728 research outputs found

    Thermodynamics predicts how confinement modifies hard-sphere dynamics

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    We study how confining the equilibrium hard-sphere fluid to restrictive one- and two-dimensional channels with smooth interacting walls modifies its structure, dynamics, and entropy using molecular dynamics and transition-matrix Monte Carlo simulations. Although confinement strongly affects local structuring, the relationships between self-diffusivity, excess entropy, and average fluid density are, to an excellent approximation, independent of channel width or particle-wall interactions. Thus, thermodynamics can be used to predict how confinement impacts dynamics.Comment: 4 pages, 4 figure

    Identifying the active ingredients of training interventions for healthcare professionals to promote and support increased levels of physical activity in adults with heart failure: a systematic review

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    Heart failure (HF) is characterised by breathlessness and fatigue that impacts negatively on patients’ intentions to prioritise physical activity (PA). Healthcare professionals (HCPs) experience challenges when motivating patients to increase PA. It is essential to develop an understanding of how to support HCPs to deliver PA interventions. We aimed to identify active ingredients of HCP training interventions to enable delivery of PA interventions to HF patients. Nine databases were searched. Data were extracted on study characteristics, active ingredients, outcomes, and fidelity measures. Data were synthesised narratively, and a promise analysis was conducted on intervention features. Ten RCTs, which reported a training intervention for HCPs were included (N = 22 HCPs: N = 1,414 HF patients). Two studies reported the use of theory to develop HCP training. Seven behaviour change techniques (BCTs) were identified across the 10 training interventions. The most ‘promising’ BCTs were ‘instruction on how to perform the behaviour’ and ‘problem solving’. Two studies reported that HCP training interventions had been formally evaluated. Fidelity domains including study design, monitoring and improving the delivery of treatment, intervention delivery, and provider training were infrequently reported. Future research should prioritise theory-informed development and robust evaluation of training interventions for HCPs to enable faithful and quality delivery of patient interventions

    Generalized Rosenfeld scalings for tracer diffusivities in not-so-simple fluids: Mixtures and soft particles

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    Rosenfeld [Phys. Rev. A 15, 2545 (1977)] noticed that casting transport coefficients of simple monatomic, equilibrium fluids in specific dimensionless forms makes them approximately single-valued functions of excess entropy. This has predictive value because, while the transport coefficients of dense fluids are difficult to estimate from first principles, excess entropy can often be accurately predicted from liquid-state theory. Here, we use molecular simulations to investigate whether Rosenfeld's observation is a special case of a more general scaling law relating mobility of particles in mixtures to excess entropy. Specifically, we study tracer diffusivities, static structure, and thermodynamic properties of a variety of one- and two-component model fluid systems with either additive or non-additive interactions of the hard-sphere or Gaussian-core form. The results of the simulations demonstrate that the effects of mixture concentration and composition, particle-size asymmetry and additivity, and strength of the interparticle interactions in these fluids are consistent with an empirical scaling law relating the excess entropy to a new dimensionless (generalized Rosenfeld) form of tracer diffusivity, which we introduce here. The dimensionless form of the tracer diffusivity follows from knowledge of the intermolecular potential and the transport / thermodynamic behavior of fluids in the dilute limit. The generalized Rosenfeld scaling requires less information, and provides more accurate predictions, than either Enskog theory or scalings based on the pair-correlation contribution to the excess entropy. As we show, however, it also suffers from some limitations, especially for systems that exhibit significant decoupling of individual component tracer diffusivities.Comment: 15 pages, 10 figure

    Development of FRET-Based Assays in the Far-Red Using CdTe Quantum Dots

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    Colloidal quantum dots (QDs) are now commercially available in a biofunctionalized form, and Förster resonance energy transfer (FRET) between bioconjugated dots and fluorophores within the visible range has been observed. We are particularly interested in the far-red region, as from a biological perspective there are benefits in pushing to ∼700 nm to minimize optical absorption (ABS) within tissue and to avoid cell autofluorescence. We report on FRET between streptavidin- (STV-) conjugated CdTe quantum dots, Qdot705-STV, with biotinylated DY731-Bio fluorophores in a donor-acceptor assay. We also highlight the changes in DY731-Bio absorptivity during the streptavidin-biotin binding process which can be attributed to the structural reorientation. For fluorescence beyond 700 nm, different alloy compositions are required for the QD core and these changes directly affect the fluorescence decay dynamics producing a marked biexponential decay with a long-lifetime component in excess of 100 nanoseconds. We compare the influence of the two QD relaxation routes upon FRET dynamics in the presence of DY731-Bio

    By design : negotiating flexible learning in the built environment discipline

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    The term ‘flexible education’ is now firmly entrenched within Australian higher education discourse, yet the term is a contested one imbued with a multiplicity of meanings. This paper describes a process designed to elucidate how the idea of flexible education can be translated into teaching models that are informed by the specific demands of disciplinary contexts. The process uses a flexible learning ‘matching’ tool to articulate the understandings and preferences of students and academics of the Built Environment to bridge the gap between student expectations of flexibility and their teacher’s willingness and ability to provide that flexibility within the limits of the pedagogical context and teaching resources. The findings suggest an informed starting point for educators in the Built Environment and other creative disciplines from which to traverse the complexities inherent in negotiating flexibility in an increasingly digital world

    Adaptive dosing of anticancer drugs in neonates: facilitating evidence-based dosing regimens

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    PURPOSE: Selection of the most appropriate chemotherapy dosing regimens for neonates treated within the first weeks of life represents a significant clinical dilemma. Due to a lack of information relating to the clinical pharmacology of anticancer drugs in these challenging patients, current dosing guidelines are based on limited scientific rationale. In the current study, we investigate the utilisation of therapeutic drug monitoring approaches in neonates with localised hepatoblastoma, Wilms' tumour and stage 4S neuroblastoma, being treated with widely used anticancer drugs. METHODS: Plasma concentrations of cisplatin, vincristine, etoposide and carboplatin were quantified in two neonates being treated within the first 3 weeks of life and in a 32-week preterm infant treated at a gestational age of 40 weeks. Therapeutic drug monitoring was carried out where appropriate, based on the pharmacokinetic data obtained in conjunction with clinical response and toxicity. RESULTS: Treatment of a child aged 2 weeks with a recommended cisplatin dose reduction for weight to 1.8 mg/kg resulted in achievement of unbound cisplatin plasma concentrations of 0.01-0.08 µg/mL, markedly lower than exposures previously reported in infants and older children. A dose increase to 2.7 mg/kg was implemented, leading to the achievement of levels more in-line with those previously reported. This increased dose level was well tolerated over six courses of treatment, resulting in a good response to cisplatin monotherapy and the patient remains in remission at 3.5 years. In contrast, a 50 % vincristine dose reduction for weight in a 3-week-old neonate resulted in plasma concentrations comparable to levels observed in older children, leading to successful treatment and continued remission at 2 years. In a third patient, etoposide and carboplatin clearance values normalised to body weight were comparable to those reported in older children, resulting in comparatively lower exposures following reduced dosing. CONCLUSIONS: The current report provides unique data on the pharmacokinetics of several widely used anticancer drugs in neonates treated within the first few weeks of life. The provision of these data acts as a useful reference point to support future dosing decisions to be made by clinicians in the treatment of these challenging patients

    Service user perspectives on social prescribing services for mental health in the UK: a systematic review

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    Aim: To thematically synthesise adult service users’ perspectives on how UK-based social prescribing services support them with their mental health management. Methods: Nine databases were systematically searched up to March 2022. Eligible studies were qualitative or mixed methods studies involving participants aged ⩾ 18 years accessing social prescribing services primarily for mental health reasons. Thematic synthesis was applied to qualitative data to create descriptive and analytical themes. Results: 51,965 articles were identified from electronic searches. Six studies were included in the review (n = 220 participants) with good methodological quality. Five studies utilised a link worker referral model, and one study a direct referral model. Modal reasons for referral were social isolation and/or loneliness (n = 4 studies). Two analytical themes were formulated from seven descriptive themes: (1) person-centred care was key to delivery and (2) creating an environment for personal change and development. Conclusions: This review provides a synthesis of the qualitative evidence on service users’ experiences of accessing and using social prescribing services to support their mental health management. Adherence to principles of person-centred care and addressing the holistic needs of service users (including devoting attention to the quality of the therapeutic environment) are important for design and delivery of social prescribing services. This will optimise service user satisfaction and other outcomes that matter to them. Keywords: systematic review, social prescribing, qualitative synthesis, mental health, public health, primary car

    A novel compartment, the 'subqpical stem' of the aerial hyphae, is the location of a sigN-dependent, developmentally distinct transcription in Streptomyces coelicolor.

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    Streptomyces coelicolor has nine SigB-like RNA polymerase sigma factors, several of them implicated in morphological differentiation and/or responses to different stresses. One of the nine, SigN, is the focus of this article. A constructed sigN null mutant was delayed in development and exhibited a bald phenotype when grown on minimal medium containing glucose as carbon source. One of two distinct sigN promoters, sigNP1, was active only during growth on solid medium, when its activation coincided with aerial hyphae formation. Transcription from sigNP1 was readily detected in several whi mutants (interrupted in morphogenesis of aerial mycelium into spores), but was absent from all bld mutants tested, suggesting that sigNP1 activity was restricted to the aerial hyphae. It also depended on sigN, thus sigN was autoregulated. Mutational and transcription studies revealed no functional significance to the location of sigN next to sigF, encoding another SigB-like sigma factor. We identified another potential SigN target, nepA, encoding a putative small secreted protein. Transcription of nepA originated from a single, aerial hyphae-specific and sigN-dependent promoter. While in vitro run-off transcription using purified SigN on the Bacillus subtilis ctc promoter confirmed that SigN is an RNA polymerase sigma factor, SigN failed to initiate transcription from sigNP1 and from the nepA promoter in vitro. Additional in vivo data indicated that further nepA upstream sequences, which are likely to bind a potential activator, are required for successful transcription. Using a nepA–egfp transcriptional fusion we located nepA transcription to a novel compartment, the ‘subapical stem’ of the aerial hyphae. We suggest that this newly recognized compartment defines an interface between the aerial and vegetative parts of the Streptomyces colony and might also be involved in communication between these two compartments
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