Governmentality and Risk: Managing ‘Ocean Space’

The term ‘fisheries management’ at first glance seems to be a reasonably unproblematic one. It implies that firstly, that there are resources called fish, and secondly, that these resources called fish can be harvested and managed. So far, so good. Next, there is the word ‘convention’. It is a commonly understood word in law in general and there are many conventions in International law and in International environmental law as well. Lastly there is the term ‘sustainable development’, a well-used term in International theory and practice, usually said to mean that although we understand the finite nature of the matter and energy that can be safely used by countries to develop, this can be tempered by putting in place measures and instruments to curb the excesses of human, and by that I mean industrialised, human activity on the environment

Cardiovascular autonomic effects of transcutaneous auricular nerve stimulation via the tragus in the rat involve spinal cervical sensory afferent pathways.

Background Electrical stimulation on select areas of the external auricular dermatome influences the autonomic nervous system. It has been postulated that activation of the Auricular Branch of the Vagus Nerve (ABVN) mediates such autonomic changes. However, the underlying neural pathways mediating these effects are unknown and, further, our understanding of the anatomical distribution of the ABVN in the auricle has now been questioned. Objective To investigate the effects of electrical stimulation of the tragus on autonomic outputs in the rat and probe the underlying neural pathways. Methods Central neuronal projections from nerves innervating the external auricle were investigated by injections of the transganglionic tracer cholera toxin B chain (CTB) into the right tragus of Wistar rats (n=4). Physiological recordings of heart rate, perfusion pressure, respiratory rate and sympathetic nerve activity were made in an anaesthetic free Working Heart Brainstem Preparation (WHBP) of the rat and changes in response to electrical stimulation of the tragus analysed. Results Neuronal tracing from the tragus revealed that the densest CTB labelling was within laminae III-IV of the dorsal horn of the upper cervical spinal cord, ipsilateral to the injection sites. In the medulla oblongata, CTB labelled afferents were observed in the paratrigeminal nucleus, spinal trigeminal tract and cuneate nucleus. Surprisingly, only sparse labelling was observed in the vagal afferent termination site, the nucleus tractus solitarius. Recordings made from rats at night time revealed more robust sympathetic activity in comparison to day time rats, thus subsequent experiments were conducted in rats at night time. Electrical stimulation was delivered across the tragus for 5 minutes. Direct recording from the sympathetic chain revealed a central sympathoinhibition by up to 36% following tragus stimulation. Sympathoinhibition remained following sectioning of the cervical vagus nerve ipsilateral to the stimulation site, but was attenuated by sectioning of the upper cervical afferent nerve roots. Conclusions Inhibition of the sympathetic nervous system activity upon electrical stimulation of the tragus in the rat is mediated at least in part through sensory afferent projections to the upper cervical spinal cord. This challenges the notion that tragal stimulation is mediated by the auricular branch of the vagus nerve and suggests that alternative mechanisms may be involved

Foundations on Silt: Jeremy Bentham, Liberalism and the Science of International Law

When the words good or bad are uttered the user generally takes their meaning derived from a system of ethics or morals. In this sense good and bad are particularist in nature and also socio-culturally specific. Let us take a simple example from Antiquity. At school in the West we learn of a figure called Alexander the Great, the Macedonian. By all accounts we are taught that he was a great, and by extension a good man. In modern day Iran Alexander of Macedonia is known as Alexander the Devil. So the question arises: was Alexander good or bad, or both? Is it possible to state unequivocally that the actions of Alexander were as a matter of fact morally good or morally bad? I think the answer to this question is fairly straightforward: it depends. Now this answer is not a simple descent into postmodern territory and moral relativism; there are genuine and empirical reasons to believe all three possibilities pertaining to the actions of Alexander. In short it is not possible to extrapolate from the particular to the general and it is not a question of semantics or even of critical hermeneutics. There is no either/or for Alexander of Macedonia. The binary opposition of good and bad cannot be applied to the particular actions of an individual and furthermore cannot be generalized as a principle, rule or otherwise. This distinction or argument between what can be deemed good and what can be deemed bad may at first sight seem irrelevant to the law but it is not. In moral philosophy natural law theory states that law is based on morality, therefore negating the possibility of a bad law. It is at this point that Jeremy Bentham comes to our attention. Bentham believed that law and morality, although connected need not necessarily be so. Under the principle of utility, which I will explore in more detail later in this essay, Bentham believed that individual intent of an action could be disassociated from the intent that ought to be in place. The principle of utility was this test. In other words when determining the right course of action and what laws should be obeyed for all circumstances and systems, the principle of utility was the foundation. And I will argue later on in this essay that although Bentham is identified as a legal positivist and a philosophical realist his negative idealism is based on an error, much in the same way that he thought he had identified the fallacy of natural law. Bentham’s foundations may not be on stilts but perhaps, more accurately, they were built on silt. Moreover Bentham’s position as a moral philosopher is rather unusual in that although he was indeed interested in the behavior of the individual he was insofar as that behavior might have some bearing on a general system of law. This essay is therefore concerned with this troubling problem. I will proceed as follows. Firstly, I will give an overview of Bentham’s criticism of natural law and of William Blackstone in particular. Secondly, I will look at Bentham’s contribution to the internationalization of the law and his use of the “principle of utility”; he coined the neologism “international” as one of many. I will then move on to see how Bentham expected to actualize his foundational principle through his efforts to persuade others of the efficacy of codifying international law as a form of ‘science’. I conclude by arguing that Bentham’s philosophical realism was, in fact a form of idealism, bordering on the religious; his ‘cosmic calculus’

Investigations into the organisation and morphology of vagal preganglionic neurones and the anatomical identification of the chemistry and origin of some of their synaptic inputs

The investigations in this thesis involve the use of neuroanatomical techniques in the study of vagal preganglionic neurones (VPNs) in the medulla oblongata of the rat and cat. Light microscopic examination of VPNs identified by the injection of horseradish peroxidase (HRP) into the cervical vagus nerve of the rat revealed that they lay mainly in two areas of the medulla - the dorsal vagal nucleus (DVN) and the nucleus ambiguus (NA). Labelled cells in the DVN (median diameter 18jim) were arranged in a tightly packed group. In contrast, labelled neurones in the NA were arranged in two identifiable groups. The most dorsal of these groups consisted of tightly packed cells with median diameter of 30μm (compact group - cNA) whereas the other group were smaller (median D 25μm) and were scattered in ventrolateral regions of the medulla (vINA). Neurones in each group were identified as being statistically different in diameter and soma area from those in other groups (Student's t-test). Cardiac vagal preganglionic neurones (CVPNs), retrogradely labelled by the injection of cholera toxin-HRP into the right atrium, were located mainly in the vINA with median soma diameter 25μm. Ultrastructural examination of the groups of VPNs revealed that they shared some morphological characteristics. VPNs in the NA, particularly those in the vINA, were observed to be intermingled with neurones retrogradely labelled from the phrenic motor nucleus in the spinal cord and were often morphologically indistinguishable. VPNs in the NA were also intermingled with neuropeptide Y immunoreactive neurones. The chemistry of inputs to VPNs was examined using a combination of retrograde tracing to identify VPNs, immunocytochemistry to detect various neurotransmitter chemicals, and electron microscopy. Serotonin, substance P and neuropeptide Y were identified in boutons forming asymmetric type synaptic contacts with VPNs in the nucleus ambiguus of the rat which were retrogradely labelled from the heart or the cervical vagus nerve. The origin of inputs to VPNs was investigated by the ionophoretic injection of HRP into regions of the cat ventral medulla where antidromic potentials were recorded to stimulation of the cervical vagus nerve. Retrogradely labelled cells were localised both contralaterally and ipsilateral ly in the nucleus tractus solitarius, raphe nuclei, parabrachial nucleus, periaqueductal gray matter and the NA. To determine if the NTS was a source of synaptic input to VPNs in the NA, VPNs were identified by retrograde tracing followed by the ionophoretic injection of the anterograde tracer biocytin into regions of the NTS where evoked potentials were recorded to stimulation of the carotid sinus or cervical vagus nerve. Light microscopic examination revealed anterogradely labelled boutons and fibres in the NA, some of which were in close association with retrogradely labelled VPNs. Subsequent electron microscopic examination revealed some of these boutons form synaptic specialisations with retrogradely labelled VPNs

The strange case of the ear and the heart: the auricular vagus nerve and its influence on cardiac control

The human ear seems an unlikely candidate for therapies aimed at improving cardiac function, but the ear and the heart share a common connection: the vagus nerve. In recent years there has been increasing interest in the auricular branch of the vagus nerve (ABVN), a unique cutaneous subdivision of the vagus distributed to the external ear. Non-invasive electrical stimulation of this nerve through the skin may offer a simple, cost-effective alternative to the established method of vagus nerve stimulation (VNS), which requires a surgical procedure and has generated mixed results in a number of clinical trials for heart failure. This review discusses the available evidence in support of modulating cardiac activity using this strange auricular nerve

Co-expression of GAD67 and choline acetyltransferase in neurons in the mouse spinal cord: a focus on lamina X

Lamina X of the spinal cord is a functionally diverse area with roles in locomotion, autonomic control and processing of mechano and nociceptive information. It is also a neurochemically diverse region. However the different populations of cells in lamina X remain to be fully characterised. To determine the co-localisation of the enzymes responsible for the production of GABA and acetylcholine (which play major roles in the spinal cord) in lamina X of the adult and juvenile mouse, we used a transgenic mouse expressing green fluorescent protein (GFP) in glutamate decarboxylase 67 (GAD67) neurons, combined with choline acetyltransferase (ChAT) immunohistochemistry. ChAT-immunoreactive (IR) and GAD67-GFP containing neurons were observed in lamina X of both adult and juvenile mice and in both age groups a population of cells containing both ChAT-IR and GAD67-GFP were observed in lumbar, thoracic and cervical spinal cord. Such dual labelled cells were predominantly located ventral to the central canal. Immunohistochemistry for vesicular acetylcholine transporter (VAChT) and GAD67 revealed a small number of double labelled terminals located lateral, dorsolateral and ventrolateral to the central canal. This study has therefore describes in detail a population of ChAT-IR/GAD67-GFP neurons predominantly ventral to the central canal of the cervical, thoracic and lumbar spinal cord of adult and juvenile mice. These cells potentially correspond to a sub-population of the cholinergic central canal cluster cells which may play a unique role in controlling spinal cord circuitry

Mediation of Cardiac Macrophage Activity via Auricular Vagal Nerve Stimulation Ameliorates Cardiac Ischemia/Reperfusion Injury

Background: Myocardial infarction (MI) reperfusion therapy causes paradoxical cardiac complications. Following restoration of blood flow to infarcted regions, a multitude of inflammatory cells are recruited to the site of injury for tissue repair. Continual progression of cardiac inflammatory responses does, however, lead to adverse cardiac remodeling, inevitably causing heart failure. Main Body: Increasing evidence of the cardioprotective effects of both invasive and non-invasive vagal nerve stimulation (VNS) suggests that these may be feasible methods to treat myocardial ischemia/reperfusion injury via anti-inflammatory regulation. The mechanisms through which auricular VNS controls inflammation are yet to be explored. In this review, we discuss the potential of autonomic nervous system modulation, particularly via the parasympathetic branch, in ameliorating MI. Novel insights are provided about the activation of the cholinergic anti-inflammatory pathway on cardiac macrophages. Acetylcholine binding to the α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages polarizes the pro-inflammatory into anti-inflammatory subtypes. Activation of the α7nAChR stimulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This inhibits the secretion of pro-inflammatory cytokines, limiting ischemic injury in the myocardium and initiating efficient reparative mechanisms. We highlight recent developments in the controversial auricular vagal neuro-circuitry and how they may relate to activation of the cholinergic anti-inflammatory pathway. Conclusion: Emerging published data suggest that auricular VNS is an inexpensive healthcare modality, mediating the dynamic balance between pro- and anti-inflammatory responses in cardiac macrophages and ameliorating cardiac ischemia/reperfusion injury

A versatile cholera toxin conjugate for neuronal targeting and tracing

Tracing of neurons plays an essential role in elucidating neural networks in the brain and spinal cord. Cholera toxin B subunit (CTB) is already widely used as a tracer although its use is limited by the need for immunohistochemical detection. A new construct incorporating non-canonical azido amino acids (azido-CTB) offers a novel way to expand the range and flexibility of this neuronal tracer. Azido-CTB can be detected rapidly in vivo following intramuscular tongue injection by ‘click’ chemistry, eliminating the need for antibodies. Cadmium selenide/zinc sulfide (CdSe/ZnS) core/shell nanoparticles were attached to azido-CTB by strain-promoted alkyne–azide cycloaddition to make a nano-conjugate. Following tongue injections the complex was detected in vivo in the brainstem by light microscopy and electron microscopy via silver enhancement. This method does not require membrane permeabilization and so ultrastructure is maintained. Azido-CTB offers new possibilities to enhance the utility of CTB as a neuronal tracer and delivery vehicle by modification using ‘click’ chemistry