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Center for Domain-Specific Computing
Postdoc Researchers
CDSC Staff, Research Scientists and Associate Faculty
Application Drivers
Modeling & Mapping
Experimental System
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Customized Architectures
Develop a framework to aid in the creation of a customizable heterogeneous platform (CHP) for a given application domain. This includes:
Leveraging domain modeling and profiling to understand the specific needs and bottlenecks of the domain.
Proposing innovative architectural solutions for domain-specific problems.
Evaluating architectural designs using our in-house cycle-accurate simulation infrastructure.
Thrust Leader: Glenn Reinman (UCLA)
Faculty: Jason Cong, Frank Chang (UCLA)
Postdoc/Research Staff: Zhenman Fang, Mohammadali Ghodrat (UCLA)
Students: Michael Gill, Beayna Grigorian, Yuchen Hao, Hui Huang, Chunyue Liu, Chunhua Xiao, Bo Yuan (UCLA)
Focused Areas:
Simulation Infrastructure: PARADE, Accelerator-Rich CMPs (ARC), Composable Heterogeneous Accelerator-Rich Microprocessor (CHARM), Composable Accelerator-rich Microprocessor Enhanced for Adaptivity and Longevity (CAMEL), Buffer-in-NUCA (BiN), Stream Arbitration, Interconnection Networks for Accelerator-Rich Architectures
Customizable Heterogeneous Platform (CHP)
A Customizable Heterogeneous Platform (CHP) consists of a heterogeneous set of adaptive computational resources connected with high-bandwidth, low-power non-traditional reconfigurable interconnects. Specifically, a CHP may include: 1) the integration of customizable cores and accelerators or co-processors that will enable power-efficient performance tuned to the specific needs of an application domain; 2) reconfigurable high-bandwidth and low-latency on-chip and off-chip interconnects, such as RF-interconnects or optical interconnect, which can be customized to specific applications or even specific phases of a given application; and 3) adaptive on-chip memory resources that help maximize data reuse for the power-efficient compute engines.
Flexibility is crucial for two reasons: first, in order for customization to be effective, our design must be adaptable to the specific needs of the application; second, prior work shows that no single architecture is best at adapting to all situations. For example, FPGAs excel in situations where there is considerable bit-level parallelism to exploit and in fixed-point bit-width optimized designs. As a further example, massively parallel engines like GPUs can readily provide high parallelism for applications using a SIMD approach, they do not perform as well for other types of parallelism, and can suffer from communication latency, particularly with respect to synchronization.
The main challenge for this Thrust is to develop a practical and implementable methodology for creating a CHP with degrees of flexibility in both its components and interconnect that are specifically tuned to a given application domain or a set of domains. CHP creation is guided by domain-specific modeling, which provides us with a variety of statically and dynamically profiled data characterizing the domain. This data guides the CHP creation phase in developing a CHP with resources and instructions customized to the needs of the domain. As any customization comes with a cost, we aim to provide only the custom resources and instructions that will be of use to the domain. Tunable resources and custom instructions will be leveraged by the compiler and runtime environment. CHP creation stage considers constraints on silicon area (determined by the cost consideration), performance (imposed by the application domain), and power (based in part on packaging and cooling constraints), as well as a library of architecture component models specific to the desired technology in which the CHP will be created.
Ultimately, CHP creation explores the best combination of cores, caches, interconnect, and other resources for the given application domain, implementing both the desired tunable ranges and custom instructions from domain-specific modeling. These will enable the efficient mapping of an application instance to a given CHP architecture so that the software layer can orchestrate these heterogeneous components and their interconnect with maximal flexibility.
Simulation Infrastructure: PARADE
To better evaluate CHP designs, we have developed our own simulation infrastructure called PARADE: the Platform for Accelerator-Rich Architectural Design and Exploration. The PARADE infrastructure is based on accelerator-rich design, with accelerators as the major building blocks of the simulator. The major components of the PARADE infrastructure are shown below:
Our infrastructure models each accelerator quickly by leveraging high-level synthesis tools. In addition, we provide a flow to automatically generate either dedicated or composable accelerator simulation modules that can be integrated into PARADE. We also provide a cycle-accurate model of the hardware global accelerator manager (GAM) that efficiently manages accelerator resources in the accelerator-rich design.
Our accelerator modeling infrastructure is combined with the widely used cycle-accurate full-system simulator Gem5. With gem5, we model the CPU and cache memory hierarchy. We also provide a cycle-accurate model of the coherent cache/scratchpad with shared memory between accelerators and CPU cores, as well as a customizable network-on-chip.
In addition to performance simulation, PARADE also models the power, energy and area using existing toolchains including McPAT for the CPU, and HLS and RTL tools for accelerators. We also add visualization support to assist architects with design space exploration.
PARADE is open source and hosted at: http://vast.cs.ucla.edu/software/parade-ara-simulator
[ICCAD15C] Jason Cong, Zhenman Fang, Michael Gill, and Glenn Reinman. PARADE: A Cycle-Accurate Full System Simulation Platform for Accelerator-Rich Architectural Design and Exploration. The 2015 IEEE/ACM International Conference on Computer-Aided Design (ICCAD 2015), Austin, Texas, November 2015.
Design Driver: Medical Imaging
Medical imaging applications often involve a pipeline of procedures: preprocessing, registration, and analysis (e.g., segmentation, feature extraction) are common steps. Each pipeline stage involves computationally intensive algorithms (each with distinct communication and processing patterns) and solutions entailing a set of (non-linear) optimizations proportional to the image size and the total number of images in a volumetric set. The amount of data requiring processing in one imaging study is dependent on several parameters, but today's cross-sectional studies range from 200-800 MB. With the rapid evolution of scanners, the amount of imaging data gathered is only expected to grow, though the size of future image datasets will likely have no difficulty fitting into the main memory of current and next-generation systems (avoiding foreseeable performance bottlenecks from I/O); however, the amount of data will outpace our ability to efficiently analyze the information.
Accelerator-Rich CMPs (ARC)
Power-efficiency has become one of the primary design goals in the many-core era. On-chip accelerators are application-specific implementations that provide power-efficient implementations of a particular functionality, and can range from simple tasks (i.e., a multiply accumulate operation) to tasks of more moderate complexity (i.e., an FFT or DCT) to even more complex tasks (i.e., complex encryption/ decryption or video encoding/decoding algorithms).
We proposed ARC, an Accelerator-Rich CMP that features a Global Accelerator Manager (GAM). The GAM is a hardware resource manager for accelerator sharing supporting sharing and arbitration of multiple cores for a common set of accelerators. It uses a hardware-based arbitration mechanism to provide feedback to cores to indicate the wait time before a particular resource becomes available and light-weight interrupts to reduce the OS overhead. A single accelerator instance can provide an average 36X performance over software running on a 4-core Xeon E5405 @ 2.0GHz.
[DAC12C] J. Cong, M.A. Ghodrat, M. Gill, B. Grigorian, and G. Reinman. Architecture support for accelerator-rich CMPs. Proceedings of the 49th Annual Design Automation Conference (DAC). June 2012.
Composable Heterogeneous Accelerator-Rich Microprocessor (CHARM)
Accelerators are inflexible, which not only limits their use for new algorithms/domains but can also be underutilized and area-inefficient due to replicated structures across different accelerators. To address these concerns, we proposed CHARM, a Composable Heterogeneous Accelerator-Rich Microprocessor design that provides scalability, flexibility, and design reuse in the space of accelerator-rich CMPs. CHARM features a hardware structure called the accelerator block composer (ABC), which can dynamically compose a set of accelerator building blocks (ABBs) into a loosely coupled accelerator (LCA) to provide orders of magnitude improvement in performance and power efficiency. Our software infrastructureprovides a data flow graph to describe the composition, and our hardware components dynamically map available resources to the data flow graph to compose the accelerator from components that may be physically distributed across the CMP. Our ABC is also capable of providing load balancing among available compute resources to increase accelerator utilization.
[ISLPED12C] J. Cong, M.A. Ghodrat, M. Gill, B. Grigorian and G. Reinman. CHARM: A Composable Heterogeneous Accelerator-Rich Microprocessor. Proceedings of the International Symposium on Low Power Electronics and Design (ISLPED 2012), Redondo, California, pp. 379-384, July-August 2012
Composable Accelerator-rich Microprocessor Enhanced for Adaptivity and Longevity (CAMEL)
While CHARM is able to provide more flexibility than monolithic accelerator architectures, the various ABBs used to compose accelerators in CHARM are still fixed at design time for a particular CHP. CHARM and other accelerator-rich platforms lack adaptivity to new algorithms and can see low accelerator utilization. To address these issues we propose CAMEL: Composable Accelerator-rich Microprocessor Enhanced for Longevity. CAMEL features programmable fabric (PF) to extend the use of ASIC composable accelerators in supporting algorithms that are beyond the scope of the baseline platform.
The figure above demonstrates the CAMEL CHP, where ABB islands (blue I's) are distributed across the chip and may be composed together and with the green programmable fabric (PF) to form accelerators. The results below show how well a set of ABBs that were designed for one domain (medical imaging) perform when combined with different amounts of programmable fabric (shown along the x-axis) for different domains (Vision, Navigation, and Commercial domains). Programmable fabric provides the flexibility for the composable approach to adapt to new domains and algorithms.
[ISLPED13C] J. Cong, M.A. Ghodrat, M. Gill, B. Grigorian, H. Huang and G. Reinman. Composable Accelerator-rich Microprocessor Enhanced for Adaptivity and Longevity. Proceedings of the International Symposium on Low Power Electronics and Design (ISLPED 2013), pp. 305-310, September 2013.
Buffer-in-NUCA (BiN)
As the number of on-chip accelerators grows rapidly to improve power-efficiency, the buffer size required by accelerators drastically increases. Existing solutions allow the accelerators to share a common pool of buffers or/and allocate buffers in cache. But no prior work considers global buffer allocation among multiple accelerators, where each has a range of buffer size requirements with different buffer utilization efficiencies. Moreover, no prior work considers the space fragmentation problem in a shared buffer, especially when allocating buffers in a non-uniform cache architecture (NUCA) with distributed cache banks. In this paper we propose a Buffer-in-NUCA (BiN) scheme with the following contributions: (1) a dynamic interval-based global allocation method to assign spaces to accelerators that can best utilize the additional buffer space, and (2) a flexible paged allocation method to limit the impact of buffer fragmentation, with only a small local page table at each accelerator. Experimental results show that, when compared to two representative schemes from the prior work, BiN improves performance by 32% and 35% and reduces energy by 12% and 29%, respectively.
[ISLPED12C] J. Cong, M.A. Ghodrat, M. Gill, C. Liu and G. Reinman. BiN: A Buffer-in-NUCA Scheme for Accelerator-Rich CMPs. International Symposium on Low Power Electronics and Design (ISLPED), Jul/Aug 2012.
Stream Arbitration
Alternative interconnects are attractive for scaling on-chip communication bandwidth in a power-efficient manner. However, efficient utilization of the bandwidth provided by these emerging interconnects still remains an open problem due to the spatial and temporal communication heterogeneity. We propose a Stream Arbitration scheme, where at runtime any source can compete for any communication channel of the interconnect to talk to any destination. We apply stream arbitration to radio frequency interconnect (RF-I). Experimental results show that compared to the representative token arbitration scheme, stream arbitration can provide an average 20% performance improvement and 12% power reduction. Below is one example of an NoC architecture using Stream Arbitration, with an RF-I transmission line (light blue) spanning the various components on the chip.
Stream Arbitration leverages an arbitration channel separate from the data channels of the RF-I. The key component of our approach is the arbitration stream that travels across the arbitration channel. Conceptually, the arbitration stream starts at a single node, which is called the stream origin. The arbitration stream starts out logically empty and will travel in a unidirectional manner across all the nodes on the chip; this is called Trip 1. In this trip, when the stream passes each node, the node logically augments a number of bits (referred to as substream) in the arbitration stream to specify whether or not this node is attempting to send to another node, and whether or not this node is capable of receiving packets. It is important to note that these two pieces of information (desire to send and availability to receive) do not require any parsing of the stream—they only rely on information known a priori at the node. So there is no dependence where the stream must be read first and then modified. Such a dependence would impact arbitration latency by bringing slow logic on the critical path of the stream propagation.
After the arbitration stream passes the last RF node in Trip 1, it circulates over all nodes a second time, which we refer to as Trip 2. In this trip, when the stream passes each node, the node receives the arbitration stream but does not modify the stream. The purpose of Trip 2 is to parse the stream in order to determine whether each node has the ability to send and to what channel each node should listen in the subsequent data transmission.
After the arbitration stream is parsed, the transmitter of a source node that has successfully acquired a data channel will be tuned to send on this channel, and the receiver of the intended destination node will be tuned to listen to the same data channel. A node can be a source and a destination simultaneously, using different channels. After Trip 2, the sources that successfully acquired data channels begin to use these data channels to communicate with their corresponding destinations. A channel is used for a single flit, and is surrendered after the flit transmitted. This does not incur a performance penalty because arbitration can be initiated every cycle, so a pair of nodes is allowed to communicate so long as the source continues to win arbitration. This requires stream arbitration and data transferring to be pipelined.
Below, the transmission line interface (left) and arbitration and data channel layout (right) is shown.
[TACO13X] C. Xiao, M. F. Chang, J. Cong, M. Gill, Z. Huang, C. Liu, G. Reinman, H. Wu. Stream arbitration: Towards efficient bandwidth utilization for emerging on-chip interconnects. ACM Transactions on Architecture and Code Optimization (TACO), Jan 2013.
Interconnection Networks for Accelerator-Rich Architectures
Hardware accelerators provide high computation capability and low energy consumption. However, hardware accelerators cannot tolerate memory and communication latency through extensive multithreading; this increases the demand for efficient memory interface and network-on-chip (NoC) designs. The NoC has considerable impact on overall system performance. Much past research has addressed NoC in homogeneous multi-core processers, lowering network latency and congestions. However, as hardware accelerators become ubiquitous in modern processors, it is necessary to examine NoC performance in the context of accelerator-rich architectures.
The throughput of an accelerator is often bound by the rate at which the accelerator is able to interact with the memory system. Existing interconnect designs for accelerator architectures use partial crossbar switches, bus and packet-switched networks to transfer data between memory and accelerators. But accelerator memory accesses exhibit predictable patterns, creating highly utilized network paths.
Leveraging this observation, we propose the Hybrid network with Predictive Reservation (HPR). By introducing circuit-switching to cover accelerator memory accesses, HPR reduces per-hop delays for accelerator traffic. Unlike previous circuit-switching proposals, HPR eliminates circuit-switching setup and teardown latency by reserving circuit-switched paths when accelerators are invoked. We use a hybrid switched router architecture as shown below. We further maximize the benefit of paths reservation by regularizing the communication traffic through TLB buffering and hybrid-switching.
The combined effect of these optimizations reduces the total execution time by 11.3% over a packet-switched mesh NoC.
[DAC15C] Jason Cong, Michael Gill, Yuchen Hao, Glenn Reinman, and Bo Yuan. On-chip Interconnection Network for Accelerator-Rich Architectures. Design Automation Conference (DAC) 2015, San Francisco, CA, June 7-11, 2015.
© 2017 UC REGENTS TERMS OF USE & PRIVACY POLICY


Excuse the cliche of pointing just out how quickly the past month has gone... but as if it's April already, how is that possible!? Thankfully it is finally starting to feel more spring like (now that storm Katie has passed- I love that name, just sayin'), I can feel summer is on it's way!
I have tried a few new things this month, along with the usual tried and tested. Having travelled a lot recently I have really cut down on the amount of products I pack, reaching just for those few essentials that I know will last well on my skin and keep me feeling a little more 'me'. In this roundup it's clear the idea of Spring has had its influence!
Chanel 'Poudre Universelle Compacte'/Natural finish pressed powder - I ran out of my usual Rimmel Clear Collection powder and had a sudden urge to try something different. Strangely it just wasn't cutting it this month, my oily patches coming through. However this powder is dreamy! For one, its the most beautiful packaging ever, and two, it keeps my makeup in place all day. What more could you want!?
Lancôme Juicy Shaker- The product that every blogger out there is talking about, but I honestly love this stuff. I treated myself during a trip to Selfridges at the beginning of the month when I went to see The 1975 and I have worn it every day since. Rather oily in texture, it doesn't last long but is so so moisturising and perfect for every day. I have the shade 'Berry Tale'- review to come soon.
Topshop Nice 'N' Neutral- I have recently grown my nails (finally, so gross), so I had been looking for a neutral varnish that doesn't highlight my nails, especially as they're still not looking 'normal'. I use a Sally Hansen nail strengthener as a base and top coat and this lasts all week, sometimes two depending on what I am doing. I don't think i'll ever use another colour!
Estée Lauder Double Wear (1N2 ECRU)- I once tried Charlotte Tilbury Magic Foundation ( I caved to the hype) and this has just heightened my love for Double Wear.. The Magic foundation really didn't suit my skin unfortunately, no longevity. I found it beautiful for an hour or so, so maybe for a meal out it would be nice, but after that my oily skin comes out to play. Double Wear without a doubt will look the same in the evening as it did in the morning- the same matt, flawless finish. Dreams.
Finally, The White Company Lime & Bay candle- A fairly subtle scent, but perfect for my bedside table. The White Company describe this as 'stepping into a colourful tropical garden' and strangely I think that is a perfect description.
What are your favourites this month? I'm looking forward to a warmer April, as well as a trip to Boston at the end with work!


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Wellness and Medical Topics
Childhood Brain Stem Glioma Treatment (PDQ®): Treatment - Health Professional Information [NCI]
[en Español]
General Information About Childhood Brain Stem Glioma
Cellular Classification of Childhood Brain Stem Glioma
Stage Information for Childhood Brain Stem Glioma
Treatment Option Overview for Childhood Brain Stem Glioma
Newly Diagnosed Childhood Brain Stem Glioma Treatment
Progressive / Recurrent Childhood Brain Stem Glioma Treatment
Changes to This Summary (09 / 28 / 2017)
About This PDQ Summary
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Primary brain tumors, including brain stem gliomas, are a diverse group of diseases that together constitute the most common solid tumor of childhood. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis.
The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization (WHO) classification of nervous system tumors.[1 ,2 ] For a full description of the classification of nervous system tumors and a link to the corresponding treatment summary for each type of brain tumor, refer to the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview.
The term brain stem glioma is a generic description that refers to any tumor of glial origin arising in the brain stem, inclusive of the midbrain, pons, and medulla. The following two histologies predominate:
Diffuse (infiltrating) astrocytomas centered in the pons, also called diffuse intrinsic pontine glioma (DIPG).
Pilocytic astrocytomas, which occur throughout the brain stem.
Approximately 300 to 400 pediatric brain stem tumors are diagnosed each year in the United States. DIPG accounts for approximately 75% to 80% of pediatric brain stem tumors.[3 ] Most children with DIPG are diagnosed between the ages of 5 and 10 years. Focal pilocytic astrocytomas in the brain stem occur less frequently.[4 ]
Anatomy of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in blue), and other parts of the brain. The posterior fossa is the region below the tentorium, which separates the cortex from the cerebellum and essentially denotes the region containing the brain stem, cerebellum, and fourth ventricle.
In children with DIPG, a classic triad of symptoms (cranial neuropathies, long tract signs, and ataxia) is often described. However, children often present with only one or two of these findings. Obstructive hydrocephalus due to expansion of the pons can also be a presenting symptom. Nonspecific symptoms may also occur, including behavioral changes and decreased school performance.
Focal pilocytic astrocytomas in the brain stem present in multiple ways depending on tumor location. Common presenting symptoms include the following:[4 ]
Raised intracranial pressure with associated hydrocephalus.
Unilateral hemiparesis.
Unilateral cranial neuropathies.
Ataxia.
Primary tumors of the brain stem are most often diagnosed based on clinical findings and on neuroimaging studies using magnetic resonance imaging (MRI).[5 ] Histologic confirmation of presumed DIPGs is usually unnecessary. However, histologic confirmation is currently performed for research studies and may be more routinely considered in the future.[6 ] Biopsy or resection may be indicated for brain stem tumors that are not diffuse and intrinsic or when there is diagnostic uncertainty based on imaging findings. New approaches with stereotactic needle biopsy may make biopsy safer.[7 ,8 ,9 ]
Children with neurofibromatosis type 1 (NF1) are at an increased risk of developing a brain stem glioma. They may present with a long history of symptoms or be identified by screening tests.
Prognosis and Prognostic Factors
The median survival for children with DIPGs is less than 1 year.[10 ] In contrast, focal astrocytomas (e.g., pilocytic astrocytomas) have a markedly improved prognosis, with 5-year overall survival exceeding 90%.[4 ]
Prognostic factors include the following:
Histology/grade of the tumor: Astrocytic tumors predominate in the brain stem. WHO grade 1 tumors (e.g., pilocytic astrocytomas and gangliogliomas) have a favorable prognosis and can arise throughout the brain stem, including the tectum of the midbrain, focally within the pons, or at the cervicomedullary junction where they are often exophytic. In contrast, DIPGs are diffuse astrocytomas which, when biopsied at diagnosis, can range from a low-grade fibrillary astrocytoma (WHO grade 2) to glioblastoma (WHO grade 4). At postmortem evaluation, DIPGs are also generally anaplastic astrocytoma (WHO grade 3) or glioblastoma (WHO grade 4) by morphological criteria, although WHO grade 2 regions can also be identified.[11 ,12 ,13 ,14 ,15 ] Low-grade fibrillary astrocytomas (WHO grade 2) occurring outside the pons in other brain stem locations tend to be focal tumors with a more favorable prognosis.[16 ]
Age at diagnosis: Children younger than 3 years diagnosed with DIPG may have a more favorable prognosis, perhaps reflecting different biologic characteristics.[17 ]
NF1: Children with NF1 and brain stem gliomas may have a better prognosis than other patients who have intrinsic lesions.[18 ,19 ]
Follow-up After Treatment
For children with brain stem tumors and anticipated long-term survival, standard follow-up tends to include interval clinical assessments and periodic imaging with MRI. The required duration of follow-up with MRI varies; it largely depends on the presence or absence of residual imaging abnormalities and the original histology of the tumor after treatment.
Louis DN, Ohgaki H, Wiestler OD, et al., eds.: WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon, France: IARC Press, 2007.
Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 (2): 97-109, 2007.
Warren KE: Diffuse intrinsic pontine glioma: poised for progress. Front Oncol 2: 205, 2012.
Klimo P Jr, Pai Panandiker AS, Thompson CJ, et al.: Management and outcome of focal low-grade brainstem tumors in pediatric patients: the St. Jude experience. J Neurosurg Pediatr 11 (3): 274-81, 2013.
Liu AK, Brandon J, Foreman NK, et al.: Conventional MRI at presentation does not predict clinical response to radiation therapy in children with diffuse pontine glioma. Pediatr Radiol 39 (12): 1317-20, 2009.
Walker DA, Liu J, Kieran M, et al.: A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method. Neuro Oncol 15 (4): 462-8, 2013.
Cage TA, Samagh SP, Mueller S, et al.: Feasibility, safety, and indications for surgical biopsy of intrinsic brainstem tumors in children. Childs Nerv Syst 29 (8): 1313-9, 2013.
Grill J, Puget S, Andreiuolo F, et al.: Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma. Pediatr Blood Cancer 58 (4): 489-91, 2012.
Puget S, Beccaria K, Blauwblomme T, et al.: Biopsy in a series of 130 pediatric diffuse intrinsic Pontine gliomas. Childs Nerv Syst 31 (10): 1773-80, 2015.
Cohen KJ, Pollack IF, Zhou T, et al.: Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group. Neuro Oncol 13 (3): 317-23, 2011.
Ballester LY, Wang Z, Shandilya S, et al.: Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas. Am J Surg Pathol 37 (9): 1357-64, 2013.
Wu G, Diaz AK, Paugh BS, et al.: The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46 (5): 444-50, 2014.
Taylor KR, Mackay A, Truffaux N, et al.: Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet 46 (5): 457-61, 2014.
Buczkowicz P, Hoeman C, Rakopoulos P, et al.: Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet 46 (5): 451-6, 2014.
Hoffman LM, DeWire M, Ryall S, et al.: Spatial genomic heterogeneity in diffuse intrinsic pontine and midline high-grade glioma: implications for diagnostic biopsy and targeted therapeutics. Acta Neuropathol Commun 4: 1, 2016.
McAbee JH, Modica J, Thompson CJ, et al.: Cervicomedullary tumors in children. J Neurosurg Pediatr 16 (4): 357-66, 2015.
Broniscer A, Laningham FH, Sanders RP, et al.: Young age may predict a better outcome for children with diffuse pontine glioma. Cancer 113 (3): 566-72, 2008.
Pascual-Castroviejo I, Pascual-Pascual SI, Viaño J, et al.: Posterior fossa tumors in children with neurofibromatosis type 1 (NF1). Childs Nerv Syst 26 (11): 1599-603, 2010.
Albers AC, Gutmann DH: Gliomas in patients with neurofibromatosis type 1. Expert Rev Neurother 9 (4): 535-9, 2009.
Cytogenetic Characteristics of Diffuse Intrinsic Pontine Gliomas (DIPGs)
The genomic characteristics of DIPGs appear to differ from those of most other pediatric high-grade gliomas and from those of adult high-grade gliomas. The molecular and clinical characteristics of DIPGs align with those of other midline high-grade gliomas with a specific H3 K27M mutation in histone H3.1 (H3F3A) or H3.3 (HIST1H3B and HIST1H3C), which led the World Health Organization to group these tumors together into a single entity.[1 ] In one report of 64 children with thalamic tumors, 50% of high-grade gliomas (11 of 22) had an H3 K27M mutation, and approximately 10% of tumors with low-grade morphological characteristics (5 of 42) had an H3 K27M mutation.[2 ] Five-year overall survival (OS) was only 6% (1 of 16). In another study that included 202 children with glioblastoma, 68 of the tumors were midline (primarily thalamic) and had an H3 K27M mutation.[3 ] Five-year OS for this group was only 5%, which was significantly inferior to the survival rates of the remaining patients in the study.
A number of chromosomal and genomic abnormalities have been reported for DIPG, including the following:
Histone H3 genes: Approximately 80% of DIPG tumors have a mutation in a specific amino acid in the histone H3.1 (H3F3A) or H3.3 (HIST1H3B and HIST1H3C) genes.[4 ,5 ,6 ,7 ,8 ] This H3 K27M mutation is observed in pediatric high-grade gliomas at other midline locations but is uncommon in cortical pediatric high-grade gliomas and in adult high-grade gliomas.[4 ,5 ,6 ,7 ,8 ,9 ] An autopsy study that examined multiple tumor sites (primary, contiguous, and metastatic) in seven DIPG patients found that the H3 K27M mutation was invariably present, supporting its role as a driver mutation for DIPG.[10 ]
Activin A receptor, type I (ACVR1) gene: Approximately 20% of DIPG cases have activating mutations in the ACVR1 gene, with most occurring concurrently with H3.3 mutations.[5 ,6 ,7 ,8 ] Germline mutations in ACVR1 cause the autosomal dominant syndrome fibrodysplasia ossificans progressiva (FOP), although there is no cancer predisposition in FOP.[11 ]
Receptor tyrosine kinase amplification: PDGFRA amplification occurs in approximately 30% of cases, with lower rates of amplification observed for some other receptor tyrosine kinases (e.g., MET and IGF1R).[12 ,13 ] An autopsy study that examined multiple tumor sites (primary, contiguous, and metastatic) in seven DIPG patients found that PDGFRA amplification was variably present across these sites, suggesting that this change is a secondary genomic alteration in DIPG.[10 ]
TP53 deletion: DIPG tumors commonly show deletion of the TP53 gene on chromosome 17p.[13 ] Additionally, TP53 is commonly mutated in DIPG tumors, particularly those with histone H3 gene mutations.[5 ,6 ,7 ,8 ,14 ] Aneuploidy is commonly observed in cases with TP53 mutations.[8 ]
The gene expression profile of DIPG differs from that of non-brain stem pediatric high-grade gliomas, further supporting a distinctive biology for this subset of pediatric gliomas.[13 ] Pediatric H3 K27M-mutant tumors rarely show MGMT promoter methylation,[3 ] which explains the lack of efficacy of temozolomide when it was tested in patients with DIPG.[15 ]
Louis DN, Perry A, Reifenberger G, et al.: The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131 (6): 803-20, 2016.
Ryall S, Krishnatry R, Arnoldo A, et al.: Targeted detection of genetic alterations reveal the prognostic impact of H3K27M and MAPK pathway aberrations in paediatric thalamic glioma. Acta Neuropathol Commun 4 (1): 93, 2016.
Korshunov A, Ryzhova M, Hovestadt V, et al.: Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathol 129 (5): 669-78, 2015.
Wu G, Broniscer A, McEachron TA, et al.: Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44 (3): 251-3, 2012.
Fontebasso AM, Papillon-Cavanagh S, Schwartzentruber J, et al.: Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat Genet 46 (5): 462-6, 2014.
Schwartzentruber J, Korshunov A, Liu XY, et al.: Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482 (7384): 226-31, 2012.
Shore EM, Xu M, Feldman GJ, et al.: A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38 (5): 525-7, 2006.
Zarghooni M, Bartels U, Lee E, et al.: Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 28 (8): 1337-44, 2010.
Paugh BS, Broniscer A, Qu C, et al.: Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29 (30): 3999-4006, 2011.
Khuong-Quang DA, Buczkowicz P, Rakopoulos P, et al.: K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124 (3): 439-47, 2012.
Cohen KJ, Heideman RL, Zhou T, et al.: Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group. Neuro Oncol 13 (4): 410-6, 2011.
There is no generally applied staging system for childhood brain stem glioma.[1 ]
Brain stem gliomas are classified according to the following:
Radiographic appearance.
Histology (when obtained).
Brain stem gliomas may occur in the pons, midbrain, tectum, dorsum of the medulla at the cervicomedullary junction, or in multiple regions of the brain stem. The tumor may contiguously involve the cerebellar peduncles, cerebellum, the cervical spinal cord, and/or thalamus. The majority of childhood brain stem gliomas are diffuse astrocytomas that involve the pons (diffuse intrinsic pontine gliomas [DIPGs]), often with contiguous involvement of other brain stem sites.[2 ,3 ]
Spread of malignant brain stem tumors is usually contiguous, with metastasis via the subarachnoid space. Such dissemination may occur prior to local relapse but usually occurs simultaneously with or after local disease relapse.[4 ]
Freeman CR, Farmer JP: Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys 40 (2): 265-71, 1998.
Laigle-Donadey F, Doz F, Delattre JY: Brainstem gliomas in children and adults. Curr Opin Oncol 20 (6): 662-7, 2008.
Khatua S, Moore KR, Vats TS, et al.: Diffuse intrinsic pontine glioma-current status and future strategies. Childs Nerv Syst 27 (9): 1391-7, 2011.
Sethi R, Allen J, Donahue B, et al.: Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma. J Neurooncol 102 (1): 121-7, 2011.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[1 ] Many of the improvements in survival in childhood cancer have been made as a result of clinical trials that have attempted to improve on the best available, accepted therapy. Clinical trials in pediatrics are designed to compare new therapy with therapy that is currently accepted as standard. This comparison may be done in a randomized study of two treatment arms or by evaluating a single new treatment and comparing the results with those that were previously obtained with existing therapy.
Because of the relative rarity of cancer in children, all patients with brain tumors should be considered for entry into a clinical trial. To determine and implement optimum treatment, planning by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors is required. Radiation therapy (including 3-dimensional conformal radiation therapy) of pediatric brain tumors is technically very demanding and should be carried out in centers that have experience in that area in order to ensure optimal results.
Table 1 describes the standard treatment options for newly diagnosed and recurrent or progressive childhood brain stem gliomas.
Table 1. Standard Treatment Options for Childhood Brain Stem Gliomas
Treatment Group
Standard Treatment Options
Newly diagnosed childhood brain stem gliomas:
Diffuse intrinsic pontine gliomas Radiation therapy
Focal brain stem gliomas Surgical resection (with or without chemotherapy and/or radiation therapy)
Observation (with or without cerebrospinal fluid diversion)
Radiation therapy, chemotherapy, or alternative approaches for unresectable tumors
Recurrent/progressive childhood brain stem gliomas:
Diffuse intrinsic pontine gliomas There is no standard treatment
Focal brain stem gliomas Repeat surgical resection
Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.
Standard Treatment Options for Diffuse Intrinsic Pontine Gliomas (DIPGs)
While numerous clinical trials are available for children with newly diagnosed DIPGs, the utility of any therapy besides radiation therapy in the treatment of patients with newly diagnosed DIPG remains unproven.[1 ,2 ,3 ,4 ,5 ,6 ]; [7 ,8 ][Level of evidence: 2A]; [9 ][Level of evidence: 3iiiA]
Currently, no chemotherapeutic strategy-including neoadjuvant, concurrent, postradiation therapy, or immunotherapy-when added to radiation therapy has led to long-term survival for children with DIPGs.[10 ,11 ,12 ]; [13 ][Level of evidence: 2A] This includes studies utilizing high-dose, marrow-ablative chemotherapy with autologous hematopoietic stem cell rescue, which have also been ineffective in extending survival.[14 ]
Standard treatment options for newly diagnosed DIPGs include the following:
Radiation therapy.
Conventional treatment for children with DIPGs is radiation therapy to involved areas. The conventional dose of radiation ranges between 54 Gy and 60 Gy given locally to the primary tumor site in single daily fractions. Such treatment will result in transient benefit for most patients, but more than 90% of patients will die within 18 months of diagnosis.[15 ]
Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.[16 ]
Research studies evaluating the efficacy of hyperfractionated and hypofractionated radiation therapy and radiosensitizers have not demonstrated improved outcomes using these radiation techniques.
Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, and studies using doses as high as 78 Gy have been completed. Evidence demonstrates that these increased radiation therapy doses do not improve the duration or rate of survival for patients with DIPGs, whether given alone [1 ,17 ] or in combination with chemotherapy.[3 ]
Hypofractionated radiation therapy results in survival rates comparable to conventional fractionated radiation therapy techniques, possibly with less treatment burden.[18 ][Level of evidence: 1iiA]; [15 ,19 ][Level of evidence: 2A]
Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of radiation therapy have been undertaken but to date have failed to show any significant improvement in outcome.[1 ,3 ,4 ,5 ,20 ,21 ]
Chemotherapy only (infants)
Similar to the treatment of other brain tumors, radiation therapy is often omitted for infants with DIPGs, and chemotherapy-only approaches are utilized. However, published data supporting the utility of this approach is lacking.
Treatment options under clinical evaluation
Early-phase therapeutic trials may be available for selected patients. These trials may be available via the Children's Oncology Group, the Pediatric Brain Tumor Consortium, or other entities. Information about National Cancer Institute (NCI)-supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
Standard Treatment Options for Focal Brain Stem Gliomas
Standard treatment options for newly diagnosed focal brain stem gliomas include the following:
Surgical resection (with or without chemotherapy and/or radiation therapy).
Observation (with or without cerebrospinal fluid diversion).
Radiation therapy, chemotherapy, or alternative approaches for unresectable tumors.
Surgical resection (with or without chemotherapy and/or radiation therapy)
In general, maximal surgical resection is attempted.[22 ,23 ]
Patients with residual tumor may be candidates for additional therapy. Treatment options include chemotherapy and/or radiation therapy.
Patients with small tectal lesions and hydrocephalus but no other neurological deficits may be treated with cerebrospinal fluid diversion alone and have follow-up with sequential neuroradiographic studies unless there is evidence of progressive disease.[22 ]
A period of observation may be indicated before instituting any treatment for patients with neurofibromatosis type 1.[24 ] Brain stem gliomas in these children may be indolent and may require no specific treatment for years.[25 ]
In selected circumstances, adjuvant therapy in the form of radiation therapy or chemotherapy can be considered in a child with a newly diagnosed focal brain stem glioma.[26 ,27 ][Level of evidence: 3iDi] Decisions regarding the need for such therapy depend on the age of the child, the extent of resection obtainable, and associated neurologic deficits.
Alternative approaches that have proven beneficial in selected cases include the following:
Stereotactic iodine I 125 brachytherapy approaches, with or without adjuvant chemotherapy.[28 ]
The use of BRAF inhibitors for tumors harboring a BRAF V600E mutation.[29 ]
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Mandell LR, Kadota R, Freeman C, et al.: There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 43 (5): 959-64, 1999.
Jennings MT, Sposto R, Boyett JM, et al.: Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children's Cancer Group. J Clin Oncol 20 (16): 3431-7, 2002.
Allen J, Siffert J, Donahue B, et al.: A phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas. Cancer 86 (6): 1064-9, 1999.
Broniscer A, Leite CC, Lanchote VL, et al.: Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group. J Clin Oncol 18 (6): 1246-53, 2000.
Doz F, Neuenschwander S, Bouffet E, et al.: Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Société Française d'Oncologie Pédiatrique. Eur J Cancer 38 (6): 815-9, 2002.
Wolff JE, Westphal S, Mölenkamp G, et al.: Treatment of paediatric pontine glioma with oral trophosphamide and etoposide. Br J Cancer 87 (9): 945-9, 2002.
Korones DN, Fisher PG, Kretschmar C, et al.: Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children's Oncology Group phase II study. Pediatr Blood Cancer 50 (2): 227-30, 2008.
Jalali R, Raut N, Arora B, et al.: Prospective evaluation of radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 77 (1): 113-8, 2010.
Frappaz D, Schell M, Thiesse P, et al.: Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial. Neuro Oncol 10 (4): 599-607, 2008.
Frazier JL, Lee J, Thomale UW, et al.: Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. J Neurosurg Pediatr 3 (4): 259-69, 2009.
Hargrave D, Bartels U, Bouffet E: Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7 (3): 241-8, 2006.
Warren K, Bent R, Wolters PL, et al.: A phase 2 study of pegylated interferon α-2b (PEG-Intron(®)) in children with diffuse intrinsic pontine glioma. Cancer 118 (14): 3607-13, 2012.
Bouffet E, Raquin M, Doz F, et al.: Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 88 (3): 685-92, 2000.
Janssens GO, Jansen MH, Lauwers SJ, et al.: Hypofractionation vs conventional radiation therapy for newly diagnosed diffuse intrinsic pontine glioma: a matched-cohort analysis. Int J Radiat Oncol Biol Phys 85 (2): 315-20, 2013.
Liu AK, Macy ME, Foreman NK: Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys 75 (4): 1148-54, 2009.
Freeman CR, Krischer JP, Sanford RA, et al.: Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study. Int J Radiat Oncol Biol Phys 27 (2): 197-206, 1993.
Zaghloul MS, Eldebawy E, Ahmed S, et al.: Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): a randomized controlled trial. Radiother Oncol 111 (1): 35-40, 2014.
Negretti L, Bouchireb K, Levy-Piedbois C, et al.: Hypofractionated radiotherapy in the treatment of diffuse intrinsic pontine glioma in children: a single institution's experience. J Neurooncol 104 (3): 773-7, 2011.
Freeman CR, Kepner J, Kun LE, et al.: A detrimental effect of a combined chemotherapy-radiotherapy approach in children with diffuse intrinsic brain stem gliomas? Int J Radiat Oncol Biol Phys 47 (3): 561-4, 2000.
Bradley KA, Zhou T, McNall-Knapp RY, et al.: Motexafin-gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a children's oncology group phase 2 study. Int J Radiat Oncol Biol Phys 85 (1): e55-60, 2013.
Vandertop WP, Hoffman HJ, Drake JM, et al.: Focal midbrain tumors in children. Neurosurgery 31 (2): 186-94, 1992.
Kestle J, Townsend JJ, Brockmeyer DL, et al.: Juvenile pilocytic astrocytoma of the brainstem in children. J Neurosurg 101 (1 Suppl): 1-6, 2004.
Bilaniuk LT, Molloy PT, Zimmerman RA, et al.: Neurofibromatosis type 1: brain stem tumours. Neuroradiology 39 (9): 642-53, 1997.
Molloy PT, Bilaniuk LT, Vaughan SN, et al.: Brainstem tumors in patients with neurofibromatosis type 1: a distinct clinical entity. Neurology 45 (10): 1897-902, 1995.
Ronghe M, Hargrave D, Bartels U, et al.: Vincristine and carboplatin chemotherapy for unresectable and/or recurrent low-grade astrocytoma of the brainstem. Pediatr Blood Cancer 55 (3): 471-7, 2010.
Ruge MI, Kickingereder P, Simon T, et al.: Stereotactic iodine-125 brachytherapy for treatment of inoperable focal brainstem gliomas of WHO grades I and II: feasibility and long-term outcome. J Neurooncol 109 (2): 273-83, 2012.
Rush S, Foreman N, Liu A: Brainstem ganglioglioma successfully treated with vemurafenib. J Clin Oncol 31 (10): e159-60, 2013.
Treatment Options for Progressive Diffuse Intrinsic Pontine Gliomas (DIPGs)
Progression of the tumor is anticipated generally within 1 year of completing radiation therapy. In most cases, biopsy at the time of clinical or radiologic progression is neither necessary nor recommended. To date, no salvage regimen has been shown to extend survival. Patients or families who desire additional disease-directed therapy should consider entering trials of novel therapeutic approaches because no standard agents have demonstrated clinically significant activity.
Regardless of whether a decision is made to pursue disease-directed therapy at the time of progression, palliative care remains a central focus of management. This ensures that quality of life is maximized while attempting to reduce symptoms and stress related to the terminal illness.
Treatment Options for Recurrent Focal Brain Stem Gliomas
At the time of recurrence, a complete evaluation to determine the extent of the relapse may be indicated for selected focal lesions. Biopsy or surgical resection should be considered for confirmation of relapse when other entities such as secondary tumor and treatment-related brain necrosis, which may be clinically indistinguishable from tumor recurrence, are in the differential diagnosis. Other tests, including positron emission tomography, magnetic resonance spectroscopy, and single-photon emission computed tomography, have not yet been shown to be reliable in distinguishing necrosis from tumor recurrence in brain stem gliomas. Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.
Treatment considerations at the time of recurrence or progression are dependent on prior treatment. Treatment options for recurrent focal brain stem gliomas include the following:
Repeat surgical resection: The need for surgical intervention must be individualized on the basis of the initial tumor type, the location within the brain stem, the length of time between initial treatment, the appearance of the mass lesion, and the clinical picture.[1 ]
Radiation therapy.[2 ]
Chemotherapy: Chemotherapy with agents such as a carboplatin and vincristine may be effective in children with recurrent focal exophytic gliomas.[3 ]
Early-phase therapeutic trials may be available for selected patients. These trials may be available via the Children's Oncology Group (COG), the Pediatric Brain Tumor Consortium, or other entities. Information about National Cancer Institute (NCI)-supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.
Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).
Bowers DC, Krause TP, Aronson LJ, et al.: Second surgery for recurrent pilocytic astrocytoma in children. Pediatr Neurosurg 34 (5): 229-34, 2001.
Huynh-Le MP, Walker AJ, Burger PC, et al.: Management of pediatric intracranial low-grade gliomas: long-term follow-up after radiation therapy. Childs Nerv Syst 32 (8): 1425-30, 2016.
Ater JL, Zhou T, Holmes E, et al.: Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol 30 (21): 2641-7, 2012.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added text to state that dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50% (cited Smith et al. as reference 1).
Progressive/Recurrent Childhood Brain Stem Glioma Treatment
Added Treatment Options Under Clinical Evaluation as a new subsection for progressive/recurrent childhood brain stem glioma.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood brain stem glioma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
be discussed at a meeting,
be cited with text, or
replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Brain Stem Glioma Treatment are:
Kenneth J. Cohen, MD, MBA (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital)
Karen J. Marcus, MD (Dana-Farber Cancer Institute/Boston Children's Hospital)
Roger J. Packer, MD (Children's National Health System)
Malcolm A. Smith, MD, PhD (National Cancer Institute)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Brain Stem Glioma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/brain/hp/child-glioma-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389253]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us.
Last Revised: 2017-09-28

redpajama_set_name: RedPajamaCommonCrawl


With Debs season in full swing, we here at Missy have been looking into what makes a great photo! Posing for photos is a love/hate thing, some people are naturals and others need a bit of help! Let's be honest, it's all about the pose and making the most your angles… Follow these tips for fab Debs photos!
If you're an America's Next Top Model fan you'll know all about "smizing". For those of you who don't know what we mean when we say smize, it's time to channel your inner Tyra Banks! Smize = smiling with your eyes. Look in a mirror and smile, see how you kind of squint and the corners of your eyes go up? Now try replicate this even when your mouth isn't in a smiling position. This helps to give your face a good shape. Your Debs photos will look bomb with this little trick!
Seeing as you'll probably have no control over the lighting at your Debs venue, or at pre-debs events, contour your face to create false shadows. Contouring involves using darker tones to sculpt out your cheekbones, forehead, nose, and neckline. Use lighter tones in areas where light will naturally hit i.e. under your eyes, centre of forehead, bridge of your nose, and just above your jawline. Make sure you blend like crazy and set with powder for a natural look that stays put!
Good posture makes a photo! Stand up straight to accentuate your body, and show off your outfit in all it's glory. Standing straight also gives you a confident look.
You know the one… Your granny probably has a few of these photos hanging in her house of your cousins or older siblings. It really isn't a great look and screams AWKWARD! You can be posing with your best friend in the whole world but somehow that dodgy hand holding pose will make you look like strangers forced into some kind of social experiment! If you're getting a professional debs photo, let the photographer know that thats not the look you're going for. Instead, take a more relaxed approach. Lean into your date at a 45 degree angle to accentuate your body, tilt your head down so your chin is slightly aimed to the floor (not too much or you'll form a double chin in the photo), smile naturally, and hold hands in a natural way.
Sometimes no matter how hard we pose or what makeup we wear, candid photos just look better. Ask your mam/dad/cousin to try get some candid snaps of you getting ready, or you and your date in the house before you leave. At the actual debs, see if you and a couple of friends can make a deal to snap a few candid shots on your phones throughout the night! You'll be grateful for the natural shots in years to come!
Have you any tips for taking Debs photos?


On Thursday VIA said that starting with the VIA EITX-3002 Em-ITX board, its x86 embedded platforms will support Android. VIA reports that the ability to run Google's OS on its x86 design will allow for increased flexibility, enhanced multimedia support and cost saving advantages for embedded applications such as interactive kiosks and in-vehicle entertainment.
"Key advantages for Android on x86 include leverage of Android development resources and existing apps, rich I/O flexibility, greater CPU performance as well as higher display resolutions of up to 1920 x 1080," VIA said. "In addition VIA has released SMART ETK, an Embedded Tool Kit which allows monitoring and control of peripheral devices through the Android OS, allowing for greater environmental control of kiosk and other installed environments."
VIA's first Android-supported board, the VIA EITX-3002, is powered by a choice of a 1.2 GHz VIA Nano X2 E-Series or 1.0 GHz VIA Eden X2 dual-core processor in combination with the VIA VX900 media system processor. The latter is what VIA calls "feature packed," an all-in-one digital media chipset that provides hardware acceleration for the latest HD video formats including MPEG-2, H.264, VC-1 and WMV9. It also supports dual independent display for superior digital signage displays.
"Designed for stability at extreme temperatures, fanless devices based on the VIA EITX-3002 can enjoy absolute stability at temperatures ranging from -10oC to 65oC," the company said. "Dual I/O coastlines include an HDMI port, VGA port, two Gigabit Ethernet ports, dual COM ports, four USB ports, two USB 3.0 ports (optional), audio jacks and power and HDD activity LEDs. The VIA EITX-3002 supports Windows 7, XP, Windows Embedded Standard 2009 and WES7 as well as Debian Linux and Android 2.2 operating systems."
For more information about the VIA EITX-3002 Em-ITX board, head here. Seen below is a video demonstration of Android running on a VIA's EITX-3002 x86 board.
Hmmm, Android-powered ultrabooks coming soon?
I think it would be funny if VIA beat Intel and AMD to the Android tablet market. If they did I would consider getting one.
It makes sense given that VIA targets the extreme low end of the x86 market. Obviously the typical VIA purchaser can't afford Windows OS so the options are steal a copy of Windows (probably done all the time in the markets where VIA operates) or go with a free OS such as Linux or Android. Android is obviously much more attractive than Linux for consumers. This could be a big win for Google as it may help to push Android into the Chinese marketplace.
A VIA chipset that can do 1080p playback smoothly, not sure if serious.
VIA talks about stuff they don't sell a lot of times. They have a good chipset CN1000, they sent out to reviewers a year ago, and you still can't get it.
But can it play Crysis ?
This is fantastic. For anything other than "real" PC use, Android works pretty well. If you make it VIA I will come, Android + HTPC = winning.
VIA still has a x86 license?
Yes - HTPC - and Carputer are the two major places I can see this being hugely applicable.
Hell, a combination of the two. Have a HTPC at home running android, and a Carputer in your car running android. Link them together over ssh proxy and you can watch your recorded TV shows while driving in your car. Take that Safety commission and your no-cell phones. I just put in an entertainment system instead!
And yes, I know you can do this with Linux already... but android would be so much cooler.
newbie_mcnoobVIA still has a x86 license?


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Entries received early can be promoted through our extensive email and social media campaign.
Sellers can use the convenient Online Entry form or download a form to complete and return by fax or email.
New sellers will find helpful information on the company website's How To page about taking photos and making videos to make a presentation that will attract buyers. Mike and Stephanie will also help owners determine how to best present their horse.
The February INTERNET Auction will be the venue to offer proven show horses, prospects and breeding stock for Halter, Western Pleasure, Hunter Under Saddle, Reining, All Around and Cattle events.
Early entries include: CERTIFIED SO HOT, a 17.2 hand, 2008 AQHA gelding by These Irons Are Hot, NSBA Reserve World Champion and Congress Reserve Champion Hunter Under Saddle; CHIC CODE, a 2012 AQHA gelding by Electric Code, that has earned $1,562 in NRHA and 145.5 Entry Level Points in Green & Rookie Reining classes; GOTA RAINY NIGHT, a 2014 AQHA gelding by Gota Lota Potential, that has shown successfully in Western Pleasure and Horsemanship in Open shows and is ready for AQHA shows; AFFLUENT, a 2016 ApHC stallion by The Real Secret (ApHC), that is a World Class Appaloosa Stallion and Reserve High Point 3 Year-old Stallion after only a few shows, plus more outstanding horses. The catalog will posted to the Internet shortly after the advertised entry deadline.
Mike and Stephanie Jennings, of Professional Horse Services, LLC are the industry leaders in Internet Auction marketing for Quarter Horses, Paints and Appaloosas. The Pro Horse Services INTERNET Auction platform has SOLD 2,090 horses for $8,437,850.
To obtain more information about selling or bidding on horses in the February INTERNET Auction contact Professional Horse Services, LLC, by email Info@ProHorseServices.com or call 855-272-3905. You can also go to https://prohorseservices.com/ Mike and Stephanie will be out of the office to catch up on some things from February 7th through the 11th, but will check for emails and messages daily.


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Rodrigue Akl, né le , est un joueur libanais de basket-ball. Il évolue au poste de meneur.

Carrière

Palmarès

Références

Liens externes

Naissance en septembre 1988
Joueur international libanais de basket-ball
Joueur du Riyadi Club Beyrouth
Joueur du Club Sagesse (basket-ball)
Joueur du Anibal Zahlé
Joueur des Blue Stars (Liban)

redpajama_set_name: RedPajamaWikipedia


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Category: world music
Review: Various artists, Tradi-Mods Vs. Rockers
When the electrifying, trancelike street music spearheaded by veteran Congolese band Konono No. 1 reached Western ears in the early 2000s, it sounded like something beamed in from Mars. Konono's music was based around traditional instruments like the likembe thumb piano, but the need to use hand-built, jury-rigged amplifiers to be heard on busy Kinshasa streets brought in heavy, loud distortion that gave Konono a rough, propulsive, hypnotic edge. It sounded weirdly and radically modern—the same kind of thing that forward-thinking punk and electronic musicians like Sonic Youth had been playing around with for years, but approached from an entirely unexpected angle.
The Konono aesthetic has had some time now to filter through Western indie-rock and electronica, and it's expanded intriguingly on the double-disc compilation Tradi-Mods Vs. Rockers, which opens up the floor to 26 American, British, and German indie bands who rework material from Konono and other Congolese bands, including Kasai Allstars. The results are largely enthralling, and sometimes nearly as revelatory as Konono itself sounded in 2004. Heard in context on Tradi-Mods, for instance, the seamlessly incorporated influence of Konono on Andrew Bird's electronically processed, looped violin is obvious. The disc is a triumph, and a great example of what a remix album should be: reverent to what made the original material fascinating, but not so much that it can't fly away in its own unexpected directions.
Originally published Nov. 30, 2010 on avclub.com. Read the complete article.
Tags: A.V. Club
African music, Andrew Bird, Kasai Allstars, Konono No. 1, music, review, world music | Christopher Bahn | November 30, 2010 5:11 pm | Comments (0)
Review: Kasai Allstars, In The 7th Moon, The Chief Turned Into A Swimming Fish And Ate The Head Of His Enemy By Magic
Central Africa's Democratic Republic Of The Congo is so huge it could fit Western Europe inside it, and its musical diversity is correspondingly vast. Kasai Allstars is a supergroup of 25 performers from five bands that each come from a different ethnic group in the central region of Kasai, with different languages, a history of strife, and artistic traditions considered incompatible until the musicians and dancers got together to try fusing them.
Originally published on avclub.com Oct. 13, 2008. Read the complete article.
African music, Kasai Allstars, music, review, world music | Christopher Bahn | October 13, 2008 10:48 am | Comments (0)
Interview: Albert Kuvezin of Yat-Kha
Russian music critic Artemi Troitsky once made the sweeping declaration that only two unique voices exist on Earth—Luciano Pavarotti, and the comparatively obscure Albert Kuvezin. Obscure or not, the latter—a singer from the small Russian republic of Tuva—can back up such praise. He's a master of khoomei, or throat-singing, a musical style that allows a singer to produce overtones—two, three, or even four notes at once—and specializes in a rare deep-bass variant called kanzat kargyraa. A founding member of the traditional Tuvan group Huun-Huur-Tu, Kuvezin left to pursue his own muse in his band Yat-Kha. He's hardly shackled by traditionalism, and has spent his career seeking bridges to other styles of music, including the American rock he collected as a teenager. Kuvezin unleashes his wild vocal style on a set of those tunes on's latest disc, Re-Covers, interpreting songs like Motörhead's "Orgasmatron" through his guttural bellow. (See Yat-Kha's website to download mp3s of "Orgasmatron" and the band's take on Joy Division's "Love Will Tear Us Apart.") There's no denying that Tuvan throatsingers like Kuvezin are an acquired taste, but really, could the world's second unique voice be anything else? The A.V. Club navigated the overloaded Tuvan cell-phone network and an 11-hour time difference to chat with Kuvezin in Tuva.
Originally published Sept. 14, 2006 on avclub.com. Read the complete article.
interview, music, Tuvan throatsinging, world music, Yat-Kha | Christopher Bahn | September 14, 2006 1:15 pm | Comments (0)
Interview: Sayan Bapa of Huun Huur Tu
Since forming their group in 1992, the members of Huun Huur Tu have been the primary musical ambassadors of Tuva, a small Russian republic in Central Asia known for a uniquely beautiful singing style. Khoomei, also known as throat-singing or overtone singing, allows vocalists to produce two, three, and sometimes four notes simultaneously. The effect can be haunting and unearthly, somewhere between Howlin' Wolf's guttural blues growl and the eerie sound of a theremin. A single throat-singer can be awe-inspiring, and as a quartet, Huun Huur Tu's power is jaw-droppingly intense, especially live. Collectively, Huun Huur Tu's four singers are masters of the several different styles of khoomei, including the ghostly, whistling sygyt and the earthquake rumble of kargyraa. Huun Huur Tu's latest, Altai Sayan Tandy-Uula, adds Western touches like keyboards and clarinet, but mostly continues the group's penchant for traditional Tuvan sounds. Earlier discs worth exploring include 60 Horses In My Herd, The Orphan's Lament, and a pair of concert CDs, Live 1 and Live 2. (For a different approach to blending Tuvan and Western music, check out ex-HHT singer Albert Kuvezin's Yat-Kha, or the collaboration between San Francisco bluesman Paul Pena and Kongar-ol Ondar in the Oscar-nominated documentary Genghis Blues.) Huun Huur Tu's current North American tour runs through February. The A.V. Club talked with founding member Sayan Bapa.
Originally published Jan. 31, 2006 on avclub.com. Read the complete article.
Huun Huur Tu, interview, music, Tuvan throatsinging, world music | Christopher Bahn | January 31, 2006 12:40 am | Comments (0)


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Fan Experiences
Click to view Fan Pictures.
From Fi...(April 8, 1998)
It was BC/EFA week the night I saw the show (which actually exceeded my expectations), so Martin was one of the people collecting, complete with a little red bucket. I gave him five bucks, undoubtedly the largest contribution I've ever made to a charitable organisation, and he gave me a little pin that says "Titanic: Ship of Dreams--Support BC/EFA." He also gave my friend Jane a pin, even though she hadn't donated anything. Oh well. I was really nervous. My voice went up an octave. And for some reason I kept staring at my shoes. They were black and white Sketchers knockoffs. I think I asked him if I could take a picture with him, because it eventually happened. In the picture I have the stupidest expression on my face. He was very nice about it, of course. But I can't really remember what he said, or what I said, because I was high on adrenaline.
From Mallory...(July 13, 1998)
After I saw Titanic (which RULED), I was outside the stage door when I saw Martin signing some autographs and talking to a few fans. So, on a bet, I had to approach him by myself and get his autograph and a picture. So I went up to him, handed him the pen and my programme, and told him that I thought he was really cool that night, because I could think of nothing more I could say that wouldn't cause him to get a restraining order. (just kidding.) He signed his name on the programme, then asked my name, which called for some quick thinking and a rather regretted "Ummm...." before I could reply. (I'm way too starstruck, you know....) So he handed me the programme, and I thanked him, and he started to leave, so the WONDERFUL, WONDERFUL Cynthia called out to him, asking if we could get a picture, so he came back and I got two with him. He was really nice about all of it.
From Joanna...(March 27th, June 24th, July 15th, August 15th....)
The first time I talked to Martin was in March, after I saw the show twice. He was really sweet and he's a great actor. While I was talking to him, Clarke Thorell came out, and anyone that knows me knows that to stop Clarke and continue talking to Martin and getting a picture and autograph means that Martin is a great actor and I almost sacrificed a lot just to talk to him. I got the chance to talk to him after my 4th time seeing it, when my friend wanted to meet him. I mentioned that I was coming back in about three weeks, so he said that he's going on vacation starting on July 16th for a few weeks, but when I said that I was coming on the 15th he said, "Well than I should be there." On July 15th I went up to him to tell him to have a good time on vacation and before I even opened my mouth he said "Hey, you did come today, I was wondering if you caught today's show." So he remembered me. On August 15th, at Brian d'Arcy James' last he gave the sweetest speech. He was all flustered for words and he was getting all choked up. He is one of the sweetest men, and also one of the most talented. He's one of the few people that I have seen all 7 times I've seen the show and I don't think that I'd want to see an understudy for Bride. When he leaves the show (which won't be for a while, I hope), it will be one of the saddest performances.
From Lindsay (February 5, 1999)
(This is an account of a concert Martin did in Oradell, NJ, and previously posted on the In Every Age mailing list)
Let's all play the "How Much Does Lindsay Love Martin" game. First off, I went with two friends of mine, Susan and Debra, neither of whom had heard of Martin before, except tidbits from me. Susan wanted to see Josie de Guzman (Sarah on the Guys & Dolls CD), and Debra was interested in the dancers from the NYC Ballet. Besides those I already mentioned, the other performers were Steve Barton, Loni Ackerman, Felicity LaFortune, and David Shire.
We got good seats (second row aisle) so I had a fabulous view of Martin the whole time. Yay! Well, they all did "I Have Dreamed" as an opening number, and he had a nice little solo... and a VERY nice suit. My friends both immediately thought he was cute. The next number he came out for was "Love in a New Tempo" -- sung to the tune of one of those John Philip Sousa marches! It was SO adorable!!! "The march of unrequited love... yadda yadda... you better give in, you better give in, because this song is getting long!" And he was all jumping around the stage and stuff... it was way too cute. You just had to be there. And hey... I didn't know he could DANCE too, for heaven's sake. He's too cool.
They did "The Proposal/The Night Was Alive" -- surprise surprise, right? They started off with some woman saying something melodramatic about a ship sailing to its icy destiny in 1912, and I was thinking that it was giving people a very cheezy impression of the show, especially when the fog machine started going. But it was GREAT!!! Steve did Barrett's part, and he was decent. He shouldn't have tried to do the accent though, because to put it bluntly, it did NOT work. And he messed up the words too, but what can you do? They did a shortened version of the dialogue before the song... you know, Barrett coming in while Bride's tapping away... oh yeah, and the set consisted of a stool and a microphone on a stand. Martin tapped on the mike handle for the dit-dit parts and pretended he had the headphones on. He was SO in character, it was great! What else is there to say about that number? Everyone here knows it, I daresay. :-) He came back for another ensemble number called "One Step" from Starting Here, Starting Now that they did in honor of David Shire, and then...
... intermission. Debra and Susan were trying to keep me under control, and we were wandering around the lobby, when I just stopped dead in my tracks. Deb was like "What?" I gestured to the other end of the room, but she apparently couldn't see anything, and Sus goes, "Hey, it's your guy!" (She's blunt -- this is the same girl who, when we went backstage at Scarlet Pimpernel, yelled out, "Omigod, it's DOUG!") He was talking with a bunch of people who were apparently leaving, and so we politely waited out of the way till he was done. He started toward the "backstage" area again, and I was like "Um, excuse me!" He looked at me for a sec and then said, "We've met, haven't we. Stage door at Titanic a few weeks ago, right?"
Needless to say, I was overjoyed. "Yeah, I was the one who said 'I love you!'" He obviously remembered that, and laughed that cute laugh he does a lot. We chatted for a little bit, I introduced him to Deb and Sus, and all of a sudden he interrupted me, stuck out his hand, and said, "I'm Martin, by the way... who are you?" Me: "I'm Lindsay... and I know you're Martin. That's why I'm here!" He found that amusing... and you know how when you're talking to him, he touches your arm occasionally? He did that a lot -- it was sweet. But after a minute or so, he said something to the effect of, "I'm not really supposed to be out here -- I just came out to say goodbye to some friends --so I'd better get back in there before they come after me." (Again, not a quote... just something to that effect.) But this IS a quote: "Maybe I'll see you after the show!" And this is another quote: "I didn't know they were gonna put FOG in that number!"
I wandered back to my seat with one of those way-too-big grins on my face. By now, Deb and Sus both think I'm nuts, although they freely admit that he's SOOO sweet and REALLY cute. Both thoughts to which I heartily agree.
The first song he did in the second act was "If I Loved You"... and it was mixed with Loni Ackerman singing "What You Don't Know About Women" -- an odd combo, I admit, but it was really great the way they did it!! Like an act, with the guy trying to get the girl and the girl going "pshaw" at him, and he doesn't even realize till the end that he ain't gettin' nowhere with her. So after the last note there was this long pause in which they looked at each other, her with a raised eyebrow and him with a puppy-dog look... and then they just turned away and walk off into opposite wings. It was SOOO funny. I could be heard yelling "Yeah Skeets!" Just because I felt like it.
His next, and last, solo song was the BEST. For anyone who has ever heard the song "There But For You Go I" -- you have NEVER heard it like this. Ever. It was completely beyond words... you could never tell he had a voice like that just by listening to Titanic! I cheered SO loud after that one... and just when the cheering died down and he was ready to leave the stage, Deb and Sus took it upon themselves to start the cheer up again! It was so funny... he just sort of stopped, took a few steps back downstage, and bowed again, all the while suspiciously checking out the audience....
Ah, but wait, he was in yet another! For all you Sondheim fans, it was "Getting Married Today" from Company, and Martin played Paul. I was thinking, "No! It's wrong! My name is NOT AMY!!!" Again, totally in character the entire time -- it was TOO great! And for the finale number, they all did "I Could Have Danced All Night" in which everyone had solos... and everyone was really rocking out. ESPECIALLY Martin! Spin-jumps are just way too fun to watch. Ahh yes, and during one of those exceptionally wonderful spin-jumps, the white rose that was pinned onto his lapel flew off. After the show, as people were leaving, I went and picked it up.
There were a few people waiting at the "stage door" -- but who cares about them. "Hey Lindsay!" says our Martin, and I proceed to tell him that I was almost crying during "There But For You Go I"... and he asked me if we were the ones yelling after the song was over. We admitted that we were, and he said, "That was cute." Me: "And you dropped this!" I held up the rose. He gave me the SWEETEST smile and said, "Aw, keep it!" Internally drooling, I just said, "Oh thanks!" (A gorgeous white rose is now sitting in the middle of my dresser, not far from the Second-Proposal-Picture of me and Doug Sills.) Again we chatted for a while... he said he had indeed gotten my letter... and he mentioned the name of the show he was going to be doing next... and like the idiot that I am, I can now not remember the name. Arg. But it's a straight play, and I think it is indeed going to be in New York. Oh yes... and at the request of a few people (um, Fiona... Mandy...) I said something to the effect of "On behalf of all the online Titanic fanatics, we all think you're really great and we're going to miss you so much!" And he responded with... you guessed it... "That's so sweet!" Well, my ride was sort of waiting for me, so I sort of had to go... but wow. He's so fabulous. Um, yeah, understatement.
Thus concludeth the "How Much Does Lindsay Love Martin" game. It was fun, wasn't it.
From Amy...(November 26, 2001)
My story starts way back in February when I first saw Bells are Ringing in Stamford, CT (I live in Fairfield, CT) before it went to Broadway. I thought that Martin did a fabulous job and he was very funny! (Even though I was seeing it for Marc Kudisch :) So, I decided to see it in NYC last May. Or was it June? Any way, I was in the second row, which is absolutely fascinating because the actors and actresses look at you...and at the end when they were taking their bows, Marc winked at me! I thought I was going to pass out! When it was all over, we went to the stage exit to catch them all leaving. When Martin came out, he was talking to my Mom for a while, then I talked to him myself about what he was doing next. He wasn't sure, but he was real polite. (After I was done talking to him, Marc came out! He was soooo friendly! He waited till the whole crowd was gone till he left. I was the last one to meet him, so I got to talk to him without feeling guilty of getting everyone else behind me angry :)
From Jessica...(June 13, 2005)
Hi. I was at your site about Martin Moran, and I have a "fan experience" to share with you. First off, I'd just like to say that Marty is my Grandmother's best friends' son. Very confusing, but it's quite nice to know that I am somehow sort-of related to him.
Anyway, I went to his book reading in Boston of "The Tricky Part." He talked for about an hour, and I bought the book, and he autographed it for me. I went with my grandmother, mother, and aunt, and we had a nice chat with him beforehand. He said that he remembered me when I was 5, the last time he saw me. I'm now 15, so it's quite a span of time. He is the nicest man I think I've ever met. His book reading was very interesting, and he kept my attention, which is quite hard for most people. He was enthusiastic, fun, and entertaining, which is hard, considering the topic of which he was talking about. I just thought I should share this "fan experience" with you.
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Thirsty? Don't worry, we have plenty of the infamous Nuka-Cola to go around! This official Fallout 76 Nuka-Cola Pin Badge Set is bursting with 9 colourful badges themed from the iconic fizzy drink of the Fallout franchise. These quirky badges are perfect for customising bags, jackets and loads more. They also come packaged in a fridge-style gift box which opens to reveal the badges in all their glory.


As a Category 1 Responder, Worcestershire County Council (WCC) plays a critical role in any emergency response. We provide a wide range of support functions that are likely to be called upon to assist the emergency services during an emergency (e.g. social services and highways) and crucially exercise a community leadership role.
The West Mercia Community Risk Register has been created to provide public information about hazards identified which could potentially have an impact upon the West Mercia Police Force Area.
The National Risk Register provides details of the risk displayed in the Risk Matrix and what actions are implemented to mitigate their impacts.
The Community Risk Register is focused on the local issues in detail and the National Risk Register looks at the generic risks that affect the whole of the UK.


Activision's marketing machine powers onwards as we near the release of helicopter-hating open-world action title Prototype 2, due out on the 24th of April on Xbox 360 and PS3. There's now a live-action short film thingy, every bit as ludicrously over the top as the game itself.
New protagonist James Heller's tragedy-fueled motivation gets some spotlight, and it really makes me hopeful that Prototype 2's story will be more than just an excuse to punch things with meaty hammer-hands and Hulk-smash tanks with their own turrets. Former protagonist Alex Mercer's in there as well, claws and all. And… well, yeah: just go watch it for yourself. It's beyond the break.


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La classe Ruler est une classe de porte-avions d'escorte construite aux États-Unis durant la Seconde Guerre mondiale et cédée à la Royal Navy dans le cadre du programme Prêt-bail.

Après la guerre, certains ont été démolis et d'autres ont subi des modifications pour une reconversion en navire marchand (les derniers ont été démolis dans les années 1970).

Conception
Ces navires étaient plus grands et possédaient une plus grande capacité de transport d'aéronef de tous les porte-avions d'escorte américains construits jusqu'à présent. Contrairement à la classe Attacker, ces navires n'étaient pas d'anciens navires marchands reconvertis. Ils avaient une longueur hors-tout de 150 mètres, un maître-bau de 21,2 mètres, un tirant d'eau de 7,8 mètres et un déplacement de  tonnes. Ils étaient propulsés par une hélice, deux chaudières Foster Wheeler de  chevaux et une turbine à vapeur Allis-Chalmers de  chevaux, propulsant le navire à 16,5 nœuds (31 km/h) et transportant  de gazole. Leur équipage est composé de 646 hommes.

Ils étaient composés d'un pont d'envol en bois recouvert de plaques d'acier doux de 137,16 x 24,38 mètres, de 9 brins d'arrêt réglés à 9 tonnes à  et une catapulte H4C hydraulique. Les avions et les  d'essence d'aviation étaient stockés dans un hangar de 79,24 x 18,89 x 5,48 mètres, situé sous la plate-forme de vol. Son armement comprenait 2 canons de 5 USN Mk 12, 8 mitrailleuses double 40 mm Bofors, 14 mitrailleuses double 20 mm Oerlikon et 7 mitrailleuses 20 mm Oerlikon. Ils pouvaient accueillir 24 avions, dont des Grumman F4F Wildcat, des Chance Vought F4U Corsair ou Hawker Hurricane et des Bombardier-torpilleurs Fairey Swordfish ou des Grumman TBF Avenger.

Navires de la classe

Premier groupe

Deuxième groupe

   (torpillé  par l'U-354, à l'ouest du Cap Nord)

  (torpillé le  par l'U-1172, dans l'estuaire de la Clyde).
  : Destiné à la lutte anti-sous-marine.
  : Destiné aux opérations terrestres.
 Tous les autres ont été principalement utilisés pour le transport d'aéronef avec une capacité d'appuis aérien rapproché supplémentaire.

Références

Voir aussi

Article connexe
 Aviation navale

Bibliographie

Porte-avions d'escorte de l'US Navy de la Seconde Guerre mondiale
Classe Bogue
Classe de porte-avions de la Royal Navy


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