Unmasking of Partial Diabetes Insipidus during Stress but Not Maintenance Dosing of Glucocorticoids in an Infant with Septo-Optic Dysplasia

<p/> <p><it>Background</it>. It is well acknowledged that glucocorticoid (GC) replacement can unmask diabetes insipidus (DI) in subjects with hypopituitarism. <it>Objective</it>. To increase the awareness and monitoring for transient and symptomatic DI in children with partial hypopituitarism during periods in which increased GC needs are required. <it>Methods/Case</it>. A 2-month-old female infant with septo-optic dysplasia (SOD; on thyroid and maintenance GC replacement therapy at 8 mg/m²/day) developed transient DI during 2 separate episodes of stress (one hypothermia, one febrile) when stress dosing of GC (25 mg/m²/day) was instituted. <it>Conclusion</it>. Children not diagnosed with DI during initial evaluation for hypopituitarism may benefit from rescreening of serum sodium levels during acute periods of stress that demand "stress" GC dosing. This will permit treatment and/or increased vigilance for ensuing permanent DI.</p

Alternative Strategies for the Treatment of Classical Congenital Adrenal Hyperplasia: Pitfalls and Promises

Despite decades of different treatment algorithms, the management of congenital adrenal hyperplasia (CAH) remains clinically challenging. This is due to the inherent difficulty of suppressing adrenal androgen production using near physiological dosing of glucocorticoids (GC). As a result, alternating cycles of androgen versus GC excess can occur and may lead to short stature, obesity, virilization, and alterations in puberty. Novel therapeutic alternatives, including new and more physiological means of GC delivery, inhibitors at the level of CRH or ACTH secretion and/or action, as well as “rescue strategies”, such as GnRH analogs, anti-androgens, aromatase inhibitors, and estrogen receptor blockers, are available; many of these agents, however, still require active investigation in CAH. Bilateral adrenalectomy is effective but it is also still an experimental approach. Gene therapy and stem cells, to provide functional adrenal cortical tissue, are at preclinical stage but provide exciting avenues for a potential cure for CAH

Optimization of Triangular and Banded Matrix Operations Using 2d-Packed Layouts

International audienceOver the past few years, multicore systems have become more and more powerful and, thereby, very useful in high-performance computing. However, many applications, such as some linear algebra algorithms, still cannot take full advantage of these systems. This is mainly due to the shortage of optimization techniques dealing with irregular control structures. In particular, the well-known polyhedral model fails to optimize loop nests whose bounds and/or array references are not affine functions. This is more likely to occur when handling sparse matrices in their packed formats. In this paper, we propose to use 2d-packed layouts and simple affine transformations to enable optimization of triangular and banded matrix operations. The benefit of our proposal is shown through an experimental study over a set of linear algebra benchmarks

Static versus Dynamic Memory Allocation: a Comparison for Linear Algebra Kernels

International audienceThe polyhedral model permits to automatically improve data locality and enable parallelism of regular linear algebra kernels. In previous work we have proposed a new data structure, 2d-packed layout, to store only the non-zeros elements of regular sparse (triangular and banded) matrices dynamically allocated for different basic linear algebra operations, and used Pluto to parallelize and optimize them. To our surprise, there were huge discrepancies in our measures of these kernels execution times that were due to the allocation mode: as statically declared arrays or as dynamically allocated arrays of pointers.In this paper we compare the performance of various linear algebra kernels, including some linear algebra kernels from the PolyBench suite, using different array allocation modes. We present our detailed investigation of the possible reasons of the performance variation on two different architectures: a dual 12-cores AMD (Magny-Cours) and a dual 10-cores Intel Xeon (Haswell-EP).We conclude that static or dynamic memory allocation has an impact on performance in many cases, and that the processor architecture and the gcc compiler's decisions can provoke significant and sometimes surprising variations, in favor of one or the other allocation mode

Pipelined Multithreading Generation in a Polyhedral Compiler

International audienceState-of-the-art automatic polyhedral parallelizers extract and express parallelism as isolated parallel loops. For example, the Pluto high-level compiler generates and annotates loops with "#pragma omp parallel for" directives. Our goal is to take advantage of pipelined multithreading, a parallelization strategy allowing to address a wider class of codes, currently not handled by automatic parallelizers. Pipelined multithreading requires to interlace iterations of some loops in a controlled way that enables the parallel execution of these iterations. We achieve this using OpenMP clauses such as ordered and nowait. The sketch of our method is to: (1) schedule a SCoP using traditional techniques such as Pluto's algorithm; (2) detect potential pipelines in groups of sequential loops; (3) fine-tune the schedule; and (4) generate the resulting code. The fully automatic generation is ongoing work, yet we show on a small set of experiments how pipelined multi-threading permits to parallelize programs which would otherwise not be parallelized

Splitting Polyhedra to Generate More Efficient Code: Efficient Code Generation in the Polyhedral Model is Harder Than We Thought

International audienceCode generation in the polyhedral model takes as inputa union of Z-polyhedra and produces code scanning all ofthem. Modern code generation tools are heavily relying onpolyhedral operations to perform this task. However, theseoperations are typically provided by general-purpose poly-hedral libraries that are not specifically designed to addressthe code generation problem. In particular, (unions of) poly-hedra may be represented in various mathematically equiv-alent ways which may have different properties with respectto code generation. In this paper, we investigate this prob-lem and try to find the best representation of polyhedra togenerate efficient code.We present two contributions. First we demonstrate thatthis problem has been largely under-estimated, showing sig-nificant control overhead deviations when using differentrepresentations of the same polyhedra. Second, we proposean improvement to the main algorithm of the state-of-the-artcode generation tool CLooG. It generates code with fewertests in the inner loops, and aims to reduce control overheadand to simplify vectorization for the compiler, at the cost ofa larger code size. It is based on a smart splitting of theunion of polyhedra while recursing on the dimensions. Weimplemented our algorithm in CLooG/PolyLib, and com-pared the performance and size of the generated code to theCLooG/isl version

Integer Affine Transformations of Parametric Z-polytopes and Applications to Loop Nest Optimization

The polyhedral model is a well-known compiler optimization framework for the analysis and transformation of affine loop nests. We present a new method concerning a difficult geometric operation that is raised by this model: the integer affine transformation of parametric Z-polytopes. The result of such a transformation is given by a worst-case exponential union of Z-polytopes. We also propose a polynomial algorithm (for fixed dimension), to count points in arbitrary unions of a fixed number of parametric Z-polytopes. We implemented these algorithms and compared them to other existing algorithms, for a set of applications to loop nest analysis and optimization

Cell Cycle-Dependent Localization of Voltage-Dependent Calcium Channels and the Mitotic Apparatus in a Neuroendocrine Cell Line(AtT-20)

Changes in intracellular calcium are necessary for the successful progression of mitosis in many cells. Both elevation and reduction in intracellular calcium can disrupt mitosis by mechanisms that remain ill defined. In this study we explore the role of transmembrane voltage-gated calcium channels (CaV channels) as regulators of mitosis in the mouse corticotroph cell line (AtT-20). We report that the nifedipine-sensitive isoform CaV1.2 is localized to the “poleward side” of kinetechores during metaphase and at the midbody during cytokinesis. A second nifedipine-sensitive isoform, CaV1.3, is present at the mid-spindle zone in telophase, but is also seen at the midbody. Nifedipine reduces the rate of cell proliferation, and, utilizing time-lapse microscopy, we show that this is due to a block at the prometaphase stage of the cell cycle. Using Fluo-4 we detect calcium fluxes at sites corresponding to the mid-spindle zone and the midbody region. Another calcium dye, Fura PE3/AM, causes an inhibition of mitosis prior to anaphase that we attribute to a chelation of intracellular calcium. Our results demonstrate a novel, isoform-specific localization of CaV1 channels during cell division and suggest a possible role for these channels in the calcium-dependent events underlying mitotic progression in pituitary corticotrophs

Adaptive Runtime Selection of Parallel Schedules in the Polytope Model

International audienceThere is often no unique version of a program that provides the best performance in all circumstances. Compilers should rely on an adaptive runtime decision to choose which optimizing and parallelizing transformations will lead to the best performance in any execution context.We present a new adaptive framework solving two drawbacks of existing methods: it is effective since the very first execution, and it handles slight variations of input data shape and size. In our proposal, different code versions of parallel loop nests are statically generated by the compiler. At install time, each version is profiled in different execution contexts. At runtime, the execution time of each code version is predicted using the profiling results, the current input data shape and the number of available processor cores. The predicted best version is then run. Our framework handles several versions of possibly tiled parallel loops, using the polytope model for both the profiling and the dynamic selection phases. We show on several benchmark programs that our runtime system selects one of the most efficient version with a very low runtime overhead. This quick and efficient selection leads to speedups compared to the usage of a unique version in every execution context