The Effects of the Selective Muscarinic M3 Receptor Antagonist Darifenacin, and of Hyoscine (scopolamine), on Motion Sickness, Skin Conductance & Cognitive Function

Aims: The aim of this study was to compare the effects of the selective M3 muscarinic acetylcholine receptor antagonist Darifenacin, oral Hyoscine hydrobromide and Placebo on motion sickness induced by cross-coupled stimulation. Methods: The effects of Darifenacin 10 mg or 20 mg, Hyoscine hydrobromide 0.6 mg and Placebo were assessed in a randomised, double-blind, 4-way cross over trial of 16 healthy subjects. Motion sickness, skin conductance (a measure of sweating) and psychomotor cognitive function tests were investigated. Results: Hyoscine hydrobromide produced significantly increased tolerance to motion versus Placebo (P<0.05 to P<0.01). The motion protection effect of Darifenacin (10 or 20 mg) was approximately one third of that of Hyoscine hydrobromide, but was not significant versus Placebo. Darifenacin and Hyoscine hydrobromide both significantly reduced skin conductance versus Placebo. Darifenacin produced either no effect or an enhanced effect on cognitive function in contrast to Hyoscine hydrobromide where there was significant impairment of psychomotor performance. Conclusion: The results suggest that selective antagonism of the M3 receptor may not be important in the prevention of motion sickness. However selective M3 antagonism does not impair cognitive function. These observations may be important given that long term treatment with non-selective anti-muscarinic agents such as Oxybutynin may lead to an increased incidence of dementia

Attenuated cortisol reactivity to psychosocial stress is associated with greater visual dependency in postural control

Despite known anatomical links between the hypothalamic-pituitary-adrenal (HPA) axis and the vestibular system, there are no studies on the relationship between postural control and HPA axis function. Visual dependence in postural control, often measured by increased postural sway on exposure to visual motion, is an indication of altered visual-vestibular integration with greater weighting towards visual cues for balance. Visual dependence is more common in older age and a range of vestibular and non-vestibular health conditions. The relationship between visual dependence in postural control was investigated in relation to cortisol reactivity to psychosocial stress (using the Trier Social Stress Test for groups: TSST-G), as an index of HPA axis function, in healthy young females. In those who exhibited a cortisol response (>2 nmol/l), a negative relationship between stress-induced cortisol reactivity and visual dependence in postural control was observed, since those with the largest cortisol response showed less visual motion induced postural sway (measured by force platform). This finding in healthy females indicates that subtle non-clinical differences in vestibular function are associated with dysregulated HPA axis activity as indicated by lower cortisol reactivity to psychosocial stress. It adds to the growing body of evidence linking blunted cortisol reactivity to stress to poor homeostatic regulation and potential negative health and behavioural outcomes

Long-Term Effectiveness and Safety of Endoscopic Vidian Neurectomy for the Treatment of Intractable Rhinitis

ObjectivesVidian neurectomy could be considered the treatment of choice for intractable rhinitis, because it is the only method that can permanently block the pathophysiological mechanism of rhinitis. The goal of this study was to evaluate the effect of vidian neurectomy on nasal symptoms and tear production, and to assess for possible complications.MethodsSix patients with intractable rhinitis who underwent endoscopic transnasal vidian neurectomy were enrolled. The degree of symptom improvement and complications were assessed through retrospective review of medical records prior to, and 1 year following surgery, and telephone survey after 6.9±2.1 years. Schirmer's test was performed before surgery, and these values were compared to postoperative results at 1 day, 1 month, and 2 months.ResultsChanges in the visual analogue scale were significant in nasal obstruction (8.5±2.5 to 3.0±2.0, P<0.05) and rhinorrhea (9.0±2.2 to 2.0±1.6, P<0.05). Improvements persisted for up to 7 years after the primary surgery. Patients complained of mild dry eyes for 1 month after vidian neurectomy. However, five out of six reported marked improvement of xerophthalmia after 2 months. Aside from mild crusting of the nasal cavity and mild postoperative pain, there were no major complications. During the entire follow-up period, no patient needed additional treatment, such as antihistamines or corticosteroids.ConclusionVidian neurectomy is effective in alleviating nasal symptoms in patients with intractable rhinitis refractory to other treatments. This effect is sustained for at least 7 years with minimal postoperative complications

The politics of innovation: why innovations need a godfather

Innovation is closely linked to the development of technology. Hence it is often assumed that when an innovation fails it is the technology that is at fault. While this may be true in many instances, there are occasions when it is not the technology that is at fault, rather, it is managerial and organisational aspects that cause problems and lead to failure. Studies have shown that individuals who take on specific roles can play an important part in avoiding these problems. These roles include the technological gatekeeper, the product champion and the sponsor/coach. In addition to these roles, this paper argues that there is another, namely that of godfather. With this role a highly respected, senior figure within an organisation provides support that is critical in ensuring the project overcomes the hurdles that lie in the path of any major new development. The nature of the godfather role is explored through three case studies. These provide examples of the role and show how it can facilitate the innovation process

Outcomes in endoscopic sinus surgery: olfaction, nose scale and quality of life in a prospective cohort study

OBJECTIVES: To determine the efficacy of endoscopic sinus surgery (ESS) on olfactory function in chronic rhinosinusitis patients with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) and to compare the nasal obstruction and symptom evaluation (NOSE) scale before and after surgery. DESIGN: A prospective cohort study. SETTING: Royal National Throat and Nose and Ear Hospital, London UK. PARTICIPANTS: One hundred and thirteen patients with CRS; 60 CRSwNP and 53 CRSsNP. OUTCOME ASSESSMENTS: Olfaction was measured using both the University of Pennsylvania Smell Investigation Test (UPSIT) and the ‘sense of smell’ visual analogue scale (VAS). The NOSE scale, the sinonasal outcome test (SNOT 22) and the Lund–Kennedy (LK) surgeon reported scores were also measured pre- and postoperatively at 6 months. RESULTS: The UPSIT psychophysical measurement significantly improved following ESS in the CRSwNP subgroup as did the patients perceived VAS sense of smell. However, in the CRSsNP subgroup, the improved VAS and UPSIT measurements were not significant. The NOSE, SNOT 22 and LK scores all improved significantly. The olfactory improvement as measured by the UPSIT correlated to the SNOT-22, but a correlation between the NOSE score and UPSIT was not found. CONCLUSIONS: Endoscopic sinus surgery significantly improved the patient's perceived and measured sense of smell in the CRSwNP subgroup which is the most surgically responsive CRS subgroup. Additionally, improved olfaction in the CRSwNP subgroup is most likely to improve the patient's quality of life. Endoscopic sinus surgery significantly improved the NOSE scale in both CRS subgroups at 6 months following surgery

Aquatic live animal radiotracing studies for ecotoxicological applications : addressing fundamental methodological deficiencies

The use of live animal gamma radioisotope tracer techniques in the field of ecotoxicology allows laboratory studies to accurately monitor contaminant biokinetics in real time for an individual organism. However, methods used in published studies for aquatic organisms are rarely described in sufficient detail to allow for study replication or an assessment of the errors associated with live animal radioanalysis to be identified. We evaluate the influence of some important methodological deficiencies through an overview of the literature on live aquatic animal radiotracer techniques and through the results obtained from our radiotracer studies on four aquatic invertebrate species. The main factors discussed are animal rinsing, radioanalysis and geometry corrections. We provide examples of three main techniques in live aquatic animal radiotracer studies to improve data quality control and demonstrate why each technique is crucial in interpreting the data from such studies. The animal rinsing technique is also relevant to non-radioisotope tracer studies, especially those involving nanoparticles. We present clear guidance on how to perform each technique and explain the importance of proper reporting of the validation of each technique for individual studies. In this paper we describe methods that are often used in lab-based radioecology studies but are rarely described in great detail. We hope that this paper will act as the basis for standard operating procedures for future radioecology studies to improve study replication and data quality control

From AAA to Junk: Credit rating agencies as news sources in the Irish print-media during the economic crisis, 2008–2013

From AAA to Junk: Credit rating agencies as news sources in the Irish print-media during the economic crisis, 2008–201

Probabilistic Programming with Densities in SlicStan: Efficient, Flexible, and Deterministic

Stan is a probabilistic programming language that has been increasingly used for real-world scalable projects. However, to make practical inference possible, the language sacrifices some of its usability by adopting a block syntax, which lacks compositionality and flexible user-defined functions. Moreover, the semantics of the language has been mainly given in terms of intuition about implementation, and has not been formalised. This paper provides a formal treatment of the Stan language, and introduces the probabilistic programming language SlicStan --- a compositional, self-optimising version of Stan. Our main contributions are: (1) the formalisation of a core subset of Stan through an operational density-based semantics; (2) the design and semantics of the Stan-like language SlicStan, which facilities better code reuse and abstraction through its compositional syntax, more flexible functions, and information-flow type system; and (3) a formal, semantic-preserving procedure for translating SlicStan to Stan

T-lymphocyte subsets in liver tissues of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls

T lymphocytes infiltrating hepatic tissues were typed and enumerated in liver biopsies of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls using monoclonal antibodies and the avidin-biotin-immunoperoxidase technique. The peripheral blood mononuclear cells were studied also by flow cytometry. In PBC, T lymphocytes were decreased (P<0.001) in the blood [absolute number was 426±200 (SE) vs 1351±416 in 15 controls], as was the helper/suppressor (T4/T8) ratio (1.0±0.1 vs normal 2.3±0.3). T lymphocytes were the most numerous mononuclear cells infiltrating portal areas of PBC livers: 749±93/5 high-power fields (HPF) in PBC vs 98±15/5 HPF (P<0.01) in controls. The T4/T8 ratios varied from 0.9 to 2.3 (mean, 1.8±0.1) in the portal triads (normal mean, 1.6±0.1), with the T4+ cells accounting for more than 75% of infiltrating T cells. In contrast, the mean T4/T8 ratio in portal triads of PSC was reduced (1.0±0.3) due to a significant increase (P<0.001) in the number of T8+ cells. The T cells around and in the walls of bile ducts in PBC were mostly T8+, and the T4/T8 ratio was 0.8±0.2. No T8+ cells were seen in this location in PSC and normal livers. Few mononuclear cells were present in hepatic lobules. Subtyping of T lymphocytes in liver tissues of patients with PBC and PSC may be helpful in the differential pathologic diagnosis. In patients with advanced PBC, a decrease in T4+ cells in the blood appeared to be accompanied by their accumulation in the portal triads. In contrast, T8+ cells accumulated preferentially around bile ducts. © 1984 Plenum Publishing Corporation