Two-dimensional Ising model with competing interactions and its application to clusters and arrays of π\pi-rings and adiabatic quantum computing

We study planar clusters consisting of loops including a Josephson $\pi$-junction ($\pi$-rings). Each $\pi$-ring carries a persistent current and behaves as a classical orbital moment. The type of particular state associated with the orientation of orbital moments at the cluster depends on the interaction between these orbital moments and can be easily controlled, i.e. by a bias current or by other means. We show that these systems can be described by the two-dimensional Ising model with competing nearest-neighbor and diagonal interactions and investigate the phase diagram of this model. The characteristic features of the model are analyzed based on the exact solutions for small clusters such as a 5-site square plaquette as well as on a mean-field type approach for the infinite square lattice of Ising spins. The results are compared with spin patterns obtained by Monte Carlo simulations for the 100 $\times$ 100 square lattice and with experiment. We show that the $\pi$-ring clusters may be used as a new type of superconducting memory elements. The obtained results may be verified in experiments and are applicable to adiabatic quantum computing where the states are switched adiabatically with the slow change of coupling constants.Comment: 32 pages, 22 figures, RevTe

A 40-Year Cohort Study of Evolving Hypothalamic Dysfunction in Infants and Young Children (<3 years) with Optic Pathway Gliomas

Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and neurobehavioural morbidity in 90 infants/children diagnosed before their third birthday and followed-up for 9.5 years (range 0.5–25.0). A total of 52 (57.8%) patients experienced endo-metabolic dysfunction (EMD), the large majority (46) of whom had hypothalamic involvement (H+) and lower endocrine event-free survival (EEFS) rates. EMD was greatly increased by a diencephalic syndrome presentation (85.2% vs. 46%, p = 0.001)), H+ (OR 6.1 95% CI 1.7–21.7, p 0.005), radiotherapy (OR 16.2, 95% CI 1.7–158.6, p = 0.017) and surgery (OR 4.8 95% CI 1.3–17.2, p = 0.015), all associated with anterior pituitary disorders. Obesity occurred in 25% of cases and was clustered with the endocrinopathies. Neurobehavioural deficits occurred in over half (52) of the cohort and were associated with H+ (OR 2.5 95% C.I. 1.1–5.9, p = 0.043) and radiotherapy (OR 23.1 C.I. 2.9–182, p = 0.003). Very young children with OPHG carry a high risk of endo-metabolic and neurobehavioural comorbidities which deserve better understanding and timely/parallel support from diagnosis to improve outcomes. These evolve in complex, hierarchical patterns over time whose aetiology appears predominantly determined by injury from the hypothalamic tumour location alongside adjuvant treatment strategies

Flow interactions with an aquatic macrophyte: a field study using stereoscopic particle image velocimetry

This paper reports the morphology of a natural patch of Ranunculus penicillatus and presents high-resolution measurements of flow velocities in its wake using a stereoscopic PIV field measurement system. The patch was 3.80 m long, 1.24 m wide and caused substantial changes to downstream mean velocities and turbulence. Vertical profiles of streamwise mean velocity were not logarithmic and flow was redirected under the positively buoyant canopy, enhancing vertical turbulent mixing in the wake and generating a large region where the velocity covariance u'w' was positive. Turbulent kinetic energy was enhanced downstream from the patch lateral shear layer, but not at the centre of the wake. Spectra downstream from the patch showed that turbulence was neither dominated by fine-scale nor large-scale structures, likely due to the low energy of the flow conditions and lack of a developed vortex street within the measurement domain. Sedimentation was observed at the upstream end of the patch, but not underneath the floating canopy. The methods and results of this work will be useful for planning other in situ studies. Also, the reported data on macrophyte geometry and biometrics will assist with the design of more realistic replicas for use in laboratory studies

Spatial and environmental drivers of macrophyte diversity and community composition in temperate and tropical calcareous rivers

The hypothesis was examined that sources of variation in macrophyte species richness (alpha-diversity: S) and community composition (“species-set”), attributable to spatial and environmental, variables, may differ in importance between tropical and temperate calcareous rivers (&gt;10 mg CaCO3 L−1). To test this hypothesis geographic, environmental, and aquatic vegetation data was acquired for 1151 sites on calcareous rivers within the British Isles, supporting 106 macrophyte species (mean S: 3.1 species per sample), and 203 sites from Zambian calcareous rivers, supporting 255 macrophyte species (mean S: 8.3 species per sample). The data were analysed using an eigenfunction spatial analysis procedure, Moran’s Eigenvector Maps (MEM), to assess spatial variation of species richness and community composition at large regional scale (&gt;105 km2: British Isles and Zambia); and at medium catchment scale (104–105 km2: British Isles only). Variation-partitioning was undertaken using multiple regression for species richness data, and partial redundancy analysis (pRDA) for community data. For the British Isles, spatial and environmental variables both significantly contributed to explaining variation in both species richness and community composition. In addition, a substantial amount of the variation in community composition, for the British Isles as a whole and for some RBUs, was accounted for by spatially-structured environmental variables. In Zambia, species richness was explained only by pure spatial variables, but environmental and spatially-structured environmental variables also explained a significant part of the variation for community composition. At medium-scale, in the British Isles, species richness was explained by spatial variables, and only for four of the six RBUs

The impact of training non-physician clinicians in Malawi on maternal and perinatal mortality : a cluster randomised controlled evaluation of the enhancing training and appropriate technologies for mothers and babies in Africa (ETATMBA) project

Background: Maternal mortality in much of sub-Saharan Africa is very high whereas there has been a steady decline in over the past 60 years in Europe. Perinatal mortality is 12 times higher than maternal mortality accounting for about 7 million neonatal deaths; many of these in sub-Saharan countries. Many of these deaths are preventable. Countries, like Malawi, do not have the resources nor highly trained medical specialists using complex technologies within their healthcare system. Much of the burden falls on healthcare staff other than doctors including non-physician clinicians (NPCs) such as clinical officers, midwives and community health-workers. The aim of this trial is to evaluate a project which is training NPCs as advanced leaders by providing them with skills and knowledge in advanced neonatal and obstetric care. Training that will hopefully be cascaded to their colleagues (other NPCs, midwives, nurses). Methods/design: This is a cluster randomised controlled trial with the unit of randomisation being the 14 districts of central and northern Malawi (one large district was divided into two giving an overall total of 15). Eight districts will be randomly allocated the intervention. Within these eight districts 50 NPCs will be selected and will be enrolled on the training programme (the intervention). Primary outcome will be maternal and perinatal (defined as until discharge from health facility) mortality. Data will be harvested from all facilities in both intervention and control districts for the lifetime of the project (3–4 years) and comparisons made. In addition a process evaluation using both quantitative and qualitative (e.g. interviews) will be undertaken to evaluate the intervention implementation. Discussion: Education and training of NPCs is a key to improving healthcare for mothers and babies in countries like Malawi. Some of the challenges faced are discussed as are the potential limitations. It is hoped that the findings from this trial will lead to a sustainable improvement in healthcare and workforce development and training. Trial registration: ISRCTN6329415

Controlled assembly of SNAP-PNA-fluorophore systems on DNA templates to produce fluorescence resonance energy transfer

The SNAP protein is a widely used self-labeling tag that can be used for tracking protein localization and trafficking in living systems. A model system providing controlled alignment of SNAP-tag units can provide a new way to study clustering of fusion proteins. In this work, fluorescent SNAP-PNA conjugates were controllably assembled on DNA frameworks forming dimers, trimers, and tetramers. Modification of peptide nucleic acid (PNA) with the O6-benzyl guanine (BG) group allowed the generation of site-selective covalent links between PNA and the SNAP protein. The modified BG-PNAs were labeled with fluorescent Atto dyes and subsequently chemo-selectively conjugated to SNAP protein. Efficient assembly into dimer and oligomer forms was verified via size exclusion chromatography (SEC), electrophoresis (SDS-PAGE), and fluorescence spectroscopy. DNA directed assembly of homo- and hetero-dimers of SNAP-PNA constructs induced homo- and hetero-FRET, respectively. Longer DNA scaffolds controllably aligned similar fluorescent SNAP-PNA constructs into higher oligomers exhibiting homo-FRET. The combined SEC and homo-FRET studies indicated the 1:1 and saturated assemblies of SNAP-PNA-fluorophore:DNA formed preferentially in this system. This suggested a kinetic/stoichiometric model of assembly rather than binomially distributed products. These BG-PNA-fluorophore building blocks allow facile introduction of fluorophores and/or assembly directing moieties onto any protein containing SNAP. Template directed assembly of PNA modified SNAP proteins may be used to investigate clustering behavior both with and without fluorescent labels which may find use in the study of assembly processes in cells

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD) : study protocol for a randomized controlled trial

Background World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. Methods/Design This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control). Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice. or Control group: Standard GP care, with referral to secondary care as required, but no access to ICCD. Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients

Reconstructing disease transmission dynamics from animal movements and test data

Disease outbreaks are often accompanied by a wealth of data, usually in the form of movements, locations and tests. This data is a valuable resource in which data scientists and epidemiologists can reconstruct the transmission pathways and parameters and thus devise control strategies. However, the spatiotemporal data gathered can be both vast whilst at the same time incomplete or contain errors frustrating the effort to accurately model the transmission processes. Fortunately, several techniques exist that can be used to infer the relevant information to help explain these processes. The aim of this article is to provide the reader with a user friendly introduction to the techniques used in dealing with the large datasets that exists in epidemiological and ecological science and the common pitfalls that are to be avoided as well as an introduction to inference techniques for estimating parameter values for mathematical models from spatiotemporal datasets