Detection of human influence on a new, validated 1500-Year temperature reconstruction

Climate records over the last millennium place the twentieth-century warming in a longer historical context. Reconstructions of millennial temperatures show a wide range of variability, raising questions about the reliability of currently available reconstruction techniques and the uniqueness of late-twentieth-century warming. A calibration method is suggested that avoids the loss of low-frequency variance. A new reconstruction using this method shows substantial variability over the last 1500 yr. This record is consistent with independent temperature change estimates from borehole geothermal records, compared over the same spatial and temporal domain. The record is also broadly consistent with other recent reconstructions that attempt to fully recover low-frequency climate variability in their central estimate. High variability in reconstructions does not hamper the detection of greenhouse gas-induced climate change, since a substantial fraction of the variance in these reconstructions from the beginning of the analysis in the late thirteenth century to the end of the records can be attributed to external forcing. Results from a detection and attribution analysis show that greenhouse warming is detectable in all analyzed high-variance reconstructions (with the possible exception of one ending in 1925), and that about a third of the warming in the first half of the twentieth century can be attributed to anthropogenic greenhouse gas emissions. The estimated magnitude of the anthropogenic signal is consistent with most of the warming in the second half of the twentieth century being anthropogenic

A methodology review on the incremental prognostic value of computed tomography biomarkers in addition to Framingham risk score in predicting cardiovascular disease: the use of association, discrimination and reclassification

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Computed tomography (CT) biomarkers claim to improve cardiovascular risk stratification. This review focuses on significant differences in incremental measures between adequate and inadequate reporting practise. METHODS: Studies included were those that used Framingham Risk Score as a baseline and described the incremental value of adding calcium score or CT coronary angiogram in predicting cardiovascular risk. Searches of MEDLINE, EMBASE, Web of Science and Cochrane Central were performed with no language restriction. RESULTS: Thirty five studies consisting of 206,663 patients (men = 118,114, 55.1%) were included. The baseline Framingham Risk Score included the 1998, 2002 and 2008 iterations. Selective reporting, inconsistent reference groupings and thresholds were found. Twelve studies (34.3%) had major and 23 (65.7%) had minor alterations and the respective Δ AUC were significantly different (p = 0.015). When the baseline model performed well, the Δ AUC was relatively lower with the addition of a CT biomarker (Spearman coefficient = − 0.46, p < 0.0001; n = 33; 76 pairs of data). Other factors that influenced AUC performance included exploration of data analysis, calibration, validation, multivariable and AUC documentation (all p < 0.05). Most studies (68.7%) that reported categorical NRI (n = 16; 46 pairs of data) subjectively drew strong conclusions along with other poor reporting practices. However, no significant difference in values of NRI was found between adequate and inadequate reporting. CONCLUSIONS: The widespread practice of poor reporting particularly association, discrimination, reclassification, calibration and validation undermines the claimed incremental value of CT biomarkers over the Framingham Risk Score alone. Inadequate reporting of discrimination inflates effect estimate, however, that is not necessarily the case for reclassification.This research was funded by the National Insitute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (NIHR CLAHRC South West Peninsula)

The acute management of trauma hemorrhage: a systematic review of randomized controlled trials.

PublishedResearch Support, Non-U.S. Gov'tReviewINTRODUCTION: Worldwide, trauma is a leading cause of death and disability. Haemorrhage is responsible for up to 40% of trauma deaths. Recent strategies to improve mortality rates have focused on optimal methods of early hemorrhage control and correction of coagulopathy. We undertook a systematic review of randomized controlled trials (RCT) which evaluated trauma patients with hemorrhagic shock within the first 24 hours of injury and appraised how the interventions affected three outcomes: bleeding and/or transfusion requirements; correction of trauma induced coagulopathy and mortality. METHODS: Comprehensive searches were performed of MEDLINE, EMBASE, CENTRAL (The Cochrane Library Issue 7, 2010), Current Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) and the National Health Service Blood and Transplant Systematic Review Initiative (NHSBT SRI) RCT Handsearch Database. RESULTS: A total of 35 RCTs were identified which evaluated a wide range of clinical interventions in trauma hemorrhage. Many of the included studies were of low methodological quality and participant numbers were small. Bleeding outcomes were reported in 32 studies; 7 reported significantly reduced transfusion use following a variety of clinical interventions, but this was not accompanied by improved survival. Minimal information was found on traumatic coagulopathy across the identified RCTs. Overall survival was improved in only three RCTs: two small studies and a large study evaluating the use of tranexamic acid. CONCLUSIONS: Despite 35 RCTs there has been little improvement in outcomes over the last few decades. No clear correlation has been demonstrated between transfusion requirements and mortality. The global trauma community should consider a coordinated and strategic approach to conduct well designed studies with pragmatic endpoints.This research project was funded by the National Institute for Health Research Programme Grant for Applied Research (RP-PG-0407-10036)

Diabetes in pregnancy and infant adiposity: systematic review and meta-analysis

Objective: Maternal glycaemia and anthropometry-derived newborn adiposity are strongly correlated. The children of mothers with diabetes are at greater risk of adverse metabolic health, and increased adiposity is a plausible mediator. We undertook a systematic review and meta-analysis to compare adiposity in infants of mothers with (IDM) and without diabetes (NIDM). Design: We identified observational studies reporting adiposity in IDM and NIDM. We searched references, traced forward citations and contacted authors for additional data. We considered all body composition techniques and compared fat mass, fat-free mass, body fat % and skinfold thickness. We used random effects meta-analyses and performed subgroup analyses by maternal diabetes type (type 1, type 2, gestational) and infant sex. We examined the influence of pre-pregnancy BMI and conducted sensitivity analyses. Results: We included data from 35 papers and over 24,000 infants. IDM have greater fat mass than NIDM (mean difference [95% CI]); 83g [49, 117]. Fat mass is greater in infants of mothers with gestational diabetes; 62g [29, 94] and type 1 diabetes; 268g [139, 397]. Insufficient studies reported data for type 2 diabetes separately. Compared with NIDM, fat mass was greater in IDM boys; 87g [30, 145], but not significantly different in IDM girls; 42g [- 33, 116]. There was no attenuation after adjustment for maternal BMI. Conclusions: IDM have significantly greater adiposity in comparison to NIDM. These findings are justification for studies to determine whether measures to reduce infant adiposity will improve later health

Generalized parton distributions and rapidity gap survival in exclusive diffractive pp scattering

We propose a new approach to the problem of rapidity gap survival (RGS) in the production of high-mass systems (H = dijet, heavy quarkonium, Higgs boson) in double-gap exclusive diffractive pp scattering, pp -> p + (gap) + H + (gap) + p. It is based on the idea that hard and soft interactions proceed over widely different time- and distance scales and are thus approximately independent. The high-mass system is produced in a hard scattering process with exchange of two gluons between the protons. Its amplitude is calculable in terms of the gluon generalized parton distributions (GPDs) in the protons, which can be measured in J/psi production in exclusive ep scattering. The hard scattering process is modified by soft spectator interactions, which we calculate in a model-independent way in terms of the pp elastic scattering amplitude. Contributions from inelastic intermediate states are suppressed. A simple geometric picture of the interplay of hard and soft interactions in diffraction is obtained. The onset of the black-disk limit in pp scattering at TeV energies strongly suppresses diffraction at small impact parameters and is the main factor in determining the RGS probability. Correlations between hard and soft interactions (e.g. due to scattering from the long-range pion field of the proton, or due to possible short-range transverse correlations between partons) further decrease the RGS probability. We also investigate the dependence of the diffractive cross section on the transverse momenta of the final-state protons ("diffraction pattern"). By measuring this dependence one can perform detailed tests of the interplay of hard and soft interactions, and even extract information about the gluon GPD in the proton. Such studies appear to be feasible with the planned forward detectors at the LHC.Comment: 26 pages, 17 figures, uses revtex

Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma‑induced coagulopathy in adult trauma patients with bleeding

This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2015, Issue 2. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.Trauma-induced coagulopathy (TIC) is a disorder of the blood clotting process that occurs soon after trauma injury. A diagnosis of TIC on admission is associated with increased mortality rates, increased burdens of transfusion, greater risks of complications and longer stays in critical care. Current diagnostic testing follows local hospital processes and normally involves conventional coagulation tests including prothrombin time ratio/international normalized ratio (PTr/INR), activated partial prothrombin time and full blood count. In some centres, thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are standard tests, but in the UK they are more commonly used in research settings

A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer.

This is the final version of the review. Available from NIHR via the DOI in this record.BACKGROUND: In breast cancer patients, sentinel lymph node biopsy is carried out at the same time as the removal of the primary tumour to postoperatively test with histopathology for regional metastases in the sentinel lymph node. Those patients with positive test results are then operated on 2-4 weeks after primary surgery to remove the lymph nodes from the axilla (axillary lymph node dissection, ALND). New molecular tests RD-100i [one-step nucleic acid amplification (OSNA); based on messenger RNA amplification to identify the cytokeratin-19 (CK19) gene marker] (Sysmex, Norderstedt, Germany) and Metasin (using the CK19 and mammaglobin gene markers) (Cellular Pathology, Princess Alexandra Hospital NHS Trust, Harlow, UK) are intended to provide an intraoperative diagnosis, thereby avoiding the need for postoperative histopathology and, in positive cases, a second operation for ALND. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of using OSNA and Metasin in the NHS in England for the intraoperative diagnosis of sentinel lymph nodes metastases, compared with postoperative histopathology, the current standard. DATA SOURCES: Electronic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library and the Health Economic Evaluations Database as well as clinical trial registries, grey literature and conference proceedings were searched up to July 2012. REVIEW METHODS: A systematic review of the evidence was carried out using standard methods. Single-gate studies were used to estimate the accuracy of OSNA with histopathology as the reference standard. The cost-effectiveness analysis adapted an existing simulation model of the long-term costs and health implications of early breast cancer diagnostic outcomes. The model accounted for the costs of an extended first operation with intraoperative testing, the loss of health-related quality of life (disutility) from waiting for postoperative test results, disutility and costs of a second operation, and long-term costs and disutility from lymphoedema related to ALND, adjuvant therapy, locoregional recurrence and metastatic recurrence. RESULTS: A total of 724 references were identified in the searches, of which 17 studies assessing test accuracy were included in the review, 15 on OSNA and two on Metasin. Both Metasin studies were unpublished. OSNA sensitivity of 84.5% [95% confidence interval (CI) 74.7% to 91.0%] and specificity of 91.8% (95% CI 87.8% to 94.6%) for patient nodal status were estimated in a meta-analysis of five studies [unadjusted for tissue allocation bias (TAB)]. At these values and a 20% node-positive rate, OSNA resulted in lifetime discounted cost-savings of £498 and a quality-adjusted life-year (QALY) loss of 0.048 relative to histopathology, that is, £4324 saved per QALY lost. The most favourable plausible scenario for OSNA in terms of the node-positive rate (range 10-40%), diagnostic accuracy values (91.3% sensitivity and 94.2% specificity, from three reports that adjusted for TAB), the costs of histopathology, OSNA and second surgery, and long-term costs and utilities resulted in a maximum saving per QALY lost of £10,500; OSNA sensitivity and specificity would need to be ≥ 95% for this figure to be ≥ £20,000. LIMITATIONS: There is limited evidence on the diagnostic test accuracy of intraoperative tests. The quality of information on costs of resource utilisation during the diagnostic pathway is low and no evidence exists on the disutility of waiting for a second surgery. No comparative studies exist that report clinical outcomes of intraoperative diagnostic tests. These knowledge gaps have more influence on the decision than current uncertainty in the performance of postoperative histopathology in standard practice. CONCLUSIONS: One-step nucleic acid amplification is not cost-effective for the intraoperative diagnosis of sentinel lymph node metastases. OSNA is less accurate than histopathology and the consequent loss of health benefits in this patient group is not compensated for by health gains elsewhere in the health system that may be obtained with the cost-savings made. The evidence on Metasin is insufficient to evaluate its cost-effectiveness. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002889. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Maternal nicotine dependence is associated with longitudinal increases in child obesogenic eating behaviors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152014/1/ijpo12541.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152014/2/ijpo12541_am.pd

Investigation of shock waves in explosive blasts using fibre optic pressure sensors

The published version of this article may be accessed at the link below. Copyright @ IOP Publishing, 2006.We describe miniature all-optical pressure sensors, fabricated by wafer etching techniques, less than 1 mm(2) in overall cross-section with rise times in the mu s regime and pressure ranges typically 900 kPa (9 bar). Their performance is suitable for experimental studies of the pressure-time history for test models exposed to shocks initiated by an explosive charge. The small size and fast response of the sensors promises higher quality data than has been previously available from conventional electrical sensors, with potential improvements to numerical models of blast effects. Results from blast tests are presented in which up to six sensors were multiplexed, embedded within test models in a range of orientations relative to the shock front.Support from the UK Engineering&Physical Sciences Research Council and Dstl Fort Halstead through the MoD Joint Grants Scheme are acknowledged. WN MacPherson is supported by an EPSRC Advanced Research Fellowship