Light as a broad spectrum antimicrobial

Antimicrobial resistance is a significant and growing concern. To continue to treat even simple infections, there is a pressing need for new alternative and complementary approaches to antimicrobial therapy. One possible addition to the current range of treatments is the use of narrow-wavelength light as an antimicrobial, which has been shown to eliminate a range of common pathogens. Much progress has already been made with blue light but the potential of other regions of the electromagnetic spectrum is largely unexplored. In order that the approach can be fully and most effectively realized, further research is also required into the effects of energy dose, the harmful and beneficial impacts of light on eukaryotic tissues, and the role of oxygen in eliciting microbial toxicity. These and other topics are discussed within this perspective

Protein-protein interactions of the cold shock protein CspE of salmonella typhimurium

Despite their name, a number of the cold shock proteins are expressed during normal growth, and not just during cold shock, in several species. The function of these constitutively expressed CspA paralogues is unclear. In Salmonella Typhimurium (a major worldwide cause of gastrointestinal disease) they have been linked to various stress responses and the establishment of virulence. Study of the cold shock proteins as gene regulators is therefore of great interest, and they also have potential as targets for antimicrobial development. CspE in Salmonella Typhimurium is constitutively expressed during normal growth. In order to determine its function, attempts were made to identify the interactions it forms with other cellular proteins. Initially, a proteomic investigation attempted to identify proteins which complex with CspE by in vivo cross-linking and affinity purification followed by mass spectrometry. Although no defined complex was consistently identified, the results suggested a handful of proteins which might interact with CspE in a weak or transient manner. These proteins included many from the nucleoid and ribosomal entry site, hinting at CspE’s cellular localisation. In order to investigate these transient interactions, a bacterial two-hybrid system was employed. Interactions between CspE and HupA, a nucleoid protein identified in the proteomic analysis, were probed, as were interactions between CspE and CsdA, an RNA helicase thought to function co-operatively with CspE. The twohybrid system also allowed investigation of CspE dimerisation, which has been reported in vitro but not investigated in vivo until this study. CspE appears not to interact significantly with either HupA, CsdA, or itself at 37oC. Finally in a further attempt to identify interactions of CspE, a genomic library was created to test CspE interactions by two-hybrid assay with random peptides derived from the whole Salmonella genome. The library was successfully created and screened for evidence of interaction, and revealed an association between CspE and a transcriptional repressor, DeoT. DeoT is a repressor of several genes for catabolic processes, suggesting a role for CspE in the regulation of central metabolism. The findings of this work present a number of novel discoveries and several interesting opportunities for further studies

Effects of incremented loads over preferred values on psychophysical and selected gait kinematic factor

This study investigated the effects of incremented loads greater than maximal acceptable loads on selected locomotor kinematic and psychophysical variables for four different hand-held load-carriage methods. Ten male and ten female subjects, between the ages of 18 and 30, participated in four experimental sessions. Data collection involved obtaining selected anthropometric, strength, maximal load and preferred load, gait kinematic, and psychophysical values. The anthropometric, strength and load capacity variables enabled absolute and morphology normalised sex-based comparisons to be made. The kinematic and psychophysical parameters were used to quantify any changes from two sets of baseline values,"unloaded" and "maximal acceptable load" values, when loads were increased and carrying methods changed. Statistical analysis revealed that males were taller, heavier and stronger than females (p<0.05). Males chose significantly greater maximal acceptable loads and absolute maximal loads than females when expressed in their absolute or relative terms. Preferred walking speeds were not significantly different for unloaded or loaded conditions, although males walked significantly faster in absolute terms (but not in relative terms) than females. Different load carrying methods and incremented loads brought. about significant changes to several of the kinematic parameters investigated. Finally, ratings of perceived exertion, as well as the number of exertion sites, were seen to increase significantly as load increased. These values were not, however, significantly affected by differences in load carriage method

Recommendations on the nature of the passenger response time distribution to be used in the MSC 1033 assembly time analysis based on data derived from sea trials

The passenger response time distributions adopted by the International Maritime Organisation (IMO)in their assessment of the assembly time for passanger ships involves two key assumptions. The first is that the response time distribution assumes the form of a uniform random distribution and the second concerns the actual response times. These two assumptions are core to the validity of the IMO analysis but are not based on real data, being the recommendations of an IMO committee. In this paper, response time data collected from assembly trials conducted at sea on a real passanger vessel using actual passangers are presented and discussed. Unlike the IMO specified response time distributions, the data collected from these trials displays a log-normal distribution, similar to that found in land based environments. Based on this data, response time distributions for use in the IMO assesmbly for the day and night scenarios are suggeste

Agent-based models of social behaviour and communication in evacuations:A systematic review

Most modern agent-based evacuation models involve interactions between evacuees. However, the assumed reasons for interactions and portrayal of them may be overly simple. Research from social psychology suggests that people interact and communicate with one another when evacuating and evacuee response is impacted by the way information is communicated. Thus, we conducted a systematic review of agent-based evacuation models to identify 1) how social interactions and communication approaches between agents are simulated, and 2) what key variables related to evacuation are addressed in these models. We searched Web of Science and ScienceDirect to identify articles that simulated information exchange between agents during evacuations, and social behaviour during evacuations. From the final 70 included articles, we categorised eight types of social interaction that increased in social complexity from collision avoidance to social influence based on strength of social connections with other agents. In the 17 models which simulated communication, we categorised four ways that agents communicate information: spatially through information trails or radii around agents, via social networks and via external communication. Finally, the variables either manipulated or measured in the models were categorised into the following groups: environmental condition, personal attributes of the agents, procedure, and source of information. We discuss promising directions for agent-based evacuation models to capture the effects of communication and group dynamics on evacuee behaviour. Moreover, we demonstrate how communication and group dynamics may impact the variables commonly used in agent-based evacuation models

Mutual Information for the Detection of Crush

Fatal crush conditions occur in crowds with tragic frequency. Event organizers and architects are often criticised for failing to consider the causes and implications of crush, but the reality is that both the prediction and prevention of such conditions offer a significant technical challenge. Full treatment of physical force within crowd simulations is precise but often computationally expensive; the more common method of human interpretation of results is computationally “cheap” but subjective and time-consuming. This paper describes an alternative method for the analysis of crowd behaviour, which uses information theory to measure crowd disorder. We show how this technique may be easily incorporated into an existing simulation framework, and validate it against an historical event. Our results show that this method offers an effective and efficient route towards automatic detection of the onset of crush

The influence of dose distribution on treatment outcome in the SCOPE 1 oesophageal cancer trial

Purpose The first aim of this study was to assess plan quality using a conformity index (CI) and analyse its influence on patient outcome. The second aim was to identify whether clinical and technological factors including planning treatment volume (PTV) volume and treatment delivery method could be related to the CI value. Methods and materials By extending the original concept of the mean distance to conformity (MDC) index, the OverMDC and UnderMDC of the 95 % isodose line (50Gy prescribed dose) to the PTV was calculated for 97 patients from the UK SCOPE 1 trial (ISCRT47718479). Data preparation was carried out in CERR, with Kaplan-Meier and multivariate analysis undertaken in EUCLID and further tests in Microsoft Excel and IBM’s SPSS. Results A statistically significant breakpoint in the overall survival data, independent of cetuximab, was found with OverMDC (4.4 mm, p < 0.05). This was not the case with UnderMDC. There was a statistically significant difference in PTV volume either side of the OverMDC breakpoint (Mann Whitney p < 0.001) and in OverMDC value dependent on the treatment delivery method (mean IMRT = 2.1 mm, mean 3D-CRT = 4.1 mm Mann Whitney p < 0.001). Re-planning the worst performing patients according to OverMDC from 3D-CRT to VMAT resulted in a mean reduction in OverMDC of 2.8 mm (1.6–4.0 mm). OverMDC was not significant in multivariate analysis that included age, sex, staging, tumour type, and position. Conclusion Although not significant when included in multivariate analysis, we have shown in univariate analysis that a patient’s OverMDC is correlated with overall survival. OverMDC is strongly related to IMRT and to a lesser extent with PTV volume. We recommend that VMAT planning should be used for oesophageal planning when available and that attention should be paid to the conformity of the 95 % to the PTV

Simulating movement devices used in hospital evacuation

In hospitals, the evacuation of those with severe movement impairments can be highly problematic for the patients, for the staff and for other evacuees. It is critical to understand the performance of horizontal and vertical evacuation procedures, including the means by which people with reduced mobility can be assisted during stair descent. Microsimulation modelling provides a useful tool to assess evacuation strategies, given the challenges of preparing and transporting patients in need of on-going care and the unfeasibility of real evacuation drills. However, current simulation models typically focus on the movement of individual agents, not the staff-patient interactions and sizable equipment required to carry out assisted evacuation. To address this, the buildingEXODUS evacuation model has been enhanced to represent moving objects in addition to moving individual agents. This paper describes the modelling theory behind this development, where dedicated data has been applied to enable the explicit specification of evacuation devices, operated by agents (for instance, representing the vertical travel speeds achieved—with averages ranging between 0.6 m/s and 0.84 m/s—when employing different movement devices). Algorithms are presented that calculate the movement of devices along corridors, through doorways and in stairway descent, including a method of geometric decomposition of the available hospital evacuation routes. This new functionality addresses the key evacuation components of repeated patient collection and has numerous applications, both in simulating hospital evacuation and in representing evacuation of other premises that include people with reduced mobility. Examination of the performance of this functionality found it predicated performance within 6% of expectation. Once further testing is completed, the resultant tool can be used to significantly enhance planning and diagnostic capabilities related to the evacuation of hospital and other healthcare facilities