Cleft palate, Retrognathia and Congenital Heart Disease in Velo-Cardio-Facial Syndrome: A Phenotype Correlation Study

Objective: Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion of approximately 40 genes from one copy of chromosome 22. Expression of the syndrome is a variable combination of over 190 phenotypic characteristics. As of yet, little is known about how these phenotypes correlate with one another or whether there are predictable patterns of expression. Two of the most common phenotypic categories, congenital heart disease and cleft palate, have been proposed to have a common genetic relationship to the deleted T-box 1 gene (TBX1). The purpose of this study is to determine if congenital heart disease and cleft palate are correlated in a large cohort of human subjects with VCFS. Methods: This study is a retrospective chart review including 316 Caucasian non-Hispanic subjects with FISH or CGH microarray confirmed chromosome 22q11.2 deletions. All subjects were evaluated by the interdisciplinary team at the Velo-Cardio-Facial Syndrome International Center at Upstate Medical University, Syracuse, NY. Each combination of congenital heart disease, cleft palates, and retrognathia was analyzed by Chi square or Fisher exact test. Results: For all categories of congenital heart disease and cleft palate or retrognathia no significant associations were found, with the exception of submucous cleft palate and retrognathia (nominal p = 0.0325) and occult submucous cleft palate and retrognathia (nominal p = 0.000013). Conclusions: Congenital heart disease and cleft palate do not appear to be correlated in human subjects with VCFS despite earlier suggestions from animal models. Possible explanations include modification of the effect of TBX1 by genes outside of the 22q11.2 region that may further influence the formation of the palate or heart, or the presence of epigenetic factors that may effect genes within the deleted region, modifying genes elsewhere, or polymorphisms on the normal copy of chromosome 22. Lastly, it is possible that TBX1 plays a role in palate formation in some species, but not in humans. In VCFS, retrognathia is caused by an obtuse angulation of the skull base. It is unknown if the correlation between retrognathia and cleft palate in VCFS indicates a developmental sequence related to skull morphology, or direct gene effects of both anomalies. Much work remains to be done to fully understand the complex relationships between phenotypic characteristics in VCFS

Planning for Sustainability in Small Municipalities: The Influence of Interest Groups, Growth Patterns, and Institutional Characteristics

How and why small municipalities promote sustainability through planning efforts is poorly understood. We analyzed ordinances in 451 Maine municipalities and tested theories of policy adoption using regression analysis.We found that smaller communities do adopt programs that contribute to sustainability relevant to their scale and context. In line with the political market theory, we found that municipalities with strong environmental interests, higher growth, and more formal governments were more likely to adopt these policies. Consideration of context and capacity in planning for sustainability will help planners better identify and benefit from collaboration, training, and outreach opportunities

Post-Newtonian Gravitational Radiation

1 Introduction 2 Multipole Decomposition 3 Source Multipole Moments 4 Post-Minkowskian Approximation 5 Radiative Multipole Moments 6 Post-Newtonian Approximation 7 Point-Particles 8 ConclusionComment: 46 pages, in Einstein's Field Equations and Their Physical Implications, B. Schmidt (Ed.), Lecture Notes in Physics, Springe

National Institutes of Health Career Development Awards for Cardiovascular Physician-Scientists: Recent Trends and Strategies for Success

Nurturing the development of cardiovascular physician-scientist investigators is critical for sustained progress in cardiovascular science and improving human health. The transition from an inexperienced trainee to an independent physician-scientist is a multifaceted process requiring a sustained commitment from the trainee, mentors, and institution. A cornerstone of this training process is a career development (K) award from the National Institutes of Health (NIH). These awards generally require 75% of the awardee's professional effort devoted to research aims and diverse career development activities carried out in a mentored environment over a 5-year period. We report on recent success rates for obtaining NIH K awards, provide strategies for preparing a successful application and navigating the early career period for aspiring cardiovascular investigators, and offer cardiovascular division leadership perspectives regarding K awards in the current era. Our objective is to offer practical advice that will equip trainees considering an investigator path for success

Modelling and simulating change in reforesting mountain landscapes using a social-ecological framework

Natural reforestation of European mountain landscapes raises major environmental and societal issues. With local stakeholders in the Pyrenees National Park area (France), we studied agricultural landscape colonisation by ash (Fraxinus excelsior) to enlighten its impacts on biodiversity and other landscape functions of importance for the valley socio-economics. The study comprised an integrated assessment of land-use and land-cover change (LUCC) since the 1950s, and a scenario analysis of alternative future policy. We combined knowledge and methods from landscape ecology, land change and agricultural sciences, and a set of coordinated field studies to capture interactions and feedback in the local landscape/land-use system. Our results elicited the hierarchically-nested relationships between social and ecological processes. Agricultural change played a preeminent role in the spatial and temporal patterns of LUCC. Landscape colonisation by ash at the parcel level of organisation was merely controlled by grassland management, and in fact depended on the farmer's land management at the whole-farm level. LUCC patterns at the landscape level depended to a great extent on interactions between farm household behaviours and the spatial arrangement of landholdings within the landscape mosaic. Our results stressed the need to represent the local SES function at a fine scale to adequately capture scenarios of change in landscape functions. These findings orientated our modelling choices in the building an agent-based model for LUCC simulation (SMASH - Spatialized Multi-Agent System of landscape colonization by ASH). We discuss our method and results with reference to topical issues in interdisciplinary research into the sustainability of multifunctional landscapes

Natural Double Inflation in Supergravity

We propose a natural double inflation model in supergravity. In this model, chaotic inflation first takes place by virtue of the Nambu-Goldstone-like shift symmetry, which guarantees the absence of the exponential factor in the potential for the inflaton field. During chaotic inflation, an initial value of the second inflation (new inflation) is set. In this model, the initial value of new inflation can be adequately far from the local maximum of the potential for new inflation due to the small linear term of the inflaton in the K\"ahler potential. Therefore, the primordial fluctuations within the present horizon scale may be attributed to both inflations; that is, the first chaotic inflation produces the primordial fluctuations on the large cosmological scales while the second new inflation on the smaller scales. The successive decay of the inflaton for new inflation leads to a reheating temperature low enough to avoid the overproduction of gravitinos in a wide range of the gravitino mass.Comment: 13 pages, to appear in Phys. Rev.

Double Inflation in Supergravity and the Large Scale Structure

The cosmological implication of a double inflation model with hybrid + new inflations in supergravity is studied. The hybrid inflation drives an inflaton for new inflation close to the origin through supergravity effects and new inflation naturally occurs. If the total e-fold number of new inflation is smaller than $\sim 60$, both inflations produce cosmologically relevant density fluctuations. Both cluster abundances and galaxy distributions provide strong constraints on the parameters in the double inflation model assuming $\Omega_0=1$ standard cold dark matter scenario. The future satellite experiments to measure the angular power spectrum of the cosmic microwave background will make a precise determination of the model parameters possible.Comment: 19 pages (RevTeX file

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809