Safety evaluation of a buffer used in the lyophilization of canine platelets: type I hypersensitivity reaction in dogs caused by bovine serum albumin.

Introduction: The present study was designed to evaluate the safety of substances generally used in the preparation of lyophilized platelet products (LPPs) because the possibility of an immune response to bovine serum albumin (BSA) was considered high when using previously described technology. Methods: An intradermal skin test, followed by a drug provocation test, was conducted to observe adverse events and identify the substances responsible for an immune response. Five male beagles (2 years old) weighing 12-14 kg were used. The dogs were clinically healthy and had no history of medication use. An intradermal skin test was conducted with each substance [i.e., 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid, sodium chloride, potassium chloride, sodium bicarbonate, theophylline, trehalose, and BSA] used in the conventional freeze-dry method. Results: In the intradermal skin test, three dogs tested positive at the BSA injection site and showed clinical signs after the intradermal injection, including nausea and vomiting. For the drug provocation test, all dogs received two intravenous injections of an LPP buffer solution. The initial injection was devoid of BSA, whereas the subsequent injection contained BSA. The three dogs that had reacted to BSA in the intradermal skin test exhibited adverse events such as lethargy, vomiting, and nausea immediately after intravenous injection of the LPP buffer containing BSA. All dogs recovered uneventfully after symptomatic treatment in both tests. Discussion: The high incidence and severity of type I hypersensitivity reactions observed in this study suggested that BSA is unsuitable as a component of canine LPP.

Direct Solution-Phase Synthesis and Functionalization of 2D WSe2 for Ambient Stability.

2H phase tungsten diselenide (WSe2 ) is a p-type 2D semiconductor from the transition metal dichalcogenides (TMDs) family with unique optoelectrical properties. Solution phase production of atomically thin WSe2 is challenging due to its instability under ambient conditions. We present a highly efficient and scalable solution method for simultaneously exfoliating and functionalizing WSe2 by leveraging the non-covalent interaction between mercapto-group and bulk WSe2 . Single and few-layer 2H phase pure WSe2 sheets of lateral size up to 5 µm with minimal basal plane defects, as revealed by XPS, Raman and FTIR spectroscopy, are produced in a water-ethanol mixture. Remarkably, WSe2 dispersion remains stable even at high concentrations (10 mg/mL) and exhibited high colloidal stability with a shelf-life exceeding a year. The findings from our study suggest that through precise manipulation of intercalation chemistry, mass production of solution-processable phase-sensitive 2D materials such as WSe2 can be achieved. This advancement holds great potential for facilitating their practical utilization in various real-world applications.

Scalable Solution Phase Synthesis of 2D Siloxene via a Two-Step Interlayer Expansion Process.

Two-dimensional (2D) siloxene is attracting considerable research interest recently principally owing to its inherent compatibility with silicon-based semiconductor technology. -The synthesis of siloxene has been mostly limited to multilayered structures using traditional topochemical reaction procedures. Herein, we report high-yield synthesis of single to few-layer siloxene nanosheets by developing a two-step interlayer expansion and subsequent liquid phase exfoliation procedure. Our protocol enables high-yield production of few-layer siloxene nanosheets with a lateral dimension of up to 4 µm and thickness ranging from 0.8 to 4.8 nm, corresponding to single to a few layers, well stabilized in water. The atomically flat nature of exfoliated siloxene can be exploited for the construction of 2D/2D heterostructure membranes via typical solution processing. We demonstrate highly ordered graphene/siloxene heterostructure films with synergistic mechanical and electrical properties, which deliver noticeably high device capacitance when assembled into a coin cell symmetric supercapacitor device structures. Additionally, we demonstrate that the mechanically flexible exfoliated siloxene-graphene heterostructure enables its direct use in flexible and wearable supercapacitor applications.

Atomically Flat, 2D Edge-Directed Self-Assembly of Block Copolymers.

Nanoscale shape engineering is an essential requirement for the practical use of 2D materials, aiming at precisely customizing optimal structures and properties. In this work, sub-10-nm-scale block copolymer (BCP) self-assembled nanopatterns finely aligned along the atomic edge of 2D flakes, including graphene, MoS2 , and h-BN, are exploited for reliable nanopatterning of 2D materials. The underlying mechanism for the alignment of the self-assembled nanodomains is elucidated based on the wetting layer alternation of the BCP film in the presence of intermediate 2D flakes. The resultant highly aligned nanocylinder templates with remarkably low levels of line edge roughness (LER) and line-width roughness (LWR) yield a sub-10-nm-wide graphene nanoribbon (GNR) array with noticeable switching characteristics (on-to-off ratio up to ≈6 × 104 ).

Multilevel Self-Assembly of Block Copolymers and Polymer Colloids for a Transparent and Sensitive Gas Sensor Platform.

The recent emerging significance of the Internet of Things (IoT) demands sensor devices to be integrated with many different functional structures and devices while conserving their original functionalities. To this end, optical transparency and mechanical flexibility of sensor devices are critical requirements for optimal integration as well as high sensitivity. In this work, a transparent, flexible, and sensitive gas sensor building platform is introduced by using multilevel self-assembly of block copolymers (BCPs) and polystyrene (PS) colloids. For the demonstration of an H2 gas sensor, a hierarchically porous Pd metal mesh structure is obtained by overlaying the two different patterned template structures with synergistic, distinctive characteristic length scales. The hierarchical Pd mesh shows not only high transparency over 90% but also superior sensing performance in terms of response and recovery time owing to enhanced Pd-to-hydride ratio and short H2 diffusion lengths from the enlarged active surface areas. The hierarchical morphology also endows high mechanical flexibility while securing reliable sensing performance even under severe mechanical deformation cycles. Our scalable self-assembly based multiscale nanopatterning offers an intriguing generalized platform for many different multifunctional devices requiring hidden in situ monitoring of environmental signals.

Application of 2D Materials for Adsorptive Removal of Air Pollutants.

Air pollution is on the priority list of global safety issues, with the concern of fatal environmental and public health deterioration. 2D materials are potential adsorbent materials for environmental decontamination, owing to their high surface area, manageable interlayer binding, large surface-to-volume ratio, specific binding capability, and chemical, thermal, and mechanistic stability. Specifically, graphene oxide and reduced graphene oxide have been attracting attention, taking advantage of their low cost synthesis, excessive oxygen containing surface functionalities, and intrinsic aqueous dispersibility, making them desirable for the development of cost-effective, high performance air filters. Many different material designs have been proposed to expand their filtration capability, including the functionalization and integration with other metals and metal oxides, which act not only as binding agents to the target pollutants but also as antimicrobial agents. This review highlights the advantages and drawbacks of 2D materials for air filtration and summarizes the interrelationships among various strategies and the resultant filtration performance in terms of structural engineering, morphology control, and material compositions. Finally, potential future directions are suggested toward the idealized designs of 2D material based air filters.

Optimization for size separation of graphene oxide sheets by flow/hyperlayer field-flow fractionation.

Graphene oxide (GO)-a chemical derivative of graphene with numerous oxygen functional groups on its surface-has attracted considerable interest because of its intriguing properties in relation to those of pristine graphene. In addition to the inherent wide lateral size distribution of GO sheets arising from the typical oxidative exfoliation of graphite, control of the lateral size of GO is critical for desired GO-based applications. Herein, flow/hyperlayer field-flow fractionation (flow/hyperlayer FFF) is optimized to separate GO sheets by lateral dimensions. Optimized fractionation is achieved by investigating the influences of carrier solvent, channel thickness, and flow rate conditions on the steric/hyperlayer separation of GO sheets by flow FFF. Due to the strong hydrodynamic lift forces of extremely thin GO sheets, a thick flow FFF channel (w = 350 µm) and a very low field strength are required to retain the GO sheets within the channel. GO sheets with narrow size fractions are successfully collected from two different graphite sources during flow/hyperlayer FFF runs and are examined to verify the size evolution. Considering the average lateral diameter of the GO fraction calculated on the basis of the assumption of a circular disk shape, the retention of the GO sheets is 2.2-5.0 times faster than that of spherical particles of the same diameter. This study demonstrates that through flow/hyperlayer FFF, the size distribution of GO sheets can be determined and narrow size fractions can be collected (which is desirable for GO-based applications), which are commonly influenced by the GO lateral dimension.

Innate immunity and protective effects of orally administered betaine against viral and bacterial diseases in the olive flounder Paralichthys olivaceus (Temminck & Schlegel).

Sustainable methods that increase farmed fish yield while controlling infections are required to prevent economic losses in aquaculture farms. In this study, we evaluated the effects of betaine-supplemented (0%, 0.1%, 0.5%, and 1.0%) feed on the growth and immunity of the olive flounder Paralichthys olivaceus. Feed conversion ratios, post-infection cumulative mortality rates and innate immune responses were monitored. Weight gain was significantly higher with 0.5% and 1.0% than with 0% and 0.1% betaine-supplemented feed. Lysozyme activity was highest with 1.0% betaine. Respiratory burst activity was highest with 0.5% and 1.0% betaine. Serum bactericidal activity against Edwardsiella tarda was highest with 1.0% betaine (40% increase in survival rates compared with those in the control). Furthermore, serum virucidal activity against the viral haemorrhagic septicaemia virus (VHSV) was higher with 1.0% betaine than with other concentrations. With 0.5% and 1.0% betaine, the survival rates against VHSV were higher than those in the control until day 11, after which they declined. Our study suggests that betaine is a promising agent for promoting the growth of and enhancing immunity against E. tarda in olive flounders. Our findings may further contribute to developing necessary alternatives to conventional antibiotics in fish farming.

A 2D Ultrathin Nanopatterned Interlayer to Suppress Lithium Dendrite Growth in High-Energy Lithium-Metal Anodes.

A novel strategy for robust and ultrathin (<1 µm) multilayered protective structures to address uncontrolled Lithium (Li) dendrite growth at Li-metal battery anodes is reported. Synergetic interaction among Ag nanoparticles (Ag NPs), reduced graphene oxide (rGO) films, and self-assembled block-copolymer (BCP) layers enables effective suppression of dendritic Li growth. While Ag NP layer confines the growth of Li metal underneath the rGO layer, BCP layer facilitates the fast and uniformly distributed flux of Li-ion transport and mechanically supports the rGO layer. Notably, highly aligned nanochannels with ≈15 nm diameter and ≈600 nm length scale interpenetrating within the BCP layer offer reversible well-defined pathways for Li-ion transport. Dramatic stress relaxation with the multilayered structure is confirmed via structural simulation considering the mechanical stress induced by filamentary-growth of Li metal. Li-metal anodes modified with the protective layer well-maintain stable reaction interfaces with limited solid-electrolyte interphase formation, yielding outstanding cycling stability and enhanced rate capability, as demonstrated by the full-cells paired with high-loading of LiFePO4 cathodes. The idealized design of multilayer protective layer provides significant insight for advanced Li-metal anodes.

Wide-Range Size Fractionation of Graphene Oxide by Flow Field-Flow Fractionation.

Many interesting properties of 2D materials and their assembled structures are strongly dependent on the lateral size and size distribution of 2D materials. Accordingly, effective size separation of polydisperse 2D sheets is critical for desirable applications. Here, we introduce flow field-flow fractionation (FlFFF) for a wide-range size fractionation of graphene oxide (GO) up to 100 µm. Two different separation mechanisms are identified for FlFFF, including normal mode and steric/hyperlayer mode, to size fractionate wide size-distributed GOs while employing a crossflow field for either diffusion or size-controlled migration of GO. Obviously, the 2D GO sheet reveals size separation behavior distinctive from typical spherical particles arising from its innate planar geometry. We also investigate 2D sheet size-dependent mechanical and electrical properties of three different graphene fibers produced from size-fractionated GOs. This FlFFF-based size selection methodology can be used as a generic approach for effective wide-range size separation for 2D materials, including rGO, TMDs, and MXene.

Block Copolymer Nanopatterning for Nonsemiconductor Device Applications.

Block copolymer (BCP) nanopatterning has emerged as a versatile nanoscale fabrication tool for semiconductor devices and other applications, because of its ability to organize well-defined, periodic nanostructures with a critical dimension of 5-100 nm. While the most promising application field of BCP nanopatterning has been semiconductor devices, the versatility of BCPs has also led to enormous interest from a broad spectrum of other application areas. In particular, the intrinsically low cost and straightforward processing of BCP nanopatterning have been widely recognized for their large-area parallel formation of dense nanoscale features, which clearly contrasts that of sophisticated processing steps of the typical photolithographic process, including EUV lithography. In this Review, we highlight the recent progress in the field of BCP nanopatterning for various nonsemiconductor applications. Notable examples relying on BCP nanopatterning, including nanocatalysts, sensors, optics, energy devices, membranes, surface modifications and other emerging applications, are summarized. We further discuss the current limitations of BCP nanopatterning and suggest future research directions to open up new potential application fields.

Effect of CES1 genetic variation on enalapril steady-state pharmacokinetics and pharmacodynamics in healthy subjects.

AIMS: Enalapril is a prodrug and needs to be activated by carboxylesterase 1 (CES1). A previous in vitro study demonstrated the CES1 genetic variant, G143E (rs71647871), significantly impaired enalapril activation. Two previous clinical studies examined the impact of G143E on single-dose enalapril PK (10 mg); however, the results were inconclusive. A prospective, multi-dose, pharmacokinetics and pharmacodynamics (PK/PD) study was conducted to determine the impact of the CES1 G143E variant on enalapril steady-state PK and PD in healthy volunteers. METHODS: Study participants were stratified to G143E non-carriers (n = 15) and G143E carriers (n = 6). All the carriers were G143E heterozygotes. Study subjects received enalapril 10 mg daily for seven consecutive days prior to a 72 hour PK/PD study. Plasma concentrations of enalapril and its active metabolite enalaprilat were quantified by an established liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: The CES1 G143E carriers had 30.9% lower enalaprilat Cmax (P = 0.03) compared to the non-carriers (38.01 vs. 55.01 ng/mL). The carrier group had 27.5% lower AUC0-∞ (P = 0.02) of plasma enalaprilat compared to the non-carriers (374.29 vs. 515.91 ng*h/mL). The carriers also had a 32.3% lower enalaprilat-to-enalapril AUC0-∞ ratio (P = 0.003) relative to the non-carriers. The average maximum reduction of systolic blood pressure in the non-carrier group was approximately 12.4% at the end of the study compared to the baseline (P = 0.001). No statistically significant blood pressure reduction was observed in the G143E carriers. CONCLUSIONS: The CES1 loss-of-function G143E variant significantly impaired enalapril activation and its systolic blood pressure-lowering effect in healthy volunteers.

Highly Aligned Carbon Nanowire Array by E-Field Directed Assembly of PAN-Containing Block Copolymers.

Nanoscale engineering of carbon materials is immensely demanded in various scientific areas. We present highly ordered nitrogen-doped carbon nanowire arrays via block copolymer (BCP) self-assembly under an electric field. Large dielectric constant difference between distinct polymer blocks offers rapid alignment of PMMA-b-PAN self-assembled nanodomains under an electric field. Lithographic patterning of the graphene electrode as well as straightforward thermal carbonization of the PAN block creates well-aligned carbon nanowire device structures. Diverse carbon nanopatterns including radial and curved arrays can be readily assembled by the modification of electrode shapes. Our carbon nanopatterns bear a nitrogen content over 26%, highly desirable for NO2 sensing, as the nitrogen element acts as adsorption sites for NO2 molecules. Aligned carbon nanowire arrays exhibits a 6-fold enhancement of NO2 sensitivity from a randomly aligned counterpart. Taking advantage of well-established benefits from device-oriented BCP nanopatterning, our approach proposes a viable route to highly ordered carbon nanostructures compatible to next-generation device architectures.

The Addition of Anaerobic Blood Cultures for Pediatric Patients with Concerns for Bloodstream Infections: Prevalence and Time to Positive Cultures.

Anaerobes are an important but uncommon cause of bloodstream infections (BSIs). For pediatric patients, routine inclusion of an anaerobic blood culture alongside the aerobic remains controversial. We implemented automatic anaerobic blood culture alongside aerobic blood cultures in a pediatric emergency department (ED) and sought to determine changes in recovery of obligate and facultative anaerobes. This was a cohort study in a pediatric ED (August 2015 to July 2018) that began in February 2017. Blood culture positivity results for true pathogens and contaminants were assessed, along with a secondary outcome of time to positivity (TTP) of blood culture. A total of 14,180 blood cultures (5,202 preimplementation and 8,978 postimplementation) were collected, with 8.8% (456) and 7.1% (635) positive cultures in the pre- and postimplementation phases, respectively. Of 635 positive cultures in the postimplementation phase, aerobic blood cultures recovered 7.6% (349/4,615), whereas anaerobic blood cultures recovered 6.6% (286/4,363). In 211/421 (50.0%) paired blood cultures, an organism was recovered in both cultures. The number of cases where organisms were only recovered from an aerobic or an anaerobic bottle in the paired cultures were 126 (30.0%) and 84 (20.0%), respectively. The TTP was comparable regardless of bottle type. Recovery of true pathogens from blood cultures was approximately 7 h faster than recovery of contaminants. Although inclusion of anaerobic blood cultures only recovered 2 (0.69%) obligate anaerobes, it did allow for recovery of clinically significant pathogens that were negative in aerobic blood cultures and supports the routine collection of both bottles in pediatric patients with a concern of bloodstream infections.

Conformal 3D Nanopatterning by Block Copolymer Lithography with Vapor-Phase Deposited Neutral Adlayer.

Block copolymer (BCP) lithography is an effective nanopatterning methodology exploiting nanoscale self-assembled periodic patterns in BCP thin films. This approach has a critical limitation for nonplanar substrate geometry arising from the reflow and modification of BCP films upon the thermal or solvent annealing process, which is inevitable to induce the mobility of BCP chains for the self-assembly process. Herein, reflow-free, 3D BCP nanopatterning is demonstrated by introducing a conformally grown adlayer by the initiated chemical vapor deposition (iCVD) process. A highly cross-linked poly(divinylbenzene) layer was deposited directly onto the BCP thin film surface by iCVD, which effectively prevented the reflow of BCP thin film during an annealing process. BCP nanopatterns could be stabilized on various substrate geometry, including a nonplanar deformed polymer substrate, a pyramid shape substrate, and a graphene fiber surface. A fiber-type hydrogen evolution reaction (HER) catalyst is suggested by stabilizing lamellar Pt nanopatterns on severely rough graphene fiber surfaces.

A Pediatric Profile of a Homeless Patient in San Jose, California.

The causes of homelessness are complex and poorly understood. This paper describes the homeless population in Santa Clara County, California in terms of Adverse Childhood Events, Traumatic Brain Injuries (TBIs), and family breakdown. Respondents reported severely traumatic childhoods; 78.7% grew up in a household with a person with drug or alcohol dependence and 64.6% endured psychological abuse as a child. Seventy-six percent of subjects recalled at least one TBI, 58.4% with loss of consciousness. Nineteen percent were in foster care as children and 40.2% reported having someone other than a parent as a primary caregiver. Fifty-three percent felt they had moved too much as children, and 37.5% had experienced homelessness as children. Santa Clara County has both the highest median income and the highest rate of unsheltered homelessness in the nation. Leaders and community members should work together to improve the lives of the home-less and to prevent another generation of homeless people.

Perceived timeliness of referral to hospice palliative care among bereaved family members in Korea.

PURPOSE: We aimed to explore the perceived timeliness of referral to hospice palliative care unit (HPCU) among bereaved family members in Korea and factors associated therewith. METHODS: Cross-sectional questionnaire survey was performed for bereaved family members of patients who utilized 40 designated HPCUs across Korea. The questionnaire assessed whether admission to the HPCU was "too late" or "appropriate" and the Good Death Inventory (GDI). RESULTS: A total of 383 questionnaires were analyzed. Of participants, 25.8 % replied that admission to HPCU was too late. Patients with hepatobiliary cancer, poor performance status, abnormal consciousness level, and unawareness of terminal status were significantly related with the too late perception. Family members with younger age and being a child of the patient were more frequently noted in the too late group. Ten out of 18 GDI scores were significantly lower in the too late group. Multiple logistic regression analysis revealed patients' unawareness of terminal status, shorter stay in the HPCU, younger age of bereaved family, and lower scores for two GDI items (staying in a favored place, living without concerning death or disease) were significantly associated with the too late group. CONCLUSIONS: To promote timely HPCU utilization and better quality of end of life care, patients need to be informed of the terminal status and their preference should be respected.

Partial maintenance of auditory-based cognitive training benefits in older adults.

The potential for short-term training to improve cognitive and sensory functions in older adults has captured the public's interest. Initial results have been promising. For example, eight weeks of auditory-based cognitive training decreases peak latencies and peak variability in neural responses to speech presented in a background of noise and instills gains in speed of processing, speech-in-noise recognition, and short-term memory in older adults. But while previous studies have demonstrated short-term plasticity in older adults, we must consider the long-term maintenance of training gains. To evaluate training maintenance, we invited participants from an earlier training study to return for follow-up testing six months after the completion of training. We found that improvements in response peak timing to speech in noise and speed of processing were maintained, but the participants did not maintain speech-in-noise recognition or memory gains. Future studies should consider factors that are important for training maintenance, including the nature of the training, compliance with the training schedule, and the need for booster sessions after the completion of primary training.

Training changes processing of speech cues in older adults with hearing loss.

Aging results in a loss of sensory function, and the effects of hearing impairment can be especially devastating due to reduced communication ability. Older adults with hearing loss report that speech, especially in noisy backgrounds, is uncomfortably loud yet unclear. Hearing loss results in an unbalanced neural representation of speech: the slowly-varying envelope is enhanced, dominating representation in the auditory pathway and perceptual salience at the cost of the rapidly-varying fine structure. We hypothesized that older adults with hearing loss can be trained to compensate for these changes in central auditory processing through directed attention to behaviorally-relevant speech sounds. To that end, we evaluated the effects of auditory-cognitive training in older adults (ages 55-79) with normal hearing and hearing loss. After training, the auditory training group with hearing loss experienced a reduction in the neural representation of the speech envelope presented in noise, approaching levels observed in normal hearing older adults. No changes were noted in the control group. Importantly, changes in speech processing were accompanied by improvements in speech perception. Thus, central processing deficits associated with hearing loss may be partially remediated with training, resulting in real-life benefits for everyday communication.