The genomic and cellular basis of biosynthetic innovation in rove beetles.

How evolution at the cellular level potentiates macroevolutionary change is central to understanding biological diversification. The >66,000 rove beetle species (Staphylinidae) form the largest metazoan family. Combining genomic and cell type transcriptomic insights spanning the largest clade, Aleocharinae, we retrace evolution of two cell types comprising a defensive gland-a putative catalyst behind staphylinid megadiversity. We identify molecular evolutionary steps leading to benzoquinone production by one cell type via a mechanism convergent with plant toxin release systems, and synthesis by the second cell type of a solvent that weaponizes the total secretion. This cooperative system has been conserved since the Early Cretaceous as Aleocharinae radiated into tens of thousands of lineages. Reprogramming each cell type yielded biochemical novelties enabling ecological specialization-most dramatically in symbionts that infiltrate social insect colonies via host-manipulating secretions. Our findings uncover cell type evolutionary processes underlying the origin and evolvability of a beetle chemical innovation.

Determinants of Plasma Alzheimer's Disease Biomarker Use by Primary Care Providers and Dementia Specialists.

BACKGROUND: The efficiencies of plasma Alzheimer's disease (AD) biomarkers could facilitate early AD diagnosis. Unfortunately, limited knowledge exists about whether and how they would be used by clinicians. OBJECTIVE: To identify and compare determinants of plasma AD biomarker use reported by primary care providers and dementia specialists. DESIGN: Semi-structured interviews with clinicians organized using Rogers' Diffusion of Innovations theory and analyzed using an iterative coding approach. PARTICIPANTS: The subjects were internal and family medicine, neurology, and geriatrics providers with varying degrees of expertise in dementia diagnosis and care. MAIN MEASURES: Factors influencing a clinician's decision to use or not use plasma AD biomarkers in clinical practice. KEY RESULTS: We interviewed 30 clinicians (16 family or internal medicine providers, 8 geriatricians, and 6 neurologists). Fifteen were dementia specialists. Hesitance to use plasma AD biomarkers was due to perceived lack of effective treatments for AD, limited access to supports, and stigma. Plasma AD biomarkers would be more readily adopted by clinicians with dementia expertise. CONCLUSIONS: Several factors will influence clinical use of plasma AD biomarkers. Some of them may inform the design of interventions to promote the effective and appropriate clinical translation of these tests.

Feasibility, safety and effectiveness of robot-assisted radical prostatectomy with a new robotic surgical system: a prospective, controlled, randomized clinical trial.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) gains increasing popularity in the surgical management of prostate cancer (PCa) but is challenged by its prohibitive expense. A domestic robotic system has been developed to address this issue, but data comparing the self-developed robot with the widely used robot is lacking. We performed a randomized clinical trial to compare KD-SR-01® and DaVinci® robots in terms of perioperative, short-term oncological and functional outcomes in RARP. MATERIALS AND METHODS: We prospectively enrolled patients with clinically localized PCa. Patients were randomized to undergo either KD-SR-01®-RARP (K-RARP) or DaVinci®-RARP (D-RARP) by the same surgical team. The baseline, perioperative, short-term oncologic and urinary functional data were collected and compared. RESULTS: We enrolled 39 patients, including 20 patients undergoing K-RARP and 19 undergoing D-RARP. Demographic and tumor characteristics were comparable between groups. All surgeries were performed successfully with no conversion to open. The operative time was similar (P = 0.095) and K-RARP offered less volume of intraoperative bleeding (P < 0.001). Four patients in the K-RARP group and three in the D-RARP group developed postoperative complications (P = 0.732). Patients undergoing K-RARP had less volume of drainage (P = 0.022). Positive surgical margins were observed in three patients undergoing K-RARP and five undergoing D-RARP (P = 0.451). During the follow up, one patient receiving K-RARP group and two receiving D-RARP group had measurable prostate specific antigen (P = 0.605). Urine leakage, urinary control and pad usage were comparable between groups at six weeks post-surgery. CONCLUSIONS: The two surgical robots yielded similar results in feasibility, safety and short-term oncologic and functional efficacy for RARP. TRIAL REGISTRATION: The trial has been registered at www.chictr.org.cn with a registration number of ChiCTR2200057000 on 25th February 2022.

Emerging innovations and advancements in the treatment of extremity and truncal soft tissue sarcomas.

In this special edition update on soft tissue sarcomas (STS), we cover classifications, emerging technologies, prognostic tools, radiation schemas, and treatment disparities in extremity and truncal STS. We discuss the importance of enhancing local control and reducing complications, including the role of innovative imaging, surgical guidance, and hypofractionated radiation. We review advancements in systemic and immunotherapeutic treatments and introduce disparities seen in this vulnerable population that must be considered to improve overall patient care.

Does Real Option Value Influence Oncologists' Treatment Recommendations? A Survey of US Oncologists.

OBJECTIVES: Survival benefit from anticancer treatments, even if modest, improves a patient's chances of accessing future innovations, thereby creating real option value. There is no empirical evidence on the impact of potential future innovations on oncologists' treatment recommendations. METHODS: We conducted a national online survey of practicing medical and hematological oncologists. We presented a hypothetical metastatic cancer patient with median survival of 6 months under 4 decision-making scenarios with varying expected efficacy and time to arrival of future innovations. We assessed the likelihood of discussing future innovations with their patients and the likelihood that future innovations would influence their current treatment recommendation, as well as factors associated with these 2 outcomes using multivariate logistic regressions. RESULTS: A total of 201 oncologists completed the survey. When future innovations were expected to improve survival by 6 months and be available in 6 months, 76% of oncologists were likely or very likely to discuss the innovations with their patients, and 68% reported they would influence their current treatment recommendations. A 1-month increase in the expected survival improvement of future innovation was associated with a 1.17 greater odds (95% CI 1.1-1.25) of reporting likely or very likely to discuss future innovations with their patients, whereas a 1-month increase in the expected time to arrival was associated with a 0.91 lower odds (95% CI 0.88-0.94). CONCLUSIONS: Given that potential future innovations seem to influence oncologists' treatments recommendations, evidence to inform clinical guidelines and value assessments should consider data on real option value impacts to support informed treatment decision making.

Back(s) to basics: The concept of backing in stone tool technologies for tracing hominins' technical innovations.

The evolution of Paleolithic stone tool technologies is characterized by gradual increase in technical complexity along with changes in the composition of assemblages. In this respect, the emergence of retouched-backed tools is an important step and, for some, a proxy for "modern" behavior. However, backed tools emerge relatively early and develop together with major changes in Middle-Upper Pleistocene stone tool technologies. We provide an updated review of the emergence and development of the "backing" concept across multiple chrono-cultural contexts and discuss its relationship to both the emergence of hafting and major evolutionary steps in the ergonomics of stone tool use. Finally, we address potential mechanisms of context-specific re-invention of backing based primarily on data from the late Middle Paleolithic of Western Europe.

Utility guideline and considerations for the novel Hugo™ RAS (robotic-assisted surgery) system in colorectal surgery: surgical outcomes and initial experience in a tertiary center.

PURPOSE: A novel robotic platform-Hugo™ RAS (robotic-assisted surgery) system-has been introduced with several innovations that may prove advantageous for surgeons, such as an open console and four interchangeable modular arms. Our study aims to evaluate this platform's safety, efficacy, and potential impact on the surgical treatment of colorectal pathology. METHODS: Patients underwent robotic-assisted colorectal procedures with the Hugo™ RAS system at the General University Hospital of Elche from October 2023 to July 2024. Patient characteristics, intraoperative and postoperative variables, and robotic technical issues were recorded. RESULTS: Forty consecutive patients were included (14 right, 13 left, and 8 rectum neoplasms; 4 left diverticulitis; and 1 ileocecal Crohn's disease). The patients' characteristics were as follows: median age, 69.5 years; 24 males and 16 females; 45% ASA III-IV; and Charlson Comorbidity Index > 5:42.5%. We recorded four medical (2 anemia, 1 phlebitis, and 1 admission to the intensive care unit) and three surgical (1 hematoma of the incision, 1 intestinal occlusion, and 1 dehiscence of the anastomosis) postoperative complications. We had no conversions neither open nor laparoscopic surgery. The average hospital stay was 3 days, with no mortality or readmission. CONCLUSIONS: The Hugo™ RAS system is safe and feasible for colorectal procedures. The modularity of the arms provides the versatility of configurations adjusted depending on the patient's body features and the surgeon's preferences and greater adaptability to operating rooms. The open console is highly comfortable and ergonomic for the surgeon, allowing communication with the operating room environment. TRIAL REGISTRATION: NCT06512480.

Using the consolidated Framework for Implementation Research to integrate innovation recipients' perspectives into the implementation of a digital version of the spinal cord injury health maintenance tool: a qualitative analysis.

BACKGROUND: Despite advances in managing secondary health complications after spinal cord injury (SCI), challenges remain in developing targeted community health strategies. In response, the SCI Health Maintenance Tool (SCI-HMT) was developed between 2018 and 2023 in NSW, Australia to support people with SCI and their general practitioners (GPs) to promote better community self-management. Successful implementation of innovations such as the SCI-HMT are determined by a range of contextual factors, including the perspectives of the innovation recipients for whom the innovation is intended to benefit, who are rarely included in the implementation process. During the digitizing of the booklet version of the SCI-HMT into a website and App, we used the Consolidated Framework for Implementation Research (CFIR) as a tool to guide collection and analysis of qualitative data from a range of innovation recipients to promote equity and to inform actionable findings designed to improve the implementation of the SCI-HMT. METHODS: Data from twenty-three innovation recipients in the development phase of the SCI-HMT were coded to the five CFIR domains to inform a semi-structured interview guide. This interview guide was used to prospectively explore the barriers and facilitators to planned implementation of the digital SCI-HMT with six health professionals and four people with SCI. A team including researchers and innovation recipients then interpreted these data to produce a reflective statement matched to each domain. Each reflective statement prefaced an actionable finding, defined as alterations that can be made to a program to improve its adoption into practice. RESULTS: Five reflective statements synthesizing all participant data and linked to an actionable finding to improve the implementation plan were created. Using the CFIR to guide our research emphasized how partnership is the key theme connecting all implementation facilitators, for example ensuring that the tone, scope, content and presentation of the SCI-HMT balanced the needs of innovation recipients alongside the provision of evidence-based clinical information. CONCLUSIONS: Understanding recipient perspectives is an essential contextual factor to consider when developing implementation strategies for healthcare innovations. The revised CFIR provided an effective, systematic method to understand, integrate and value recipient perspectives in the development of an implementation strategy for the SCI-HMT. TRIAL REGISTRATION: N/A.

Development Trends and Prospects of Technology-Based Solutions for Health Challenges in Aging Over the Past 25 Years: Bibliometric Analysis.

BACKGROUND: As the global population ages, we witness a broad scientific and technological revolution tailored to meet the health challenges of older adults. Over the past 25 years, technological innovations, ranging from advanced medical devices to user-friendly mobile apps, are transforming the way we address these challenges, offering new avenues to enhance the quality of life and well-being of the aging demographic. OBJECTIVE: This study aimed to systematically review the development trends in technology for managing and caring for the health of older adults over the past 25 years and to project future development prospects. METHODS: We conducted a comprehensive bibliometric analysis of literatures related to technology-based solutions for health challenges in aging, published up to March 18, 2024. The search was performed using the Web of Science Core Collection, covering a span from 1999 to 2024. Our search strategy was designed to capture a broad spectrum of terms associated with aging, health challenges specific to older adults, and technological interventions. RESULTS: A total of 1133 publications were found in the Web of Science Core Collection. The publication trend over these 25 years showed a gradual but fluctuating increase. The United States was the most productive country and participated in international collaboration most frequently. The predominant keywords identified through this analysis included "dementia," "telemedicine," "older-adults," "telehealth," and "care." The keywords with citation bursts included "telemedicine" and "digital health." CONCLUSIONS: The scientific and technological revolution has significantly improved older adult health management, particularly in chronic disease monitoring, mobility, and social connectivity. The momentum for innovation continues to build, with future research likely to focus on predictive analytics and personalized health care solutions, further enhancing older adults' independence and quality of life.

Breathing in danger: Understanding the multifaceted impact of air pollution on health impacts.

Air pollution, a pervasive environmental threat that spans urban and rural landscapes alike, poses significant risks to human health, exacerbating respiratory conditions, triggering cardiovascular problems, and contributing to a myriad of other health complications across diverse populations worldwide. This article delves into the multifarious impacts of air pollution, utilizing cutting-edge research methodologies and big data analytics to offer a comprehensive overview. It highlights the emergence of new pollutants, their sources, and characteristics, thereby broadening our understanding of contemporary air quality challenges. The detrimental health effects of air pollution are examined thoroughly, emphasizing both short-term and long-term impacts. Particularly vulnerable populations are identified, underscoring the need for targeted health risk assessments and interventions. The article presents an in-depth analysis of the global disease burden attributable to air pollution, offering a comparative perspective that illuminates the varying impacts across different regions. Furthermore, it addresses the economic ramifications of air pollution, quantifying health and economic losses, and discusses the implications for public policy and health care systems. Innovative air pollution intervention measures are explored, including case studies demonstrating their effectiveness. The paper also brings to light recent discoveries and insights in the field, setting the stage for future research directions. It calls for international cooperation in tackling air pollution and underscores the crucial role of public awareness and education in mitigating its impacts. This comprehensive exploration serves not only as a scientific discourse but also as a clarion call for action against the invisible but insidious threat of air pollution, making it a vital read for researchers, policymakers, and the general public.

Relationship of adaptive expertise of health professions educators with age, experience, academic rank, and their work performance during an altered academic environment.

BACKGROUND: Health professionals and health professions educators (HPEs) worldwide were confronted by the COVID-19 pandemic, which disrupted standard practice and forced HPEs to develop creative, alternative modes of training and education. The ability of people to work successfully and efficiently in non-standard situations can be called adaptive expertise in which people quickly overcome changes in work requirements using their expert knowledge in novel ways. The objectives of the current study were to investigate how the adaptive expertise of a group of HPEs influenced perceived work performance in a non-standard situation and to see whether there were relationships between the level of adaptive expertise and academic ranking and work experience of HPEs. METHODS: A descriptive, cross-sectional, single-site study was conducted using a self-reported study tool about adaptive expertise developed by Carbonell et al. (2016), and three questions were asked about participants' perceptions of work performance, amount of work done, and teaching quality. The sample consisted of HPEs from the University of Twente, Netherlands. RESULTS: Among 123 eligible participants, 40 individuals completed the survey. Kaiser-Meyer-Olkin and Bartlett's Test of Sphericity indicated the adequacy of the sample size (KMO = 0.633, P < 0.0001). Participants were lecturers, senior lecturers, assistant professors, associate professors and full professors. The average adaptive expertise score of the sample was 4.18 ± 0.57 on a scale from 1 (low) to 5 (high). The domain and innovative skills are the principal distinct dimensions of adaptive expertise among HPEs. Professors showed higher adaptive expertise scores than the other ranks. Statistically significant correlations were found between scores of adaptive expertise and perceived work performance (r = 0.41, p < 0.05 and academic ranking (r = 0.42, p < 0.05). Adaptive expertise scores were not associated with work experience or HPEs' age. CONCLUSIONS: Our finding of a lack of relationships between self-reported level of adaptive expertise and experience and age but significant relationships with work performance and academic ranking of HPEs suggests that adaptive expertise is not auto-generated or acquired with seniority and experience but is a 'mastery' that should be developed deliberately.

Measuring paw preferences in dogs, cats and rats: Design requirements and innovations in methodology.

Studying behavioural lateralization in animals holds great potential for answering important questions in laterality research and clinical neuroscience. However, comparative research encounters challenges in reliability and validity, requiring new approaches and innovative designs to overcome. Although validated tests exist for some species, there is yet no standard test to compare lateralized manual behaviours between individuals, populations, and animal species. One of the main reasons is that different fine-motor abilities and postures must be considered for each species. Given that pawedness/handedness is a universal marker for behavioural lateralization across species, this article focuses on three commonly investigated species in laterality research: dogs, cats, and rats. We will present six apparatuses (two for dogs, three for cats, and one for rats) that enable an accurate assessment of paw preference. Design requirements and specifications such as zoometric fit for different body sizes and ages, reliability, robustness of the material, maintenance during and after testing, and animal welfare are extremely important when designing a new apparatus. Given that the study of behavioural lateralization yields crucial insights into animal welfare, laterality research, and clinical neuroscience, we aim to provide a solution to these challenges by presenting design requirements and innovations in methodology across species.

Impact of public-private partnerships investment and FDI on CO2 emissions: A study of six global investment countries.

This study investigates the impact of public-private partnerships investment in energy and FDI on environmental quality in global investment countries during 1995-2018. Economic growth, technological innovations and consumption of clean energy are also considered as additional determinants of environmental quality. The study applied advanced panel econometric models. Our empirical results affirm the evidence of a long-run association between environmental quality and its determinants. Specifically, economic growth as well as clean energy use improves quality of environment by lowering carbon emissions. Public-private partnerships investment in energy, FDI and technological innovations decrease carbon emissions. Energy consumption (generated from fossil fuel) increases carbon emissions. Heterogeneous causality evidence indicates the presence of a unidirectional causality relation from carbon emissions to public-private partnerships investment in energy and a feedback causality occurs between consumption of clean energy and CO2 emissions. This empirical evidence provides new insights for both policymakers and governments to support public-private partnership investments in energy for the improvement of quality of environment in global investment countries.

Achieving zero emission targets: The influence of green bonds on clean energy investment and environmental quality.

The effectiveness of green finance in driving clean energy and environmental sustainability in the current era is receiving attention. Therefore, this study proposes an empirical framework highlighting the effects of green bonds (GB) on clean energy investment (CEI), clean energy investment efficiency (CEE) and environmental sustainability of 29 green bond issuing countries between 2014 and 2022. Using system and difference GMM approaches, this study finds that (i) green bond issuance drives clean energy investment. (ii) Green bonds sufficiently enhance the selected countries' environmental quality. These results supplement the promotion of green bonds in increasing the transfer of funds towards renewable energy projects by reducing reliance on fossil fuels. (iii) Using Driscoll & Kraay, Fully Modified-OLS, and changing the dependent variable, this study further supported the idea that green bonds effectively promote the CEE and environmental sustainability of the chosen countries. (iv) Similarly, this study conducted income heterogeneity, showing that green bonds improve high- and middle-income countries' CEI and environmental quality. (v) Finally, the results indicate that resource consumption escalates CO2 emissions by declining the CEI. Technological innovations increase CEI, whereas they do not mitigate CO2 emissions directly, hinting at the requirement for a comprehensive approach. Therefore, inclusive policies on green bond frameworks, robust incentives, and rigorous environmental criteria should be implemented to attract investment in clean energy development and ensure the environmental sustainability of the selected countries.

Advancing noise management in aviation: Strategic approaches for preventing noise-induced hearing loss.

As urbanization and population growth escalate, the challenge of noise pollution intensifies, particularly within the aviation industry. This review examines current insights into noise-induced hearing loss (NIHL) in aviation, highlighting the risks to pilots, cabin crew, aircraft maintenance engineers, and ground staff from continuous exposure to high-level noise. It evaluates existing noise management and hearing conservation strategies, identifying key obstacles and exploring new technological solutions. While progress in developing protective devices and noise control technologies is evident, gaps in their widespread implementation persist. The study underscores the need for an integrated strategy combining regulatory compliance, technological advances, and targeted educational efforts. It advocates for global collaboration and policy development to safeguard the auditory health of aviation workers and proposes a strategic framework to enhance hearing conservation practices within the unique challenges of the aviation sector.

Comparative Analysis of Psychophysiological Responses in Fibromyalgia Patients: Evaluating Neuromodulation Alone, Neuromodulation Combined with Virtual Reality, and Exercise Interventions.

BACKGROUND AND OBJECTIVES: Fibromyalgia, a chronic condition, manifests as widespread musculoskeletal pain, fatigue, sleep disturbances, autonomic and cognitive dysfunction, hypersensitivity to stimuli, and various somatic and psychiatric symptoms. This study, a controlled and randomized experiment, aimed to evaluate and compare the immediate effects of different treatments on fibromyalgia patients. MATERIALS AND METHODS: The treatments included the EXOPULSE Mollii suit, a combination of the EXOPULSE Mollii suit with a virtual reality (VR) protocol, and a physical exercise regimen. A cohort of 89 female fibromyalgia patients was randomly assigned to one of four groups: Control (n = 20), Suit only (n = 22), Suit combined with VR (n = 21), and Exercise (n = 26). RESULTS: This study found notable differences across the groups in several key parameters. In the Control group, significant changes were observed in Forced Expiratory Volume (FEV 1/FEV 6), the Numeric Rating Scale (NRS) for pain, Pressure Pain Threshold (PPT) at the epicondyle, cortical arousal levels, the 10 m up-and-go test, and in all measured variables related to temperature and muscle oxygenation. For the group using the suit alone, there were significant differences noted in the NRS, the chair stand test, palm temperature, and all muscle oxygenation parameters. The Suit + VR group showed significant changes in the NRS, PPT at the knee, handgrip strength test, the 10 m up-and-go test, one-leg balance test with the right leg, muscle oxygen saturation (SmO2), deoxygenated hemoglobin (HHb), and oxygenated hemoglobin (O2Hb). Finally, the Exercise group exhibited significant differences in FEV 1/FEV 6, chest perimeter difference, NRS, PPT at both the epicondyle and knee, cortical arousal, the chair stand test, the 10-m up-and-go test, and in SmO2, HHb, and O2Hb levels. CONCLUSIONS: combining neuromodulation with VR and targeted exercise regimens can effectively alleviate fibromyalgia symptoms, offering promising avenues for non-pharmacological management.

Ethical Considerations in Pediatric Surgery.

Pediatric surgeons need to learn to give as much importance to the ethical approach as they have been giving to the systemic methodology in their clinical approach all along. The law of the land and the governmental rules also need to be kept in mind before deciding the final solution. They need to always put medical problems in the background of ethical context, reach a few solutions keeping in mind the available resources, and apply the best solution in the interest of their pediatric patients.

Phylogenomics and historical biogeography of Hydrangeeae (Hydrangeaceae) elucidate the effects of geologic and climatic dynamics on diversification.

Demonstrating the process of transregional biogeography and mechanisms underlying evolutionary radiations is crucial to understanding biological evolution. Here, we use Hydrangeeae (Hydrangeaceae), a tribe with a unique disjunct distribution and complex trait variations, using a solid phylogenetic framework, to investigate how geographical and climatic factors interact with functional traits to trigger plant evolutionary radiations. We constructed the first highly supported and dated phylogenetic framework using 79 protein-coding genes obtained from 81 plastomes, representing 63 species and all major clades, and found that most extant species originated from asynchronous diversification of two lineages undergoing repeated expansion and retraction, at middle and high latitudes of the Northern Hemisphere between East Asia and North America, during the Eocene to Pleistocene (driven by geologic and climatic dynamics). In accordance with these drivers, interactions of flora between central-eastern China and Japan occurred frequently after the Late Tertiary. We found that resource limitation and range fragmentation probably accelerated the diversification of Hydrangeeae, which supports the resource-use hypothesis. Our study sheds light on the evolutionary radiation and assembly of flora within East Asia, and the East Asian-North American disjunction, through integration of phylogenomic and biogeographic data with functional trait and ecological data.

Unlocking Dysprosium Constraints for China's 1.5 °C Climate Target.

Some key low-carbon technologies, ranging from wind turbines to electric vehicles, are underpinned by the strong rare-earth-based permanent magnets of the Nd, Pr (Dy)-Fe-Nb type (NdFeB). These NdFeB magnets, which are sensitive to demagnetization with temperature elevation (the Curie point), require the addition of variable amounts of dysprosium (Dy), where an elevation of the Curie point is needed to meet operational conditions. Given that China is the world's largest REE supplier with abundant REE reserves, the impact of an ambitious 1.5 °C climate target on China's Dy supply chain has sparked widespread concern. Here, we explore future trends and innovation strategies associated with the linkage between Dy and NdFeBs under various climate scenarios in China. We find China alone is expected to exhaust the global present Dy reserve within the next 2-3 decades to facilitate the 1.5 °C climate target. By implementing global available innovation strategies, such as material substitution, reduction, and recycling, it is possible to avoid 48%-68% of China's cumulative demand for Dy. Nevertheless, ongoing efforts in REE exploration and production are still required to meet China's growing Dy demand, which will face competition from the United States, European Union, and other countries with ambitious climate targets. Thus, our analysis urges China and those nations to form wider cooperation in REE supply chains as well as in NdFeB innovation for the realization of a global climate-safe future.

Clinical Trials in the Brain Tumour Population: Challenges and Strategies for the Future.

PURPOSE OF REVIEW: This review identifies challenges and barriers to successful development of drugs in neuro-oncology trials at the preclinical, clinical and translational stages that we believe has contributed to poor outcomes for patients over the last 30 years. RECENT FINDINGS: Several key strategies have been proposed by leading groups to address these and improve patient outcomes. Better preclinical testing using more sophisticated and clinically relevant models is needed. A greater focus on assessing blood-brain barrier penetrance and targeting key biological processes such as tumour heterogeneity and immune response is vital. Adopting innovative trial designs permitting faster results and addressing key issues (including molecular heterogeneity and combinatorial approaches) is highly desirable. A stronger translational focus is also clearly needed. Implementation of these strategies is already starting to occur. Maintaining and increasing these novel approaches will require coordinated efforts between clinicians, scientists, industry and funding/regulator bodies.