Making and shaping endochondral and intramembranous bones

Skeletal elements have a diverse range of shapes and sizes specialized to their various roles including protecting internal organs, locomotion, feeding, hearing, and vocalization. The precise positioning, size, and shape of skeletal elements is therefore critical for their function. During embryonic development, bone forms by endochondral or intramembranous ossification and can arise from the paraxial and lateral plate mesoderm or neural crest. This review describes inductive mechanisms to position and pattern bones within the developing embryo, compares and contrasts the intrinsic vs extrinsic mechanisms of endochondral and intramembranous skeletal development, and details known cellular processes that precisely determine skeletal shape and size. Key cellular mechanisms are employed at distinct stages of ossification, many of which occur in response to mechanical cues (eg, joint formation) or preempting future load‐bearing requirements. Rapid shape changes occur during cellular condensation and template establishment. Specialized cellular behaviors, such as chondrocyte hypertrophy in endochondral bone and secondary cartilage on intramembranous bones, also dramatically change template shape. Once ossification is complete, bone shape undergoes functional adaptation through (re)modeling. We also highlight how alterations in these cellular processes contribute to evolutionary change and how differences in the embryonic origin of bones can influence postnatal bone repair

Parameterized lower bound and NP-completeness of some HH-free Edge Deletion problems

For a graph $H$, the $H$-free Edge Deletion problem asks whether there exist at most $k$ edges whose deletion from the input graph $G$ results in a graph without any induced copy of $H$. We prove that $H$-free Edge Deletion is NP-complete if $H$ is a graph with at least two edges and $H$ has a component with maximum number of vertices which is a tree or a regular graph. Furthermore, we obtain that these NP-complete problems cannot be solved in parameterized subexponential time, i.e., in time $2^{o(k)}\cdot |G|^{O(1)}$, unless Exponential Time Hypothesis fails.Comment: 15 pages, COCOA 15 accepted pape

Higher derivative type II string effective actions, automorphic forms and E11

By dimensionally reducing the ten-dimensional higher derivative type IIA string theory effective action we place constraints on the automorphic forms that appear in the effective action in lower dimensions. We propose a number of properties of such automorphic forms and consider the prospects that E11 can play a role in the formulation of the higher derivative string theory effective action.Comment: 34 page

Coronary CT angiography features of ruptured and high-risk atherosclerotic plaques: Correlation with intra-vascular ultrasound

BACKGROUND: Features of ruptured and high-risk plaque have been described on coronary computed tomography angiography (coronary CTA), but not systematically assessed against intravascular ultrasound (IVUS). We examined the ability of coronary CTA to identify IVUS defined ruptured plaque and Virtual Histology Intravascular Ultrasound (VH-IVUS) defined thin-cap fibroatheroma (TCFA). METHODS: Sixty-three patients (32 with acute coronary syndrome and 31 with stable angina) underwent coronary CTA, IVUS and VH-IVUS. Plaque rupture on CTA was defined as intra-plaque contrast and its frequency compared with IVUS-defined plaque rupture. We then examined the relationship of conventional coronary CTA high-risk features (low attenuation plaque, positive remodeling, spotty calcification and the Napkin-Ring sign) in VH-IVUS-defined TCFA. We compared these with a novel index based on quantifying the ratio of necrotic core to fibrous plaque using x-ray attenuation cut-offs derived from the relationship of plaque to luminal contrast attenuation. RESULTS: Of the 71 plaques interrogated with IVUS, 39 were ruptured. Coronary CTA correctly detected 13-ruptured plaques with 3 false positives giving high specificity (91%) but low sensitivity (33%). None of the conventional coronary CTA high-risk features were significantly more frequent in the higher-risk (VH-IVUS defined thin-cap) compared with thick-cap fibroatheroma. However, the new index (necrotic core/fibrous plaque ratio) was higher in thin-cap (mean 0.90) vs. thick-cap fibroatheroma (mean 0.59), p < 0.05. CONCLUSIONS: Compared with intravascular ultrasound, coronary CTA identifies ruptured plaque with good specificity but poor sensitivity. We have identified a novel high-risk feature on coronary CTA (necrotic core/fibrous plaque ratio that is associated with VH-IVUS defined-TCFA.Supported by a British Heart Foundation grant FS/10/025/2819

Duality Invariant Actions and Generalised Geometry

We construct the non-linear realisation of the semi-direct product of E(11) and its first fundamental representation at lowest order and appropriate to spacetime dimensions four to seven. This leads to a non-linear realisation of the duality groups and introduces fields that depend on a generalised space which possess a generalised vielbein. We focus on the part of the generalised space on which the duality groups alone act and construct an invariant action.Comment: 59 pages (typos fixed and added comments

Self-Organization, Layered Structure, and Aggregation Enhance Persistence of a Synthetic Biofilm Consortium

Microbial consortia constitute a majority of the earth’s biomass, but little is known about how these cooperating communities persist despite competition among community members. Theory suggests that non-random spatial structures contribute to the persistence of mixed communities; when particular structures form, they may provide associated community members with a growth advantage over unassociated members. If true, this has implications for the rise and persistence of multi-cellular organisms. However, this theory is difficult to study because we rarely observe initial instances of non-random physical structure in natural populations. Using two engineered strains of Escherichia coli that constitute a synthetic symbiotic microbial consortium, we fortuitously observed such spatial self-organization. This consortium forms a biofilm and, after several days, adopts a defined layered structure that is associated with two unexpected, measurable growth advantages. First, the consortium cannot successfully colonize a new, downstream environment until it selforganizes in the initial environment; in other words, the structure enhances the ability of the consortium to survive environmental disruptions. Second, when the layered structure forms in downstream environments the consortium accumulates significantly more biomass than it did in the initial environment; in other words, the structure enhances the global productivity of the consortium. We also observed that the layered structure only assembles in downstream environments that are colonized by aggregates from a previous, structured community. These results demonstrate roles for self-organization and aggregation in persistence of multi-cellular communities, and also illustrate a role for the techniques of synthetic biology in elucidating fundamental biological principles

Constraints on Automorphic Forms of Higher Derivative Terms from Compactification

By dimensionally reducing the higher derivative corrections of ten-dimensional IIB theory on a torus we deduce constraints on the E_{n+1} automorphic forms that occur in d=10-n dimensions. In particular we argue that these automorphic forms involve the representation of E_{n+1} with fundamental weight \lambda^{n+1}, which is also the representation to which the string charges in d dimensions belong. We also consider a similar calculation for the reduction of higher derivative terms in eleven-dimensional M-theory.Comment: Minor corrections, to appear in JHE

Trial Protocol: Randomised controlled trial of the effects of very low calorie diet, modest dietary restriction, and sequential behavioural programme on hunger, urges to smoke, abstinence and weight gain in overweight smokers stopping smoking

Background\ud Weight gain accompanies smoking cessation, but dieting during quitting is controversial as hunger may increase urges to smoke. This is a feasibility trial for the investigation of a very low calorie diet (VLCD), individual modest energy restriction, and usual advice on hunger, ketosis, urges to smoke, abstinence and weight gain in overweight smokers trying to quit. \ud \ud Methods\ud This is a 3 armed, unblinded, randomized controlled trial in overweight (BMI > 25 kg/$m^2$), daily smokers (CO > 10 ppm); with at least 30 participants in each group. Each group receives identical behavioural support and NRT patches (25 mg(8 weeks),15 mg(2 weeks),10 mg(2 weeks)). The VLCD group receive a 429-559 kcal/day liquid formula beginning 1 week before quitting and continuing for 4 weeks afterwards. The modest energy restricted group (termed individual dietary and activity planning(IDAP)) engage in goal-setting and receive an energy prescription based on individual basal metabolic rate(BMR) aiming for daily reduction of 600 kcal. The control group receive usual dietary advice that accompanies smoking cessation i.e. avoiding feeling hungry but eating healthy snacks. After this, the VLCD participants receive IDAP to provide support for changing eating habits in the longer term; the IDAP group continues receiving this support. The control group receive IDAP 8 weeks after quitting. This allows us to compare IDAP following a successful quit attempt with dieting concurrently during quitting. It also aims to prevent attrition in the unblinded, control group by meeting their need for weight management. Follow-up occurs at 6 and 12 months. \ud \ud Outcome measures include participant acceptability, measured qualitatively by semi-structured interviewing and quantitatively by recruitment and attrition rates. Feasibility of running the trial within primary care is measured by interview and questionnaire of the treatment providers. Adherence to the VLCD is verified by the presence of urinary ketones measured weekly. Daily urges to smoke, hunger and withdrawal are measured using the Mood and Physical Symptoms Scale-Combined (MPSS-C) and a Hunger Craving Score (HCS). 24 hour, 7 day point prevalence and 4-week prolonged abstinence (Russell Standard) is confirmed by CO < 10 ppm. Weight, waist and hip circumference and percentage body fat are measured at each visit. \ud \ud Trial Registration\ud Current controlled trials ISRCTN83865809\ud \u

Refining the content and design of an alcohol reduction app, Drink Less, to improve its usability and effectiveness: a mixed methods approach

Background: Digital interventions have the potential to reduce alcohol consumption, although evidence on the effectiveness of apps is lacking. Drink Less is a popular, evidence-informed app with good usability, putting it in a strong position to be improved upon prior to conducting a confirmatory evaluation. This paper describes the process of refining Drink Less to improve its usability and likely effectiveness. // Methods: The refinement consisted of three phases and involved qualitative and quantitative (mixed) methods: i) identifying changes to app content, based on findings from an initial evaluation of Drink Less, an updated review of digital alcohol interventions and a content analysis of user feedback; ii) designing new app modules with public input and a consultation with app developers and researchers; and iii) improving the app’s usability through user testing. Results: As a result of the updated review of digital alcohol interventions and user feedback analysis in Phase 1, three new modules: ‘Behaviour Substitution’, ‘Information about Antecedents’ and ‘Insights’, were added to the app. One existing module – ‘Identity Change’ – was removed based on the initial evaluation of Drink Less. Phases 2 and 3 resulted in changes to existing features, such as improving the navigational structure and onboarding process, and clarifying how to edit drinks and goals. // Conclusions: A mixed methods approach was used to refine the content and design of Drink Less, providing insights into how to improve its usability and likely effectiveness. Drink Less is now ready for a confirmatory evaluation

Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

"© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)