European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average survival for all European cancer patients by 2035.

Bookshelf 2021

Covid-19 has continued to affect book reviewing this year, as reviewers whom we had to remind wrote us back saying everything from "I'm stuck in Dakar" or "I crushed my right index finger in an anchor mishap two months ago [and] ... typing was problematic for a number of weeks" to "in the midst of the pandemic I fell and broke my leg in two places," not to mention people's frequent child-care/remote learning challenges (for some books, we had to identify and ask as many as nine potential reviewers before one agreed) or the difficulties of getting books from publishers to reviewers in pandemic-bombed Brazil. Rowman & Littlefield Publishers, 2020, cloth US$ 79.00) Celia Sánchez Manduley: The Life andLegacy of a Cuban Revolutionary, by Tiffany A. Sippial (Chapel Hill: University of North Carolina Press, 2020, paper US$29.95) Staging Discomfort: Performance and Queerness in Contemporary Cuba, by Bretton White (Gainesville: University Press of Florida, 2020, cloth US$ 85.00) The World That Fear Made: Slave Revolts and Conspiracy Scares in Early America, by Jason T. Sharples (Philadelphia: University of Pennsylvania Press, 2020, cloth US$ 45.00) Afrocubanas: History, Thought, and Cultural Practices, edited by Devyn Spence Benson & Daisy Rubiera Castillo (Lanham MD: Monster in the Middle (New York: Riverhead Books [Penguin/Random House], 2021, cloth US$27.00), is the second novel by Virgin Islands-born Tiphanie Yanique-in "Bookshelf 2014," we called her first one, the multiple prize-winning Land of Love and Drowning, "a gem," and this one is as well. In the fictional town of Pleasantview, we meet Syrian shopkeepers, Muslimeen converts, Pentecostal churchgoers, street gang members, Hindus with roadside fruit and vegetable stands, sex workers trafficked from Venezuela and Colombia, lawyers, politicians, and police, as well as myriads of Black women, but the focus, always, is on family relations-misogyny, poverty, violence, and the allure and perils of migration (to New York, Barbados ...)

A natively flexible 32-bit Arm microprocessor.

Nearly 50 years ago, Intel created the world's first commercially produced microprocessor-the 4004 (ref. 1), a modest 4-bit CPU (central processing unit) with 2,300 transistors fabricated using 10 µm process technology in silicon and capable only of simple arithmetic calculations. Since this ground-breaking achievement, there has been continuous technological development with increasing sophistication to the stage where state-of-the-art silicon 64-bit microprocessors now have 30 billion transistors (for example, the AWS Graviton2 (ref. 2) microprocessor, fabricated using 7 nm process technology). The microprocessor is now so embedded within our culture that it has become a meta-invention-that is, it is a tool that allows other inventions to be realized, most recently enabling the big data analysis needed for a COVID-19 vaccine to be developed in record time. Here we report a 32-bit Arm (a reduced instruction set computing (RISC) architecture) microprocessor developed with metal-oxide thin-film transistor technology on a flexible substrate (which we call the PlasticARM). Separate from the mainstream semiconductor industry, flexible electronics operate within a domain that seamlessly integrates with everyday objects through a combination of ultrathin form factor, conformability, extreme low cost and potential for mass-scale production. PlasticARM pioneers the embedding of billions of low-cost, ultrathin microprocessors into everyday objects.

Neurochemical biomarkers to study CNS effects of COVID-19: A narrative review and synthesis.

Neurological symptoms are frequently reported in patients suffering from COVID-19. Common CNS-related symptoms include anosmia, caused by viral interaction with either neurons or supporting cells in nasal olfactory tissues. Diffuse encephalopathy is the most common sign of CNS dysfunction, which likely results from the CNS consequences of the systemic inflammatory syndrome associated with severe COVID-19. Additionally, microvascular injuries and thromboembolic events likely contribute to the neurologic impact of acute COVID-19. These observations are supported by evidence of CNS immune activation in cerebrospinal fluid (CSF) and in autopsy tissue, along with the detection of microvascular injuries in both pathological and neuroimaging studies. The frequent occurrence of thromboembolic events in patients with COVID-19 has generated different hypotheses, among which viral interaction with perivascular cells is particularly attractive, yet unproven. A distinguishing feature of CSF findings in SARS-CoV-2 infection is that clinical signs characteristic of neurotropic viral infections (CSF pleocytosis and blood-brain barrier injury) are mild or absent. Moreover, virus detection in CSF is rare and often of uncertain significance. In this review, we provide an overview of the neurological impact that occurs in the acute phase of COVID-19, and the role of CSF biomarkers in the clinical management and research to better treat and understand the disease. In addition to aiding as diagnostic and prognostic tools during acute infection, the use of comprehensive and well-characterized CSF and blood biomarkers will be vital in understanding the potential impact on the CNS in the rapidly increasing number of individuals recovering from COVID-19.

Guidelines for Mountain Rescue During the COVID-19 Pandemic: Official Guidelines of the International Commission for Alpine Rescue.

Roy, Steven, Inigo Soteras, Alison Sheets, Richard Price, Kazue Oshiro, Simon Rauch, Don McPhalen, Maria Antonia Nerin, Giacomo Strapazzon, Myron Allen, Alistair Read, and Peter Paal. Guidelines for mountain rescue during the COVID-19 pandemic: official guidelines of the International Commission for Alpine Rescue. High Alt Med Biol. 22: 128-141, 2021. Background: In mountain rescue, uncertainty exists on the best practice to prevent coronavirus disease 2019 (COVID-19) transmission. The aim of this work was to provide a state-of-the-art overview of the challenges caused by the COVID-19 pandemic in mountain rescue. Methods: Original articles or reviews, published until December 27, 2020 in Cochrane COVID-19 Study Register, EMBASE, PubMed, and Google Scholar were included. Articles were limited to English, French, German, or Spanish with the article topic COVID-19 or other epidemics, addressing transmission, transport, rescue, or cardiopulmonary resuscitation. Results: The literature search yielded 6,190 articles. A total of 952 were duplicates and 5,238 were unique results. After exclusion of duplicates and studies that were not relevant to this work, 249 articles were considered for this work. Finally, 72 articles and other sources were included. Conclusions: Recommendations are provided for protection of the rescuer (including screening, personal protective equipment [PPE], and vaccination), protection of the patient (including general masking if low risk, specific PPE if high risk), equipment hygiene (including disinfection after every mission), use of single-use products, training and medical measures under COVID-19 precautions, and psychological wellbeing of rescuers during the COVID-19 pandemic. Adapted COVID-19 precautions for low-and-medium-income countries are also discussed.

Eliminating HPV-caused cancers in Europe: Achieving the possible.

The 690,000 cases of cancer caused worldwide each year by HPV (human papillomavirus) are among the easiest of all cancers to prevent. However, the actions so far taken in terms of both policy and practice by health systems in many European states have neither matched the scale of the problem nor seized the opportunities for disease prevention potentially offered by vaccination and screening. Treatments for HPV-caused cancers are also inequitably provided across the region and widespread misinformation about HPV undermines efforts to improve public health. The European Cancer Organisation's HPV Action Network has made the case for action for the elimination of all the cancers caused by HPV through gender-neutral vaccination, effective cervical cancer screening, better quality treatments, and public and professional education across Europe. The World Health Organisation's new global strategy for the elimination of cervical cancer (launched in November 2020), together with Europe's Beating Cancer Plan (February 2021), together provide a major opportunity to tackle decisively all the cancers caused by HPV. The Beating Cancer Plan, which was significantly influenced by evidence provided by the HPV Action Network, commits to supporting EU member states' efforts to extend routine vaccination of girls and boys and to creating a new EU-supported Cancer Screening Scheme to help Member States ensure that 90% of the EU population who qualify for cervical cancer screening are offered it by 2025. The goal of HPV cancer elimination is now both possible and achievable. The challenge is to ensure implementation and delivery by EU member states and more widely across the European region.

CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series.

OBJECTIVE: To explore whether hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neurologic symptoms have evidence of CNS infection, inflammation, and injury using CSF biomarker measurements. METHODS: We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, ß2-microglobulin, and immunoglobulin G index), blood-brain barrier integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe coronavirus disease 2019 (COVID-19) and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4 of 6), suspected meningitis (1 of 6), and dysgeusia (1 of 6). SARS-CoV-2 infection was confirmed by real-time PCR analysis of nasopharyngeal swabs. RESULTS: SARS-CoV-2 RNA was detected in the plasma of 2 patients (cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in 1 but not in a second real-time PCR assay. CSF neopterin (median 43.0 nmol/L) and ß2-microglobulin (median 3.1 mg/L) were increased in all. Median immunoglobulin G index (0.39), albumin ratio (5.35), and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients. CONCLUSION: Our results in patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.

Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.

OBJECTIVE: To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury. METHODS: We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort. RESULTS: The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury. CONCLUSION: We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.