself has no or only minimal effect on tumour growth, an increase in local concentrations of chemotherapeutic drugs might well be the main mechanism for the synergistic anti-tumour effects. © 2000 Cancer Research Campaig

Impaired neutralising antibody formation and high transduction efficacy after isolated hepatic perfusion with adenoviral vectors

Local adenoviral gene transfer can be performed by means of isolated hepatic perfusion (IHP). This methodology is a very effective and safe way to deliver adenoviral vectors. We studied the immune response after IHP, A decreased neutralising antibody formation was observed, offering possibilities for further research in the field of gene therapy in isolated perfusion settings

Lack of efficacy of Doxil® in TNF-α-based isolated limb perfusion in sarcoma-bearing rats

textabstractHere we show that Doxil® has minimal antitumour activity in the isolated limb perfusion (ILP) setting and its activity was not enhanced by the addition of tumour necrosis factor (TNF). Doxil® accumulation in tumour tissue was low and also not augmented by TNF. In contrast, activity of free conventional doxorubicin was enhanced by TNF. We conclude that application of Doxil® in a TNF-based ILP is not a useful alternative to free conventional doxorubicin or melphalan

Improving acute kidney injury alerts in tertiary care by linking primary care data: An observational cohort using routine care data

OBJECTIVE: Acute kidney injury (AKI) is easily missed and underdiagnosed in routine clinical care. Timely AKI management is important to decrease morbidity and mortality risks. We recently implemented an AKI e-alert at the University Medical Center Utrecht, comparing plasma creatinine concentrations with historical creatinine baselines, thereby identifying patients with AKI. This alert is limited to data from tertiary care, and primary care data can increase diagnostic accuracy for AKI. We assessed the added value of linking primary care data to tertiary care data, in terms of timely diagnosis or excluding AKI. METHODS: With plasma creatinine tests for 84,984 emergency department (ED) visits, we applied the Kidney Disease Improving Global Outcome guidelines in both tertiary care-only data and linked data and compared AKI cases. RESULTS: Using linked data, the presence of AKI could be evaluated in an additional 7886 ED visits. Sex- and age-stratified analyses identified the largest added value for women (an increase of 4095 possible diagnoses) and patients ≥60 years (an increase of 5190 possible diagnoses). We observed 398 additional visits where AKI was diagnosed, as well as 185 cases where AKI could be excluded. We observed no overall decrease in time between baseline and AKI diagnosis (28.4 days vs. 28.0 days). For cases where AKI was diagnosed in both data sets, we observed a decrease of 2.8 days after linkage, indicating a timelier diagnosis of AKI. CONCLUSIONS: Combining primary and tertiary care data improves AKI diagnostic accuracy in routine clinical care and enables timelier AKI diagnosis