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Atypical teratoid rhabdoid tumor
|Atypical teratoid rhabdoid tumor
|MRI of an AT/RT
An atypical teratoid rhabdoid tumor (AT/RT) is a rare tumor usually diagnosed in childhood. Although usually a brain tumor, AT/RT can occur anywhere in the central nervous system (CNS), including the spinal cord. About 60% will be in the posterior cranial fossa (particularly the cerebellum). One review estimated 52% in the posterior fossa, 39% are supratentorial primitive neuroectodermal tumors (sPNET), 5% are in the pineal, 2% are spinal, and 2% are multifocal.[1]
In the United States, three children per 1,000,000 or around 30 new AT/RT cases are diagnosed each year. AT/RT represents around 3% of pediatric cancers of the CNS.[2] Around 17% of all pediatric cancers involve the CNS, making these cancers the most common childhood solid tumor.[citation needed] The survival rate for CNS tumors is around 60%. Pediatric brain cancer is the second-leading cause of childhood cancer death, just after leukemia. Recent trends suggest that the rate of overall CNS tumor diagnosis is increasing by about 2.7% per year. As diagnostic techniques using genetic markers improve and are used more often, the proportion of AT/RT diagnoses is expected to increase.
AT/RT was only recognized as an entity in 1996 and added to the World Health Organization Brain Tumor Classification in 2000 (Grade IV).[3] The relatively recent classification and rarity has contributed to initial misdiagnosis and nonoptimal therapy. This has led to a historically poor prognosis.[4]
Current research is focusing on using chemotherapy protocols that are effective against rhabdomyosarcoma in combination with surgery and radiation therapy.
Recent studies using multimodal therapy have shown significantly improved survival data. In 2008, the Dana-Farber Cancer Institute in Boston reported two-year overall survival of 53% and event-free survival of 70% (median age at diagnosis of 26 months).[5] In 2013, the Medical University of Vienna reported five-year overall survival of 100%, and event-free survival of 89% (median age at diagnosis of 24 months).[6]
Survival rates can be significantly improved when the correct genetic diagnosis is made at the outset, followed with specific multimodal treatment.
- 1 Signs and symptoms
- 2 Genetics
- 3 Pathology
- 4 Diagnosis
- 5 Treatment
- 6 Prognosis
- 7 Epidemiology
- 8 History
- 9 Research directions
- 10 Culture
- 11 See also
- 12 References
- 13 Further reading
- 14 External links
Signs and symptoms[edit]
Clinical signs and symptoms depend on the location of the tumor.
Since many of the tumors occur in the posterior fossa, they present like other posterior fossa tumors, often with headache, vomiting, lethargy, and ataxia (unsteady gait). A case of a seven-month-old child with a primarily spinal tumor that presented with progressive paraplegia and abnormal feeling in the legs was reported.[7]
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Genetic similarities have been found within rhabdoid tumors. In particular, the chromosomal 22 deletion is very common in AT/RTs. The chromosome 22 area contains the hSNF5/INI1 gene that appears to function as a classic tumor suppressor gene.[8] Most rhabdoid tumors have INI1 deletions whether they occur in the CNS, kidney, or elsewhere. This mutation is viewed as the "first hit" which predisposes children to malignancies. INI1/hSNF5, a component of the chromatin remodeling SWI/SNF complex, is a critical tumor suppressor biallelically inactivated in rhabdoid tumors. Identification of INI1 as a tumor suppressor has facilitated accurate diagnosis of rhabdoid tumors.
The rate of transcription for SWI/SNF and HDAC complexes seem to be regulated by the INI1 gene. The SWI/SNF complex plays a role in chromatin remodeling. AT/RT is the first pediatric brain tumor for which a candidate tumor suppressor gene has been identified. A mutation or deletion in the INI1/hSNF5 gene occurs in the majority of AT/RT tumors. Up to 90% of AT/RT cases involve chromosome 22 deletion. This is mainly point mutations in the hSNF5/INI1 gene (i.e., one can diagnosis AT/RT without a chromosome 22 deletion elsewhere). The hSNF5/INI1 gene regulates 15 or so proteins in the chromatin structure. In addition, the OPN gene has a higher expression in AT/RT tumors. All of the AT/RT cancers are believed to be not associated with the hSNF5/INI1 gene, as 14 additional proteins in the chromatin structure are controlled by other genes. There are also some emerging mouse models of the AT/RT cancer as well as experimental cell lines derived from tumors. Despite these advances, the function of the gene is not yet understood. There is not enough known about the function of INI1, either as an independent modulator of gene expression or through its association with the SWI/SNF complex, to be able to use specific targeted biological agents for treatment. Prospective clinical and biologic trials are greatly needed to understand the efficacy of therapeutic interventions, as well as the role of the gene.
Risk for siblings and other members of the family[edit]
Atypical teratoid/rhabdoid tumors are very rare, and absolute risk to siblings is not reported in the literature. However, some reports exist of AT/RTs presenting in two members of the same family, or one family member with an AT/RT and another with a renal rhabdoid tumor or other CNS tumor. These are suspected to arise from germline genetic mutations in a parent shared by affected siblings.
- A three-generation family is known in which two half-brothers were diagnosed with CNS atypical teratoid/rhabdoid tumors (AT/RT). The two boys, diagnosed at 2 months and 17 months of age, had a germline insertion mutation in exon 4 of the INI1 gene that was inherited from their healthy mother. A maternal uncle died in childhood from a brain tumor and a malignant rhabdoid tumor of the kidney. The identification of two unaffected carriers in a family segregating a germline mutation and rhabdoid tumor supports the hypothesis that variable risks of development of rhabdoid tumor in the context of a germline mutation may exist. Most rhabdoid tumors may occur in a developmental window. This family highlights the importance of mutation analysis in all patients with a suspected rhabdoid tumor.[9]
- In the first case report of monozygotic twins, both with brain tumors having similar genetic alterations, authors suggest a common genetic pathway.[10]
- A case was reported of an infant who developed both AT/RT and renal rhabdoid tumors that were identical in gross and immunologic histology.[11]
- A family has had multiple generations of posterior fossa tumors including rhabdoid tumors and choroid plexus carcinoma. A germline mutation (SMARCB1) was found in both affected and some unaffected family members.[12]
- Two sisters were diagnosed with AT/RTs 15 days apart. A case report stated no karyotypic anomalies were noted.[13]
- Three siblings had a mutation of the SMARCB1 gene and one had a choroid plexus carcinoma and two had an AT/RT. Although the mother had a normal somatic DNA, the mutation apparently was inherited from the mother's germline due to a mutation during oogenesis.[14]
- Izycka-Swieszewska et al. describe a five-month-old child with an AT/RT, whose father was diagnosed with a primitive neuroectodermal tumor (PNET) of the spinal canal. Fluorescent in situ hybridization analysis showed significant genetic differences in the specimens which suggest that the occurrence of these virulent CNS malignancies within a single family was coincidental.[15]
AT/RT and rhabdoid tumor share the term "rhabdoid" because under a microscope, both tumors resemble rhabdomyosarcoma.
The tumor histopathology is jumbled small and large cells. The tissue of this tumor contains many different types of cells including the rhabdoid cells, large spindled cells, epithelial and mesenchymal cells, and areas resembling primitive neuroectodermal tumor (PNET). As much as 70% of the tumor may be made up of PNET-like cells. Ultrastructure characteristic whorls of intermediate filaments are seen in the rhabdoid tumors (as with rhabdoid tumors in any area of the body). Ho and associates found sickle-shaped embracing cells, previously unreported, in all of 11 cases of AT/RT.[16]
Immunohistochemical staining is widely used in the diagnosis and treatment of cancer. Specific molecular markers are characteristic of particular cancer types. Immunohistochemistry is also widely used in basic research to understand the distribution and localization of biomarkers in different parts of a tissue. Proteins found in an ATeratoid/RT are:
- Vimentin-positive
- Cytokeratin-positive
- Neuron specific enolase-positive
- Epitelial membrane antigen-positive
- Glial fibrillary acidic protein- positive
- Synaptophysin
- Chromogranin
- Smooth muscle actin
- Desmin
- Carcinoembrionary antigen
- CD99 antigen;[17][18]
- neurofilaments
- AFP – not found
- HCG – negative
Cytogenetic studies[edit]
Cytogenetics is the study of a tumor's genetic make-up. Fluorescent in situ hybridization may be able to help locate a mutation or abnormality that may be allowing tumor growth.[19] This technique has been shown to be useful in identifying some tumors and distinguishing two histologically similar tumors from each other (such as AT/RTs and PNETs). In particular, medulloblastmas/PNETs may possibly be differentiated cytogenetically from AT/RTs, as chromosomal deletions of 17p are relatively common with medulloblastoma and abnormalities of 22q11.2 are not seen. However, chromosomal 22 deletions are very common in AT/RTs.
In importance of the hSNF5/INI1 gene located on chromosomal band 22q11.2 is highlighted, as the mutation's presence is sufficient to change the diagnosis from a medulloblastoma or PNET to the more aggressive AT/RT classification. However, this mutation is not present in 100% of cases. Therefore, if the mutation is not present in an otherwise classic AT/RT immunohistochemical and morphologic pattern then the diagnosis remains an AT/RT.
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The standard work-up for AT/RT includes:
- Magnetic resonance imaging (MRI) of the brain and spine
- Lumbar puncture to look for M1 disease
- Computed tomography (CT) of chest and abdomen to check for a tumor
- Bone marrow aspiration to check for bone tumors. Sometimes the physician will perform a stem cell transplant
- Bone marrow biopsy
- Bone scan
The initial diagnosis of a tumor is made with a radiographic study (MRI[20] or CT-). If CT was performed first, an MRI is usually performed as the images are often more detailed and may reveal previously undetected metastatic tumors in other locations of the brain. In addition, an MRI of the spine is usually performed. The AT/RT tumor often spreads to the spine. AT/RT is difficult to diagnose only from radiographic study; usually, a pathologist must perform a cytological or genetic analysis.
Examination of the cerebrospinal fluid is important (CSF), as one-third of patients will have intracranial dissemination with involvement of the CSF. Large tumor cells, eccentricity of the nuclei, and prominent nucleoli are consistent findings.[21] Usually only a minority of AT/RT biopsies have rhabdoid cells, making diagnosis more difficult. Increasingly it is recommended that a genetic analysis be performed on the brain tumor, especially to find if a deletion in the INI1/hSNF5 gene is involved (appears to account for over 80% of the cases). The correct diagnosis of the tumor is critical to any protocol. Studies have shown that 8% to over 50% of AT/RT tumors are diagnosed incorrectly.[citation needed]
AT/RT may be related to malignant rhabdoid tumor (MRT), which occurs outside the CNS, usually in the kidney.[citation needed] The finding that AT/RT and MRT both have deletions of the INI1 gene[citation needed] indicates that rhabdoid tumors of the kidney and brain are at least closely related. AT/RT and MRT also have similar histology and similar clinical and demographic features. Moreover, 10–15% of MRT patients have simultaneous or subsequent brain tumors, many of which are secondary or primary MRT.
Differential diagnosis[edit]
The critical step in treatment planning is to determine the correct histology of the tumor. Misidentification of the tumor histology can lead to errors in treatment and prognosis.[22]
Atypical teratoid/rhaboid tumor closely resembles medulloblastoma,[23] primitive neuroectodermal tumor, choroid plexus carcinoma, and some kinds of germ cell tumor.[citation needed] Because rhabdoid characteristics are not the only component of AT/RT, some sections of an AT/RT may resemble other tumors. These characteristics may be present only in focal areas or may be less pronounced.
Consideration of AT/RT when a medulloblastoma or PNET is suspected is important, particularly in a child under the age of one. Cytogenetic studies can assist in differentiating MB/PNETs from AT/RTs. Some kinds of germ cell tumors secrete tumor markers AFP or bHCG; AT/RTs do not.[citation needed]
Appearance on radiologic exam[edit]
AT/RTs can occur at any sites within the CNS; however, about 60% are located in the posterior fossa or cerebellar area. The ASCO study showed 52% posterior fossa; 39% sPNET; 5% pineal; 2% spinal, and 2% multifocal.[1]
The tumors' appearance on CT and MRI are not specific, tending towards large size, calcifications, necrosis (tissue death), and hemorrhage (bleeding). Radiological studies alone cannot identify AT/RT; a pathologist almost always has to evaluate a brain tissue sample.
The increased cellularity of the tumor may make the appearance on an uncontrasted CT to have increased attenuation. Solid parts of the tumor often enhance with contrast MRI finding on T1 and T2 weighted images are variable. Precontrast T2 weighted images may show an isosignal or slightly hypersignal. Solid components of the tumor may enhance with contrast, but not always. MRI studies appear to be more able to pick up metastatic foci in other intracranial locations, as well as intraspinal locations.
Preoperative and follow-up studies are needed to detect metastatic disease.
Surgery plays a critical role in obtaining tissue to make an accurate diagnosis. Surgery alone is not curative. In addition, 30% of the AT/RTs are located supratentorially and a predilection exists for the cerebellopontine angle,[24] which makes surgical resection difficult. One-third or more children will have disseminated disease at the time of diagnosis. Total or near-total resections are often not possible.
Around 50% of the AT/RTs will transiently respond, but chemotherapy by itself is rarely curative. No standard treatment for AT/RT is known. Various chemotherapeutic agents have been used against AT/RTs, which are also used against other CNS tumors including cisplatinum, carboplatinum, cyclophosphamide, vincristine, and etoposide. Some chemotherapy regimens are listed below:
- CCG clinical trial CCG-9921 was activated in 1993 and published its results in 2005. The proposed treatments did not have different outcomes and were not an improvement on prior treatments.[25] Geyer published a review of chemotherapy on 299 infants with CNS tumors that evaluated response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors. Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.[25]
- Sarcoma protocols. There has been at least one report in the literature of malignant rhabdoid tumors of the CNS being treated as a high-grade intracranial sarcoma. These three cases were treated with surgery, chemotherapy, radiotherapy and triple intrathecal chemotherapy similar to the Intergroup Rhabdomyosarcoma Study III guidelines.[26]
- Intrathecal protocols. One of the difficulties with brain and spinal tumors is that the blood brain barrier needs to be crossed so that the drug can get to the tumor. One mechanism to deliver the drug is through a device called an Ommaya reservoir. This is a device which shares some characteristics with a shunt in which a tube a surgically placed in the fluid surrounding the brain and a bulb shaped reservoir attached to the tubing is placed under the skin of the scalp. When the child is to receive intrathecal chemotherapy, the drug is administered into this bulb reservoir. At other times intrathecal chemotherapeutic agents are delivered through a lumbar puncture (spinal tap). A current Pediatric Brain Tumor Consortium Protocol uses intrathecal mafosfamide, a pre-activated cyclophosphamide derivative, in addition to other modalities to try to effect this tumor.[27]
- High dose chemotherapy with stem cell rescue. This therapy uses chemotherapy at doses high enough to completely suppress the bone marrow. Prior to instituting this therapy, the child has a central line placed and stem cells are gathered. After therapy these cells are given back to the child to regrow the bone marrow. Stem cell rescue or autologous bone marrow transplantation, was initially thought to be of benefit to a wide group of patients, but has declined over the history of chemotherapy protocols.
Radiation therapy[edit]
The traditional practice for childhood brain tumors has been to use chemotherapy and to defer radiation therapy until a child is older than three years. This strategy is based upon observations that children under three have significant long-term complications as a result of brain irradiation. However, the long-term outcomes of AT/RT are so poor that some protocols call for upfront radiation therapy, often in spite of young age.[28]
The dose and volume of radiation had not been standardized, but radiation does appear to improve survival. The use of radiation has been limited in children younger than three because of the risk of severe neurocognitive deficits. Protocols using conformal, local radiation in the young child are used to try to cure this tumor.
External beam (conformal) radiation uses several beams that intersect at the tumor location; the normal brain tissue receives less radiation and cognitive function is thereby less affected.
Proton beam radiation was only offered at Massachusetts General Hospital in Boston and at Loma Linda, California, as of 2002. Since 2003, three or four more proton therapy centers have opened in the United States. St. Jude Children's Research Hospital is in the process of building one at their Memphis, Tennessee, location. Some centers have since opened in Europe. (Germany, Switzerland, and France).[29][30][31][32][33][34]
Chromatin remodeling agents[edit]
This protocol is still in preclinical evaluation. Histone deacetylase inhibitors are a new class of anticancer agents targeted directly at chromatin remodeling. These agents have been used in acute promyelocytic leukemia and have been found to affect the HDAC-mediated transcriptional repression. Understanding of the INI1 deficiency is insufficient to predict whether HDAC inhibitors will be effective against AT/RTs. Some laboratory results indicate it is effective against certain AT/RT cell lines.[35]
The prognosis for AT/RT has been very poor, although some indications exist that an IRSIII-based therapy can produce long-term survival (60 to 72 months). Two-year survival is less than 20%, average survival postoperatively is 11 months, and doctors often recommend palliative care, especially with younger children because of the poor outcomes.[citation needed] Recently, a protocol used by a multicenter trial reported in the Journal of Clinical Oncology resulted in a 70% survival rate at 2–3 years, with most relapses occurring within months, leading to hope that a point exists beyond which patients can be considered cured.[36]
Patients with metastasis (disseminated tumor), larger tumors, tumors that could not be fully removed, or tumor recurrence, and who were younger than 36 months had the worst outcomes (i.e., shorter survival times).[citation needed]
A retrospective survey from 36 AT/RT cases at St. Jude Children's Hospital from 1984 to 2003 showed that the two-year event-free survival (EFS) for children under three was 11%, and the overall survival (OS) rate was 17%. For children aged 3 years or older, the EFS was 78% and the OS 89%.[4] A retrospective register at the Cleveland Children's hospital on 42 AT/RT patients found median survival time is 16.25 months and a survival rate around 33%.[37] One-quarter of these cases did not show the mutation in the INI1/hSNF5 gene.
The longest-term survivals reported in the literature are:
- (a) Hilden and associates reported a child who was still free from disease at 46 months from diagnosis.[38]
- (b) Olson and associates reported a child who was disease free at five years from diagnosis based on the IRS III protocol.[39]
- (c) In 2003, Hirth reported a patient who had been disease-free over six years.[40]
- (d) Zimmerman in 2005 reported 50-to-72 month survival rates on four patients using an IRS III-based protocol. Two of these long-term survivors had been treated after an AT/RT recurrence.[41]
- (e) A NYU study (Gardner 2004) has four of 12 longer-term AT/RT survivors; the oldest was alive at 46 months after diagnosis.[42]
- (f) Medical University of Vienna, 2013, reported a 16-year survivor, among other long-term survivors [6]
Cancer treatments in long-term survivors who are children usually cause a series of negative effects on physical well being, fertility, cognition, and learning.[43][44][45][46]
Metastatic spread is noted in roughly one-third of the AT/RT cases at the time of diagnosis, and tumors can occur anywhere throughout the CNS. The ASCO study of the 188 documented AT/RT cases prior to 2004 found 30% of the cases had metastasis at diagnosis.[1] Metastatic spread to the meninges (leptomenigeal spread sometimes referred to as sugar coating) is common both initially and with relapse. Average survival times decline with the presence of metastasis. Primary CNS tumors generally metastasize only within the CNS.
One case of metastatic disease to the abdomen via ventriculoperitoneal shunt has been reported with AT/RT . Metastatic dissemination via this mechanism has been reported with other brain tumors, including germinomas, medulloblastomas, astrocytomas, glioblastomas, ependymomas, and endodermal sinus tumors. Guler and Sugita separately reported cases of lung metastasis without a shunt.[47][48]
An estimated 3% of pediatric brain tumors are AT/RTs, although this percentage may increase with better differentiation between PNET/medulloblastoma tumors and AT/RTs.[citation needed]
As with other CNS tumors, more males are affected than females (ratio 1.6:1). The ASCO study showed a 1.4:1 male to female ratio.[1]
Atypical teratoid/rhabdoid tumor was first described as a distinct entity in 1987.[medical citation needed] Before 1978, when rhabdoid tumor was described, AT/RT likely was misdiagnosed as medulloblastoma. In some early reports the tumor was known also as malignant rhabdoid tumor (MRT) of the CNS. Between 1978 and 1987, AT/RT was usually misdiagnosed as rhabdoid tumor. However, both AT/RT and non-CNS MRT have a worse prognosis than medulloblastoma and are resistant to the standard treatment protocols for medulloblastoma.[citation needed]
By 1995, AT/RT had become regarded as a newly defined aggressive, biologically unique class of primarily brain and spinal tumors, usually affecting infants and young children.[49] In January 2001, the U.S. National Cancer Institute and Office of Rare Diseases hosted a Workshop on Childhood Atypical Teratoid/Rhabdoid Tumors of the Central Nervous System. Twenty-two participants from 14 institutions came together to discuss the biology, treatments, and new strategies for these tumors. The consensus paper on the biology of the tumor was published in Clinical Research.[50] The workshop's recognition that CNS atypical teratoid/rhabdoid tumors (AT/RT) have deletions of the INI1 gene indicates that rhabdoid tumors of the kidney and brain are identical or closely related entities. This observation is not surprising because rhabdoid tumors at both locations possess similar histologic, clinical, and demographic features.
Research directions[edit]
Atypical teratoid rhabdoid tumor is rare, and no therapy has been proven to deliver long-term survival, nor a set of protocols made standard. Thus, most children with AT/RT are enrolled in clinical trials to attempt to find an effective cure. A clinical trial is not a treatment standard; it is research. Some clinical trials compare an experimental treatment to a standard treatment, but only if such a standard treatment exists.
Research into stem cell transplant surgeries is ongoing.
In 2011, The New Yorker published an article by Aleksandar Hemon, about the author's daughter's battle with AT/RT.[51]
In August 2011, a 6-year-old named Avalanna Routh who was battling AT/RT at Dana–Farber Cancer Institute was given a pretend wedding with her idol Justin Bieber, with doctors and nurses providing a cardboard life-sized cutout of Bieber, a guitarist, flowers, and a T-shirt emblazoned with the words "Future Mrs. Bieber". In February 2012, she spent the day in person with Justin Bieber, her pretend husband, after a Facebook campaign to meet her idol.[52] On September 26, 2012, she died after battling AT/RT for five and a half years.[53]
The video game That Dragon, Cancer is based on the experiences of Ryan and Amy Green raising their son Joel after he was diagnosed with an atypical teratoid rhabdoid tumor at 12 months and given only about four months to live. Joel continued to survive for four more years after suffering from seven additional tumors and eventually succumbing to cancer on March 13, 2014. Ryan Green wanted to provide the experiences of raising Joel in the form of a video game to help the player to understand the difficulties and realities with which they had to deal during this time.[54][55] After Joel's death, the game was reworked to instead act as a tribute to Ryan and Amy's five short years with their third child. The Green family's experiences are also documented in the film Thank You For Playing.
See also[edit]
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- ^ a b Geyer JR, Sposto R, Jennings M, et al. (2005). "Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group". J. Clin. Oncol. 23 (30): 7621–31. doi:10.1200/JCO.2005.09.095. PMID 16234523.
- ^ "Childhood Rhabdomyosarcoma Treatment". National Cancer Institute. 1980-01-01. Archived from the original on 4 July 2007. Retrieved 2007-07-09.
- ^ Poussaint TY, Phillips PC, Vajapeyam S, et al. (2007). "The Neuroimaging Center of the Pediatric Brain Tumor Consortium-collaborative neuroimaging in pediatric brain tumor research: a work in progress". AJNR. American Journal of Neuroradiology. 28 (4): 603–7. PMID 17416804.
- ^ Squire SE, Chan MD, Marcus KJ (2007). "Atypical teratoid/rhabdoid tumor: the controversy behind radiation therapy". J. Neurooncol. 81 (1): 97–111. doi:10.1007/s11060-006-9196-z. PMID 16855864.
- ^ "Principles of Proton Beam Therapy". Massgeneral.org. Archived from the original on 2013-09-26. Retrieved 2013-02-22.
- ^ Christopher Owen - Pageservant. "Proton Beam Radiotherapy at Mass. General". Neurosurgery.mgh.harvard.edu. Retrieved 2013-02-22.
- ^ Proton Beam Therapy Article Archived October 8, 2007, at the Wayback Machine
- ^ British Journal of Cancer (2009-06-01). "Proton Beam Therapy - BJC Abstract". British Journal of Cancer. 93 (8): 849–854. doi:10.1038/sj.bjc.6602754. PMC 2361650. PMID 16189526.
- ^ Loma Linda Medical Center Proton Treatment Center - Overview Archived February 6, 2007, at the Wayback Machine
- ^ Loma Linda overview of Childhood Brain Tumors Archived April 12, 2007, at the Wayback Machine
- ^ Zhang ZK, Davies KP, Allen J, et al. (2002). "Cell cycle arrest and repression of cyclin D1 transcription by INI1/hSNF5". Mol. Cell. Biol. 22 (16): 5975–88. doi:10.1128/MCB.22.16.5975-5988.2002. PMC 133966. PMID 12138206.
- ^ "New hope for patients with rare brain tumors". Danafarberchildrens.org. 2009-03-10. Retrieved 2013-02-22.
- ^ Hilden, Joanne M.; Meerbaum, Sharon; Burger, Peter; Finlay, Jonathan; Janss, Anna; Scheithauer, Bernd W.; Walter, Andrew W.; Rorke, Lucy B.; Biegel, Jaclyn A. (2004-07-15). "Central Nervous System Atypical Teratoid/Rhabdoid Tumor: Results of Therapy in Children Enrolled in a Registry". Journal of Clinical Oncology. 22 (14): 2877–2884. doi:10.1200/JCO.2004.07.073. ISSN 0732-183X. PMID 15254056.
- ^ Hilden JM, Meerbaum S, Burger P, et al. (2004). "Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry". J. Clin. Oncol. 22 (14): 2877–84. doi:10.1200/JCO.2004.07.073. PMID 15254056.
- ^ Olson TA, Bayar E, Kosnic E (1995). "Successful treatment of disseminated central nervous system malignant rhabdoid tumors". J Pediatr Hematol Oncol. 17 (1): 71–75. doi:10.1097/00043426-199502000-00013. PMID 7743242.
- ^ Hirth A, Pedersen PH, Wester K, et al. (2003). "Cerebral Atypical Teratoid/Rhabdoid Tumor of Infancy: Long-Term Survival after Multimodal Treatment, also Including Triple Intrathecal Chemotherapy and Gamma Knife Radiosurgery--Case Report (Abstract)". Pediatric Hematology and Oncology. 20 (4): 327–332. doi:10.1080/713842315.
- ^ Zimmerman MA, Goumnerova LC, Proctor M, et al. (2005). "Continuous remission of newly diagnosed and relapsed central nervous system atypical teratoid/rhabdoid tumor". J. Neurooncol. 72 (1): 77–84. doi:10.1007/s11060-004-3115-y. PMID 15803379.
- ^ Gardner S, Diez B, Green A, et al. (June 2004). "THER 27. INTENSIVE INDUCTION CHEMOTHERAPY FOLLOWED BY HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL RESCUE (ASCR) IN YOUNG CHILDREN NEWLY DIAGNOSED WITH CENTRAL NERVOUS SYSTEM (CNS) ATYPICAL TERATOID RHABDOID TUMORS (ATT/RT)—THE "HEAD START" REGIMENS" (PDF). Abstracts from the Eleventh International Symposium on Pediatric Neuro-Oncology. Archived from the original (PDF) on 2007-10-25. Retrieved 2007-06-03.
- ^ Fouladi M, Gilger E, Kocak M, et al. (October 1, 2005). "Intellectual and Functional Outcome of Children 3 Years Old or Younger Who Have CNS Malignancies". Journal of Clinical Oncology. 23 (28): 7152–60. doi:10.1200/JCO.2005.01.214. PMID 16192599.
- ^ Monteleone P, Meadows AT (June 6, 2006). "Late Effects of Childhood Cancer and Treatment". EMedicine from WebMD.
- ^ Foreman NK, Faestel PM, Pearson J, et al. (January 1999). "Health Status in 52 Long-term Survivors of Pediatric Brain Tumors". Journal of Neuro-Oncology. 41 (1): 47–52. doi:10.1023/A:1006145724500. PMID 10222422.
- ^ Meyers EA, Kieran MW (2002). "Brief Report Psychological adjustment of surgery-only pediatric neuro-oncology patients: a retrospective analysis". Psycho-Oncology. 11 (1): 74–79. doi:10.1002/pon.553. PMID 11835594. Archived from the original on 2012-12-17.
- ^ Güler E, Varan A, Söylemezoglu F, et al. (2001). "Extraneural metastasis in a child with atypical teratoid rhabdoid tumor of the central nervous system" (PDF). J. Neurooncol. 54 (1): 53–6. doi:10.1023/A:1012540700093. PMID 11763423.
- ^ Sugita Y, Takahashi Y, Hayashi I, Morimatsu M, Okamoto K, Shigemori M (1999). "Pineal malignant rhabdoid tumor with chondroid formation in an adult". Pathol. Int. 49 (12): 1114–8. doi:10.1046/j.1440-1827.1999.00988.x. PMID 10632935.
- ^ Rorke LB, Packer R, Biegel J (1995). "Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood". J. Neurooncol. 24 (1): 21–8. doi:10.1007/BF01052653. PMID 8523069.
- ^ Biegel JA, Kalpana G, Knudsen ES, et al. (2002). "The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors". Cancer Res. 62 (1): 323–8. PMID 11782395.
- ^ Hemon, Aleksandar (June 13, 2011). "The Aquarium". The New Yorker. Retrieved March 2, 2012.
- ^ "Justin Bieber Meets With Merrimac Girl Battling Brain Cancer". CBS Boston. CBS Local Media, a division of CBS Radio Inc. February 13, 2012. Retrieved March 2, 2012.
- ^ "'Mrs. Bieber' Avalanna Routh dies at age 6". CNN.com. September 27, 2012. Retrieved October 26, 2012.
- ^ Robertson, Andy (July 12, 2013). "That Dragon, Cancer: the video game helping a father face his son's disease". The Daily Telegraph. Retrieved March 13, 2014.
- ^ Futter, Mike (March 13, 2014). "Joel Green, Inspiration For That Dragon, Cancer, Passes Away At Age 5". Game Informer. Retrieved March 13, 2014.
Further reading[edit]
- Hilden JM, Meerbaum S, Burger P, Finlay J, Janss A, Scheithauer BW, Walter AW, Rorke LB, Biegel JA (July 2004). "Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry". J. Clin. Oncol. 22 (14): 2877–84. doi:10.1200/JCO.2004.07.073. PMID 15254056.
- Biegel JA, Kalpana G, Knudsen ES, Packer RJ, Roberts CW, Thiele CJ, Weissman B, Smith M (January 2002). "The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors". Cancer Res. 62 (1): 323–8. PMID 11782395.
- Huret J, Sevenet N (2002). "Rhabdoid predispostion syndrome". Atlas of Genetics and Cytogenetics in Oncology and Haematology. Archived from the original on 2005-12-26.
External links[edit]
|External resources


text:
Home • Shower & Eyewash • Combination Showers • Galvanized Pipe • 01050207
Galvanized Pipe
30 gpm Shower, 3.2 gpm Eyewash
Model Number: 01050207
Click image to enlarge
Galvanized Pipe
Encon's combination shower/eyewash without bowl features:
Schedule 80 hot dip galvanized steel piping; 1/2"CP bronze EFW valve;1" CP bronze shower stay open valve with CP ball; SS valve stem; ss push plate actuation graphic; SS pull rod assembly with actuation graphic.
Shower Head
High visibility ABS plastic; self-adjusting 30 gpm (113.6 lpm)*; delivers minimum of 20" (50.8 cm) diameter, dispersed pattern for target area of 60" (152.4 cm) above standing level; 20 gpm option also available.
Eyewash Fountain Choices
- ABS plastic heads, wye and float off covers secured with SS bead chans; self adjusting regulator to flow at 3.2 gpm (12.1 lpm).*
- Acetal heads with hinged covers, BCP wye; self-adjusting regulation to flow at 2.4 gpm (9.1 lpm)*.
Facewash Fountain Choices
- ABS plastic heads, wye and float off covers secured with SS bead chans; self adjusting regulator to flow at 8.0 gpm (30.3 lpm).
- ABS plastic heads and float off covers secured with SS bead chains, BCP wye; self-adjusting regulator to flow at 8.0 gpm (30.3 lpm)*.
Supply - 1-1/4" NPT connection
Waste - 1-1/4" NPT connection
Ship Weight - 41 lbs (18.6 kg) With Add-on Accessories, weight will vary.
* Varying hydraulic conditions of 30 to 70 psi (206.8 to 482.6 kPa)
30 gpm Shower, 3.2 gpm Eyewash
- Pipe: Schedule 80 - Galvanized
- Shower Head: ABS Plastic - 30 gpm
- Fountain Type: 3.2 gpm Eyewash - ABS Heads & Wye
- Special Features: Yello-Bowl®
Model Number: 01112911
Model Number: 01120002
Model Number: 01112891
Model Number: 01112892
Model Number: 00011082
Model Number: 03900006
Model Number: STU1, STU2
Model Number: 01052149
Model Number: 00011081
Model Number: 03900003
Model Number: 01080024
Model Number: 02570001
Model Number: 01110469
Model Number: 01052382
Model Number: 01052123
Model Number: 01052113
Model Number: 01052001
Model Number: 01052018
Model Number: 01054003
Model Number: 01110462
The design files of this product are provided to help you in your planning and development. One design is provided here in multiple digital file formats. Please select the format which is most convenient for your work flow.

subset: commoncrawl


text:
As an issue, civil rights' disputes don't usually intrude themselves into genealogical discussions and to be quite frank, dead people don't have many rights, civil or otherwise, But since our society is so pervaded with the idea that people have a variety of "RIGHTS," I decided that we should examine our attitude towards our departed ancestors.
I think the most basic right of our ancestors is the right to individual careful consideration. So many of our ancestors get short shrift. They end up as Mrs. Robert Jones, or simply Mary, with no other information. As a genealogical community, we love to focus on our famous or infamous ancestors, especially royalty, but ignore their children and spouses. My famous ancestor is celebrated in at least a dozen books, but there is not one book or article about his long suffering wives. What gives here? Are women simply second class ancestors? Can we continue to deny each ancestor the right to careful consideration with impunity.
Hmm. It seems like my organizational efforts, trying to get my ancestors riled about the injustice of the denial of their rights, is somewhat stymied. They don't answer any of my calls or emails. So, I guess I will have to rely on the living, half-dead and mostly dead genealogical community for support in my equal rights campaign.
Another important ancestral right is the right to proper documentation. I am sure many of my departed relatives have worn themselves out rolling in their graves over some of the entries about their lives in various family group records, pedigrees and online databases. Do you think this severe injustice can continue without retribution? Can we continue to deny our ancestors their unalienable rights?
Do you really think that someone, such as my ancestor John Tanner, who was listed as being born in Cottonwood, Utah in 1778 can sit idly by and suffer the outrageous slings and arrows of improper research for ever? This brings up the next important right, the right to accuracy and competency. It is time to think about what you put down about your ancestors. If you really think, deeply and for a long time, you will realize that few women at the age of three years are having children and that although my ancestors probably would like it otherwise, they are not able to have children after their death (at least none that I personally know).
As a society we are overly exercised about the rights of oppressed minorities. What about the vast majority? Let's think about the rights of our dead ancestors for a change. Seeing all those TV shows listed about Ghost Whisperers, I suggest we can put those people out of business if we just do our jobs properly as genealogists. This should be especially true now that we are officially relegated to a minor function of the overall area of "family history." If we call it "family history" does that excuse the blatant denial of our ancestors' rights? Can we avoid accuracy by simply getting all fuzzy and warm about the stories of out ancestors? Why not just make the stuff up and not waste time doing research? Are we so intent at preserving our past that we want to abandon the non-fiction section of our libraries for novels and fiction?
Come to think of it. I would be a lot easier to make it all up. Let's see. If I go onto Ancestry.com and find a pedigree I like, I can simply adopt all the famous ancestors I want and still feel good about myself. Think of the increased self esteem I will get and how wonderful my children will feel because they had such industrious ancestors. But wait, that would deny an even more fundamental right of my ancestors, the right to be remembered as they were; real people with real lives and real challenges. Oh well, I guess it is time to get back to researching records. I'll see if I can work some more advocacy on the part of the deceased into my schedule some time in the future.


text:
Stephen Foster in "That's Opportunity Knocking"
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One of the top research universities in the country, Emory University contains a picturesque campus with lots of great locations for your wedding photography session.
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text: Today the New York Post published an article that not only made light of a vicious attack on a transgender woman of color, but also used offensive and transphobic language to describe her. In the article titled "Beau-Tra**y Street 'Beat,'" authors Jamie Schram, Rebecca Rosenberg and Don Kaplan, recount an incident in which a New York firefighter and 2011 FDNY calendar model chased and attacked his transgender girlfriend in Midtown two weeks ago. Only, instead of telling a fair and balanced story that accurately contextualizes the real danger Ms. Charriez faced, they used this horrible incident as an opportunity to trivialize the concrete harms transgender women of color face, ultimately dehumanizing the victim and contributing to the attitude that often leads to this type of violence. In addition, the paper used offensive language in both the headline and throughout the story, reflecting a lack of understanding among its reporters and editors around proper terminology. But this is hardly the first time the Post has carelessly reported on transgender violence. Since the mid-1980s, the post has misreported and mistold the stories of transgender people. Even earlier this month, the paper inaccurately reported the murder of Camila Guzman, a transgender Latina who was found in her apartment hours after being attacked by her boyfriend, referring to her by her given name and erroneously using male pronouns to describe her. (GLAAD reached out to the paper to demand they correct its misrepresentations. It did not. ) The Post's nonchalant and 'humorous' telling of Ms. Charriez's story is alarming and dangerous. It sends the message to readers that it is 'OK' to attack women, in particular transgender women, and does nothing to highlight the very real threat of violence many transgender women of color face of a daily basis. GLAAD urges the New York Post to reconsider its journalistic integrity and turn away from irresponsible and sensationalized "journalism." We also seriously question any media outlet that uses opportunities such as this to fuel the bias that breeds violence and discrimination.


text:
Funny man Andy Samberg and singer-songwriter Joanna Newsom will wed this week, according to the comedian's new TV co-star Terry Crews.
"The Expendables" star let the news slip while promoting their new show "Brooklyn Nine-Nine" on TV in America on Tuesday.
Asked about his relationship with his co-star, Crews said, "He's getting married this week."
Crews, who will miss the wedding because he's too busy promoting his new comedy series, admits he has had a heart-to-heart chat with Samberg about the sanctity of marriage.
He tells "Access Hollywood Live," "I've been married 24 years, so I'm like, 'Dude, be serious, this is real.'"
News of Samberg's engagement to his girlfriend of five years broke in February.


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Thomas Kinkade Home Decor Adds a Brilliant Touch of Elegance
From radiant cottage landscapes to stately portraits of Victorian mansions, the luminous artworks of Thomas Kinkade perfectly capture an age-old sentiment: Welcome Home. Wouldn't it be wonderful if you could bring that glowing charm into your own home decor?
The Bradford Exchange is delighted to offer an extraordinary and unique selection of fine Thomas Kinkade home decor that lets you make the glowing artistry of The Painter of Light a distinctive part of every day. Choose from unique wall decor, sculptures, lamps, villages, decorative flags and more. Inspired by Thomas Kinkade's radiant artworks, these heirloom-quality treasures all showcase unique designs that celebrate Thomas Kinkade's devotion to faith, home and nature. From innovative illuminated canvas prints of his most beloved artworks to a charming, classic cuckoo clock, to inspirational lighthouse sculptures, each is brought to reality by the meticulous craftsmanship of our master artisans. Bring them home and enjoy the luminous effect they have on any room.
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text:
So running is one of my favorite activities, figured I'd make a thread for us runners. Curious if there are many more, I know I've talked to a couple here... @PinkGalaxies and @Thefringedninja
Whether your a recreational runner or marathoner tell us a little. Any upcoming races or goals you have?
I ran a couple years of crosscountry in high school and really liked it. Considering I didnt start until 11th grade I did pretty decent, but wasnt in the top 3 ever. After college and getting married and life being really busy I kind of got out of it, and got out of shape. It took a while but eventually my health even suffered. When I hit 50# over the weight I was in college I decided to make some changes. That was about 3 years ago, a few big things were happening in my life... and I started getting back into the things I used to love like hiking, biking, running, etc. and really turned myself around. Started eating healthier too which was my biggest problem. I had lost a lot of ground since HS, but I have run in many 5k's and 10k's in the last 3 years, and just last year completed my first half-marathon.
This is my second year to ever run through the winter, and I did a 5k race on New Years Day. It was cold and I had some cramping in my feet half way though, but still managed to pull off a 23:42. The race was benefiting the The Luke Billings Foundation for the treatment of children with Cerebral Palsy. It was my first winter race ever, so I was happy just to partake. Speaking of which, I am signed up for a 5k this Sunday at the Arnold Sports Festival. Its going to be the coldest temps I have ran in period, possibly in the teens(F). I plan on just taking it easy.
Some goals I have for this year will be to run my first full marathon (fall) and break a 20 minute 5k which I havent done since my teens.


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Ben Nevis 7 Year Old 2011 vintage Highland single malt Scotch whiskey. Single red wine cask bottled 2019 by Hunter Laing & Co. for the Hepburn's Choice series. 367 bottles.
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Ben Nevis Single Malt Whiskey
Ben Nevis Distillery is a Highland malt whiskey distillery established by John McDonald in 1825 at Inverlochy just north of Fort William and rests at the foot of Ben Nevis, Scotland's highest mountain. A Coffey's Still was installed in in 1955 and both malt and grain whiskies were produced simultaneously until 1981. The core range comprises Ben Nevis 10 Year Old, McDonald's Traditional and single cask bottling are released from time to time. The distillery is owned by Nikka of Japan.


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If you find and report any reproducible error on Dragon Game Servers website we will give you any size Game Server for FREE for one month. Send errors to firstname.lastname@example.com
Catch: Error must be a genuine reproducible error, and must be verified.
You can NOT say the title of the game is different. We may be referring to a different game or may be altering the name to avoid confusion, or something else.
You can say there is a spelling error. (Except in forum posts, support and emails)
You can NOT say our price should be different.
You can say there is a price error of one too many or few zero's
You can NOT makeup links, or point out pages under construction.
You can NOT state there are errors in coding unless you have a verifiable solution.
You can identify broken links and graphics that won't load.
You can NOT complain about the look.
You can point out graphics that won't load.
Apr 14 2008, 09:52 AM
Post #2
Group: Root Admin
Posts: 144
Joined: 15-June 06
Member No.: 1
While I feel these things should be self evident, recent arguments have shown they are not with some.
The error must be a current error, you can't go surfing old caches of our website and say oh there was an error.
Along these lines screenshots should include the full screenshot, if our staff doesn't see the error and you have trimmed down to where the only thing visible in the screenshot is the error, no documentation of where you are surfing for that error. Then it won't count unless you can provide an untrimmed screenshot.
Also ALL screenshots are date checked, when a screenshot is made the date is embedded in the code, we check this and if we catch you submitting old screen shots we will not accept requests for free servers from you. It will be deemed that you are trying to multi use errors amongst friends, for a one error to many servers situation.
We have given away several free servers and do honor our special. But our special is not there for people to cheat and steal from us. You must follow the rules of the special!
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text:
snooptb necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 31 diseños de 13 diseñadores freelance.
I need a Logo and Buttons for my new Projekt. It is a German Car Smart Repair Search Site. Please take a look in teh Description.
Accepted File Formats:
Adobe Illustrator (AI), Adobe Photoshop (PSD)
Hello everybody,
first I must say that I write from Germany and I cannot write unfortunately perfect English.
I need a Logo for my new side http://www.waschstrasse.info
For the moment is still old side on the server. Here in the screen SHOT from the starting side you could see, how the side should look once. I need a new Logo for the header. It does not have to remain existing necessarily the individual Google advertisement. You can exclude you you gladly. On the side it concerns the topic of the Smart Repair switching for completely Germany. Thereby this kind acts of service for your city seeks to find can around a side where people. Explanation of Smart Repair: Among other things over PAINTLESS DENT REM OVAL goes. A system ton remove dents, thing, creases and hail damage from your vehicle without the need for expensive resprays. The Paint Doctor alternative CAN save you thousands OF dollar into expensive paint repairs. Incoming goods CAN disguise those unsightly scratches and stone chips with our revolutionary Paint Perfecting and touch UP of system. This kind of work among other things leather seats, material seats, glass violating etc. are feasible for autorims. You have with the organization of the Logos free hand. Particularly well the Web 2,0 Design pleases me. Beautiful would be also, if the Germany map flows also into the Logo. It does not have to be however, if you a better idea have. The name waschstrasse.info should appear in the Logo. I saw 2 photos here it can:
older draft http://www.flickr.com/photo_zoom.gn…392&size=o
New draft http://www.flickr.com/photo_zoom.gn…608&size=o
Then we need still Buttons for the respective techniques:
(The Buttons should be suitable the existing Buttons to be, which one sees in this screen SHOT! The Marked Buttons is by of you provided to be supplemented.Here the Screenshot: http://www.flickr.com/photo_zoom.gn…908&size=o
PAINTLESS DENT REM OVAL Button. A system ton remove dents, thing, creases and hail damage from your vehicle without the need for expensive resprays. http://auto-bender.com/lackierfreie…ulendoktor
The Paint Doctor Button. Alternative CAN save you thousands OF dollar into expensive paint repairs. Incoming goods CAN disguise those unsightly scratches and stone chips with our revolutionary Paint Perfecting and touch UP of system. http://auto-bender.com/lackreperatur-lackdoktor
Carwash Button
Wheeldoctor Button: http://www. wheelrepairs. co.uk/
Leather/Venyl Doctor Button http://www. bvif. de/technik/smart-repair/index. html
PadDoctor Button: http://auto-bender.com/polsterreparatur
SmellDoctor Button: http://auto-bender.com/ozon-geruchs…ralisation
Car polish Button: http://auto-bender.com/fahrzeugaufbereitung
Foils technology Button: http://www. bvif. de/technik/folie/index. html
Nano Technology Button: only nano write into the Button
Car Window Doctor Button: http://www. scheibendoktor. de/
engine washing Button: http://auto-bender.com/motorwaesche
Forum Button
Web log Button
This style pleases me for buttons very well: http://www.istockphoto.com/file_clo…id=3291938
If you ask have simply to announce.
Thank you all.
Tobias B.
This contest was originally listed in multiple categories:
- Logo Design
- Buttons & Icons
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


text:
Director Bigelow brings 'Zero Dark Thirty' to D.C.
- 'Zero Dark Thirty' opens nationwide Friday
- "We had no agenda in making this film," Bigelow said
- The guest list for the private screening, held at the Newseum, was not made public
Director Kathryn Bigelow and screenwriter Mark Boal brought their controversial film, Zero Dark Thirty, to Washington, D.C., Tuesday night, just days before the film opens nationwide Friday.
And despite much talk in the nation's capital in recent weeks about what some consider the film's controversial content, the audience applauded Bigelow, who spoke before the movie was shown.
The guest list for the private screening, held at the Newseum, was not made public, but Bigelow, in opening remarks, welcomed "the members of the armed forces, Special Forces and intelligence professionals and families of victims of Sept. 11 who are here tonight. That's incredibly gratifying to us, and thank you for being here." A huge contingent of D.C.-based media were also in attendance.
USA TODAY REVIEW:'Zero Dark Thirty'
The film, about the 10-year hunt for Osama bin Laden, has had its share of controversy and it has come from both sides of the political aisle. Sens. John McCain (R-Ariz.) and Dianne Feinstein (D-Calif.) and others have criticized the film's depictions of torture. They say the film implies that the CIA's use of aggressive interrogation techniques, including water boarding, resulted in the key information that lead to the discovery of Osama bin Laden's compound in Pakistan and his death.
"Mark and I are truly awed by the national conversation the movie has spurred," Bigelow said. "As filmmakers nothing is more flattering, humbling and quite frankly somewhat intimidating" as creating a film that has sparked so much "thoughtful dialogue and debate."
She also said "to be clear, we had no agenda in making this film, and we were not trying to generate controversy. Quite to the contrary, Mark and I wanted to present the story as we understood it based on the extraordinary research that Mark did."
Bigelow went on to say that most of us are familiar with the "greatest manhunt in history. Many of us know how it ended, but perhaps very few or nobody knows every detail of how it happened. We tried to bring the story to the screen in a faithful way." She said it's up to the audience to interpret the film and that each person will have their own experience. Her goal, she said, was "to illustrate the ambiguities and the contradictions and the complexities of this 10-year manhunt."
The Directors Guild of America announced Tuesday that Bigelow was among the nominees for Outstanding Directorial Achievement in Feature Film award for 2012. The winner will be announced Feb. 2.
And on Monday, Bigelow and Boal accepted best director and best film awards from the New York Film Critics Circle Awards for Zero Dark Thirty.
The film, starring Jessica Chastain, Jason Clarke, Joel Edgerton, Chris Pratt, Kyle Chandler and Mark Strong, has also received four Golden Globe nominations.


text: Tuesday, July 09, 2013 Resolution Calls for Broadened Efforts to Reduce Administrative Burdens That Limit Care and Increase Recognition of Value of Physical Therapist Services As further evidence that the physical therapy profession is moving away from an internal focus and looking out toward the needs of health care consumers and society, APTA has resolved to focus advocacy efforts on demonstrating to society the value of physical therapist (PT) participation in the health care system and on achieving access for consumers to necessary PT services. At the same time, the association rescinded a House of Delegates policy calling for attainment of "physician status" under Medicare (HOD P06-05-16-08). Because of drawbacks to pursuing "physician status" APTA noted that efforts were better directed toward the goals of the new resolution, Public Policy Efforts to Improve Consumer Access to Physical Therapists. Under this resolution, the association can pursue multiple strategies to improve access to physical therapist services and take any statutory opportunities that present in the current and evolving environment. [RC 19-13, RC 20-13] Draft language adopted by the 2013 House of Delegates will be available on the House Community no later than July 12. Final language for all actions taken by the June 2013 House will be available by September after the minutes have been approved. See more results of the 2013 House of Delegates by following this link, or click on July 9 from the News Now calendar. Comments This is unfortunate we have every right to obtain physician status in all situations as well as under Medicare. If the APTA won't stand up for obtaining physician status then who will? Posted by ConcernedPT on 7/13/2013 9:25 AM


text:
Winnebago County Sheriff's Police
News Media Release
News Release Number
Information: Stabbing Death/ 4949 Linden Rd
Date: 10-1-2013
Time: 7:15 a.m.
Page of 1
On Monday September 30, 2013 at approximately 11:33P.M. Winnebago County Sheriff's Deputies were sent to an apartment at 4949 Linden Rd. in regards to a stabbing. Upon arrival the deputies located a 30yr old male deceased in apartment 1023 from an apparent stab wound.
The victim did not live in the apartment but was visiting.
A 27yr old female was located and taken into custody, however at this point has not been charged.
The incident appears to be domestic related and Sheriff's Detectives are conducting a follow-up investigation working with the Winnebago County State's Attorney's Office.
An autopsy will be conducted later today by the Winnebago County Coroner's Office.
The name of the victim will be released by the Coroner's office once family members have been contacted.


text:
Carn Lithuania.
Carn Lithuania.
See plucky little Scotland holding the mighty Lichtensteininans too.
Cricket Web's current Premier League Tipping Champion
- As featured in The Independent.
"Ben Stokes, that most unlikely saint, worked the second of the two miracles he needs for his canonisation." - The Guardian's Andy Bell on the England all-rounder's Headingley ton
Need Scotland to win a game tbf, though having Jimmeh as my avatar isn't at all bad
England doing their best to royally **** this up.
HAHAHA @ Jocks nil Liechtenstein one
World Scrabble Champion 2014. National Scrabble Champion 2009, 2015.
Author of Word Addict
Countdown Series 57 Champion
King of the Arcade
ECB - you are a complete ****ing disgrace, #FTECB
A follower of the schools of Machiavelli, Bentham, Locke, Hobbes, Sutcliffe, Bradman, Lindwall, Miller, Hassett, Benaud and Thunberg
I had a glimpse of Eureka
Chewing me up, chewing me up and spitting me out
-jected, I was rejected
I wasn't good enough to be elected
Lava, it was like lava
Moving through my body like fire
MSN Messenger: minardineil2000 at hotmail dot com | AAAS Chairman
CricketWeb Black | CricketWeb XI Captain
ClarkeWatch: We're Watching Rikki - Are You?
Up The Grecians - Exeter City FC
Completing the Square: My Cricket Web Blog
2105: GOALFLASH Scotland 0-1 Liechtenstein (Frick)
Such terrible defending. How can you let him have that much time?
Last edited by Jamee999; 07-09-2010 at 03:11 PM. Reason: fricking liechtenstein
Or something.
RIP Fardin Qayyumi (AKA "cricket player"; "Bob"), 1/11/1990 - 15/4/2006
Haha Mario Frick WAG, didn't realise he was still around.
2-0; Johnson's a kwality act, isn't he? Kept his head and trusted his technique.
How the blue feck Capello thought SW-P was a better bet, etc, etc
EDIT: Adam Johnson, obv
2nd EDIT: 2-1. Some strike from Shaqiri, but a challenge might've been nice too
Last edited by BoyBrumby; 07-09-2010 at 03:15 PM.
Top goal from Johnson, now England shut up shop, I've got money on him last goalscorer.
Do I contradict myself?
Very well then I contradict myself,
(I am large, I contain multitudes.
Walt Whitman
England trying to do a Scotland and **** up a 2-0 lead against a ****house team with a man advantage.
We are no longer losing to Liechtenstein.
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text:
A lemon citrine gemstone suspended from a sterling silver bail of twining leaves. The large, faceted pear shaped stone has brilliant play of light and sparkle and the color is a delicate pale lemon.
This Arts Nouveau pendant is the style of the designer Bernard Instone and quite possibly by this designer.
+All the details
The pendant is not stamped; it is testing strongly as sterling and is guaranteed to be such.
The Stone:
Citrine, multifaceted pear-cut.
The pendant measures .65 x 1.6 inches or 22 x 35mm including the silver bail and is 9mm in thickness. Shown on a life size torso in image 2.
The Chain
Presented on a new sterling silver chain 22 inches or 56cm long, stamped 925 to the clasp.
Condition: Excellent. No chips or nibbles, all facet edges are crisp. There is beautiful dark patina to the silver leaves.
Age: 1910s (possibly earlier)
Weight: 8.8gms without the chain
Janne's Notes:
A luscious combination of sterling silver and gemstone. Tasteful, elegant and just plain gorgeous.
For more Vintage Pendants & Necklaces:
Back to Closetgothic here:
1 business day
I'll do my best to meet these shipping estimates, but can't guarantee them. Actual delivery time will depend on the shipping method you choose.
Buyers are responsible for any customs and import taxes that may apply. I'm not responsible for delays due to customs.
Just contact me within: 3 days of delivery
Ship items back to me within: 7 days of delivery
Request a cancellation within: 1 hours of purchase
But please contact me if you have any problems with your order.
Because of the nature of these items, unless they arrive damaged or defective, I can't accept returns for:
Buyers are responsible for return shipping costs. If the item is not returned in its original condition, the buyer is responsible for any loss in value.
Please contact me if you have any problems with your order.
Privacy Policy:
This Privacy Policy describes how and when I collect, use, and share information when you purchase an item from me, contact me, or otherwise use my services through Etsy.com or its related sites and services.
This Privacy Policy doesn't apply to the practices of third parties that I do not own or control, including Etsy or any third party services you access through Etsy. You can reference the Etsy Privacy Policy to learn more about its privacy practices.
1. Information I Collect
To fulfil your order, you must provide me with certain information (which you authorized Etsy to provide to me), such as your name, email address, postal address, payment information, and the details of the product that you're ordering. You may also choose to provide me with additional personal information (for a custom order of jewelry, for example), if you contact me directly.
2. Why I Need Your Information and How I Use It
I rely on a number of legal bases to collect, use, and share your information, including:
- As needed to provide my services, such as when I use your information to fulfil your order, to settle disputes, or to provide customer support.
- If necessary to comply with a legal obligation or court order or in connection with a legal claim, such as retaining information about your purchases if required by tax law;
a) providing and improving my services. I use your information to provide the services you requested and in my legitimate interest to improve my services; and
b) Compliance with the Etsy Seller Policy and Terms of Use. I use your information as necessary to comply with my obligations under the Etsy Seller Policy and Terms of Use.
3. Information Sharing and Disclosure
Information about my customers is important to my business. I share your personal information for very limited reasons and in limited circumstances, as follows:
Etsy. I share information with Etsy as necessary to provide you my services and comply with my obligations under both the Etsy Seller Policy and Etsy Terms of Use.
Service providers. I engage certain trusted third parties to perform functions and provide services to my shop, such as delivery companies. I will share your personal information with these third parties, but only to the extent necessary to perform these services.
Business transfers. If I sell or merge my business, I may disclose your information as part of that transaction, only to the extent permitted by law.
Compliance with laws. I may collect, use, retain, and share your information if I have a good faith belief that it is reasonably necessary to: (a) respond to legal process or to government requests; (b) enforce my agreements, terms and policies; (c) prevent, investigate, and address fraud and other illegal activity, security, or technical issues; or (d) protect the rights, property, and safety of my customers, or others.
Data Retention
I retain your personal information only for as long as necessary to provide you with my services and as described in my Privacy Policy. However, I may also be required to retain this information to comply with my legal and regulatory obligations, to resolve disputes, and to enforce my agreements.
5. Transfers of Personal Information Outside the EU
I may store and process your information through third-party hosting services in the US and other jurisdictions. As a result, I may transfer your personal information to a jurisdiction with different data protection and government surveillance laws than your jurisdiction. If I am deemed to transfer information about you outside of the EU, I rely on Privacy Shield as the legal basis for the transfer, as Google Cloud is Privacy Shield certified.
6. Your Rights
If you reside in certain territories, including the EU, you have a number of rights in relation to your personal information. While some of these rights apply generally, certain rights apply only in certain limited cases. I describe these rights below:
Access. You may have the right to access and receive a copy of the personal information I hold about you by contacting me using the contact information below.
Change, restrict, delete. You may also have rights to change, restrict my use of, or delete your personal information. Absent exceptional circumstances (like where I am required to store data for legal reasons) I will generally delete your personal information upon request.
Object. You can object to (i) my processing of some of your information based on my legitimate interests and (ii) receiving marketing messages from me after providing your express consent to receive them. In such cases, I will delete your personal information unless I have compelling and legitimate grounds to continue using that information or if it is needed for legal reasons.
Complain. If you reside in the EU and wish to raise a concern about my use of your information (and without prejudice to any other rights you may have), you have the right to do so with your local data protection authority.
How to Contact Me
For purposes of EU data protection law, I, Janne Perry, am the data controller of your personal information. If you have any questions or concerns, you may contact me at
Alternately, you may mail me at:
Janne Perry 5 Kiwi Crescent, Tauranga 3112, New Zealand
PLEASE NOTE: We are unable to offer Layaways during November and December each year.
During the rest of the year we offer a one month layaway on items over $100 with a 1/3rd initial deposit and two further payments over the next 4 weeks.
Please convo for further information and queries.
All orders are shipped via NZ Post Priority International Air Satchel with a target delivery time of 6-10 business days.
***Meeting these targets can be dependent on border controls/delays at destination and Holiday Season mail delays.
Your order is insured and tracked to destination - a tracking number will be on your Etsy order and can be found here:
I gift wrap all purchases, you'll see a sample of Closetgothic wrapping on our About page and in every listing. Talk to us if you have any special requirement - I am most happy to hand write a note on request.
No. Being outside of the UK and the EU, we are not entitled to collect VAT. You will be responsible for any associated VAT and handling charges that are levied by your government or postal service.
Tracking is provided for all orders. Your purchase is insured during transit.
I am unable to ship antique jewelry to The Russian Federation and Ukraine. No options are available to me - sincere apologies for this situation.
Jun 15, 2019
My gosh, this pendant is even more stunning in real life than in the photos. I can't believe it, I had high expectations and they were exceeded! Absolutely lovely seller too, very knowledgeable and friendly. I cannot recommend this store highly enough :)


text:
Hello once again, guys! I'm back with another tutorial again, but this is going to be a switch up from the more cartoony and vector artwork I've been squeezing out. In this tutorial, I will give you a basic breakdown on 'how to draw an eagle', step by step. I loved working on this tutorial, especially the shading process on the wings. Remember to prepare yourself with a varied softness/hardness graphite penciling kit if you want an outcome presented in the first image. I would also recommend using a kneaded eraser (preferably a Prismacolor Kneaded Eraser) to have a thicker and stable molding power for erasing highlights. I used the Prismacolor Scholar Graphite Pencils which comes with the high quality kneaded eraser. Anyways, hopefully you guys will enjoy this tut! Peace and have a great time :)
DragoArt members upload artwork and drawing tutorials! They are also allowed to leave comments on tutorials, profiles, etc. Many more features, as well; it's way better than just being a boring guest! Register Now!


text:
This Gefen Publication is an attractive easy to read book with short, but not too short, messages, Divrai Torah, Torah thoughts about the various Parshot Shavua, weekly Torah Portions. Each concentrates on one short aspect.
It's the perfect book for someone who wants to enrich his/her Shabbat meal with Torah words or just wants to learn a bit something extra about the weekly Torah Portion. Each chapter is short enough to be read at the table during the meal and can be used to begin a discussion.
For me, The Fire and the Cloud is a departure from my usual Torah and Tanach (Bible) studies. I'm generally very text oriented, and Rabbi Bigman takes a different approach. I've found something new and interesting in every chapter. Rabbi Bigman uses all sorts of references, Medrash, Chaza"l, Kuzari and other Torah chapters to enrich the learning.
Yes, I highly recommend The Fire and the Cloud by Rabbi David Bigman.
*Publicists are invited to contact me.


text:
Holidays in Ritten/Renon
The local mountain of South Tyrol's capital city is easy to ascend with the Ritten cable car, providing a fantastic, 360° view of Dolomite peaks, hikes from vineyards all the way up to 2,200 m, and the earth pyramids, a unique natural phenomenon. Holidaymakers will find particularly diverse vegetation due to the various elevations on this sunny high plateau as well as numerous possibilities for being active: The entire spectrum is available, from simple strolls to the many farmhouse inns to skiing in the Rittner Horn ski area. A ride with the narrow-gauge railway is a particularly rewarding experience. It was built in 1907 to connect the villages of Santa Maria Assunta/Maria Himmelfahrt, Soprabolzano/Oberbozen, Costalovara/Wolfsgruben, Stella di Renon/Lichtenstern, and Collalbo/Klobenstein.


text:
How much would you pay for an extra pair of hands? Forty-five dollars sounds low. That's the price for this awesome set of cooking utensils with notches that let them rest on the side of your saucepan, freeing up your hands for more multitasking in the kitchen.
And hell, how many times have you dropped a spoon or a spatula into what you're cooking? It's annoying. Danish design firm KiBiSi have solved that horrible problem with this set. [BLTD]


text:
After the project "smockshop" was archived we realized that we were really going to miss working together. So we started a new group called "formerly known as smockshop" – or more casually referred to as FKAS. Our new products won't be entirely clothing based and will eventually be available for sale both at pop-up sales, and via an on-line store. And since every startup I'm involved in has a rule, so does this one. The dictate for FKAS is that all of the products have to be made in the form of a rectangle – so each item is a "panel" of one sort or another – though these are all intended to be useful objects (similar to the "A-Z Personal Panels", "A-Z Carpet Furniture", and "A-Z Cover" pieces that I have made in the past). Each member of FKAS is supposed to come up with their own panel product line so I'm trying out a new and very simple pattern that is loosely based on Guatemalan Huipil. Here is my second try (sewn out of left over fabric from the bathroom curtain) – I thought that the first turned out great until I realized that the neck was sewn in crooked.. dang!
First FKAS Product
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