A mixed methods protocol to investigate medication adherence in patients with rheumatoid arthritis of White British and South Asian origin

BACKGROUND: Low adherence to medicines is an important issue as up to 40% of patients with chronic diseases do not take their medications as prescribed. This leads to suboptimal clinical benefit. In the context of rheumatoid arthritis, there is a dearth of data on adherence to disease-modifying antirheumatic drugs among minority ethnic groups. This study aims to assess the relationship between adherence to medicines and biopsychosocial variables in patients with rheumatoid arthritis of South Asian and White British origin. METHODS/ANALYSIS: A mixed methods approach will be used, encompassing a cross-sectional survey of 176 patients collecting demographic and clinical data, including information on adherence behaviour collected using a series of questionnaires. This will be followed by indepth qualitative interviews. ETHICS AND DISSEMINATION: This study has been approved by the South Birmingham (10/H1207/89) and Coventry and Warwickshire (12/WM/0041) Research Ethics Committees. The authors will disseminate the findings in peer-reviewed publications

Remnants of an ancient forest provide ecological context for Early Miocene fossil apes

The lineage of apes and humans (Hominoidea) evolved and radiated across Afro-Arabia in the early Neogene during a time of global climatic changes and ongoing tectonic processes that formed the East African Rift. These changes probably created highly variable environments and introduced selective pressures influencing the diversification of early apes. However, interpreting the connection between environmental dynamics and adaptive evolution is hampered by difficulties in locating taxa within specific ecological contexts: time-averaged or reworked deposits may not faithfully represent individual palaeohabitats. Here we present multiproxy evidence from Early Miocene deposits on Rusinga Island, Kenya, which directly ties the early ape Proconsul to a widespread, dense, multistoried, closed-canopy tropical seasonal forest set in a warm and relatively wet, local climate. These results underscore the importance of forested environments in the evolution of early apes

Early human impacts and ecosystem reorganization in southern-central Africa

Modern Homo sapiens engage in substantial ecosystem modification, but it is difficult to detect the origins or early consequences of these behaviors. Archaeological, geochronological, geomorphological, and paleoenvironmental data from northern Malawi document a changing relationship between forager presence, ecosystem organization, and alluvial fan formation in the Late Pleistocene. Dense concentrations of Middle Stone Age artifacts and alluvial fan systems formed after ca. 92 thousand years ago, within a paleoecological context with no analog in the preceding half-million-year record. Archaeological data and principal coordinates analysis indicate that early anthropogenic fire relaxed seasonal constraints on ignitions, influencing vegetation composition and erosion. This operated in tandem with climate-driven changes in precipitation to culminate in an ecological transition to an early, pre-agricultural anthropogenic landscape.info:eu-repo/semantics/publishedVersio

Poised Transcription Factories Prime Silent uPA Gene Prior to Activation

The association of poised genes with transcription factories may contribute to rapid transcriptional activation in response to stimuli and to silencing when genes are located at the interior of their chromosome territories

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Late Pleistocene artefacts and fauna from Rusinga and Mfangano islands, Lake Victoria, Kenya

Surveys and excavations in 2009-2011 recovered fossil and artefact assemblages from late Pleistocene sediments on Rusinga and Mfangano islands (Lake Victoria, Kenya). Radiometric age estimates suggest that the Rusinga material dates to between 100 and 33 kya, whereas that from Mfangano may date to 35 kya. The preservation of a large and diverse suite of vertebrate fossils is unusual for Pleistocene sites in the Lake Victoria region and the composition of the faunal assemblages from both islands strongly suggest an open, arid, grassland setting very different from that found in western Kenya today. Middle Stone Age (MSA) artefacts from Rusinga and possible Later Stone Age (LSA) or MSA/LSA assemblages from Mfangano are distinct from Lupemban MSA sites characteristic of the Lake Victoria region and instead share a number of typological and technological features with late Pleistocene sites from open grassland settings in the East African Rift System. This highlights the complex roles that shifting environments, as well as temporal change, may have played in the development of regional variation among Equatorial African artefact assemblages in the Pleistocene

Ecological risk, demography and technological complexity in the Late Pleistocene of northern Malawi: implications for geographical patterning in the Middle Stone Age

The Late Pleistocene Middle Stone Age (MSA) record of Africa provides early examples of standardised stone tool production and complex manufacturing sequences, superficially implying a long‐term trend towards greater complexity in MSA technology at a continental scale. However, at this scale, spatial and temporal expressions of technological complexity are uneven. New lithic and chronometric data from the East-Central African record add further regional perspective to these patterns. Stone artefact assemblages from Karonga, northern, Malawi (92-22 ka), persistently lack the complexity demonstrated elsewhere in Africa at the same times, despite similar lithic raw materials. These new data provide an essential avenue for exploring hypotheses about the roles of environmental risk and demography in shaping the expression of MSA technology across the continent, not just at a local scale. When set within this framework, the simplicity of the Karonga MSA is best explained by its position in an environment that was persistently low in relative extrinsic subsistence risk. These results reinforce that motivations to invest in complex tools were variable through space and time, and that this variation, more than factors relating to behavioural capacity, may explain the patchy evidence for lithic complexity in the later MSA

Evaluating the potential for tactical hunting in the Middle Stone Age: insights from a bonebed of the extinct bovid, Rusingoryx atopocranion

The foraging behaviors of Middle Stone Age (MSA) early modern humans have largely been based on evidence from well-stratified cave sites in South Africa. Whereas these sites have provided an abundance of data for behavioral reconstruction that are unmatched elsewhere in Africa, they are unlikely to preserve evidence of the diversity of foraging strategies employed by MSA hunters who lived in a variety of ecological and landscape settings across the African continent. Here we describe the results of recent excavations at the open-air site of Bovid Hill at Wakondo, Rusinga Island, Kenya, which yielded 24 in situ MSA artifacts within an assemblage of bones comprised exclusively of the extinct alcelaphin bovid Rusingoryx atopocranion. The excavated faunal assemblage is characterized by a prime-age-dominated mortality profile and includes cut-marked specimens and an associated MSA Levallois blade-based artifact industry recovered from a channel deposit dated to 68\ua0±\ua05\ua0ka by optically stimulated luminescence. Taphonomic, geologic, and faunal evidence points to mass exploitation of Rusingoryx by humans at Bovid Hill, which likely represents an initial processing site that was altered post-depositionally by fluvial processes. This site highlights the importance of rivers and streams for mass procurement in an open and seasonal landscape, and provides important new insights into MSA behavioral variability with respect to environmental conditions, site function, and tactical foraging strategies in eastern Africa. Bovid Hill thus joins a growing number of MSA and Middle Paleolithic localities that are suggestive of tactical hunting behaviors and mass capture of gregarious ungulate prey

Lean Enterprise Value Second Edition

The 2002 edition of Lean Enterprise Value elevated prevailing lean production thinking into a bold new framework for lean enterprise value creation, focused on the challenge of transforming the greater aerospace enterprise. The book’s core message was that an enterprise must create value throughout its value stream, for all stakeholders, to achieve lasting success in an environment of fundamental and continuing change. This second edition enriches the book’s original message by bringing an important new insight: lean enterprise value creation can be significantly enhanced by a dynamic learning and value creating community. This concept is explored by focusing directly on the evolution of the Lean Advancement Initiative (LAI), since the initiative itself represents a model for such a community. Drawing principally on the initiative’s work in its second decade, the authors develop a new framework for evolving dynamic learning and value creating communities – defining their enablers, core attributes, and the overarching principles guiding their evolution. The framework is supported by concrete examples, case studies, and stories from LAI’s lived experience. This work is reported in an extensive new Epilogue and accompanying appendices, which contain a wealth of publicly available background material, references, resources, and tools, capturing LAI’s legacy. The second edition offers new insights into the challenge of creating value in technically complex modern enterprises, industries, and industrial ecosystems, reaching beyond aerospace. A major concluding suggestion is that LAI’s model as a dynamic learning and value creating community can be replicated as a template to tackle a variety of complex, large-scale, “messy” transformational challenges