Cancer in Sub-Saharan Africa: The need for new paradigms in global health

This repository item contains a single issue of The Pardee Papers, a series papers that began publishing in 2008 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. The Pardee Papers series features working papers by Pardee Center Fellows and other invited authors. Papers in this series explore current and future challenges by anticipating the pathways to human progress, human development, and human well-being. This series includes papers on a wide range of topics, with a special emphasis on interdisciplinary perspectives and a development orientation.Cancer is the leading global cause of death, and has been on the rise in low- and middle-income countries in sub-Saharan Africa and worldwide, which are projected to account for roughly 80 percent of global cancer diagnoses by 2030. Much like the inadequate funding and priority-setting that plagued the treatment of HIV/AIDS early in the epidemic, cancer treatment is suffering from a cycle of inaction in sub-Saharan Africa. In this paper, Maia Olsen, a 2013 Pardee Graduate Summer Fellow, examines the lessons learned from the global response to the HIV/AIDS epidemic in sub-Saharan Africa and applies them to the future of political advocacy, funding, and treatment of cancer in the region. Maia Olsen is a Program Manager for the NCD Synergies project at Partners In Health, a policy and advocacy program focused on non-communicable diseases (NCDs) and injuries among the poorest populations worldwide. She holds an MPH in International Health from Boston University and a BA in Anthropology and Global Development Studies from Grinnell College

Nucleation of (4)R^{(4)}R Brane Universes

The creation of brane universes induced by a totally antisymmetric tensor living in a fixed background spacetime is presented, where a term involving the intrinsic curvature of the brane is considered. A canonical quantum mechanical approach employing Wheeler-DeWitt equation is done. The probability nucleation for the brane is calculated taking into account both an instanton method and a WKB approximation. Some cosmological implications arose from the model are presented.Comment: 19 pages, 2 figure

Nanopore ReCappable sequencing maps SARS-CoV-2 5′ capping sites and provides new insights into the structure of sgRNAs

The SARS-CoV-2 virus has a complex transcriptome characterised by multiple, nested subgenomic RNAsused to express structural and accessory proteins. Long-read sequencing technologies such as nanopore direct RNA sequencing can recover full-length transcripts, greatly simplifying the assembly of structurally complex RNAs. However, these techniques do not detect the 5 ' cap, thus preventing reliable identification and quantification of full-length, coding transcript models. Here we used Nanopore ReCappable Sequencing (NRCeq), a new technique that can identify capped full-length RNAs, to assemble a complete annotation of SARS-CoV-2 sgRNAs and annotate the location of capping sites across the viral genome. We obtained robust estimates of sgRNA expression across cell lines and viral isolates and identified novel canonical and non-canonical sgRNAs, including one that uses a previously un-annotated leader-to-body junction site. The data generated in this work constitute a useful resource for the scientific community and provide important insights into the mechanisms that regulate the transcription of SARS-CoV-2 sgRNAs

Citrullination regulates pluripotency and histone H1 binding to chromatin.

Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.Cancer Research UKThis is the author accepted manuscript. The final version is available from the Nature Publishing Group via http://dx.doi.org/10.1038/nature1294

Improvising Prescription: Evidence from the Emergency Room

© 2016 British Academy of Management. Global medical practice is increasingly standardizing through evidence-based approaches and quality certification procedures. Despite this increasing standardization, medical work in emergency units necessarily involves sensitivity to the individual, the particular and the unexpected. While much medical practice is routine, important improvisational elements remain significant. Standardization and improvisation can be seen as two conflicting logics. However, they are not incompatible, although the occurrence of improvisation in highly structured and institutionally complex environments remains underexplored. The study presents the process of improvisation in the tightly controlled work environment of the emergency room. The authors conducted an in situ ethnographic observation of an emergency unit. An inductive approach shows professionals combining ostensive compliance with protocols with necessary and occasional 'underlife' improvisations. The duality of improvisation as simultaneously present and absent is related to pressures in the institutional domain as well as to practical needs emerging from the operational realm. The intense presence of procedures and work processes enables flexible improvised performances that paradoxically end up reinforcing institutional pressures for standardization

No detection of methane on Mars from early ExoMars Trace Gas Orbiter observations

The detection of methane on Mars has been interpreted as indicating that geochemical or biotic activities could persist on Mars today. A number of different measurements of methane show evidence of transient, locally elevated methane concentrations and seasonal variations in background methane concentrations. These measurements, however, are difficult to reconcile with our current understanding of the chemistry and physics of the Martian atmosphere, which-given methane's lifetime of several centuries-predicts an even, well mixed distribution of methane. Here we report highly sensitive measurements of the atmosphere of Mars in an attempt to detect methane, using the ACS and NOMAD instruments onboard the ESA-Roscosmos ExoMars Trace Gas Orbiter from April to August 2018. We did not detect any methane over a range of latitudes in both hemispheres, obtaining an upper limit for methane of about 0.05 parts per billion by volume, which is 10 to 100 times lower than previously reported positive detections. We suggest that reconciliation between the present findings and the background methane concentrations found in the Gale crater would require an unknown process that can rapidly remove or sequester methane from the lower atmosphere before it spreads globally

Hydroclimatic Controls on the Isotopic (δ18 O, δ2 H, d-excess) Traits of Pan-Arctic Summer Rainfall Events

Arctic sea-ice loss is emblematic of an amplified Arctic water cycle and has critical feedback implications for global climate. Stable isotopes (delta O-18, delta H-2, d-excess) are valuable tracers for constraining water cycle and climate processes through space and time. Yet, the paucity of well-resolved Arctic isotope data preclude an empirically derived understanding of the hydrologic changes occurring today, in the deep (geologic) past, and in the future. To address this knowledge gap, the Pan-Arctic Precipitation Isotope Network (PAPIN) was established in 2018 to coordinate precipitation sampling at 19 stations across key tundra, subarctic, maritime, and continental climate zones. Here, we present a first assessment of rainfall samples collected in summer 2018 (n = 281) and combine new isotope and meteorological data with sea ice observations, reanalysis data, and model simulations. Data collectively establish a summer Arctic Meteoric Water Line where delta H-2 = 7.6.delta O-18-1.8 (r(2) = 0.96, p 0.75 parts per thousand/degrees C) were observed at continental sites, while statistically significant temperature relations were generally absent at coastal stations. Model outputs indicate that 68% of the summer precipitating air masses were transported into the Arctic from mid-latitudes and were characterized by relatively high delta O-18 values. Yet 32% of precipitation events, characterized by lower delta O-18 and high d-excess values, derived from northerly air masses transported from the Arctic Ocean and/or its marginal seas, highlighting key emergent oceanic moisture sources as sea ice cover declines. Resolving these processes across broader spatial-temporal scales is an ongoing research priority, and will be key to quantifying the past, present, and future feedbacks of an amplified Arctic water cycle on the global climate system

Martian dust storm impact on atmospheric H₂O and D/H observed by ExoMars Trace Gas Orbiter

Global dust storms on Mars are rare but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere, primarily owing to solar heating of the dust. In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars. Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes, as well as a decrease in the water column at low latitudes. Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H2O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals. The observed changes in H2O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700