Enhancing the dielectric constant of zwitterionic liquids via dipole moment and anion chemistry.

The dielectric constant is a critical parameter in many energy-related applications. Typically, increasing the dielectric constant of soft materials involves adding high dielectric constant polar liquids or inorganic fillers, but there are limitations to this approach due to safety concerns with volatile and flammable solvents and the agglomeration of inorganic fillers. An alternative approach is to add zwitterionic liquids that exhibit exceptionally high dielectric constants with negligible volatility. Here, we report the synthesis of a series of zwitterionic liquids containing an imidazolium cation, exhibiting the highest dielectric constant among all organic molecules (∼350 at 293 K). The cation-anion linkage was tailored in a wide range between three and nine carbons, rendering the zwitterion dipole from 25 to 52 D. Comparing the dielectric constant for zwitterions with different anions (i.e., sulfonylimide, sulfonate, and carboxylate) reveals the beneficial impacts of the delocalized sulfonylimide anion vs the carboxylate anion due to the enlarged molecular dipole and more homogenous liquid morphology. Molecular dipole and liquid morphology are identified as the keys to developing high dielectric constant zwitterionic liquids. The extremely high dielectric constant accessible with the proposed molecular design paves new avenues for developing high dielectric constant zwitterions that act as dielectricizers.

Working Memory Recovery in Adolescents with Concussion: Longitudinal fMRI Study.

Background: Understanding the behavioral and neural underpinnings of the post-concussion recovery of working memory function is critically important for improving clinical outcomes and adequately planning return-to-activity decisions. Previous studies provided inconsistent results due to small sample sizes and the use of a mixed population of participants who were at different post-injury time points. We aimed to examine working memory recovery during the first 6 months post-concussion in adolescents. Methods: We used functional magnetic resonance imaging (fMRI) to scan 45 concussed adolescents [CONCs] at baseline (<10 days post-concussion) and at 6 months post-concussion. Healthy control adolescents [HCs; n = 32] without a history of concussion were scanned once. During the scans, participants performed one-back and two-back working memory tasks with letters as the stimuli and angry, happy, neutral, and sad faces as distractors. Results: All affected adolescents were asymptomatic and cleared to return to activity 6 months after concussion. Working memory recovery was associated with faster and more accurate responses at 6 months vs. baseline (p-values < 0.05). It was also characterized by significant difficulty-related activation increases in the left inferior frontal gyrus (LIFG) and the left orbitofrontal cortex (LOFC) at 6 months vs. baseline. Although the activation differences between one-back and two-back were comparable between HCs and CONCs at 6 months, HCs had more pronounced activation in the LIFG than concussed adolescents. Conclusions: Post-concussion recovery is associated with significant performance improvements in speed and accuracy, as well as the normalization of brain responses in the LIFG and LOFC during the n-back task. The observed patterns of LOFC activation might reflect compensatory strategies to distribute neural processing and reduce neural fatigue post-concussion.

Respiratory Syncytial Virus-Associated Hospitalizations Among Children <5 Years Old: 2016 to 2020.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospitalization in US infants. Accurate estimates of severe RSV disease inform policy decisions for RSV prevention. METHODS: We conducted prospective surveillance for children <5 years old with acute respiratory illness from 2016 to 2020 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested midturbinate nasal ± throat swabs by reverse transcription polymerase chain reaction for RSV and other respiratory viruses. We describe characteristics of children hospitalized with RSV, risk factors for ICU admission, and estimate RSV-associated hospitalization rates. RESULTS: Among 13 524 acute respiratory illness inpatients <5 years old, 4243 (31.4%) were RSV-positive; 2751 (64.8%) of RSV-positive children had no underlying condition or history of prematurity. The average annual RSV-associated hospitalization rate was 4.0 (95% confidence interval [CI]: 3.8-4.1) per 1000 children <5 years, was highest among children 0 to 2 months old (23.8 [95% CI: 22.5-25.2] per 1000) and decreased with increasing age. Higher RSV-associated hospitalization rates were found in premature versus term children (rate ratio = 1.95 [95% CI: 1.76-2.11]). Risk factors for ICU admission among RSV-positive inpatients included: age 0 to 2 and 3 to 5 months (adjusted odds ratio [aOR] = 1.97 [95% CI: 1.54-2.52] and aOR = 1.56 [95% CI: 1.18-2.06], respectively, compared with 24-59 months), prematurity (aOR = 1.32 [95% CI: 1.08-1.60]) and comorbid conditions (aOR = 1.35 [95% CI: 1.10-1.66]). CONCLUSIONS: Younger infants and premature children experienced the highest rates of RSV-associated hospitalization and had increased risk of ICU admission. RSV prevention products are needed to reduce RSV-associated morbidity in young infants.

Revealing Deformation Mechanisms in Polymer-Grafted Thermoplastic Elastomers via In Situ Small-Angle X-ray Scattering.

The tunable properties of thermoplastic elastomers (TPEs), through polymer chemistry manipulations, enable these technologically critical materials to be employed in a broad range of applications. The need to "dial-in" the mechanical properties and responses of TPEs generally requires the design and synthesis of new macromolecules. In these designs, TPEs with nonlinear macromolecular architectures outperform the mechanical properties of their linear copolymer counterparts, but the differences in the deformation mechanism providing enhanced performance are unknown. Here, in situ small-angle X-ray scattering (SAXS) measurements during uniaxial extension reveal distinct deformation mechanisms between a commercially available linear poly(styrene)-poly(butadiene)-poly(styrene) (SBS) triblock copolymer and the grafted SBS version containing grafted poly(styrene) (PS) chains from the poly(butadiene) (PBD) midblock. The neat SBS (φSBS = 100%) sample deforms congruently with the macroscopic dimensions, with the domain spacing between spheres increasing and decreasing along and transverse to the stretch direction, respectively. At high extensions, end segment pullout from the PS-rich domains is detected, which is indicated by a disordering of SBS. Conversely, the PS-grafted SBS that is 30 vol % SBS and 70% styrene (φSBS = 30%) exhibits a lamellar morphology, and in situ SAXS measurements reveal an unexpected deformation mechanism. During deformation, there are two simultaneous processes: significant lamellar domain rearrangement to preferentially orient the lamellae planes parallel to the stretch direction and crazing. The samples whiten at high strains as expected for crazing, which corresponds with the emergence of features in the 2D SAXS pattern during stretching consistent with fibril-like structures that bridge the voids in crazes. The significant domain rearrangement in the grafted copolymers is attributed to the new junctions formed across multiple PS domains by the grafting of a single chain. The in situ SAXS measurements provide insights into the enhanced mechanical properties of grafted copolymers that arise through improved physical cross-linking that leads to nanostructure domain reorientation for self-reinforcement and craze formation where fibrils help to strengthen the polymer.

Radiographic pneumonia in young febrile infants presenting to the emergency department: secondary analysis of a prospective cohort study.

OBJECTIVE: The lack of evidence-based criteria to guide chest radiograph (CXR) use in young febrile infants results in variation in its use with resultant suboptimal quality of care. We sought to describe the features associated with radiographic pneumonias in young febrile infants. STUDY DESIGN: Secondary analysis of a prospective cohort study in 18 emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Febrile (≥38°C) infants aged ≤60 days who received CXRs were included. CXR reports were categorised as 'no', 'possible' or 'definite' pneumonia. We compared demographics, clinical signs and laboratory tests among infants with and without pneumonias. RESULTS: Of 2612 infants, 568 (21.7%) had CXRs performed; 19 (3.3%) had definite and 34 (6%) had possible pneumonias. Patients with definite (4/19, 21.1%) or possible (11/34, 32.4%) pneumonias more frequently presented with respiratory distress compared with those without (77/515, 15.0%) pneumonias (adjusted OR 2.17; 95% CI 1.04 to 4.51). There were no differences in temperature or HR in infants with and without radiographic pneumonias. The median serum procalcitonin (PCT) level was higher in the definite (0.7 ng/mL (IQR 0.1, 1.5)) vs no pneumonia (0.1 ng/mL (IQR 0.1, 0.3)) groups, as was the median absolute neutrophil count (ANC) (definite, 5.8 K/mcL (IQR 3.9, 6.9) vs no pneumonia, 3.1 K/mcL (IQR 1.9, 5.3)). No infants with pneumonia had bacteraemia. Viral detection was frequent (no pneumonia (309/422, 73.2%), definite pneumonia (11/16, 68.8%), possible pneumonia (25/29, 86.2%)). Respiratory syncytial virus was the predominant pathogen in the pneumonia groups and rhinovirus in infants without pneumonias. CONCLUSIONS: Radiographic pneumonias were uncommon in febrile infants. Viral detection was common. Pneumonia was associated with respiratory distress, but few other factors. Although ANC and PCT levels were elevated in infants with definite pneumonias, further work is necessary to evaluate the role of blood biomarkers in infant pneumonias.

Small molecule targeting of transcription-replication conflict for selective chemotherapy.

Targeting transcription replication conflicts, a major source of endogenous DNA double-stranded breaks and genomic instability could have important anticancer therapeutic implications. Proliferating cell nuclear antigen (PCNA) is critical to DNA replication and repair processes. Through a rational drug design approach, we identified a small molecule PCNA inhibitor, AOH1996, which selectively kills cancer cells. AOH1996 enhances the interaction between PCNA and the largest subunit of RNA polymerase II, RPB1, and dissociates PCNA from actively transcribed chromatin regions, while inducing DNA double-stranded breaks in a transcription-dependent manner. Attenuation of RPB1 interaction with PCNA, by a point mutation in RPB1's PCNA-binding region, confers resistance to AOH1996. Orally administrable and metabolically stable, AOH1996 suppresses tumor growth as a monotherapy or as a combination treatment but causes no discernable side effects. Inhibitors of transcription replication conflict resolution may provide a new and unique therapeutic avenue for exploiting this cancer-selective vulnerability.

Therapeutic Targeting of DNA Replication Stress in Cancer.

This article reviews the currently used therapeutic strategies to target DNA replication stress for cancer treatment in the clinic, highlighting their effectiveness and limitations due to toxicity and drug resistance. Cancer cells experience enhanced spontaneous DNA damage due to compromised DNA replication machinery, elevated levels of reactive oxygen species, loss of tumor suppressor genes, and/or constitutive activation of oncogenes. Consequently, these cells are addicted to DNA damage response signaling pathways and repair machinery to maintain genome stability and support survival and proliferation. Chemotherapeutic drugs exploit this genetic instability by inducing additional DNA damage to overwhelm the repair system in cancer cells. However, the clinical use of DNA-damaging agents is limited by their toxicity and drug resistance often arises. To address these issues, the article discusses a potential strategy to target the cancer-associated isoform of proliferating cell nuclear antigen (caPCNA), which plays a central role in the DNA replication and damage response network. Small molecule and peptide agents that specifically target caPCNA can selectively target cancer cells without significant toxicity to normal cells or experimental animals.

Etiologies of Poor Weight Gain and Ultimate Diagnosis in Children Admitted for Growth Faltering.

BACKGROUND AND OBJECTIVES: Growth faltering (GF) (previously failure to thrive) is a common reason for hospital admission, but there is little data on whether diagnoses made during initial admission remain accurate in follow-up. We sought to characterize infants admitted for isolated GF and identify diagnoses at discharge and ultimate diagnoses determined over 2 years of follow-up, to determine how diagnoses changed. We also sought to identify patient factors on admission associated with ultimate diagnosis. METHODS: We conducted a retrospective study of children aged 2 weeks to 2 years with index admissions for GF from 2013 to 2017. We reviewed clinical data and documentation to determine discharge and ultimate diagnosis, and identify factors associated with ultimate diagnosis. RESULTS: Of 497 patients, 292 (59%) had insufficient intake, 103 (20%) had organic disease including 36 genetic disorders, 52 (11%) had mechanical feeding difficulties, and 50 (10%) had mixed or unknown diagnoses 2 years after admission. Over 90% of cases of insufficient intake were diagnosed during admission. Sixty-five percent of organic diseases, and only 39% of genetic disorders, were diagnosed during admission. Patient factors associated with genetic disorders included previous NICU stay, low birth weight, dysphagia, hypotonia, and dysmorphisms. CONCLUSIONS: Insufficient intake remains the most common diagnosis, and this diagnosis was accurately made during admission. Organic disease, especially genetic disease, was often not diagnosed during admission. Better tools are needed to identify patients with organic disease. We identified patient factors on admission associated with ultimate diagnosis, which could be used to prioritize evaluation and expedite follow-up.

The Effects of Rest on Concussion Symptom Resolution and Recovery Time: A Meta-analytic Review and Subgroup Analysis of 4329 Patients.

BACKGROUND: Numerous individual studies suggest that rest may have a negative effect on outcomes following concussion. PURPOSE: To perform a systematic meta-analysis of the effects of prescribed rest compared with active interventions after concussion. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: A meta-analysis (using the Hedges g) of randomized controlled trials and cohort studies was conducted to evaluate the effects of prescribed rest on symptoms and recovery time after concussion. Subgroup analyses were performed for methodological, study, and sample characteristics. Data sources were obtained from systematic search of key terms using Ovid Medline, Embase, Cochrane Database of Systematic Reviews, APA PsycINFO, Web of Science, SPORTDiscus, and ProQuest dissertations and theses through May 28, 2021. Eligible studies were those that (1) assessed concussion or mild traumatic brain injury; (2) included symptoms or days to recovery for ≥2 time points; (3) included 2 groups with 1 group assigned to rest; and (4) were written in the English language. RESULTS: In total, 19 studies involving 4239 participants met criteria. Prescribed rest had a significant negative effect on symptoms (k = 15; g = -0.27; SE = 0.11; 95% CI, -0.48 to -0.05; P = .04) but not on recovery time (k = 8; g = -0.16; SE = 0.21; 95% CI, -0.57 to 0.26; P = .03). Subgroup analyses suggested that studies with shorter duration (<28 days) (g = -0.46; k = 5), studies involving youth (g = -0.33; k = 12), and studies focused on sport-related concussion (g = -0.38; k = 8) reported higher effect sizes. CONCLUSION: The findings support a small negative effect for prescribed rest on symptoms after concussion. Younger age and sport-related mechanisms of injury were associated with a greater negative effect size. However, the lack of support for an effect for recovery time and the relatively small overall numbers of eligible studies highlight ongoing concerns regarding the quantity and rigor of clinical trials in concussion. REGISTRATION: CRD42021253060 (PROSPERO).

Prediction of Suicide Attempts and Suicide-Related Events Among Adolescents Seen in Emergency Departments.

Importance: Screening adolescents in emergency departments (EDs) for suicidal risk is a recommended strategy for suicide prevention. Comparing screening measures on predictive validity could guide ED clinicians in choosing a screening tool. Objective: To compare the Ask Suicide-Screening Questions (ASQ) instrument with the Computerized Adaptive Screen for Suicidal Youth (CASSY) instrument for the prediction of suicidal behavior among adolescents seen in EDs, across demographic and clinical strata. Design, Setting, and Participants: The Emergency Department Study for Teens at Risk for Suicide is a prospective, random-series, multicenter cohort study that recruited adolescents, oversampled for those with psychiatric symptoms, who presented to the ED from July 24, 2017, through October 29, 2018, with a 3-month follow-up to assess the occurrence of suicidal behavior. The study included 14 pediatric ED members of the Pediatric Emergency Care Applied Research Network and 1 Indian Health Service ED. Statistical analysis was performed from May 2021 through January 2023. Main Outcomes and Measures: This study used a prediction model to assess outcomes. The primary outcome was suicide attempt (SA), and the secondary outcome was suicide-related visits to the ED or hospital within 3 months of baseline; both were assessed by an interviewer blinded to baseline information. The ASQ is a 4-item questionnaire that surveys suicidal ideation and lifetime SAs. A positive response or nonresponse on any item indicates suicidal risk. The CASSY is a computerized adaptive screening tool that always includes 3 ASQ items and a mean of 8 additional items. The CASSY's continuous outcome is the predicted probability of an SA. Results: Of 6513 adolescents available, 4050 were enrolled, 3965 completed baseline assessments, and 2740 (1705 girls [62.2%]; mean [SD] age at enrollment, 15.0 [1.7] years; 469 Black participants [17.1%], 678 Hispanic participants [24.7%], and 1618 White participants [59.1%]) completed both screenings and follow-ups. The ASQ and the CASSY showed a similar sensitivity (0.951 [95% CI, 0.918-0.984] vs 0.945 [95% CI, 0.910-0.980]), specificity (0.588 [95% CI, 0.569-0.607] vs 0.643 [95% CI, 0.625-0.662]), positive predictive value (0.127 [95% CI, 0.109-0.146] vs 0.144 [95% CI, 0.123-0.165]), and negative predictive value (both 0.995 [95% CI, 0.991-0.998], respectively). Area under the receiver operating characteristic curve findings were similar among patients with physical symptoms (ASQ, 0.88 [95% CI, 0.81-0.95] vs CASSY, 0.94 [95% CI, 0.91-0.96]). Among patients with psychiatric symptoms, the CASSY performed better than the ASQ (0.72 [95% CI, 0.68-0.77] vs 0.57 [95% CI, 0.55-0.59], respectively). Conclusions and Relevance: This study suggests that both the ASQ and the CASSY are appropriate for universal screening of patients in pediatric EDs. For the small subset of patients with psychiatric symptoms, the CASSY shows greater predictive validity.

Intranasal fentanyl and discharge from the emergency department among children with sickle cell disease and vaso-occlusive pain: A multicenter pediatric emergency medicine perspective.

Children with sickle cell disease (SCD) commonly experience vaso-occlusive pain episodes (VOE) due to sickling of erythrocytes, which often requires care in the emergency department. Our objective was to assess the use and impact of intranasal fentanyl for the treatment of children with SCD-VOE on discharge from the emergency department in a multicenter study. We conducted a cross-sectional study at 20 academic pediatric emergency departments in the United States and Canada. We used logistic regression to test bivariable and multivariable associations between the outcome of discharge from the emergency department and candidate variables theoretically associated with discharge. The study included 400 patients; 215 (54%) were female. The median age was 14.6 (interquartile range 9.8, 17.6) years. Nineteen percent (n = 75) received intranasal fentanyl in the emergency department. Children who received intranasal fentanyl had nearly nine-fold greater adjusted odds of discharge from the emergency department compared to those who did not (adjusted odds ratio 8.99, 95% CI 2.81-30.56, p < .001). The rapid onset of action and ease of delivery without intravenous access offered by intranasal fentanyl make it a feasible initial parenteral analgesic in the treatment of children with SCD presenting with VOE in the acute-care setting. Further study is needed to determine potential causality of the association between intranasal fentanyl and discharge from the emergency department observed in this multicenter study.

Increased Fellow Scholarly Publication Rate After Implementation of a Comprehensive Research Curriculum and Milestone-Based Research Timeline for Pediatric Emergency Medicine Fellows.

OBJECTIVE: Pediatric subspecialty fellows are required to complete a scholarly product during training; however, many do not bring the work to publication. To amplify our fellows' publication success, our pediatric emergency medicine fellowship program implemented a comprehensive research curriculum and established a milestone-based research timeline for each component of a project. Our objective was to assess whether these interventions increased the publication rate and enhanced the graduated fellows' perceived ability to perform independent research. METHODS: Our study was conducted at a tertiary children's hospital affiliated with an academic university, enrolling 3 fellows each year in its pediatric emergency medicine program. A comprehensive research curriculum and a milestone-based research timeline were implemented in 2011. We analyzed the publication rate of our graduating fellows before (2004-2011) and after (2012-2016) our intervention. In addition, in 2017 we surveyed our previous fellows who graduated from 2004 to 2016 and analyzed factors favoring manuscript publication and confidence with various research skills. RESULTS: During the study period, 38 trainees completed the fellowship program. Publication rate increased from 26% ± 17% to 87% ± 30 % ( P < 0.05). When scoring the importance of various factors, fellows most valued mentorship (5 ± 0 vs 4.3 ± 1.0, P < 0.05, postintervention vs preintervention) for the completion of the fellowship study and manuscript. Fellows after the intervention reported greater confidence in performing an analysis of variance (89% vs 36%, odds ratio, 6.3; 95% confidence interval, 1.4-150.1). CONCLUSIONS: Implementation of a comprehensive research curriculum and a milestone-based research timeline was associated with an increase in the publication rate within 3 years of graduation of our pediatric emergency medicine fellows. After implementation, fellows reported an increased importance of mentorship and greater confidence in performing an analysis of variance. We provide a comprehensive curriculum and a research timeline that may serve as a model for other fellowship programs.

Effect of ketamine on transcranial Doppler Gosling pulsatility index in children undergoing procedural sedation: A pilot study.

Objectives: There has been controversy over whether ketamine affects intracranial pressure (ICP) in children. Transcranial Doppler ultrasound (TCD) is a validated technique used to assess ICP changes noninvasively. Gosling pulsatility index (PI) directly correlates with ICP changes. The objective of this study was to quantify PI changes as a surrogate marker for ICP changes in previously healthy children receiving intravenous ketamine for procedural sedation. Methods: We performed a prospective, observational study of patients 5-18 years old who underwent sedation with intravenous ketamine as monotherapy. ICP changes were assessed by surrogate PI at baseline, immediately after ketamine administration, and every 5 minutes until completion of the procedure. The primary outcome measure was PI change after ketamine administration compared to baseline (denoted ΔPI). Results: We enrolled 15 participants. Mean age was 9.9 ± 3.4 years. Most participants underwent sedation for fracture reduction (87%). Mean initial ketamine dose was 1.4 ± 0.3 mg/kg. PI decreased at all time points after ketamine administration. Mean ΔPI at sedation onset was -0.23 (95% confidence interval [CI] = -0.30 to -0.15), at 5 minutes was -0.23 (95% CI = -0.28 to -0.18), at 10 minutes was -0.14 (95% CI = -0.21 to -0.08), at 15 minutes was -0.18 (95% CI = -0.25 to -0.12), and at 20 minutes was -0.19 (95% CI = -0.26 to -0.12). Using a clinically relevant threshold of ΔPI set at +1 (+8 cm H2O), no elevation in ICP, based on the PI surrogate marker, was demonstrated with 95% confidence at all time points after ketamine administration. Conclusions: Ketamine did not significantly increase PI, which was used as a surrogate marker for ICP in this sample of previously healthy children. This pilot study demonstrates a model for evaluating ICP changes noninvasively in the emergency department.

Nanostructured block copolymer muscles.

High-performance actuating materials are necessary for advances in robotics, prosthetics and smart clothing. Here we report a class of fibre actuators that combine solution-phase block copolymer self-assembly and strain-programmed crystallization. The actuators consist of highly aligned nanoscale structures with alternating crystalline and amorphous domains, resembling the ordered and striated pattern of mammalian skeletal muscle. The reported nanostructured block copolymer muscles excel in several aspects compared with current actuators, including efficiency (75.5%), actuation strain (80%) and mechanical properties (for example, strain-at-break of up to 900% and toughness of up to 121.2 MJ m-3). The fibres exhibit on/off rotary actuation with a peak rotational speed of 450 r.p.m. Furthermore, the reported fibres demonstrate multi-trigger actuation (heat and hydration), offering switchable mechanical properties and various operating modes. The versatility and recyclability of the polymer fibres, combined with the facile fabrication method, opens new avenues for creating multifunctional and recyclable actuators using block copolymers.

Understanding Variation in Rotavirus Vaccine Effectiveness Estimates in the United States: The Role of Rotavirus Activity and Diagnostic Misclassification.

BACKGROUND: Estimates of rotavirus vaccine effectiveness (VE) in the United States appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses. METHODS: We analyzed 6 years of data from eight US surveillance sites on 8- to 59-month olds with acute gastroenteritis symptoms. Children's stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention. We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with Centers for Disease Control and Prevention confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year-vaccination interaction, and the second including the annual percent of rotavirus-positive tests plus a percent positive-vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone. RESULTS: Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year-vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive-vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification. CONCLUSIONS: Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.

Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Importance: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship. Objective: To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI. Design, Setting, and Participants: This prospective multicenter diagnostic study enrolled 755 children and adults with febrile ARI of 7 or fewer days' duration from 10 US emergency departments. Participants were enrolled from October 3, 2014, to September 1, 2019, followed by additional enrollment of patients with COVID-19 from March 20 to December 3, 2020. Clinical adjudication of enrolled participants identified 616 individuals as having bacterial or viral infection. The primary analysis cohort included 334 participants with high-confidence reference adjudications (based on adjudicator concordance and the presence of an identified pathogen confirmed by microbiological testing). A secondary analysis of the entire cohort of 616 participants included cases with low-confidence reference adjudications (based on adjudicator discordance or the absence of an identified pathogen in microbiological testing). Thirty-three participants with COVID-19 were included post hoc. Interventions: The HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection. Main Outcomes and Measures: Performance characteristics for the HR-B/V test compared with clinical adjudication were reported as either bacterial or viral infection or categorized into 4 likelihood groups (viral very likely [probability score <0.19], viral likely [probability score of 0.19-0.40], bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability score >0.73]) and compared with procalcitonin measurement. Results: Among 755 enrolled participants, the median age was 26 years (IQR, 16-52 years); 360 participants (47.7%) were female, and 395 (52.3%) were male. A total of 13 participants (1.7%) were American Indian, 13 (1.7%) were Asian, 368 (48.7%) were Black, 131 (17.4%) were Hispanic, 3 (0.4%) were Native Hawaiian or Pacific Islander, 297 (39.3%) were White, and 60 (7.9%) were of unspecified race and/or ethnicity. In the primary analysis involving 334 participants, the HR-B/V test had sensitivity of 89.8% (95% CI, 77.8%-96.2%), specificity of 82.1% (95% CI, 77.4%-86.6%), and a negative predictive value (NPV) of 97.9% (95% CI, 95.3%-99.1%) for bacterial infection. In comparison, the sensitivity of procalcitonin measurement was 28.6% (95% CI, 16.2%-40.9%; P < .001), the specificity was 87.0% (95% CI, 82.7%-90.7%; P = .006), and the NPV was 87.6% (95% CI, 85.5%-89.5%; P < .001). When stratified into likelihood groups, the HR-B/V test had an NPV of 98.9% (95% CI, 96.1%-100%) for bacterial infection in the viral very likely group and a positive predictive value of 63.4% (95% CI, 47.2%-77.9%) for bacterial infection in the bacterial very likely group. The HR-B/V test correctly identified 30 of 33 participants (90.9%) with acute COVID-19 as having a viral infection. Conclusions and Relevance: In this study, the HR-B/V test accurately discriminated bacterial from viral infection among patients with febrile ARI and was superior to procalcitonin measurement. The findings suggest that an accurate point-of-need host response test with high NPV may offer an opportunity to improve antibiotic stewardship and patient outcomes.

Investigating the morphological transitions in an associative surfactant ternary system.

Associative surfactants systems involving polar oils have recently been shown to stabilize immiscible liquids by forming nanostructures at the liquid interface and have been used to print soft materials. Although these associating surfactant systems show great promise for creating nanostructured soft materials, a fundamental understanding of the self-assembly process is still unknown. In this study, a ternary phase diagram for a system of cationic surfactant cetylpyridinium chloride monohydrate (CPCl), a polar oil (oleic acid), and water is established using experiment and simulation, to study the equilibrium phase behavior. A combination of visual inspection, small-angle X-ray scattering (SAXS), and rheological measurements was employed to establish the phase behavior and properties of the self-assembled materials. Dissipative particle dynamics (DPD) is used to simulate the formation of the morphologies in this system and support the experimental results. The ternary phase diagram obtained from the simulations agrees with the experimental results, indicating the robustness of the computational simulation as a supplement to the mesoscale experimental systems. We observe that morphological transitions (e.g., micelle-to-bilayer and vesicle-to-lamellar) are in agreement between experiments and simulations across the ternary diagram. DPD simulations correctly predict that associative surfactant systems form new nanoscale phases due to the co-assembly of the components. The established ternary phase diagram and the DPD model pave the way towards predicting and controlling the formation of different mesostructures like lamellar or vesicles, opening new avenues to tailor and synthesize desired morphologies for applications related to liquid-in-liquid 3D printing.

Lewis Adduct-Induced Phase Transitions in Polymer/Solvent Mixtures.

Functionalization-induced phase transitions in polymer systems in which a postpolymerization reaction drives polymers to organize into colloidal aggregates are a versatile method to create nanoscale structures with applications related to biomedicine and nanoreactors. Current functionalization methods to stimulate polymer self-assembly are based on covalent bond formation. Therefore, there is a need to explore alternative reactions that result in noncovalent bond formation. Here, we demonstrate that when the Lewis acid, tris(pentafluorophenyl) borane (BCF), is added to a solution containing poly(4-diphenylphosphino styrene) (PDPPS), the system will either macrophase-separate or form micelles if PDPPS is a homopolymer or a block in a copolymer, respectively. The Lewis adduct-induced phase transition is hypothesized to result from the favorable interaction between the PDPPS and BCF, which results in a negative interaction parameter (χ). A modified Flory-Huggins model was used to determine the predicted phase behavior for a ternary system composed of a polymer, a solvent, and a small molecule. The model indicates that there is a demixing region (i.e., macrophase separation) when the polymer and small molecule have favorable interactions (e.g., χ < 0) and that the phase separation region coincides well with the experimentally determined two-phase region for mixtures containing PDPPS, BCF, and toluene. The work presented here highlights that Lewis adduct-induced phase separation is a new approach to functionalization-induced self-assembly (FISA) and that ternary mixtures will undergo phase separation if two of the components exhibit a sufficiently negative χ.

Zwitterions Raise the Dielectric Constant of Soft Materials.

Materials exhibiting high dielectric constants (ϵ_{s}) are critical for energy storage and actuators. A successful approach to increase ϵ_{s} is to incorporate polar additives (with high ϵ_{s}) but controlling the resulting dispersion state is difficult. Here, we show that significant ϵ_{s} increases are realized by adding zwitterions, which are small molecules with a cation and an anion separated by covalent bonds. The increase in ϵ_{s} with zwitterion addition is attributed to the large molecular dipole of zwitterions, ranging from 35 to 41 D, as experimentally quantified and confirmed using density functional theory. At elevated zwitterion concentration in an ethylene glycol medium, there is a nonlinear increase of ϵ_{s} that eventually saturates due to the strong Coulombic interactions between zwitterions. The presented work provides a fundamental molecular understanding of why zwitterions are effective additives in boosting ϵ_{s} in soft materials.