Structural relaxation in the hydrogen-bonding liquids N-methylacetamide and water studied by optical Kerr-effect spectroscopy

Structural relaxation in the peptide model N-methylacetamide (NMA) is studied experimentally by ultrafast optical Kerr-effect spectroscopy over the normal-liquid temperature range and compared to the relaxation measured in water at room temperature. It is seen that in both hydrogen-bonding liquids, beta relaxation is present and in each case it is found that this can be described by the Cole-Cole function. For NMA in this temperature range, the alpha and beta relaxations are each found to have an Arrhenius temperature dependence with indistinguishable activation energies. It is known that the variations on the Debye function, including the Cole-Cole function, are unphysical, and we introduce two general modifications: one allows for the initial rise of the function, determined by the librational frequencies, and the second allows the function to be terminated in the alpha relaxation

GABA-B receptor function in healthy volunteers, a pharmacokinetic and pharmacodynamic study of two doses of baclofen compared to placebo

AIMS AND HYPOTHESIS To assess the subjective and objective effects of baclofen on brain function in healthy volunteers. BACKGROUND Recent evidence suggests baclofen, a γ-aminobutyric acid type B (GABA-B) receptor agonist, reduces alcohol consumption and craving and promotes abstinence in alcoholics. However, characterisation of the GABA-B receptor system in clinical addiction is limited, and it is unclear why some patients require, or tolerate, higher doses to treat alcoholism. This study assesses the effects of baclofen on brain function in healthy volunteers to inform future studies investigating the sensitivity of GABA-B receptors in alcohol addiction. METHODS Eight healthy male volunteers completed a double blind randomised 3-way cross over study, receiving oral placebo (vitamin C 100mg), 10mg and 60mg baclofen. Subjective and objective measurements were taken at baseline (before medication) and at +30mins, 1, 2, 3, 4 and 6 hours after dosing. Objective measures included blood plasma samples, heart rate and blood pressure. Subjective measures included; the Subjective High Assessment Questionnaire (SHAS), visual analogue scales for sleepy, relaxed, tense and alert and a motor coordination task (zig-zag task). Pharmacokinetic data was obtained using liquid chromatography mass-spectrometry (LC-MS) to measure plasma baclofen concentrations. RESULTS 60mg Baclofen showed changes in subjective measures peaking at 2 hours post dosing compared with placebo, including a significant increase (p<0.05) in total SHAS scores with individual items, including feeling ‘drunk or intoxicated’, effects of alcohol and ‘muddled or confused’ particular affected.. Systolic blood pressure was significantly increased (p<0.05) at the 2 hours post 60mg dose. For both 10mg and 60mg baclofen, peak plasma concentration was achieved 60 minutes post dose. Pharmacokinetic data will be presented. There were no significant changes in these measures between 10mg Baclofen and placebo. CONCLUSIONS The objective and subjective measures used in this study are able to differentiate between placebo and 60mg baclofen. These findings will inform further research investigating the sensitivity of GABA-B receptors in alcohol addiction

Waterborne Elizabethkingia meningoseptica in adult critical care

Elizabethkingia meningoseptica is an infrequent colonizer of the respiratory tract; its pathogenicity is uncertain. In the context of a 22-month outbreak of E. meningoseptica acquisition affecting 30 patients in a London, UK, critical care unit (3% attack rate) we derived a measure of attributable morbidity and determined whether E. meningoseptica is an emerging nosocomial pathogen. We found monomicrobial E. meningoseptica acquisition (n = 13) to have an attributable morbidity rate of 54% (systemic inflammatory response syndrome >2, rising C-reactive protein, new radiographic changes), suggesting that E. meningoseptica is a pathogen. Epidemiologic and molecular evidence showed acquisition was water-source–associated in critical care but identified numerous other E. meningoseptica strains, indicating more widespread distribution than previously considered. Analysis of changes in gram-negative speciation rates across a wider London hospital network suggests this outbreak, and possibly other recently reported outbreaks, might reflect improved diagnostics and that E. meningoseptica thus is a pseudo-emerging pathogen

Genomic epidemiology of clinical Campylobacter spp. at a single health trust site

© 2018 The Authors. Published by Microbiology Society. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1099/mgen.0.000227Campylobacter is the leading cause of bacterial enteritis in the developed world, and infections with the organism are largely sporadic in nature. Links between sporadic cases have not been established, with the majority of infections thought to be caused by genetically distinct isolates. Using a read-mapping approach, 158 clinical isolates collected during 2014 from the greater Nottinghamshire area were analysed to assess the local population structure and investigate potential case linkages between sporadic cases of campylobacteriosis. Four instances (2.5 %) of case linkage were observed across the dataset. This study demonstrates that case linkage does occur between sporadic Campylobacter infections, and provides evidence that a dual multi-locus sequence typing/within-lineage single nucleotide polymorphism typing approach to Campylobacter genomic epidemiology provides a benefit to public-health investigations.Nottingham Trent Universit

The development of the Quality Indicator for Rehabilitative Care (QuIRC): a measure of best practice for facilities for people with longer term mental health problems.

BACKGROUND: Despite the progress over recent decades in developing community mental health services internationally, many people still receive treatment and care in institutional settings. Those most likely to reside longest in these facilities have the most complex mental health problems and are at most risk of potential abuses of care and exploitation. This study aimed to develop an international, standardised toolkit to assess the quality of care in longer term hospital and community based mental health units, including the degree to which human rights, social inclusion and autonomy are promoted. METHOD: The domains of care included in the toolkit were identified from a systematic literature review, international expert Delphi exercise, and review of care standards in ten European countries. The draft toolkit comprised 154 questions for unit managers. Inter-rater reliability was tested in 202 units across ten countries at different stages of deinstitutionalisation and development of community mental health services. Exploratory factor analysis was used to corroborate the allocation of items to domains. Feedback from those using the toolkit was collected about its usefulness and ease of completion. RESULTS: The toolkit had excellent inter-rater reliability and few items with narrow spread of response. Unit managers found the content highly relevant and were able to complete it in around 90 minutes. Minimal refinement was required and the final version comprised 145 questions assessing seven domains of care. CONCLUSIONS: Triangulation of qualitative and quantitative evidence directed the development of a robust and comprehensive international quality assessment toolkit for units in highly variable socioeconomic and political contexts

The role of healthcare professionals in encouraging parents to see and hold their stillborn baby: a meta-synthesis of qualitative studies.

Background: Globally, during 2013 there were three million recorded stillbirths. Where clinical guidelines exist some recommend that professionals do not encourage parental contact. The guidance is based on quantitative evidence that seeing and holding the baby is not beneficial for everyone, but has been challenged by bereaved parents' organisations. We aim to inform future guideline development through a synthesis of qualitative studies reporting data relevant to the research question; how does the approach of healthcare professionals to seeing and holding the baby following stillbirth impact parents views and experiences? Methods/Findings: Using a predetermined search strategy of PubMed and PsychINFO we identified robust qualitative studies reporting bereaved parental views and/or experiences relating to seeing and holding their stillborn baby (final search 24 February, 2014). Eligible studies were English language, reporting parental views, with gestational loss >20weeks. Quality was independently assessed by three authors using a validated tool. We used meta-ethnographic techniques to identify key themes and a line of argument synthesis. We included 12 papers, representing the views of 333 parents (156 mothers, 150 fathers, and 27 couples) from six countries. The final themes were: "[Still]birth: Nature of care is paramount", "Real babies: Perfect beauties, monsters and spectres", and "Opportunity of a lifetime lost." Our line-of-argument synthesis highlights the contrast between all parents need to know their baby, with the time around birth being the only time memories can be made, and the variable ability that parents have to articulate their preferences at that time. Thus, we hypothesised that how health professionals approach contact between parents and their stillborn baby demands a degree of active management. An important limitation of this paper is all included studies originated from high income, westernised countries raising questions about the findings transferability to other cultural contexts. We do not offer new evidence to answer the question "Should parents see and hold their stillborn baby?", instead our findings advance understanding of how professionals can support parents to make appropriate decisions in a novel, highly charged and dynamic situation. Conclusions: Guidelines could be more specific in their recommendations regarding parental contact. The role of healthcare professionals in encouraging parents to see and hold their stillborn baby is paramount. Parental choice not to see their baby, apprehension, or uncertainty should be continuously revisited in the hours after birth as the opportunity for contact is fleeting and final

Genomic epidemiology of a protracted hospital outbreak caused by multidrug-resistant Acinetobacter baumannii in Birmingham, England

BACKGROUND: Multidrug-resistant Acinetobacter baumannii commonly causes hospital outbreaks. However, within an outbreak, it can be difficult to identify the routes of cross-infection rapidly and accurately enough to inform infection control. Here, we describe a protracted hospital outbreak of multidrug-resistant A. baumannii, in which whole-genome sequencing (WGS) was used to obtain a high-resolution view of the relationships between isolates. METHODS: To delineate and investigate the outbreak, we attempted to genome-sequence 114 isolates that had been assigned to the A. baumannii complex by the Vitek2 system and obtained informative draft genome sequences from 102 of them. Genomes were mapped against an outbreak reference sequence to identify single nucleotide variants (SNVs). RESULTS: We found that the pulsotype 27 outbreak strain was distinct from all other genome-sequenced strains. Seventy-four isolates from 49 patients could be assigned to the pulsotype 27 outbreak on the basis of genomic similarity, while WGS allowed 18 isolates to be ruled out of the outbreak. Among the pulsotype 27 outbreak isolates, we identified 31 SNVs and seven major genotypic clusters. In two patients, we documented within-host diversity, including mixtures of unrelated strains and within-strain clouds of SNV diversity. By combining WGS and epidemiological data, we reconstructed potential transmission events that linked all but 10 of the patients and confirmed links between clinical and environmental isolates. Identification of a contaminated bed and a burns theatre as sources of transmission led to enhanced environmental decontamination procedures. CONCLUSIONS: WGS is now poised to make an impact on hospital infection prevention and control, delivering cost-effective identification of routes of infection within a clinically relevant timeframe and allowing infection control teams to track, and even prevent, the spread of drug-resistant hospital pathogens

ESBL-producing Enterobacteriaceae in 24 neonatal units and associated networks in the south of England: no clustering of ESBL-producing Escherichia coli in units or networks.

OBJECTIVES: The objectives of this study were to characterize ESBL-producing Enterobacteriaceae present in 24 neonatal units (NNUs) in eight networks participating in a multicentre probiotic study and to test the hypothesis that specific strains would cluster within individual units and networks. METHODS: We performed analysis of stool samples for the presence of ESBL-producing Enterobacteriaceae at 2 weeks post-natal age and 36 weeks post-menstrual age. ESBL-producing Enterobacteriaceae were characterized and typed using molecular methods. RESULTS: ESBL-producing Enterobacteriaceae (n = 71) were isolated from 67/1229 (5.5%) infants from whom we received a sample at either sampling time or both sampling times, and from infants in 18 (75%) of the 24 recruiting NNUs. Thirty-three Escherichia coli, 23 Klebsiella spp. and 6 Enterobacter spp. strains were characterized. ESBL-producing E. coli were all distinguishable within individual NNUs by antibiotic resistance genotype, serogroup (O25b), phenotype, phylotype or ST. Ten of the 33 were ST131 and 9 of the 10 ST131 isolates were ciprofloxacin resistant. Seven of the 10 ST131 isolates carried genes encoding CTX-M group 1 enzymes. ST131 isolates were isolated from centres within five of the eight NNU networks. There were clusters of indistinguishable ESBL-producing Klebsiella and Enterobacter isolates associated with specific NNUs. CONCLUSIONS: Strains of E. coli ST131 were distributed across neonatal networks in the south of England. There was no evidence of clustering of clonally related ESBL-producing E. coli strains, by contrast with Klebsiella spp. and Enterobacter spp., which did cluster within units. The possibility that ESBL-producing E. coli strains are spread by vertical transmission requires further investigation

A systematic review of the international published literature relating to quality of institutional care for people with longer term mental health problems.

BACKGROUND: A proportion of people with mental health problems require longer term care in a psychiatric or social care institution. However, there are no internationally agreed quality standards for institutional care and no method to assess common care standards across countries. We aimed to identify the key components of institutional care for people with longer term mental health problems and the effectiveness of these components. METHODS: We undertook a systematic review of the literature using comprehensive search terms in 11 electronic databases and identified 12,182 titles. We viewed 550 abstracts, reviewed 223 papers and included 110 of these. A "critical interpretative synthesis" of the evidence was used to identify domains of institutional care that are key to service users' recovery. RESULTS: We identified eight domains of institutional care that were key to service users' recovery: living conditions; interventions for schizophrenia; physical health; restraint and seclusion; staff training and support; therapeutic relationship; autonomy and service user involvement; and clinical governance. Evidence was strongest for specific interventions for the treatment of schizophrenia (family psychoeducation, cognitive behavioural therapy (CBT) and vocational rehabilitation). CONCLUSION: Institutions should, ideally, be community based, operate a flexible regime, maintain a low density of residents and maximise residents' privacy. For service users with a diagnosis of schizophrenia, specific interventions (CBT, family interventions involving psychoeducation, and supported employment) should be provided through integrated programmes. Restraint and seclusion should be avoided wherever possible and staff should have adequate training in de-escalation techniques. Regular staff supervision should be provided and this should support service user involvement in decision making and positive therapeutic relationships between staff and service users. There should be clear lines of clinical governance that ensure adherence to evidence-based guidelines and attention should be paid to service users' physical health through regular screening