Targeted learning in observational studies with multi-valued treatments: An evaluation of antipsychotic drug treatment safety.

We investigate estimation of causal effects of multiple competing (multi-valued) treatments in the absence of randomization. Our work is motivated by an intention-to-treat study of the relative cardiometabolic risk of assignment to one of six commonly prescribed antipsychotic drugs in a cohort of nearly 39 000 adults with serious mental illnesses. Doubly-robust estimators, such as targeted minimum loss-based estimation (TMLE), require correct specification of either the treatment model or outcome model to ensure consistent estimation; however, common TMLE implementations estimate treatment probabilities using multiple binomial regressions rather than multinomial regression. We implement a TMLE estimator that uses multinomial treatment assignment and ensemble machine learning to estimate average treatment effects. Our multinomial implementation improves coverage, but does not necessarily reduce bias, relative to the binomial implementation in simulation experiments with varying treatment propensity overlap and event rates. Evaluating the causal effects of the antipsychotics on 3-year diabetes risk or death, we find a safety benefit of moving from a second-generation drug considered among the safest of the second-generation drugs to an infrequently prescribed first-generation drug known for having low cardiometabolic risk.

Disparate participation by gender of conference attendants in scientific discussions.

One important metric of a radiologist's visibility and influence is their ability to participate in discussion within their community. The goal of our study was to compare the participation level of men and women in scientific discussions at the annual meeting of the Radiological Society of North America (RSNA). Eleven volunteers collected participation data by gender in 59 sessions (286 presentations) at the 2018 RSNA meeting. Data was analyzed using a combination of Chi-squared, paired Wilcoxon signed-rank and T-test. Of all RSNA professional attendees at the RSNA, 68% were men and 32% were women. Of the 2869 presentations listed in the program, 65% were presented by men and 35% were presented by women. Of the 286 presentations in our sample, 177 (61.8%) were presented by men and 109 (38.1%) were presented by women. Of these 286 presentations, 81 (63%) were moderated by men and 47 (37%) were moderated by women. From the audience, 190 male attendees participated in 134 question-and-answer (Q&A) sessions following presentations and 58 female attendees participated in 52 Q&A sessions (P<0.001). Female attendees who did participate in Q&A sessions talked for a significantly shorter period of time (mean 7.14 ± 17.7 seconds, median 0) compared to male attendees (28.7 ± 29.6 seconds, median 16; P<0.001). Overall, our findings demonstrate that women participated less than men in the Q&A sessions at RSNA 2018, and talked for a shorter period of time. The fact that women were outnumbered among their male peers may explain the difference in behavior by gender.

Artificial intelligence enables whole-body positron emission tomography scans with minimal radiation exposure.

PURPOSE: To generate diagnostic 18F-FDG PET images of pediatric cancer patients from ultra-low-dose 18F-FDG PET input images, using a novel artificial intelligence (AI) algorithm. METHODS: We used whole-body 18F-FDG-PET/MRI scans of 33 children and young adults with lymphoma (3-30 years) to develop a convolutional neural network (CNN), which combines inputs from simulated 6.25% ultra-low-dose 18F-FDG PET scans and simultaneously acquired MRI scans to produce a standard-dose 18F-FDG PET scan. The image quality of ultra-low-dose PET scans, AI-augmented PET scans, and clinical standard PET scans was evaluated by traditional metrics in computer vision and by expert radiologists and nuclear medicine physicians, using Wilcoxon signed-rank tests and weighted kappa statistics. RESULTS: The peak signal-to-noise ratio and structural similarity index were significantly higher, and the normalized root-mean-square error was significantly lower on the AI-reconstructed PET images compared to simulated 6.25% dose images (p < 0.001). Compared to the ground-truth standard-dose PET, SUVmax values of tumors and reference tissues were significantly higher on the simulated 6.25% ultra-low-dose PET scans as a result of image noise. After the CNN augmentation, the SUVmax values were recovered to values similar to the standard-dose PET. Quantitative measures of the readers' diagnostic confidence demonstrated significantly higher agreement between standard clinical scans and AI-reconstructed PET scans (kappa = 0.942) than 6.25% dose scans (kappa = 0.650). CONCLUSIONS: Our CNN model could generate simulated clinical standard 18F-FDG PET images from ultra-low-dose inputs, while maintaining clinically relevant information in terms of diagnostic accuracy and quantitative SUV measurements.

Global quieting of high-frequency seismic noise due to COVID-19 pandemic lockdown measures.

Human activity causes vibrations that propagate into the ground as high-frequency seismic waves. Measures to mitigate the coronavirus disease 2019 (COVID-19) pandemic caused widespread changes in human activity, leading to a months-long reduction in seismic noise of up to 50%. The 2020 seismic noise quiet period is the longest and most prominent global anthropogenic seismic noise reduction on record. Although the reduction is strongest at surface seismometers in populated areas, this seismic quiescence extends for many kilometers radially and hundreds of meters in depth. This quiet period provides an opportunity to detect subtle signals from subsurface seismic sources that would have been concealed in noisier times and to benchmark sources of anthropogenic noise. A strong correlation between seismic noise and independent measurements of human mobility suggests that seismology provides an absolute, real-time estimate of human activities.

Therapy Response Assessment of Pediatric Tumors with Whole-Body Diffusion-weighted MRI and FDG PET/MRI.

Background Whole-body diffusion-weighted (DW) MRI can help detect cancer with high sensitivity. However, the assessment of therapy response often requires information about tumor metabolism, which is measured with fluorine 18 fluorodeoxyglucose (FDG) PET. Purpose To compare tumor therapy response with whole-body DW MRI and FDG PET/MRI in children and young adults. Materials and Methods In this prospective, nonrandomized multicenter study, 56 children and young adults (31 male and 25 female participants; mean age, 15 years ± 4 [standard deviation]; age range, 6-22 years) with lymphoma or sarcoma underwent 112 simultaneous whole-body DW MRI and FDG PET/MRI between June 2015 and December 2018 before and after induction chemotherapy (ClinicalTrials.gov identifier: NCT01542879). The authors measured minimum tumor apparent diffusion coefficients (ADCs) and maximum standardized uptake value (SUV) of up to six target lesions and assessed therapy response after induction chemotherapy according to the Lugano classification or PET Response Criteria in Solid Tumors. The authors evaluated agreements between whole-body DW MRI- and FDG PET/MRI-based response classifications with Krippendorff α statistics. Differences in minimum ADC and maximum SUV between responders and nonresponders and comparison of timing for discordant and concordant response assessments after induction chemotherapy were evaluated with the Wilcoxon test. Results Good agreement existed between treatment response assessments after induction chemotherapy with whole-body DW MRI and FDG PET/MRI (α = 0.88). Clinical response prediction according to maximum SUV (area under the receiver operating characteristic curve = 100%; 95% confidence interval [CI]: 99%, 100%) and minimum ADC (area under the receiver operating characteristic curve = 98%; 95% CI: 94%, 100%) were similar (P = .37). Sensitivity and specificity were 96% (54 of 56 participants; 95% CI: 86%, 99%) and 100% (56 of 56 participants; 95% CI: 54%, 100%), respectively, for DW MRI and 100% (56 of 56 participants; 95% CI: 93%, 100%) and 100% (56 of 56 participants; 95% CI: 54%, 100%) for FDG PET/MRI. In eight of 56 patients who underwent imaging after induction chemotherapy in the early posttreatment phase, chemotherapy-induced changes in tumor metabolism preceded changes in proton diffusion (P = .002). Conclusion Whole-body diffusion-weighted MRI showed significant agreement with fluorine 18 fluorodeoxyglucose PET/MRI for treatment response assessment in children and young adults. © RSNA, 2020 Online supplemental material is available for this article.

Hierarchical classification of snowmelt episodes in the Pyrenees using seismic data.

In recent years the analysis of the variations of seismic background signal recorded in temporal deployments of seismic stations near river channels has proved to be a useful tool to monitor river flow, even for modest discharges. The objective of this work is to apply seismic methods to the characterization of the snowmelt process in the Pyrenees, by developing an innovative approach based on the hierarchical classification of the daily spectrograms. The CANF seismic broad-band station, part of the Geodyn facility in the Laboratorio Subterráneo de Canfranc (LSC), is located in an underground tunnel in the Central Pyrenees, at about 400 m of the Aragón River channel, hence providing an excellent opportunity to explore the possibilities of the seismic monitoring of hydrological events at long term scale. We focus here on the identification and analysis of seismic signals generated by variations in river discharge due to snow melting during a period of six years (2011-2016). During snowmelt episodes, the temporal variations of the discharge at the drainage river result in seismic signals with specific characteristics allowing their discrimination from other sources of background vibrations. We have developed a methodology that use seismic data to monitor the time occurrence and properties of the thawing stages. The proposed method is based on the use of hierarchical clustering techniques to classify the daily seismic spectra according to their similarity. This allows us to discriminate up to four different types of episodes, evidencing changes in the duration and intensity of the melting process which in turn depends on variations in the meteorological and hydrological conditions. The analysis of six years of continuous seismic data from this innovative procedure shows that seismic data can be used to monitor snowmelt on long-term time scale and hence contribute to climate change studies.

On the Relationship between Exposure to Particles and Dustiness during Handling of Powders in Industrial Settings.

Exposure to ceramic powders, which is frequent during handling operations, is known to cause adverse health effects. Finding proxy parameters to quantify exposure is useful for efficient and timely exposure assessments. Worker exposure during handling of five materials [a silica sand (SI1), three quartzes (Q1, Q2, and Q3), and a kaolin (K1)] with different particle shape (prismatic and platy) and sizes (3.4-120 µm) was assessed. Materials handling was simulated using a dry pendular mill under two different energy settings (low and high). Three repetitions of two kilos of material were carried out per material and energy conditions with a flow rate of 8-11 kg h-1. The performance of the dustiness index as a predictor of worker exposure was evaluated correlating material's dustiness indexes (with rotating drum and continuous drop) with exposure concentrations. Significant impacts on worker exposure in terms of inhalable and respirable mass fractions were detected for all materials. Mean inhalable mass concentrations during background were always lower than 40 µg m-3 whereas during material handling under high energy settings mean concentrations were 187, 373, 243, 156, and 430 µg m-3 for SI1, Q1, Q2, Q3, and K1, respectively. Impacts were not significant with regard to particle number concentration: background particle number concentrations ranged between 10 620 and 46 421 cm-3 while during handling under high energy settings they were 20 880 - 40 498 cm-3. Mean lung deposited surface area during background ranged between 27 and 101 µm2 cm-3 whereas it ranged between 22 and 42 µm2 cm-3 during materials handling. TEM images evidenced the presence of nanoparticles (≤100 nm) in the form of aggregates (300 nm-1 µm) in the worker area, and a slight reduction on mean particle size during handling was detected. Dustiness and exposure concentrations showed a high degree of correlation (R2 = 0.77-0.97) for the materials and operating conditions assessed, suggesting that dustiness could be considered a relevant predictor for workplace exposure. Nevertheless, the relationship between dustiness and exposure is complex and should be assessed for each process, taking into account not only material behaviour but also energy settings and workplace characteristics.

The non-cylindrical crustal architecture of the Pyrenees.

We exploit the data from five seismic transects deployed across the Pyrenees to characterize the deep architecture of this collisional orogen. We map the main seismic interfaces beneath each transect by depth migration of P-to-S converted phases. The migrated sections, combined with the results of recent tomographic studies and with maps of Bouguer and isostatic anomalies, provide a coherent crustal-scale picture of the belt. In the Western Pyrenees, beneath the North Pyrenean Zone, a continuous band of high density/velocity material is found at a very shallow level (~10 km) beneath the Mauleon basin and near Saint-Gaudens. In the Western Pyrenees, we also find evidence for northward continental subduction of Iberian crust, down to 50-70 km depth. In the Eastern Pyrenees, these main structural features are not observed. The boundary between these two domains is near longitude 1.3 °E, where geological field studies document a major change in the structure of the Cretaceous rift system, and possibly a shift of its polarity, suggesting that the deep orogenic architecture of the Pyrenees is largely controlled by structural inheritance.

Urban Seismology: on the origin of earth vibrations within a city.

Urban seismology has become an active research field in the recent years, both with seismological objectives, as obtaining better microzonation maps in highly populated areas, and with engineering objectives, as the monitoring of traffic or the surveying of historical buildings. We analyze here the seismic records obtained by a broad-band seismic station installed in the ICTJA-CSIC institute, located near the center of Barcelona city. Although this station was installed to introduce visitors to earth science during science fairs and other dissemination events, the analysis of the data has allowed to infer results of interest for the scientific community. The main results include the evidence that urban seismometers can be used as a easy-to-use, robust monitoring tool for road traffic and subway activity inside the city. Seismic signals generated by different cultural activities, including rock concerts, fireworks or football games, can be detected and discriminated from its seismic properties. Beside the interest to understand the propagation of seismic waves generated by those rather particular sources, those earth shaking records provide a powerful tool to gain visibility in the mass media and hence have the opportunity to present earth sciences to a wider audience.

La gran revolución de lo pequeño: nanotecnologías y prevención de riesgos laborales / The great revolution of the small: nanotechnology and occupational risk prevention

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Optical imaging beyond the diffraction limit by SNEM: effects of AFM tip modifications with thiol monolayers on imaging quality.

Tip-enhanced nanoscale optical imaging techniques such as apertureless scanning near-field optical microscopy (a-SNOM) and scanning near-field ellipsometric microscopy (SNEM) applications can suffer from a steady degradation in performance due to adhesion of atmospheric contaminants to the metal coated tip. Here, we demonstrate that a self-assembled monolayer (SAM) of ethanethiol (EtSH) is an effective means of protecting gold-coated atomic force microscopy (AFM) probe tips from accumulation of surface contaminants during prolonged exposure to ambient air. The period over which they yield consistent and reproducible results for scanning near-field ellipsometric microscopy (SNEM) imaging is thus extended. SNEM optical images of a microphase separated polystyrene-block-poly (methylmethacrylate) (PS-b-PMMA) diblock copolymer film, which were captured with bare and SAM-protected gold-coated AFM probes, both immediately after coating and following five days of storage in ambient air, were compared. During this period the intensity of the optical signals from the untreated gold tip fell by 66%, while those from the SAM protected tip fell by 14%. Additionally, gold coated AFM probe tips were modified with various lengths of alkanethiols to measure the change in intensity variation in the optical images with SAM layer thickness. The experimental results were compared to point dipole model calculations. While a SAM of 1-dodecanethiol (DoSH) was found to strongly suppress field enhancement we find that it can be locally removed from the tip apex by deforming the molecules under load, restoring SNEM image contrast.

Scanning Near-Field Ellipsometry Microscopy: imaging nanomaterials with resolution below the diffraction limit.

We introduce a simple Scanning Near-Field Ellipsometer Microscopy (SNEM) setup to address the rapidly increasing need for simple, routine optical imaging techniques with resolution well below the diffraction limit. Our setup is based on the combination of commercially available atomic force microscope (AFM) and ellipsometry equipment with gold-coated AFM tips to obtain near-field optical images with a demonstrated resolution below λ/10. AFM topographical data, obtained in contact mode, and near-field optical data were acquired simultaneously using a combined AFM-ellipsometer. The highly enhanced field due to lightning-rod effects and localized surface plasmons excited at the end of the gold-coated tip allowed us to resolve and identify metallic nanoparticles embedded in poly(methyl methacrylate) as well as microphases in microphase-separated block copolymer films.

GC x GC-ECD: a promising method for the determination of dioxins and dioxin-like PCBs in food and feed.

There is a need for cost-efficient alternatives to gas chromatography (GC)-high-resolution mass spectrometry (HRMS) for the analysis of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (PCBs) in food and feed. Comprehensive two-dimensional GC-micro electron capture detection (GC x GC-microECD) was tested and all relevant (according to the World Health Organisation, WHO) PCDD/Fs and PCBs could be separated when using a DB-XLB/LC-50 column combination. Validation tests by two laboratories showed that detectability, repeatability, reproducibility and accuracy of GC x GC-microECD are all statistically consistent with GC-HRMS results. A limit of detection of 0.5 pg WHO PCDD/F tetrachlorodibenzo-p-dioxin equivalency concentration per gram of fish oil was established. The reproducibility was less than 10%, which is below the recommended EU value for reference methods (less than 15%). Injections of vegetable oil extracts spiked with PCBs, polychlorinated naphthalenes and diphenyl ethers at concentrations of 200 ng/g showed no significant impact on the dioxin results, confirming in that way the robustness of the method. The use of GC x GC-microECD as a routine method for food and feed analysis is therefore recommended. However, the data evaluation of low dioxin concentrations is still laborious owing to the need for manual integration. This makes the overall analysis costs higher than those of GC-HRMS. Further developments of software are needed (and expected) to reduce the data evaluation time. Combination of the current method with pressurised liquid extraction with in-cell cleanup will result in further reduction of analysis costs.

The use of scanning polarization force microscopy to study the miscibility of a molecular wire candidate and an insulating fatty acid in mixed films.

Mixed films containing a conjugated "molecular wire" candidate and an "insulating" fatty acid have been prepared by the Langmuir-Blodgett technique. Specifically, this paper reports the fabrication of mixed films as well as miscibility studies of 4-[4-(4-hexyloxyphenylethynyl)phenylethynyl]benzoic acid (HBPEB) and docosanoic (or behenic) acid (BA). Surface pressure vs. area per molecule isotherms were recorded, with excess area and excess Gibbs energy of mixing calculated. Surface potential-area per molecule isotherms were also recorded for mixtures over the whole range of mole fractions, with negative deviations from the additivity rule revealing orientational changes induced in the HBPEB molecules. The Langmuir films were transferred onto solid supports and characterized by SPM techniques, with atomic force microscopy (AFM) revealing that well-ordered, defect-free films are obtained. The use of scanning polarization force microscopy (SPFM), which provides non-contact imaging based on differences in surface charge distribution, i.e., surface potential, provides complimentary information regarding distribution of the components within the mixed films. From the comprehensive miscibility study performed, which includes thermodynamic and imaging methods, it can be concluded that the wire-like molecule and the fatty acid are miscible over the 0-0.1 and 0.8-1 ranges of HBPEB mole fraction while phase separation occurs for HBPEB mole fractions over the 0.1-0.8 range.

[Ischemic colitis: two forms of clinical presentation and outcome]. / Colitis isquémica: dos formas de evolución clínica.

OBJECTIVES: To characterize the clinical presentation and outcomes of ischemic colitis in our environment with a view to identifying risk factors. METHOD: Fifty-one patients diagnosed in our hospital with ischemic colitis over a 5-year period (1998-2002) were retrospectively analyzed. Demographic data, clinical symptoms, diagnosis and treatment were studied. Two groups (surgical patients [n = 28] and nonsurgical patients [n = 23]) were compared. RESULTS: No significant differences between the two groups were found in demographic data and associated disease. Diagnosis was performed by colonoscopy in nonsurgical patients and by analysis of the surgical specimen in almost all surgical patients. The presenting symptom was lower gastrointestinal bleeding in nonsurgical patients (p < 0.05) and peritonism in surgical patients (p < 0.05). Mortality was significantly higher in patients older than 80 years than in younger patients. CONCLUSIONS: Lower gastrointestinal bleeding was more common as the presenting symptom in transitory forms of ischemic colitis. An acute abdomen indicates serious forms requiring surgery. Therefore the initial clinical symptoms determine the treatment provided. Advanced age is a poor prognostic factor for ischemic colitis. Risk factors in our series were presentation as acute abdomen and advanced age.

Colitis isquémica: dos formas de evolución clínica / Ischemic colitis: two forms of clinical presentation and outcome

Objetivos. Caracterizar la presentación y los resultados de la enfermedad en nuestro medio con el fin de identificar los factores de riesgo. Método. Se ha estudiado retrospectivamente, en un período de 5 años (1998-2002), a 51 pacientes diagnosticados de colitis isquémica en nuestro centro, mediante la revisión de los datos demográficos, los síntomas clínicos, los métodos diagnósticos y el tratamiento. Se comparan 2 grupos: el de pacientes operados (grupo O; n = 28) y el de no operados (grupo NO; n = 23). Resultados. No encontramos diferencias significativas entre los 2 grupos en cuanto a los datos demográficos ni a la enfermedad asociada. En los pacientes tratados médicamente, la enfermedad se diagnostica a través de una colonoscopia, mientras que en los operados prácticamente siempre se consigue el diagnóstico gracias al análisis de la pieza de resección. Los pacientes del grupo NO comienzan con rectorragia (p < 0,05) mientras que los del grupo O acuden por clínica de peritonismo (p < 0,05). La mortalidad entre los pacientes mayores de 80 años es significativamente mayor que en los de menor edad. Conclusiones. La presentación clínica en forma de rectorragia es más frecuente en las formas de colitis isquémica transitorias, mientras que el abdomen agudo define las formas graves que precisan intervención quirúrgica; la clínica inicial es la que determina el tratamiento recibido. Asimismo, la edad avanzada es un factor de mal pronóstico de la enfermedad. En nuestra serie, la presentación en forma de abdomen agudo y la edad avanzada se definen como factores de riesgo (AU)

Objectives. To characterize the clinical presentation and outcomes of ischemic colitis in our environment with a view to identifying risk factors. Method. Fifty-one patients diagnosed in our hospital with ischemic colitis over a 5-year period (1998-2002) were retrospectively analyzed. Demographic data, clinical symptoms, diagnosis and treatment were studied. Two groups (surgical patients [n = 28] and nonsurgical patients [n = 23]) were compared. Results. No significant differences between the two groups were found in demographic data and associated disease. Diagnosis was performed by colonoscopy in nonsurgical patients and by analysis of the surgical specimen in almost all surgical patients. The presenting symptom was lower gastrointestinal bleeding in nonsurgical patients (p < 0.05) and peritonism in surgical patients (p < 0.05). Mortality was significantly higher in patients older than 80 years than in younger patients. Conclusions. Lower gastrointestinal bleeding was more common as the presenting symptom in transitory forms of ischemic colitis. An acute abdomen indicates serious forms requiring surgery. Therefore the initial clinical symptoms determine the treatment provided. Advanced age is a poor prognostic factor for ischemic colitis. Risk factors in our series were presentation as acute abdomen and advanced age (AU)

Determination of aflatoxins B1, G1, B2 and G2 in medicinal herbs by liquid chromatography-tandem mass spectrometry.

An easy method for the determination of aflatoxins B1, G1, B2 and G2 in Rhammus purshiana by LC coupled to mass spectrometry has been developed. Aflatoxins were extracted with a mixture of methanol and water and then it was purified by solid-phase clean-up using a polymeric sorbent, not described previously, for the determination of these toxins. The eluted extract was injected into the chromatographic system using a reversed-phase C18 short column with an isocratic mobile phase composed of methanol-water (30:70). A single-quadruple mass spectrometry using an electrospray ionization source operating in the positive ion mode was used to detect aflatoxins due to derivatization presenting several disadvantages. Recoveries of the full analytical procedure were 110% for aflatoxin B1, 89% for aflatoxin B2, 81% for aflatoxin G1 and 77% for aflatoxin G2. Detection limit (S/N = 3) was 10 ng and quantification limit (S/N = 10) was 25 ng, calculated as amount in medicinal herb.