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

Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial

Contains fulltext : 96247.pdf (publisher's version ) (Open Access)BACKGROUND: The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences.Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. METHODS/DESIGN: This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning).Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory.Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional status of the wrist, including assessment by means of the patient rated wrist evaluation (PRWE) questionnaire and quality of life using SF-36 health survey questionnaire.Primary endpoint is number of scaphoid unions at six weeks, secondary endpoints are time interval to clinical and radiological consolidation, number of non-unions, functional status at 52 weeks and non-adherence to the treatment protocol. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2064