Administering LAAIs: an education and training workshop

This is the second of two articles that focus on the inter-collaborative work, between education and practice, to enhance theoretical and practical delivery for mental health nurses when administrating long-acting antipsychotic injections (LAAIs). By designing two questionnaires, we were able to evaluate knowledge gain and the satisfaction level of the course delivery by the mental health nurses. These appear initially to identify that such educational strategies can make a positive impact in clinical practice

Mental health and learning disability nursing students' perceptions of the usefulness of the objective structured clinical examination to assess their competence in medicine administration

The aim of this study was to evaluate mental health and learning disability nursing students’ perceptions of the usefulness of the objective structured clinical examination (OSCE) in assessing their administration of medicine competence. Learning disability (n = 24) and mental health (n = 46) students from a single cohort were invited to evaluate their experience of the OSCE. A 10-item survey questionnaire was used, comprising open- and closed-response questions. Twelve (50%) learning disability and 32 (69.6%) mental health nursing students participated. The OSCE was rated highly compared to other theoretical assessments; it was also reported as clinically real and as a motivational learning strategy. However, it did not rate as well as clinical practice. Content analysis of written responses identified four themes: (i) benefits of the OSCE; (ii) suggestions to improve the OSCE; (iii) concern about the lack of clinical reality of the OSCE; and (iv) OSCE-induced stress. The themes, although repeating some of the positive statistical findings, showed that participants were critical of the university setting as a place to conduct clinical assessment, highlighted OSCE-related stress, and questioned the validity of the OSCE as a real-world assessment. The OSCE has an important role in the development of student nurses’ administration of medicine skills. However, it might hinder their performance as a result of the stress of being assessed in a simulated environment

Internally and externally driven flows of complex fluids: viscoelastic active matter, flows in porous media and contact line dynamics

We consider three varied soft matter topics from a continuum fluid mechanics perspective, namely: viscoelastic active matter, viscoelastic flows in porous media, and contact line dynamics. Active matter. For the purposes of this thesis, the term active matter describes a collection of active particles which absorb energy from their local environment or from an internal fuel tank and dissipate it to the surrounding fluid. We explore the stability and dynamics of active matter in a biological context in the presence of a polymeric background fluid. Using a novel coarse-grained model, we generalise earlier linear stability analyses (without polymer) and demonstrate that the bulk orientationally ordered phase remains intrinsically unstable to spontaneous flow instabilities. This instability remains even as one takes an ’elastomeric limit’ in which the polymer relaxation time τC → ∞. The 1D nonlinear dynamics in this limit are oscillatory on a timescale set by the rate of active forcing. Then, by considering the rheological response of our model under shear, we explore the mechanism behind the above generic flow instability, which we show exists not only for orientationally ordered phases but also for disordered states deep in the isotropic phase. Our linear stability analysis in 1D for sheared suspensions predicts that initially homogeneous states represented by negatively sloping regions of the constitutive curve are unstable to shear-banding flow instabilities. In some cases, the shear-bands themselves are unstable which leads to a secondary instability that produces rheochaotic flow states. Consistent with recent experiments on active cellular extracts (without applied shear) which show apparently chaotic flow states, we find that the dynamics of active matter are significantly more complex in 2D. Focusing on the turbulent phase that occurs when the activity ζ (or energy input) is large, we show that the characteristic lengthscale of structure in the fluid l∗ scales as l∗ ∝ 1/ √ζ. While this lengthscale decreases with ζ, it also increases with the polymer relaxation time. This can produce a novel ‘drag reduction’ effect in confined geometries where the system forms more coherent flow states, characterised by net material transport. In the elastomeric limit spontaneous flows may still occur, though these appear to be transient in nature. Examples of exotic states that arise when the polymer is strongly coupled to the active particles are also given. Flows in porous media. The second topic treats viscoelastic flows in porous media, which we approximate numerically using geometries consisting of periodic arrays of cylinders. Experimentally, the normalised drag χ (i.e., the ratio of the pressure drop to the flow rate) is observed to undergo a large increase as the Weissenberg number We (which describes the ratio of the polymer relaxation time to the characteristic velocity-gradient timescale) is increased. An analysis of steady flow in the Newtonian limit identifies regions dominated by shear and extension; these are mapped to the rheological behaviour of several popular models for polymer viscoelasticity in simple viscometric protocols, allowing us to study and influence the upturn in the drag. We also attempt to reproduce a recent study in the literature which reported fluctuations for cylinders confined to a channel at high We. At low numerical resolution, we observe fluctuations which increase in magnitude with the same scaling observed in that study. However, these disappear at very high resolutions, suggesting that numerical convergence was not properly obtained by the earlier authors. Contact line dynamics. We finish by investigating the dynamics of the contact line, i.e., the point at which a fluid-fluid interface meets a solid surface, under an externally applied shear flow. The contact line moves relative to the wall, apparently contradicting the conventional no-slip boundary conditions employed in continuum fluid dynamics. A mechanism where material is transported within a ‘slip region’ via diffusive processes resolves this paradox, though the question of how the size of this region (i.e., slip length ξ) scales with fluid properties such as the viscosity η and the width of the interface between phases l, remains disputed within the literature. We reconcile two apparently contradictory scalings, which are shown to describe different limits: (a) a diffuse interface limit where ξ/l is small and (b) a sharp interface limit for large ξ/l. We demonstrate that the physics of the latter (which more closely resembles real fluids in macroscopic experimental geometries) can be captured using simulations in the former regime (which are numerically more accessible)

The origins, development and influence of William Shenstone’s landscape garden design at The Leasowes, Halesowen

William Shenstone was a polymath. He wrote letters, essays, composed poetry, painted water-colours, played musical instruments and indulged in architectural design, but above all he created a landscape garden at The Leasowes in the West Midlands that became a celebrated place to visit in the eighteenth century. Shenstone worked during the early days of the English landscape garden movement, and while others created grounds with political and/or historical themes he fashioned a garden in a 'naturesque' style. He created a version, called a ferme ornée that was a distinctive form of English garden at the time. This thesis is the first detailed study of The Leasowes and presents a re-evaluation of his garden. Though many people have written about the landscape in the past, few have had the opportunity to look at it from a multidisciplinary perspective which marries an exploration of archival and literary material with landscape studies and archaeological evidence. The study evaluates why and how Shenstone created his garden. It explores his cultural networks and influences and what he did to make it distinctive. It looks at the planting regime and the verse and poetry that illuminated the garden. Finally, it discovers other gardeners who were influenced by his work before and after his death

A national initiative in data science for health: an evaluation of the UK Farr Institute

ObjectiveTo evaluate the extent to which the inter-institutional, inter-disciplinary mobilisation of data and skills in the Farr Institute contributed to establishing the emerging field of data science for health in the UK.&#x0D; Design and Outcome measuresWe evaluated evidence of six domains characterising a new field of science:&#x0D; &#x0D; defining central scientific challenges,&#x0D; demonstrating how the central challenges might be solved,&#x0D; creating novel interactions among groups of scientists,&#x0D; training new types of experts,&#x0D; re-organising universities,&#x0D; demonstrating impacts in society.&#x0D; &#x0D; We carried out citation, network and time trend analyses of publications, and a narrative review of infrastructure, methods and tools.&#x0D; SettingFour UK centres in London, North England, Scotland and Wales (23 university partners), 2013-2018.&#x0D; Results1. The Farr Institute helped define a central scientific challenge publishing a research corpus, demonstrating insights from electronic health record (EHR) and administrative data at each stage of the translational cycle in 593 papers with at least one Farr Institute author affiliation on PubMed. 2. The Farr Institute offered some demonstrations of how these scientific challenges might be solved: it established the first four ISO27001 certified trusted research environments in the UK, and approved more than 1000 research users, published on 102 unique EHR and administrative data sources, although there was no clear evidence of an increase in novel, sustained record linkages. The Farr Institute established open platforms for the EHR phenotyping algorithms and validations (&gt;70 diseases, CALIBER). Sample sizes showed some evidence of increase but remained less than 10% of the UK population in primary care-hospital care linked studies. 3.The Farr Institute created novel interactions among researchers: the co-author publication network expanded from 944 unique co-authors (based on 67 publications in the first 30 months) to 3839 unique co-authors (545 papers in the final 30 months). 4. Training expanded substantially with 3 new masters courses, training &gt;400 people at masters, short-course and leadership level and 48 PhD students. 5. Universities reorganised with 4/5 Centres established 27 new faculty (tenured) positions, 3 new university institutes. 6. Emerging evidence of impacts included: &gt; 3200 citations for the 10 most cited papers and Farr research informed eight practice-changing clinical guidelines and policies relevant to the health of millions of UK citizens.&#x0D; ConclusionThe Farr Institute played a major role in establishing and growing the field of data science for health in the UK, with some initial evidence of benefits for health and healthcare. The Farr Institute has now expanded into Health Data Research (HDR) UK but key challenges remain including, how to network such activities internationally.</jats:p

The fabric of a career in mental health nursing from an Australian and UK perspective

As the prevalence of mental illness increases globally, Australia and the United Kingdom (UK) share concerns regarding the recruitment and retention of nurses to the field of mental health care. The level of preparedness of nurses is thought to have a bearing on recruitment and retention in mental health nursing practice. This study sought to uncover what Australian and UK undergraduate students perceived as motivational in choosing a career in, and being prepared for, working in mental health settings. METHOD This study employed mixed methods, using a questionnaire comprising of both quantitative and qualitative questions. Quantitative data was analysed using SPSS (V.16.0) and content analysis was undertaken for analysing the qualitative data. FINDINGS Following ethical approval, data was collected from, four universities in Australia and two in the UK. A total of 447 undergraduate nursing and midwifery students, who had completed a mental health placement, completed the questionnaire. Findings revealed that motivational factors influencing their interest in mental health nursing were clinical experience (49.7%), personal/life experiences (42.9%) and the role of the lecturer (23%). However, 47.7% of all participants had some previous experience of mental illness, with only 18.4% having had work experience in the field prior to starting their course. IMPLICATIONS This study adds to extant knowledge of what encourages people to choose a career trajectory in mental health nursing and what could be harnessed with regard to retention. The knowledge gained from these findings is useful in informing recruitment processes and can also inform curriculum

Cytochrome P450associated with insecticide resistance catalyzes cuticular hydrocarbon production in Anopheles gambiae.

The role of cuticle changes in insecticide resistance in the major malaria vector Anopheles gambiae was assessed. The rate of internalization of 14C deltamethrin was significantly slower in a resistant strain than in a susceptible strain. Topical application of an acetone insecticide formulation to circumvent lipid-based uptake barriers decreased the resistance ratio by ∼50%. Cuticle analysis by electron microscopy and characterization of lipid extracts indicated that resistant mosquitoes had a thicker epicuticular layer and a significant increase in cuticular hydrocarbon (CHC) content (∼29%). However, the CHC profile and relative distribution were similar in resistant and susceptible insects. The cellular localization and in vitro activity of two P450 enzymes, CYP4G16 and CYP4G17, whose genes are frequently overexpressed in resistant Anopheles mosquitoes, were analyzed. These enzymes are potential orthologs of the CYP4G1/2 enzymes that catalyze the final step of CHC biosynthesis in Drosophila and Musca domestica, respectively. Immunostaining indicated that both CYP4G16 and CYP4G17 are highly abundant in oenocytes, the insect cell type thought to secrete hydrocarbons. However, an intriguing difference was indicated; CYP4G17 occurs throughout the cell, as expected for a microsomal P450, but CYP4G16 localizes to the periphery of the cell and lies on the cytoplasmic side of the cell membrane, a unique position for a P450 enzyme. CYP4G16 and CYP4G17 were functionally expressed in insect cells. CYP4G16 produced hydrocarbons from a C18 aldehyde substrate and thus has bona fide decarbonylase activity similar to that of dmCYP4G1/2. The data support the hypothesis that the coevolution of multiple mechanisms, including cuticular barriers, has occurred in highly pyrethroid-resistant An. gambiae.Fil: Balabanidou, Vasileia. Foundation for Research and Technology-Hellas; Grecia. Universidad de Creta; GreciaFil: Kampouraki, Anastasia. Universidad de Creta; GreciaFil: Mac Lean, Marina. University of Nevada; Estados UnidosFil: Blomquist, Gary J.. University of Nevada; Estados UnidosFil: Tittiger, Claus. University of Nevada; Estados UnidosFil: Juarez, Marta Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Mijailovsky, Sergio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Chalepakis, George. Universidad de Creta; GreciaFil: Anthousi, Amalia. Universidad de Creta; GreciaFil: Lynd, Amy. Liverpool School of Tropical Medicine; Reino UnidoFil: Antoine, Sanou. Liverpool School of Tropical Medicine; Reino UnidoFil: Hemingway, Janet. Liverpool School of Tropical Medicine; Reino UnidoFil: Ranson, Hilary. Liverpool School of Tropical Medicine; Reino UnidoFil: Lycett, Gareth J.. Liverpool School of Tropical Medicine; Reino UnidoFil: Vontas, John. Foundation for Research and Technology-Hellas; Grecia. Agricultural University of Athens; Greci

A Simple Colorimetric Assay for Specific Detection of Glutathione-S Transferase Activity Associated with DDT Resistance in Mosquitoes

Aedes mosquitoes transmit many human viral pathogens including dengue, yellow fever and chikungunya. Most of these pathogens have no specific treatment or vaccine and hence their control is reliant on controlling the mosquito vectors, which usually involves the use of insecticides. In order to prevent the alarming prospect of mosquito control failure due to the rapid selection and spread of insecticide resistance in several mosquito populations worldwide, it is essential that effective resistance management strategies are implemented and adhered to. The development of simple diagnostic tests for the early identification and monitoring of resistance is an important prerequisite for this task. Here, we describe the development of a simple colorimetric test for the detection of GSTE2-2/DDTase-based resistance in individual mosquitoes. The novel assay combines the most desirable features of specificity and sensitivity with the low cost and ease of use required for a routine test in endemic countries. It can have direct application in routine vector monitoring as a resistance indicator and help improve the sustainability of insecticide based control strategies

Mapping a Quantitative Trait Locus (QTL) conferring pyrethroid resistance in the African malaria vector Anopheles funestus

BACKGROUND: Pyrethroid resistance in Anopheles funestus populations has led to an increase in malaria transmission in southern Africa. Resistance has been attributed to elevated activities of cytochrome P450s but the molecular basis underlying this metabolic resistance is unknown. Microsatellite and SNP markers were used to construct a linkage map and to detect a quantitative trait locus (QTL) associated with pyrethroid resistance in the FUMOZ-R strain of An. funestus from Mozambique. RESULTS: By genotyping 349 F(2 )individuals from 11 independent families, a single major QTL, rp1, at the telomeric end of chromosome 2R was identified. The rp1 QTL appears to present a major effect since it accounts for more than 60% of the variance in susceptibility to permethrin. This QTL has a strong additive genetic effect with respect to susceptibility. Candidate genes associated with pyrethroid resistance in other species were physically mapped to An. funestus polytene chromosomes. This showed that rp1 is genetically linked to a cluster of CYP6 cytochrome P450 genes located on division 9 of chromosome 2R and confirmed earlier reports that pyrethroid resistance in this strain is not associated with target site mutations (knockdown resistance). CONCLUSION: We hypothesize that one or more of these CYP6 P450s clustered on chromosome 2R confers pyrethroid resistance in the FUMOZ-R strain of An. funestus

Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals

Background: Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014. Methods: For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages ( > 0 years). Findings: From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91–0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [SD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37–1·20; mean number of comorbidities 3·4 [SD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9–2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58–1·64), and did so earlier in life than those from the most affluent group (adjusted difference −3·51 years, 95% CI −3·77 to −3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age. Interpretation: Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled. Funding: British Heart Foundation and National Institute for Health Research