The open future, bivalence and assertion

It is highly intuitive that the future is open and the past is closed—whereas it is unsettled whether there will be a fourth world war, it is settled that there was a first. Recently, it has become increasingly popular to claim that the intuitive openness of the future implies that contingent statements about the future, such as ‘there will be a sea battle tomorrow,’ are non-bivalent (neither true nor false). In this paper, we argue that the non-bivalence of future contingents is at odds with our pre-theoretic intuitions about the openness of the future. These are revealed by our pragmatic judgments concerning the correctness and incorrectness of assertions of future contingents. We argue that the pragmatic data together with a plausible account of assertion shows that in many cases we take future contingents to be true (or to be false), though we take the future to be open in relevant respects. It follows that appeals to intuition to support the non-bivalence of future contingents is untenable. Intuition favours bivalence

Protocol for the Smoking, Nicotine and Pregnancy (SNAP) trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy

Background: Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking, nicotine and pregnancy ( SNAP) trial will investigate whether or not nicotine replacement therapy ( NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. Methods/Design: Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date ( defined before randomisation and set within two weeks of this) and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups. Discussion: This trial is designed to ascertain whether or not standard doses of NRT ( as transdermal patches) are effective and safe when used for smoking cessation during pregnancy

The SOS Pilot Study: a RCT of routine oxygen supplementation early after acute stroke—effect on recovery of neurological function at one week

Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke

Real-time non-invasive measurement and monitoring of wheel-rail contact using ultrasonic reflectometry

Rail stress levels are vital to the lifespan of rail tracks, and are responsible for the safe operation and ride comfort of train services. In particular, wheel–rail contact stress is a dominating factor affecting wear, cracking, fatigue and failure of both wheel and rail. The wheel–rail interaction problem has long been investigated, yet detailed contact information on real cases remains obscure due to the interface complexity, including the varying wheel and rail profiles and lack of effective stress characterisation methods. Ultrasound image study, as an excellent non-destructive evaluation (NDE) method, is widely used in railway systems for defect detection, stress determination and rail profile checking. Specifically, ultrasonic reflectometry has proved successful in making static machine-element contact measurements. This article introduces a novel measuring method for both short-term and long-term dynamic wheel–rail contact monitoring purposes based on ultrasonic reflectometry. The method is investigated in detail, including the study of ultrasound propagation pathways in the rail, and the optimum placement of ultrasonic elements as well as actuator–receiver combinations. The proposed monitoring technique is expected to characterise and monitor the contact behaviour of operating high-speed rail system in real-time

Illocutionary harm

A number of philosophers have become interested in the ways that individuals are subject to harm as the performers of illocutionary acts. This paper offers an account of the underlying structure of such harms: I argue that speakers are the subjects of illocutionary harm when there is interference in the entitlement structure of their linguistic activities. This interference comes in two forms: denial and incapacitation. In cases of denial, a speaker is prevented from achieving the outcomes to which they are entitled by their speech. In cases of incapacitation, a speaker’s standing to expect certain outcomes is itself undermined. I also discuss how individual speakers are subject to interference along two dimensions: as exercisers of certain non-linguistic capacities, and as producers of meaningful speech

Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis.

Angiogenesis and the development of a vascular network are required for tumour progression, and they involve the release of angiogenic factors, including vascular endothelial growth factor (VEGF-A), from both malignant and stromal cell types. Infiltration by cells of the myeloid lineage is a hallmark of many tumours, and in many cases the macrophages in these infiltrates express VEGF-A. Here we show that the deletion of inflammatory-cell-derived VEGF-A attenuates the formation of a typical high-density vessel network, thus blocking the angiogenic switch in solid tumours in mice. Vasculature in tumours lacking myeloid-cell-derived VEGF-A was less tortuous, with increased pericyte coverage and decreased vessel length, indicating vascular normalization. In addition, loss of myeloid-derived VEGF-A decreases the phosphorylation of VEGF receptor 2 (VEGFR2) in tumours, even though overall VEGF-A levels in the tumours are unaffected. However, deletion of myeloid-cell VEGF-A resulted in an accelerated tumour progression in multiple subcutaneous isograft models and an autochthonous transgenic model of mammary tumorigenesis, with less overall tumour cell death and decreased tumour hypoxia. Furthermore, loss of myeloid-cell VEGF-A increased the susceptibility of tumours to chemotherapeutic cytotoxicity. This shows that myeloid-derived VEGF-A is essential for the tumorigenic alteration of vasculature and signalling to VEGFR2, and that these changes act to retard, not promote, tumour progression

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio