Early Education and Employment Outcomes After Cancer in Adolescents and Young Adults

Purpose: This study describes the early educational and vocational outcomes of Australian adolescents and young adults (AYAs) after cancer diagnosis and examines factors associated with these outcomes. Methods: Within this cross-sectional national Australian study, 196 AYAs aged 15-25 years at cancer diagnosis and within 6-24 months of diagnosis were recruited from 18 sites. Participants completed a survey that included questions about school and work outcomes, support received regarding necessary changes to education and vocation, and validated measures of anxiety, depression, and post-traumatic stress. Results: Almost half of the sample (43%) was not fully "back on track" with their previous educational and vocational plans. Post-traumatic stress and emotional symptoms were associated with poorer school/work functioning (beta = -0.95, p = 0.009 and beta = -1.27, p = 0.001, respectively). Higher PedsQL school/work functioning was associated with a slightly greater likelihood of being "back on track" with education and work plans (OR 1.03, p = 0.001). AYAs who felt well supported regarding changes to education and work plans more frequently reported receiving support from formal sources and from more sources than those who felt less supported. Unmet need of accessing an educational or vocational advisor was significantly more frequent in adult than in pediatric settings (42% vs. 17%; p = 0.024). Parents were the most common source of educational or vocational support for AYAs rather than professionals. Conclusion: This study highlights the connection between school and work participation and mental health in a national sample of AYAs with cancer. It suggests distinct benefits of educational and vocational support.Peer reviewe

Genomic screening of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential

There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine complete genomes, including two novel coronavirus species, across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk warrants closer surveillance

A review of the scientific knowledge of the seascape off Dronning Maud Land, Antarctica

Despite the exclusion of the Southern Ocean from assessments of progress towards achieving the Convention on Biological Diversity (CBD) Strategic Plan, the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) has taken on the mantle of progressing efforts to achieve it. Within the CBD, Aichi Target 11 represents an agreed commitment to protect 10% of the global coastal and marine environment. Adopting an ethos of presenting the best available scientific evidence to support policy makers, CCAMLR has progressed this by designating two Marine Protected Areas in the Southern Ocean, with three others under consideration. The region of Antarctica known as Dronning Maud Land (DML; 20°W to 40°E) and the Atlantic sector of the Southern Ocean that abuts it conveniently spans one region under consideration for spatial protection. To facilitate both an open and transparent process to provide the vest available scientific evidence for policy makers to formulate management options, we review the body of physical, geochemical and biological knowledge of the marine environment of this region. The level of scientific knowledge throughout the seascape abutting DML is polarized, with a clear lack of data in its eastern part which is presumably related to differing levels of research effort dedicated by national Antarctic programmes in the region. The lack of basic data on fundamental aspects of the physical, geological and biological nature of eastern DML make predictions of future trends difficult to impossible, with implications for the provision of management advice including spatial management. Finally, by highlighting key knowledge gaps across the scientific disciplines our review also serves to provide guidance to future research across this important region.publishedVersio

A Critical Role for CD8 T Cells in a Nonhuman Primate Model of Tuberculosis

The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell–mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the specificity and functions of CD8 T cells, such as the expression of group 1 CD1 proteins that are capable of presenting Mycobacterium tuberculosis lipids antigens and the cytotoxic/bactericidal protein granulysin. Employing a more relevant nonhuman primate model of human tuberculosis, we examined the contribution of BCG- or M. tuberculosis-elicited CD8 T cells to vaccine-induced immunity against tuberculosis. CD8 depletion compromised BCG vaccine-induced immune control of M. tuberculosis replication in the vaccinated rhesus macaques. Depletion of CD8 T cells in BCG-vaccinated rhesus macaques led to a significant decrease in the vaccine-induced immunity against tuberculosis. Consistently, depletion of CD8 T cells in rhesus macaques that had been previously infected with M. tuberculosis and cured by antibiotic therapy also resulted in a loss of anti-tuberculosis immunity upon M. tuberculosis re-infection. The current study demonstrates a major role for CD8 T cells in anti-tuberculosis immunity, and supports the view that CD8 T cells should be included in strategies for development of new tuberculosis vaccines and immunotherapeutics

Home-based care of low-risk febrile neutropenia in children-an implementation study in a tertiary paediatric hospital

BACKGROUND: Home-based management of low-risk febrile neutropenia (FN) is safe, improves quality of life and reduces healthcare expenditure. A formal low-risk paediatric program has not been implemented in Australia. We aimed to describe the implementation process and evaluate the clinical impact. METHOD: This prospective study incorporated three phases: implementation, intervention and evaluation. A low-risk FN implementation toolkit was developed, including a care-pathway, patient information, home-based assessment and educational resources. The program had executive-level endorsement, a multidisciplinary committee and a nurse specialist. Children with cancer and low-risk FN were eligible to be transferred home with a nurse visiting daily after an overnight period of observation for intravenous antibiotics. Low-risk patients were identified using a validated decision rule, and suitability for home-based care was determined using disease, chemotherapy and patient-level criteria. Plan-Do-Study-Act methodology was used to evaluate clinical impact and safety. RESULTS: Over 18 months, 292 children with FN were screened: 132 (45%) were low-risk and 63 (22%) were transferred to home-based care. Compared with pre-implementation there was a significant reduction in in-hospital median LOS (4.0 to 1.5 days, p < 0.001) and 291 in-hospital bed days were saved. Eight (13%) patients needed readmission and there were no adverse outcomes. A key barrier was timely screening of all patients and program improvements, including utilising the electronic medical record for patient identification, are planned. CONCLUSION: This program significantly reduces in-hospital LOS for children with low-risk FN. Ongoing evaluation will inform sustainability, identify areas for improvement and support national scale-up of the program

The SOS-framework (Systems of Sedentary behaviours): an international transdisciplinary consensus framework for the study of determinants, research priorities and policy on sedentary behaviour across the life course: a DEDIPAC-study.

BACKGROUND: Ecological models are currently the most used approaches to classify and conceptualise determinants of sedentary behaviour, but these approaches are limited in their ability to capture the complexity of and interplay between determinants. The aim of the project described here was to develop a transdisciplinary dynamic framework, grounded in a system-based approach, for research on determinants of sedentary behaviour across the life span and intervention and policy planning and evaluation. METHODS: A comprehensive concept mapping approach was used to develop the Systems Of Sedentary behaviours (SOS) framework, involving four main phases: (1) preparation, (2) generation of statements, (3) structuring (sorting and ranking), and (4) analysis and interpretation. The first two phases were undertaken between December 2013 and February 2015 by the DEDIPAC KH team (DEterminants of DIet and Physical Activity Knowledge Hub). The last two phases were completed during a two-day consensus meeting in June 2015. RESULTS: During the first phase, 550 factors regarding sedentary behaviour were listed across three age groups (i.e., youths, adults and older adults), which were reduced to a final list of 190 life course factors in phase 2 used during the consensus meeting. In total, 69 international delegates, seven invited experts and one concept mapping consultant attended the consensus meeting. The final framework obtained during that meeting consisted of six clusters of determinants: Physical Health and Wellbeing (71% consensus), Social and Cultural Context (59% consensus), Built and Natural Environment (65% consensus), Psychology and Behaviour (80% consensus), Politics and Economics (78% consensus), and Institutional and Home Settings (78% consensus). Conducting studies on Institutional Settings was ranked as the first research priority. The view that this framework captures a system-based map of determinants of sedentary behaviour was expressed by 89% of the participants. CONCLUSION: Through an international transdisciplinary consensus process, the SOS framework was developed for the determinants of sedentary behaviour through the life course. Investigating the influence of Institutional and Home Settings was deemed to be the most important area of research to focus on at present and potentially the most modifiable. The SOS framework can be used as an important tool to prioritise future research and to develop policies to reduce sedentary time

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

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

Surveillance for Health Behaviors of American Indians and Alaska Natives—Findings From the Behavioral Risk Factor Surveillance System, 2000–2006

BACKGROUND. The authors compared estimates for cancer risk factors, use of cancer screening tests, health status indicators, and access to care for American Indians and Alaska Natives (AI/ANs) and non-Hispanic whites (NHWs) in the US and for AI/ANs in 6 Indian Health Service regions. METHODS. Behavioral Risk Factor Surveillance System data were aggregated from the years 2000 through 2006 and were used to calculate weighted prevalence estimates by gender for key variables except demographic variables. RESULTS. Compared with NHWs, AI/ANs had lower prevalence estimates for income, educational attainment, insurance coverage, and access to personal healthcare providers. AI/ANs in Alaska and NHWs had similar estimates for diabetes (approximately 6%); however, the prevalence was nearly twice as high among AI/ANs in the other regions. The prevalence of obesity was higher for AI/ ANs (29.6%) than for NHWs (20.9%). The prevalence of binge drinking was higher among AI/AN males (24.9%) than among AI/AN females (8.5%). Heavy drinking was more prevalent among NHW females (5.3%) than among AI/AN females (3.5%). AI/ANs were more likely to be current smokers (31.1%) than NHWs (22.8%). The prevalence of AI/ANs who never smoked ranged from 31.5% in Alaska to 56.9% in the Southwest. In 5 of the 6 regions, AI/AN females had lower prevalence estimates of both Papanicolaou and mammography testing than NHW females. The use of colorectal cancer screening tests was more common among NHWs (53.8%) than among AI/ANs (44%). CONCLUSIONS. Although cancer health disparities persist among AI/ANs, the current analysis indicated that variation in the prevalence of their chronic disease risk factors may be obscured when national data are not examined by smaller geographic areas such as regions