Copy number variations and cancer

DNA copy number variations (CNVs) are an important component of genetic variation, affecting a greater fraction of the genome than single nucleotide polymorphisms (SNPs). The advent of high-resolution SNP arrays has made it possible to identify CNVs. Characterization of widespread constitutional (germline) CNVs has provided insight into their role in susceptibility to a wide spectrum of diseases, and somatic CNVs can be used to identify regions of the genome involved in disease phenotypes. The role of CNVs as risk factors for cancer is currently underappreciated. However, the genomic instability and structural dynamism that characterize cancer cells would seem to make this form of genetic variation particularly intriguing to study in cancer. Here, we provide a detailed overview of the current understanding of the CNVs that arise in the human genome and explore the emerging literature that reveals associations of both constitutional and somatic CNVs with a wide variety of human cancers

Applying a 6 DoF robotic arm and digital twin to automate fan-blade reconditioning for aerospace maintenance, repair, and overhaul

The UK is home to several major air commercial and transport hubs. As a result, there is a high demand for Maintenance, Repair, and Overhaul (MRO) services to ensure that fleets of aircraft are in airworthy conditions. MRO services currently involve heavy manual labor. This creates bottlenecks, low repeatability, and low productivity. Presented in this paper is an investigation to create an automation cell for the fan-blade reconditioning component of MRO. The design and prototype of the automation cell is presented. Furthermore, a digital twin of the grinding process is developed and used as a tool to explore the required grinding force parameters needed to effectively remove surface material. An integration of a 6-DoF industrial robot with an end-effector grinder and a computer vision system was undertaken. The computer vision system was used for the digitization of the fan-blade surface as well as tracking and guidance of material removal. Our findings reveal that our proposed system can perform material removal, track the state of the fan blade during the reconditioning process and do so within a closed-loop automated robotic work cell

Medulloblastoma has a global impact on health related quality of life: Findings from an international cohort.

BackgroundUnderstanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients.MethodsSeventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables on HRQL was considered-including molecular subgroup.ResultsThe majority of patients reported having moderate or severe overall burden of morbidity for both the HUI2 and HUI3 (HUI2 = 60%; HUI3 = 72.1%) when proxy-assessed. Self-care in the HUI2 was rated as higher (ie better outcome) for patients from Western versus Eastern sites, P = .02. Patients with nonmetastatic status had higher values (ie better outcomes) for the HUI3 hearing, HUI3 pain, and HUI2 pain, all P < .05. Patients treated with a gross total resection also had better outcomes for the HUI3 hearing (P = .04). However, those who underwent a gross total resection reported having worse outcomes on the HUI3 vision (P = .02). No differences in HRQL were evident as a function of subgroup.ConclusionsBy examining an international sample of survivors, we characterized the worldwide impact of medulloblastoma. This is a critical first step in developing global standards for evaluating long-term outcomes

Quantum evolution across singularities: the case of geometrical resolutions

We continue the study of time-dependent Hamiltonians with an isolated singularity in their time dependence, describing propagation on singular space-times. In previous work, two of us have proposed a "minimal subtraction" prescription for the simplest class of such systems, involving Hamiltonians with only one singular term. On the other hand, Hamiltonians corresponding to geometrical resolutions of space-time tend to involve multiple operator structures (multiple types of dependence on the canonical variables) in an essential way. We consider some of the general properties of such (near-)singular Hamiltonian systems, and further specialize to the case of a free scalar field on a two-parameter generalization of the null-brane space-time. We find that the singular limit of free scalar field evolution exists for a discrete subset of the possible values of the two parameters. The coordinates we introduce reveal a peculiar reflection property of scalar field propagation on the generalized (as well as the original) null-brane. We further present a simple family of pp-wave geometries whose singular limit is a light-like hyperplane (discontinuously) reflecting the positions of particles as they pass through it.Comment: 25 pages, 1 figur

Social referencing and the security of attachment

The second episode of the Strange Situation procedure was used to study individual differences in infants' social referencing and relationships to the security of attachment. This 3-min episode entails interaction with an unfamiliar adult in which infants may seek emotional cues from mother. Forty-three 19 1/2 -month-old infants were observed. From videotaped records, the security of attachment was assessed using Ainsworth's criteria. For episode 2, minute-by-minute ratings of infant referencing and proximity to mother, and the quality of maternal utterances (to assess maternal emotional cuing) were performed. Referencing declined throughout the episode and was negatively related to proximity. A marginally significant (p <.06) main effect for attachment classification revealed that insecureresistant infants referenced most frequently (and showed persistent referencing early in the episode), insecure-avoidant babies referenced least frequently, with securely attached infants in between. Mothers displayed a positive vocal tone to the baby but did not vary with infant attachment status. These findings suggest that referencing may reflect aspects of secure base behavior which distinguish securely from insecurely attached infants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24687/1/0000106.pd

Trauma Focussed-CBT and EMDR for young people with trauma and psychosis (using a phasic treatment approach):two early intervention service case studies

The relationship between trauma and psychosis is well established with a large amount of overlap between the ICD/DSM (International Classification of Diseases/Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria for post-traumatic stress disorder (PTSD) and psychosis and/or schizophrenia. In spite of co-morbidity and evidence of the links and underlying mechanisms, trauma is rarely a focus of intervention in psychosis. Psychosis has often been on the list of exclusion criteria for PTSD research studies. There is a lack of literature on the impact of trauma work with people experiencing psychosis. The National Institute for Health and Care Excellence (NICE) (2014) suggests that Early Intervention in Psychosis (EIP) service users should be assessed for PTSD, and PTSD guidelines (NICE, 2005) followed for those who show signs of post-traumatic stress. There is a need to evaluate the effectiveness of therapeutic approaches for people with PTSD and co-morbid psychosis. These case studies aim to provide initial evidence of how two EIP clients experienced and responded to NICE-recommended psychological therapy for trauma. This study aims to test the feasibility of trauma work delivered via a phasic approach in a novel population. Two EIP clients received psychological therapy [including traumafocused cognitive behavioural therapy (CBT) and eye movement desensitization and reprocessing (EMDR)] for identified traumatic experiences. Assessment outcome measures were utilized to establish the effectiveness of the interventions. Both clients reported significant improvements following therapy, including reduced trauma-related distress, reduced distress from symptoms of psychosis and improved quality of life. Clients with co-morbid PTSD and symptoms of psychosis are likely to benefit from recommended psychological treatments for PTSD. Further research is required to address generalizability to a larger population