All-Wales licensed premises intervention (AWLPI): a randomised controlled trial to reduce alcohol-related violence

Background: Alcohol-related violence in and in the vicinity of licensed premises continues to place a considerable burden on the United Kingdom’s (UK) health services. Robust interventions targeted at licensed premises are therefore required to reduce the costs of alcohol-related harm. Previous evaluations of interventions in licensed premises have a number of methodological limitations and none have been conducted in the UK. The aim of the trial was to determine the effectiveness of the Safety Management in Licensed Environments intervention designed to reduce alcohol-related violence in licensed premises, delivered by Environmental Health Officers, under their statutory authority to intervene in cases of violence in the workplace.<p></p> Methods/Design: A national randomised controlled trial, with licensed premises as the unit of allocation. Premises were identified from all 22 Local Authorities in Wales. Eligible premises were those with identifiable violent incidents on premises, using police recorded violence data. Premises were allocated to intervention or control by optimally balancing by Environmental Health Officer capacity in each Local Authority, number of violent incidents in the 12 months leading up to the start of the project and opening hours. The primary outcome measure is the difference in frequency of violence between intervention and control premises over a 12 month follow-up period, based on a recurrent event model. The trial incorporates an embedded process evaluation to assess intervention implementation, fidelity, reach and reception, and to interpret outcome effects, as well as investigate its economic impact.<p></p> Discussion: The results of the trial will be applicable to all statutory authorities directly involved with managing violence in the night time economy and will provide the first formal test of Health and Safety policy in this environment. If successful, opportunities for replication and generalisation will be considered.<p></p&gt

Immunomodulatory therapeutic strategies in stroke

The role of immunity in all stages of stroke is increasingly being recognised, from the pathogenesis of risk factors to tissue repair, leading to the investigation of a range of immunomodulatory therapies. In the acute phase of stroke, proposed therapies include drugs targeting pro-inflammatory cytokines, matrix metalloproteinases, and leukocyte infiltration, with a key objective to reduce initial brain cell toxicity. Systemically, the early stages of stroke are also characterised by stroke-induced immunosuppression, where downregulation of host defences predisposes patients to infection. Therefore, strategies to modulate innate immunity post-stroke have garnered greater attention. A complementary objective is to reduce longer term sequelae, by focusing on adaptive immunity. Following stroke onset, the integrity of the blood-brain barrier is compromised, exposing central nervous system (CNS) antigens to systemic adaptive immune recognition, potentially inducing autoimmunity. Some pre-clinical efforts have been made to tolerise the immune system to CNS antigens pre-stroke. Separately, immune cell populations which exhibit a regulatory phenotype (T and B regulatory cells) have been shown to ameliorate post-stroke inflammation and contribute to tissue repair. Cell-based therapies, established in oncology and transplantation, could become a strategy to treat the acute and chronic stages of stroke. Furthermore, a role for the gut microbiota in ischemic injury has received attention. Finally, the immune system may play a role in remote ischemic preconditioning-mediated neuroprotection against stroke. The development of stroke therapies involving organs distant to the infarct site, therefore, should not be overlooked. This review will discuss the immune mechanisms of various therapeutic strategies, surveying published data and discussing more theoretical mechanisms of action that have yet to be exploited

Is liver transplantation using organs donated after cardiac death cost‐effective or does it decrease waitlist death by increasing recipient death?

AbstractObjectivesThe aim of this study was to evaluate the cost‐effectiveness in liver transplantation (LT) of utilizing organs donated after cardiac death (DCD) compared with organs donated after brain death (DBD).MethodsA Markov‐based decision analytic model was created to compare two LT waitlist strategies distinguished by organ type: (i) DBD organs only, and (ii) DBD and DCD organs. The model simulated outcomes for patients over 10 years with annual cycles through one of four health states: survival; ischaemic cholangiopathy; retransplantation, and death. Baseline values and ranges were determined from an extensive literature review. Sensitivity analyses tested model strength and parameter variability.ResultsOverall survival is decreased, and biliary complications and retransplantation are increased in recipients of DCD livers. Recipients of DBD livers gained 5.6 quality‐adjusted life years (QALYs) at a cost of US$69 000/QALY, whereas recipients on the DBD + DCD LT waitlist gained 6.0 QALYs at a cost of US$61 000/QALY. The DBD + DCD organ strategy was superior to the DBD organ‐only strategy.conclusionsThe extension of life and quality of life provided by DCD LT to patients on the waiting list who might otherwise not receive a liver transplant makes the continued use of DCD livers cost‐effective

Determination of parameters for successful spray coating of silicon microneedle arrays

Coated microneedle patches have demonstrated potential for effective, minimally invasive, drug and vaccine delivery. To facilitate cost-effective, industrial-scale production of coated microneedle patches, a continuous coating method which utilises conventional pharmaceutical processes is an attractive prospect. Here, the potential of spray-coating silicon microneedle patches using a conventional film-coating process was evaluated and the key process parameters which impact on coating coalescence and weight were identified by employing a fractional factorial design to coat flat silicon patches. Processing parameters analysed included concentration of coating material, liquid input rate, duration of spraying, atomisation air pressure, gun-to-surface distance and air cap setting. Two film-coating materials were investigated; hydroxypropylmethylcellulose (HPMC) and carboxymethylcellulose (CMC). HPMC readily formed a film-coat on silicon when suitable spray coating parameter settings were determined. CMC films required the inclusion of a surfactant (1%, w/w Tween 80) to facilitate coalescence of the sprayed droplets on the silicon surface. Spray coating parameters identified by experimental design, successfully coated 280 μm silicon microneedle arrays, producing an intact film-coat, which follows the contours of the microneedle array without occlusion of the microneedle shape. This study demonstrates a novel method of coating microneedle arrays with biocompatible polymers using a conventional film-coating process. It is the first study to indicate the thickness and roughness of coatings applied to microneedle arrays. The study also highlights the importance of identifying suitable processing parameters when film coating substrates of micron dimensions. The ability of a fractional factorial design to identify these critical parameters is also demonstrated. The polymer coatings applied in this study can potentially be drug loaded for intradermal drug and vaccine delivery

The Productivity Consequences of Two Ergonomic Interventions

Pre- and post-intervention data on health outcomes, absenteeism, and productivity from a longitudinal, quasi-experimental design field study of office workers was used to evaluate the economic consequences of two ergonomic interventions. Researchers assigned individuals in the study to three groups: a group that received an ergonomically designed chair and office ergonomics training; a group that received office ergonomics training only; and a control group. The results show that while training alone has neither a statistically significant effect on health nor productivity, the chair-with-training intervention substantially reduced pain and improved productivity. Neither intervention affected sick leave hours

Beam Test of a Segmented Foil SEM Grid

A prototype Secondary-electron Emission Monitor (SEM) was installed in the 8 GeV proton transport line for the MiniBooNE experiment at Fermilab. The SEM is a segmented grid made with 5 um Ti foils, intended for use in the 120 GeV NuMI beam at Fermilab. Similar to previous workers, we found that the full collection of the secondary electron signal requires a bias voltage to draw the ejected electrons cleanly off the foils, and this effect is more pronounced at larger beam intensity. The beam centroid and width resolutions of the SEM were measured at beam widths of 3, 7, and 8 mm, and compared to calculations. Extrapolating the data from this beam test, we expect a centroid and width resolutions of 20um and 25 um, respectively, in the NuMI beam which has 1 mm spot size.Comment: submitted to Nucl. Instr. Meth.

Fluctuations in viscous fingering

Our experiments on viscous (Saffman-Taylor) fingering in Hele-Shaw channels reveal finger width fluctuations that were not observed in previous experiments, which had lower aspect ratios and higher capillary numbers Ca. These fluctuations intermittently narrow the finger from its expected width. The magnitude of these fluctuations is described by a power law, Ca^{-0.64}, which holds for all aspect ratios studied up to the onset of tip instabilities. Further, for large aspect ratios, the mean finger width exhibits a maximum as Ca is decreased instead of the predicted monotonic increase.Comment: Revised introduction, smoothed transitions in paper body, and added a few additional minor results. (Figures unchanged.) 4 pages, 3 figures. Submitted to PRE Rapi