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\"Celebrating the work of Keith McLachlan, a well-known and much-admired geographer of the Middle East and North Africa, this book combines three interrelated topics that define the region. The Middle East has been integral to the growth of the global oil industry, an aspect of its evolution since 1908 which has had profound geopolitical implications as well. The territory was also the arena for the last European experiment in colonialism, a development that has left its legacy even today. And, historically, it has been the location of the great hydraulic civilisations of Egypt and Mesopotamia, yet is still dependent on the flow of its two major river systems - the Nile and the Tigris-Euphrates - in an era of impending climate crisis. These themes form the essence of themes that are discussed in the chapters that follow. Keith McLachlan played a significant role in our understanding of these themes and of their effects in the contemporary world, as the comments of those who worked with him and have contributed towards this book reveal. Examining agriculture, oil and state construction, this volume offers an insight into how the contemporary Middle East was constructed after the collapse of the Ottoman Empire. It is a key resource for scholars and students interested in geopolitics and the geography of the Middle East\"-- Provided by publisher.

This paper chronicles critical chapters in the delimitation of Iraq's boundaries with Iran and Kuwait, paradoxically in the period preceding the Great War. For such territorial definition took place before the Iraqi state was even formed, yet it would create many of the strategic problems that Iraq has since faced with its two neighbors. Narrowing the Perso-Ottoman land frontier in the mid-19th century had been an Anglo-Russian project, though it was largely Britain's interests that proved conclusive in its final settlement in 1914. The discovery of oil in Persia in the first decade of the 20th century added a new dimension to settling the southern end of the frontier along the Shatt al-Arab river. Britain's interest in maintaining the Persian Gulf as a British lake in order to defend British India was the chief determinant of the contemporary territorial definition of Kuwait. In shaping these territorial limits and dealing with the Ottoman Empire, Britain could not have realized that it was essentially creating the explosive contemporary strategic issue of Iraqi access to the Persian Gulf. With hindsight, it seems that Britain bequeathed to the Iraqi state an eastern question of its own.

In this study of a cohort of adults with genetic mutations that cause autosomal dominant Alzheimer's disease, researchers identified abnormalities in cerebrospinal fluid biomarkers and neuroimaging tests that develop decades before the onset of dementia. Alzheimer's disease is the most common cause of dementia and is currently estimated to affect more than 5 million people in the United States, with an expected increase to 13 million by the year 2050. The typical clinical presentation is progressive loss of memory and cognitive function, ultimately leading to a loss of independence and causing a heavy personal toll on the patient and the family. The costs of care of patients with Alzheimer's disease in 2010 were estimated at more than $172 billion in the United States, an annual cost that is predicted to increase to a trillion dollars . . .

The JmjC histone demethylases (KDMs) are linked to tumour cell proliferation and are current cancer targets; however, very few highly selective inhibitors for these are available. Here we report cyclic peptide inhibitors of the KDM4A-C with selectivity over other KDMs/2OG oxygenases, including closely related KDM4D/E isoforms. Crystal structures and biochemical analyses of one of the inhibitors (CP2) with KDM4A reveals that CP2 binds differently to, but competes with, histone substrates in the active site. Substitution of the active site binding arginine of CP2 to N -ɛ-trimethyl-lysine or methylated arginine results in cyclic peptide substrates, indicating that KDM4s may act on non-histone substrates. Targeted modifications to CP2 based on crystallographic and mass spectrometry analyses results in variants with greater proteolytic robustness. Peptide dosing in cells manifests KDM4A target stabilization. Although further development is required to optimize cellular activity, the results reveal the feasibility of highly selective non-metal chelating, substrate-competitive inhibitors of the JmjC KDMs. JmjC histone demethylases (KDMs) are cancer targets due to their links to cell proliferation, but selective inhibition remains a challenge. Here the authors identify potent inhibitors of KDM4A-C—via in vitro selection from a vast library of cyclic peptides—that show selectivity over other KDMs.

Understanding the mechanisms by which climate variability affects multiple trophic levels in food webs is essential for determining ecosystem responses to climate change. Here we use over two decades of data collected by the Palmer Long Term Ecological Research program (PAL-LTER) to determine how large-scale climate and local physical forcing affect phytoplankton, zooplankton and an apex predator along the West Antarctic Peninsula (WAP). We show that positive anomalies in chlorophyll- a (chl- a ) at Palmer Station, occurring every 4–6 years, are constrained by physical processes in the preceding winter/spring and a negative phase of the Southern Annular Mode (SAM). Favorable conditions for phytoplankton included increased winter ice extent and duration, reduced spring/summer winds, and increased water column stability via enhanced salinity-driven density gradients. Years of positive chl- a anomalies are associated with the initiation of a robust krill cohort the following summer, which is evident in Adélie penguin diets, thus demonstrating tight trophic coupling. Projected climate change in this region may have a significant, negative impact on phytoplankton biomass, krill recruitment and upper trophic level predators in this coastal Antarctic ecosystem. The Western Antarctic Peninsular is subject to climate change, including increased winter temperatures and melting sea ice. In this study, the authors demonstrate that climate change in this area effects bacteria and phytoplankton levels, which culminates in an altered diet for the apex predator, the Adélie penguin.

Introduction Stair falls can be caused by inconsistent stair dimensions. During ascent, inconsistently taller stair risers lead to reduced foot clearances as the inconsistency goes unnoticed. A stair horizontal-vertical illusion increases perceived riser heights and foot clearance and could offset reduced foot clearances over inconsistently taller risers, though this might impact other stair safety measures. Method Twelve participants (age: 22 (3) years) ascended a seven-step staircase under three conditions: i) all steps consistent in riser height (consistent), ii) a 1cm increase in step 5 riser height (inconsistent) and iii) a 1cm increase in step 5 riser height, superimposed with a stair horizontal-vertical illusion (illusion). Vertical foot clearance, foot overhang, and margins of stability were assessed over step 4, 5 and 6. Perceived riser height due to the illusion was determined through a computer perception test. A One-Way Repeated Measures ANOVA compared biomechanical variables between conditions. A One Sample t test compared perceived riser height to the true height. Results Over the inconsistent step 5, foot clearance reduced by 0.8cm compared to consistent. Illusion increased foot clearance by 1.1cm and decreased foot overhang by 4% compared to inconsistent. On step 4 the illusion led to more anterior instability compared to inconsistent. Illusion and inconsistent led to more mediolateral stability compared to consistent. The illusion increased perceived riser height by 12%. Discussion Foot clearance reductions over inconsistently taller risers can be offset by a stair horizontal-vertical illusion. Additional benefits included a safer foot overhang and unaffected stability over the inconsistent riser. Changes to step 4 stability might have resulted from leaning forward to look at the step 5 illusion. The stair horizontal-vertical illusion could be a practical solution for inconsistently taller stair risers, where a rebuild is usually the only solution.

Summary Background Autosomal dominant familial Alzheimer's disease (ADAD) is a rare disorder with non-amnestic neurological symptoms in some clinical presentations. We aimed to compile and compare data from symptomatic participants in the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS) with those reported in the literature to estimate the prevalences of non-amnestic neurological symptoms in participants with ADAD. Methods We prospectively collected data from the DIAN-OBS database, which recruited participants from study centres in the USA, Europe, and Australia, between Feb 29, 2008, and July 1, 2014. We also did a systematic review of publications to extract individual-level clinical data for symptomatic participants with ADAD. We used data for age of onset (from first report of cognitive decline), disease course from onset to death, and the presence of 13 neurological findings that have been reported in association with ADAD. Using multivariable linear regression, we investigated the prevalences of various non-amnestic neurological symptoms and the contributions of age of onset and specific mutation type on symptoms. Findings The DIAN-OBS dataset included 107 individuals with detailed clinical data (forming the DIAN-OBS cohort). Our systematic review yielded 188 publications reporting on 1228 symptomatic individuals, with detailed neurological examination descriptions available for 753 individuals (forming the published data cohort). The most prevalent non-amnestic cognitive manifestations in participants in the DIAN-OBS cohort were those typical of mild to moderate Alzheimer's disease, including visual agnosia (55·1%, 95% CI 45·7–64·6), aphasia (57·9%, 48·6–67·3), and behavioural changes (61·7%, 51·5–70·0). Non-amnestic cognitive manifestations were less prevalent in the published data cohort (eg, visual agnosia [5·6%, 3·9–7·2], aphasia [23·0%, 20·0–26·0], and behavioural changes [31·7%, 28·4–35·1]). Prevalence of non-cognitive neurological manifestations in the DIAN-OBS cohort was low, including myoclonus and spasticity (9·3%, 95% CI 3·8–15·0), and seizures (2·8%, 0·5–5·9) and moderate for parkinsonism (11·2%, 5·3–17·1). By constrast, prevalence was higher in the published data cohort for myoclonus and spasticity (19·4%, 16·6–22·2 and 15·0%, 12·5–17·6, respectively), parkinsonism (12·5%, 10·1–15·0), and seizures (20·3%, 17·4–23·2). In an analysis of the published data cohort, ischaemic stroke was more prevalent at older ages of onset of symptoms of ADAD (odds ratio 1·09 per 1 year increase in age of onset, 95% CI 1·04–1·14, p=0·0003); and motor symptoms were more common at younger age of onset (myoclonus 0·93, 0·90–0·97, p=0·0007; seizures 0·95, 0·92–0·98, p=0·0018; corticobulbar deficits 0·91, 0·86–0·96, p=0·0012; and cerebellar ataxia 0·82, 0·74–0·91, p=0·0002). In the DIAN-OBS cohort, non-cognitive symptoms were more common at more severe stages of disease. Interpretation The non-cognitive clinical manifestations of Alzheimer's disease seem to affect a small proportion of participants with mild to moderate ADAD, and are probably influenced by disease severity, environmental, and genetic factors. When evaluating patients with potential ADAD, clinicians should note that cognitive symptoms typical of sporadic Alzheimer's disease are the most consistent finding, with some patients manifesting non-cognitive neurological symptoms. Future work is needed to determine the environmental and genetic factors that cause these neurological symptoms. Funding National Institutes of Health and German Center for Neurodegenerative Diseases.