Validation of T2* in-line analysis for tissue iron quantification at 1.5 T.

BACKGROUND: There is a need for improved worldwide access to tissue iron quantification using T2* cardiovascular magnetic resonance (CMR). One route to facilitate this would be simple in-line T2* analysis widely available on MR scanners. We therefore compared our clinically validated and established T2* method at Royal Brompton Hospital (RBH T2*) against a novel work-in-progress (WIP) sequence with in-line T2* measurement from Siemens (WIP T2*). METHODS: Healthy volunteers (n = 22) and patients with iron overload (n = 78) were recruited (53 males, median age 34 years). A 1.5 T study (Magnetom Avanto, Siemens) was performed on all subjects. The same mid-ventricular short axis cardiac slice and transaxial slice through the liver were used to acquire both RBH T2* images and WIP T2* maps for each participant. Cardiac white blood (WB) and black blood (BB) sequences were acquired. Intraobserver, interobserver and interstudy reproducibility were measured on the same data from a subset of 20 participants. RESULTS: Liver T2* values ranged from 0.8 to 35.7 ms (median 5.1 ms) and cardiac T2* values from 6.0 to 52.3 ms (median 31 ms). The coefficient of variance (CoV) values for direct comparison of T2* values by RBH and WIP were 6.1-7.8 % across techniques. Accurate delineation of the septum was difficult on some WIP T2* maps due to artefacts. The inability to manually correct for noise by truncation of erroneous later echo times led to some overestimation of T2* using WIP T2* compared with the RBH T2*. Reproducibility CoV results for RBH T2* ranged from 1.5 to 5.7 % which were better than the reproducibility of WIP T2* values of 4.1-16.6 %. CONCLUSIONS: Iron estimation using the T2* CMR sequence in combination with Siemens' in-line data processing is generally satisfactory and may help facilitate global access to tissue iron assessment. The current automated T2* map technique is less good for tissue iron assessment with noisy data at low T2* values

The Affective Impact of Financial Skewness on Neural Activity and Choice

Few finance theories consider the influence of “skewness” (or large and asymmetric but unlikely outcomes) on financial choice. We investigated the impact of skewed gambles on subjects' neural activity, self-reported affective responses, and subsequent preferences using functional magnetic resonance imaging (FMRI). Neurally, skewed gambles elicited more anterior insula activation than symmetric gambles equated for expected value and variance, and positively skewed gambles also specifically elicited more nucleus accumbens (NAcc) activation than negatively skewed gambles. Affectively, positively skewed gambles elicited more positive arousal and negatively skewed gambles elicited more negative arousal than symmetric gambles equated for expected value and variance. Subjects also preferred positively skewed gambles more, but negatively skewed gambles less than symmetric gambles of equal expected value. Individual differences in both NAcc activity and positive arousal predicted preferences for positively skewed gambles. These findings support an anticipatory affect account in which statistical properties of gambles—including skewness—can influence neural activity, affective responses, and ultimately, choice

Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity

Towards comprehensive assessment of mitral regurgitation using cardiovascular magnetic resonance

Cardiovascular magnetic resonance (CMR) is increasingly used to assess patients with mitral regurgitation. Its advantages include quantitative determination of ventricular volumes and function and the mitral regurgitant fraction, and in ischemic mitral regurgitation, regional myocardial function and viability. In addition to these, identification of leaflet prolapse or restriction is necessary when valve repair is contemplated. We describe a systematic approach to the evaluation of mitral regurgitation using CMR which we have used in 149 patients with varying etiologies and severity of regurgitation over a 15 month period

Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer

BACKGROUND: Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection. METHODS: Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method. RESULTS: Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration. CONCLUSION: Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed

Sensitivity and Bias in Decision-Making under Risk: Evaluating the Perception of Reward, Its Probability and Value

BACKGROUND: There are few clinical tools that assess decision-making under risk. Tests that characterize sensitivity and bias in decisions between prospects varying in magnitude and probability of gain may provide insights in conditions with anomalous reward-related behaviour. OBJECTIVE: We designed a simple test of how subjects integrate information about the magnitude and the probability of reward, which can determine discriminative thresholds and choice bias in decisions under risk. DESIGN/METHODS: Twenty subjects were required to choose between two explicitly described prospects, one with higher probability but lower magnitude of reward than the other, with the difference in expected value between the two prospects varying from 3 to 23%. RESULTS: Subjects showed a mean threshold sensitivity of 43% difference in expected value. Regarding choice bias, there was a 'risk premium' of 38%, indicating a tendency to choose higher probability over higher reward. An analysis using prospect theory showed that this risk premium is the predicted outcome of hypothesized non-linearities in the subjective perception of reward value and probability. CONCLUSIONS: This simple test provides a robust measure of discriminative value thresholds and biases in decisions under risk. Prospect theory can also make predictions about decisions when subjective perception of reward or probability is anomalous, as may occur in populations with dopaminergic or striatal dysfunction, such as Parkinson's disease and schizophrenia

Higher risk of gastrointestinal parasite infection at lower elevation suggests possible constraints in the distributional niche of Alpine marmots

Alpine marmots Marmota marmota occupy a narrow altitudinal niche within high elevation alpine environments. For animals living at such high elevations where resources are limited, parasitism represents a potential major cost in life history. Using occupancy models, we tested if marmots living at higher elevation have a reduced risk of being infected with gastrointestinal helminths, possibly compensating the lower availability of resources (shorter feeding season, longer snow cover and lower temperature) than marmots inhabiting lower elevations. Detection probability of eggs and oncospheres of two gastro-intestinal helminthic parasites, Ascaris laevis and Ctenotaenia marmotae, sampled in marmot feces, was used as a proxy of parasite abundance. As predicted, the models showed a negative relationship between elevation and parasite detectability (i.e. abundance) for both species, while there appeared to be a negative effect of solar radiance only for C. marmotae. Site-occupancy models are used here for the first time to model the constrains of gastrointestinal parasitism on a wild species and the relationship existing between endoparasites and environmental factors in a population of free-living animals. The results of this study suggest the future use of site-occupancy models as a viable tool to account for parasite imperfect detection in ecoparasitological studies, and give useful insights to further investigate the hypothesis of the contribution of parasite infection in constraining the altitudinal niche of Alpine marmots

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013