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\"\"Bold Venture\" tells an important and riveting wartime story of the American airmen who flew combat missions over Hong Kong during the Second World War.\"--Provided by publisher.

The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.

PurposeThe safeguard subject of the Area of Protection “natural Resources,” particularly regarding mineral resources, has long been debated. Consequently, a variety of life cycle impact assessment methods based on different concepts are available. The Life Cycle Initiative, hosted by the UN Environment, established an expert task force on “Mineral Resources” to review existing methods (this article) and provide guidance for application-dependent use of the methods and recommendations for further methodological development (Berger et al. in Int J Life Cycle Assess, 2020).MethodsStarting in 2017, the task force developed a white paper, which served as its main input to a SETAC Pellston Workshop® in June 2018, in which a sub-group of the task force members developed recommendations for assessing impacts of mineral resource use in LCA. This article, based mainly on the white paper and pre-workshop discussions, presents a thorough review of 27 different life cycle impact assessment methods for mineral resource use in the “natural resources” area of protection. The methods are categorized according to their basic impact mechanisms, described and compared, and assessed against a comprehensive set of criteria.Results and discussionFour method categories have been identified and their underlying concepts are described based on existing literature: depletion methods, future efforts methods, thermodynamic accounting methods, and supply risk methods. While we consider depletion and future efforts methods more “traditional” life cycle impact assessment methods, thermodynamic accounting and supply risk methods are rather providing complementary information. Within each method category, differences between methods are discussed in detail, which allows for further sub-categorization and better understanding of what the methods actually assess.ConclusionsWe provide a thorough review of existing life cycle impact assessment methods addressing impacts of mineral resource use, covering a broad overview of basic impact mechanisms to a detailed discussion of method-specific modeling. This supports a better understanding of what the methods actually assess and highlights their strengths and limitations. Building on these insights, Berger et al. (Int J Life Cycle Assess, 2020) provide recommendations for application-dependent use of the methods, along with recommendations for further methodological development.

Since their widespread introduction more than half a century ago, intensive care units (ICUs) have become an integral part of the health care system. Although most ICUs are found in high-income countries, they are increasingly a feature of health care systems in low- and middle-income countries. The World Federation of Societies of Intensive and Critical Care Medicine convened a task force whose objective was to answer the question “What is an ICU?” in an internationally meaningful manner and to develop a system for stratifying ICUs on the basis of the intensity of the care they provide. We undertook a scoping review of the peer-reviewed and gray literature to assemble existing models for ICU stratification. Based on these and on discussions among task force members by teleconference and 2 face-to-face meetings, we present a proposed definition and classification of ICUs. An ICU is an organized system for the provision of care to critically ill patients that provides intensive and specialized medical and nursing care, an enhanced capacity for monitoring, and multiple modalities of physiologic organ support to sustain life during a period of life-threatening organ system insufficiency. Although an ICU is based in a defined geographic area of a hospital, its activities often extend beyond the walls of the physical space to include the emergency department, hospital ward, and follow-up clinic. A level 1 ICU is capable of providing oxygen, noninvasive monitoring, and more intensive nursing care than on a ward, whereas a level 2 ICU can provide invasive monitoring and basic life support for a short period. A level 3 ICU provides a full spectrum of monitoring and life support technologies, serves as a regional resource for the care of critically ill patients, and may play an active role in developing the specialty of intensive care through research and education. A formal definition and descriptive framework for ICUs can inform health care decision-makers in planning and measuring capacity and provide clinicians and patients with a benchmark to evaluate the level of resources available for clinical care.

Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional’s approach to pain management. A multidisciplinary task force including professionals and patient representatives conducted a systematic literature review of systematic reviews to evaluate evidence regarding effects on pain of multiple treatment modalities. Overarching principles and recommendations regarding assessment and pain treatment were specified on the basis of reviewed evidence and expert opinion. From 2914 review studies initially identified, 186 met inclusion criteria. The task force emphasised the importance for the health professional to adopt a patient-centred framework within a biopsychosocial perspective, to have sufficient knowledge of IA and OA pathogenesis, and to be able to differentiate localised and generalised pain. Treatment is guided by scientific evidence and the assessment of patient needs, preferences and priorities; pain characteristics; previous and ongoing pain treatments; inflammation and joint damage; and psychological and other pain-related factors. Pain treatment options typically include education complemented by physical activity and exercise, orthotics, psychological and social interventions, sleep hygiene education, weight management, pharmacological and joint-specific treatment options, or interdisciplinary pain management. Effects on pain were most uniformly positive for physical activity and exercise interventions, and for psychological interventions. Effects on pain for educational interventions, orthotics, weight management and multidisciplinary treatment were shown for particular disease groups. Underpinned by available systematic reviews and meta-analyses, these recommendations enable health professionals to provide knowledgeable pain-management support for people with IA and OA.

Objective Recently, the 7 Tesla (7 T) Epilepsy Task Force published recommendations for 7 T magnetic resonance imaging (MRI) in patients with pharmaco-resistant focal epilepsy in pre-surgical evaluation. The objective of this study was to implement and evaluate this consensus protocol with respect to both its practicability and its diagnostic value/potential lesion delineation surplus effect over 3 T MRI in the pre-surgical work-up of patients with pharmaco-resistant focal onset epilepsy. Methods The 7 T MRI protocol consisted of T1-weighted, T2-weighted, high-resolution-coronal T2-weighted, fluid-suppressed, fluid-and-white-matter-suppressed, and susceptibility-weighted imaging, with an overall duration of 50 min. Two neuroradiologists independently evaluated the ability of lesion identification, the detection confidence for these identified lesions, and the lesion border delineation at 7 T compared to 3 T MRI. Results Of 41 recruited patients > 12 years of age, 38 were successfully measured and analyzed. Mean detection confidence scores were non-significantly higher at 7 T (1.95 ± 0.84 out of 3 versus 1.64 ± 1.19 out of 3 at 3 T, p = 0.050). In 50% of epilepsy patients measured at 7 T, additional findings compared to 3 T MRI were observed. Furthermore, we found improved border delineation at 7 T in 88% of patients with 3 T-visible lesions. In 19% of 3 T MR-negative cases a new potential epileptogenic lesion was detected at 7 T. Conclusions The diagnostic yield was beneficial, but with 19% new 7 T over 3 T findings, not major. Our evaluation revealed epilepsy outcomes worse than ILAE Class 1 in two out of the four operated cases with new 7 T findings.

Voluntary Standard Setting Organizations (SSOs) use a consensus process to create new compatibility standards. Practitioners have suggested that SSOs are increasingly politicized and perhaps incapable of producing timely standards. This article develops a simple model of standard setting committees and tests its predictions using data from the Internet Engineering Task Force, an SSO that produces many of the standards used to run the Internet. The results show that an observed slowdown in standards production between 1993 and 2003 can be linked to distributional conflicts created by the rapid commercialization of the Internet.

Finance is a precondition for many of the activities that harm ecosystems, but how to address this underlying driver of biodiversity loss remains a topic of debate. This paper reviews the Task Force on Nature‐Related Financial Disclosures (TNFD), a corporate‐led effort that aims to identify how changes to biodiversity may create financial risks for companies and investors. This approach is also promoted as a strategy for managing the impact of business on biodiversity, with the assumption that risk disclosure will more effectively price biodiversity‐harming activities. We assess the potential of the TNFD toward this end, and invite conservation scientists, practitioners, and policymakers to engage critically with its theory of change. We find that the relationship between disclosing biodiversity risk and redirecting finance away from environmental degradation is tenuous and unproven, making this mechanism insufficient for addressing the impact of the financial sector on nature. We question the embrace of another industry‐led mechanism that implies that a lack of information is the greatest barrier to stopping biodiversity loss. Further, there are risks that this financial sector approach to biodiversity will reinforce the highly unequal concentration of power and wealth, which is itself inimical to transformative change, as called for by the Intergovernmental Science–Policy Platform on Biodiversity and Ecosystem Services.

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

The ocean is key to understanding societal threats including climate change, sea level rise, ocean warming, tsunamis, and earthquakes. Because the ocean is difficult and costly to monitor, we lack fundamental data needed to adequately model, understand, and address these threats. One solution is to integrate sensors into future undersea telecommunications cables. This is the mission of the SMART subsea cables initiative (Science Monitoring And Reliable Telecommunications). SMART sensors would “piggyback” on the power and communications infrastructure of a million kilometers of undersea fiber optic cable and thousands of repeaters, creating the potential for seafloor-based global ocean observing at a modest incremental cost. Initial sensors would measure temperature, pressure, and seismic acceleration. The resulting data would address two critical scientific and societal issues: the long-term need for sustained climate-quality data from the under-sampled ocean (e.g., deep ocean temperature, sea level, and circulation), and the near-term need for improvements to global tsunami warning networks. A Joint Task Force (JTF) led by three U.N. agencies (ITU/WMO/UNESCO-IOC) is working to bring this initiative to fruition. This paper explores the ocean science and early warning improvements available from SMART cable data, and the societal, technological, and financial elements of realizing such a global network. Simulations show that deep ocean temperature and pressure measurements can improve estimates of ocean circulation and heat content, and cable-based pressure and seismic-acceleration sensors can improve tsunami warning times and earthquake parameters. The technology of integrating these sensors into fiber optic cables is discussed, addressing sea and land-based elements plus delivery of real-time open data products to end users. The science and business case for SMART cables is evaluated. SMART cables have been endorsed by major ocean science organizations, and JTF is working with cable suppliers and sponsors, multilateral development banks and end-users to incorporate SMART capabilities into future cable projects. By investing now, we can build up a global ocean network of long-lived SMART cable sensors, creating a transformative addition to the global ocean observing system.