Short sea shipping: Lessons for or from Australia?

Over the past decade, there has been a substantial volume of research on short sea shipping and related national maritime transport regulation. In spite of significant support for the policy of growing the volume of short sea shipping in Europe, and the signing of a Memorandum of Cooperation within NAFTA in 2003, there has not been the level of adoption by cargo interests or shipping lines expected. In Australia, where the regulatory environment is somewhat different from Europe or North America, the industry is more focused on the bulk sector and the Rudd Government is contemplating an agenda of maritime reform. This situation presents an opportunity to build an understanding of why, how and whether short sea shipping works, and, in particular, what lessons from the Australian experience might apply to the Canadian and/or North American context and vice versa. This paper builds on two separate but linked streams of research. On one hand, it will review the research conducted in North America. Large-scale studies have been undertaken for Transport Canada over the past five years, and several studies have also been conducted in the U.S. On the other, it reviews the studies undertaken in Australia, where short sea shipping received considerable attention from both consultants and academics, and there has been a recent government investigation into the coastal shipping industry. In its examination of research done to date, this paper explores the lessons from these studies by answering four research questions. It draws preliminary conclusions about the role of the regulatory environment in promoting or deterring the development of land transport– competitive short sea services and about which research agenda gaps remain to be filled. The paper does not focus on bulk shipping; the key emphasis is on what governments need to consider if they seek to induce switching from land modes, like truck or rail, to coastal shipping in order to revitalise the domestic industry or improve GHG-efficiency in the transport sector or both

The Homeobox Transcription Factor Barx2 Regulates Plasticity of Young Primary Myofibers

Adult mammalian muscle retains incredible plasticity. Muscle growth and repair involves the activation of undifferentiated myogenic precursors called satellite cells. In some circumstances, it has been proposed that existing myofibers may also cleave and produce a pool of proliferative cells that can re-differentiate into new fibers. Such myofiber dedifferentiation has been observed in the salamander blastema where it may occur in parallel with satellite cell activation. Moreover, ectopic expression of the homeodomain transcription factor Msx1 in differentiated C2C12 myotubes has been shown to induce their dedifferentiation. While it remains unclear whether dedifferentiation and redifferentiaton occurs endogenously in mammalian muscle, there is considerable interest in induced dedifferentiation as a possible regenerative tool.We previously showed that the homeobox protein Barx2 promotes myoblast differentiation. Here we report that ectopic expression of Barx2 in young immature myotubes derived from cell lines and primary mouse myoblasts, caused cleavage of the syncytium and downregulation of differentiation markers. Microinjection of Barx2 cDNA into immature myotubes derived from primary cells led to cleavage and formation of mononucleated cells that were able to proliferate. However, injection of Barx2 cDNA into mature myotubes did not cause cleavage. Barx2 expression in C2C12 myotubes increased the expression of cyclin D1, which may promote cell cycle re-entry. We also observed differential muscle gene regulation by Barx2 at early and late stages of muscle differentiation which may be due to differential recruitment of transcriptional activator or repressor complexes to muscle specific genes by Barx2.We show that Barx2 regulates plasticity of immature myofibers and might act as a molecular switch controlling cell differentiation and proliferation

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF Therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Ship investment under uncertainty: A real option approach

Discounted cash flow (DCF) methodology has long been advocated as the appropriate theoretical underpinning for maritime investments (Bendall, 1979; Evans, 1984; Gardner, Goss and Marlow, 1984). However, its limitations are also well-known and can relegate its practical use to a confirmatory role, or management may override its results in favour of an alternative preferred strategy (Teisberg, 1995; Bendall, 2002). Uncertainty, and the difficulty to value the flexibility that management has in adapting plans after a project is underway are significant limiting factors. This paper considers a maritime investment where there is uncertainty and alternative strategies, and uses real option analysis to value a flexible strategy that adapts to conditions as uncertainty is resolved. The proposed investment is a new service based on a new technology: high speed container ships (Bendall and Stent, 1998). The service would be based in South East Asia with Singapore as a hub port and offer fast turn-around times to neighbouring ports, Klang and Penang. The level of service that is offered depends on the number of ships purchased for the project. Being a new technology they must be purchased new and, clearly, in discrete units. There is a one year time to build. The demand for the service is the main uncertainty. Besides day to day variations in demand and economic cycles which affect long run achievable load factors, there are the initial uncertainties associated with the new type of service and technology. While market research might reduce this latter uncertainty, it can only be resolved over time as customers gain experience and adapt or otherwise to the particular characteristics. It could be, for instance, that an eventual high level of demand would favour putting two ships on the service whereas an eventual low level of demand might favour just one. Competition is a consideration. Offering an inadequate level of service to either port leaves an opportunity for a competitor and adversely affects a strategy such as servicing just one port initially with a view to extending the service to the other port if conditions prove favourable. Freight rates also have a significant bearing upon the decision. The paper considers the case where demand for the service as well as freight rates are uncertain. It provides a methodology using Real Option Analysis for adapting the number of ships employed to actual market experience. Real option analysis, ROA, is a methodology for valuing flexible strategies in an uncertain world (Trigeorgis, 1995). It builds on the traditional DCF technique. It owes its quantitative antecedents to the seminal works of Black and Scholes (1973), Merton (1973) and to the binomial approach of Cox, Ross and Rubinstein (1979) in pricing financial options. Like financial options, real options are the owner’s right but not obligation to trade an underlying asset or income stream under predetermined conditions. The simplest financial options are the right to buy (call) or sell (put) the asset at a predetermined price (exercise price) for a predetermined period of time (life of the option). Real option parallels are management’s ability to expand or contract a project in light of actual outcomes after it is underway. Like financial options, management’s strategies can be far more complex than simple calls and puts, such as abandoning or delaying a project. The methodology, including risk-neutral valuation as a general principle, has evolved to price complex financial options and can be applied to real options too. There is the matter of selecting an appropriate underlying asset which spans the project’s uncertain states. Although projects are not usually traded per se, the process of capital budgeting models the market value of their cash flows (Kasanen and Trigeorgis, 1993). Copeland and Antikarov (2000) advance the concept of Marketable Asset Disclaimer to justify the use of the present value of inflexible strategies, estimated by the traditional discounted cash flow techniques, as the appropriate underlying asset. No stronger assumption is required than for the traditional analysis. This is the method employed to value the strategies in the present paper. A simulation model is first built to model particular fixed services. These are the underlying assets. The model provides estimates of their present values which are used as market prices. It also provides estimates of their volatilities and correlations which are used to model the evolution of their prices in a second step when options are valued. The particular option used in the paper is that to exchange one risky income stream for another. The different income streams are the alternative services which are to be valued as a flexible strategy. The methodology is applied to a hub and spoke system. It is readily adaptable to other situations.UnpublishedNon Peer ReviewedBendall, HB. 1979. Coal-fired turbines versus diesel: an Australian context. Maritime Management and Policy 6: 209-215. Bendall, HB. 2002. Valuing Maritime Investments Using Real Options Analysis. Grammenos CTh. (ed.) The Handbook of Maritime Economics and Business. LLP, London. Bendall, HB. and Stent, AF. 1998. Fast Transportation by Sea. The Royal Institution of Naval Architects International Conference: Fast Transportation by Sea. London. ISBN 0 903055 48X: 1-9. Bendall, HB. and Stent, AF. 2001. A Scheduling Model for a High Speed Containership Service: A Hub and Spoke Short-Sea Application. International Journal of Maritime Economics 3: 262-277. Black, F. and Scholes, M. 1973. The Pricing of Options and Corporate Liabilities. Journal of Political Economy 81: 637-659. Boyle, PP., Evnine, J. and Gibbs. S. 1989. Numerical Evaluation of Multivariate Contingent Claims. The Review of Financial Studies 2: 241-250. Copeland, T. and Antikarov, V. 2000. Real Options, a practitioner’s guide, TEXERE LLC, New York. Cox, JC., Ross, SA. and Rubinstein, M. 1979. Option Pricing: a Simplified Approach. Journal of Financial Economics 7: 229-263. Dall’Aglio, G., Kotz, S. and Salinetti, G. 1991. Advances in Probability Distributions with Given Marginals. Beyond the Copulas, Kluwer Academic Publishers, Dordrecht. Evans, JJ. 1984. Some practical aspects of investment appraisal in shipping. Maritime Gardner, BM., Goss, RO. and Marlow, P.B. 1984. Ship Finance and Fiscal Policy. Maritime Management and Policy 11: 153-196. Johnson, H. 1981. Options on the Maximum or the Minimum of Several Assets. Journal of Financial and Quantitative Analysis 22: 277-283. Kamrad, B. and Ritchken, P. 1991. Multinomial Approximating Models For Options With k State Variables. Management Science 37: 1640-1652. Law, ML. and Kelton, WD. 1991. Simulation Modeling & Analysis, 2nd Edition, McGraw-Hill Book Co. Merton, RC. 1973. Theory of Rational Option Pricing. Bell Journal of Economics and Management Science 4: 141-183. Teisberg, EO. 1995. Methods for Evaluating Capital Investment Decisions Under Uncertainty. Trigeorgis, L (ed.) Real Options in Capital Investment. Models, Strategies and Applications. Praeger, London. Trigeorgis, L (ed.). 1995. Real Options in Capital Investment. Models, Strategies and Applications. Praeger, London

Ship Investment under Uncertainty: Valuing a Real Option on the Maximum of Several Strategies

This paper demonstrates the use of real option analysis to value the flexibility available to management decision making in introducing an express liner service using a new technology. The ship operator's decision is framed as an option to exchange the risky income stream of one strategy (asset) for the maximum of several alternatives as uncertainty is resolved over time. Copeland's and Antikarov's Marketable Asset Disclaimer is invoked; the intrinsic values of the underlying assets and their volatilities and correlations are modelled using traditional discounted cash flow techniques. The option is valued numerically in a multinomial tree. The result is the value of flexibility and is added to the present value of the original strategy to derive the present value of the flexible strategy. A sensitivity analysis is performed to examine the value of the flexible strategy as both the levels of uncertain factors and their volatilities change. Maritime Economics & Logistics (2005) 7, 19–35. doi:10.1057/palgrave.mel.9100122