An adaptive prefix-assignment technique for symmetry reduction

This paper presents a technique for symmetry reduction that adaptively assigns a prefix of variables in a system of constraints so that the generated prefix-assignments are pairwise nonisomorphic under the action of the symmetry group of the system. The technique is based on McKay's canonical extension framework [J.~Algorithms 26 (1998), no.~2, 306--324]. Among key features of the technique are (i) adaptability---the prefix sequence can be user-prescribed and truncated for compatibility with the group of symmetries; (ii) parallelizability---prefix-assignments can be processed in parallel independently of each other; (iii) versatility---the method is applicable whenever the group of symmetries can be concisely represented as the automorphism group of a vertex-colored graph; and (iv) implementability---the method can be implemented relying on a canonical labeling map for vertex-colored graphs as the only nontrivial subroutine. To demonstrate the practical applicability of our technique, we have prepared an experimental open-source implementation of the technique and carry out a set of experiments that demonstrate ability to reduce symmetry on hard instances. Furthermore, we demonstrate that the implementation effectively parallelizes to compute clusters with multiple nodes via a message-passing interface.Comment: Updated manuscript submitted for revie

Regular Incidence Complexes, Polytopes, and C-Groups

Regular incidence complexes are combinatorial incidence structures generalizing regular convex polytopes, regular complex polytopes, various types of incidence geometries, and many other highly symmetric objects. The special case of abstract regular polytopes has been well-studied. The paper describes the combinatorial structure of a regular incidence complex in terms of a system of distinguished generating subgroups of its automorphism group or a flag-transitive subgroup. Then the groups admitting a flag-transitive action on an incidence complex are characterized as generalized string C-groups. Further, extensions of regular incidence complexes are studied, and certain incidence complexes particularly close to abstract polytopes, called abstract polytope complexes, are investigated.Comment: 24 pages; to appear in "Discrete Geometry and Symmetry", M. Conder, A. Deza, and A. Ivic Weiss (eds), Springe

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen

The Hubble Constant

I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. There are two broad categories of measurements. The first uses individual astrophysical objects which have some property that allows their intrinsic luminosity or size to be determined, or allows the determination of their distance by geometric means. The second category comprises the use of all-sky cosmic microwave background, or correlations between large samples of galaxies, to determine information about the geometry of the Universe and hence the Hubble constant, typically in a combination with other cosmological parameters. Many, but not all, object-based measurements give $H_0$ values of around 72-74km/s/Mpc , with typical errors of 2-3km/s/Mpc. This is in mild discrepancy with CMB-based measurements, in particular those from the Planck satellite, which give values of 67-68km/s/Mpc and typical errors of 1-2km/s/Mpc. The size of the remaining systematics indicate that accuracy rather than precision is the remaining problem in a good determination of the Hubble constant. Whether a discrepancy exists, and whether new physics is needed to resolve it, depends on details of the systematics of the object-based methods, and also on the assumptions about other cosmological parameters and which datasets are combined in the case of the all-sky methods.Comment: Extensively revised and updated since the 2007 version: accepted by Living Reviews in Relativity as a major (2014) update of LRR 10, 4, 200

An objective spinal motion imaging assessment (OSMIA): reliability, accuracy and exposure data.

BACKGROUND: Minimally-invasive measurement of continuous inter-vertebral motion in clinical settings is difficult to achieve. This paper describes the reliability, validity and radiation exposure levels in a new Objective Spinal Motion Imaging Assessment system (OSMIA) based on low-dose fluoroscopy and image processing. METHODS: Fluoroscopic sequences in coronal and sagittal planes were obtained from 2 calibration models using dry lumbar vertebrae, plus the lumbar spines of 30 asymptomatic volunteers. Calibration model 1 (mobile) was screened upright, in 7 inter-vertebral positions. The volunteers and calibration model 2 (fixed) were screened on a motorized table comprising 2 horizontal sections, one of which moved through 80 degrees. Model 2 was screened during motion 5 times and the L2-S1 levels of the volunteers twice. Images were digitised at 5fps. Inter-vertebral motion from model 1 was compared to its pre-settings to investigate accuracy. For volunteers and model 2, the first digitised image in each sequence was marked with templates. Vertebrae were tracked throughout the motion using automated frame-to-frame registration. For each frame, vertebral angles were subtracted giving inter-vertebral motion graphs. Volunteer data were acquired twice on the same day and analysed by two blinded observers. The root-mean-square (RMS) differences between paired data were used as the measure of reliability. RESULTS: RMS difference between reference and computed inter-vertebral angles in model 1 was 0.32 degrees for side-bending and 0.52 degrees for flexion-extension. For model 2, X-ray positioning contributed more to the variance of range measurement than did automated registration. For volunteer image sequences, RMS inter-observer variation in intervertebral motion range in the coronal plane was 1.86 degrees and intra-subject biological variation was between 2.75 degrees and 2.91 degrees. RMS inter-observer variation in the sagittal plane was 1.94 degrees. Radiation dosages in each view were below the levels recommended for a plain film. CONCLUSION: OSMIA can measure inter-vertebral angular motion patterns in routine clinical settings if modern image intensifier systems are used. It requires skillful radiography to achieve optimal positioning and dose limitation. Reliability in individual subjects can be judged from the variance of their averaged inter-vertebral angles and by observing automated image registration

Mammalian microRNAs predominantly act to decrease target mRNA levels

MicroRNAs (miRNAs) are endogenous ~22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.National Institutes of Health (U.S.

Effect of Information and Telephone-Guided Access to Community Support for People with Chronic Kidney Disease: Randomised Controlled Trial

Background: Implementation of self-management support in traditional primary care settings has proved difficult, encouraging the development of alternative models which actively link to community resources. Chronic kidney disease (CKD) is a common condition usually diagnosed in the presence of other co-morbidities. This trial aimed to determine the effectiveness of an intervention to provide information and telephone-guided access to community support versus usual care for patients with stage 3 CKD. Methods and Findings: In a pragmatic, two-arm, patient level randomised controlled trial 436 patients with a diagnosis of stage 3 CKD were recruited from 24 general practices in Greater Manchester. Patients were randomised to intervention (215) or usual care (221). Primary outcome measures were health related quality of life (EQ-5D health questionnaire), blood pressure control, and positive and active engagement in life (heiQ) at 6 months. At 6 months, mean health related quality of life was significantly higher for the intervention group (adjusted mean difference = 0.05; 95% CI = 0.01, 0.08) and blood pressure was controlled for a significantly greater proportion of patients in the intervention group (adjusted odds ratio = 1.85; 95% CI = 1.25, 2.72). Patients did not differ significantly in positive and active engagement in life. The intervention group reported a reduction in costs compared with control. Conclusions: An intervention to provide tailored information and telephone-guided access to community resources was associated with modest but significant improvements in health related quality of life and better maintenance of blood pressure control for patients with stage 3 CKD compared with usual care. However, further research is required to identify the mechanisms of action of the intervention

Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization.

We have previously demonstrated that Stat3 regulates lysosomal-mediated programmed cell death (LM-PCD) during mouse mammary gland involution in vivo. However, the mechanism that controls the release of lysosomal cathepsins to initiate cell death in this context has not been elucidated. We show here that Stat3 regulates the formation of large lysosomal vacuoles that contain triglyceride. Furthermore, we demonstrate that milk fat globules (MFGs) are toxic to epithelial cells and that, when applied to purified lysosomes, the MFG hydrolysate oleic acid potently induces lysosomal leakiness. Additionally, uptake of secreted MFGs coated in butyrophilin 1A1 is diminished in Stat3-ablated mammary glands and loss of the phagocytosis bridging molecule MFG-E8 results in reduced leakage of cathepsins in vivo. We propose that Stat3 regulates LM-PCD in mouse mammary gland by switching cellular function from secretion to uptake of MFGs. Thereafter, perturbation of lysosomal vesicle membranes by high levels of free fatty acids results in controlled leakage of cathepsins culminating in cell death.This work was supported by a grant from the Medical Research Council programme grant no. MR/J001023/1 (T.J.S. and B. L-L.) and a Cancer Research UK Cambridge Cancer Centre PhD studentship (H.K.R.).This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3043.html

Risky business: factor analysis of survey data – assessing the probability of incorrect dimensionalisation

This paper undertakes a systematic assessment of the extent to which factor analysis the correct number of latent dimensions (factors) when applied to ordered categorical survey items (so-called Likert items). We simulate 2400 data sets of uni-dimensional Likert items that vary systematically over a range of conditions such as the underlying population distribution, the number of items, the level of random error, and characteristics of items and item-sets. Each of these datasets is factor analysed in a variety of ways that are frequently used in the extant literature, or that are recommended in current methodological texts. These include exploratory factor retention heuristics such as Kaiser’s criterion, Parallel Analysis and a non-graphical scree test, and (for exploratory and confirmatory analyses) evaluations of model fit. These analyses are conducted on the basis of Pearson and polychoric correlations.We find that, irrespective of the particular mode of analysis, factor analysis applied to ordered-categorical survey data very often leads to over-dimensionalisation. The magnitude of this risk depends on the specific way in which factor analysis is conducted, the number of items, the properties of the set of items, and the underlying population distribution. The paper concludes with a discussion of the consequences of overdimensionalisation, and a brief mention of alternative modes of analysis that are much less prone to such problems

Exploring the quiet eye in archery using field- and laboratory-based tasks.

The 'quiet eye' (QE)-a period of extended gaze fixation on a target-has been reported in many tasks that require accurate aiming. Longer quiet eye durations (QEDs) are reported in experts compared to non-experts and on successful versus less successful trials. The QE has been extensively studied in the field; however, the cognitive mechanisms underlying the QE are not yet fully understood. We investigated the QEDs of ten expert and ten novice archers in the field and in the laboratory using a computer-based archery task. The computer task consisted of shooting archery targets using a joystick. Random 'noise' (visual motion perturbation) was introduced at high and low levels to allow for the controlled examination of the effects of task complexity and processing demands. In this computer task, we also tested an additional group of ten non-archers as controls. In both field and computer tasks, eye movements were measured using electro-oculography. The expert archers exhibited longer QED compared to the novice archers in the field task. In the computer task, the archers again exhibited longer QEDs and were more accurate compared to non-archers. Furthermore, expert archers showed earlier QE onsets and longer QEDs during high noise conditions compared to the novices and non-archers. Our findings show skill-based effects on QED in field conditions and in a novel computer-based archery task, in which online (visual) perturbations modulated experts' QEDs. These longer QEDs in experts may be used for more efficient programming in which accurate predictions are facilitated by attention control