JCOERE Consortium. Report 1: Identifying substantive and procedural rules in preventive restructuring frameworks including the Preventive Restructuring Directive which may be incompatible with judicial co-operation obligations

Judicial Co-operation Supporting Economic Recovery in Europe (JCOERE).This report provides a comprehensive analysis of the nature of substantive and procedural aspects that may arise in complex preventive restructuring or rescue regimes as envisaged by the Preventive Restructuring Directive (2019/1023). The report includes a comparative analysis of eleven European Member State jurisdictions, considering their pre-existing systems and approaches, and their responses taken to the Preventive Restructuring Directive

Cancer Cachexia: Mechanisms and Clinical Implications

Cachexia is a multifactorial process of skeletal muscle and adipose tissue atrophy resulting in progressive weight loss. It is associated with poor quality of life, poor physical function, and poor prognosis in cancer patients. It involves multiple pathways: procachectic and proinflammatory signals from tumour cells, systemic inflammation in the host, and widespread metabolic changes (increased resting energy expenditure and alterations in metabolism of protein, fat, and carbohydrate). Whether it is primarily driven by the tumour or as a result of the host response to the tumour has yet to be fully elucidated. Cachexia is compounded by anorexia and the relationship between these two entities has not been clarified fully. Inconsistencies in the definition of cachexia have limited the epidemiological characterisation of the condition and there has been slow progress in identifying therapeutic agents and trialling them in the clinical setting. Understanding the complex interplay of tumour and host factors will uncover new therapeutic targets

A five year record of high-frequency in situ measurements of non-methane hydrocarbons at Mace Head, Ireland

Continuous high-frequency in situ measurements of a range of non-methane hydrocarbons have been made at Mace Head since January 2005. Mace Head is a background Northern Hemispheric site situated on the eastern edge of the Atlantic. Five year measurements (2005–2009) of six C<sub>2</sub>–C<sub>5</sub> non-methane hydrocarbons have been separated into baseline Northern Hemispheric and European polluted air masses, among other sectors. Seasonal cycles in baseline Northern Hemispheric air masses and European polluted air masses arriving at Mace Head have been studied. Baseline air masses show a broad summer minima between June and September for shorter lived species, longer lived species show summer minima in July/August. All species displayed a winter maxima in February. European air masses showed baseline elevated mole fractions for all non-methane hydrocarbons. Largest elevations (of up to 360 ppt for ethane maxima) from baseline data were observed in winter maxima, with smaller elevations observed during the summer. Analysis of temporal trends using the Mann-Kendall test showed small (<6 % yr<sup>−1</sup>) but statistically significant decreases in the butanes and <i>i</i>-pentane between 2005 and 2009 in European air. No significant trends were found for any species in baseline air

A Combined Technique for Randomisation of a Small Number of Participants with a Variety of Covariates into Treatment and Control Groups in Randomised Controlled Trials

Background: Randomised controlled trials are widely favoured in research design as the most rigorous way of determining the effectiveness of a treatment. For assigning a small number of participants who are identified before the start of the randomisation into treatment and control, the simple randomization technique can lead to imbalance of covariates among the groups. Furthermore while the stratified randomization method can control for the effect of covariates, in smaller clinical trials, the allocation of participants to groups by flip of a coin can result in uneven arms when the number of participants in each stratum in low. Despite the ability of covariate adaptive randomization technique in minimising the difference in covariate between the arms, the techniques comes with an unnecessary increase in the computational process specifically when number of covariates increases, and when all participants are identified prior to the randomisation. The purpose of this study was to propose a method of assigning small number of participants (68) who are identified before the start of randomisation, into treatment and control arms. Methods: The participants were first assigned into strata. For strata with even number of participants, the participants are sequentially pulled out of the strata on a random basis and assigned to arms by flip of a coin until half of the participants are assigned to any of the two arms. Then the remaining participants were assigned to the other arm. When the number of participants in a stratum is odd the first participants was pulled out of the stratum on a random basis and kept separate, then the remaining even number of participants were assigned to arms according to the method for strata that contain even number of participants. The first participants that were pulled out of the strata with odd number of participants were assigned sequentially using covariate adaptive randomisation method. Results: Two arms were created with minimal difference between the two arms and with the sum of absolute difference equal to 12. Conclusions: The method showed to be able to assign small number of participants into balanced arms with minimal computational costs when a number of covariates exist

Linking microbial community structure and function during the acidified anaerobic digestion of grass

This research was funded by the Irish Higher Education Authority Program for Research in Third Level Institutions Cycle 5: – PRTLI-5 ESI Ph.D. ENS Program. This work was also supported by the Wellcome Trust (grant number 094476/Z/10/Z for the TripleTOF 5600 mass spectrometer at the University of St Andrews), NERC (grant number NE/L011956/1), and a Royal Irish Academy Mobility Grant.Harvesting valuable bioproducts from various renewable feedstocks is necessary for the critical development of a sustainable bioeconomy. Anaerobic digestion is a well-established technology for the conversion of wastewater and solid feedstocks to energy with the additional potential for production of process intermediates of high market values (e.g. carboxylates). In recent years, first-generation biofuels typically derived from food crops have been widely utilised as a renewable source of energy. The environmental and socioeconomic limitations of such strategy, however, have led to the development of second-generation biofuels utilising, amongst other feedstocks, lignocellulosic biomass. In this context, the anaerobic digestion of perennial grass holds great promise for the conversion of sustainable renewable feedstock to energy and other process intermediates. The advancement of this technology however, and its implementation for industrial applications, relies on a greater understanding of the microbiome underpinning the process. To this end, microbial communities recovered from replicated anaerobic bioreactors digesting grass were analysed. The bioreactors leachates were not buffered and acidic pH (between 5.5 and 6.3) prevailed at the time of sampling as a result of microbial activities. Community composition and transcriptionally active taxa were examined using 16S rRNA sequencing and microbial functions were investigated using metaproteomics. Bioreactor fraction, i.e. grass or leachate, was found to be the main discriminator of community analysis across the three molecular level of investigation (DNA, RNA and proteins). Six taxa, namely Bacteroidia, Betaproteobacteria, Clostridia, Gammaproteobacteria, Methanomicrobia and Negativicutes accounted for the large majority of the three datasets. The initial stages of grass hydrolysis were carried out by Bacteroidia, Gammaproteobacteria and Negativicutes in the grass biofilms, in addition to Clostridia in the bioreactor leachates. Numerous glycolytic enzymes and carbohydrate transporters were detected throughout the bioreactors in addition to proteins involved in butanol and lactate production. Finally, evidence of the prevalence of stressful conditions within the bioreactors and particularly impacting Clostridia was observed in the metaproteomes. Taken together, this study highlights the functional importance of Clostridia during the anaerobic digestion of grass and thus research avenues allowing members of this taxon to thrive should be explored.Publisher PDFPeer reviewe

Detection of Hepatitis E Virus Antibodies in Dogs in the United Kingdom.

Hepatitis E virus (HEV) genotypes 3 and 4 are zoonotic pathogens, with pigs predominantly implicated in disease transmission. The rapid rise in human cases in developed countries over the past decade indicates a change in epidemiology of HEV, and it has been suggested that additional animal species may be involved in transmission of infection. Multiple studies have identified contact with dogs as a risk factor for HEV infection in industrialised nations, and a low seroprevalence to HEV has previously been reported in dogs in low-income countries. In this study we aimed to evaluate the possibility that dogs are susceptible to HEV, and determine the frequency with which this occurs. Serum samples from UK dogs with and without hepatitis were screened for HEV-specific antibodies, and canine liver and stool samples were analysed by qPCR for the presence of HEV RNA. We describe evidence to show HEV infection occurs at low levels in dogs in the UK, but the strain of origin is undetermined. The low seroprevalence level of HEV in dogs implies the risk of zoonotic disease transmission is likely to be limited, but further investigations will be required to determine if HEV-infected dogs can transmit HEV to man.This project was made possible by a Wellcome Trust Vacation Scholarship to AM, and was supported by a PhD studentship from the Medical Research Council to SC, a Wellcome Trust Research Training Fellowship to NB (Ref: WT088619MA) and a Wellcome Trust Senior Fellowship to IG (Ref: WT097997MA).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.012870

Young at Heart: Pioneering Approaches to Model Nonischaemic Cardiomyopathy with Induced Pluripotent Stem Cells

A mere 9 years have passed since the revolutionary report describing the derivation of induced pluripotent stem cells from human fibroblasts and the first in-patient translational use of cells obtained from these stem cells has already been achieved. From the perspectives of clinicians and researchers alike, the promise of induced pluripotent stem cells is alluring if somewhat beguiling. It is now evident that this technology is nascent and many areas for refinement have been identified and need to be considered before induced pluripotent stem cells can be routinely used to stratify, treat and cure patients, and to faithfully model diseases for drug screening purposes. This review specifically addresses the pioneering approaches to improve induced pluripotent stem cell based models of nonischaemic cardiomyopathy

Special Report: Judicial Co-Operation in the European Union: Insolvency and Rescue

Judicial Co-Operation for Economic Recovery in Europe (JCOERE) is a research action project funded by the EU Commission DG Justice. JCOERE focuses on substantive and procedural rules typical to restructuring frameworks that are likely to present obstacles to court co-operation as mandated by the European Insolvency Regulation Recast. In its first Report (JCOERE 1) the Project surveys a range of rescue frameworks in European jurisdictions, benchmarked against core concepts in the Preventive Restructuring Directive. In its second phase, engaging proactively with national EU judiciary, JCOERE will document experiences with co-operation including utilisation of co-operation guidelines. It will disseminate its findings to support co-operation in corporate rescue. This report summarises the first steps and some of the preliminary findings that are fully described in JCOERE Report 1

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

The “Worktivity” mHealth intervention to reduce sedentary behaviour in the workplace: a feasibility cluster randomised controlled pilot study

Background Office work generally consists of high amounts of sedentary behaviour (SB) which has been associated with negative health consequences. We developed the “WorktivIty” mobile app to help office workers reduce their SB through self-monitoring and feedback on sedentary time, prompts to break sedentary time, and educational facts. The aim of this paper is to report the feasibility of delivering the Worktivity intervention to desk-based office workers in the workplace setting and describe methodological considerations for a future trial. Methods We conducted a three-arm feasibility cluster randomised controlled pilot study over an 8-week period with full time-desk based employees. Clustered randomisation was to one of three groups: Worktivity mobile app (MA; n = 20), Worktivity mobile app plus SSWD (MA+SSWD; n = 20), or Control (C; n = 16). Feasibility was assessed using measures of recruitment and retention, intervention engagement, intervention delivery, completion rates and usable data, adverse events, and acceptability. Results Recruitment of companies to participate in this study was challenging (8% of those contacted), but retention of individual participants within the recruited groups was high (81% C, 90% MA + SSWD, 95% MA). Office workers’ engagement with the app was moderate (on average 59%). Intervention delivery was partially compromised due to diminishing user engagement and technical issues related to educational fact delivery. Sufficient amounts of useable data were collected, however either missing or unusable data were observed with activPAL™, with data loss increasing at each follow up time point. No serious adverse events were identified during the study. The majority of participants agreed that the intervention could be implemented within the workplace setting (65% MA; 72% MA + SSWD) but overall satisfaction with the intervention was modest (58% MA; 39% MA + SSWD). Conclusions The findings suggest that, in principle, it is feasible to implement a mobile app-based intervention in the workplace setting however the Worktivity intervention requires further technical refinements before moving to effectiveness trials. Challenges relating to the initial recruitment of workplaces and maintaining user engagement with the mHealth intervention over time need to be addressed prior to future large-scale implementation. Further research is needed to identify how best to overcome these challenges.ISSN:1471-245