Application of Incident Command Structure to clinical trial management in the academic setting: principles and lessons learned

Background Clinical trial success depends on appropriate management, but practical guidance to trial organisation and planning is lacking. The Incident Command System (ICS) is the ‘gold standard’ management system developed for managing diverse operations in major incident and public health arenas. It enables effective and flexible management through integration of personnel, procedures, resources, and communications within a common hierarchical organisational structure. Conventional ICS organisation consists of five function modules: Command, Planning, Operations, Logistics, and Finance/Administration. Large clinical trials will require a separate Regulatory Administrative arm, and an Information arm, consisting of dedicated data management and information technology staff. We applied ICS principles to organisation and management of the Prehospital Use of Plasma in Traumatic Haemorrhage (PUPTH) trial. This trial was a multidepartmental, multiagency, randomised clinical trial investigating prehospital administration of thawed plasma on mortality and coagulation response in severely injured trauma patients. We describe the ICS system as it would apply to large clinical trials in general, and the benefits, barriers, and lessons learned in utilising ICS principles to reorganise and coordinate the PUPTH trial. Results Without a formal trial management structure, early stages of the trial were characterised by inertia and organisational confusion. Implementing ICS improved organisation, coordination, and communication between multiple agencies and service groups, and greatly streamlined regulatory compliance administration. However, unfamiliarity of clinicians with ICS culture, conflicting resource allocation priorities, and communication bottlenecks were significant barriers. Conclusions ICS is a flexible and powerful organisational tool for managing large complex clinical trials. However, for successful implementation the cultural, psychological, and social environment of trial participants must be accounted for, and personnel need to be educated in the basics of ICS

The many assembly histories of massive void galaxies as revealed by integral field spectroscopy

We present the first detailed integral field spectroscopy study of nine central void galaxies with M*>10¹⁰Mʘ using the Wide Field Spectrograph to determine how a range of assembly histories manifest themselves in the current day Universe.While the majority of these galaxies are evolving secularly, we find a range of morphologies, merger histories and stellar population distributions, though similarly low Hα-derived star formation rates (10¹⁰Mʘ have similarly low star formation rates

The Law of Contract Modifications: The Uncertain Quest for a Bench Mark of Enforceability

The law of contract modifications poses an analytical paradox: Modifications should be presumptively invalid because they may encourage extortionary, coercive, opportunistic or monopolistic behaviour. Modifications should be presumptively valid because they represent the parties\u27 assessment of their own best interests. A summary of the case-law reveals theoretical difficulties in the tests of enforceability. The authors use an economic framework of analysis in which they argue that the law of contract modification may be used to minimize the costs of contracting. Dynamic efficiency considerations argue against enforcement of all modifications although static efficiency considerations point in the opposite direction. The potential for opportunistic behaviour and moral hazard problems suggest some variables that are relevant to formulating legal rules which will aid in reducing the long-run costs of contracting

The Law of Contract Modifications: The Uncertain Quest for a Bench Mark of Enforceability

The law of contract modifications poses an analytical paradox: Modifications should be presumptively invalid because they may encourage extortionary, coercive, opportunistic or monopolistic behaviour. Modifications should be presumptively valid because they represent the parties\u27 assessment of their own best interests. A summary of the case-law reveals theoretical difficulties in the tests of enforceability. The authors use an economic framework of analysis in which they argue that the law of contract modification may be used to minimize the costs of contracting. Dynamic efficiency considerations argue against enforcement of all modifications although static efficiency considerations point in the opposite direction. The potential for opportunistic behaviour and moral hazard problems suggest some variables that are relevant to formulating legal rules which will aid in reducing the long-run costs of contracting

Playing the odds in clinical decision making: lessons from berry aneurysms undetected by magnetic resonance angiography

No description supplie

Goldberg's Conjecture is true for random multigraphs

In the 70s, Goldberg, and independently Seymour, conjectured that for any multigraph $G$, the chromatic index $\chi'(G)$ satisfies $\chi'(G)\leq \max \{\Delta(G)+1, \lceil\rho(G)\rceil\}$, where $\rho(G)=\max \{\frac {e(G[S])}{\lfloor |S|/2\rfloor} \mid S\subseteq V \}$. We show that their conjecture (in a stronger form) is true for random multigraphs. Let $M(n,m)$ be the probability space consisting of all loopless multigraphs with $n$ vertices and $m$ edges, in which $m$ pairs from $[n]$ are chosen independently at random with repetitions. Our result states that, for a given $m:=m(n)$, $M\sim M(n,m)$ typically satisfies $\chi'(G)=\max\{\Delta(G),\lceil\rho(G)\rceil\}$. In particular, we show that if $n$ is even and $m:=m(n)$, then $\chi'(M)=\Delta(M)$ for a typical $M\sim M(n,m)$. Furthermore, for a fixed $\varepsilon>0$, if $n$ is odd, then a typical $M\sim M(n,m)$ has $\chi'(M)=\Delta(M)$ for $m\leq (1-\varepsilon)n^3\log n$, and $\chi'(M)=\lceil\rho(M)\rceil$ for $m\geq (1+\varepsilon)n^3\log n$.Comment: 26 page

Efficiency Improvements with Low Heat Rejection Concepts Applied to Low Temperature Combustion

With increasingly stringent governmental regulations on engine emissions such as oxides of nitrogen (NO_(X)) and particulate matter (PM), there is a strong motivation to decrease the production and release of these harmful substances from internal combustion engines. Simultaneously, there are on-going efforts to increase fuel efficiency to curb usage of natural resources and emission of carbon. In general, improvements in one of these areas comes at the cost of the other; however, the results of a previous computational study have indicated that emissions can be decreased while simultaneously increasing efficiency through the application of low heat rejection (LHR) techniques to low temperature combustion (LTC). The goal of this study is to experimentally confirm these findings using a light duty, multi-cylinder diesel engine. LTC is realized through high levels of exhaust gas recirculation (EGR) and retarded injection timings while different degrees of LHR are achieved by means of higher coolant temperatures which should serve to decrease the temperature gradients across the cylinder walls. An energy balance is conducted on the engine to ensure the validity of the efficiency findings. By applying LHR techniques to LTC operation, the undesirable side effects of LTC were found to be mitigated. Specifically, the emissions of carbon monoxide (CO) and unburned hydrocarbons (HC) were reduced and the loss in engine efficiency was also diminished. NO_(X) and PM emissions did increase but they remained at acceptably low levels. In addition, the results of the energy balance substantiated these trends by properly accounting for the bulk of the input energy. While the full potential of improvements in LTC were not explored due to current engine limitations, these results point to the viability of further research into LHR-LTC concepts

Impact of DNA ligase IV on the fidelity of end joining in human cells

A DNA ligase IV (LIG4)‐null human pre‐B cell line and human cell lines with hypomorphic mutations in LIG4 are significantly impaired in the frequency and fidelity of end joining using an in vivo plasmid assay. Analysis of the null line demonstrates the existence of an error‐prone DNA ligase IV‐independent rejoining mechanism in mammalian cells. Analysis of lines with hypomorphic mutations demonstrates that residual DNA ligase IV activity, which is sufficient to promote efficient end joining, nevertheless can result in decreased fidelity of rejoining. Thus, DNA ligase IV is an important factor influencing the fidelity of end joining in vivo. The LIG4‐defective cell lines also showed impaired end joining in an in vitro assay using cell‐free extracts. Elevated degradation of the terminal nucleotide was observed in a LIG4‐defective line, and addition of the DNA ligase IV–XRCC4 complex restored end protection. End protection by DNA ligase IV was not dependent upon ligation. Finally, using purified proteins, we demonstrate that DNA ligase IV–XRCC4 is able to protect DNA ends from degradation by T7 exonuclease. Thus, the ability of DNA ligase IV–XRCC4 to protect DNA ends may contribute to the ability of DNA ligase IV to promote accurate rejoining in vivo

Tidal interactions at the edge of the Local Group: New evidence for tidal features in the Antlia Dwarf Galaxy

Using deep B band imaging down to mu_{B} = 26 mag arcsec^{-2}, we present evidence for tidal tails in the Antlia Dwarf galaxy, one of the most distant members of the Local Group. This elongation is in the direction of Antlia's nearest neighbor, the Magellanic-type NGC 3109. The tail is offset by less than 10 degrees from a vector linking the centers of the two galaxies, indicative of interactions between the pair. Combined with the warped disc previously identified in NGC 3109, Antlia and NGC 3109 must be at a small separation for tidal features to be present in Antlia. We calculate that Antlia cannot be completely disrupted by NGC 3109 in a single interaction unless its orbit pericenter is less than 6 kpc, however multiple interactions could significantly alter its morphology. Therefore despite being located right at the edge of the Local Group, environmental effects are playing an important role in Antlia's evolution.Comment: 8 pages, 4 figures, accepted for publication in ApJ

Reforestation success can be enhanced by improving tree planting methods

Successful cost-effective reforestation plantings depend substantially on maximising sapling survival from the time of planting, yet in reforestation programs remarkably little attention is given to management of saplings at the planting stage and to planting methods used. Critical determinants of sapling survival include their vigour and condition when planted, the wetness of the soil into which saplings are planted, the trauma of transplant shock from nursery to natural field soils, and the method and care taken during planting. While some determinants are outside planters' control, careful management of specific elements associated with outplanting can significantly lessen transplanting shock and improve survival rates. Results from three reforestation experiments designed to examine cost-effective planting methods in the Australian wet tropics provided the opportunity to examine the effects of specific planting treatments, including (1) watering regime prior to planting, (2) method of planting and planter technique, and (3) site preparation and maintenance, on sapling survival and establishment. Focusing on sapling root moisture and physical protection during planting improved sapling survival by at least 10% (>91% versus 81%) at 4 months. Survival rates of saplings under different planting treatments were reflected in longer-term survival of trees at 18–20 months, differing from a low of 52% up to 76–88%. This survival effect was evident more than 6 years after planting. Watering saplings immediately prior to planting, careful planting using a forester's planting spade in moist soil and suppressing grass competition using appropriate herbicides were critical to improved plant survival