The Host Defence Peptide LL-37 is Susceptible to Proteolytic Degradation by Wound Fluid Isolated from Foot Ulcers of Diabetic Patients

The pleiotropic effects of host defence peptides (HDPs), including the ability to kill microorganisms, enhance re-epithelialisation and increase angiogenesis, indicates a role for these important peptides as potential therapeutic agents in the treatment of chronic, non-healing wounds. However, the maintenance of peptide integrity, through resistance to degradation by the array of proteinases present at the wound site, is a prerequisite for clinical success. In this study we explored the degradation of exogenous LL-37, one such HDP, by wound fluid from diabetic foot ulcers to determine its susceptibility to proteolytic degradation. Our results suggest that LL-37 is unstable in the diabetic foot ulcer microenvironment. Following overnight treatment with wound fluid, LL-37 was completely degraded. Analysis of cleavage sites suggested potential involvement of both host- and bacterial-derived proteinases. The degradation products were shown to retain some antibacterial activity against Pseudomonas aeruginosa but were inactive against Staphylococcus aureus. In conclusion, our data suggest that stabilising selected peptide bonds within the sequence of LL-37 would represent an avenue for future research prior to clinical studies to address its potential as an exogenously-applied therapeutic in diabetic wounds. 

In and out of home care decisions: The influence of confirmation bias in developing decision supportive reasoning

The aims of this study were to identify the themes Social Workers regard as important in supporting decisions to remove children from, or return them to, the care of their parents. To further elicit underlying hypotheses that are discernible in interpretation of evidence. A case study, comprising a two-part vignette with a questionnaire, recorded demographic information, child welfare attitudes and risk assessments, using scales derived from standardised instruments, was completed by 202 Social Workers in Northern Ireland. There were two manipulated variables, mother’s attitude to removal and child’s attitude to reunification2 years later. In this paper we use data derived from respondents’ qualitative comments explaining their reasoning for in and out of home care decisions. Some 60.9% of respondent’s chose the parental care option at part one, with 94% choosing to have the child remain in foster care at part two. The manipulated variables were found to have no significant statistical effect. However, three underlying hypotheses were found to underpin decisions; (a)child rescue, (b) kinship defence and (c) a hedged position on calculation of risk subject to further assessment. Reasoning strategies utilised by social workers to support their decision making suggest that they tend to selectively interpret information either positively or negatively to support pre-existing underlying hypotheses. This finding is in keeping with the literature on ‘confirmation bias.’ The research further draws attention to the need to incorporate open questions in quantitative studies, to help guard against surface reading of data, which often does not ‘speak for itself.’

Precision Teaching in IV Fluid Prescribing and Patient Safety

OBJECTIVES: Precision Teaching (PT) has been shown to be an effective intervention to assess teaching method effectiveness and evaluate learning outcomes. SAFMEDS (Say All Fast Minute Every Day Shuffled) are a practice/assessment procedure within the PT framework to assist learning and fluency. We explored the effects of a brief intervention with PT, to impart high frequency performance in safe intravenous fluid prescription in a group of final year undergraduate medical students.
METHODS: 133 final year undergraduate medical students completed a multiple choice question (MCQ) test on safe IV fluid prescription at the beginning and end of the study. The control group (n= 76) of students were taught using a current standardized teaching method. Students allocated to the intervention arm of the study were additionally instructed on PT and the use of SAFMEDS. The study group (n = 57) received 50 SAFMEDS cards containing information on the principles of IV fluid prescription scenarios. These students were trained/tested twice per day for 1 minute.
RESULTS: Interim analysis showed that the study group displayed an improvement in fluency and accuracy as the study progressed. There was a statistically significant improvement in MCQ performance for the PT group compared with the control group between the beginning and end of the study (35% vs 15%).
CONCLUSION: These results suggest PT employing SAFMEDS is an effective method for improving fluency, accuracy and patient safety in intravenous fluid prescribing amongst undergraduate medical students.

Evidence reasoning for event inference in smart transport video surveillance

In this paper we present a new event recognition framework, based on the Dempster-Shafer theory of evidence, which combines the evidence from multiple atomic events detected by low-level computer vision analytics. The proposed framework employs evidential network modelling of composite events. This approach can effectively handle the uncertainty of the detected events, whilst inferring high-level events that have semantic meaning with high degrees of belief. Our scheme has been comprehensively evaluated against various scenarios that simulate passenger behaviour on public transport platforms such as buses and trains. The average accuracy rate of our method is 81% in comparison to 76% by a standard rule-based method.

Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study

Introduction: In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT).

Methods: We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors.

Results: In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 mu mol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did not modify the association of mean daily fluid balance with mortality.

Conclusions: In this cohort of patients with AKI requiring RRT, a more positive mean daily fluid balance and intradialytic hypotension were associated with hospital mortality but not with RRT dependence at hospital discharge in survivors.

Reasoning Rights: Comparative judicial engagement

This edited book is about comparative reasoning in human rights cases, exploring the questions: How is it that notionally universal norms are reasoned by courts in such dramatically different ways? What is the shape of this reasoning? What techniques are common across the transnational jurisprudence? What techniques are diverse? With contributions by a team of world-leading human rights scholars, the book moves beyond simply addressing the institutional questions concerning courts and human rights, which too often dominate discussions of this kind. Instead, it seeks a deeper examination of the similarities and divergence in the content of reasons being developed by different courts when addressing comparable human rights questions. These differences, while partly influenced by institutional issues, cannot be attributable to them alone. The book explores the diverse and rich underlying spectrum of human rights reasoning, as a distinctive and particular form of legal reasoning, evident in the case studies across the selected jurisdictions. It is a fascinating study for all those interested in human rights law and legal reasoning.

Using Comparative Reasoning in Human Rights Adjudication:The Court of Justice of the European Union and the European Court of Human Rights Compared

This article examines the relationship between the methods that the European Court of Human Rights (ECtHR) and the Court of Justice of the European Union (CJEU) use to decide disputes that involve ‘human’ or ‘fundamental’ rights claims, and the substantive outcomes that result from the use of these particular methods. It has a limited aim: in attempting to understand the interrelationship between human rights methodology and human rights outcomes, it considers primarily the use of ‘comparative reasoning’ in ‘human’ and ‘fundamental’ rights claims by these courts. It is not primarily concerned with examining the extent to which the use of comparative reasoning is based on an appropriate methodology or whether there is a persuasive normative theory underpinning the use of comparative reasoning. The issues considered in this chapter do some of the groundwork, however, that is necessary in order to address these methodological and normative questions.