Effects of lithium isotopes on sodium/lithium co-transport and calcium efflux through the sodium/calcium/lithium exchanger in mitochondria.

The effects of lithium (Li) isotopes and their impact on biological processes have recently gained increased attention due to the significance of Li as a pharmacological agent and the potential that Li isotopic effects in neuroscience contexts may constitute a new example of quantum effects in biology. Previous studies have shown that the two Li isotopes, which differ in mass and nuclear spin, have unusual different effects in vivo and in vitro and, although some molecular targets for Li isotope fractionation have been proposed, it is not known whether those result in observable downstream neurophysiological effects. In this work we studied fluxes of Li+, sodium (Na+) and calcium (Ca2+) ions in the mitochondrial sodium/calcium/lithium exchanger (NCLX), the only transporter known with recognized specificity for Li+. We studied the effect of Li+ isotopes on Ca2+ efflux from heart mitochondria in comparison to natural Li+ and Na+ using Ca2+-induced fluorescence and investigated a possible Li isotope fractionation in mitochondria using inductively coupled plasma mass spectrometry (ICP-MS). Our fluorescence data indicate that Ca2+ efflux increases with higher concentrations of either Li+ or Na+. We found that the simultaneous presence of Li+ and Na+ increases Ca2+ efflux compared to Ca2+ efflux caused by the same concentration of Li+ alone. However, no differentiation in the Ca2+ efflux between the two Li+ isotopes was observed, either for Li+ alone or in mixtures of Li+ and Na+. Our ICP-MS data demonstrate that there is selectivity between Na+ and Li+ (greater Na+ than Li+ uptake) and, most interestingly, between the Li+ isotopes (greater 6Li+ than 7Li+ uptake) by the inner mitochondrial membrane. In summary, we observed no Li+ isotope differentiation for Ca2+ efflux in mitochondria via NCLX but found a Li+ isotope fractionation during Li+ uptake by mitochondria with NCLX active or blocked. Our results suggest that the transport of Li+ via NCLX is not the main pathway for Li+ isotope fractionation and that this differentiation does not affect Ca2+ efflux in mitochondria. Therefore, explaining the puzzling effects of Li+ isotopes observed in other contexts will require further investigation to identify the molecular targets for Li+ isotope differentiation.

Lithium isotopes differentially modify mitochondrial amorphous calcium phosphate cluster size distribution and calcium capacity.

Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7Li acted more potently than 6Li on calcium capacity, yet 6Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics.

Pseudo-Goldstone Modes and Dynamical Gap Generation from Order by Thermal Disorder.

Accidental ground state degeneracies-those not a consequence of global symmetries of the Hamiltonian-are inevitably lifted by fluctuations, often leading to long-range order, a phenomenon known as "order-by-disorder" (ObD). The detection and characterization of ObD in real materials currently lacks clear, qualitative signatures that distinguish ObD from conventional energetic selection. We show that for order by thermal disorder (ObTD) such a signature exists: a characteristic temperature dependence of the fluctuation-induced pseudo-Goldstone gap. We demonstrate this in a minimal two-dimensional model that exhibits ObTD, the ferromagnetic Heisenberg-compass model on a square lattice. Using spin-dynamics simulations and self-consistent mean-field calculations, we determine the pseudo-Goldstone gap, Δ, and show that at low temperatures it scales as the square root of temperature, sqrt[T]. We establish that a power-law temperature dependence of the gap is a general consequence of ObTD, showing that all key features of this physics can be captured in a simple model of a particle moving in an effective potential generated by the fluctuation-induced free energy.

Search for lithium isotope effects in neuronal HT22 cells.

Lithium has been used as a treatment for bipolar disorder for over half a century, but there has thus far been no clinical differentiation made between the two naturally occurring stable isotopes (6Li and 7Li). While the natural lithium salts commonly used in treatments are composed of a mixture of these two stable isotopes (approximately 7.59% 6Li and 92.41% 7Li), some preliminary research indicates the above two stable isotopes of lithium may have differential effects on rat behaviour and neurophysiology. Here, we evaluate whether lithium isotopes may have distinct effects on HT22 neuronal cell viability, GSK-3-ß phosphorylation in HT22 cells, and GSK-3-ß kinase activity. We report no significant difference in lithium isotope toxicity on HT22 cells, nor in GSK-3-ß phosphorylation, nor in GSK-3-ß kinase activity between the two isotopes of lithium.

Relationship Between the Degree of Carotid Stenosis and the Risk of Stroke in Patients Undergoing Cardiac Surgery.

BACKGROUND: The impact of carotid stenosis (CS) in patients undergoing cardiac surgery remains controversial. The aim of this study was to evaluate the association between carotid stenosis and stroke and/or transient ischemic attack (TIA) in patients undergoing cardiac surgery on cardiopulmonary bypass. METHODS: This was a retrospective cohort study including patients undergoing cardiac surgery on cardiopulmonary bypass from January 2006 to March 2018 at the Québec Heart and Lung Institute. Data of patients' preoperative demographic characteristics, operative and postoperative variables were taken from a computerised database and patients' charts. Univariate and multivariate analyses were performed. RESULTS: A total of 20,241 patients were included in the study. Among those who had received preoperative carotid ultrasound, 516 (2.6% of the total population) had unilateral or bilateral CS ≥ 50%. Categorised levels of CS severity were identified as independent risk factors for postoperative stroke and/or TIA. There was an almost 3-fold increased risk of postoperative neurologic events in 80%-99% CS vs less severe 50%-79% CS (odds ratio 2.91, 95% confidence interval 1.30-6.54), suggesting that the degree of severity of CS is potentially a strong independent predictor of postoperative neurologic events. CONCLUSIONS: CS is an independent risk factor of postoperative stroke and/or TIA. This study suggests for the first time that the risk of stroke increases with the degree of severity of CS, with the greatest risk being for CS of 80%-99%. The strength of this relationship and potential causality effect should be further explored in a prospective study focusing on this population most at risk.

Large Intramural Aortic Hematoma with Intimal Tear.

A 72-year-old man presented with excruciating epigastric pain. A chest computed tomography angiography revealed an aortic intramural hematoma. A filling defect within the distal ascending aorta was noted. Images of an intramular hematoma and surgical details of an ascending aortic replacement under deep hypothermic circulatory arrest are provided.

Caseous Calcification of the Mitral Annulus: A Role for Surgery.

An 80-year-old man followed for aortic stenosis was found to have an intracardiac mass. Multiple imaging modalities were inconclusive in characterizing the mass but raised concerns about the potential malignancy of the mass. Fear of operating on an elderly patient with a potential for cardiac neoplasia led to a percutaneous transseptal biopsy that failed to provide a clear diagnosis. Cardiac valvular surgery was performed in addition to excisional biopsy of the mass that turned out to be caseous necrosis of mitral annular calcifications.

Right upper lobe anatomy revisited: a computed tomography scan study.

BACKGROUND: The double lumen tube (DLT) has become the most popular way to isolate the lungs for thoracic surgery. The variable anatomy of the right main stem bronchus (RMSB) seems to be the main reason clinicians are unwilling to use the right-sided DLT (R-DLT). The factors that could compromise the adequate ventilation of the right lung are mostly the variable length of the RMSB and the misalignment of the lateral orifice of the R-DLT in regard to the right upper lobe bronchus (RULB). The objectives of this study were to validate an alternative method to estimate the RMSB length, and to determine the distribution of the angulation of the ostium of the RULB. METHODS: From high-resolution computed tomography scans of the thorax of 106 consecutive patients, the length of the RMSB was measured using Kim's method and the carina-to-carina method. The angle between the RULB origin and the lateral aspect of the RMSB was also measured. All these measurements were correlated and inter-observer variation documented. RESULTS: From the Kim's method, the mean (standard deviation [SD]) length of the RMSB was 25.5 (4.7) mm. From the alternative carina-to-carina method, the mean (SD) length of RMSB was 29.4 (4.6) mm. The inter-observer agreement was substantial with both methods (Kim's method: intraclass correlation coefficient [ICC] = 0.84; carina-to-carina method: ICC = 0.95). Both measures were closely related (ICC = 0.93; P < 0.001). The RULB presented a wide range angulation [mean (SD), 0.1 (9.5)°; range, -28.6 to 21.2]. CONCLUSION: These anatomic observations provide a better understanding of the variable anatomy of the right bronchial tree and may guide thoracic anesthesiologists in the choice of the best lung isolation device for their patients.

RéSUMé: CONTEXTE: Le tube double lumière (TDL) est actuellement la modalité la plus populaire pour isoler les poumons lors d'une chirurgie thoracique. L'anatomie variable de la bronche souche droite (BSD) semble être la principale raison qui freine l'engouement des cliniciens à utiliser un TDL droit (TDL-d). Les facteurs pouvant compliquer la ventilation adéquate du poumon droit sont surtout la longueur variable de la BSD et le mauvais alignement entre l'orifice latéral du TDL-d et de la bronche lobaire supérieure droite (BLSD). Les objectifs de cette étude étaient de valider une méthode alternative d'estimation de la longueur de la BSD ainsi que de déterminer la distribution de l'angulation de l'orifice de la BLSD. MéTHODE: En nous basant sur des images de tomodensitométrie (TDM) thoracique haute résolution de 106 patients consécutifs, la longueur de la BSD a été mesurée à l'aide de la méthode de Kim et de la méthode de carène à carène. L'angle entre l'origine de la BLSD et l'aspect latéral de la BSD a également été mesuré. Toutes ces mesures ont ensuite été corrélées et la variation inter-observateur documentée. RéSULTATS: En se fondant sur la méthode de Kim, la longueur moyenne (écart type [ÉT]) de la BSD était de 25,5 (4,7) mm. En se fondant sur la méthode alternative de carène à carène, la longueur moyenne (ÉT) de la BSD était de 29,4 (4,6) mm. La concordance inter-observateur était élevée lors de l'utilisation des deux méthodes (méthode de Kim : coefficient de corrélation intraclasse [CCI] = 0,84; méthode carène à carène : 0,95). Les deux mesures étaient très rapprochées (CCI = 0,93; P < 0,001). La BLSD présentait une angulation très variable [(ÉT) moyen, 0.1 (9,5)°; éventail, -28,6 à 21,2]. CONCLUSION: Ces observations anatomiques nous permettent de mieux comprendre l'anatomie variable de l'arbre bronchique droit et pourrait aider les anesthésiologistes thoraciques à choisir le dispositif le mieux adapté pour isoler le poumon de leur patient.

Prediction of lung cancer risk at follow-up screening with low-dose CT: a training and validation study of a deep learning method.

Background: Current lung cancer screening guidelines use mean diameter, volume or density of the largest lung nodule in the prior computed tomography (CT) or appearance of new nodule to determine the timing of the next CT. We aimed at developing a more accurate screening protocol by estimating the 3-year lung cancer risk after two screening CTs using deep machine learning (ML) of radiologist CT reading and other universally available clinical information. Methods: A deep machine learning (ML) algorithm was developed from 25,097 participants who had received at least two CT screenings up to two years apart in the National Lung Screening Trial. Double-blinded validation was performed using 2,294 participants from the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). Performance of ML score to inform lung cancer incidence was compared with Lung-RADS and volume doubling time using time-dependent ROC analysis. Exploratory analysis was performed to identify individuals with aggressive cancers and higher mortality rates. Findings: In the PanCan validation cohort, ML showed excellent discrimination with a 1-, 2- and 3-year time-dependent AUC values for cancer diagnosis of 0·968±0·013, 0·946±0·013 and 0·899±0·017. Although high ML score cohort included only 10% of the PanCan sample, it identified 94%, 85%, and 71% of incident and interval lung cancers diagnosed within 1, 2, and 3 years, respectively, after the second screening CT. Furthermore, individuals with high ML score had significantly higher mortality rates (HR=16·07, p<0·001) compared to those with lower risk. Interpretation: ML tool that recognizes patterns in both temporal and spatial changes as well as synergy among changes in nodule and non-nodule features may be used to accurately guide clinical management after the next scheduled repeat screening CT.

Predicting Malignancy Risk of Screen-Detected Lung Nodules-Mean Diameter or Volume.

OBJECTIVE: In lung cancer screening practice low-dose computed tomography, diameter, and volumetric measurement have been used in the management of screen-detected lung nodules. The aim of this study was to compare the performance of nodule malignancy risk prediction tools using diameter or volume and between computer-aided detection (CAD) and radiologist measurements. METHODS: Multivariable logistic regression models were prepared by using data from two multicenter lung cancer screening trials. For model development and validation, baseline low-dose computed tomography scans from the Pan-Canadian Early Detection of Lung Cancer Study and a subset of National Lung Screening Trial (NLST) scans with lung nodules 3 mm or more in mean diameter were analyzed by using the CIRRUS Lung Screening Workstation (Radboud University Medical Center, Nijmegen, the Netherlands). In the NLST sample, nodules with cancer had been matched on the basis of size to nodules without cancer. RESULTS: Both CAD-based mean diameter and volume models showed excellent discrimination and calibration, with similar areas under the receiver operating characteristic curves of 0.947. The two CAD models had predictive performance similar to that of the radiologist-based model. In the NLST validation data, the CAD mean diameter and volume models also demonstrated excellent discrimination: areas under the curve of 0.810 and 0.821, respectively. These performance statistics are similar to those of the Pan-Canadian Early Detection of Lung Cancer Study malignancy probability model with use of these data and radiologist-measured maximum diameter. CONCLUSION: Either CAD-based nodule diameter or volume can be used to assist in predicting a nodule's malignancy risk.

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

BACKGROUND: Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. METHODS: We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. FINDINGS: 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer): one diagnosed between T0 and T1, and nine between T1 and T4. Cumulative incidence was significantly higher than that observed in NLST (4·0%; p<0·0001). Compared with 593 (57%) of 1040 lung cancers observed in NLST, 133 (77%) of 172 lung cancers in the PanCan Study were early stage (I or II; p<0·0001). INTERPRETATION: The PanCan model was effective in identifying individuals who were subsequently diagnosed with early, potentially curable, lung cancer. The incidence of cancers detected and the proportion of early stage cancers in the screened population was higher than observed in previous studies. This approach should be considered for adoption in lung cancer screening programmes. FUNDING: Terry Fox Research Institute and Canadian Partnership Against Cancer.

Spin slush in an extended spin ice model.

We present a new classical spin liquid on the pyrochlore lattice by extending spin ice with further neighbour interactions. We find that this disorder-free spin model exhibits a form of dynamical heterogeneity with extremely slow relaxation for some spins, while others fluctuate quickly down to zero temperature. We thus call this state spin slush, in analogy to the heterogeneous mixture of solid and liquid water. This behaviour is driven by the structure of the ground-state manifold which extends the celebrated two-in/two-out ice states to include branching structures built from three-in/one-out, three-out/one-in and all-in/all-out tetrahedra defects. Distinctive liquid-like patterns in the magnetic correlations serve as a signature of this intermediate range order. Possible applications to materials as well the effects of quantum tunnelling are discussed.

Computer Vision Tool and Technician as First Reader of Lung Cancer Screening CT Scans.

OBJECTIVES: To implement a cost-effective low-dose computed tomography (LDCT) lung cancer screening program at the population level, accurate and efficient interpretation of a large volume of LDCT scans is needed. The objective of this study was to evaluate a workflow strategy to identify abnormal LDCT scans in which a technician assisted by computer vision (CV) software acts as a first reader with the aim to improve speed, consistency, and quality of scan interpretation. METHODS: Without knowledge of the diagnosis, a technician reviewed 828 randomly batched scans (136 with lung cancers, 556 with benign nodules, and 136 without nodules) from the baseline Pan-Canadian Early Detection of Lung Cancer Study that had been annotated by the CV software CIRRUS Lung Screening (Diagnostic Image Analysis Group, Nijmegen, The Netherlands). The scans were classified as either normal (no nodules ≥1 mm or benign nodules) or abnormal (nodules or other abnormality). The results were compared with the diagnostic interpretation by Pan-Canadian Early Detection of Lung Cancer Study radiologists. RESULTS: The overall sensitivity and specificity of the technician in identifying an abnormal scan were 97.8% (95% confidence interval: 96.4-98.8) and 98.0% (95% confidence interval: 89.5-99.7), respectively. Of the 112 prevalent nodules that were found to be malignant in follow-up, 92.9% were correctly identified by the technician plus CV compared with 84.8% by the study radiologists. The average time taken by the technician to review a scan after CV processing was 208 ± 120 seconds. CONCLUSIONS: Prescreening CV software and a technician as first reader is a promising strategy for improving the consistency and quality of screening interpretation of LDCT scans.

Nematicity in stripe-ordered cuprates probed via resonant x-ray scattering.

In underdoped cuprate superconductors, a rich competition occurs between superconductivity and charge density wave (CDW) order. Whether rotational symmetry-breaking (nematicity) occurs intrinsically and generically or as a consequence of other orders is under debate. Here, we employ resonant x-ray scattering in stripe-ordered superconductors (La,M)2CuO4 to probe the relationship between electronic nematicity of the Cu 3d orbitals, structure of the (La,M)2O2 layers, and CDW order. We find distinct temperature dependences for the structure of the (La,M)2O2 layers and the electronic nematicity of the CuO2 planes, with only the latter being enhanced by the onset of CDW order. These results identify electronic nematicity as an order parameter that is distinct from a purely structural order parameter in underdoped striped cuprates.

Fluctuation-driven selection at criticality in a frustrated magnetic system: the case of multiple-k partial order on the pyrochlore lattice.

We study the problem of partially ordered phases with periodically arranged disordered (paramagnetic) sites on the pyrochlore lattice, a network of corner-sharing tetrahedra. The periodicity of these phases is characterized by one or more wave vectors k={1/21/21/2}. Starting from a general microscopic Hamiltonian including anisotropic nearest-neighbor exchange, long-range dipolar interactions, and second- and third-nearest neighbor exchange, we use standard mean-field theory (SMFT) to identify an extended range of interaction parameters that support partially ordered phases. We demonstrate that thermal fluctuations ignored in SMFT are responsible for the selection of one particular partially ordered phase, e.g., the "4-k" phase over the "1-k" phase. We suggest that the transition into the 4-k phase is continuous with its critical properties controlled by the cubic fixed point of a Ginzburg-Landau theory with a four-component vector order parameter. By combining an extension of the Thouless-Anderson-Palmer method originally used to study fluctuations in spin glasses with parallel-tempering Monte Carlo simulations, we establish the phase diagram for different types of partially ordered phases. Our results elucidate the long-standing puzzle concerning the origin of the 4-k partially ordered phase observed in the Gd2Ti2O7 dipolar pyrochlore antiferromagnet below its paramagnetic phase transition temperature.

Plasma pro-surfactant protein B and lung function decline in smokers.

Plasma pro-surfactant protein B (pro-SFTPB) levels have recently been shown to predict the development of lung cancer in current and ex-smokers, but the ability of pro-SFTPB to predict measures of chronic obstructive pulmonary disease (COPD) severity is unknown. We evaluated the performance characteristics of pro-SFTPB as a biomarker of lung function decline in a population of current and ex-smokers. Plasma pro-SFTPB levels were measured in 2503 current and ex-smokers enrolled in the Pan-Canadian Early Detection of Lung Cancer Study. Linear regression was performed to determine the relationship of pro-SFTPB levels to changes in forced expiratory volume in 1 s (FEV1) over a 2-year period as well as to baseline FEV1 and the burden of emphysema observed in computed tomography (CT) scans. Plasma pro-SFTPB levels were inversely related to both FEV1 % predicted (p=0.024) and FEV1/forced vital capacity (FVC) (p<0.001), and were positively related to the burden of emphysema on CT scans (p<0.001). Higher plasma pro-SFTPB levels were also associated with a more rapid decline in FEV1 at 1 year (p=0.024) and over 2 years of follow-up (p=0.004). Higher plasma pro-SFTPB levels are associated with increased severity of airflow limitation and accelerated decline in lung function. Pro-SFTPB is a promising biomarker for COPD severity and progression.

Are Multiphase Competition and Order by Disorder the Keys to Understanding Yb(2)Ti(2)O(7)?

If magnetic frustration is most commonly known for undermining long-range order, as famously illustrated by spin liquids, the ability of matter to develop new collective mechanisms in order to fight frustration is perhaps no less fascinating, providing an avenue for the exploration and discovery of unconventional behaviors. Here, we study a realistic minimal model where a number of such mechanisms converge, which, incidentally, pertain to the perplexing quantum spin ice candidate Yb(2)Ti(2)O(7). Specifically, we explain how thermal and quantum fluctuations, optimized by order-by-disorder selection, conspire to expand the stability region of a degenerate continuous U(1) manifold against the classical splayed ferromagnetic ground state that is displayed by the sister compound Yb(2)Ti(2)O(7). The resulting competition gives rise to multiple phase transitions, in striking similitude with recent experiments on Yb(2)Ti(2)O(7) [Lhotel et al., Phys. Rev. B 89, 224419 (2014)]. By combining a gamut of numerical techniques, we obtain compelling evidence that such multiphase competition is a natural engine for the substantial sample-to-sample variability observed in Yb(2)Ti(2)O(7) and is the missing key to ultimately understand the intrinsic properties of this material. As a corollary, our work offers a pertinent illustration of the influence of chemical pressure in rare-earth pyrochlores.

Probability of cancer in pulmonary nodules detected on first screening CT.

BACKGROUND: Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. METHODS: We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. RESULTS: In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. CONCLUSIONS: Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

Transcatheter aortic valve implantation for the treatment of surgical valve dysfunction ("valve-in-valve"): assessing the risk of coronary obstruction.

Acute coronary obstruction is one of the most feared complications associated with transcatheter aortic valve-in-valve implantation. Strategies for assessing the risk of coronary occlusion during these procedures as well as preventive measures are discussed.