Computational inference in systems biology

Parameter inference in mathematical models of biological pathways, expressed as coupled ordinary differential equations (ODEs), is a challenging problem. The computational costs associated with repeatedly solving the ODEs are often high. Aimed at reducing this cost, new concepts using gradient matching have been proposed. This paper combines current adaptive gradient matching approaches, using Gaussian processes, with a parallel tempering scheme, and conducts a comparative evaluation with current methods used for parameter inference in ODEs

Building momentum for business school curriculum change: Measurable lessons from a pilot course in real business experience

Curriculum change requires thoughtful planning and a willingness to experiment with different modes of content delivery. While many business schools are experimenting, few measure student outcomes against the traditional courses they replace. One element of Butler University\u27s College of Business Administration curriculum revision was a pilot course, Real Business Experience , in which students developed a professional business plan, sought and received funding from a professional level funding panel, and ran their businesses. To determine whether the pilot course was successful in reaching its goal of teaching students about the messiness of business and developing more adaptable and confident business leaders assessment instruments were used to identify student development in both the pilot and traditional courses. The analysis presented in this article suggests that the pilot course utilizing the constructivist approach was successful in achieving its goal, but not always in the ways expected

Using diffusion tensor imaging to identify corticospinal tract projection patterns in children with unilateral spastic cerebral palsy.

AIM: To determine whether diffusion tensor imaging (DTI) can be an independent assessment for identifying the corticospinal tract (CST) projecting from the more-affected motor cortex in children with unilateral spastic cerebral palsy (CP). METHOD: Twenty children with unilateral spastic CP participated in this study (16 males, four females; mean age 9y 2mo [standard deviation (SD) 3y 2mo], Manual Ability Classification System [MACS] level I-III). We used DTI tractography to reconstruct the CST projecting from the more-affected motor cortex. We mapped the motor representation of the more-affected hand by stimulating the more- and the less-affected motor cortex measured with single-pulse transcranial magnetic stimulation (TMS). We then verified the presence or absence of the contralateral CST by comparing the TMS map and DTI tractography. Fisher's exact test was used to determine the association between findings of TMS and DTI. RESULTS: DTI tractography successfully identified the CST controlling the more-affected hand (sensitivity=82%, specificity=78%). INTERPRETATION: Contralateral CST projecting from the lesioned motor cortex assessed by DTI is consistent with findings of TMS mapping. Since CST connectivity may be predictive of response to certain upper extremity treatments, DTI-identified CST connectivity may potentially be valuable for determining such connectivity where TMS is unavailable or inadvisable for children with seizures.K08 NS073796 - NINDS NIH HHS; TL1 RR024158 - NCRR NIH HHS; K01 NS062116 - NINDS NIH HHS; UL1 RR024156 - NCRR NIH HHS; KL2 RR024157 - NCRR NIH HHS; R01 HD076436 - NICHD NIH HHSPublished versio

Extended Stromgren Photoelectric Photometry in NGC 752

Photoelectric photometry on the extended Stromgren system (uvbyCa) is presented for 7 giants and 21 main sequence stars in the old open cluster, NGC 752. Analysis of the hk data for the turnoff stars yields a new determination of the cluster mean metallicity. From 10 single-star members, [Fe/H] = -0.06 +/- 0.03, where the error quoted is the standard error of the mean and the Hyades abundance is set at [Fe/H] = +0.12. This result is unchanged if all 20 stars within the limits of the hk metallicity calibration are included. The derived [Fe/H] is in excellent agreement with past estimates using properly-zeroed m1 data, transformed moderate-dispersion spectroscopy, and recent high dispersion spectroscopy.Comment: 14 tex'd pages including 2 tables; 2 separate files with eps figures Accepted for PASP March 200

Stellar Evolution in NGC 6791: Mass Loss on the Red Giant Branch and the Formation of Low Mass White Dwarfs

We present the first detailed study of the properties (temperatures, gravities, and masses) of the NGC 6791 white dwarf population. This unique stellar system is both one of the oldest (8 Gyr) and most metal-rich ([Fe/H] ~ 0.4) open clusters in our Galaxy, and has a color-magnitude diagram (CMD) that exhibits both a red giant clump and a much hotter extreme horizontal branch. Fitting the Balmer lines of the white dwarfs in the cluster, using Keck/LRIS spectra, suggests that most of these stars are undermassive, = 0.43 +/- 0.06 Msun, and therefore could not have formed from canonical stellar evolution involving the helium flash at the tip of the red giant branch. We show that at least 40% of NGC 6791's evolved stars must have lost enough mass on the red giant branch to avoid the flash, and therefore did not convert helium into carbon-oxygen in their core. Such increased mass loss in the evolution of the progenitors of these stars is consistent with the presence of the extreme horizontal branch in the CMD. This unique stellar evolutionary channel also naturally explains the recent finding of a very young age (2.4 Gyr) for NGC 6791 from white dwarf cooling theory; helium core white dwarfs in this cluster will cool ~3 times slower than carbon-oxygen core stars and therefore the corrected white dwarf cooling age is in fact ~7 Gyr, consistent with the well measured main-sequence turnoff age. These results provide direct empirical evidence that mass loss is much more efficient in high metallicity environments and therefore may be critical in interpreting the ultraviolet upturn in elliptical galaxies.Comment: 15 pages, 9 figures, 2 tables. Accepted for publication in Astrophys. J. Very minor changes from first versio

The cessation in pregnancy incentives trial (CPIT): study protocol for a randomized controlled trial

Background: Seventy percent of women in Scotland have at least one baby, making pregnancy an opportunity to help most young women quit smoking before their own health is irreparably compromised. By quitting during pregnancy their infants will be protected from miscarriage and still birth as well as low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. In the UK, the NICE guidelines: 'How to stop smoking in pregnancy and following childbirth' (June 2010) highlighted that little evidence exists in the literature to confirm the efficacy of financial incentives to help pregnant smokers to quit. Its first research recommendation was to determine: Within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? <p/>Design and Methods: This study is a phase II exploratory individually randomised controlled trial comparing standard care for pregnant smokers with standard care plus the additional offer of financial voucher incentives to engage with specialist cessation services and/or to quit smoking during pregnancy. Participants (n=600) will be pregnant smokers identified at maternity booking who when contacted by specialist cessation services agree to having their details passed to the NHS Smokefree Pregnancy Study Helpline to discuss the trial. The NHS Smokefree Pregnancy Study Helpline will be responsible for telephone consent and follow-up in late pregnancy. The primary outcome will be self reported smoking in late pregnancy verified by cotinine measurement. An economic evaluation will refine cost data collection and assess potential cost-effectiveness while qualitative research interviews with clients and health professionals will assess the level of acceptance of this form of incentive payment. Research questions What is the likely therapeutic efficacy? Are incentives potentially cost-effective? Is individual randomisation an efficient trial design without introducing outcome bias? Can incentives be introduced in a way that is feasible and acceptable? <p/>Discussion: This phase II trial will establish a workable design to reduce the risks associated with a future definitive phase III multicentre randomised controlled trial and establish a framework to assess the costs and benefits of financial incentives to help pregnant smokers to quit

A proposed approach to monitor private-sector policies and practices related to food environments, obesity and non-communicable disease prevention

Private-sector organizations play a critical role in shaping the food environments of individuals and populations. However, there is currently very limited independent monitoring of private-sector actions related to food environments. This paper reviews previous efforts to monitor the private sector in this area, and outlines a proposed approach to monitor private-sector policies and practices related to food environments, and their influence on obesity and non-communicable disease (NCD) prevention. A step-wise approach to data collection is recommended, in which the first (‘minimal’) step is the collation of publicly available food and nutrition-related policies of selected private-sector organizations. The second (‘expanded’) step assesses the nutritional composition of each organization’s products, their promotions to children, their labelling practices, and the accessibility, availability and affordability of their products. The third (‘optimal’) step includes data on other commercial activities that may influence food environments, such as political lobbying and corporate philanthropy. The proposed approach will be further developed and piloted in countries of varying size and income levels. There is potential for this approach to enable national and international benchmarking of private-sector policies and practices, and to inform efforts to hold the private sector to account for their role in obesity and NCD prevention

Monitoring the impacts of trade agreements on food environments

The liberalization of international trade and foreign direct investment through multilateral, regional and bilateral agreements has had profound implications for the structure and nature of food systems, and therefore, for the availability, nutritional quality, accessibility, price and promotion of foods in different locations. Public health attention has only relatively recently turned to the links between trade and investment agreements, diets and health, and there is currently no systematic monitoring of this area. This paper reviews the available evidence on the links between trade agreements, food environments and diets from an obesity and non-communicable disease (NCD) perspective. Based on the key issues identified through the review, the paper outlines an approach for monitoring the potential impact of trade agreements on food environments and obesity/NCD risks. The proposed monitoring approach encompasses a set of guiding principles, recommended procedures for data collection and analysis, and quantifiable ‘minimal’, ‘expanded’ and ‘optimal’ measurement indicators to be tailored to national priorities, capacity and resources. Formal risk assessment processes of existing and evolving trade and investment agreements, which focus on their impacts on food environments will help inform the development of healthy trade policy, strengthen domestic nutrition and health policy space and ultimately protect population nutrition.The following organizations provided funding support for the travel of participants to Italy for this meeting and the preparation of background research papers: The Rockefeller Foundation, International Obesity Taskforce (IOTF), University of Auckland, Deakin University, The George Institute, University of Sydney, Queensland University of Technology, University of Oxford, University of Pennsylvania Perelman School of Medicine, World Cancer Research Fund International, University of Toronto, and The Australian National University. The Faculty of Health at Deakin University kindly supported the costs for open access availability of this paper, and the Australian National Health and Medical Research Council Centre for Research Excellence in Obesity Policy and Food Systems (APP1041020) supported the coordination and finalizing of INFORMAS manuscripts