Ichthyophthirius multifiliis Fouquet: development and assessment of in vitro systems for long term maintenance

Merged with duplicate record 10026.1/785 on 15.02.2017 by CS (TIS)Twelve isolates of lchthyophthirius multifiliis were successfully established and maintained by serial passage through naive carp, for a maximum of 39 laboratory cycles. The management system employed was such that large numbers of the parasite were available for all investigations. The ability to induce exit of immature trophonts through media incubation was used to confirm events in the initial stages of host colonisation. The normal course of primary infection was also established providing useful criteria for assessing success of the in vitro systems tested. Survival of both theronts and tomonts within selected monophasic media was investigated. Theronts in Eagles Minimum Essential medium (EMEM). survived and were viable for 120 hours. 72 hours longer than water controls. No further development of the theronts was observed. Tomonts also demonstrated an increased survival time in comparison to the controls with tomites surviving within the cyst for 22 days within EMEM-S media diluted 50:50 with sterile distilled water. Division of tomonts was identified as being precystic, post divisional cystic or cystic, and the frequency of such divisions was dependent upon dilution of media, Sterile viable theronts were recovered at 168h from tomonts that had been incubated within EMEM diluted 30:70 with distilled water. Delayed encystment was achieved by incubation in concentrated media, theront production being delayed for 96h, 72h later than seen in the aquatic environment. Cultured cell monolayers were used as associates within culture systems. Behaviour of theronts on introduction into the culture systems indicated recognition of the cultured tissue as potential host material, sustained contact of up to 120hours was observed between the introduced parasite and cells. However, no developmental markers were identified within the cultured parasite and no significant growth was achieved. Attempts to simulate the situation in vivo by use of multilayered systems and crude cell explants were also unsuccessful. Transmission electron microscopy of the parasite within a cell aggregate system was undertaken at daily intervals up to 120h providing evidence that the parasite was attempting to gain nutrients by phagocytosis. However, increased vacuolation of the parasite during the period of culture was clearly evident leading eventually to parasite death. The significance of the results is discussed in relation to the normal course of infection and the future promise of a long term culture method for this important pathogen

The Information in Term Structure Interest Rate Spreads: The Irish Case

The study of the term structure of interest rates looks at how the yields on bonds vary w i t h time to maturity. Yield curves can be upward sloping, humped or downward sloping and their shape is often taken to be an indication of whether interest rates and/or inflation rates are expected to rise or fall. This forecasting potential results from the decision-making process of profitseeking investors, which must involve the formation of expectations on future inflation and interest rates. Theory suggests that, if markets are efficient, it should be possible to extract the aggregate of these expectations of inflation and interest rates from observable term structure data. I t then only requires that expectations be rational for forecasting power to be deduced. The study of the term structure is of interest to policy-makers for many reasons beyond its use as a forecasting tool. However, this paper limits itself to the study of whether interest rate spreads hold information for future interest rates and/or inflation rates, in a manner consistent with theory. In this i t draws on a long series of papers looking at using term structure to forecast interest rates (Modigliani and Shiller, 1973; Fama, 1984, 1990; Mankiw, 1986; Fama and Bliss, 1987; Hardouvelis, 1988), and also on the recent papers which have looked at the predictive power of the term structure for changes in inflation (Mishkin, 1988, 1990; Browne and Manasse, 1989). This paper examines the information in Irish yield spreads, and compares the results from Irish data w i t h the international results. The second section of the paper briefly reviews theories of the term structure, the next, following Mankiw (1986) and Mishkin (1988) shows how these theories imply that the interest rate spread w i l l have forecasting power. Sect i on IV reports and discusses results, with some comments on the data and econometric problems of the approach taken. Section V concludes

The Information in Term Structure Interest Rate Spreads: The Irish Case

The study of the term structure of interest rates looks at how the yields on bonds vary w i t h time to maturity. Yield curves can be upward sloping, humped or downward sloping and their shape is often taken to be an indication of whether interest rates and/or inflation rates are expected to rise or fall. This forecasting potential results from the decision-making process of profitseeking investors, which must involve the formation of expectations on future inflation and interest rates. Theory suggests that, if markets are efficient, it should be possible to extract the aggregate of these expectations of inflation and interest rates from observable term structure data. I t then only requires that expectations be rational for forecasting power to be deduced. The study of the term structure is of interest to policy-makers for many reasons beyond its use as a forecasting tool. However, this paper limits itself to the study of whether interest rate spreads hold information for future interest rates and/or inflation rates, in a manner consistent with theory. In this i t draws on a long series of papers looking at using term structure to forecast interest rates (Modigliani and Shiller, 1973; Fama, 1984, 1990; Mankiw, 1986; Fama and Bliss, 1987; Hardouvelis, 1988), and also on the recent papers which have looked at the predictive power of the term structure for changes in inflation (Mishkin, 1988, 1990; Browne and Manasse, 1989). This paper examines the information in Irish yield spreads, and compares the results from Irish data w i t h the international results. The second section of the paper briefly reviews theories of the term structure, the next, following Mankiw (1986) and Mishkin (1988) shows how these theories imply that the interest rate spread w i l l have forecasting power. Sect i on IV reports and discusses results, with some comments on the data and econometric problems of the approach taken. Section V concludes

Determinants of Money Demand in Ireland 1971 to 1988: Rounding up the Usual Suspects

The first question to be tackled when estimating such a function is to decide on the appropriate variables to be included. Conventional theory suggests that money demand should depend on some measure of economic activity, normally income, and some variable representing the opportunity cost of holding money, usually a short-term interest rate or an inflation rate. There is also the question of whether money should be defined broadly or narrowly. Here we take a pragmatic approach and state that the measures of money

Explaining Stock Market Correlation: A Gravity Model Approach

A gravity model, frequently used to explain trade patterns, is used to explain stock market correlations. The main result of the trade literature is that geography matters for goods markets. Physical location and trading costs should be less of an issue in asset markets. However we find that geographical variables still matter when examining equity market linkages. In particular, the number of overlapping opening hours and sharing a common border tends to increase cross-country stock market correlation. These results may stem from asymmetrical information and investor sentiment, lending some empirical support for these explanations of the international diversification puzzle

Explaining Stock Market Correlation: A Gravity Model Approach

A gravity model, frequently used to explain trade patterns, is used to explain stock market correlations. The main result of the trade literature is that geography matters for goods markets. Physical location and trading costs should be less of an issue in asset markets. However we find that geographical variables still matter when examining equity market linkages. In particular, the number of overlapping opening hours and sharing a common border tends to increase cross-country stock market correlation. These results may stem from asymmetrical information and investor sentiment, lending some empirical support for these explanations of the international diversification puzzle

Real Options? Labour Contracts for an Uncertain World

The standard labour contract is no more. Increasingly it is replaced by flexible and diverse alternative work arrangements that can often be characterized as real options. In this paper we examine optimal labour contracts from the perspective of a competitive firm facing uncertainty concerning both the cost of production and demand for its product or service. We initially restrict the firm to offering ‘standard’ contracts then add various alternative flexibility enhancing contracts. We discuss the circumstances under which these alternative contracts are real options, interpret the strike, compare them to employment contracts currently found in the labour market, and assess the benefits and costs

Assessing the unintended health impacts of road transport policies and interventions: translating research evidence for use in policy and practice

Background: Transport and its links to health and health inequalities suggest that it is important to assess both the direct and unintended indirect health and related impacts of transport initiatives and policies. Health Impact Assessment (HIA) provides a framework to assess the possible health impacts of interventions such as transport. Policymakers and practitioners need access to well conducted research syntheses if research evidence is to be used to inform these assessments. The predictive validity of HIA depends heavily on the use and careful interpretation of supporting empirical evidence. Reviewing and digesting the vast volume and diversity of evidence in a field such as transport is likely to be beyond the scope of most HIAs. Collaborations between HIA practitioners and specialist reviewers to develop syntheses of best available evidence applied specifically to HIA could promote the use of evidence in practice. Methods: Best available research evidence was synthesised using the principles of systematic review. The synthesis was developed to reflect the needs of HIA practitioners and policymakers. Results: Aside from injury reduction measures, there is very little empirical data on the impact of road transport interventions. The possibility of impacts on a diverse range of outcomes and differential impacts across groups, make it difficult to assess overall benefit and harm. In addition, multiple mediating factors in the pathways between transport and hypothesised health impacts further complicate prospective assessment of impacts. Informed by the synthesis, a framework of questions was developed to help HIA practitioners identify the key questions which need to be considered in transport HIA. Conclusion: Principles of systematic review are valuable in producing syntheses of best available evidence for use in HIA practice. Assessment of the health impacts of transport interventions is characterised by much uncertainty, competing values, and differential or conflicting impacts for different population groups at a local or wider level. These are issues pertinent to the value of HIA generally. While uncertainty needs explicit acknowledgement in HIA, there is still scope for best available evidence to inform the development of healthy public policy

Treatment of bullous pemphigoid with dupilumab: A case report

Introduction: Bullous Pemphigoid (BP) is an autoimmune blistering condition that results from formation of autoantibodies against basement membrane hemidesmosome proteins, specifically BP180 and BP230. Classic BP presents as pruritic, tense blisters on the trunk and extremities, most commonly in the elderly. BP’s pathophysiology involves IL4/IL5/IL13 and eosinophils. Dupilumab is an IgG monoclonal antibody targeted at the IL4-α receptor that works to attenuate the IL4/IL13 pathway involved in T2 differentiation. Dupilumab has clinical applications for T2 mediated disease and shows promise in the therapy of BP. Case Description: We report a case of an 83-year-old Asian male who presented in the spring of 2019 with a chief complaint of blistering lesions accompanied by significant pruritus. Medical history was positive for hypertension controlled on amlodipine and losartan and hypercholesterolemia not on any medical therapy. Past medical history and family history were negative for any autoimmune or skin disorders. Tense bullae were noted in the arm, hands, thighs, feet, groin and the head. The blistering rash appeared to be urticarial lesions which were unresponsive to prednisone therapy. Hypersensitivity reaction and drug eruption were suspected. Initial biopsy revealed spongiotic dermatitis with eosinophilic spongiosis and there was suggestion of BP. A diagnosis of BP was later confirmed on a second biopsy via direct immunofluorescence. Initial treatment with oral prednisone and doxycycline 100mg bid, topical 0.1% triamcinolone bid and topical 1% silver sulfadiazine was unsuccessful. Every time prednisone was tapered the patient would have flares of new blisters. Sarna was used for managing pruritus. Mycophenolate mofetil (1g BID) and dapsone (25 mg BID and eventually 2x25mg tablets, BID) were attempted but gradually discontinued because of significant neuropathy and paresthesias. 5 rounds of Gamunex IVIG (2 gm/kg per cycle) were conducted in 2020 without significant relief. The patient also failed to respond to three rounds of rituximab therapy (1000 cc over 6 hours) that took place in the months of January, February and September of 2022. The patient was then tried on Dupilumab therapy and after a 600mg dose at day 0 and a 300 mg dose delivered two weeks later, there was a clinically significant improvement with no new flares. The patient remains on concomitant oral doxycycline (100 mg) once daily and topical 0.1% triamcinolone as needed. The patient denies any adverse drug reactions with the new addition of Dupilumab and is continuing therapy with biweekly 300 mg injections. Discussion: Bullous Pemphigoid is an autoimmune blistering disease with variable responses to standard therapies. Our case and the literature have shown promising therapeutic results with the use of Dupilumab in treatment resistant BP

Longitudinal and cross-sectional modelling of health related quality of life in people with cystic fibrosis

People with cystic fibrosis (CF) must endure up to four hours treatment per day to maintain health and are vulnerable to complications. The Cystic Fibrosis Quality of Life Questionnaire was developed to measure health related quality of life (HRQoL) in the UK. Most studies on HRQoL are cross-sectional in design with HRQoL measured once per patient. However, the Cystic Fibrosis Quality of Life Questionnaire has been used to monitor HRQoL longitudinally with measures taken over a 12 year period at one clinic in the UK. These data were modelled with a binomial distribution for a domain score and with fixed and random coefficients for the patient-level clinical and demographic variables. The longitudinal study included 182 patients whose HRQoL was first measured within a single calendar year and were then followed-up. These data provided an opportunity to compare, directly and by simulation, the modelling of a cross-sectional with the modelling of a longitudinal study and so provided insights into the statistical merits of longitudinal studies compared to cross-sectional studies in HRQoL