The two-way linear fixed effects regression (2FE) has become a default method for estimating causal effects from panel data. Many applied researchers use the 2FE estimator to adjust for unobserved ...unit-specific and time-specific confounders at the same time. Unfortunately, we demonstrate that the ability of the 2FE model to simultaneously adjust for these two types of unobserved confounders critically relies upon the assumption of linear additive effects. Another common justification for the use of the 2FE estimator is based on its equivalence to the difference-in-differences estimator under the simplest setting with two groups and two time periods. We show that this equivalence does not hold under more general settings commonly encountered in applied research. Instead, we prove that the multi-period difference-in-differences estimator is equivalent to the weighted 2FE estimator with some observations having negative weights. These analytical results imply that in contrast to the popular belief, the 2FE estimator does not represent a design-based, nonparametric estimation strategy for causal inference. Instead, its validity fundamentally rests on the modeling assumptions.
Matching methods improve the validity of causal inference by reducing model dependence and offering intuitive diagnostics. Although they have become a part of the standard tool kit across ...disciplines, matching methods are rarely used when analysing time‐series cross‐sectional data. We fill this methodological gap. In the proposed approach, we first match each treated observation with control observations from other units in the same time period that have an identical treatment history up to the prespecified number of lags. We use standard matching and weighting methods to further refine this matched set so that the treated and matched control observations have similar covariate values. Assessing the quality of matches is done by examining covariate balance. Finally, we estimate both short‐term and long‐term average treatment effects using the difference‐in‐differences estimator, accounting for a time trend. We illustrate the proposed methodology through simulation and empirical studies. An open‐source software package is available for implementing the proposed methods.
Magnetic, fluorescent core–shell nanoparticles consist of a single Fe3O4 nanocrystal core and a dye‐doped mesoporous silica shell with a poly(ethylene glycol) coating (see picture of TEM images and ...schematic depictions). These nanoparticles can be used as magnetic resonance and fluorescence imaging agents, and as drug delivery vehicles, thus making them novel candidates for simultaneous cancer diagnosis and therapy.
Objective
To report the efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS).
Methods
In the SELECT‐AXIS 1 study, adults with active AS and an inadequate ...response to nonsteroidal antiinflammatory drugs were randomized to receive upadacitinib 15 mg once daily or placebo. At week 14, patients who had been randomized to receive placebo were switched to upadacitinib, and all patients continued in the open‐label extension and received upadacitinib up to week 104; interim data up to week 64 are reported herein.
Results
Of 187 patients, 178 completed week 14 on study drug and entered the open‐label extension. Similar proportions of patients in either group (continuous upadacitinib or placebo‐to‐upadacitinib) achieved Assessment of SpondyloArthritis international Society 40% response (ASAS40) or Ankylosing Spondylitis Disease Activity Score (ASDAS) showing low disease activity at week 64: ≥70% of patients achieved these end points based on nonresponder imputation (NRI) and ≥81% based on as‐observed analyses. Furthermore, ≥34% (NRI) and ≥39% (as‐observed analysis) achieved ASDAS showing inactive disease or ASAS showing partial remission at week 64. Mean changes from baseline (week 0) to week 64 in pain, function, and inflammation showed consistent improvement or sustained maintenance through the study. Among 182 patients receiving upadacitinib (237.6 patient‐years), 618 adverse events (260.1 per 100 patient‐years) were reported. No serious infections, major adverse cardiovascular events, venous thromboembolic events, gastrointestinal perforation, or deaths were reported.
Conclusion
Upadacitinib 15 mg once daily showed sustained and consistent efficacy over 1 year. Patients who switched from placebo to upadacitinib at week 14 showed similar efficacy versus those who received continuous upadacitinib.
Fast and accurate confirmation of metastasis on the frozen tissue section of intraoperative sentinel lymph node biopsy is an essential tool for critical surgical decisions. However, accurate ...diagnosis by pathologists is difficult within the time limitations. Training a robust and accurate deep learning model is also difficult owing to the limited number of frozen datasets with high quality labels. To overcome these issues, we validated the effectiveness of transfer learning from CAMELYON16 to improve performance of the convolutional neural network (CNN)-based classification model on our frozen dataset (N = 297) from Asan Medical Center (AMC). Among the 297 whole slide images (WSIs), 157 and 40 WSIs were used to train deep learning models with different dataset ratios at 2, 4, 8, 20, 40, and 100%. The remaining, i.e., 100 WSIs, were used to validate model performance in terms of patch- and slide-level classification. An additional 228 WSIs from Seoul National University Bundang Hospital (SNUBH) were used as an external validation. Three initial weights, i.e., scratch-based (random initialization), ImageNet-based, and CAMELYON16-based models were used to validate their effectiveness in external validation. In the patch-level classification results on the AMC dataset, CAMELYON16-based models trained with a small dataset (up to 40%, i.e., 62 WSIs) showed a significantly higher area under the curve (AUC) of 0.929 than those of the scratch- and ImageNet-based models at 0.897 and 0.919, respectively, while CAMELYON16-based and ImageNet-based models trained with 100% of the training dataset showed comparable AUCs at 0.944 and 0.943, respectively. For the external validation, CAMELYON16-based models showed higher AUCs than those of the scratch- and ImageNet-based models. Model performance for slide feasibility of the transfer learning to enhance model performance was validated in the case of frozen section datasets with limited numbers.
Objective
To predict the hand‐wrist maturation stages based on the cervical vertebrae (CV) images, and to analyse the accuracy of the proposed algorithms.
Settings and population
A total of 499 pairs ...of hand‐wrist radiographs and lateral cephalograms of 455 orthodontic patients aged 6‐18 years were used for developing the prediction model for hand‐wrist skeletal maturation stages.
Materials and Methods
The hand‐wrist radiographs and the lateral cephalograms were collected from two university hospitals and a paediatric dental clinic. After identifying the 13 anatomic landmarks of the CV, the width‐height ratio, width‐perpendicular height ratio and concavity ratio of the CV were used as the morphometric features of the CV. Patients’ chronological age and sex were also included as input data. The ground truth data were the Fishman SMI based on the hand‐wrist radiographs. Three specialists determined the ground truth SMI. An ensemble machine learning methods were used to predict the Fishman SMI. Five‐fold cross‐validation was performed. The mean absolute error (MAE), round MAE and root mean square error (RMSE) values were used to assess the performance of the final ensemble model.
Results
The final ensemble model consisted of eight machine learning models. The MAE, round MAE and RMSE were 0.90, 0.87 and 1.20, respectively.
Conclusion
Prediction of hand‐wrist SMI based on CV images is possible using machine learning methods. Chronological age and sex increased the prediction accuracy. An automated diagnosis of the skeletal maturation may aid as a decision‐supporting tool for evaluating the optimal treatment timing for growing patients.
Background
Optimal pain management after insertion of a central venous catheter in children remains unclear.
Aim
This study aimed to evaluate the effects of a selective supraclavicular nerve block on ...postoperative analgesia in pediatric patients undergoing hickman catheter or chemoport insertion.
Methods
Fifty patients aged 3–18 years scheduled for elective Hickman or chemoport insertion were randomized into two groups of 25 each: one group received an ultrasound‐guided selective supraclavicular nerve block with 0.1 mL/kg of 0.5% ropivacaine (SSCNB group), and the other group did not receive a nerve block (control group). The primary outcome was the postoperative Wong‐Baker Faces Pain Rating Scale score measured between 10 and 30 min after surgery. Secondary outcomes included pain scores at 1, 3, and 24 h after the surgery, block‐related complications, length of stay in the postanesthesia care unit, postoperative analgesic consumption, and time to first analgesic use 24 h after surgery.
Results
The worst pain score within 30 min in the recovery room was significantly lower in the SSCNB group compared to the control group (6 5–7 vs. 3 2–4; median difference, −3; 95% CI, −4 to −1; p < .001). Pain scores at 1, 3, and 24 h after surgery were also significantly lower in the SSCNB group. The need for both opioid and non‐opioid analgesics in the postoperative period was significantly lower in the SSCNB group (36.0% vs. 0%; p = .002 and 44.0% vs. 16.0%; mean difference, −28%; 95% CI, −56 to 0.19; p = .033, respectively), while other secondary outcomes were not significantly different between the two groups.
Conclusions
Ultrasound‐guided SSCNB is an effective method for managing postoperative pain in children undergoing Hickman catheter or chemoport insertion, reducing the need for analgesics within 24 h after surgery.
Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the ...observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.
Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of ...explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.
Nitrogen-, vanadium-, aluminum-, boron-, and scandium-doped porous SiC ceramics were fabricated to investigate the effects of dopants on electrical, thermal, and mechanical properties of porous SiC ...ceramics. The electrical resistivity of a nitrogen-doped porous SiC ceramic was 2.1 × 10−1 Ω cm four orders of magnitude lower than that of an undoped porous SiC ceramic (1.2 × 103 Ω cm). A B-doped porous SiC ceramic exhibited the highest thermal conductivity (16.6 W/(m K)) and flexural strength (25.9 MPa), whereas a Sc-doped porous SiC ceramic exhibited the lowest thermal conductivity (7.7 W/(m K)) and flexural strength (10.5 MPa) among the doped porous SiC ceramics. The electrical resistivity was strongly influenced by the doping, whereas the thermal and mechanical properties were dependent primarily on the necking area between SiC grains. The results suggest that the electrical conductivities of porous SiC ceramics can be successfully tuned independently of the thermal conductivity by a suitable doping.
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