A lanthanide-rich kilonova in the aftermath of a long gamma-ray burst.

Observationally, kilonovae are astrophysical transients powered by the radioactive decay of nuclei heavier than iron, thought to be synthesized in the merger of two compact objects1-4. Over the first few days, the kilonova evolution is dominated by a large number of radioactive isotopes contributing to the heating rate2,5. On timescales of weeks to months, its behaviour is predicted to differ depending on the ejecta composition and the merger remnant6-8. Previous work has shown that the kilonova associated with gamma-ray burst 230307A is similar to kilonova AT2017gfo (ref. 9), and mid-infrared spectra revealed an emission line at 2.15 micrometres that was attributed to tellurium. Here we report a multi-wavelength analysis, including publicly available James Webb Space Telescope data9 and our own Hubble Space Telescope data, for the same gamma-ray burst. We model its evolution up to two months after the burst and show that, at these late times, the recession of the photospheric radius and the rapidly decaying bolometric luminosity (Lbol ∝ t-2.7±0.4, where t is time) support the recombination of lanthanide-rich ejecta as they cool.

Heavy-element production in a compact object merger observed by JWST.

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs)1, sources of high-frequency gravitational waves (GWs)2 and likely production sites for heavy-element nucleosynthesis by means of rapid neutron capture (the r-process)3. Here we present observations of the exceptionally bright GRB 230307A. We show that GRB 230307A belongs to the class of long-duration GRBs associated with compact object mergers4-6 and contains a kilonova similar to AT2017gfo, associated with the GW merger GW170817 (refs. 7-12). We obtained James Webb Space Telescope (JWST) mid-infrared imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns, which we interpret as tellurium (atomic mass A = 130) and a very red source, emitting most of its light in the mid-infrared owing to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy-element nucleosynthesis across the Universe.

Lagrangian large eddy simulations via physics-informed machine learning.

High-Reynolds number homogeneous isotropic turbulence (HIT) is fully described within the Navier-Stokes (NS) equations, which are notoriously difficult to solve numerically. Engineers, interested primarily in describing turbulence at a reduced range of resolved scales, have designed heuristics, known as large eddy simulation (LES). LES is described in terms of the temporally evolving Eulerian velocity field defined over a spatial grid with the mean-spacing correspondent to the resolved scale. This classic Eulerian LES depends on assumptions about effects of subgrid scales on the resolved scales. Here, we take an alternative approach and design LES heuristics stated in terms of Lagrangian particles moving with the flow. Our Lagrangian LES, thus L-LES, is described by equations generalizing the weakly compressible smoothed particle hydrodynamics formulation with extended parametric and functional freedom, which is then resolved via Machine Learning training on Lagrangian data from direct numerical simulations of the NS equations. The L-LES model includes physics-informed parameterization and functional form, by combining physics-based parameters and physics-inspired Neural Networks to describe the evolution of turbulence within the resolved range of scales. The subgrid-scale contributions are modeled separately with physical constraints to account for the effects from unresolved scales. We build the resulting model under the differentiable programming framework to facilitate efficient training. We experiment with loss functions of different types, including physics-informed ones accounting for statistics of Lagrangian particles. We show that our L-LES model is capable of reproducing Eulerian and unique Lagrangian turbulence structures and statistics over a range of turbulent Mach numbers.

Survival Following Tumor Recurrence in Children With Medulloblastoma.

Medulloblastoma is the most common malignant brain tumor in children. Published survival rates for this tumor are ∼70%; however, there is limited published information on outcome after disease recurrence. This was an observational study which included all persons under the age of 18 years diagnosed with medulloblastoma from 1990 to 2009 inclusive in Canada. Data collected included date of diagnosis, age at diagnosis, sex, stage, pathology, treatment, recurrence, and current status. Survival rates were determined. In total, 550 cases were ascertained meeting the study criteria. The overall survival rate at 1 year was 83.6%±1.7%, at 3 years 77.2%±1.9%, and at 5 years 72.5%±20%. The progression-free survival rates were 78%±1.9%, 70%±2.1%, and 69±2.1% at 1, 3, and 5 years from initial diagnosis. In total, 173 (31.2%) were reported to have had tumor recurrence and 23 (11.4%) of them were alive at the time of survey with an overall survival rate at 1 year of 38.3%±4%, at 2 years of 16.9%±3.3%, and at 5 years of 12.4%±2.8%. Our data confirm that children with recurrent medulloblastoma have a poor prognosis, supporting the need for novel treatment approaches for this group.

Neutron-Star-Black-Hole Binaries Produced by Binary-Driven Hypernovae.

Binary-driven hypernovae (BdHNe) within the induced gravitational collapse paradigm have been introduced to explain energetic (E_{iso}≳10^{52} erg), long gamma-ray bursts (GRBs) associated with type Ic supernovae (SNe). The progenitor is a tight binary composed of a carbon-oxygen (CO) core and a neutron-star (NS) companion, a subclass of the newly proposed "ultrastripped" binaries. The CO-NS short-period orbit causes the NS to accrete appreciable matter from the SN ejecta when the CO core collapses, ultimately causing it to collapse to a black hole (BH) and producing a GRB. These tight binaries evolve through the SN explosion very differently than compact binaries studied in population synthesis calculations. First, the hypercritical accretion onto the NS companion alters both the mass and the momentum of the binary. Second, because the explosion time scale is on par with the orbital period, the mass ejection cannot be assumed to be instantaneous. This dramatically affects the post-SN fate of the binary. Finally, the bow shock created as the accreting NS plows through the SN ejecta transfers angular momentum, braking the orbit. These systems remain bound even if a large fraction of the binary mass is lost in the explosion (well above the canonical 50% limit), and even large kicks are unlikely to unbind the system. Indeed, BdHNe produce a new family of NS-BH binaries unaccounted for in current population synthesis analyses and, although they may be rare, the fact that nearly 100% remain bound implies that they may play an important role in the compact merger rate, important for gravitational waves that, in turn, can produce a new class of ultrashort GRBs.

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice.

PURPOSE: Pediatric patients treated with cranial radiation are at high risk of developing lasting cognitive impairments. We sought to identify anatomical changes in both gray matter (GM) and white matter (WM) in radiation-treated patients and in mice, in which the effect of radiation can be isolated from other factors, the time course of anatomical change can be established, and the effect of treatment age can be more fully characterized. Anatomical results were compared between species. METHODS AND MATERIALS: Patients were imaged with T1-weighted magnetic resonance imaging (MRI) after radiation treatment. Nineteen radiation-treated patients were divided into groups of 7 years of age and younger (7-) and 8 years and older (8+) and were compared to 41 controls. C57BL6 mice were treated with radiation (n=52) or sham treated (n=52) between postnatal days 16 and 36 and then assessed with in vivo and/or ex vivo MRI. In both cases, measurements of WM and GM volume, cortical thickness, area and volume, and hippocampal volume were compared between groups. RESULTS: WM volume was significantly decreased following treatment in 7- and 8+ treatment groups. GM volume was unchanged overall, but cortical thickness was slightly increased in the 7- group. Results in mice mostly mirrored these changes and provided a time course of change, showing early volume loss and normal growth. Hippocampal volume showed a decreasing trend with age in patients, an effect not observed in the mouse hippocampus but present in the olfactory bulb. CONCLUSIONS: Changes in mice treated with cranial radiation are similar to those in humans, including significant WM and GM alterations. Because mice did not receive any other treatment, the similarity across species supports the expectation that radiation is causative and suggests mice provide a representative model for studying impaired brain development after cranial radiation and testing novel treatments.

Survival of children with medulloblastoma in Canada diagnosed between 1990 and 2009 inclusive.

The treatment of medulloblastoma, the most common malignant brain tumor in children, has evolved over the last few decades. The objectives of this paper were to determine the survival of pediatric medulloblastoma in Canada, to determine if there has been an improvement in the survival rates between the years of 1990 and 2009, inclusive, and to determine prognostic factors for survival. All patients under the age of 18 years diagnosed with medulloblastoma from 1990 to 2009, inclusive, in Canada were included. Data collected included date of diagnosis, age at diagnosis, gender, stage, pathology, treatment, recurrence and current status. From these, survival rates were determined. Data were obtained on 628 eligible patients. The overall 5-year survival rate for the study time period was 69.2 ± 3.3 %. The survival rate increased during the interval of 1996-2000, then remained stable; 1990-1994: 60.2 ± 4.3 %; 1995-1999: 73.2 ± 3.5 %; 2000-2004: 68.8 ± 3.7 %; and 2005-2009: 72.1 ± 4.9 %, p = 0.05. Children over 14 years of age had a significantly better overall survival than those age 5-14 and those under 5 (85.7 ± 5.5 % vs 76.1 ± 2.7 % and 60.8 ± 3 % respectively, p = 0.001). Histologic medulloblastoma subtype and M stage of disease did not result in significant differences in survival. Despite changes in approaches to therapy, we demonstrate a steady survival rate for children with medulloblastoma after 1996. In our analyses, age over 14 years was associated with a higher survival rate.

Low grade astrocytoma in children under the age of three years: a report from the Canadian pediatric brain tumour consortium.

In children under the age of 3 years, the most common solid tumors are brain tumors. Low grade astrocytomas represent 30-40 % of brain tumours in this age group. This study reviewed the incidence, characteristics, therapy, and outcome of children less than 36 months of age diagnosed with a low grade astrocytoma from 1990 to 2005 in Canada. A data bank was established using data collected from Canadian pediatric oncology centers on children less than age 3 diagnosed with brain tumors between 1990 and 2005. Cases of low grade astrocytoma were extracted from this data bank and their characteristics summarized. From the 579 cases in the data bank, 153 cases of low grade astrocytoma (26 %) were identified. The mean duration of symptoms prior to presentation was 13 weeks, and 53 % of patients underwent a greater than 90 % resection of their tumor, while 30 % underwent 10-90 % resection. Seventy-one percent of patients received no further therapy after surgery and of the 45 who received therapy following surgery, 43 received chemotherapy, and 5 received radiation therapy. Sixty-eight patients had recurrence or progression of their tumor. Eighty-seven percent of patients were alive at the time of the survey with a 2 year survival rate of 95.3 ± 1.8 %, 5 year survival rate of 93.1 ± 2.1 % and 10 year survival rate of 89.1 ± 2.8 %. The 5 year survival rate for Canadian children less than 36 months of age with a low grade astrocytoma was 93.0 ± 2.8 % which is similar to that for older children with this tumor.

Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis.

BACKGROUND: Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. METHODS: We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. FINDINGS: Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0·004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0·033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0·001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2·02 (95% CI 1·04-3·85; p=0·038) and 3·98 (1·71-9·26; p=0·001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. INTERPRETATION: An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours. FUNDING: C17 Research Network, Genome Canada, b.r.a.i.n.child, Mitchell Duckman, Tal Doron and Suri Boon foundations.

Neurocognitive evaluation of long term survivors of atypical teratoid rhabdoid tumors (ATRT): The Canadian registry experience.

BACKGROUND: Because atypical teratoid rhabdoid tumor(ATRT) is a rare disease of infancy carrying a grim prognosis, focus on long-term outcome, especially neurocognitive remained very limited. With new era of multimodality therapy, an increasing proportion of patients are now long-term survivors. PROCEDURE: Retrospective review of neuropsychological (NP) status of survivors from the Canadian ATRT registry. RESULTS: Among 77 patients diagnosed between 1995-2012, 16(22%) were survivors. Formal NP assessments were available in eight patients. Partial information on academic achievement was available on three additional patients. There were four girls and seven boys diagnosed at a median age of 27.5 months. Seven patients underwent complete resection and three had metastatic disease. All but one received sequential high dose chemotherapy. Five patients received intrathecal chemotherapy. Three patients underwent radiation. Median age at time of formal NP assessment was 7.6 years (3.9-9.8). Full Scale Intellectual Quotient (FSIQ) ranged from less than 50-119 (mean 78). Simple expressive and receptive language appeared relatively preserved. Three recently diagnosed patients (median time assessment from diagnosis 2.6 years (1.6-4.7)) had average to high average FSIQ, academic and visual spatial skills, visual, and verbal memory. Five other patients diagnosed earlier and tested at a median time of 4.9 years (3.3-8.3) post-diagnosis had a FSIQ ranging from <50 to 71. Approximately 50% of their scores were in the impaired range. CONCLUSION: Overall this cohort appears significantly impaired at school age despite the absence of systematic radiotherapy. Larger series focusing on neurocognitive outcome are needed in the current context where treatment strategies include adjuvant radiation.

White matter compromise predicts poor intellectual outcome in survivors of pediatric low-grade glioma.

BACKGROUND: While the impact of cranial radiation on white matter following treatment for pediatric brain tumor has been the focus of many recent studies, the effect of treatment in the absence of radiation has received little attention. The relations between white matter and cognitive outcome have not been explored in patients who have undergone radiation-free treatment. As most patients treated without cranial radiation survive long after their diagnosis, it is critical to identify factors that may impact structural and neurocognitive outcomes. METHODS: Using diffusion tensor imaging, we examined white matter structure in 32 patients with pediatric low-grade glioma (PLGG) (19 with subtentorial location and 13 with supratentorial location) and 32 healthy participants. Indices of intellectual functioning were also evaluated. Radiation was not used to treat this cohort, aged 8-19 years. RESULTS: We detected evidence of deficits in IQ and compromised supra- and subtentorial white matter in patients relative to healthy children (P < .05). Compromise of supratentorial white matter mediated the impact of treatment for PLGG on IQ. Greater white matter compromise was observed in patients who presented without multiple symptoms, were treated with biopsy/no surgery, had positive neurofibromatosis 1 status, were younger age at diagnosis, and whose parents had lower levels of education (P < .05). CONCLUSIONS: Our findings provide evidence of increased risk of intellectual and white matter compromise in patients treated for PLGG without radiation. We identify a neural origin of cognitive deficit useful for predicting outcome and mitigating long-term adverse effects in pediatric brain tumor patients treated without cranial radiation.

The role of resection alone in select children with intracranial ependymoma: the Canadian Pediatric Brain Tumour Consortium experience.

PURPOSE: Gross total resection (GTR) of intracranial ependymoma is an accepted goal. More controversial is radiotherapy deferral. This study reports on children treated with gross total resection who did not receive upfront adjuvant radiotherapy. METHODS: We conducted a retrospective review of children with intracranial ependymoma in 12 Canadian centers. Patients who had GTR of their tumor and no upfront radiotherapy were identified. Immunostaining was performed for Ki-67, epidermal growth factor receptor (EGFR), and EZH2 on archived tissue. The Kaplan-Meier survival analysis was performed and compared with those who had GTR followed by radiation. RESULTS: Twenty-six children were identified treated with GTR alone at diagnosis; 12 posterior fossa ependymoma (PFE) WHO grade II, and 14 supratentorial ependymoma (STE). Progression-free survival (PFS) in ependymoma treated with GTR alone at diagnosis was inferior in those with high Ki-67 or positive EZH2 immunostaining. Survival was inferior for patients less than 2 years old at diagnosis (p = 0.002). Survival was comparable to PFE WHO grade II and STE who had GTR followed by radiation (p = 0.62). Five-year PFS and overall survival (OS) of those treated with GTR alone were 60 and 70% respectively for PFE and 45 and 70% respectively for STE (p = 0.2; 0.55). CONCLUSIONS: This study suggests that there is a subset of children with certain biologic features who, in the setting of a prospective clinical trial, might be candidates for observation following GTR. Good risk factors for this approach include age of 2 years or older, low Ki-67, and negative EZH2. If relapse occurs, it may be confined to the primary site, allowing for possible salvage with GTR followed by XRT.

Incidence of medulloblastoma in Canadian children.

Medulloblastoma is the most common malignant brain tumor in children. There was a perception of pediatric neuro-oncologists that the incidence had declined in Canada. An epidemiological survey was undertaken to determine the incidence of this tumor in Canada and if a change had indeed occurred. All patients 14 years and under diagnosed with medulloblastoma from 1990 to 2009 inclusive in Canada were included. Data collected included date of diagnosis, age at diagnosis, gender, stage, pathology, treatment, recurrence and current status. Data were analysed for change in incidence over time. Data were obtained on 574 eligible patients. The mean overall incidence per 1,000,000 persons was 4.82 (95 % CI 4.28-5.35) for the study time period. The mean age at diagnosis was 5.8 years, and there was a male predominance. Although there was an increase in incidence over the first three time periods (24 % for 1990-1994, 27.5 % for 1995-1999, 27.7 % for 2000-2004), the most recent time period (2005-2009) showed a decrease (21 %). This was true for male children while the incidence was stable for females. The mean incidence rate was double for children under the age of 5 years (7.92 per million) compared to those over 5 years (3.64 per million).This study showed that from 1990 to 2009 the incidence of medulloblastoma was relatively stable, with a slight decrease in the last five-year time period.

De-escalation of therapy for pediatric medulloblastoma: trade-offs between quality of life and survival.

BACKGROUND: Treatment intensity for pediatric medulloblastoma may vary depending on the type of medulloblastoma. In some cases, the dose of radiation may be reduced or eliminated. Correspondingly, there may be trade-offs between quality of life and survival. In this study, focus groups were conducted with parents and clinicians to explore their opinions about these trade-offs as well as the alignment/misalignment between parents and clinicians regarding the trade-offs. METHODS: One hour semi-structured focus groups were conducted with parents of children with medulloblastoma and health care providers who were involved in the care of these children. RESULTS: Parents and providers showed differences in which factors they believe have the greatest impact on quality of life for children with medulloblastoma and their families. For parents, the most important factor is social functioning and their child's ability to make friends and have a social life. In contrast, providers thought that parents cared most about their child's cognitive functioning and ability to attend and perform in school. CONCLUSION: Understanding parents' perspectives on quality of life is important in terms of providing support services that target the areas that the parents prioritize. The types of functioning that are most strongly correlated with quality of life from the parents' perspective may be the ones that should be targeted to protect during treatment. Pediatr Blood Cancer 2014;61:1300-1304. © 2014 Wiley Periodicals, Inc.

Ependymoma in children under the age of 3 years: a report from the Canadian Pediatric Brain Tumour Consortium.

The determination of optimal therapy for ependymoma (EP) in infants is ongoing. We describe the incidence, management and outcomes of Canadian infants with EP to discern potential future research questions. Of 579 cases registered in a national database of children <36 months of age diagnosed with a brain tumor from 1990 to 2005, inclusive, 75 (13 %) were EP. These cases were analyzed. A mean annual age-adjusted incidence rate of 4.6 per 100,000 children years was calculated. The male:female ratio was 1.77. Of the tumors, 80 % were infratentorial in location, 67 % were WHO grade II histology, and 29 % were metastatic at diagnosis. All patients underwent a surgical procedure. A complete resection of the tumor was achieved in 56 % of the cases; 43 % of these patients survive while 36 % of the patients with tumors less than completely resected survive. Initial therapy consisted of surgery alone in 23 % of patients, or surgery plus chemotherapy (37 %), radiation therapy (RT; 19 %), or both (21 %). Any use of RT increased with patient age. The 5-year EFS rates for patients in each of the four treatment groups was 22, 11.5, 46.2 and 64.8 %, respectively. For all patients the median survival was 63 ± 6 months and 5-year overall survival was 55 ± 6 %. Patients treated with surgery and chemotherapy alone were younger and had a lower rate of survival than older patients who were more often treated with radiation therapy containing regimens. Further study is needed to determine which patients are optimally served with these treatment modalities.

Spinal cord tumors in children under the age of 3 years: a retrospective Canadian review.

BACKGROUND: Tumors of the spinal cord are exceedingly rare in infancy and only a paucity of literature exists describing the spectrum of this disease and its management. The objectives of our study were to describe the demographic characteristics of spinal cord tumors (SCT) in children less than 3 years of age at diagnosis and to review their treatment and outcome. METHODS: A national retrospective chart review was conducted on patients under the age of 3 years diagnosed with a primary tumor of the central nervous system (CNS) between 1990 and 2005 across Canada. Inclusion criteria were: age ≤ 3 years, histologic confirmation of the diagnosis, and residency in Canada. A centralized database was created and information regarding SCT was extracted. RESULTS: Twenty-five of five hundred seventy-nine patients (4.3%) in the data bank had a SCT. The majority of tumors were low-grade astrocytomas (14/25). Leptomeningeal dissemination based on neuroradiologic imaging and/or cerebrospinal fluid cytology was present in five (20%) patients. The majority of patients underwent an incomplete surgical resection (52%). Most patients (64%) did not receive postoperative radiotherapy or chemotherapy. Seventy-two percent (18/25) developed recurrent/progression of disease. Overall 2- and 5-year survival for low- and high-grade malignancies was 93 ± 6.4% and 37.5 ± 17.1% respectively. Significant predictors of survival included mean duration of symptoms prior to initial diagnosis and recurrence/progression of disease. CONCLUSIONS: Relapse/progression of disease in infant SCT is frequent. Prolonged survival of low-grade tumors is possible with further therapy; however, the prognosis of high-grade malignancies remains poor.

Choroid plexus tumors in children less than 36 months: the Canadian Pediatric Brain Tumor Consortium (CPBTC) experience.

BACKGROUND: Choroid plexus tumors (CPT) are rare pediatric tumors. A population-based study on choroid plexus carcinoma (CPC) and choroid plexus papilloma (CPP) was carried out to describe the incidence, demographic, and outcome data and to identify potential prognostic factors. METHODS: The CPT population from the Canadian databank of CNS tumor in children ≤ 36 months diagnosed between 1990 and 2005 was reviewed RESULTS: Out of the 579 reported cases of CNS tumors, 37 were CPT. The annual age-adjusted incidence rate was 0.22 + 0.12 (95% CI 0.16-0.28)/100,000 children < 3 years. There were 21 (56.7%) CPP and 16 (43.3.5%) CPC. Twenty patients (54%) were males. Median age at diagnosis was 7 months(range 0-30). Ten patients(62.5%) with CPC and one with CPP were metastatic at diagnosis. Twenty patients with CPP (95%) had a complete resection, whereas 6/16 CPC (37.5%) achieved a resection >90%. Fourteen CPC patients received adjuvant chemotherapy. None of the 37 patients received adjuvant radiation. At completion of survey, all CPP and five CPC were alive. Median survival time for CPC patients was 15 months (0-120). One death was related to intraoperative hemorrhage, another to chemotherapy-induced toxicity, and one to secondary AML. Age at diagnosis, degree of resection and metastatic status were not significant prognostic factors for CPC. CONCLUSION: By contrast to CPC, CPP have an excellent prognosis following surgery alone. Survival of CPC remains poor. However, these data may suggest adjuvant chemotherapy can alter the aggressive natural history of CPC. As with other rare CNS tumors, international collaboration is required to identify optimal therapy.

Gravitational Waves from Gravitational Collapse.

Gravitational-wave emission from stellar collapse has been studied for nearly four decades. Current state-of-the-art numerical investigations of collapse include those that use progenitors with more realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non-axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with ground-based and space-based interferometric observatories. This review covers the entire range of stellar collapse sources of gravitational waves: from the accretion-induced collapse of a white dwarf through the collapse down to neutron stars or black holes of massive stars to the collapse of supermassive stars. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.12942/lrr-2011-1.

Late mortality in pediatric patients with craniopharyngioma.

Ten year survival rates for patients with craniopharyngioma vary from 24 to 100%. A review of the database of all children diagnosed with craniopharyngioma in British Columbia (BC) revealed that several patients died >10 years after diagnosis. This retrospective study investigates the causes and timing of deaths and reports the overall survival in this population based group of patients. A chart review was conducted on all patients aged <17 years, diagnosed in BC with craniopharyngioma between 1967 and 2003. Imaging studies were reviewed by a neuroradiologist. All deaths in the province are reported to a central agency, which allowed identification of patients who died after being lost to clinical follow up. Forty-one patients were identified with nine deaths (aged 11.9-36.9 years). The four patients who died more than 10 years after diagnosis represent 23% of the 17 patients followed for more than 10 years. Three died more than 20 years after diagnosis. The known causes of death were progressive disease (1), uncontrolled diabetes insipidus (1), panhypopituitarism with multi-organ failure (1), pontine infarction (1) and middle cerebral artery infarction in a patient with Moyamoya disease secondary to radiotherapy (1). Two deaths appeared to be seizure related and 1 occurred after orthopedic surgery and remains unexplained. One patient died due to liver failure of unknown etiology. The 10 year overall survival (OS) was 84.1% (95% CI 71.2, 97.1) and the 20 year OS 76.5% (95% CI 58.1, 94.9). Patients remain at risk of premature death more than 10 years after diagnosis. The cause specific late mortality was multifactorial but was rarely due to disease progression. New approaches to craniopharyngioma treatment and life long follow up of cases are required.

Patterns of enrollment of infants with central nervous system tumours on cooperative group studies: a report from the Canadian Pediatric Brain Tumour Consortium.

In children under the age of 3, the most common solid tumours are brain tumors. Treatment for many of these patients includes surgery, chemotherapy and rarely radiation therapy. Many clinical trials have been performed in an attempt to establish the best treatment for these patients. Patients enrolled on clinical trials contribute to the establishment of the best therapy. We performed a national survey of all children less than the age of three with brain tumours and examined the contribution these patients made to clinical trials. A data bank was established using data collected from Canadian pediatric oncology centers on children less than age 3 diagnosed with brain tumours between 1990 and 2005. Data were collected on the use of adjunctive treatment after surgery, treatment on a protocol, reasons patients were not registered on a protocol, and reasons for discontinuation of therapy. From the 579 cases in the data bank, 302 (52%) patients were treated with further therapy after surgery. The use of further therapy after surgery was significantly higher in patients with cerebellar and brain stem tumors, patients who were over 1 year of age, patients with ependymal and embryonal tumors, and patients with high grade malignant tumors. Only 62 (21%) patients were enrolled on a protocol for therapy. No factor was significant for being enrolled on a protocol. Reasons for not being registered on a protocol were mainly that there was no open COG/POG/CCG study or the study was not open at the institution. The therapy was stopped because of completion of the protocol in 50% and because of disease progression in 34%. In Canada, about half of children under the age of 36 months with brain tumors are undergoing therapy following surgery for their malignancy but only a small fraction of them are enrolled on a clinical trial. There needs to be improved availability of clinical trials for these patients so that novel therapies can be evaluated and survival improved.