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In this chapter, I ask how the current generation should accept responsibility for the injustices of its forebears in a way that helps all citizens to progress towards reconciliation. Here, I address the challenge of reconciliation with First Nations given the role of settler states, including Canada and the United States, in intentionally destabilizing Indigenous communities and families through the residential school system, child welfare interventions, and the criminal justice system. Here, I argue for three linked responses to the intergenerational legacy of policies that separated Indigenous families and destabilized their communities and political life. The first involves building immigrant-settler-Indigenous alliances. The second involves the government’s responsibility to avoid perpetuating Indigenous family separation and community destabilization through its criminal justice and child welfare policies. The third involves strengthening Indigenous political sovereignty by expanding their self-governance, participation, and free movement rights across their territories divided by settler state borders.

Chapter 3 argues that political communities should not be free to decide whether to deny citizenship, and its substantial protections, to infants based on their parents’ immigration status, actions, or allegiances. Territorial birthright citizenship offers the promise of integration on equal terms with other citizens. In the United States, equal protection of the law for the children of irregular immigrants means a free public education, on the grounds that “legislation directing the onus of a parent’s misconduct against his children” that “does not comport with fundamental conceptions of justice” (Plyler v. Doe 1982, 220). Immigrants who entered a country without authorization as children should not be held culpable for their parents’ immigration violations. Children of irregular immigrants deserve separate consideration for immigration benefits and citizenship apart from citizens’ judgment of their parents’ conduct as irregular entrants or visa overstayers.

Chapter 1 introduces the problem of holding children responsible for their actions and loyalties of their caregivers. Modern liberal democratic countries prohibit intergenerational punishments like attainder, forfeiture, and corruption of blood for treason. Still, children continue to suffer the consequences of their parent’s actions, behaviors, and legal status. In the criminal justice system, children experience lapses in their parent’s caregiving following incarceration or immigration detention. Citizenship laws and policies provide a number of ways in which children may be ineligible to acquire citizenship at birth based on a parent’s immigration status, national origin, diplomatic status, or questionable allegiances. Proposals to denationalize parents for terrorist affiliations or to deny children citizenship based on their irregular immigration status compound this problem. The author shows how children and other vulnerable persons are suffering from intergenerational punishment directed at their parents, caregivers, and communities.

Penal policy that supports getting tough on crime and giving offenders their just deserts minimizes the plight of children and other dependents as mere necessary collateral consequences of the overriding social benefit of punishment. This approach overlooks the lasting intergenerational social costs of incarceration for offenders who might otherwise be the focus of rehabilitation as caregivers and citizens. This chapter argues in favor of restorative justice approaches that aim to rehabilitate and reintegrate persons convicted of a crime into their communities whenever possible. Reintegration involves preparing a former offender to take on more productive roles and responsibilities in society. Carceral officials should allow inmates to provide emotionally and financially for their dependents during their sentence through visitation, flexible sentencing, and training leading to paid employment. Incarceration and parole should be rehabilitative, with the goal of helping all offenders to become better caregivers and citizens upon their release.

Chapter 7 provides a summary and postscript to the discussion of state-mandated family separation and remedies to this problem as they relate to immigration detentions, citizenship, criminal justice, the fate of the children of foreign fighters, and the legacy of Indigenous child welfare removals. In the United States, the author covers the first year of President Biden’s administration and its approach to reuniting immigrant families, criminal justice reform, and the impact of the war on terror on the children of foreign fighters stranded abroad. In Canada, the same themes are covered with an emphasis on recent developments in Indigenous child welfare protections that could serve as a model for other jurisdictions. More broadly, the chapter addresses the ongoing impact of the COVID-19 crisis on issues related to immigration, citizenship, criminal justice, and Indigenous rights from a comparative North American perspective.

This chapter argues that political communities should not deny citizenship and its protections to children based on their parents’ allegiances or alleged offenses at the time of their child’s birth. Citizenship deprivation is an intergenerational punishment when children lose entitlement to citizenship at birth based on their parent’s denationalization, as is the case for stateless children born abroad to parents affiliated with a terrorist organization. As for the collateral consequences of anti-terrorism sanctions, the primary concern in this chapter is to ensure that the dependents of suspects and offenders do not lose status-based entitlements to citizenship and its rights based on their parents’ actions. The author then questions whether harsh retributory punishments including citizenship deprivation, banishment, and execution are warranted for political crimes committed by minors.

Chapter 2 argues that state actions that undermine caregivers’ capacities to support their families inflict undeserved collateral consequences on their innocent dependents. Scholars of criminology, political science, and sociolegal studies have expanded the understanding of what it means to experience punishment. There is a cross-national trend toward the criminalization of regulatory offenses such as immigration violations and thought or allegiance “pre-crimes” in anti-terrorism prosecutions. Despite formal divisions in the law between administrative sanctions and criminal punishment, immigration enforcement actions, denials of citizenship, denationalizations, and preventive detentions for inchoate offenses are equally punitive. Suspects, offenders, and those who depend on them should be entitled to counsel and other protections reserved for offenders in the criminal justice system. The state should assume responsibility for ensuring the adequate protection and well-being of those who are dependent on persons detained on immigration and terrorism charges.

The ability of Convolutional Neural Networks (CNNs) to accurately process real-time telemetry has boosted their use in safety-critical and high-performance computing systems. As such systems require high levels of resilience to errors, CNNs must execute correctly in the presence of hardware faults. Full duplication provides the needed assurance but incurs a prohibitive 100% overhead. Algorithmic techniques are known to offer low-cost solutions, but the practical feasibility and performance of such techniques have never been studied for CNN deployment platforms (e.g., TensorFlow or TensorRT on GPUs). In this paper, we focus on algorithmically verifying Convolutions, which are the most resource-demanding operations in CNNs. We use checksums to verify convolutions, adding a small amount of redundancy, far less than full-duplication. We first identify the challenges that arise in employing Algorithm-Based Error Detection (ABED) for Convolutions in optimized inference platforms that fuse multiple network layers and use reduced-precision operations, and demonstrate how to overcome them. We propose and evaluate variations of ABED techniques that offer implementation complexity, runtime overhead, and coverage trade-offs. Results show that ABED can detect all transient hardware errors that might otherwise corrupt output and does so while incurring low runtime overheads (6-23%), offering at least 1.6X throughput to workloads compared to full duplication.

This book advances a normative argument that vicarious punishment is re-emerging in a variety of state actions resulting in the separation of families and confinement of caregivers. States deny individuals birthright citizenship based on the actions, behaviors, status, or group identity of their parents. Economically disadvantaged and minority citizens suffer the collateral consequences of mass incarceration when the state detains their parents or caregivers. Children in mixed-citizenship status families are experiencing the loss of a parent or caregiver through detention and deportation. The children of foreign fighters are suffering the vicarious punitive effects of denationalization and other state actions targeting their parents for their actions in a conflict zone as an anti-terrorism measure by their former country of citizenship. Vicarious punishment never went away in the case of Indigenous children separated from their families to punish their community for resisting assimilation and the extinguishment of their land claims. Their families continue to suffer from intergenerational trauma and child welfare interventions. Beneath these policy problems and legal issues lie two deeper ethical dilemmas that are the focus of this book. The first question is: What does the state and citizens owe to the individuals it detains, given their ongoing contributions in relationships to dependents? The second is: What does the state and citizens owe to innocent dependents in view of the collateral consequences of their caregivers’ detention, which has so often been influenced by prejudice against disadvantaged minority communities?

Children with low-grade gliomas have excellent long-term survival outcomes. The development of therapies targeted to the driver mutations along the Mitogen Activated Protein (MAP) kinase signalling pathway are providing long-term stability for many patients with these tumours. Given the frequency of these tumours residing within or near the suprasellar region, our patients commonly suffer from hormone deficiencies. In Australia, the Pharmaceutical Benefits Scheme currently restricts growth hormone therapy to patients who are not being actively treated for cancer, including those receiving targeted therapies. This viewpoint hopes to facilitate an important discussion amongst our colleagues as to whether this should be changed to allow growth hormone to become available to children on chronic tumour suppressive therapy.

Background: Our understanding of the importance of microbiomes on large aquatic animals—such as whales, sea turtles and manatees—has advanced considerably in recent years. Recent activity describing the epizoic diatoms growing on marine vertebrates suggests that these epibiotic diatom communities constitute diverse, polyphyletic, and compositionally stable assemblages that include both putatively obligate epizoic and generalist species. Here, we outline a successful attempt to culture putatively obligate epizoic diatoms without their hosts and propose further applications and research avenues in this growing area of study. Results: We cultured cells of epizoic diatoms from multiple host species sampled in the wild and captivity. Analyzing the DNA sequences of these cultures, we found that several unique diatom taxa have independently evolved to occupy in epibiotic habitats. We created a library of reference sequence data for use in metabarcoding surveys of sea turtle and manatee microbiomes that will further facilitate the use of environmental DNA for studying host specificity in epizoic diatoms and the utility of diatoms as indicators of host ecology and health. Conclusions: Our discovery that epizoic diatoms can be cultured independently from their hosts raises several questions about the nature of the interaction between these diatom species and their hosts. We encourage the interdisciplinary community working with marine megafauna to consider including diatom sampling and diatom analysis into their routine practices.

GPUs are used in high-reliability systems, including high-performance computers and autonomous vehicles. Because GPUs employ a high-bandwidth, wide-interface to DRAM and fetch each memory access from a single DRAM device, implementing full-device correction through ECC is expensive and impractical. This challenge is compounded by worsening relative rates of multi-bit DRAM errors and increasing GPU memory capacities. This paper first presents high-energy neutron beam testing results for the HBM2 memory on a compute-class GPU. These results uncovered unexpected intermittent errors that we determine to be caused by cell damage from the high-intensity beam. As these errors are an artifact of the testing apparatus, we provide best-practice guidance on how to identify and filter them from the results of beam testing campaigns. Second, we use the soft error beam testing results to inform the design and evaluation of system-level error protection mechanisms by reporting the relative error rates and error patterns from soft errors in GPU DRAM. We observe locality in the multi-bit errors, which we attribute to the underlying structure of the HBM2 memory. Based on these error patterns, we propose several novel ECC schemes to decrease the silent data corruption risk by up to five orders of magnitude relative to SEC-DED ECC, while also reducing the number of uncorrectable errors by up to 7.87 ×. We compare novel binary and symbol-based ECC organizations that differ in their design complexity, hardware overheads, and permanent error correction abilities, ultimately recommending two promising organizations. These schemes replace SEC-DED ECC with no additional redundancy, likely no performance impacts, and modest area and complexity costs.

Cisplatin is a highly effective chemotherapy medicine used in the treatment of many childhood cancers. Like all medications, cisplatin has many side effects and as always the treatment of cancer in children is a balance between the risks of the medications used and their potential benefits. While many side effects of cisplatin chemotherapy are reversible, one major side effect is permanent and irreversible hearing loss (ototoxicity) in both ears which may worsen with time. The severity of cisplatin-related ototoxicity is associated with age and the cumulative dose received: the younger the child and the higher the total dose, the more severe the hearing loss may be. The spectrum of hearing loss varies from mild to moderate high tone hearing loss, to profound loss across the hearing range and permanent deafness. In addition to hearing loss, some children, especially adolescents, also experience tinnitus and vertigo. Cisplatin ototoxicity is one of most important of the many long-term effects experienced by children who are cured of their cancer. The burden of this toxicity may be compounded by other long-term health issues that emerge with time. This chapter will focus on cisplatin-induced hearing loss, its mechanisms, its health impact on the young person and ways to mitigate or reduce the severity of ototoxicity. This chapter has been written by a multi-disciplinary team including paediatric oncologists, audiologists, a psychologist, a health scientist and a parent of a child growing up with high frequency hearing loss.

This article highlights the role that US Chamber of Commerce lobbyists and border politicians played in limiting restrictions on Mexican labour migration to the United States in the 1920s. Together, they successfully resisted calls for stricter statutory limitations on the admission of Mexican migrants by emphasizing their economic and civic contributions.

The issue of gender diversity on corporate boards is attracting research interest because of purported contributions of women directors, including improved monitoring, ethical focus, and democratic leadership. This rationale forms part of the economic case for women’s participation on corporate boards, as opposed to alternative arguments based on social or equality considerations. In this study, we examined the effect of board diversity for Philippine firms during the period 2003 to 2014. Using an unbalanced panel of 2648 firm-years, we found that greater board diversity did not significantly affect either short-term firm performance or long-term firm value. Our findings show that female and male corporate leaders have comparable competency levels and that increasing women’s presence on corporate boards has no discernible effect on firm performance.

Background The emerging role of genomically guided precision medicine in pediatric cancer care presents significant clinical, practical, and ethical challenges. We investigated the factors that influence decision-making in genomic medicine from the perspective of different stakeholders in the context of difficult-to-treat childhood cancer. Methods Health care providers (HCPs), parents of childhood cancer survivors, and general community members completed an online discrete choice experiment survey. Respondents considered whether to recommend (HCPs) or choose (parents/community) a genomically guided approach to pediatric cancer treatment. Respondents completed eight choice questions varying by survival benefit, prognosis, likelihood of finding a target, quality of life (QoL), HCP/parent preference, need for biopsy, cost, and who pays. Data were analyzed using a probability regression model, with findings expressed as relative importance, stated importance, and marginal willingness to pay (mWTP). Results One hundred twenty-six HCPs, 130 parents, and 531 community members participated. The probability of recommending/choosing genomically guided treatment increased significantly with better prognosis, survival benefit, improvements in QoL, and decision-making partner support. It decreased with increasing costs and if parents paid for treatment. HCPs were more responsive to all factors but were most influenced by survival outcomes, and parents and community members by QoL. In contrast to these forced choice preference results, HCPs stated they were most influenced by QoL and community members by survival. Conclusion Our findings support the primacy of QoL in genomic decision-making, with some differences across stakeholders in the other factors influencing decision-making. These findings emphasize the need for high-quality information giving and communication to support genomic medicine choices.

This paper proposes an automated AV safety evaluation framework, Suraksha that quantifies and analyzes the sensitivities of different design parameters on AV safety. It employs a set of driving scenarios generated based on a user-specified difficulty level. It enables the exploration of tradeoffs in requirements either in existing AV implementations to find opportunities for improvement or during the development process to explore the component-level requirements for an optimal and safe AV architecture. As perception is a resource demanding task, we employ Suraksha to analyze the safety effects of using various perception parameters on an industrial AV system.

GPUs have found wide acceptance in domains such as high-performance computing and autonomous vehicles, which require fast processing of large amounts of data along with provisions for reliability, availability, and safety. A key component of these dependability characteristics is the propagation of errors and their eventual effect on system outputs. In addition to analytical and simulation models, fault injection is an important technique that can evaluate the effect of errors on a complete computing system running the full software stack. However, the complexity of modern GPU systems and workloads challenges existing fault injection tools. Some tools require the recompilation of source code that may not be available, struggle to handle dynamic libraries, lack support for modern GPUs, or add unacceptable performance overheads. We introduce the NVBitFI tool for fault injection into GPU programs. In contrast with existing tools, NVBitFI performs instrumentation of code dynamically and selectively to instrument the minimal set of target dynamic kernels; as it requires no access to source code, NVBitFI provides improvements in performance and usability. The NVBitFI tool is publicly available for download and use at https://github.com/NVlabs/nvbitfi.

PURPOSE SJMB03 (ClinicalTrials.gov identifier: NCT00085202 ) was a phase III risk-adapted trial that aimed to determine the frequency and clinical significance of biological variants and genetic alterations in medulloblastoma. PATIENTS AND METHODS Patients 3-21 years old were stratified into average-risk and high-risk treatment groups based on metastatic status and extent of resection. Medulloblastomas were molecularly classified into subgroups (Wingless [WNT], Sonic Hedgehog [SHH], group 3, and group 4) and subtypes based on DNA methylation profiles and overlaid with gene mutations from next-generation sequencing. Coprimary study end points were (1) to assess the relationship between ERBB2 protein expression in tumors and progression-free survival (PFS), and (2) to estimate the frequency of mutations associated with WNT and SHH tumors. Clinical and molecular risk factors were evaluated, and the most robust were used to model new risk-classification categories. RESULTS Three hundred thirty eligible patients with medulloblastoma were enrolled. Five-year PFS was 83.2% (95% CI, 78.4 to 88.2) for average-risk patients (n = 227) and 58.7% (95% CI, 49.8 to 69.1) for high-risk patients (n = 103). No association was found between ERBB2 status and PFS in the overall cohort ( P = .74) or when patients were stratified by clinical risk ( P = .71). Mutations in CTNNB1 (96%), DDX3X (37%), and SMARCA4 (24%) were most common in WNT tumors and PTCH1 (38%), TP53 (21%), and DDX3X (19%) in SHH tumors. Methylome profiling classified 53 WNT (17.4%), 48 SHH (15.7%), 65 group 3 (21.3%), and 139 group 4 (45.6%) tumors. A comprehensive clinicomolecular risk factor analysis identified three low-risk groups (WNT, low-risk SHH, and low-risk combined groups 3 and 4) with excellent (5-year PFS > 90%) and two very high-risk groups (high-risk SHH and high-risk combined groups 3 and 4) with poor survival (5-year PFS < 60%). CONCLUSION These results establish a new risk stratification for future medulloblastoma trials.

The COVID-19 pandemic quickly led to an abundance of publications and recommendations, despite a paucity of information on how COVID-19 affects children with cancer. This created a dire need for a trusted resource with curated information and a space for the pediatric oncology community to share experiences. The Global COVID-19 Observatory and Resource Center for Childhood Cancer was developed, launched, and maintained by the International Society of Pediatric Oncology and St. Jude Children's Research Hospital. The three components (Resource Library, Global Registry, and Collaboration Space) complement each other, establishing a mechanism to generate and transfer knowledge rapidly throughout the community. Fil: Moreira, Daniel C.. St. Jude Children's Research Hospital; Estados Unidos Fil: Sniderman, Elizabeth. St. Jude Children's Research Hospital; Estados Unidos Fil: Mukkada, Sheena. St. Jude Children's Research Hospital; Estados Unidos Fil: Chantada, Guillermo Luis. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina Fil: Bhakta, Nickhill. St. Jude Children's Research Hospital; Estados Unidos Fil: Foster, Whitney. St. Jude Children's Research Hospital; Estados Unidos Fil: Avula, Meghana. St. Jude Children's Research Hospital; Estados Unidos Fil: Homsi, Maysam R.. St. Jude Children's Research Hospital; Estados Unidos Fil: Faughnan, Lane. St. Jude Children's Research Hospital; Estados Unidos Fil: Happ, Brooke. St. Jude Children's Research Hospital; Estados Unidos Fil: Andujar, Allyson. St. Jude Children's Research Hospital; Estados Unidos Fil: Sonnenfelt, Jason. St. Jude Children's Research Hospital; Estados Unidos Fil: Dalvi, Rashmi. Bombay Hospital And Medical Research Centre; India Fil: Frazier, A. Lindsay. No especifíca; Fil: Hessissen, Laila. Universite Mohammed V. Rabat; Otros paises de África Fil: Kearns, Pamela R.. No especifíca; Fil: Luna Fineman, Sandra. No especifíca; Fil: Moreno, Arturo. Hospital Universitario de Puebla; México Fil: Saghir Khan, Muhammad. No especifíca; Fil: Sullivan, Michael. Royal Children's Hospital, Melbourne; Australia Fil: Devidas, Meenakshi. St. Jude Children's Research Hospital; Estados Unidos Fil: Santana, Victor. St. Jude Children's Research Hospital; Estados Unidos Fil: Caniza, Miguela. St. Jude Children's Research Hospital; Estados Unidos Fil: Pritchard Jones, Kathy. University College London; Estados Unidos Fil: Rodriguez Galindo, Carlos. St. Jude Children's Research Hospital; Estados Unidos

The COVID-19 pandemic poses an unprecedented health crisis in all socio-economic regions across the globe. While the pandemic has had a profound impact on access to and delivery of health care by all services, it has been particularly disruptive for the care of patients with life-threatening noncommunicable diseases (NCDs) such as the treatment of children and young people with cancer. The reduction in child mortality from preventable causes over the last 50 years has seen childhood cancer emerge as a major unmet health care need. Whilst survival rates of 85% have been achieved in high income countries, this has not yet been translated into similar outcomes for children with cancer in resource-limited settings where survival averages 30%. Launched in 2018, by the World Health Organization (WHO), the Global Initiative for Childhood Cancer (GICC) is a pivotal effort by the international community to achieve at least 60% survival for children with cancer by 2030. The WHO GICC is already making an impact in many countries but the disruption of cancer care during the COVID-19 pandemic threatens to set back this global effort to improve the outcome for children with cancer, wherever they may live. As representatives of the global community committed to fostering the goals of the GICC, we applaud the WHO response to the COVID-19 pandemic, in particular we support the WHO's call to ensure the needs of patients with life threatening NCDs including cancer are not compromised during the pandemic. Here, as collaborative partners in the GICC, we highlight specific areas of focus that need to be addressed to ensure the immediate care of children and adolescents with cancer is not disrupted during the pandemic; and measures to sustain the development of cancer care so the long-term goals of the GICC are not lost during this global health crisis. Fil: Pritchard Jones, Kathy. University College London; Estados Unidos Fil: de Abib, Simone C.V.. International Society Of Paediatric Surgical Oncology; Surinam. Universidade Federal de Sao Paulo; Brasil Fil: Esiashvili, Natia. University of Emory; Estados Unidos Fil: Kaspers, Gertjan J.L.. Princess Máxima Center for Pediatric Oncology; Países Bajos Fil: Rosser, Jon. No especifíca; Fil: van Doorninck, John A.. Rocky Mountain Hospital for Children; Estados Unidos Fil: Braganca, João M.L.. No especifíca; Fil: Hoffman, Ruth I.. No especifíca; Fil: Rodriguez Galindo, Carlos. St Jude Children’s Research Hospital; Estados Unidos Fil: Adams, Cary. Union for International Cancer Control; Suiza Fil: Connor, Stephen R.. Worldwide Hospice Palliative Care Alliance; Estados Unidos Fil: Abdelhafeez, Abdelhafeez H.. International Society of Paediatric Surgical Oncology; Suiza. St. Jude Children’s Research Hospital; Estados Unidos Fil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; Canadá. International Society of Paediatric Surgical Oncology; Suiza Fil: Howard, Scott C.. International Society of Paediatric Surgical Oncology; Suiza. University of Tennessee; Estados Unidos Fil: Challinor, Julia M.. International Society of Paediatric Surgical Oncology; Suiza. University of California; Estados Unidos Fil: Hessissen, Laila. Children Hospital of Rabat; Marruecos. International Society of Paediatric Surgical Oncology; Suiza Fil: Dalvi, Rashmi B.. Bombay Hospital Institute of Medical Sciences; India. International Society of Paediatric Surgical Oncology; Suiza Fil: Kearns, Pamela. International Society of Paediatric Surgical Oncology; Suiza Fil: Chantada, Guillermo Luis. International Society of Paediatric Surgical Oncology; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Frazier, Lindsay A.. International Society of Paediatric Surgical Oncology; Suiza. Dana-Farber Cancer Institute; Estados Unidos Fil: Sullivan, Michael J.. University of Melbourne; Australia. International Society of Paediatric Surgical Oncology; Suiza Fil: Schulte, Fiona S.M.. University of Calgary; Canadá. International Society of Paediatric Surgical Oncology; Suiza Fil: Morrissey, Lisa K.. Boston Children’s Hospital; Estados Unidos. International Society of Paediatric Surgical Oncology; Suiza Fil: Kozhaeva, Olga. European Society for Paediatric Oncology; Bélgica Fil: Luna Fineman, Sandra. Children’s Hospital Colorado; Estados Unidos. International Society of Paediatric Oncology; Suiza Fil: Khan, Muhammad S.. Tawam Hospital; Emiratos Arabes Unidos

Background Sarcomas represent 10%–15% of cancers in adolescent and young adult (AYA) patients, and survival for those with metastatic disease or relapse is poor. Immunotherapy with checkpoint inhibition has improved outcomes in multiple tumor types, but data in advanced sarcomas, particularly within the AYA population, are limited. Aim We aim to evaluate response and toxicity for AYA patients with sarcoma treated with pembrolizumab. Methods and results We retrospectively reviewed AYA patients with advanced bone and soft tissue sarcoma who received self‐funded pembrolizumab between May 2015 and January 2019. Eighteen patients were identified. One patient with Ewing sarcoma had a sustained complete response to therapy. Two patients with alveolar soft part sarcoma received a clinical benefit from pembrolizumab: one had a radiological partial response with an excellent clinical response and one patient achieved stable disease. Four patients died of disease prior to first scheduled assessment and thus were not evaluable. The remaining eleven patients had progressive disease. Conclusion The role of immunotherapy in AYA sarcoma warrants further investigation. Biomarkers of response need to be further evaluated in order to guide patient selection.

BACKGROUND The GCCCR is a collaboration between SIOP and SJCRH to describe the natural history of SARS-CoV-2 in children with cancer across the world. METHODS The GCCCR is a deidentified registry of patients RESULTS As of August 10th 2020, the GCCCR included 730 cases from 35 countries, including 64 children with CNS tumors (8.8%) from 17 countries. The most frequent diagnoses were embryonal tumors (31.2%) and low-grade glioma (17.2%). Thirty-nine (60.9%) children were asymptomatic from infection, while 19 (29.7%) patients required hospital admission and 2 (6.3%) transferred to the intensive care unit. There was a significant association between infection severity and ANC CONCLUSION The frequency and severity of COVID infection among children with CNS tumors appears to be proportionally lower compared to other children with cancer. Although this is the largest cohort of patients reported to date, additional insight is needed, including the effects of treatment modifications on outcomes.

Fault injection (FI) techniques are typically used to determine the reliability profiles of programs under soft errors. However, these techniques are highly resource- and time-intensive. Prior research developed a model, TRIDENT to analytically predict Silent Data Corruption (SDC, i.e., incorrect output without any indication) probabilities of single-threaded CPU applications without requiring FIs. Unfortunately, TRIDENT is incompatible with GPU programs, due to their high degree of parallelism and different memory architectures than CPU programs. The main challenge is that modeling error propagation across thousands of threads in a GPU kernel requires enormous amounts of data to be profiled and analyzed, posing a major scalability bottleneck for HPC applications.In this paper, we propose GPU-TRIDENT, an accurate and scalable technique for modeling error propagation in GPU programs. We find that GPU-TRIDENT is 2 orders of magnitude faster than FI-based approaches, and nearly as accurate in determining the SDC rate of GPU programs.

This paper proposes AV-FUZZER, a testing framework, to find the safety violations of an autonomous vehicle (AV) in the presence of an evolving traffic environment. We perturb the driving maneuvers of traffic participants to create situations in which an AV can run into safety violations. To optimally search for the perturbations to be introduced, we leverage domain knowledge of vehicle dynamics and genetic algorithm to minimize the safety potential of an AV over its projected trajectory. The values of the perturbation determined by this process provide parameters that define participants’ trajectories. To improve the efficiency of the search, we design a local fuzzer that increases the exploitation of local optima in the areas where highly likely safety-hazardous situations are observed. By repeating the optimization with significantly different starting points in the search space, AV-FUZZER determines several diverse AV safety violations. We demonstrate AV-FUZZER on an industrial-grade AV platform, Baidu Apollo, and find five distinct types of safety violations in a short period of time. In comparison, other existing techniques can find at most two. We analyze the safety violations found in Apollo and discuss their overarching causes.

Replication repair deficiency (RRD) leading to hypermutation is an important driving mechanism of high-grade glioma (HGG) occurring predominantly in the context of germline mutations in RRD-associated genes. Although HGG presents specific patterns of DNA methylation corresponding to oncogenic mutations, this has not been well studied in replication repair-deficient tumors. We analyzed 51 HGG arising in the background of gene mutations in RRD utilizing either 450 k or 850 k methylation arrays. These were compared with HGG not known to be from patients with RRD. RRD HGG harboring secondary mutations in glioma genes such as IDH1 and H3F3A displayed a methylation pattern corresponding to these methylation subgroups. Strikingly, RRD HGG lacking these known secondary mutations clustered together with an incompletely described group of HGG previously labeled “Wild type-C” or “Paediatric RTK 1”. Independent analysis of two comparator HGG cohorts showed that other RRD/hypermutant tumors clustered within these subgroups, suggesting that undiagnosed RRD may be driving some HGG clustering in this location. RRD HGG displayed a unique CpG Island Demethylator Phenotype in contrast to the CpG Island Methylator Phenotype described in other cancers. Hypomethylation was enriched at gene promoters with prominent demethylation in genes and pathways critical to cellular survival including cell cycle, gene expression, cellular metabolism, and organization. These data suggest that methylation arrays may provide diagnostic information for the detection of RRD HGG. Furthermore, our findings highlight the unique natural selection pressures in these highly dysregulated, hypermutant cancers and provide the novel impact of hypermutation and RRD on the cancer epigenome.

GPUs accelerate high-throughput applications, which require orders-of-magnitude higher memory bandwidth than traditional CPU-only systems. However, the capacity of such high-bandwidth memory tends to be relatively small. Buddy Compression is an architecture that makes novel use of compression to utilize a larger buddy-memory from the host or disaggregated memory, effectively increasing the memory capacity of the GPU. Buddy Compression splits each compressed 128B memory-entry between the high-bandwidth GPU memory and a slower-but-larger buddy memory such that compressible memory-entries are accessed completely from GPU memory, while incompressible entries source some of their data from off-GPU memory. With Buddy Compression, compressibility changes never result in expensive page movement or re-allocation. Buddy Compression achieves on average $1.9 \times$ effective GPU memory expansion for representative HPC applications and $1.5 \times$ for deep learning training, performing within 2% of an unrealistic system with no memory limit. This makes Buddy Compression attractive for performance-conscious developers that require additional GPU memory capacity.

Population-based cancer registries (PBCRs) generate measures of cancer incidence and survival that are essential for cancer surveillance, research, and cancer control strategies. In 2014, the Toronto Paediatric Cancer Stage Guidelines were developed to standardise how PBCRs collect data on the stage at diagnosis for childhood cancer cases. These guidelines have been implemented in multiple jurisdictions worldwide to facilitate international comparative studies of incidence and outcome. Robust stratification by risk also requires data on key non-stage prognosticators (NSPs). Key experts and stakeholders used a modified Delphi approach to establish principles guiding paediatric cancer NSP data collection. With the use of these principles, recommendations were made on which NSPs should be collected for the major malignancies in children. The 2014 Toronto Stage Guidelines were also reviewed and updated where necessary. Wide adoption of the resultant Paediatric NSP Guidelines and updated Toronto Stage Guidelines will enhance the harmonisation and use of childhood cancer data provided by PBCRs.

In pediatric low‐grade gliomas not amenable to complete resection, various chemotherapy regimens are the mainstream of treatment. An excellent overall survival of these patients makes justification of the intensification of chemotherapy difficult and calls for the development of new strategies. Bevacizumab, a humanized monoclonal antibody directed against Vascular endothelial growth factor (VEGF), has been successfully used in combination with irinotecan in a number of adult and pediatric studies and reports. Fifteen patients at median age of 7 years old (range 3 months to 15 years) were treated with bevacizumab in combination with conventional low‐toxicity chemotherapy. The majority had chiasmatic/hypothalamic and midline tumors, seven had confirmed BRAF pathway alterations including neurofibromatosis type 1 (2). Fourteen patients had more than one progression and three had radiotherapy. No deaths were documented, PFS at 11 and 15 months was 71.5% ± 13.9% and 44.7% ± 17.6% respectively. At the end of follow‐up 40% of patients has radiologically stable disease, three patients progressed shortly after completion of bevacizumab and two showed mixed response with progression of cystic component. Rapid visual improvement was seen in 6/8 patients, resolution of endocrine symptoms in 2/4 and motor function improvement in 4/6. No relation between histology or BRAF status and treatment response was observed. Treatment‐limiting toxicities included grade 4 proteinuria (2) and hypertension (2) managed with cessation (1) and pausing of therapy plus antihypertensives (1). In conclusion, bevacizumab is well tolerated and appears most effective for rapid tumor control to preserve vision and improve morbidity.

Until now only one group of diatoms, the Bacillariaceae, was known to contain heterotrophic representatives. We show that a second group, represented by species in the genus Tursiocola, has undergone evolutionary loss of photosynthesis within the Bacillariophyta. Heterotrophy was evidenced by the presence of only apochlorotic cells in live and motile specimens. Three species of Tursiocola (T. bondei sp. nov., T. alata sp. nov., and T. gracilis sp. nov.), of which at least two are apochlorotic, are described as new to science from the skin of Florida manatees. T. ziemanii and T. varicopulifera were also observed to be apochlorotic. A new morphological feature termed a "fastigium" was observed on some Tursiocola spp. and is described as an extension of the mantle margin at the valve apex that overhangs the apex and extends towards the valve face. The presence of greatly elevated marginal ridges on the valve face of T. alata sp. nov. is a newly observed morphological character within the genus. Phylogenetic analyses using ribosomal RNA sequences indicate that Tursiocola is monophyletic, though morphological character analysis suggests paraphyly as species of the closely related Epiphalaina genus are embedded within a larger Tursiocola clade.

Canada grants citizenship expansively to most persons born subject to its territorial jurisdiction. Canada’s Charter of Rights and Freedoms also treats naturalized and native-born citizens as equal...

Childhood pilocytic astrocytomas (PA) are low‐grade tumours with an excellent prognosis. However, a minority, particularly those in surgically inaccessible locations, have poorer long‐term outcome. At present, it is unclear whether anatomical location in isolation, or in combination with underlying biological variation, determines clinical behaviour. Here, we have tested the utility of DNA methylation profiling to inform tumour biology and to predict behaviour in paediatric PA. Genome‐wide DNA methylation profiles were generated for 117 paediatric PAs. Using a combination of analyses, we identified DNA methylation variants specific to tumour location and predictive of behaviour. Receiver‐operating characteristic analysis was used to test the predictive utility of clinical and/or DNA methylation features to classify tumour behaviour at diagnosis. Unsupervised analysis distinguished three methylation clusters associated with tumour location (cortical, midline and infratentorial). Differential methylation of 5404 sites identified enrichment of genes involved in ‘embryonic nervous system development’. Specific hypermethylation of NEUROG1 and NR2E1 was identified as a feature of cortical tumours. A highly accurate method to classify tumours according to behaviour, which combined three clinical features (age, location and extent of resection) and methylation level at a single site, was identified. Our findings show location‐specific epigenetic profiles for PAs, potentially reflecting their cell type of origin. This may account for differences in clinical behaviour according to location independent of histopathology. We also defined an accurate method to predict tumour behaviour at diagnosis. This warrants further testing in similar patient cohorts.

In this article, I make a policy argument in defense of family and relationship-based immigration preferences in U.S. immigration law that accounts for economic objections and calls for solidarity among socioeconomically disadvantaged U.S. residents on this issue. I begin with a historical account of policy arguments for limiting family-based immigration. I challenge the view that family-based immigration is a fiscal burden on the nation as a whole and acts against the interests of disadvantaged native-born workers. Then, I present and respond to perception-based objections to family-based immigration by disadvantaged citizens who believe that they are suffering from competition with mixed-skilled immigrants, including those sponsored by family members. Advocates of family unity in immigration policy are fighting the perception of zero-sum competition between immigrants and disadvantaged citizens by organizing together for improvements in wages and working conditions, leveraging arguments from the U.S. civil rights struggle to advocate for inclusive immigration policies.