Photoactivatable metal complexes : from theory to applications in biotechnology and medicine

This short review highlights some of the exciting new experimental and theoretical developments in the field of photoactivatable metal complexes and their applications in biotechnology and medicine. The examples chosen are based on some of the presentations at the Royal Society Discussion Meeting in June 2012, many of which are featured in more detail in other articles in this issue. This is a young field. Even the photochemistry of well-known systems such as metal–carbonyl complexes is still being elucidated. Striking are the recent developments in theory and computation (e.g. time-dependent density functional theory) and in ultrafast-pulsed radiation techniques which allow photochemical reactions to be followed and their mechanisms to be revealed on picosecond/nanosecond time scales. Not only do some metal complexes (e.g. those of Ru and Ir) possess favourable emission properties which allow functional imaging of cells and tissues (e.g. DNA interactions), but metal complexes can also provide spatially controlled photorelease of bioactive small molecules (e.g. CO and NO)—a novel strategy for site-directed therapy. This extends to cancer therapy, where metal-based precursors offer the prospect of generating excited-state drugs with new mechanisms of action that complement and augment those of current organic photosensitizers

Preformed metal crowns for decayed primary molar teeth

BackgroundPreformed metal crowns (PMCs) are recommended by the British Society of Paediatric Dentistry (BSPD) for restoring badly broken down primary molar teeth. However, few dental practitioners adopt this technique in clinical practice, citing cost and clinical difficulty as reasons for this. Whilst there is a subjective impression by clinical academics that PMCs provide a more durable restoration than filling materials, there appears to be little evidence within the literature to support this.ObjectivesThe primary aim of this systematic review was to compare clinical outcomes for primary molar teeth restored using PMCs compared to those restored with filling materials.Search methodsThe literature was searched using: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 3); MEDLINE (1966 to August 2005); EMBASE (1980 to August 2005); System for Information on Grey Literature in Europe (SIGLE) (1976 to August 2005). Relevant publications' reference lists were reviewed for relevant articles. The most recent search was carried out on 24 August 2005.Selection criteriaRandomised controlled trials (RCTs) that assessed the effectiveness of PMCs compared with filling materials or where there had been no treatment in children with untreated tooth decay in one or more primary molar teeth.Data collection and analysisTwo review authors independently assessed the title and abstracts for each article from the search results to decide whether it was likely to be relevant. Full papers were obtained for relevant articles and all three review authors studied these.Main resultsForty‐seven records were retrieved by the search strategies of which some were duplicates. Of these, 14 studies were scrutinised. No studies met the inclusion criteria and six studies were excluded from the review as they were either retrospective in design or reported as prospective outcomes but not randomised. No data were available for extraction and analysis and therefore, no conclusion could be made as to whether PMCs were more successful than filling materials for restoring primary molar teeth.Authors' conclusionsNo RCTs were available for appraisal. Whilst this technique is recommended by the BSPD for use in clinical practice, the evidence to support this is not strong, consisting mainly of case reports and uncontrolled studies. It is important that the absence of evidence for PMCs is not misinterpreted as evidence for their lack of efficacy.There is a strong need for prospective RCTs comparing PMCs and fillings for managing decayed primary molar teeth. The lower levels of evidence that have been produced, however, have strength in that the clinical outcomes are consistently in favour of PMCs, despite many of the studies placing PMCs on the most damaged of the pair of teeth being analysed

Dielectric Response of Periodic Systems from Quantum Monte Carlo Calculations

We present a novel approach that allows to calculate the dielectric response of periodic systems in the quantum Monte Carlo formalism. We employ a many-body generalization for the electric enthalpy functional, where the coupling with the field is expressed via the Berry-phase formulation for the macroscopic polarization. A self-consistent local Hamiltonian then determines the ground-state wavefunction, allowing for accurate diffusion quantum Monte Carlo calculations where the polarization's fixed point is estimated from the average on an iterative sequence, sampled via forward-walking. This approach has been validated for the case of an isolated hydrogen atom, and then applied to a periodic system, to calculate the dielectric susceptibility of molecular-hydrogen chains. The results found are in excellent agreement with the best estimates obtained from the extrapolation of quantum-chemistry calculations.Comment: 5 page 2figure

Use of in vitro and haptic assessments in the characterisation of surface lubricity

Lubricity is a key property of hydrophilic-coated urinary catheter surfaces. In vitro tests are commonly employed for evaluation of surface properties in the development of novel catheter coating technologies, however, their value in predicting the more subjective feeling of lubricity requires validation. We herein perform a range of in vitro assessments and human organoleptic studies to characterise surface properties of developmental hydrophilic coating formulations, including water wettability, coefficient of friction, dry-out kinetics and lubricity. Significant reductions of up to 40% in the contact angles and coefficient of friction values of the novel coating formulations in comparison to the control poly(vinyl pyrrolidone)-coated surfaces were demonstrated during quantitative laboratory assessments. In contrast, no significant differences in the more subjective feeling of lubricity between the novel formulations and the control-coated surfaces were observed when formulations were haptically assessed by the techniques described herein. This study, importantly, highlights the need for optimisation of in vitro and human haptic assessments to more reliably predict patient preferences

Microfluidic integration of photonic crystal fibers for online photochemical reaction analysis

Liquid-filled hollow-core photonic crystal fibers (HC-PCFs) are perfect optofluidic channels, uniquely providing low-loss optical guidance in a liquid medium. As a result, the overlap of the dissolved specimen and the intense light field in the micronsized core is increased manyfold compared to conventional bioanalytical techniques, facilitating highly-efficient photoactivation processes. Here we introduce a novel integrated analytical technology for photochemistry by microfluidic coupling of a HC-PCF nanoflow reactor to supplementary detection devices. Applying a continuous flow through the fiber, we deliver photochemical reaction products to a mass spectrometer in an online and hence rapid fashion, which is highly advantageous over conventional cuvette-based approaches

VA Accountability Act of 2015 (H.R. 1994), as Reported to the House

[Excerpt] This report describes the VA Accountability Act of 2015 (H.R. 1994) as reported to the House by the Committee on Veterans Affairs on July 23 2015 and compares it to current law where appropriate. A press account has reported that Chairman Jeff Miller may meet with all committee members to seek views of the minority before floor action. As a result of this meeting, it is possible that the final bill that will go to the House floor may have some provisions that differ from those that the Committee reported. This report provides a section-by-section description of the act

In-plane structure and ordering at liquid sodium surfaces and interfaces from ab initio molecular dynamics

Atoms at liquid metal surfaces are known to form layers parallel to the surface. We analyze the two-dimensional arrangement of atoms within such layers at the surface of liquid sodium, using ab initio molecular dynamics (MD) simulations based on density functional theory. Nearest neighbor distributions at the surface indicate mostly 5-fold coordination, though there are noticeable fractions of 4-fold and 6-fold coordinated atoms. Bond angle distributions suggest a movement toward the angles corresponding to a six-fold coordinated hexagonal arrangement of the atoms as the temperature is decreased towards the solidification point. We rationalize these results with a distorted hexagonal order at the surface, showing a mixture of regions of five and six-fold coordination. The liquid surface results are compared with classical MD simulations of the liquid surface, with similar effects appearing, and with ab initio MD simulations for a model solid-liquid interface, where a pronounced shift towards hexagonal ordering is observed as the temperature is lowered

Aortic calcification and femoral bone density are independently associated with left ventricular mass in patients with chronic kidney disease

Background Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a cross-sectional observational study. Methodology and Principal Findings A total of 120 patients were recruited (54% male, mean age 55±14 years, mean glomerular filtration rate 50±13 ml/min/1.73 m2). Abdominal aortic calcification was assessed using lateral lumbar spine radiography and was present in 48%. Mean femoral Z-score measured using dual energy x-ray absorptiometry was 0.60±1.06. Cardiovascular magnetic resonance imaging was used to determine left ventricular mass. One patient had left ventricular hypertrophy. Subjects with aortic calcification had higher left ventricular mass compared to those without (56±16 vs. 48±12 g/m2, P = 0.002), as did patients with femoral Z-scores below zero (56±15 vs. 49±13 g/m2, P = 0.01). In univariate analysis presence of aortic calcification correlated with left ventricular mass (r = 0.32, P = 0.001); mean femoral Z-score inversely correlated with left ventricular mass (r = −0.28, P = 0.004). In a multivariate regression model that included presence of aortic calcification, mean femoral Z-score, gender and 24-hour systolic blood pressure, 46% of the variability in left ventricular mass was explained (P<0.001). Conclusions In patients with stage 3 non-diabetic chronic kidney disease, lower mean femoral Z-score and presence of aortic calcification are independently associated with increased left ventricular mass. Further research exploring the pathophysiology that underlies these relationships is warranted

Spectral centrality measures in complex networks

Complex networks are characterized by heterogeneous distributions of the degree of nodes, which produce a large diversification of the roles of the nodes within the network. Several centrality measures have been introduced to rank nodes based on their topological importance within a graph. Here we review and compare centrality measures based on spectral properties of graph matrices. We shall focus on PageRank, eigenvector centrality and the hub/authority scores of HITS. We derive simple relations between the measures and the (in)degree of the nodes, in some limits. We also compare the rankings obtained with different centrality measures.Comment: 11 pages, 10 figures, 5 tables. Final version published in Physical Review

Noise and nonlinearities in high-throughput data

High-throughput data analyses are becoming common in biology, communications, economics and sociology. The vast amounts of data are usually represented in the form of matrices and can be considered as knowledge networks. Spectra-based approaches have proved useful in extracting hidden information within such networks and for estimating missing data, but these methods are based essentially on linear assumptions. The physical models of matching, when applicable, often suggest non-linear mechanisms, that may sometimes be identified as noise. The use of non-linear models in data analysis, however, may require the introduction of many parameters, which lowers the statistical weight of the model. According to the quality of data, a simpler linear analysis may be more convenient than more complex approaches. In this paper, we show how a simple non-parametric Bayesian model may be used to explore the role of non-linearities and noise in synthetic and experimental data sets.Comment: 12 pages, 3 figure