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A history of Canberra
\"Beginning with Aboriginal occupation and European settlement of the region, Brown covers Canberra's selection as the site of the national capital, the turbulent path of Walter Burley Griffin's plan for the city, and the many phases of its construction. He surveys citizens' diverse experiences of the city and the impact of the Second World War on Canberra's growth, and explores the city's political history with insight and wit\"--Back cover.
Book
Fixing science means an end to gaming the system
During the last decade, there has been a substantial acceleration in the open science movement. Most people would probably hope to have seen signs of positive change in that time, yet it seems that the process of improving the practice of science is moving at a glacial pace.
Journal Article
Is the future of peer review automated?
The rising rate of preprints and publications, combined with persistent inadequate reporting practices and problems with study design and execution, have strained the traditional peer review system. Automated screening tools could potentially enhance peer review by helping authors, journal editors, and reviewers to identify beneficial practices and common problems in preprints or submitted manuscripts. Tools can screen many papers quickly, and may be particularly helpful in assessing compliance with journal policies and with straightforward items in reporting guidelines. However, existing tools cannot understand or interpret the paper in the context of the scientific literature. Tools cannot yet determine whether the methods used are suitable to answer the research question, or whether the data support the authors’ conclusions. Editors and peer reviewers are essential for assessing journal fit and the overall quality of a paper, including the experimental design, the soundness of the study’s conclusions, potential impact and innovation. Automated screening tools cannot replace peer review, but may aid authors, reviewers, and editors in improving scientific papers. Strategies for responsible use of automated tools in peer review may include setting performance criteria for tools, transparently reporting tool performance and use, and training users to interpret reports.
Journal Article
Harnessing the immune system in glioblastoma
Glioblastoma is the most common primary malignant brain tumour. Survival is poor and improved treatment options are urgently needed. Although immunotherapies have emerged as effective treatments for a number of cancers, translation of these through to brain tumours is a distinct challenge, particularly due to the blood–brain barrier and the unique immune tumour microenvironment afforded by CNS-specific cells. This review discusses the immune system within the CNS, mechanisms of immune escape employed by glioblastoma, and the immunological effects of conventional glioblastoma treatments. Novel therapies for glioblastoma that harness the immune system and their current clinical progress are outlined, including cancer vaccines, T-cell therapies and immune checkpoint modulators.
Journal Article
Integrin-Mediated TGFβ Activation Modulates the Tumour Microenvironment
TGFβ (transforming growth factor-beta) is a pleotropic cytokine with contrasting effects in cancer. In normal tissue and early tumours, TGFβ acts as a tumour suppressor, limiting proliferation and inducing apoptosis. However, these effects are eventually abrogated by the loss or inactivation of downstream signalling within the TGFβ pathway, and in established tumours, TGFβ then acts as a tumour promotor through multiple mechanisms including inducing epithelial-to-mesenchymal transition (EMT), promoting formation of cancer-associated fibroblasts (CAFs) and increasing angiogenesis. TGFβ is secrereted as a large latent complex and is embedded in the extracellular matrix or held on the surface of cells and must be activated before mediating its multiple functions. Thus, whilst TGFβ is abundant in the tumour microenvironment (TME), its functionality is regulated by local activation. The αv-integrins are major activators of latent-TGFβ. The potential benefits of manipulating the immune TME have been highlighted by the clinical success of immune-checkpoint inhibitors in a number of solid tumour types. TGFβ is a potent suppressor of T-cell-mediated immune surveillance and a key cause of resistance to checkpoint inhibitors. Therefore, as certain integrins locally activate TGFβ, they are likely to have a role in the immunosuppressive TME, although this remains to be confirmed. In this review, we discussed the role of TGFβ in cancer, the role of integrins in activating TGFβ in the TME, and the potential benefits of targeting integrins to augment immunotherapies.
Journal Article
A survey of experts to identify methods to detect problematic studies: stage 1 of the INveStigating ProblEmatic Clinical Trials in Systematic Reviews project
Randomized controlled trials (RCTs) inform health-care decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesize all RCTs which have been conducted on a given topic. This means that any of these ‘problematic studies’ are likely to be included, but there are no agreed methods for identifying them. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project is developing a tool to identify problematic RCTs in systematic reviews of health care-related interventions. The tool will guide the user through a series of ‘checks’ to determine a study's authenticity. The first objective in the development process is to assemble a comprehensive list of checks to consider for inclusion.
We assembled an initial list of checks for assessing the authenticity of research studies, with no restriction to RCTs, and categorized these into five domains: Inspecting results in the paper; Inspecting the research team; Inspecting conduct, governance, and transparency; Inspecting text and publication details; Inspecting the individual participant data. We implemented this list as an online survey, and invited people with expertise and experience of assessing potentially problematic studies to participate through professional networks and online forums. Participants were invited to provide feedback on the checks on the list, and were asked to describe any additional checks they knew of, which were not featured in the list.
Extensive feedback on an initial list of 102 checks was provided by 71 participants based in 16 countries across five continents. Fourteen new checks were proposed across the five domains, and suggestions were made to reword checks on the initial list. An updated list of checks was constructed, comprising 116 checks. Many participants expressed a lack of familiarity with statistical checks, and emphasized the importance of feasibility of the tool.
A comprehensive list of trustworthiness checks has been produced. The checks will be evaluated to determine which should be included in the INSPECT-SR tool.
Journal Article
Easy as (Happiness) Pie? A Critical Evaluation of a Popular Model of the Determinants of Well-Being
An underlying principle behind much of the research in positive psychology is that individuals have considerable leeway to increase their levels of happiness. In an influential article that is frequently cited in support of such claims, Lyubomirsky et al. (Rev Gen Psychol 9:111–131, 2005. 10.1037/1089-2680.9.2.111) put forward a model (subsequently popularized under the name of the “happiness pie”) in which approximately 50% of individual differences in happiness are due to genetic factors and 10% to life circumstances, leaving 40% available to be changed via volitional activities. We re-examined Lyubomirsky et al.’s claims and found several apparent deficiencies in their chain of arguments on both the empirical and the conceptual level. We conclude that there is little empirical evidence for the variance decomposition suggested by the “happiness pie,” and that even if it were valid, it is not necessarily informative with respect to the question of whether individuals can truly exert substantial influence over their own chronic happiness level. We believe that our critical re-examination of Lyubomirsky et al.’s seminal article offers insights into some common misconceptions and pitfalls of scientific inference, and we hope that it might contribute to the construction of a more rigorous and solid empirical basis for the field of positive psychology.
Journal Article
Late swing running mechanics influence hamstring injury susceptibility in elite rugby athletes: A prospective exploratory analysis
Hamstring injuries are one of the most prevalent injuries in rugby union and many other running-based sports, such as track sprinting and soccer. The majority of these injuries occur during running; however, the relationship between running mechanics and hamstring injury is unclear. Obtaining large samples of prospective injury data to examine this relationship is difficult, and therefore exploratory analysis frameworks may assist in deriving valuable information from studies with small but novel samples. The aim of this study was to undertake a prospective exploratory analysis of the relationship between running mechanics and hamstring injury. Kinematic and kinetic data of the trunk, pelvis and lower limbs were collected during maximal overground running efforts for ten elite rugby union athletes. Subsequently, hamstring injury occurrence was recorded for the following Super Rugby season, during which three athletes sustained a running-based hamstring injury. Functional principal component analysis was used to visualise patterns of variability in running mechanics during the late swing phase between athletes. Results indicated that subsequently injured athletes demonstrated a tendency for greater thoracic lateral flexion, greater hip extension moments and greater knee power absorption, compared to uninjured athletes. All variables demonstrated an ability to descriptively differentiate between injured and uninjured athletes at approximately 60% of the late swing phase. Therefore, we hypothesize that greater thoracic lateral flexion, a greater hip extension moment and greater knee power absorption between peak hip flexion and peak knee extension during the late swing phase may put rugby athletes at greater risk of running-based hamstring injury.
Journal Article
Sublethal effects of imidacloprid-contaminated honey stores on colony performance, queens, and worker activities in fall and early winter colonies
Neonicotinoid-contaminated sugar stores can have both near term and long term effects on honey bees due to their persistence in honey stores. Effects of imidacloprid food stores contaminants were examined in subtropical colonies that experience reduced brood rearing and foraging during overwintering. Colonies were given treatment sugar syrup containing 0 ppb (control), 20 ppb (field relevant), or 100 ppb (above field relevant) imidacloprid over six weeks to simulate contaminated fall nectar. Colonies were evaluated immediately (post-treatment) and 10 weeks (mid-winter) after treatment to compare proximal and latent effects. Post-treatment 0 ppb and 20 ppb colonies had more workers than 100 ppb colonies while 0 ppb colonies more brood than 20 ppb or 100 ppb colonies. Mid-winter 0 ppb and 20 ppb colonies had more workers than 100 ppb colonies and 0 ppb colonies more brood than 100 ppb colonies. Colonies experienced seasonal declines in stored pollen but no treatment effects. Lower 100 ppb colony performance was associated with reduced effort rather than lifespan. RFID (Radio Frequency Identification) tracking revealed that workers had similar adult lifespans across treatments; however, 100 ppb workers engaged in activities outside the colony for less time than 0 ppb workers. Imidacloprid exposure affected queen but not worker nutritional physiology. Nurses retained well-developed hypopharyngeal glands (as indicated by head protein) across treatments. Mid-winter queens from 0 ppb colonies had marginally higher ovary protein than queens from 100 ppb colonies and more ovary lipids than queens from 20 ppb colonies. However, queen nutrient stores in non-reproductive tissues (fat bodies) did not differ across treatments. Queens from different treatments were attended by comparable numbers of retinue workers and had similar gland contents of four QMP (Queen Mandibular Pheromone) components essential to queen care. High levels of imidacloprid in sugar stores can negatively affect colony performance months after initial storage.
Journal Article