Analysis of a Model Biological Switch

A model mechanism proposed by Murray [Phil. Traps. Roy. Soc. London B, 295 (1981), pp. 473–496] for generating wing patterns and eyespots on butterflies and moths is based on a morphogen (S) activated biological switch for a gene product (g). We analyse one of the resulting partial differential equation systems, namely S_t = DΔS - kS, g_t = k_tS + αg (g-k_2) (g_c-g ), where D,k,k_1 ,k_2 ,g_c > k_2 and α are positive constants. We determine analytically the size of the spatial domain where g → g_c as t → ∞ after an influx of S at the origin. This gives the size of the eyespot in terms of the mechanism parameters. The analytical problem is a nontrivial singular perturbation expansion which we discuss in detail

Metallierung von Pyridylmetallocenen durch Platin(II), Gold(III), Quecksilber(II) und Iridium(III)

Weight management is a game of chance for most children and young people, and is dependent on service availability and the expertise of the provider. Many localities are without established weight-management services, and the effectiveness of those provided is often not well-known. SHINE (Self Help, Independence, Nutrition and Exercise) is the only documented tier 3 community-based service provider in the UK. It offers a plethora of interventions tailored to each child or young person using a stepped-care approach (SCA) to treat severe obesity: as the severity of obesity increases, so does the intensity of intervention. This article describes an SCA and uses this model to demonstrate a range of appropriate, available interventions. A SCA can provide a holistic and integrative care pathway for children and young people with severe obesity when implemented at tier 3

Health economic burden that wounds impose on the National Health Service in the UK

OBJECTIVE: To estimate the prevalence of wounds managed by the UK's National Health Service (NHS) in 2012/2013 and the annual levels of healthcare resource use attributable to their management and corresponding costs. METHODS: This was a retrospective cohort analysis of the records of patients in The Health Improvement Network (THIN) Database. Records of 1000 adult patients who had a wound in 2012/2013 (cases) were randomly selected and matched with 1000 patients with no history of a wound (controls). Patients' characteristics, wound-related health outcomes and all healthcare resource use were quantified and the total NHS cost of patient management was estimated at 2013/2014 prices. RESULTS: Patients' mean age was 69.0 years and 45% were male. 76% of patients presented with a new wound in the study year and 61% of wounds healed during the study year. Nutritional deficiency (OR 0.53; p<0.001) and diabetes (OR 0.65; p<0.001) were independent risk factors for non-healing. There were an estimated 2.2 million wounds managed by the NHS in 2012/2013. Annual levels of resource use attributable to managing these wounds and associated comorbidities included 18.6 million practice nurse visits, 10.9 million community nurse visits, 7.7 million GP visits and 3.4 million hospital outpatient visits. The annual NHS cost of managing these wounds and associated comorbidities was pound5.3 billion. This was reduced to between pound5.1 and pound4.5 billion after adjusting for comorbidities. CONCLUSIONS: Real world evidence highlights wound management is predominantly a nurse-led discipline. Approximately 30% of wounds lacked a differential diagnosis, indicative of practical difficulties experienced by non-specialist clinicians. Wounds impose a substantial health economic burden on the UK's NHS, comparable to that of managing obesity ( pound5.0 billion). Clinical and economic benefits could accrue from improved systems of care and an increased awareness of the impact that wounds impose on patients and the NHS.Ye

Household waste management in the UK: current practices and challenges

The UK’s reliance on landfill sites for waste disposal has been addressed in recent years with the Landfill Directive and Landfill Tax. This has encouraged Local Authorities to seek alternative methods of treating household waste, introducing and expanding kerbside collections of recyclates and organic waste. This paper assesses current household waste management practices and challenges in the UK. Drivers and instruments for change and various approaches to kerbside waste collections are discussed. The current household waste management challenges in the UK are identified, including the division of responsibility for household waste management between various Local Authorities and Government Departments and the methods available to tackle these issues. The research revealed adopting an integrated management system for household waste to comply with legislation and behavioural attitudes towards recycling and waste reduction activities are obstacles facing Local Authorities. Conversely, segregation of household waste by material is increasing, with separate kerbside collections for recyclates, organic waste and bulky waste collections, some of which is selected for reuse. The challenge now is to improve the yield of recyclates, reach people that do not segregate their waste for recycling and increase the quantity of material from participating householders with imaginative ways for reuse and recycling

Exploring the validity of estimating EQ-5D and SF-6D utility values from the health assessment questionnaire in patients with inflammatory arthritis

<p>Abstract</p> <p>Background</p> <p>Utility scores are used to estimate Quality Adjusted Life Years (QALYs), applied in determining the cost-effectiveness of health care interventions. In studies where no preference based measures are collected, indirect methods have been developed to estimate utilities from clinical instruments. The aim of this study was to evaluate a published method of estimating the EuroQol-5D (EQ-5D) and Short Form-6D (SF-6D) (preference based) utility scores from the Health Assessment Questionnaire (HAQ) in patients with inflammatory arthritis.</p> <p>Methods</p> <p>Data were used from 3 cohorts of patients with: early inflammatory arthritis (<10 weeks duration); established (>5 years duration) stable rheumatoid arthritis (RA); and RA being treated with anti-TNF therapy. Patients completed the EQ-5D, SF-6D and HAQ at baseline and a follow-up assessment. EQ-5D and SF-6D scores were predicted from the HAQ using a published method. Differences between predicted and observed EQ-5D and SF-6D scores were assessed using the paired t-test and linear regression.</p> <p>Results</p> <p>Predicted utility scores were generally higher than observed scores (range of differences: EQ-5D 0.01 - 0.06; SF-6D 0.05 - 0.10). Change between predicted values of the EQ-5D and SF-6D corresponded well with observed change in patients with established RA. Change in predicted SF-6D scores was, however, less than half of that in observed values (p < 0.001) in patients with more active disease. Predicted EQ-5D scores underestimated change in cohorts of patients with more active disease.</p> <p>Conclusion</p> <p>Predicted utility scores overestimated baseline values but underestimated change. Predicting utility values from the HAQ will therefore likely underestimate the QALYs of interventions, particularly for patients with active disease. We recommend the inclusion of at least one preference based measure in future clinical studies.</p

Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: observational study from the British Society of Rheumatology Biologics Register

Objectives. To evaluate the risk–benefit profile of anti-TNF therapies in PsA and to study the predictors of treatment response and disease remission [disease activity score (DAS)-28 < 2.6]. Methods. The study included PsA patients (n = 596) registered with the British Society for Rheumatology Biologics Register (BSRBR). Response was assessed using the European League against Rheumatism (EULAR) improvement criteria. Univariate and multivariate logistic regression models were developed to examine factors associated with EULAR response and disease remission using a range of covariates. Poisson regression was used to calculate incidence rate ratios (IRRs) for serious adverse events (SAEs) vs seronegative RA controls receiving DMARDs, adjusting for age, sex and baseline co-morbidity. Results. At baseline, the mean (s.d.) DAS-28 was 6.4 (5.6). Of the patients, 70.3% were EULAR responders at 12 months. At 6 months, older patients [adjusted odds ratio (OR) 0.97 per year; 95% CI 0.95, 0.99], females (adjusted OR 0.51; 95% CI 0.34, 0.78) and patients on corticosteroids (adjusted OR 0.45; 95% CI 0.28, 0.72) were less likely to achieve a EULAR response. Over 1776.2 person-years of follow-up (median 3.07 per person), the IRR of SAEs compared with controls was not increased (0.9; 95% CI 0.8, 1.3). Conclusions. Anti-TNF therapies have a good response rate in PsA, and have an adverse event profile similar to that seen in a control cohort of patients with seronegative arthritis receiving DMARD therapy

Rigid upper bounds for the angular momentum and centre of mass of non-singular asymptotically anti-de Sitter space-times

We prove upper bounds on angular momentum and centre of mass in terms of the Hamiltonian mass and cosmological constant for non-singular asymptotically anti-de Sitter initial data sets satisfying the dominant energy condition. We work in all space-dimensions larger than or equal to three, and allow a large class of asymptotic backgrounds, with spherical and non-spherical conformal infinities; in the latter case, a spin-structure compatibility condition is imposed. We give a large class of non-trivial examples saturating the inequality. We analyse exhaustively the borderline case in space-time dimension four: for spherical cross-sections of Scri, equality together with completeness occurs only in anti-de Sitter space-time. On the other hand, in the toroidal case, regular non-trivial initial data sets saturating the bound exist.Comment: improvements in the presentation; some statements correcte

Exchange between Escherichia coli polymerases II and III on a processivity clamp

Escherichia coli has three DNA polymerases implicated in the bypass of DNA damage, a process called translesion synthesis (TLS) that alleviates replication stalling. Although these polymerases are specialized for different DNA lesions, it is unclear if they interact differently with the replication machinery. Of the three, DNA polymerase (Pol) II remains the most enigmatic. Here we report a stable ternary complex of Pol II, the replicative polymerase Pol III core complex and the dimeric processivity clamp, β. Single-molecule experiments reveal that the interactions of Pol II and Pol III with β allow for rapid exchange during DNA synthesis. As with another TLS polymerase, Pol IV, increasing concentrations of Pol II displace the Pol III core during DNA synthesis in a minimal reconstitution of primer extension. However, in contrast to Pol IV, Pol II is inefficient at disrupting rolling-circle synthesis by the fully reconstituted Pol III replisome. Together, these data suggest a β-mediated mechanism of exchange between Pol II and Pol III that occurs outside the replication fork

Stationary solutions of driven fourth- and sixth-order Cahn-Hilliard type equations

New types of stationary solutions of a one-dimensional driven sixth-order Cahn-Hilliard type equation that arises as a model for epitaxially growing nano-structures such as quantum dots, are derived by an extension of the method of matched asymptotic expansions that retains exponentially small terms. This method yields analytical expressions for far-field behavior as well as the widths of the humps of these spatially non-monotone solutions in the limit of small driving force strength which is the deposition rate in case of epitaxial growth. These solutions extend the family of the monotone kink and antikink solutions. The hump spacing is related to solutions of the Lambert $W$ function. Using phase space analysis for the corresponding fifth-order dynamical system, we use a numerical technique that enables the efficient and accurate tracking of the solution branches, where the asymptotic solutions are used as initial input. Additionally, our approach is first demonstrated for the related but simpler driven fourth-order Cahn-Hilliard equation, also known as the convective Cahn-Hilliard equation