Eight problems with literature reviews and how to fix them.

Traditional approaches to reviewing literature may be susceptible to bias and result in incorrect decisions. This is of particular concern when reviews address policy- and practice-relevant questions. Systematic reviews have been introduced as a more rigorous approach to synthesizing evidence across studies; they rely on a suite of evidence-based methods aimed at maximizing rigour and minimizing susceptibility to bias. Despite the increasing popularity of systematic reviews in the environmental field, evidence synthesis methods continue to be poorly applied in practice, resulting in the publication of syntheses that are highly susceptible to bias. Recognizing the constraints that researchers can sometimes feel when attempting to plan, conduct and publish rigorous and comprehensive evidence syntheses, we aim here to identify major pitfalls in the conduct and reporting of systematic reviews, making use of recent examples from across the field. Adopting a 'critical friend' role in supporting would-be systematic reviews and avoiding individual responses to police use of the 'systematic review' label, we go on to identify methodological solutions to mitigate these pitfalls. We then highlight existing support available to avoid these issues and call on the entire community, including systematic review specialists, to work towards better evidence syntheses for better evidence and better decisions

Genetic association of wool quality characteristics in United States Rambouillet sheep

Introduction: Fine wool production is an important source of revenue, accounting for up to 13% of total revenue in extensively managed wool sheep production systems of the United States. The Rambouillet are a predominant breed that excels in wool quality characteristics. Understanding the genetic basis of wool quality characteristics would aid in the development of genomic breeding strategies to facilitate genetic improvement.Methods: Wool characteristics and DNA were collected for rams enrolled in the North Dakota State University and University of Wyoming annual central performance ram tests over a three-year period (2019–2021, N = 313). The relationships of wool quality characteristics including grease fleece weight adjusted 365 days (wt. 365 adj.), clean fleece wt. 365 adj., staple length 365 adj., average fiber diameter, face wool cover, amount of skin wrinkles and belly wool were evaluated through genome-wide association studies (GWAS), Pearson correlation and ANOVA.Results: The GWAS identified four genome-wide significant genetic markers (p-value <1.19e-06) and five chromosome-wide significant markers (p-value <1.13e-05) on chromosomes 1, 2, 4, 15, and 19. Significant markers were associated with genes notable for relevant wool biological functions, including the gene ABCC8 which codes for SUR1, an ATP-sensitive potassium channel known to affect hair growth and 60S ribosomal protein L17-like, previously found to be expressed during follicle formation. The strongest Pearson correlation coefficients were identified between clean fleece wt. 365 adj. and grease fleece wt. 365 adj. (r = 0.83) and between clean fleece wt. 365 adj. and staple length 365 adj. (r = 0.53). Additionally, clean fleece wt. 365 adj. was correlated with final body weight (r = 0.35) and scrotal circumference (r = 0.16). Staple length 365 adj. (p-value = 5e-04), average fiber diameter (p-value = .0053) and clean fleece wt. 365 adj. (p-value = .014) were significantly associated with belly wool score.Discussion: The results of this study provide important insight into the relationships between wool quality characteristics and report specific markers that Rambouillet sheep producers may use to help inform selection and breeding decisions for improved wool quality

Locating and building knowledges outside of the academy : approaches to engaged teaching at the University of Sheffield

This article draws on three case studies, which illuminate a number of practical, ethical and intellectual issues that arise from engaged teaching activities within the curriculum. Projects from the disciplines of Architecture, English and Journalism Studies illustrate the possibilities offered by learning and teaching projects which emphasise public facing, co-produced knowledge as central components. It is argued that such approaches enable dynamic forms of learning to emerge, which work to expand the parameters of subject-specific knowledge while enabling the development of citizenship attributes and employability skills amongst students in ways that deepen, rather than dilute, intellectual rigour. The article locates these practical pedagogical reflections within theoretical frameworks offered by those working (largely in North America* on publicly engaged approaches to scholarship and seeks to draw connections with contemporary developments in learning and teaching in the UK. Keywords: civic university; engaged teaching; engaged scholarship; co-productio

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Evidence Synthesis International (ESI): Position Statement

This paper is the initial Position Statement of Evidence Synthesis International, a new partnership of organizations that produce, support and use evidence synthesis around the world. The paper (i) argues for the importance of synthesis as a research exercise to clarify what is known from research evidence to inform policy, practice and personal decision making; (ii) discusses core issues for research synthesis such as the role of research evidence in decision making, the role of perspectives, participation and democracy in research and synthesis as a core component of evidence ecosystems; (iii) argues for 9 core principles for ESI on the nature and role of research synthesis; and (iv) lists the 5 main goals of ESI as a coordinating partnership for promoting and enabling the production and use of research synthesis

Detection of astrocytic tau pathology facilitates recognition of chronic traumatic encephalopathy neuropathologic change

Traumatic brain injury (TBI) is associated with the development of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy (CTE). Current consensus diagnostic criteria define the pathognomonic cortical lesion of CTE neuropathologic change (CTE-NC) as a patchy deposition of hyperphosphorylated tau in neurons, with or without glial tau in thorn-shaped astrocytes, typically towards the depths of sulci and clustered around small blood vessels. Nevertheless, although incorporated into consensus diagnostic criteria, the contribution of the individual cellular components to identification of CTE-NC has not been formally evaluated. To address this, from the Glasgow TBI Archive, cortical tissue blocks were selected from consecutive brain donations from contact sports athletes in which there was known to be either CTE-NC (n = 12) or Alzheimer’s disease neuropathologic change (n = 4). From these tissue blocks, adjacent tissue sections were stained for tau antibodies selected to reveal either solely neuronal pathology (3R tau; GT-38) or mixed neuronal and astroglial pathologies (4R tau; PHF-1). These stained sections were then randomised and independently assessed by a panel of expert neuropathologists, blind to patient clinical history and primary antibody applied to each section, who were asked to record whether CTE-NC was present. Results demonstrate that, in sections stained for either 4R tau or PHF-1, consensus recognition of CTE-NC was high. In contrast, recognition of CTE-NC in sections stained for 3R tau or GT-38 was poor; in the former no better than chance. Our observations demonstrate that the presence of both neuronal and astroglial tau pathologies facilitates detection of CTE-NC, with its detection less consistent when neuronal tau pathology alone is visible. The combination of both glial and neuronal pathologies, therefore, may be required for detection of CTE-NC

Environmental change: prospects for conservation and agriculture in a southwest Australia biodiversity hotspot

Accelerating environmental change is perhaps the greatest challenge for natural resource management; successful strategies need to be effective for decades to come. Our objective is to identify opportunities that new environmental conditions may provide for conservation, restoration, and resource use in a globally recognized biodiversity hotspot in southwestern Australia. We describe a variety of changes to key taxonomic groups and system-scale characteristics as a consequence of environmental change (climate and land use), and outline strategies for conserving and restoring important ecological and agricultural characteristics. Opportunities for conservation and economic adaptation are substantial because of gradients in rainfall, temperature, and land use, extensive areas of remnant native vegetation, the ability to reduce and ameliorate areas affected by secondary salinization, and the existence of large national parks and an extensive network of nature reserves. Opportunities presented by the predicted environmental changes encompass agricultural as well as natural ecosystems. These may include expansion of aquaculture, transformation of agricultural systems to adapt to drier autumns and winters, and potential increases in spring and summer rain, carbon-offset plantings, and improving the network of conservation reserves. A central management dilemma is whether restoration/preservation efforts should have a commercial or biodiversity focus, and how they could be integrated. Although the grand challenge is conserving, protecting, restoring, and managing for a future environment, one that balances economic, social, and environmental values, the ultimate goal is to establish a regional culture that values the unique regional environment and balances the utilization of natural resources against protecting remaining natural ecosystems

Crowdsourcing the Perception of Machine Teaching

Teachable interfaces can empower end-users to attune machine learning systems to their idiosyncratic characteristics and environment by explicitly providing pertinent training examples. While facilitating control, their effectiveness can be hindered by the lack of expertise or misconceptions. We investigate how users may conceptualize, experience, and reflect on their engagement in machine teaching by deploying a mobile teachable testbed in Amazon Mechanical Turk. Using a performance-based payment scheme, Mechanical Turkers (N = 100) are called to train, test, and re-train a robust recognition model in real-time with a few snapshots taken in their environment. We find that participants incorporate diversity in their examples drawing from parallels to how humans recognize objects independent of size, viewpoint, location, and illumination. Many of their misconceptions relate to consistency and model capabilities for reasoning. With limited variation and edge cases in testing, the majority of them do not change strategies on a second training attempt.Comment: 10 pages, 8 figures, 5 tables, CHI2020 conferenc

Predicting microbiologically defined infection in febrile neutropenic episodes in children : global individual participant data multivariable meta-analysis

BACKGROUND: Risk-stratified management of fever with neutropenia (FN), allows intensive management of high-risk cases and early discharge of low-risk cases. No single, internationally validated, prediction model of the risk of adverse outcomes exists for children and young people. An individual patient data (IPD) meta-analysis was undertaken to devise one. METHODS: The 'Predicting Infectious Complications in Children with Cancer' (PICNICC) collaboration was formed by parent representatives, international clinical and methodological experts. Univariable and multivariable analyses, using random effects logistic regression, were undertaken to derive and internally validate a risk-prediction model for outcomes of episodes of FN based on clinical and laboratory data at presentation. RESULTS: Data came from 22 different study groups from 15 countries, of 5127 episodes of FN in 3504 patients. There were 1070 episodes in 616 patients from seven studies available for multivariable analysis. Univariable analyses showed associations with microbiologically defined infection (MDI) in many items, including higher temperature, lower white cell counts and acute myeloid leukaemia, but not age. Patients with osteosarcoma/Ewings sarcoma and those with more severe mucositis were associated with a decreased risk of MDI. The predictive model included: malignancy type, temperature, clinically 'severely unwell', haemoglobin, white cell count and absolute monocyte count. It showed moderate discrimination (AUROC 0.723, 95% confidence interval 0.711-0.759) and good calibration (calibration slope 0.95). The model was robust to bootstrap and cross-validation sensitivity analyses. CONCLUSIONS: This new prediction model for risk of MDI appears accurate. It requires prospective studies assessing implementation to assist clinicians and parents/patients in individualised decision making