Morse homology for the heat flow

We use the heat flow on the loop space of a closed Riemannian manifold to construct an algebraic chain complex. The chain groups are generated by perturbed closed geodesics. The boundary operator is defined in the spirit of Floer theory by counting, modulo time shift, heat flow trajectories that converge asymptotically to nondegenerate closed geodesics of Morse index difference one.Comment: 89 pages, 3 figure

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

Resolving Stellar Populations outside the Local Group: MAD observations of UKS2323-326

We present a study aimed at deriving constraints on star formation at intermediate ages from the evolved stellar populations in the dwarf irregular galaxy UKS2323-326. These observations were also intended to demonstrate the scientific capabilities of the multi-conjugated adaptive optics demonstrator (MAD) implemented at the ESO Very Large Telescope as a test-bench of adaptive optics (AO) techniques. We perform accurate, deep photometry of the field using J and Ks band AO images of the central region of the galaxy. The near-infrared (IR) colour-magnitude diagrams clearly show the sequences of asymptotic giant branch (AGB) stars, red supergiants, and red giant branch (RGB) stars down to ~1 mag below the RGB tip. Optical-near-IR diagrams, obtained by combining our data with Hubble Space Telescope observations, provide the best separation of stars in the various evolutionary stages. The counts of AGB stars brighter than the RGB tip allow us to estimate the star formation at intermediate ages. Assuming a Salpeter initial mass function, we find that the star formation episode at intermediate ages produced ~6x10^5 M_sun of stars in the observed region.Comment: 4 pages, 4 figures, Accepted for publication in A&A Letter

Surface photochemistry of the herbicide napropamide. The role of the media and environmental factors in directing the fates of intermediates

The photochemical behaviour of the herbicide napropamide is studied on cellulose and silica surfaces, using steady-state and laser-flash diffuse ectance techniques. The results are used to probe how the reaction sites of the host matrices influence the photo-reactive pathways. Napropamide undergoes reaction when irradiated with UV (lamps) or visible (sunlight) radiation on both solid supports. The nature of the intermediates and final products depend strongly on the presence or absence of molecular oxygen. The triplet state of napropamide adsorbed on cellulose is detected by both time-resolved luminescence and transient absorption spectroscopies. The triplet sate was not observed on silica, but transients which include the participation of molecular oxygen are detected during. ash photolysis studies. The keto intermediates of the photo-Claisen rearrangement products are observed on both solids. Substituted 1-naphthols from photo-Claisen reactions and 1-naphthol are among the main reaction products. 1,4-Naphthoquinone is a major photoproduct in the presence of molecular oxygen and is expected to be prevalent when napropamide undergoes photodegradation in the environment (i. e., after being applied to plants and fields)

The Diabetes Manual trial protocol – a cluster randomized controlled trial of a self-management intervention for type 2 diabetes [ISRCTN06315411]

Background The Diabetes Manual is a type 2 diabetes self-management programme based upon the clinically effective 'Heart Manual'. The 12 week programme is a complex intervention theoretically underpinned by self-efficacy theory. It is a one to one intervention meeting United Kingdom requirements for structured diabetes-education and is delivered within routine primary care. Methods/design In a two-group cluster randomized controlled trial, GP practices are allocated by computer minimisation to an intervention group or a six-month deferred intervention group. We aim to recruit 250 participants from 50 practices across central England. Eligibility criteria are adults able to undertake the programme with type 2 diabetes, not taking insulin, with HbA1c over 8% (first 12 months) and following an agreed protocol change over 7% (months 13 to 18). Following randomisation, intervention nurses receive two-day training and delivered the Diabetes Manual programme to participants. Deferred intervention nurses receive the training following six-month follow-up. Primary outcome is HbA1c with total and HDL cholesterol; blood pressure, body mass index; self-efficacy and quality of life as additional outcomes. Primary analysis is between-group HbA1c differences at 6 months powered to give 80% power to detect a difference in HbA1c of 0.6%. A 12 month cohort analysis will assess maintenance of effect and assess relationship between self-efficacy and outcomes, and a qualitative study is running alongside. Discussion This trial incorporates educational and psychological diabetes interventions into a single programme and assesses both clinical and psychosocial outcomes. The trial will increase our understanding of intervention transferability between conditions, those diabetes related health behaviours that are more or less susceptible to change through efficacy enhancing mechanisms and how this impacts on clinical outcomes

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients

Background: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design: 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. Discussion: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. Trial registration: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826Not peer reviewedPublisher PD

The FDA guidance for industry on PROs: the point of view of a pharmaceutical company

The importance of the patients point of view on their health status is widely recognised. Patient-reported outcomes is a broad term encompassing a large variety of different health data reported by patients, as symptoms, functional status, Quality of Life and Health-Related Quality of Life. Measurements of Health-Related Quality of Life have been developed during many years of researches, and a lot of validated questionnaires exist. However, few attempts have been made to standardise the evaluation of instruments characteristics, no recommendations are made about interpretation on Health-Related Quality of Life results, especially regarding the clinical significance of a change leading a therapeutic approach. Moreover, the true value of Health-Related Quality of Life evaluations in clinical trials has not yet been completely defined. An important step towards a more structured and frequent use of Patient-Reported Outcomes in drug development is represented by the FDA Guidance, issued on February 2006. In our paper we aim to report some considerations on this Guidance. Our comments focus especially on the characteristics of instruments to use, the Minimal Important Difference, and the methods to calculate it. Furthermore, we present the advantages and opportunities of using the Patient-Reported Outcomes in drug development, as seen by a pharmaceutical company. The Patient-Reported Outcomes can provide additional data to make a drug more competitive than others of the same pharmacological class, and a well demonstrated positive impact on the patient' health status and daily life might allow a higher price and/or the inclusion in a reimbursement list. Applying extensively the FDA Guidance in the next trials could lead to a wider culture of subjective measurement, and to a greater consideration for the patient's opinions on his/her care. Moreover, prescribing doctors and payers could benefit from subjective information to better define the value of drugs

Women on boards and firm performance

This study investigates the financial performance of Dutch companies both with and without women on their boards. The analysis extends earlier methods used in research by Catalyst (The bottom line: corporate performance and women's representation on boards, 2007) and McKinsey (Women matter. Gender diversity, a corporate performance driver. McKinsey & Company, USA, 2007), two studies that are often cited in the literature, although, each has a number of methodological shortcomings. This article adds to the international debate, which is often normative, through examining 99 listed companies in the Dutch Female Board Index. Our results show that firms with women directors perform better than those without women on their boards

Synthesis and photophysical properties of iron-carbonyl complex-coumarin conjugates as potential bimodal IR-fluorescent probes

An expedient synthesis of the first examples of iron-carbonyl complex-coumarin conjugates is reported. 7-Amino/7-hydroxycoumarin derivatives have been readily derivatized through an easily implemented single-step reaction involving the tricarbonyl(η5-cyclohexadienyl)iron(1+) cation [(C6H7)Fe(CO)3]+. The scope and limitations of this N-/O-alkylation reaction were also investigated. The fluorescence properties of these novel metal-carbonyl complexes have been studied and support their further use as valuable building blocks in the design of bimodal contrast agents for combined vibrational and fluorescence imaging

Concussion knowledge and experience among Welsh amateur rugby union coaches and referees

Background Rugby union is a collision sport where participants are at high risk of sustaining a concussion. In settings where there is little qualified medical supervision, certain stakeholders (eg, coaches and officials) should possess sufficient knowledge in regard to the recognition and management of concussion. Aim The aim of this study was to assess the knowledge and experience of various aspects of concussion among coaches and referees involved in Welsh amateur rugby union. Methods A questionnaire was distributed to 1843 coaches and 420 referees. Results A total of 333 coaches and 283 referees completed the questionnaire (18% and 68% response rates, respectively). Participants exhibited greater knowledge of concussion symptom recognition relative to knowledge of both the consequences of concussion and associated return-to-play protocols, both of which could be considered poor. There were no differences in knowledge levels between coaches and referees or between participants with or without a history of concussion. Two-thirds of participants incorrectly believed that headgear could prevent concussion, and nearly 30% of coaches reported having witnessed other coaches allowing a potentially concussed player to continue playing. Conclusions Identification of several misconceptions indicates that concussion management within Welsh amateur rugby union needs to be improved, warranting a multi-faceted educational intervention