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"Roberts, Andrew"
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Elegy : the first day on the Somme
On 1st July 1916, after a five-day bombardment, 11 British and 5 French divisions launched their long-awaited 'Big Push' on German positions on high ground above the Rivers Ancre and Somme on the Western Front. Some ground was gained, but at a terrible cost. In killing-grounds whose names are indelibly imprinted on 20th-century memory, German machine-guns - manned by troops who had sat out the storm of shellfire in deep dugouts - inflicted terrible losses on the British infantry. Andrew Roberts evokes the pity and the horror of the blackest day in the history of the British army - a summer's day-turned-hell-on-earth by modern military technology - in the words of casualties, survivors, and the bereaved.
Book
Dynamics of Green Sahara Periods and Their Role in Hominin Evolution
Astronomically forced insolation changes have driven monsoon dynamics and recurrent humid episodes in North Africa, resulting in green Sahara Periods (GSPs) with savannah expansion throughout most of the desert. Despite their potential for expanding the area of prime hominin habitats and favouring out-of-Africa dispersals, GSPs have not been incorporated into the narrative of hominin evolution due to poor knowledge of their timing, dynamics and landscape composition at evolutionary timescales. We present a compilation of continental and marine paleoenvironmental records from within and around North Africa, which enables identification of over 230 GSPs within the last 8 million years. By combining the main climatological determinants of woody cover in tropical Africa with paleoenvironmental and paleoclimatic data for representative (Holocene and Eemian) GSPs, we estimate precipitation regimes and habitat distributions during GSPs. Their chronology is consistent with the ages of Saharan archeological and fossil hominin sites. Each GSP took 2-3 kyr to develop, peaked over 4-8 kyr, biogeographically connected the African tropics to African and Eurasian mid latitudes, and ended within 2-3 kyr, which resulted in rapid habitat fragmentation. We argue that the well-dated succession of GSPs presented here may have played an important role in migration and evolution of hominins.
Journal Article
The storm of war : a new history of the Second World War
A comprehensive history of World War II analyzes the factors that affected the war's outcome and presents stories of many little-known individuals whose experiences displayed the epitome of courage and self-sacrifice.
Book
Targeting GM-CSF in inflammatory diseases
Key Points
GM-CSF (granulocyte-macrophage colony stimulating factor) is a multifunctional cytokine that regulates inflammatory responses, including emergency responses in the bone marrow
Mice deficient in GM-CSF develop normally, apart from displaying a lung phenotype similar to pulmonary alveolar proteinosis in humans
GM-CSF antagonism has beneficial effects in multiple autoimmune and inflammatory preclinical disease models, including inflammatory arthritis and inflammatory disease of the central nervous system
A monoclonal antibody specific to GM-CSFRα (GM-CSF ligand-binding α-chain) was well tolerated in early phase clinical trials in rheumatoid arthritis (RA), leading to impressive clinical responses that included rapid pain relief
Therapeutic agents targeting GM-CSF signalling are currently undergoing evaluation in a number of diseases, including RA and multiple sclerosis, among others
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine with a wide range of biological effects that span innate and adaptive immunity processes. As our knowledge of the biology of GM-CSF improves, its potential as a therapeutic target in rheumatic diseases is being acknowledged, and the first early phase clinical trials of GM-CSF inhibition in patients with inflammatory disorders have produced encouraging results.
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a growth factor first identified as an inducer of differentiation and proliferation of granulocytes and macrophages derived from haematopoietic progenitor cells. Later studies have shown that GM-CSF is involved in a wide range of biological processes in both innate and adaptive immunity, with its production being tightly linked to the response to danger signals. Given that the functions of GM-CSF span multiple tissues and biological processes, this cytokine has shown potential as a new and important therapeutic target in several autoimmune and inflammatory disorders — particularly in rheumatoid arthritis. Indeed, GM-CSF was one of the first cytokines detected in human synovial fluid from inflamed joints. Therapies that target GM-CSF or its receptor have been tested in preclinical studies with promising results, further supporting the potential of targeting the GM-CSF pathway. In this Review, we discuss our expanding view of the biology of GM-CSF, outline what has been learnt about GM-CSF from studies of animal models and human diseases, and summarize the results of early phase clinical trials evaluating GM-CSF antagonism in inflammatory disorders.
Journal Article
Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder; it is the most common cause of dementia and has no treatment. It is characterized by two pathological hallmarks, the extracellular deposits of amyloid beta (Aβ) and the intraneuronal deposits of Neurofibrillary tangles (NFTs). Yet, those two hallmarks do not explain the full pathology seen with AD, suggesting the involvement of other mechanisms. Neuroinflammation could offer another explanation for the progression of the disease. This review provides an overview of recent advances on the role of the immune cells’ microglia and astrocytes in neuroinflammation. In AD, microglia and astrocytes become reactive by several mechanisms leading to the release of proinflammatory cytokines that cause further neuronal damage. We then provide updates on neuroinflammation diagnostic markers and investigational therapeutics currently in clinical trials to target neuroinflammation.
Journal Article
Orbital climate variability on the northeastern Tibetan Plateau across the Eocene–Oligocene transition
The first major build-up of Antarctic glaciation occurred in two consecutive stages across the Eocene–Oligocene transition (EOT): the EOT-1 cooling event at ~34.1–33.9 Ma and the Oi-1 glaciation event at ~33.8–33.6 Ma. Detailed orbital-scale terrestrial environmental responses to these events remain poorly known. Here we present magnetic and geochemical climate records from the northeastern Tibetan Plateau margin that are dated precisely from ~35.5 to 31 Ma by combined magneto- and astro-chronology. These records suggest a hydroclimate transition at ~33.7 Ma from eccentricity dominated cycles to oscillations paced by a combination of eccentricity, obliquity, and precession, and confirm that major Asian aridification and cooling occurred at Oi-1. We conclude that this terrestrial orbital response transition coincided with a similar transition in the marine benthic δ
18
O record for global ice volume and deep-sea temperature variations. The dramatic reorganization of the Asian climate system coincident with Oi-1 was, thus, a response to coeval atmospheric CO
2
decline and continental-scale Antarctic glaciation.
Marine records indicate a greenhouse to icehouse climate transition at ~34 million years ago, but how the climate changed within continental interiors at this time is less well known. Here, the authors show an orbital climate response shift with aridification on the northeastern Tibetan Plateau during this time.
Journal Article