The reduced cost of providing a nationally recognised service for familial hypercholesterolaemia

OBJECTIVE: Familial hypercholesterolaemia (FH) affects 1 in 500 people in the UK population and is associated with premature morbidity and mortality from coronary heart disease. In 2008, National Institute for Health and Care Excellence (NICE) recommended genetic testing of potential FH index cases and cascade testing of their relatives. Commissioners have been slow to respond although there is strong evidence of cost and clinical effectiveness. Our study quantifies the recent reduced cost of providing a FH service using generic atorvastatin and compares NICE costing estimates with three suggested alternative models of care (a specialist-led service, a dual model service where general practitioners (GPs) can access specialist advice, and a GP-led service).METHODS: Revision of existing 3?year costing template provided by NICE for FH services, and prediction of costs for running a programme over 10?years. Costs were modelled for the first population-based FH service in England which covers Southampton, Hampshire, Isle of Wight and Portsmouth (SHIP). Population 1.95 million.RESULTS: With expiry of the Lipitor (Pfizer atorvastatin) patent the cost of providing a 10-year FH service in SHIP reduces by 42.5% (£4.88 million on patent vs £2.80 million off patent). Further cost reductions are possible as a result of the reduced cost of DNA testing, more management in general practice, and lower referral rates to specialists. For instance a dual-care model with GP management of patients supported by specialist advice when required, costs £1.89 million.CONCLUSIONS: The three alternative models of care are now <50% of the cost of the original estimates undertaken by NICE

Continuum modelling of gigahertz nano-oscillators

Fullerenes and carbon nanotubes are of considerable interest throughout many scientific areas due to their unique and exceptional properties, such as low weight, high strength, flexibility, high thermal conductivity and chemical stability. These nanostructures have many potential applications in nano-devices. One concept that has attracted much attention is the creation of nano-oscillators, which can produce frequencies in the gigahertz range, for applications such as ultra-fast optical filters and nano-antennae. In this paper, we provide the underlying mechanisms of the gigahertz nano-oscillators and we review some recent results derived by the authors using the Lennard-Jones potential together with the continuum approach to mathematically model three different types of nano-oscillators including double-walled carbon nanotube, C60-nanotube and C60-nanotorus oscillators

Chloroquine-enhanced gene delivery mediated by carbon nanotubes

Polyethyleneimine-coated double-walled carbon nanotubes (DWCNTs) were used for dual gene and drug delivery, after loading the DWCNTs with the drug chloroquine, a lysosomotropic compound that is able to promote escape from the lysosomal compartment. Different forms of functionalization of the DWCNTs were examined in order to optimize this system. They included the testing of different treatments on DWCNTs to optimize the loading and delivery of chloroquine and the selection of a cationic polymer for coating the DWCNTs for optimum DNA binding and delivery. An acid oxidation treatment of DWCNTs was selected for optimum chloroquine loading together with polyethyleneimine as optimum cationic coating agent for plasmid DNA binding. Optimization of the conditions for choroquine-enhanced gene delivery were developed using luciferase expression as a model system. We have demonstrated that chloroquine-loading increases the ability of polyethyleneimine-coated DWCNTs to deliver functional nucleic acid to human cells. Cell viability tests have shown no cytotoxicity of the functionalized DWCNTs at the concentrations needed for optimum gene delivery. These results support the potential applications of this methodology in gene therapy

Preparing linked population data for research: cohort study of prisoner perinatal health outcomes.

ABSTRACTObjectivesThis paper assessed linkage quality and describes the generation of population representative samples of perinatally exposed and non-exposed mothers for cohort analysis and “own-control” analysis from the linked data. ApproachA study of pregnancy outcomes related to pregnancy in prison in New South Wales, Australia, used record linkage to add information about incarceration and serious mental health morbidity (MHM) to birth data. MHM data were oversampled and all available prisoner alias identities were requested for the linkage. Data custodians applied restrictions limiting the control group to a sample of unlinked records and required that year and person age in days be used instead of dates for all events. Linkage was performed by a dedicated state-wide data linkage authority.Multiple-matched identities were counted. Linked data was assessed to quantify duplicated births; excessive births; non-chronological progression of year of birth and to maternal age; concurrent pregnancies; concurrent incarcerations; and conception during incarceration. Exposure status was determined by interrogation of the temporal relationships of all incarceration periods with each to identify prisoner maternities. Maternities with incarceration status for each mother distinguished prisoner mothers from prisoner controls. The subset of prisoner mothers with both types maternity were “own controls”. Standard descriptive statistics are used to provide population prevalence of exposures and compare data quality across study stratified population sub-groups.ResultsLinked records for 3,260 prisoners and 3087 women who had given birth were resolved to 3085 unique person records. Linked person records inconsistent with a singular identity based on maternity factors only were within the predicted limit of the false positive rate set by the linkage authority (<0.5%) for non-prisoners with no mental health morbidity, but were twice as high for women with MHM (RR 2.2; 95%CI 1.9, 2.6) and tenfold higher among prisoners (RR 9.9; 95%CI 8.2, 11.9). The 2,589 prisoners not excluded comprised 558 prisoners (238 “own controls”) pregnant while in prison and 2,031 prisoner controls. The population estimated from study data represents 99.7% of the 404,144 women who actually birthed in NSW, of whom <1% were prisoners (68% with MHM) and 7% had serious mental health morbidity. ConclusionAlthough not set up to test use of alias identities for record linkage, these results suggest that the expected improved linkage sensitivity from including aliases was offset by reduced linkage specificity. The capacity to report results for prisoners against the whole population increased their utility.</jats:p

Prospects for local co-governance

British local authorities and their partners are increasingly developing new ways of working together with local communities. The nature of this co-working, however, is complex, multi-faceted and little understood. This article argues for greater clarity of thinking on the topic, by analysing this co-working as a form of political co-governance, and drawing attention in particular to issues of scale and democracy. Using evidence from a study of 43 local authority areas, 16 authorities are identified where co-governance is practised, following three main types of approach: service-influencing, service-delivering and parish council developing. It is concluded that strengthening political co-governance is essential for a healthy democracy

Timing of elective pre-labour caesarean section : A decision analysis

BWM is supported by a NHMRC Practitioner Fellowship (GNT1082548), and reports consultancy for ObsEva, Merck and Guerbet.Peer reviewedPublisher PD

Selective foraging behavior of seabirds in small-scale slicks

Lieber L, Füchtencordsjürgen C, Hilder RL, et al. Selective foraging behavior of seabirds in small-scale slicks. Limnology and Oceanography Letters . 2022.Marine predator foraging opportunities are often driven by dynamic physical processes enhancing prey accessibility. Surface slicks are ubiquitous yet ephemeral ocean features where convergent flows accumulate flotsam, concentrating marine organisms and pollutants. Slicks can manifest on the sea surface as meandering lines and seabirds often associate with slicks. Yet, how slicks may influence the fine-scale foraging behavior of seabirds is only coarsely resolved. Here we show that seabirds selectively forage in small-scale slicks. We used aerial drone technology to track surface-foraging terns (Sternidae, 107 tracks) over evolving slicks advected by the mean flow and reshaped by localized turbulence at scales of meters and seconds. Terns were more likely to switch into high-tortuosity foraging behavior when over slicks, with plunge-dive events occurring significantly more often within slicks. As we demonstrate that terns select dynamic slicks for foraging, our approach will also lend itself to interaction studies with pollutants, plumes, and fronts

Restricted three body problems at the nanoscale

In this paper, we investigate some of the classical restricted three body problems at the nanoscale, such as the circular planar restricted problem for three C60 fullerenes, and a carbon atom and two C60 fullerenes. We model the van der Waals forces between the fullerenes by the Lennard-Jones potential. In particular, the pairwise potential energies between the carbon atoms on the fullerenes are approximated by the continuous approach, so that the total molecular energy between two fullerenes can be determined analytically. Since we assume that such interactions between the molecules occur at sufficiently large distance, the classical three body problems analysis is legitimate to determine the collective angular velocity of the two and three C60 fullerenes at the nanoscale. We find that the maximum angular frequency of the two and three fullerenes systems reach the terahertz range and we determine the stationary points and the points which have maximum velocity for the carbon atom for the carbon atom and the two fullerenes system

Exploring Self-Repair in a Coupled Spiking Astrocyte Neural Network

It is now known that astrocytes modulate the activity at the tripartite synapses where indirect signaling via the retrograde messengers, endocannabinoids, leads to a localized self-repairing capability. In this paper, a self-repairing spiking astrocyte neural network (SANN) is proposed to demonstrate a distributed self-repairing capability at the network level. The SANN uses a novel learning rule that combines the spike-timing-dependent plasticity (STDP) and Bienenstock, Cooper, and Munro (BCM) learning rules (hereafter referred to as the BSTDP rule). In this learning rule, the synaptic weight potentiation is not only driven by the temporal difference between the presynaptic and postsynaptic neuron firing times but also by the postsynaptic neuron activity. We will show in this paper that the BSTDP modulates the height of the plasticity window to establish an input-output mapping (in the learning phase) and also maintains this mapping (via self-repair) if synaptic pathways become dysfunctional. It is the functional dependence of postsynaptic neuron firing activity on the height of the plasticity window that underpins how the proposed SANN self-repairs on the fly. The SANN also uses the coupling between the tripartite synapses and γ -GABAergic interneurons. This interaction gives rise to a presynaptic neuron frequency filtering capability that serves to route information, represented as spike trains, to different neurons in the subsequent layers of the SANN. The proposed SANN follows a feedforward architecture with multiple interneuron pathways and astrocytes modulate synaptic activity at the hidden and output neuronal layers. The self-repairing capability will be demonstrated in a robotic obstacle avoidance application, and the simulation results will show that the SANN can maintain learned maneuvers at synaptic fault densities of up to 80% regardless of the fault locations

Efecto de la fertilización y aplicación de fitohormonas sobre la floración y rendimiento de Hylocereus megalanthus (K.Schum. ex Vaupel)

El objetivo del estudio fue evaluar el efecto de la aplicación de distintas dosis de fertilización y fitohormonas, sobre la floración y el rendimiento de H. megalanthus (K.Schum. ex Vaupel). Las evaluaciones se realizaron en unidades experimentales homogéneas, con plantación de pitahaya de 2,5 años de edad. Se estableció un diseño experimental de bloques completamente al azar con arreglo factorial compuesto por nueve tratamientos y tres repeticiones. Los datos obtenidos se sometieron a un análisis de varianza y comparación de medias (Tukey, p<0,05). Los resultados mostraron que la aplicación de fertilización, fitohormonas y su interacción influyeron significativamente en la floración, fructificación y rendimiento, logrando incrementar sus valores con la aplicación 136 g planta-1 de NPK+ 138 ppm de fitohormonas. Sin embargo, las características de los frutos (peso, longitud y diámetro) no fueron modificadas significativamente por los tratamientos.The objective of the study was to evaluate the effect of the application of different doses of fertilization and phytohormones on the flowering and yield of H. megalanthus (K.Schum. ex Vaupel). The evaluations were carried inhomogeneous experimental units, with 2.5-year-old pitahaya plantations. A completely randomized block experimental design with a factorial arrangement was established, consisting of nine treatments and three replications. The data obtained were subjected to an analysis of variance and a comparison of means (Tukey, p<0.05). The results showed that the application of fertilization, phytohormones, and their interaction significantly influenced flowering, fruiting, and yield, managing to increase their values with the application of 136 g plant-1 of NPK + 138 ppm of phytohormones. However, fruit characteristics (weight, length, and diameter) were not significantly modified by the treatments.Gerencia de Contenidos Periodísticos y Editoriales, DNACI, INTAFil: Sánchez Herrera, José Hilder. Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas. Instituto de Investigación para el Desarrollo Sustentable de Ceja de Selva; PerúFil: Oliva, M. Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas. Instituto de Investigación para el Desarrollo Sustentable de Ceja de Selva; PerúFil: Collazos Silva, Roicer. Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas. Instituto de Investigación para el Desarrollo Sustentable de Ceja de Selva; PerúFil: Meléndez Mori, Jegnes Benjamín. Universidad Nacional Toribio Rodríguez de Mendoza de Amazonas. Instituto de Investigación para el Desarrollo Sustentable de Ceja de Selva; Per