Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

End-Stage Renal Disease Among HIV-Infected Adults in North America

Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks

The family cancer experience : a qualitative study of families in which an adult member is living with cancer

This study was designed to elicit the perceptions of families who are experiencing cancer in one of their adult members for the purpose of describing and explaining psychosocial aspects of the cancer experience from a family perspective. The method used in conducting this study was the phenomenological paradigm of qualitative research. Data were collected through a series of interviews with eight families comprised of a total of seventeen members. The eight cancer-patient members were all between the ages of 59 and 66. The initial interviews were loosely guided by the research questions, and addressed the families' perceptions of the impact of cancer upon psychosocial aspects of their everyday lives. The data were comprised of the accounts given by families in these interviews. Constant comparative analysis was employed throughout the data collection phase to permit analytic material to guide and focus the process of constructing accounts. The families described their everyday lives with cancer as being normal lives notwithstanding a number of changes directly associated with having cancer. They perceived themselves to have minimized the impact of change through a number of consciously-chosen strategic approaches. They explained the normalcy of their experiences in terms of the successfulness of these strategic approaches. Further, they explained the success of their strategies in terms of the relationship of these strategies to their family self-concept and philosophy. The data revealed the capacity of older families to modify and make sense of their cancer experiences. By applying attitudes which conformed to their histories and philosophies, they minimized changes in everyday life, created support networks, facilitated the quality of their medical care, and generated hope. In terms of nursing practice, these findings reinforce the value of incorporating family beliefs and attitudes into all phases of the nursing process. They therefore strengthen the argument for evaluating effective and ineffective coping on an individual basis rather than according to commonly-held assumptions. Implications for future nursing research include further exploration of selected themes that emerged from the study, and expansion of the body of knowledge about family functioning to include the family's perspective.Applied Science, Faculty ofNursing, School ofGraduat

The rocks and hard places of MAiD: a qualitative study of nursing practice in the context of legislated assisted death

Background: Medical Assistance in Dying (MAiD) was legalized in Canada in June, 2016. The Canadian government’s decision to legislate assisted dying, an approach that requires a high degree of obligation, precision, and delegation, has resulted in unique challenges for health care and for nursing practice. The purpose of this study was to better understand the implications of a legislated approach to assisted death for nurses’ experiences and nursing practice. Methods: The study used a qualitative approach guided by Interpretive Description. Semi-structured interviews were conducted with 59 registered nurses and nurse practitioners. Interviews were audio-recorded, transcribed, and managed using qualitative analysis software. Analysis followed a procedure of data immersion, open coding, constant comparative analysis, and the construction of a thematic and interpretive account. Results: Nurses in this study described great variability in how MAiD had been enacted in their work context and the practice supports available to guide their practice. The development of systems to support MAiD, or lack thereof, was largely driven by persons in influential leadership positions. Workplaces that supported a range of nurses’ moral responses to MAiD were most effective in supporting nurses’ well-being during this impactful change in practice. Participants cited the importance of teamwork in providing high quality MAiD-related care; although, many worked without the benefit of a team. Nursing work related to MAiD was highly complex, largely because of the need for patient-centered care in systems that were not always organized to support such care. In the absence of adequate practice supports, some nurses were choosing to limit their involvement in MAiD. Conclusions: Data obtained in this study suggested that some workplace contexts still lack the necessary supports for nurses to confidently meet the precision required of a legislated approach to MAiD. Without accessible palliative care, sufficient providers, a supportive team, practice supports, and a context that allowed nurses to have a range of responses to MAiD, nurses felt they were legally and morally at risk. Nurses seeking to provide the compassionate care consistent with such a momentous moment in patients’ lives, without suitable supports, find themselves caught between the proverbial rock and hard place.Other UBCNon UBCReviewedFacult

Perceptions of the family physician from adolescents and their caregivers preparing to transition to adult care

Background: Adolescents with chronic health conditions and/or disabilities (CHC/D’s) often face challenges when transitioning to adult care, which leads to a higher risk of morbidity and mortality. Although it is recommended that establishing the medical home and family physician (FP) attachment prior to transfer will improve health outcomes, there is little evidence or policy surrounding the role of the FP during this transition. This study explores the described use of health services by adolescents with CHC/D’s, as well as the adolescent’s and caregiver’s perceptions of their FP. Methods: Participants were recruited from the British Columbia Children’s Hospital, Canada and a multi-method phased approach was used. In Phase 1, 84 adolescent and caregiver pairs completed questionnaires asking what medical services they accessed for specific health needs. In Phase 2, another cohort of 21 adolescent and caregiver pairs completed the same questionnaires and were interviewed regarding their perception of their FP. Results: 96% (n = 81) of adolescents with CHC/D’s in phase 1 had a FP. Thirty four percent (n = 34) of adolescents had not seen their FP in the last 6 months. While adolescents with CHC/D mostly accessed their FP for primary health issues, they frequently also accessed specialists for prescription refills (50%, n = 51), mental health (29%, n = 30) and sexual health (16%, n = 16). While most adolescent/caregiver participants reported positive communication and trust in their FP, some had a poor understanding of the FP’s role in coordinating care. Conclusion: As many adolescents with CHC/D may see their FP infrequently and may not clearly understand their role, opportunities exist for strengthening primary care home attachment as well as adolescent and caregiver literacy around the potential contribution of the FP during and after transfer to adult services. Responsibility for improving care coordination for this population should be ideally shared between FPs and pediatric specialists.Applied Science, Faculty ofOther UBCNon UBCNursing, School ofReviewedFacult

Interaction between professionals and cancer survivors in the context of Brazilian and Canadian care

ABSTRACT Objective: analyze cancer survivors’ reports about their communication with health professional team members and describe the similarities and differences in interactional patterns between Brazilian and Canadian health care contexts. Method: This study adopted a qualitative health research approach to secondary analysis, using interpretive description as the methodology, allowing us to elaborate a new research question and look at the primary data from a different perspective. There were in total eighteen participants; all of them were adults and elderly diagnosed with urologic cancer. After being organized and read, the data sets were classified into categories, and an analytic process was performed through inductive thematic analysis. Results: This resulted in three categories of findings which we have framed as: Communication between professional and survivor; The symptoms, the doubts, the questions; and Actions and reaction. Conclusion: This comparative study allowed us to bring to the attention of health professionals, especially nurses, findings regarding effective communication, humanization and empathy, supporting both inside and outside support groups, giving pieces of advice, and advocating for the survivor as is necessary. The study also showed the importance of self-development of these professionals as they fight for better quality in the health system for their patients