The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data repository : structural and functional MRI, MEG, and cognitive data from a cross-sectional adult lifespan sample

Peer reviewe

Removal of the Northern Paleo-Teton Range along the Yellowstone Hotspot Track

Classically held mechanisms for removing mountain topography (e.g., erosion and gravitational collapse) require 10-100 Myr or more to completely remove tectonically generated relief. Here, we propose that mountain ranges can be completely and rapidly (\u3c 2 Myr) removed by a migrating hotspot. In western North America, multiple mountain ranges, including the Teton Range, terminate at the boundary with the relatively low relief track of the Yellowstone hotspot. This abrupt transition leads to a previously untested hypothesis that preexisting mountainous topography along the track has been erased. We integrate thermochronologic data collected from the footwall of the Teton fault with flexural-kinematic modeling and length-displacement scaling to show that the paleo-Teton fault and associated Teton Range was much longer (min. original length 190-210 km) than the present topographic expression of the range front (~65 km) and extended across the modern-day Yellowstone hotspot track. These analyses also indicate that the majority of fault displacement (min. 11.4-12.6 km) and the associated footwall mountain range growth had accumulated prior to Yellowstone encroachment at ~2 Ma, leading us to interpret that eastward migration of the Yellowstone hotspot relative to stable North America led to removal of the paleo-Teton mountain topography via posteruptive collapse of the range following multiple supercaldera (VEI 8) eruptions from 2.0 Ma to 600 ka and/or an isostatic collapse response, similar to ranges north of the Snake River plain. While this extremely rapid removal of mountain ranges and adjoining basins is probably relatively infrequent in the geologic record, it has important implications for continental physiography and topography over very short time spans

The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) study protocol: a cross-sectional, lifespan, multidisciplinary examination of healthy cognitive ageing.

BACKGROUND: As greater numbers of us are living longer, it is increasingly important to understand how we can age healthily. Although old age is often stereotyped as a time of declining mental abilities and inflexibility, cognitive neuroscience reveals that older adults use neural and cognitive resources flexibly, recruiting novel neural regions and cognitive processes when necessary. Our aim in this project is to understand how age-related changes to neural structure and function interact to support cognitive abilities across the lifespan. METHODS/DESIGN: We are recruiting a population-based cohort of 3000 adults aged 18 and over into Stage 1 of the project, where they complete an interview including health and lifestyle questions, a core cognitive assessment, and a self-completed questionnaire of lifetime experiences and physical activity. Of those interviewed, 700 participants aged 18-87 (100 per age decile) continue to Stage 2 where they undergo cognitive testing and provide measures of brain structure and function. Cognition is assessed across multiple domains including attention and executive control, language, memory, emotion, action control and learning. A subset of 280 adults return for in-depth neurocognitive assessment in Stage 3, using functional neuroimaging experiments across our key cognitive domains.Formal statistical models will be used to examine the changes that occur with healthy ageing, and to evaluate age-related reorganisation in terms of cognitive and neural functions invoked to compensate for overall age-related brain structural decline. Taken together the three stages provide deep phenotyping that will allow us to measure neural activity and flexibility during performance across a number of core cognitive functions. This approach offers hypothesis-driven insights into the relationship between brain and behaviour in healthy ageing that are relevant to the general population. DISCUSSION: Our study is a unique resource of neuroimaging and cognitive measures relevant to change across the adult lifespan. Because we focus on normal age-related changes, our results may contribute to changing views about the ageing process, lead to targeted interventions, and reveal how normal ageing relates to frail ageing in clinicopathological conditions such as Alzheimer's disease.The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1).This is the final published version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12883-014-0204-

Mixed-methods exploration of views on choice in a university asymptomatic COVID-19 testing programme.

Funder: Wellcome TrustFunder: Healthcare Improvement Studies Institute (THIS Institute), University of CambridgeFunder: Health Foundation; Id: http://dx.doi.org/10.13039/501100000724Asymptomatic COVID-19 testing programmes are being introduced in higher education institutions, but stakeholder views regarding the acceptability of mandating or incentivizing participation remain little understood. A mixed-method study (semi-structured interviews and a survey including open and closed questions) was undertaken in a case study university with a student testing programme. Survey data were analysed descriptively; analysis for interviews was based on the framework method. Two hundred and thirty-nine people participated in the study: 213 in the survey (189 students, 24 staff), and 26 in interviews (19 students, 7 staff). There was majority (62%) but not universal support for voluntary participation, with a range of concerns expressed about the potentially negative effects of mandating testing. Those who supported mandatory testing tended to do so on the grounds that it would protect others. There was also majority (64%) opposition to penalties for refusing to test. Views on restricting access to face-to-face teaching for non-participants were polarized. Three-quarters (75%) supported incentives, though there were some concerns about effectiveness and unintended consequences. Participants emphasized the importance of communication about the potential benefits of testing. Preserving the voluntariness of participation in student asymptomatic testing programmes is likely to be the most ethically sound policy unless circumstances change.Caitriona Cox, lead researcher, is a National Institute for Health Research (NIHR) academic clinical fellow. This study is funded by Mary Dixon-Woods’ NIHR Senior Investigator award (NF-SI-0617-10026), by the Wellcome Trust through a contract award for a project on ethical issues in COVID-19 testing, and by The Healthcare Improvement Studies Institute (THIS Institute), University of Cambridge. THIS Institute is supported by the Health Foundation, an independent charity committed to bringing about better health and healthcare for people in the UK

Contrasting inducible knockdown of the auxiliary PTEX component PTEX88 in P. falciparum and P. berghei unmasks a role in parasite virulence

Pathogenesis of malaria infections is linked to remodeling of erythrocytes, a process dependent on the trafficking of hundreds of parasite-derived proteins into the host erythrocyte. Recent studies have demonstrated that the Plasmodium translocon of exported proteins (PTEX) serves as the central gateway for trafficking of these proteins, as inducible knockdown of the core PTEX constituents blocked the trafficking of all classes of cargo into the erythrocyte. However, the role of the auxiliary component PTEX88 in protein export remains less clear. Here we have used inducible knockdown technologies in P. falciparum and P. berghei to assess the role of PTEX88 in parasite development and protein export, which reveal that the in vivo growth of PTEX88-deficient parasites is hindered. Interestingly, we were unable to link this observation to a general defect in export of a variety of known parasite proteins, suggesting that PTEX88 functions in a different fashion to the core PTEX components. Strikingly, PTEX88-deficient P. berghei were incapable of causing cerebral malaria despite a robust pro-inflammatory response from the host. These parasites also exhibited a reduced ability to sequester in peripheral tissues and were removed more readily from the circulation by the spleen. In keeping with these findings, PTEX88-deficient P. falciparum-infected erythrocytes displayed reduced binding to the endothelial cell receptor, CD36. This suggests that PTEX88 likely plays a specific direct or indirect role in mediating parasite sequestration rather than making a universal contribution to the trafficking of all exported proteins

ERP and four dimensions of absorptive capacity: lessons from a developing country

Enterprise resource planning systems can grant crucial strategic, operational and information-based benefits to adopting firms when implemented successfully. However, a failed implementation can often result in financial losses rather than profits. Until now, the research on the failures and successes were focused on implementations in large manufacturing and service organizations firms located in western countries, particularly in USA. Nevertheless, IT has gained intense diffusion to developing countries through declining hardware costs and increasing benefits that merits attention as much as developed countries. The aim of this study is to examine the implications of knowledge transfer in a developing country, Turkey, as a paradigm in the knowledge society with a focus on the implementation activities that foster successful installations. We suggest that absorptive capacity is an important characteristic of a firm that explains the success level of such a knowledge transfer.Publicad

Performance measurement : challenges for tomorrow

This paper demonstrates that the context within which performance measurement is used is changing. The key questions posed are: Is performance measurement ready for the emerging context? What are the gaps in our knowledge? and Which lines of enquiry do we need to pursue? A literature synthesis conducted by a team of multidisciplinary researchers charts the evolution of the performance-measurement literature and identifies that the literature largely follows the emerging business and global trends. The ensuing discussion introduces the currently emerging and predicted future trends and explores how current knowledge on performance measurement may deal with the emerging context. This results in identification of specific challenges for performance measurement within a holistic systems-based framework. The principle limitation of the paper is that it covers a broad literature base without in-depth analysis of a particular aspect of performance measurement. However, this weakness is also the strength of the paper. What is perhaps most significant is that there is a need for rethinking how we research the field of performance measurement by taking a holistic systems-based approach, recognizing the integrated and concurrent nature of challenges that the practitioners, and consequently the field, face

A Microchip CD4 Counting Method for HIV Monitoring in Resource-Poor Settings

BACKGROUND: More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. METHODS AND FINDINGS: Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. CONCLUSION: Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality

State of the Antarctic and Southern Ocean Climate System

This paper reviews developments in our understanding of the state of the Antarctic and Southern Ocean climate and its relation to the global climate system over the last few millennia. Climate over this and earlier periods has not been stable, as evidenced by the occurrence of abrupt changes in atmospheric circulation and temperature recorded in Antarctic ice core proxies for past climate. Two of the most prominent abrupt climate change events are characterized by intensification of the circumpolar westerlies (also known as the Southern Annular Mode) between ∼6000 and 5000 years ago and since 1200–1000 years ago. Following the last of these is a period of major trans-Antarctic reorganization of atmospheric circulation and temperature between A.D. 1700 and 1850. The two earlier Antarctic abrupt climate change events appear linked to but predate by several centuries even more abrupt climate change in the North Atlantic, and the end of the more recent event is coincident with reorganization of atmospheric circulation in the North Pacific. Improved understanding of such events and of the associations between abrupt climate change events recorded in both hemispheres is critical to predicting the impact and timing of future abrupt climate change events potentially forced by anthropogenic changes in greenhouse gases and aerosols. Special attention is given to the climate of the past 200 years, which was recorded by a network of recently available shallow firn cores, and to that of the past 50 years, which was monitored by the continuous instrumental record. Significant regional climate changes have taken place in the Antarctic during the past 50 years. Atmospheric temperatures have increased markedly over the Antarctic Peninsula, linked to nearby ocean warming and intensification of the circumpolar westerlies. Glaciers are retreating on the peninsula, in Patagonia, on the sub-Antarctic islands, and in West Antarctica adjacent to the peninsula. The penetration of marine air masses has become more pronounced over parts of West Antarctica. Above the surface, the Antarctic troposphere has warmed during winter while the stratosphere has cooled year-round. The upper kilometer of the circumpolar Southern Ocean has warmed, Antarctic Bottom Water across a wide sector off East Antarctica has freshened, and the densest bottom water in the Weddell Sea has warmed. In contrast to these regional climate changes, over most of Antarctica, near-surface temperature and snowfall have not increased significantly during at least the past 50 years, and proxy data suggest that the atmospheric circulation over the interior has remained in a similar state for at least the past 200 years. Furthermore, the total sea ice cover around Antarctica has exhibited no significant overall change since reliable satellite monitoring began in the late 1970s, despite large but compensating regional changes. The inhomogeneity of Antarctic climate in space and time implies that recent Antarctic climate changes are due on the one hand to a combination of strong multidecadal variability and anthropogenic effects and, as demonstrated by the paleoclimate record, on the other hand to multidecadal to millennial scale and longer natural variability forced through changes in orbital insolation, greenhouse gases, solar variability, ice dynamics, and aerosols. Model projections suggest that over the 21st century the Antarctic interior will warm by 3.4° ± 1°C, and sea ice extent will decrease by ∼30%. Ice sheet models are not yet adequate enough to answer pressing questions about the effect of projected warming on mass balance and sea level. Considering the potentially major impacts of a warming climate on Antarctica, vigorous efforts are needed to better understand all aspects of the highly coupled Antarctic climate system as well as its influence on the Earth\u27s climate and oceans