RCTs: How compatible are they with policy-making?

Randomised controlled trials (RCTs) have been promoted as a means of improving policy-making by testing new policies. While testing before full-scale roll-out is commendable, this paper discusses the challenges of using RCTs in contemporary (national) health policy-making in England. There are at least two challenges in particular that are currently underrepresented in the debate: The first arises from the complexity of many policies which are often too diffuse and unclear in focus to allow for the clear distinction between a policy ‘mechanism’ and its context to be drawn that is required for a RCT. The second challenge relates to the timing of RCTs, which tend to take place either too early in the life of a policy to be meaningful or too late to have an effect on policy formulation. We therefore encourage policy-makers and researchers to be clear about the types of uncertainties ‘field experiments’ are meant to address which may be addressed better by other types of knowledge generation

Complexity of Bradley-Manna-Sipma Lexicographic Ranking Functions

In this paper we turn the spotlight on a class of lexicographic ranking functions introduced by Bradley, Manna and Sipma in a seminal CAV 2005 paper, and establish for the first time the complexity of some problems involving the inference of such functions for linear-constraint loops (without precondition). We show that finding such a function, if one exists, can be done in polynomial time in a way which is sound and complete when the variables range over the rationals (or reals). We show that when variables range over the integers, the problem is harder -- deciding the existence of a ranking function is coNP-complete. Next, we study the problem of minimizing the number of components in the ranking function (a.k.a. the dimension). This number is interesting in contexts like computing iteration bounds and loop parallelization. Surprisingly, and unlike the situation for some other classes of lexicographic ranking functions, we find that even deciding whether a two-component ranking function exists is harder than the unrestricted problem: NP-complete over the rationals and $\Sigma^P_2$-complete over the integers.Comment: Technical report for a corresponding CAV'15 pape

Investigations on the Peach 4 Debrite, a Late Pleistocene Mass Movement on the Northwest British Continental Margin

The Peach 4 debrite is the most recent in a series of large scale Pleistocene MTDs within the Barra fan on the northwest British continental margin. Geophysical data indicate that Peach 4 was formed through a combination of blocky and muddy debris flows and affects an area of ~ 700 km2. BGS core sample 56 -10 36, located directly over the Peach 4 debrite, provides a minimum age of 14.68 ka cal BP for the last major failure. An upwards fining turbidite sequence in BGS core sample 56 -10 239 is associ-ated with increased As and S concentrations, indicators of diagenetic pyrite which forms under anoxic conditions. It is proposed that As and S concentrations may pro-vide a method of distinguishing between contourite and turbidite sedimentation, though further research is required

Estimation of Dietary Iron Bioavailability from Food Iron Intake and Iron Status

Currently there are no satisfactory methods for estimating dietary iron absorption (bioavailability) at a population level, but this is essential for deriving dietary reference values using the factorial approach. The aim of this work was to develop a novel approach for estimating dietary iron absorption using a population sample from a sub-section of the UK National Diet and Nutrition Survey (NDNS). Data were analyzed in 873 subjects from the 2000–2001 adult cohort of the NDNS, for whom both dietary intake data and hematological measures (hemoglobin and serum ferritin (SF) concentrations) were available. There were 495 men aged 19–64 y (mean age 42.7±12.1 y) and 378 pre-menopausal women (mean age 35.7±8.2 y). Individual dietary iron requirements were estimated using the Institute of Medicine calculations. A full probability approach was then applied to estimate the prevalence of dietary intakes that were insufficient to meet the needs of the men and women separately, based on their estimated daily iron intake and a series of absorption values ranging from 1–40%. The prevalence of SF concentrations below selected cut-off values (indicating that absorption was not high enough to maintain iron stores) was derived from individual SF concentrations. An estimate of dietary iron absorption required to maintain specified SF values was then calculated by matching the observed prevalence of insufficiency with the prevalence predicted for the series of absorption estimates. Mean daily dietary iron intakes were 13.5 mg for men and 9.8 mg for women. Mean calculated dietary absorption was 8% in men (50th percentile for SF 85 µg/L) and 17% in women (50th percentile for SF 38 µg/L). At a ferritin level of 45 µg/L estimated absorption was similar in men (14%) and women (13%). This new method can be used to calculate dietary iron absorption at a population level using data describing total iron intake and SF concentration

Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial : FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)

Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Fullthickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2–3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity ≤ 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence on the role of ILM peeling in FTMH surgery. Trial registration: This trial is registered with Current Controlled Trials ISRCTN number 33175422 and Clinical Trials.gov identifier NCT00286507.Chief Scientist Office, Scotland (project ref no CZH/4/235), NHS GrampianPeer reviewedPublisher PD

Adapted motivational interviewing to improve the uptake of treatment for glaucoma in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: Glaucoma is a chronic eye disease associated with irreversible visual loss. In Africa, glaucoma patients often present late, with very advanced disease. One-off procedures, such as laser or surgery, are recommended in Africa because of lack of or poor adherence to medical treatment. However, acceptance of surgery is usually extremely low. To prevent blindness, adherence to treatment needs to improve, using acceptable, replicable and cost-effective interventions. After reviewing the literature and interviewing patients in Bauchi (Nigeria) motivational interviewing (MI) was selected as the intervention for this trial, with adaptation for glaucoma (MIG). MI is designed to strengthen personal motivation for, and commitment to a specific goal by eliciting and exploring a person's reasons for change within an atmosphere of acceptance and compassion. The aim of this study is to assess whether MIG increases the uptake of laser or surgery amongst glaucoma patients where this is the recommended treatment. The hypothesis is that MIG increases the uptake of treatment. This will be the first trial of MI in Africa. METHODS: This is a hospital based, single centre, randomized controlled trial of MIG plus an information sheet on glaucoma and its treatment (the latter being "standard care") compared with standard care alone for glaucoma patients where the treatment recommended is surgery or laser.Those eligible for the trial are adults aged 17 years and above who live within 200 km of Bauchi with advanced glaucoma where the examining ophthalmologist recommends surgery or laser. After obtaining written informed consent, participants will be randomly allocated to MIG plus standard care, or standard care alone. Motivational interviewing will be delivered in Hausa or English by one of two MIG trained personnel. One hundred and fifty participants will be recruited to each arm. The primary outcome is the proportion of participants undergoing laser or surgery within two months of the date given to re attend for the procedure. MIG quality will be assessed using the validated MI treatment integrity scale. DISCUSSION: Motivational interviewing may be an important tool to increase the acceptance of treatment for glaucoma. The approach is potentially scalable and may be useful for other chronic conditions in Africa. TRIAL REGISTRATION: ISRCTN79330571 (Controlled-Trials.com)

Could Work Be a Source of Behavioural Disorders? A Study in Horses

Stress at work, as shown by a number of human studies, may lead to a variety of negative and durable effects, such as impaired psychological functioning (anxiety, depression…). Horses share with humans this characteristic of working on a daily basis and are submitted then to work stressors related to physical constraints and/or more “psychological” conflicts, such as potential controversial orders from the riders or the requirement to suppress emotions. On another hand, horses may perform abnormal repetitive behaviour (“stereotypies”) in response to adverse life conditions. In the present study, we investigated whether the type of work the horses are used for may have an impact on their tendency to show stereotypic behaviour (and its type) outside work. Observations in their box of 76 horses all living in the same conditions, belonging to one breed and one sex, revealed that the prevalence and types of stereotypies performed strongly depended upon the type of work they were used for. The stereotypies observed involved mostly mouth movements and head tossing/nodding. Work constraints probably added to unfavourable living conditions, favouring the emergence of chronic abnormal behaviours. This is especially remarkable as the 23 hours spent in the box were influenced by the one hour work performed every day. To our knowledge, this is the first evidence of potential effects of work stressors on the emergence of abnormal behaviours in an animal species. It raises an important line of thought on the chronic impact of the work situation on the daily life of individuals

Contribution of magnetic resonance imaging in the diagnosis of talus skip metastases of Ewing's sarcoma of the calcaneus in a child: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ewing's sarcoma of the calcaneus is rare. About thirty cases with calcaneus involvement have been reported in the literature. Talus skip metastases have rarely been described in the available literature</p> <p>Case presentation</p> <p>We report a case of a 14-year-old Moroccan boy, who presented with Ewing's sarcoma of his right calcaneus, diagnosed by swelling of the calcaneus evolving over a year. Radiography, computed tomography and magnetic resonance imaging showed an important tumoral process of the calcaneus and talus skip metastases. The diagnosis was confirmed with histology after a biopsy. In spite of amputation and postoperative chemotherapy, our patient died six months later due to secondary respiratory distress after lung metastasis.</p> <p>Conclusion</p> <p>Imaging, especially magnetic resonance, is important in the diagnosis of Ewing sarcoma and skeletal skip metastases. Treatment of Ewing's sarcoma consists of chemotherapy, radiation therapy and surgical resection depending on the stage and extent of the disease. With the exception of lesions in the calcaneus, the prognosis for disease-free survival of Ewing's sarcoma of the foot is excellent.</p

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes