Subject-specific, multiscale simulation of electrophysiology: a software pipeline for image-based models and application examples

Many simulation studies in biomedicine are based on a similar sequence of processing steps, starting from images and running through geometric model generation, assignment of tissue properties, numerical simulation and visualization of the results—a process known as image-based geometric modelling and simulation. We present an overview of software systems for implementing such a sequence both within highly integrated problem-solving environments and in the form of loosely integrated pipelines. Loose integration in this case indicates that individual programs function largely independently but communicate through files of a common format and support simple scripting, so as to automate multiple executions wherever possible. We then describe three specific applications of such pipelines to translational biomedical research in electrophysiology

The clinical profile of moderate amblyopia in children younger than 7 years

Objective To describe the demographic and clinical characteristics of a cohort of children with moderate amblyopia participating in the Amblyopia Treatment Study 1, a randomized trial comparing atropine and patching. Methods The children enrolled were younger than 7 years and had strabismic, anisometropic, or combined strabismic and anisometropic amblyopia. Visual acuity, measured with a standardized testing protocol using single-surround HOTV optotypes, was 20/40 to 20/100 in the amblyopic eye, with an intereye acuity difference of 3 or more logMAR lines. There were 419 children enrolled, 409 of whom met these criteria and were included in the analyses. Results The mean age of the 409 children was 5.3 years. The cause of the amblyopia was strabismus in 38%, anisometropia in 37%, and both strabismus and anisometropia in 24%. The mean visual acuity of the amblyopic eyes (approximately 20/60) was similar among the strabismic, anisometropic, and combined groups (P = .24), but visual acuity of the sound eyes was worse in the strabismic group compared with the anisometropic group (P<.001). For the patients randomized into the patching group, 43% were initially treated for 6 hours per day, whereas 17% underwent full-time patching. Patients with poorer visual acuity in the amblyopic eye were prescribed more hours of patching than patients with better acuity (P = .003). Conclusions In the Amblyopia Treatment Study 1, there were nearly equal proportions of patients with strabismic and anisometropic amblyopia. A similar level of visual impairment was found irrespective of the cause of amblyopia. There was considerable variation in treatment practices with regard to the number of hours of initial patching prescribed

Impact of Patching and Atropine Treatment on the Child and Family in the Amblyopia Treatment Study

Objective To assess the psychosocial impact on the child and family of patching and atropine as treatments for moderate amblyopia in children younger than 7 years. Methods In a randomized, controlled clinical trial, 419 children younger than 7 years with amblyopic eye visual acuity in the range of 20/40 to 20/100 were assigned to receive treatment with either patching or atropine at 47 clinical sites. After 5 weeks of treatment, a parental quality-of-life questionnaire was completed for 364 (87%) of the 419 patients. Main Outcome Measure Overall and subscale scores on the Amblyopia Treatment Index. Results High internal validity and reliability were demonstrated for the Amblyopia Treatment Index questionnaire. The overall Amblyopia Treatment Index scores and the 3 subscale scores were consistently higher (worse) in the patching group compared with the atropine-treated group (overall mean, 2.52 vs 2.02, P<.001; adverse effects of treatment: mean, 2.35 vs 2.11, P = .002; difficulty with compliance: mean, 2.46 vs 1.99, P<.001; and social stigma: mean, 3.09 vs 1.84, P<.001, respectively). Conclusion Although the Amblyopia Treatment Index questionnaire results indicated that both atropine and patching treatments were well tolerated by the child and family, atropine received more favorable scores overall and on all 3 questionnaire subscales

Walking, Gross Motor Development, and Brain Functional Connectivity in Infants and Toddlers

Infant gross motor development is vital to adaptive function and predictive of both cognitive outcomes and neurodevelopmental disorders. However, little is known about neural systems underlying the emergence of walking and general gross motor abilities. Using resting state fcMRI, we identified functional brain networks associated with walking and gross motor scores in a mixed cross-sectional and longitudinal cohort of infants at high and low risk for autism spectrum disorder, who represent a dimensionally distributed range of motor function. At age 12 months, functional connectivity of motor and default mode networks was correlated with walking, whereas dorsal attention and posterior cingulo-opercular networks were implicated at age 24 months. Analyses of general gross motor function also revealed involvement of motor and default mode networks at 12 and 24 months, with dorsal attention, cingulo-opercular, frontoparietal, and subcortical networks additionally implicated at 24 months. These findings suggest that changes in network-level brain-behavior relationships underlie the emergence and consolidation of walking and gross motor abilities in the toddler period. This initial description of network substrates of early gross motor development may inform hypotheses regarding neural systems contributing to typical and atypical motor outcomes, as well as neurodevelopmental disorders associated with motor dysfunction

Professionalism, Golf Coaching and a Master of Science Degree: A commentary

As a point of reference I congratulate Simon Jenkins on tackling the issue of professionalism in coaching. As he points out coaching is not a profession, but this does not mean that coaching would not benefit from going through a professionalization process. As things stand I find that the stimulus article unpacks some critically important issues of professionalism, broadly within the context of golf coaching. However, I am not sure enough is made of understanding what professional (golf) coaching actually is nor how the development of a professional golf coach can be facilitated by a Master of Science Degree (M.Sc.). I will focus my commentary on these two issues

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Mammographic Density Change With Estrogen and Progestin Therapy and Breast Cancer Risk

Background: Estrogen plus progestin therapy increases both mammographic density and breast cancer incidence. Whether mammographic density change associated with estrogen plus progestin initiation predicts breast cancer risk is unknown. Methods: We conducted an ancillary nested case-control study within the Women's Health Initiative trial that randomly assigned postmenopausal women to daily conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg or placebo. Mammographic density was assessed from mammograms taken prior to and one year after random assignment for 174 women who later developed breast cancer (cases) and 733 healthy women (controls). Logistic regression analyses included adjustment for confounders and baseline mammographic density when appropriate. Results: Among women in the estrogen plus progestin arm (97 cases/378 controls), each 1% positive change in percent mammographic density increased breast cancer risk 3% (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01 to 1.06). For women in the highest quintile of mammographic density change (>19.3% increase), breast cancer risk increased 3.6-fold (95% CI = 1.52 to 8.56). The effect of estrogen plus progestin use on breast cancer risk (OR = 1.28, 95% CI = 0.90 to 1.82) was eliminated in this study, after adjusting for change in mammographic density (OR = 1.00, 95% CI = 0.66 to 1.51). Conclusions: We found the one-year change in mammographic density after estrogen plus progestin initiation predicted subsequent increase in breast cancer risk. All of the increased risk from estrogen plus progestin use was mediated through mammographic density change. Doctors should evaluate changes in mammographic density with women who initiate estrogen plus progestin therapy and discuss the breast cancer risk implications

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results