Association between major surgical admissions and the cognitive trajectory: 19 year follow-up of Whitehall II cohort study

Objective: To quantify the association between major surgery and the age related cognitive trajectory. / Design: Prospective longitudinal cohort study. / Setting: United Kingdom. / Participants: 7532 adults with as many as five cognitive assessments between 1997 and 2016 in the Whitehall II study, with linkage to hospital episode statistics. Exposures of interest included any major hospital admission, defined as requiring more than one overnight stay during follow-up. / Main outcomes measures: The primary outcome was the global cognitive score established from a battery of cognitive tests encompassing reasoning, memory, and phonemic and semantic fluency. Bayesian linear mixed effects models were used to calculate the change in the age related cognitive trajectory after hospital admission. The odds of substantial cognitive decline induced by surgery defined as more than 1.96 standard deviations from a predicted trajectory (based on the first three cognitive waves of data) was also calculated. / Results: After accounting for the age related cognitive trajectory, major surgery was associated with a small additional cognitive decline, equivalent on average to less than five months of aging (95% credible interval 0.01 to 0.73 years). In comparison, admissions for medical conditions and stroke were associated with 1.4 (1.0 to 1.8) and 13 (9.6 to 16) years of aging, respectively. Substantial cognitive decline occurred in 2.5% of participants with no admissions, 5.5% of surgical admissions, and 12.7% of medical admissions. Compared with participants with no major hospital admissions, those with surgical or medical events were more likely to have substantial decline from their predicted trajectory (surgical admissions odds ratio 2.3, 95% credible interval 1.4 to 3.9; medical admissions 6.2, 3.4 to 11.0). / Conclusions: Major surgery is associated with a small, long term change in the average cognitive trajectory that is less profound than for major medical admissions. The odds of substantial cognitive decline after surgery was about doubled, though lower than for medical admissions. During informed consent, this information should be weighed against the potential health benefits of surgery

Association between major surgical admissions and the cognitive trajectory: 19 year follow-up of Whitehall II cohort study

OBJECTIVE: To quantify the association between major surgery and the age related cognitive trajectory. // DESIGN: Prospective longitudinal cohort study. // SETTING: United Kingdom. // PARTICIPANTS: 7532 adults with as many as five cognitive assessments between 1997 and 2016 in the Whitehall II study, with linkage to hospital episode statistics. Exposures of interest included any major hospital admission, defined as requiring more than one overnight stay during follow-up. // MAIN OUTCOMES MEASURES: The primary outcome was the global cognitive score established from a battery of cognitive tests encompassing reasoning, memory, and phonemic and semantic fluency. Bayesian linear mixed effects models were used to calculate the change in the age related cognitive trajectory after hospital admission. The odds of substantial cognitive decline induced by surgery defined as more than 1.96 standard deviations from a predicted trajectory (based on the first three cognitive waves of data) was also calculated. // RESULTS: After accounting for the age related cognitive trajectory, major surgery was associated with a small additional cognitive decline, equivalent on average to less than five months of aging (95% credible interval 0.01 to 0.73 years). In comparison, admissions for medical conditions and stroke were associated with 1.4 (1.0 to 1.8) and 13 (9.6 to 16) years of aging, respectively. Substantial cognitive decline occurred in 2.5% of participants with no admissions, 5.5% of surgical admissions, and 12.7% of medical admissions. Compared with participants with no major hospital admissions, those with surgical or medical events were more likely to have substantial decline from their predicted trajectory (surgical admissions odds ratio 2.3, 95% credible interval 1.4 to 3.9; medical admissions 6.2, 3.4 to 11.0). // CONCLUSIONS: Major surgery is associated with a small, long term change in the average cognitive trajectory that is less profound than for major medical admissions. The odds of substantial cognitive decline after surgery was about doubled, though lower than for medical admissions. During informed consent, this information should be weighed against the potential health benefits of surgery

First estimation of the diffusive methane flux and concentrations from Lake Winnipeg, a large, shallow and eutrophic lake

Freshwater lakes are increasingly recognized as significant sources of atmospheric methane (CH4), potentially offsetting the terrestrial carbon sink. We present the first study of dissolved CH4 distributions and lake-air flux from Lake Winnipeg, based on two-years of observations collected during all seasons. Methane concentrations across two years had a median of value of 24.6 nmol L-1 (mean: 41.6 ± 68.2 nmol L-1) and ranged between 5.0 and 733.8 nmol L-1, with a 2018 annual median of 24.4 nmol L-1 (mean: 46.8 ± 99.3 nmol L-1) and 25.1 nmol L-1 (mean: 38.8 ± 45.2 nmol L-1) in 2019. The median lake-air flux was 1.1 µmol m−2 h−1 (range: 0.46–70.1 µmol m−2h−1, mean: 2.9 ± 10.2 µmol m−2 h−1) in 2018, and 5.5 µmol m−2h−1 (range: 0.0–78.4 µmol m−2 h−1, mean: 2.7 ± 8.5 µmol m−2 h−1) in 2019, for a total diffusive emission of 0.001 Tg of CH4-C yr−1. We found evidence of consistent spatial variability, with higher concentrations near river inflows. Significant seasonal trends in CH4 concentrations were not observed, though fluxes were highest during the fall season due to strong winds. Our findings suggest Lake Winnipeg is a CH4 source of similar mean magnitude to Lake Erie, with lower concentrations and fluxes per unit area than smaller mid- to high-latitude lakes. Additional work is needed to understand the factors underlying observed spatial variability in dissolved gas concentration, including estimations of production and consumption rates in the water column and sediments

A Human Development Framework for CO2 Reductions

Although developing countries are called to participate in CO2 emission reduction efforts to avoid dangerous climate change, the implications of proposed reduction schemes in human development standards of developing countries remain a matter of debate. We show the existence of a positive and time-dependent correlation between the Human Development Index (HDI) and per capita CO2 emissions from fossil fuel combustion. Employing this empirical relation, extrapolating the HDI, and using three population scenarios, the cumulative CO2 emissions necessary for developing countries to achieve particular HDI thresholds are assessed following a Development As Usual approach (DAU). If current demographic and development trends are maintained, we estimate that by 2050 around 85% of the world's population will live in countries with high HDI (above 0.8). In particular, 300Gt of cumulative CO2 emissions between 2000 and 2050 are estimated to be necessary for the development of 104 developing countries in the year 2000. This value represents between 20% to 30% of previously calculated CO2 budgets limiting global warming to 2{\deg}C. These constraints and results are incorporated into a CO2 reduction framework involving four domains of climate action for individual countries. The framework reserves a fair emission path for developing countries to proceed with their development by indexing country-dependent reduction rates proportional to the HDI in order to preserve the 2{\deg}C target after a particular development threshold is reached. Under this approach, global cumulative emissions by 2050 are estimated to range from 850 up to 1100Gt of CO2. These values are within the uncertainty range of emissions to limit global temperatures to 2{\deg}C.Comment: 14 pages, 7 figures, 1 tabl

Random Numbers Certified by Bell's Theorem

Randomness is a fundamental feature in nature and a valuable resource for applications ranging from cryptography and gambling to numerical simulation of physical and biological systems. Random numbers, however, are difficult to characterize mathematically, and their generation must rely on an unpredictable physical process. Inaccuracies in the theoretical modelling of such processes or failures of the devices, possibly due to adversarial attacks, limit the reliability of random number generators in ways that are difficult to control and detect. Here, inspired by earlier work on nonlocality based and device independent quantum information processing, we show that the nonlocal correlations of entangled quantum particles can be used to certify the presence of genuine randomness. It is thereby possible to design of a new type of cryptographically secure random number generator which does not require any assumption on the internal working of the devices. This strong form of randomness generation is impossible classically and possible in quantum systems only if certified by a Bell inequality violation. We carry out a proof-of-concept demonstration of this proposal in a system of two entangled atoms separated by approximately 1 meter. The observed Bell inequality violation, featuring near-perfect detection efficiency, guarantees that 42 new random numbers are generated with 99% confidence. Our results lay the groundwork for future device-independent quantum information experiments and for addressing fundamental issues raised by the intrinsic randomness of quantum theory.Comment: 10 pages, 3 figures, 16 page appendix. Version as close as possible to the published version following the terms of the journa

Niche as a determinant of word fate in online groups

Patterns of word use both reflect and influence a myriad of human activities and interactions. Like other entities that are reproduced and evolve, words rise or decline depending upon a complex interplay between {their intrinsic properties and the environments in which they function}. Using Internet discussion communities as model systems, we define the concept of a word niche as the relationship between the word and the characteristic features of the environments in which it is used. We develop a method to quantify two important aspects of the size of the word niche: the range of individuals using the word and the range of topics it is used to discuss. Controlling for word frequency, we show that these aspects of the word niche are strong determinants of changes in word frequency. Previous studies have already indicated that word frequency itself is a correlate of word success at historical time scales. Our analysis of changes in word frequencies over time reveals that the relative sizes of word niches are far more important than word frequencies in the dynamics of the entire vocabulary at shorter time scales, as the language adapts to new concepts and social groupings. We also distinguish endogenous versus exogenous factors as additional contributors to the fates of words, and demonstrate the force of this distinction in the rise of novel words. Our results indicate that short-term nonstationarity in word statistics is strongly driven by individual proclivities, including inclinations to provide novel information and to project a distinctive social identity.Comment: Supporting Information is available here: http://www.plosone.org/article/fetchSingleRepresentation.action?uri=info:doi/10.1371/journal.pone.0019009.s00

Predicting active site residue annotations in the Pfam database

<p>Abstract</p> <p>Background</p> <p>Approximately 5% of Pfam families are enzymatic, but only a small fraction of the sequences within these families (<0.5%) have had the residues responsible for catalysis determined. To increase the active site annotations in the Pfam database, we have developed a strict set of rules, chosen to reduce the rate of false positives, which enable the transfer of experimentally determined active site residue data to other sequences within the same Pfam family.</p> <p>Description</p> <p>We have created a large database of predicted active site residues. On comparing our active site predictions to those found in UniProtKB, Catalytic Site Atlas, PROSITE and <it>MEROPS </it>we find that we make many novel predictions. On investigating the small subset of predictions made by these databases that are not predicted by us, we found these sequences did not meet our strict criteria for prediction. We assessed the sensitivity and specificity of our methodology and estimate that only 3% of our predicted sequences are false positives.</p> <p>Conclusion</p> <p>We have predicted 606110 active site residues, of which 94% are not found in UniProtKB, and have increased the active site annotations in Pfam by more than 200 fold. Although implemented for Pfam, the tool we have developed for transferring the data can be applied to any alignment with associated experimental active site data and is available for download. Our active site predictions are re-calculated at each Pfam release to ensure they are comprehensive and up to date. They provide one of the largest available databases of active site annotation.</p

Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

<div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div

Continuing medical education in Turkey: Recent developments

BACKGROUND: The Turkish Association of Medicine founded a Continuing Medical Education Accreditation Committee in 1993 to evaluate and accredit scientific meetings and publications. The aims of this project were to raise the standards of meetings and to introduce compulsory revalidation and re-certification for physicians in Turkey. DISCUSSION: Since the year 1994, 2348 applications to the Continuing Medical Education board have been made (mostly for scientific meetings), and 95% of these applications have been accepted. Physicians received 139.014 credits during this time. This number is increasing every year. Meeting organisers' demand for such a kind of evaluation is increasing, because participants increasingly request it. SUMMARY: Efforts for revalidation and re-certification of physicians have not been completely successful yet. In the near future the Co-ordination Council of Medical Speciality Societies is going to oblige member associations to establish speciality boards. This will be the first step to the conventional use of Continuing Medical Education credits in occupational evaluation. Time-limited re-certification of physicians is the principal goal of Turkish Medical Association. Efforts to implement this change in legislation are being made