A mean score method for sensitivity analysis to departures from the missing at random assumption in randomised trials

Most analyses of randomised trials with incomplete outcomes make untestable assumptions and should therefore be subjected to sensitivity analyses. However, methods for sensitivity analyses are not widely used. We propose a mean score approach for exploring global sensitivity to departures from missing at random or other assumptions about incomplete outcome data in a randomised trial. We assume a single outcome analysed under a generalised linear model. One or more sensitivity parameters, specified by the user, measure the degree of departure from missing at random in a pattern mixture model. Advantages of our method are that its sensitivity parameters are relatively easy to interpret and so can be elicited from subject matter experts; it is fast and non-stochastic; and its point estimate, standard error and confidence interval agree perfectly with standard methods when particular values of the sensitivity parameters make those standard methods appropriate. We illustrate the method using data from a mental health trial

Gulf of Mexico oil blowout increases risks to globally threatened species

Fourteen marine species in the Gulf of Mexico are protected by the US Endangered Species Act, the Marine Mammal Protection Act, and the Migratory Bird Treaty Act. As the British Petroleum oil spill recovery and remediation proceed, species internationally recognized as having an elevated risk of extinction should also receive priority for protection and restoration efforts, whether or not they have specific legal protection. Forty additional marine species-unprotected by any federal laws-occur in the Gulf and are listed as threatened on the International Union for Conservation of Nature's (IUCN) Red List. The Red List assessment process scientifically evaluates species' global status and is therefore a key mechanism for transboundary impact assessments and for coordinating international conservation action. Environmental impact assessments conducted for future offshore oil and gas development should incorporate available data on globally threatened species, including species on the IUCN Red List. This consideration is particularly important because US Natural Resource Damage Assessments may not account for injury to highly migratory, globally threatened species. © 2011 by American Institute of Biological Sciences. All rights reserved.published_or_final_versio

Initial fixation placement in face images is driven by top-down guidance

The eyes are often inspected first and for longer period during face exploration. To examine whether this saliency of the eye region at the early stage of face inspection is attributed to its local structure properties or to the knowledge of its essence in facial communication, in this study we investigated the pattern of eye movements produced by rhesus monkeys (Macaca mulatta) as they free viewed images of monkey faces. Eye positions were recorded accurately using implanted eye coils, while images of original faces, faces with scrambled eyes, and scrambled faces except for the eyes were presented on a computer screen. The eye region in the scrambled faces attracted the same proportion of viewing time and fixations as it did in the original faces, even the scrambled eyes attracted substantial proportion of viewing time and fixations. Furthermore, the monkeys often made the first saccade towards to the location of the eyes regardless of image content. Our results suggest that the initial fixation placement in faces is driven predominantly by ‘top-down’ or internal factors, such as the prior knowledge of the location of “eyes” within the context of a face

Phenomenological Aspects of Gauge Mediation with Sequestered Supersymmetry Breaking in light of Dark Matter Detection

In a recent work, a model of gauge mediation with sequestered supersymmetry (SUSY) breaking was proposed. In this model, the mass of the gravitino is O(100) GeV without causing the flavor-changing neutral-current problem. In contrast to traditional gauge mediation, the gravitino is not the lightest SUSY particle and the neutralino is the candidate of the dark matter. In this paper, we investigate phenomenological aspects of this model and discuss the possibility of the direct detection of the dark matter. In particular, we focus on the light neutralino case and find that the light-Higgsino scenario such as the focus point is interesting, taking account of the recent CDMS result.Comment: 17 pages, 8 figures; v2:references added, some corrections; v3:version accepted for publication in JHE

Computer simulation of syringomyelia in dogs

Syringomyelia is a pathological condition in which fluid-filled cavities (syringes) form and expand in the spinal cord. Syringomyelia is often linked with obstruction of the craniocervical junction and a Chiari malformation, which is similar in both humans and animals. Some brachycephalic toy breed dogs such as Cavalier King Charles Spaniels (CKCS) are particularly predisposed. The exact mechanism of the formation of syringomyelia is undetermined and consequently with the lack of clinical explanation, engineers and mathematicians have resorted to computer models to identify possible physical mechanisms that can lead to syringes. We developed a computer model of the spinal cavity of a CKCS suffering from a large syrinx. The model was excited at the cranial end to simulate the movement of the cerebrospinal fluid (CSF) and the spinal cord due to the shift of blood volume in the cranium related to the cardiac cycle. To simulate the normal condition, the movement was prescribed to the CSF. To simulate the pathological condition, the movement of CSF was blocked

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

What impact do assumptions about missing data have on conclusions? A practical sensitivity analysis for a cancer survival registry

Medical Research Council Clinical Trails Unit at UCL [Studentship to MS; MC EX G0800814 to JRC,TPM]

Common Functional Correlates of Head-Strike Behavior in the Pachycephalosaur Stegoceras validum (Ornithischia, Dinosauria) and Combative Artiodactyls

BACKGROUND: Pachycephalosaurs were bipedal herbivorous dinosaurs with bony domes on their heads, suggestive of head-butting as seen in bighorn sheep and musk oxen. Previous biomechanical studies indicate potential for pachycephalosaur head-butting, but bone histology appears to contradict the behavior in young and old individuals. Comparing pachycephalosaurs with fighting artiodactyls tests for common correlates of head-butting in their cranial structure and mechanics. METHODS/PRINCIPAL FINDINGS: Computed tomographic (CT) scans and physical sectioning revealed internal cranial structure of ten artiodactyls and pachycephalosaurs Stegoceras validum and Prenocephale prenes. Finite element analyses (FEA), incorporating bone and keratin tissue types, determined cranial stress and strain from simulated head impacts. Recursive partition analysis quantified strengths of correlation between functional morphology and actual or hypothesized behavior. Strong head-strike correlates include a dome-like cephalic morphology, neurovascular canals exiting onto the cranium surface, large neck muscle attachments, and dense cortical bone above a sparse cancellous layer in line with the force of impact. The head-butting duiker Cephalophus leucogaster is the closest morphological analog to Stegoceras, with a smaller yet similarly rounded dome. Crania of the duiker, pachycephalosaurs, and bighorn sheep Ovis canadensis share stratification of thick cortical and cancellous layers. Stegoceras, Cephalophus, and musk ox crania experience lower stress and higher safety factors for a given impact force than giraffe, pronghorn, or the non-combative llama. CONCLUSIONS/SIGNIFICANCE: Anatomy, biomechanics, and statistical correlation suggest that some pachycephalosaurs were as competent at head-to-head impacts as extant analogs displaying such combat. Large-scale comparisons and recursive partitioning can greatly refine inference of behavioral capability for fossil animals

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions