'Choosing shoes': a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients

Background: Footwear has been accepted as a therapeutic intervention for the foot affected by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in patients with RA is limited. The aims of this study were to identify current footwear styles, footwear characteristics, and factors that influence footwear choice experienced by patients with RA. Methods: Eighty patients with RA were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Current footwear, footwear characteristics and the factors associated with choice of footwear were identified. Suitability of footwear was recorded using pre-determined criteria for assessing footwear type, based on a previous study of foot pain. Results: The patients had longstanding RA with moderate-to severe disability and impairment. The foot and ankle assessment demonstrated a low-arch profile with both forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were opentype footwear. More than 70% of patients’ footwear was defined as being poor. Poor footwear characteristics such as heel rigidity and sole hardness were observed. Patients reported comfort (17%) and fit (14%) as important factors in choosing their own footwear. Only five percent (5%) of patients wore therapeutic footwear. Conclusions: The majority of patients with RA wear footwear that has been previously described as poor. Future work needs to aim to define and justify the specific features of footwear that may be of benefit to foot health for people with RA

R^4 counterterm and E7(7) symmetry in maximal supergravity

The coefficient of a potential R^4 counterterm in N=8 supergravity has been shown previously to vanish in an explicit three-loop calculation. The R^4 term respects N=8 supersymmetry; hence this result poses the question of whether another symmetry could be responsible for the cancellation of the three-loop divergence. In this article we investigate possible restrictions from the coset symmetry E7(7)/SU(8), exploring the limits as a single scalar becomes soft, as well as a double-soft scalar limit relation derived recently by Arkani-Hamed et al. We implement these relations for the matrix elements of the R^4 term that occurs in the low-energy expansion of closed-string tree-level amplitudes. We find that the matrix elements of R^4 that we investigated all obey the double-soft scalar limit relation, including certain non-maximally-helicity-violating six-point amplitudes. However, the single-soft limit does not vanish for this latter set of amplitudes, which suggests that the E7(7) symmetry is broken by the R^4 term.Comment: 33 pages, typos corrected, published versio

Discrete Information from CHL Black Holes

AdS_2/CFT_1 correspondence predicts that the logarithm of a Z_N twisted index over states carrying a fixed set of charges grows as 1/N times the entropy of the black hole carrying the same set of charges. In this paper we verify this explicitly by calculating the microscopic Z_N twisted index for a class of states in the CHL models. This demonstrates that black holes carry more information about the microstates than just the total degeneracy.Comment: LaTeX file, 24 pages; v2: references adde

The first legal mortgagor: a consumer without adequate protection?

This article contends that the UK government’s attempt to create a well-functioning consumer credit market will be undermined if it fails to reform the private law framework relating to the first legal mortgage. Such agreements are governed by two distinct regulatory regimes that are founded upon very different conceptions of the mortgagor. The first, the regulation of financial services overseen by the Financial Conduct Authority, derives from public law and is founded upon a conception of the mortgagor as “consumer”. The other is land law, private law regulation implemented by the judiciary and underpinned by a conception of the mortgagor as “landowner”. Evidence suggests that the operation of these two regimes prevents mortgagors from receiving fair and consistent treatment. The current reform of financial services regulation therefore will change only one part of this governance regime and will leave mortgagors heavily reliant upon a regulator that still has to prove itself. What this article argues is that reform of the rules of private law must also be undertaken with the aim of initiating a paradigm shift in the conception of the mortgagor from “landowner” to “consumer”. Cultural shifts of this kind take time but the hope is that this conceptual transformation will occur in time to deter the predicted rise in mortgage possessions

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

A Twist in the Dyon Partition Function

In four dimensional string theories with N=4 and N=8 supersymmetries one can often define twisted index in a subspace of the moduli space which captures additional information on the partition function than the ones contained in the usual helicity trace index. We compute several such indices in type IIB string theory on K3 x T^2 and T^6, and find that they share many properties with the usual helicity trace index that captures the spectrum of quarter BPS states in N=4 supersymmetric string theories. In particular the partition function is a modular form of a subgroup of Sp(2,Z) and the jumps across the walls of marginal stability are controlled by the residues at the poles of the partition function. However for large charges the logarithm of this index grows as 1/n times the entropy of a black hole carrying the same charges where n is the order of the symmetry generator that is used to define the twisted index. We provide a macroscopic explanation of this phenomenon using quantum entropy function formalism. The leading saddle point corresponding to the attractor geometry fails to contribute to the twisted index, but a Z_n orbifold of the attractor geometry produces the desired contribution.Comment: LaTeX file, 35 pages; v2: references adde

Fecundity, spore recruitment and size in Gelidium sesquipedale (Gelidiales,Rhodophyta)

Gelidium sesquipedale fecundity was quantified by counting tetrasporangial sori and cystocarps per meter squared and by estimating the number of spores contained inside them . These were obtained by regression on a size metric of reproductive structures . Tetrasporangial sori length and cystocarp thickness were the best estimators of spore number. To assess spore recruitment, 12 pottery tiles were fixed to the bottom, and the appearance of small fronds was monitored. No clear seasonal pattern of reproduction was found . Tetraspore production peaked in March 1990 with 10.4 x 106 spores m-2, whereas the carpospore peak was lower, 4.9 x 10 5 spores m-2 in July 1989. Recruitment followed tetraspore peaks . The probability of a G. sesquipedale tetraspore making the transition to a recruit was 4.7 x 10-5. Frond length was significantly related to tetrasporangial sori number, while cystocarp number was only related to frond branching order. Minimum size for reproduction was 6.9 cm for gametophytes and 5.4 cm for tetrasporophytes; very rarely were cystocarpic fronds smaller than 9 cm, while tetrasporic fronds were often longer than 15 cm . Cystocarpic fronds were significantly shorter and had more branches than tetrasporic fronds

Repeat Transanal Advancement Flap Repair: Impact on the Overall Healing Rate of High Transsphincteric Fistulas and on Fecal Continence

PURPOSE: Transanal advancement flap repair (TAFR) has been advocated as the treatment of choice for transsphincteric fistulas passing through the upper or middle third of the external anal sphincter. It is not clear whether previous attempts at repair adversely affect the outcome of TAFR. The purpose of the present study was to evaluate the success rate of a repeat TAFR and to assess the impact of such a second procedure on the overall healing rate of high transsphincteric fistulas and on fecal continence. METHODS: Between January 2001 and January 2005, a consecutive series of 87 patients (62 males; median age, 49 (range, 27-73) years) underwent TAFR. Median follow-up was 15 (range, 2-50) months. Patients in whom the initial operation failed were offered two further treatment options: a second flap repair or a long-term indwelling seton drainage. Twenty-six patients (male:female ratio, 5:2; median age, 51 (range, 31-72) years) preferred a repeat repair. Continence status was evaluated before and after the procedures by using the Rockwood Faecal Incontinence Severity Index (RFISI). RESULTS: The healing rate after the first TAFR was 67 percent. Of the 29 patients in whom the initial procedure failed, 26 underwent a repeat TAFR. The healing rate after this second procedure was 69 percent, resulting in an overall success rate of 90 percent. Both before and after the first attempt of TAFR, the median RFISI was 7 (range, 0-34). In patients who underwent a second TAFR, the median RFISI before and after this procedure was 9 (range, 0-34) and 8 (range, 0-34), respectively. None of these changes were statistically significant. CONCLUSIONS: Repeat TAFR increases the overall healing rate of high transsphincteric fistulas from 67 percent after one attempt to 90 percent after two attempts without a deteriorating effect on fecal continence

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio