Background. It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. Methods. A prospective intervention study was ...performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010–2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40–60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography–tandem mass spectrometry. Results. Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated. Conclusions. We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B. Clinical Trials Registration. ClinicalTrials.gov, NCT01052961.
Electronic nematic materials are characterized by a lowered symmetry of the electronic system compared to the underlying lattice, in analogy to the directional alignment without translational order ...in nematic liquid crystals. Such nematic phases appear in the copper- and iron-based high-temperature superconductors, and their role in establishing superconductivity remains an open question. Nematicity may take an active part, cooperating or competing with superconductivity, or may appear accidentally in such systems. Here we present experimental evidence for a phase of fluctuating nematic character in a heavy-fermion superconductor, CeRhIn
(ref. 5). We observe a magnetic-field-induced state in the vicinity of a field-tuned antiferromagnetic quantum critical point at H
≈ 50 tesla. This phase appears above an out-of-plane critical field H* ≈ 28 tesla and is characterized by a substantial in-plane resistivity anisotropy in the presence of a small in-plane field component. The in-plane symmetry breaking has little apparent connection to the underlying lattice, as evidenced by the small magnitude of the magnetostriction anomaly at H*. Furthermore, no anomalies appear in the magnetic torque, suggesting the absence of metamagnetism in this field range. The appearance of nematic behaviour in a prototypical heavy-fermion superconductor highlights the interrelation of nematicity and unconventional superconductivity, suggesting nematicity to be common among correlated materials.
New organic dyes that contain variable lengths of conjugation, featuring oligothiophene and arylamines at the 2- and 3-position, have been synthesized. These compounds are characterized by ...photophysical, electrochemical, and theoretical computational methods. Nanocrystalline TiO2-based dye-sensitized solar cells were fabricated using these molecules as light-harvesting sensitizers. The overall efficiencies of the sensitized cells range from 4.11 to 6.15%, compared to a cis-di(thiocyanato)-bis(2,2′-bipyridyl)-4,4′-dicarboxylate ruthenium(II)-sensitized device (7.86%) fabricated and measured under similar conditions. The devices made from these compounds have higher open-circuit voltage (V OC) compared to oligothiophene congeners with arylamines at the 2-position only. The hydrophobic segment at the 3-position appears to help retarding the charge transfer from the conduction band of TiO2 to the electrolyte, I3 −. Supplementary studies of the transient photovoltage and electrochemical impedance are in support of retarded charge transfer of TiO2 (e−) with both oxidized sensitizer and I3 −. Computation on a pair of compounds with and without arylamines at 3-position indicates that the former has larger charge transfer efficiency at the electronically excited state.
We introduce an unsupervised machine learning (ML) based technique for the identification and characterization of microstructures in three-dimensional (3D) samples obtained from molecular dynamics ...simulations, particle tracking data, or experiments. Our technique combines topology classification, image processing, and clustering algorithms, and can handle a wide range of microstructure types including grains in polycrystalline materials, voids in porous systems, and structures from self/directed assembly in soft-matter complex solutions. Our technique does not require a priori microstructure description of the target system and is insensitive to disorder such as extended defects in polycrystals arising from line and plane defects. We demonstrate quantitively that our technique provides unbiased microstructural information such as precise quantification of grains and their size distributions in 3D polycrystalline samples, characterizes features such as voids and porosity in 3D polymeric samples and micellar size distribution in 3D complex fluids. To demonstrate the efficacy of our ML approach, we benchmark it against a diverse set of synthetic data samples representing nanocrystalline metals, polymers and complex fluids as well as experimentally published characterization data. Our technique is computationally efficient and provides a way to quickly identify, track, and quantify complex microstructural features that impact the observed material behavior.
Reinforcement learning (RL) approaches that combine a tree search with deep learning have found remarkable success in searching exorbitantly large, albeit discrete action spaces, as in chess, Shogi ...and Go. Many real-world materials discovery and design applications, however, involve multi-dimensional search problems and learning domains that have continuous action spaces. Exploring high-dimensional potential energy models of materials is an example. Traditionally, these searches are time consuming (often several years for a single bulk system) and driven by human intuition and/or expertise and more recently by global/local optimization searches that have issues with convergence and/or do not scale well with the search dimensionality. Here, in a departure from discrete action and other gradient-based approaches, we introduce a RL strategy based on decision trees that incorporates modified rewards for improved exploration, efficient sampling during playouts and a "window scaling scheme" for enhanced exploitation, to enable efficient and scalable search for continuous action space problems. Using high-dimensional artificial landscapes and control RL problems, we successfully benchmark our approach against popular global optimization schemes and state of the art policy gradient methods, respectively. We demonstrate its efficacy to parameterize potential models (physics based and high-dimensional neural networks) for 54 different elemental systems across the periodic table as well as alloys. We analyze error trends across different elements in the latent space and trace their origin to elemental structural diversity and the smoothness of the element energy surface. Broadly, our RL strategy will be applicable to many other physical science problems involving search over continuous action spaces.
This study presents a model for the early identification of students who are likely to fail in an academic course. To enhance predictive accuracy, sentiment analysis is used to identify affective ...information from text‐based self‐evaluated comments written by students. Experimental results demonstrated that adding extracted sentiment information from student self‐evaluations yields a significant improvement in early‐stage prediction quality. The results also indicate the limited early‐stage predictive value of structured data, such as homework completion, attendance, and exam grades, due to data sparseness at the beginning of the course. Thus, applying sentiment analysis to unstructured data (e.g., self‐evaluation comments) can play an important role in improving the accuracy of early‐stage predictions. The findings present educators with an opportunity to provide students with real‐time feedback and support to help students become self‐regulated learners. Using the exploring results for improvement in teaching and learning initiatives is important to maintain students' performances and the effectiveness of the learning process.
Lay Description
What is already known about this topic:
The impact of emotional state on academic performance
Early intervention is a key factor in preventing academic failure by at‐risk students.
What this paper adds:
Apply sentiment analysis to enhance predictive accuracy in early stage.
Built a Chinese affective resource with valence ratings for each affective word, and use it to automatically extract emotions from self‐evaluation comments.
Implications for practice and/or policy:
Point out the limited early‐stage predictive ability of structured data and using unstructured data to bridge the gap.
Using information visualization to build self‐regulated system by structured and unstructured data. For educators, easy to recognize students' emotion during the class; for students, easy to understand how well they are performing in a class in a timely manner.
Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or ...metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented.
KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population.
Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months 95% confidence interval (CI) 11.7-22.9 months with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262). Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage).
Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.
•No difference was observed in efficacy between pembrolizumab and chemotherapy in advanced platinum-pretreated NPC.•Median OS was 17.2 months with pembrolizumab versus 15.3 with chemotherapy (median PFS, 4.1 versus 5.5 months.•Pembrolizumab had manageable safety and a lower incidence of treatment-related adverse events (AEs) than chemotherapy.•Grade 3-5 treatment-related AEs occurred in 10.3% of participants treated with pembrolizumab versus 43.8% with chemotherapy.
Aberrant functional connectivity within the default network is generally assumed to be involved in the pathophysiology of obsessive compulsive disorder (OCD); however, the genetic risk of default ...network connectivity in OCD remains largely unknown.
Here, we systematically investigated default network connectivity in 15 OCD patients, 15 paired unaffected siblings and 28 healthy controls. We sought to examine the profiles of default network connectivity in OCD patients and their siblings, exploring the correlation between abnormal default network connectivity and genetic risk for this population.
Compared with healthy controls, OCD patients exhibited reduced strength of default network functional connectivity with the posterior cingulate cortex (PCC), and increased functional connectivity in the right inferior frontal lobe, insula, superior parietal cortex and superior temporal cortex, while their unaffected first-degree siblings only showed reduced local connectivity in the PCC.
These findings suggest that the disruptions of default network functional connectivity might be associated with family history of OCD. The decreased default network connectivity in both OCD patients and their unaffected siblings may serve as a potential marker of OCD.
A novel series of dipolar organic dyes containing diarylamine as the electron donor, 2‐cyanoacrylic acid as the electron acceptor, and fluorene and a heteroaromatic ring as the conjugating bridge ...have been developed and characterized. These metal‐free dyes exhibited very high molar extinction coefficients in the electronic absorption spectra and have been successfully fabricated as efficient nanocrystalline TiO2 dye‐sensitized solar cells (DSSCs). The solar‐energy‐to‐electricity conversion efficiencies of DSSCs ranged from 4.92 to 6.88 %, which reached 68–96 % of a standard device of N719 fabricated and measured under the same conditions. With a TiO2 film thickness of 6 μm, DSSCs based on these dyes had photocurrents surpassing that of the N719‐based device. DFT computation results on these dyes also provide detailed structural information in connection with their high cell performance.
Dipolar organic dyes containing diarylamine as a donor and fluorene and a heteroaromatic ring as the conjugating bridge (see scheme) have been developed for highly efficient nanocrystalline TiO2 dye‐sensitized solar cells (DSSCs). The overall efficiencies of DSSCs range from 4.92–6.88 %, which reach 68–96 % of a standard device of N‐719 that was fabricated and measured under the same conditions.
PDF
