It's time to regulate - The importance of accurate surgical-grade tourniquet autoregulation in blood flow restriction exercise applications.

OBJECTIVE: Evaluate the efficacy of five common blood flow restriction (BFR) systems to accurately maintain and autoregulate BFR pressure in the tourniquet cuff near target pressure throughout exercise. DESIGN: Randomised crossover design. SETTING: Laboratory. PARTICIPANTS: 15 healthy individuals. OUTCOME MEASURES: 1) Percentage of total BFR time that surgical-grade tourniquet autoregulation, defined as automatic and rapid self-regulation of cuff pressure to within ±15 mmHg of initial target pressure within 1 s in the presence of transient pressure changes associated with exercise, was provided; 2) pressure change in the BFR cuff throughout exercise, by comparing the initial target pressure to the measured pressure at completion of BFR exercise. RESULTS: One BFR system could provide surgical-grade tourniquet autoregulation for the whole duration (100 ± 0%) of the BFR exercise in all subjects. In two of the five BFR systems evaluated, measured cuff pressure at the end of exercise was not different (p < 0.05) to the initial target pressure. CONCLUSIONS: Surgical-grade tourniquet autoregulation is important to consistently and reliably apply a targeted BFR pressure stimulus. This may allow BFR methodology and protocols to be accurately implemented and controlled so that the results can be more meaningfully compared, leading to the potential optimization of applications.

Influences on nurses' engagement in antimicrobial stewardship behaviours: a multi-country survey using the Theoretical Domains Framework.

BACKGROUND: Antimicrobial resistance (AMR) is affected significantly by inappropriate antibiotic use, and is one of the greatest threats to human health. Antimicrobial stewardship (AMS) is a programme of actions promoting responsible use of antimicrobials, and is essential for limiting AMR. Nurses have an important role to play in this context. AIM: To investigate the determinants of nurse AMS behaviours and the impact of past training. METHODS: A cross-sectional multi-country survey design with mixed methods was employed. Participants were 262 nurses {223 female; mean age 44.45 [standard deviation (SD) 10.77] years} of 10 nationalities, with individual survey links sent via professional networks in five countries, alongside Twitter. Nine AMS behaviours and 14 behavioural determinants were assessed quantitatively using the Theoretical Domains Framework (TDF), and mapped to the Capability, Opportunity, Motivation - Behaviour (COM-B) model. Analysis identified differences between nurses with and without AMS training. The influence of coronavirus disease 2019 (COVID-19) on AMS behaviour was investigated qualitatively using free-text data. FINDINGS: Nurses performed all nine AMS behaviours, which were significantly higher [t (238) -4.14, P<0.001] among those who had received AMS training [mean 53.15 (SD 7.40)] compared with those who had not received AMS training [mean 48.30 (SD 10.75)]. Nurses who had received AMS training scored significantly higher in all of the TDF domains. The TDF was able to explain 27% of the variance in behaviour, with 'Skills' and 'Behavioural regulation' (e.g. ability to self-monitor and plan) shown to be the most predictive of AMS actions. Both of these domains are situated in the 'Capability' construct of the COM-B model, which can be enhanced with the intervention strategies of education and training. An increase in AMS behaviours was reported since the COVID-19 pandemic, regardless of previous training. Six core themes were linked to AMS: (1) infection prevention and control; (2) antimicrobials and antimicrobial resistance; (3) diagnosis of infection and use of antibiotics; (4) antimicrobial prescribing practice; (5) person-centred care; and (6) interprofessional collaborative practice. CONCLUSION: Nurse training has a significant beneficial effect on AMS behaviour and its determinants. Nurses who had received AMS training scored higher in all TDF determinants of behaviour compared with those who had not received AMS training, resulting in higher capability, opportunity and motivation to perform AMS behaviour. AMS education and training should be offered to nurses to enhance these factors. Future research should consider the optimal level of training to optimize AMS behaviour, with a focus on developing skills and behavioural regulation.

Development of consensus-based international antimicrobial stewardship competencies for undergraduate nurse education.

BACKGROUND: There is growing recognition by national and international policymakers of the contribution nurses make towards antimicrobial stewardship. Although undergraduate education provides an ideal opportunity to prepare nurses for antimicrobial stewardship roles and activities, only two-thirds of undergraduate nursing programmes incorporate any antimicrobial stewardship teaching and only 12% cover all the recommended antimicrobial stewardship principles. Nurses also report that they do not have a good knowledge of antibiotics, and many have not heard of the term antimicrobial stewardship. AIM: To provide international consensus on the antimicrobial stewardship competency descriptors appropriate for undergraduate nurse education. METHODS: A modified Delphi approach comprising two online surveys delivered to an international panel of 15 individuals reflecting expertise in prescribing and medicines management in the education and practice of nurses; and antimicrobial stewardship. Data collection took place between February and March 2019. FINDINGS: A total of 15 participants agreed to become members of the expert panel, of whom 13 (86%) completed round 1 questionnaire, and 13 (100%) completed round 2. Consensus was achieved, with consistently high levels of agreement across panel members, on six overarching competency domains and 63 descriptors, essential for antimicrobial stewardship practice. CONCLUSION: The competency descriptors should be used to direct undergraduate nurse education and the antimicrobial stewardship practices of qualified nurses (including those working in new roles such as Nursing Associates) due to the high levels of agreement reached on competency descriptors.

Prioritizing research areas for antibiotic stewardship programmes in hospitals: a behavioural perspective consensus paper.

SCOPE: Antibiotic stewardship programmes (ASPs) are necessary in hospitals to improve the judicious use of antibiotics. While ASPs require complex change of key behaviours on individual, team organization and policy levels, evidence from the behavioural sciences is underutilized in antibiotic stewardship studies across the world, including high-income countries (HICs). A consensus procedure was performed to propose research priority areas for optimizing effective implementation of ASPs in hospital settings using a behavioural perspective. METHODS: A workgroup for behavioural approaches to ASPs was convened in response to the fourth call for leading expert network proposals by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). Eighteen clinical and academic specialists in antibiotic stewardship, implementation science and behaviour change from four HICs with publicly funded healthcare systems (e.g. Canada, Germany, Norway and the UK) met face-to-face to agree on broad research priority areas using a structured consensus method. Question addressed and recommendations: The consensus process assessing the ten identified research priority areas resulted in recommendations that need urgent scientific interest and funding to optimize effective implementation of ASPs for hospital inpatients in HICs with publicly funded healthcare systems. We suggest and detail behavioural science evidence-guided research efforts in the following areas: (a) comprehensively identifying barriers and facilitators to implementing ASPs and clinical recommendations intended to optimize antibiotic prescribing; (b) identifying actors ('who') and actions ('what needs to be done') of ASPs and clinical teams; (c) synthesizing available evidence to support future research and planning for ASPs; (d) specifying the activities in current ASPs with the purpose of defining a control group for comparison with new initiatives; (e) defining a balanced set of outcomes and measures to evaluate the effects of interventions focused on reducing unnecessary exposure to antibiotics; (f) conducting robust evaluations of ASPs with built-in process evaluations and fidelity assessments; (g) defining and designing ASPs; (h) establishing the evidence base for impact of ASPs on resistance; (i) investigating the role and impact of government and policy contexts on ASPs; and (j) understanding what matters to patients in ASPs in hospitals. CONCLUSIONS: Assessment, revisions and updates of our priority-setting exercise should be considered at intervals of 2 years. To propose research priority areas in low- and middle-income countries, the methodology reported here could be applied.

Normative and conceptual ELSI research: what it is, and why it's important.

The Ethical, Legal, and Social Implications (ELSI) Research Program of the National Human Genome Research Institute sponsors research examining ethical, legal, and social issues arising in the context of genetics/genomics. The ELSI Program endorses an understanding of research not as the sole province of empirical study, but instead as systematic study or inquiry, of which there are many types and methods. ELSI research employs both empirical and nonempirical methods. Because the latter remain relatively unfamiliar to biomedical and translational scientists, this paper seeks to elucidate the relationship between empirical and nonempirical methods in ELSI research. It pays particular attention to the research questions and methods of normative and conceptual research, which examine questions of value and meaning, respectively. To illustrate the distinct but interrelated roles of empirical and nonempirical methods in ELSI research, including normative and conceptual research, the paper demonstrates how a range of methods may be employed both to examine the evolution of the concept of incidental findings (including the recent step toward terming them 'secondary findings'), and to address the normative question of how genomic researchers and clinicians should manage incidental such findings.

Development of consensus-based national antimicrobial stewardship competencies for UK undergraduate healthcare professional education.

BACKGROUND: Healthcare professionals are involved in an array of patient- and medicine-related stewardship activities, for which an understanding and engagement with antimicrobial stewardship (AMS) is important. Undergraduate education provides an ideal opportunity to prepare healthcare professionals for these roles and activities. AIM: To provide UK national consensus on a common set of antimicrobial stewardship competencies appropriate for undergraduate healthcare professional education. METHODS: A modified Delphi approach comprising two online surveys delivered to a UK national panel of 21 individuals reflecting expertise in prescribing and medicines management with regards to the education and practice of nurses and midwives, pharmacists, physiotherapists, and podiatrists; and antimicrobial prescribing and stewardship. Data collection took place between October and December 2017. FINDINGS: A total of 21 participants agreed to become members of the expert panel, of whom 19 (90%) completed round 1 questionnaire, and 17 (89%) completed round 2. Panelists reached a consensus, with consistently high levels of agreement reached, on six overarching competency statements (subdivided into six domains), and 55 individual descriptors essential for antimicrobial stewardship by healthcare professionals. CONCLUSION: Due to the consistently high levels of agreement reached on competency statements and their associated descriptors, this competency framework should be used to direct education for undergraduate healthcare professionals, and those working in new clinical roles to support healthcare delivery where an understanding of, and engagement with, AMS is important. Although the competencies target basic education, they can also be used for continuing education.

How low can you go? Minimum energy pathways for O2 dissociation on Pt(111).

Many DFT studies of O(2) dissociation on Pt(111) give conflicting information on preferred paths and final states. Here we report large p(4 × 4) unit cell minimum energy pathway evaluations and compare O(2) adsorption and dissociated states on Pt(111). Calculations reveal how the pathways for O(2) dissociation starting from top-fcc-bridge, top-hcp-bridge, and top-bridge-top sites are interconnected. They also provide a direct reaction pathway for the dissociation of an O(2) molecule from a top-fcc-bridge into an hcp and an fcc site, which is consistent with low temperature scanning tunneling microscope experiments. Such a pathway is shown to be considerably perturbed by the presence of co-adsorbed oxygen atoms. We quantify the coverage dependence through the construction of a Brønsted-Evans-Polanyi relationship relating the O(2) dissociation activation energies to the binding energies of the dissociated O atoms. We also show that all pathways starting from a top-fcc-bridge site give the smallest barriers for O(2) dissociation.

Organising a World Congress of Epidemiology (WCE): reflections and lessons from the XIX WCE, Scotland.

The 3-yearly World Congress of Epidemiology is the premier, international, scientific conference organised under the auspices of the International Epidemiological Association (in open competition). This paper explores the justification for seeking to host the Congress and reflects on the structures and processes adopted in making the XIXth Congress in Scotland happen. Preparing the bid was invaluable for forming collaborations, generating scientific ideas, and garnering opinion. After the bid was accepted, we formed a local organising committee, named the Management Executive Committee to signal its decision making authority; and scientific, fundraising, marketing, international and social subcommittees. There was uncertainty about critical matters such as delegate numbers, costs and the total budget. Early decisions had to be made on, for example, the fee and fundraising target (£250,000), despite financial risks. Development of the scientific programme was a critical step that underpinned fundraising and marketing and permitted involvement of the international committee. Overall the 2011 WCE succeeded. The key ingredients to success were: a large collaboration of institutions and individuals; early pledges of financial support mostly from the UK; the valuable and relevant experience of the professional conference organisers; unstinting support and advice from IEA; and the effectiveness of the committee structure. The educational and professional development benefits of this WCE will reach a worldwide community and not just delegates, because of video, PowerPoint and textual accounts being open access on the Internet. This reach is unprecedented for IEA's World Congresses. We anticipate that the Congress will translate into better public health practice, better future Congresses, advances in epidemiology and improved population health.

Gene expression during activation of Paracoccidioides brasiliensis conidia.

This study focuses on gene expression during crucial biological phenomena of the dimorphic fungal human pathogen Paracoccidioides brasiliensis, the conidia-to-yeast (C-Y) transition and the conidia-to-mycelia (C-M) germination. We studied 10 genes involved in different cellular functions: oxidative stress response (alternative oxidase (AOX), superoxide dismutase (SOD), flavodoxin, conserved hypothetical protein (Y20)); cell metabolism (glyceraldehyde-3-phosphate dehydrogenase (GADPH), cholestenol Delta-isomerase (ChDI), glycine dehydrogenase (GDh)) and heat shock response (Heat shock protein 90 (HSP90)), and cell synthesis and wall structure (glucan synthase-1 (GS-1), α-1,3-glucan synthase (αGS), and mannosyltransferase (MT)). Gene expression was measured during the first 72 h and 96 h of C-Y and C-M, respectively, previously shown to be a fundamental time frame for the consolidation of these cellular processes. The gene expression of AOX, GAPDH, HSP90, MT, αGS, and GDh was significantly increased during the C-Y transition, while SOD, ChDI, GAPDH, MT, GDh, and GS-1 were increased during C-M germination. Additionally, some were highly expressed in each process: AOX, HSP90, and αGS during C-Y; SOD, ChDI, and GS-1 during C-M. Altogether, these data add new information regarding gene expression during the C-Y and C-M processes. Future research will be targeted to further characterize the true relevance of the studied genes during the morphological transition, either during adaptation to the environment or to the infected host.

Differential PbP27 expression in the yeast and mycelial forms of the Paracoccidioides brasiliensis species complex.

p27 is an antigenic protein produced by Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis (PCM). Despite its unknown function, it has been suggested as a putative virulence factor, proposed as a suitable target for the design of diagnostic tools and vaccines, and considered as an enhancer in antifungal treatment of PCM. We evaluated sequence polymorphisms of PbP27 gene sequence among isolates, finding some polymorphisms associated with the isolates' phylogenetic origin. In order to determine if there was a differential expression pattern between morphological states and among isolates, we also evaluated PbP27 expression, at transcriptional and translational levels, in mycelia and yeast cultures in 14 isolates belonging to the P. brasiliensis species complex (S1, PS2, PS3, and "Pb01-like", proposed to be named Paracoccidioides lutzii) by two techniques, real time RT-PCR (RT-qPCR) and protein dot blot. For the latter, four protein extracts from different cell localizations (SDS or ß-mercaptoethanol, cytoplasmic and extracellular proteins) were analyzed for each isolate. p27 was present in the four extracts evaluated, mainly in the SDS extract, corresponding to an extract containing proteins loosely attached to the cell wall. This information correlates with immunohistochemical analysis, where positive staining of the yeasts' cell wall was observed. We found that p27 was present in all isolates, mainly in the yeast form. This pattern was corroborated by RT-qPCR results, with higher expression levels found in the yeast form for most of the isolates. The results provide new insights into the expression patterns of this protein, and further characterize it in view of potential uses as a diagnostic and/or therapeutic tool.

Control of an outbreak of diarrhoea in a vascular surgery unit caused by a high-level clindamycin-resistant Clostridium difficile PCR ribotype 106.

This report describes an outbreak of Clostridium difficile infection (CDI) in a vascular surgery ward in 2009 caused by a high-level clindamycin-resistant ribotype 106. A case of CDI was defined as a patient with diarrhoea, positive for C. difficile toxin and negative for other enteric pathogens. Cultures were sent to the Scottish Salmonella Shigella and Clostridium difficile Reference Laboratory (SSSCDRL) for PCR ribotyping, antibiotic susceptibility testing and PCR detection of ermB. The mean age of the nine patients was 73 years (range: 38-90 years). All had received clindamycin and ciprofloxacin. All cases were typed as PCR ribotype 106 and they showed high-level resistance to clindamycin. Five of these isolates were tested by PCR for the presence of the ermB gene and no amplification was detected. This strain has rarely been isolated from patients on this ward. The outbreak was controlled successfully by closure of the ward with terminal cleaning, reinforcement of infection control precautions and the introduction of a new antibiotic policy. It is notable that this outbreak was caused by a strain with high-level clindamycin resistance not mediated by ermB. It also re-emphasizes that outbreaks of CDI can be caused by C. difficile PCR ribotypes other than 027. The outbreak was most likely associated with the use of clindamycin and ciprofloxacin cross-infection with spores in this environment. Implementation of strict infection control precautions, antimicrobial stewardship and enhanced environmental cleaning are key components in managing such an outbreak successfully. The number of meticillin-resistant Staphylococcus aureus acquisitions also fell substantially after these interventions.

Effect of ultrafast diffusion on adsorption, desorption, and reaction processes over heterogeneous surfaces.

The effect of ultrafast diffusion is studied on reaction-diffusion processes in heterogeneous media, as encountered in catalysis and field emission microscopy. The reaction-diffusion equations describe adsorption, desorption, and reaction processes for two adspecies, for instance, on a paraboloidal heterogeneous surface in the presence of an external electric field. Using multiscale analysis, we show that the fast adspecies rapidly reaches a quasiequilibrium spatial distribution, characterized by a nonequilibrium chemical potential of the fast adspecies. An ordinary differential equation is derived for the time evolution of the nonequilibrium chemical potential. Numerical simulations are performed under different conditions, which confirm the convergence of the dynamics for finite diffusion toward the ultrafast diffusion limit predicted by our multiscale analysis. The numerical simulations also demonstrate that electric fields may induce important diffusive currents on heterogeneous surfaces under the conditions of field emission microscopy.

Catalytic reduction of NO2 with hydrogen on Pt field emitter tips: kinetic instabilities on the nanoscale.

The catalytic reduction of NO(2) with hydrogen on a Pt field emitter tip is investigated using both field electron microscopy (FEM) and field ion microscopy (FIM). A rich variety of nonlinear behavior and unusually high catalytic activity around the {012} facets are observed. Our FEM investigations reveal that the correlation function exhibits damped oscillations with a decaying envelope, showing that molecular noise will influence the dynamics of the oscillations. The dependence of the oscillatory period on the P(H(2))/P(NO(2)) pressure ratios is analyzed. Similar patterns are reported under FIM conditions. Corresponding density functional theory (DFT) calculations for the adsorption of NO(2) on Pt{012} in the presence of an external electric field are performed in order to gain an atomistic understanding of the underlying nonlinear phenomena.

Presence and expression of the mating type locus in Paracoccidioides brasiliensis isolates.

Paracoccidioides brasiliensis has been classified in the phylum Ascomycota, order Onygenales, family Ajellomycetaceae, even in the absence of a known sexual cycle or mating system. The objective of this work was to determine the presence of the mating type locus in 71 P. brasiliensis isolates from various sources. A PCR assay using specific primers for the MAT 1 gene was developed and applied for the detection of such genes. Two heterothallic groups (MAT1-1 or MAT1-2) were recognized and, in some isolates, gene expression was confirmed indicating the existence of a basal gene expression. The distribution of two mating type loci in the studied population suggested that sexual reproduction might occur in P. brasiliensis. This finding points towards the possibility of applying a more precise definition of the concept of biological species to P. brasiliensis. Further studies should be conducted to confirm the sexual capacity of this fungus and its implications among phylogenetic species and geographical distribution.

Interaction between silver nanowires and CO on a stepped platinum surface.

We studied the interplay between Ag decoration of a stepped Pt(355) surface and CO adsorption by in situ high-resolution x-ray photoelectron spectroscopy. Varying amounts of Ag deposited at 300 K initially lead to a row-by-row growth starting from the lower Pt step edges. Such decoration of the step sites results in a change in the CO adsorption behavior. An apparent blocking of step sites for low CO coverages is attributed to a change in the electronic structure, resulting in a C 1s binding energy of CO at step sites being equal to that for CO at terrace on-top sites in the presence of Ag. Higher CO coverages induce the formation of embedded Ag clusters within the upper terraces, thus freeing up a part of the original Pt step sites for CO adsorption, as was derived by a comparison to density functional theory calculations in the corresponding surface models.

Phase diagram and adsorption-desorption kinetics of CO on Ru(0001) from first principles.

A kinetic lattice gas model is used to study the equilibrium properties and the desorption kinetics of CO on Ru(0001). The authors compute all relevant on-site binding and interaction energies of CO molecules within density functional theory and import them in two different models. The first model allows the CO molecules to adsorb upright on top and hollow sites. The authors calculate the phase diagram, coverage isobars, and temperature programed desorption spectra. Up to a coverage of 1/3 ML, very good agreement is obtained between theory and experiment when considering top sites only. For coverages beyond 1/3 ML, hollow sites are included and disagreement between theory and experiment occurs. The second model allows adsorption on top sites only but allows them to tilt and shift from their upright positions. The authors show that this model resolves many of the deficiencies of their first one. Furthermore, the authors demonstrate that this model is more consistent with experiment since it is the only model that is able to explain the results from IR-spectroscopy experiments.