Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.
Contributors: Cnossen, Maryse C, Polinder, Suzanne, Lingsma, Hester F, Maas, Andrew IR, Menon, David Krishna, Steyerberg, Ewout W, CENTER-TBI Investigators and Participants,
... Introduction The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Methods We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. Results All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. Conclusion Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches.
Contributors: Farrell, Ruaidhri, Mair, Robert James, Sciotti, Alessandra, Pigorini, Andrea
... Understanding how buildings respond to tunnelling-induced ground movements is an area of great importance for urban tunnelling projects, particularly for risk management. In this paper, observations of building response to tunnelling, from both centrifuge modelling and a field study in Bologna, are used to identify mechanisms governing the soil–structure interaction. Centrifuge modelling was carried out on an 8-m-diameter beam centrifuge at Cambridge University, with buildings being modelled as highly simplified elastic and inelastic beams of varying stiffness and geometry. The Bologna case study presents the response of two different buildings to the construction of a sprayed concrete lining (SCL) tunnel, 12 m in diameter, with jet grouting and face reinforcement. In both studies, a comparison of the building settlement and horizontal displacement profiles, with the greenfield ground movements, enables the soil structure interaction to be quantified. Encouraging agreement between the modification to the greenfield settlement profile, displayed by the buildings, and estimates made from existing predictive tools is observed. Similarly, both studies indicate that the horizontal strains, induced in the buildings, are typically at least an order of magnitude smaller than the greenfield values. This is consistent with observations in the literature. The potential modification to the settlement distortions is shown to have significant implications on the estimated level of damage. Potential issues for infrastructures connected to buildings, arising from the embedment of rigid buildings into the soil, are also highlighted.
Dissociable Effects of Subthalamic Stimulation in Obsessive Compulsive Disorder on Risky Reward and Loss Prospects.
Contributors: Voon, Valerie, Droux, Fabien, Chabardes, Stephan, Bougerol, Thierry, Kohl, Sina, David, Olivier, Krack, Paul, Polosan, Mircea
... Our daily decisions involve an element of risk, a behavioural process that is potentially modifiable. Here we assess the role of the associative-limbic subthalamic nucleus in obsessive compulsive disorder (OCD) testing on and off deep brain stimulation (DBS) on anticipatory risk taking to obtain rewards and avoid losses. We assessed 12 OCD STN DBS in a randomized double-blind within-subject cross-over design. STN DBS decreased risk taking to rewards (p=0.02) and greater risk taking to rewards was positively correlated with OCD severity (p=0.01) and disease duration (p=0.01). STN DBS was also associated with impaired subjective discrimination of loss magnitude (p<0.05), an effect mediated by acute DBS rather than chronic DBS. We highlight a role for the STN in mediating dissociable valence prospects on risk seeking. STN stimulation decreases risk taking to rewards and impairs discrimination of loss magnitude. These findings may have implications for behavioural symptoms related to STN DBS and the potential for STN DBS for the treatment of psychiatric disorders.
Contributors: Challinor, Anthony David, Allison, R, Carron, J, Errard, J, Feeney, S, Kitching, T, Lesgourgues, J, Lewis, A, Zubeldia, I, Achucarro, A
Contributors: Cope, Andrew P, Barnes, Michael R, Belson, Alexandra, Binks, Michael, Brockbank, Sarah, Bonachela-Capdevila, Francisco, Carini, Claudio, Fisher, Benjamin A, Goodyear, Carl S, Emery, Paul
... Collaboration can be challenging; nevertheless, the emerging successes of large, multi-partner, multi-national cooperatives and research networks in the biomedical sector have sustained the appetite of academics and industry partners for developing and fostering new research consortia. This model has percolated down to national funding agencies across the globe, leading to funding for projects that aim to realise the true potential of genomic medicine in the 21st century and to reap the rewards of 'big data'. In this Perspectives article, the experiences of the RA-MAP consortium, a group of more than 140 individuals affiliated with 21 academic and industry organizations that are focused on making genomic medicine in rheumatoid arthritis a reality are described. The challenges of multi-partner collaboration in the UK are highlighted and wide-ranging solutions are offered that might benefit large research consortia around the world.
TCBH Duncan Tanner Essay Prize Winner 2017 The ‘Progress of a Slogan’: Youth, Culture, and the Shaping of Everyday Political Languages in Late 1940s Britain
Contributors: Cowan, David
... In 1948, worried that young people would take full employment and the welfare state for granted, the Labour Party trialled a new slogan: ‘Ask your Dad’. This slogan encouraged the young to learn about the hardships which their parents had experienced in the inter-war years, largely under Conservative governments. Using archived interviews and letters sent to the press, this article provides the first study of the popular reception of this slogan. Most people had not heard of this slogan, and most of those who had heard of the phrase showed no knowledge that it was associated with politics, turning instead to popular culture. Those who understood the slogan were not the passive conduits of their party’s message; often, they reworked political ideas to fit their own memories. Because repeating slogans was associated with a lack of political independence, not listening to party politics could conceal an intense interest in creating political change—an attitude which was, apparently, pronounced amongst the young. This article uses these responses to suggest how political language was as much produced by ordinary people’s memories and daily discussion, as it was something drawn from professional campaigners.
Contributors: Becker, Jonas N, Pingault, Benjamin Jean-Pierre, Groß, David, Gündoğan, Mustafa, Kukharchyk, Nadezhda, Markham, Matthew, Edmonds, Andrew, Atatüre, Mete, Bushev, Pavel, Becher, Christoph
... The silicon-vacancy center in diamond offers attractive opportunities in quantum photonics due to its favorable optical properties and optically addressable electronic spin. Here, we combine both to achieve all-optical coherent control of its spin states. We utilize this method to explore spin dephasing effects in an impurity-rich sample beyond the limit of phonon-induced decoherence: Employing Ramsey and Hahn-echo techniques at temperatures down to 40 mK we identify resonant coupling to a substitutional nitrogen spin bath as limiting decoherence source for the electron spin.
Data supporting "Analysis of 13C and 14C labeling in pyruvate and lactate in tumor and blood of lymphoma-bearing mice injected with 13C- and 14C-labeled pyruvate"
Contributors: Pereira Mendes Serrao, Eva Carolina
... Measurements of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool can give an apparent first order rate constant for the exchange. Determination of isotope flux, however, requires an estimate of the labeled pyruvate concentration in the tumor. This was achieved here by measuring tumor uptake of [1-14C]pyruvate, which showed that <2% of the injected pyruvate reached the tumor site. Multiplication of this estimated labeled pyruvate concentration in the tumor with the apparent first order rate constant for hyperpolarized 13C label exchange gave an isotope flux that showed good agreement with a flux determined directly by injecting non polarized [3-13C]pyruvate and then rapidly excising the tumor after 30 s and measuring 13C-labeled lactate concentrations in tumor extracts. The distribution of labeled lactate between intra- and extracellular compartments and the blood pool was investigated by imaging, by measuring labeled lactate concentration in blood and tumor, and by examining the effects of a gadolinium contrast agent and a lactate transport inhibitor on the intensity of the hyperpolarized [1-13C]lactate signal. These measurements showed that there was significant export of labeled lactate from the tumor but that labeled lactate in the blood pool produced by injection of hyperpolarized [1-13C]pyruvate has only relatively low levels of polarization. This study has shown that measurements of hyperpolarized 13C label exchange between pyruvate and lactate in a murine tumor model can provide an estimate of the true isotope flux if the concentration of labeled pyruvate that reaches the tumor can be determined.
Contributors: Cowburn, Andrew Stephen, Takeda, Norihiko, Boutin, Adam T, Kim, Jung-Whan, Sterling, Jane Carolyn, Nakasaki, Manando, Southwood, Mark, Goldrath, Ananda W, Jamora, Colin, Nizet, Victor
... Vascular flow through tissues is regulated via a number of homeostatic mechanisms. Localized control of tissue blood flow, or autoregulation, is a key factor in regulating tissue perfusion and oxygenation. We show here that the net balance between two hypoxia-inducible factor (HIF) transcription factor isoforms, HIF-1α and HIF-2α, is an essential mechanism regulating both local and systemic blood flow in the skin of mice. We also show that balance of HIF isoforms in keratinocyte-specific mutant mice affects thermal adaptation, exercise capacity, and systemic arterial pressure. The two primary HIF isoforms achieve these effects in opposing ways that are associated with HIF isoform regulation of nitric oxide production. We also show that a correlation exists between altered levels of HIF isoforms in the skin and the degree of idiopathic hypertension in human subjects. Thus, the balance between HIF-1α and HIF-2α expression in keratinocytes is a control element of both tissue perfusion and systemic arterial pressure, with potential implications in human hypertension.
Time trends in service provision and survival outcomes for patients with renal cancer treated by nephrectomy in England 2000-2010.
Contributors: Hsu, Ray Chin, Barclay, Matthew, Loughran, Molly A, Lyratzopoulos, Georgios, Gnanapragasam, Vincent Jeyaseelan, Armitage, James N
... OBJECTIVE To describe the temporal trends in nephrectomy practice and outcomes for English renal cell carcinoma (RCC) patients. PATIENTS & METHODS Adult RCC nephrectomy patients treated between 2000 and 2010 were identified in the National Cancer Data Repository (NCDR) and Hospital Episode Statistics (HES) and followed up for death through 2015 (n=30,763). We estimated the annual frequency for each nephrectomy type, the hospital and surgeon numbers and their case volumes. We analysed short-term surgical outcomes, as well as 1 and 5-year relative survivals. RESULTS Annual RCC nephrectomy number increased by 66% during the study period. Hospital number decreased by 24% while the median annual hospital volume increased from 10 to 23 (p<0.01). Surgeon number increased by 27% (p<0.01), doubling the median consultant number per hospital. Proportion of minimally-invasive nephrectomy rose from 1% to 46%, while the proportion of nephron-sparing surgery increased from 5% to 16%, with 29% of all T1 disease treated with partial nephrectomy in 2010 (p<0.01). 30-day mortality halved from 2.4% to 1.1% and 90-day mortality decreased from 4.9% to 2.6% (p<0.01). 1-year relative survival increased from 86.9% to 93.4% while 5-year relative survival rose from 68.2% to 81.2% (p<0.01). Improvements were most notable in patients 65 years and over and those with T3 and T4 disease. CONCLUSIONS Surgical RCC management has changed considerably with nephrectomy centralisation and increased nephron-sparing and minimally-invasive surgeries. In parallel, we observed significant improvements in short-term and long-term survival particularly for elderly patients and those with locally advanced disease.