Biological SERS-active sensor platform based on flexible silk fibroin film and gold nanoislands.

In contrast to conventional surface-enhanced Raman scattering (SERS) platforms implemented on non-biological substrates, silk fibroin has the unique advantages of long-term biosafety and controllable biodegradability for in vitro and in vivo biomedical applications, as well as flexibility and process-compatibility. In this study, a silk fibroin film was developed to fabricate a flexible SERS sensor template with nanogap-rich gold nanoislands. The proposed biological SERS platform presents fairly good enhancements in detection performance such as detection limit, sensitivity, and signal-to-noise ratio. In particular, the sensitivity improvement was by more than 10 times compared to that of the counterpart sample, and an excellent spatial reproducibility of 2.8% was achieved. In addition, the near-field calculation results were consistent with the experimental results, and the effect of surface roughness of the silk substrate was investigated in a quantitative way. It is believed that biological SERS-active sensors could provide the potential for highly sensitive, cost-effective, and easily customizable nanophotonic platforms that include new capabilities for future healthcare devices.

Combining Participatory Mapping and Geospatial Analysis Techniques to Assess Wildfire Risk in Rural North Vietnam.

Participatory mapping (PM) is a valuable research tool for assessing fire risk, especially in regions where data are difficult to collect or inconsistent; in such areas, the integration between crowdsourced data and geospatial techniques plays a fundamental role in gathering more consistent and reliable information. This study combines a participatory (community-based) mapping approach with geospatial techniques to assess fire risk in Van Chan district, northern Vietnam, an area where the economy relies mainly on forestry activities. Local stakeholders designed a map of wildfires, which was modelled as a function of a set of physical and socio-economic variables. A fire-probability map of the district was obtained and compared with MODIS data (2000-2020). The results suggest that higher fire probability occurs in areas with lower human pressure, and they provide information on related socio-economic drivers that affect this phenomenon. This study highlights the importance of combining participatory approaches and geospatial techniques to assess fire dynamics and prevent wildfires in terms of understanding and predicting the risks. The involvement of local communities is fundamental to this innovative participatory approach with regard to better supporting decision-making and prevention actions and to developing fire control management guidelines.

Identification of bacterial factors involved in type 1 fimbria expression using an Escherichia coli K12 proteome chip.

Type 1 fimbriae are filamentous structures on Escherichia coli. These structures are important adherence factors. Because binding to the host cells is the first step of infection, type 1 fimbria is an important virulence factor of pathogenic E. coli. Expression of type 1 fimbria is regulated by a phase variation in which each individual bacterium can alternate between fimbriated (phase-ON) and nonfimbriated (phase-OFF) states. The phase variation is regulated by the flipping of the 314-bp fimS fragment, which contains the promoter driving the expression of the genes required for the synthesis of type 1 fimbria. Thus, the bacterial proteins able to interact with fimS are likely to be involved in regulating the expression of type 1 fimbria. To identify novel type 1 fimbria-regulating factors, we used an E. coli K12 proteome chip to screen for the bacterial factors able to interact with a 602-bp DNA fragment containing fimS and its adjacent regions. The Spr protein was identified by the proteome chip-based screening and further confirmed to be able to interact with fimS by electrophoretic mobility shift assay. Deletion of spr in the neonatal meningitis E. coli strain RS218 significantly increased the ratio of the bacterial colonies that contained the type 1 fimbria phase-ON cells on agar plates. In addition, Spr interfered with the interactions of fimS with the site-specific recombinases, FimB and FimE, which are responsible for mediating the flipping of fimS. These results suggest that Spr is involved in the regulation of type 1 fimbria expression through direct interaction with the invertible element fimS. These findings facilitate our understanding of the regulation of type 1 fimbria.

Accelerated and Biopredictive In Vitro Release Testing Strategy for Single Agent and Combination Long-Acting Injectables.

The purpose of this study was to develop an in vitro release testing (IVRT) strategy to predict the pre-clinical performance of single agent and combination long acting injectable (LAI) suspension products. Two accelerated IVRT methods were developed using USP apparatus 2 to characterize initial, intermediate, and terminal phases of drug release. Initial and intermediate phases were captured using a suspension cup with moderate agitation to ensure a constant, low surface area exposure of the LAI suspension to the release media. The terminal phase was obtained by exposing the LAI suspension to a high initial paddle speed. This resulted in smaller suspension particulates with high cumulative surface area that were dispersed throughout the release media, enabling rapid drug release. The in vitro release profiles obtained with these two methods in 48 h or less were independently time scaled to reflect the in vivo time scale of approximately 1800 h. Level-A in vitro in vivo correlations (IVIVCs) were separately developed for each method and active pharmaceutical ingredient (API) using in vivo absorption profiles obtained by deconvolution of rat plasma concentration-time profiles. The IVIVCs were successfully validated for each API. This work provides a framework for evaluating individual phases of drug release of complex LAIs to ultimately predict their in vivo performance.

The spatialization of decent work and the role of employability empowerment for minority ethnic young people in emerging economies.

Global rises in precarious labour conditions have prompted further empirical work in Decent Work, a special category of employment characterised by equitable pay, treatment, and healthy working conditions. Despite this, research has tended to be conducted in developed countries with privileged groups such as those with typical working arrangements and rely on psychologically framed individual characteristics to explain marginalising factors. We propose a more sociologically framed, spatialised perspective on Decent Work which posits that marginalising factors are spatially variable and determined but moderated by employability empowerment. We measure our propositions across three spatially different sites of Vietnam through (1) a survey of minority ethnic students and graduates (N = 1071) and (2) a survey of stakeholders involved in the recruitment and employment of this group (N = 204). We find support for most of our propositions and call for more spatialised empirical work in the field of Decent Work.

A simple and universal headspace GC-FID method for accurate quantitation of volatile amines in pharmaceuticals.

Volatile amines are reagents commonly used in pharmaceutical manufacturing of intermediates, active pharmaceutical ingredients (APIs), and drug products as participating regents for chemical reactions and optimization of product yield. Due to their compound specific daily allowable intake, residual volatile amines are required by regulatory agencies to be monitored and controlled in pharmaceutical products intended for human consumption. However, the accurate quantification of residual volatile amines in pharmaceutical entities can often be challenging as these analytes may chemically react and/or interact with the sample matrix. Herein, we describe a simple and universal headspace gas chromatography with flame ionization detection (HS-GC-FID) method capable of separating 14 commonly used volatile amines. The chemical activity of the volatile amines with the API matrix were mitigated by using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as an additive to reduce matrix effects in conventional high-boiling diluents. The addition of DBU drastically improved the detectability and method accuracy of the residual volatile amines in an acidic API, namely, Ketoprofen®. Additionally, DBU was employed as a GC deactivation reagent to ensure interfacial adsorption of the analytes to GC components were reduced, thereby improving method precision. Method validation showed acceptable linearity, limit of detection, limit of quantitation, solution stability, precision, and robustness. Separation specificity, evaluated by observing the chromatographic resolution of the volatile amines with one-another and against a set of 23 common residual solvents, were shown to be acceptable for most peak pairs.

Versatile Effects of GABA Oolong Tea on Improvements in Diastolic Blood Pressure, Alpha Brain Waves, and Quality of Life.

Emerging evidence has demonstrated that using a new manufacturing technology to produce γ-aminobutyric acid (GABA)-fortified oolong (GO) tea could relieve human stress and exert versatile physiological benefits. The purpose of this human study was to investigate the therapeutic effects of daily GO tea consumption on improvements in blood pressure, relaxation-related brain waves, and quality of life (QOL) over a period of 28 consecutive days. Total polyphenols, major catechins, and free amino acids were analyzed via an HPLC assay. Changes in heart rate, blood pressure, α brain waves (index of relaxation), and the eight-item QOL score were investigated on days 0, 7, 14, 21, and 28. The chemical analysis results showed that GO tea contained the most abundant amino acids and GABA, contributing to the relaxation activity. Among all study participants, the daily consumption of GO tea could reduce systolic blood pressure on day 21 and diastolic blood pressure on day 28 (p < 0.05 for both). For participants with pre-hypertension, GO tea could effectively reduce heart rate and systolic and diastolic blood pressure on day 28 (p < 0.05). At the end of the study, incremental changes in alpha brain waves and QOL scores were also demonstrated (p < 0.05 for both). This study suggests that GO tea might potentially serve as a natural source for alternative therapy to improve blood pressure, stress relief, and QOL.

Ultraviolet photoinitiated on-fiber copolymerization of ionic liquid sorbent coatings for headspace and direct immersion solid-phase microextraction.

A high-throughput method for the production of solid-phase microextraction (SPME) sorbent coatings via ultraviolet (UV) photoinitiated copolymerization of ionic liquid (IL) monomers on a fused silica support is described. The copolymerization of monocationic and dicationic IL cross-linkers was performed "on-fiber" using UV initiated free radical polymerization. Mixtures composed of various amounts of the IL cross-linker, UV initiator (DAROCUR 1173), and IL monomer were dip-coated onto an etched and derivatized fused silica support and placed in a high-capacity UV reactor. The method requires no organic dispersive solvent and is much more rapid compared to traditional methods in which polymeric ionic liquid (PIL) sorbent coatings are prepared by 2,2'-azobis(2-methylpropionitrile) (AIBN)-initiated polymerization. Two ionic liquid-based cross-linkers, namely, 1,8-di (3-vinylimidazolium) octane dibromide ([(VIM)(2)C(8)] 2[Br]) and 1,12-di (3-vinylimidazolium) dodecane dibromide ([(VIM)(2)C(12)] 2[Br]), were copolymerized with an ionic liquid monomer, 1-vinyl-3-hexylimidazolium chloride ([VHIM][Cl]), to produce polar cross-linked PIL-based SPME sorbent coatings. The cross-linking and immobilization of these coatings make them particularly applicable in direct immersion SPME. The coatings were applied in the extraction of polar analytes, including alcohols, aldehydes, and esters, from aqueous solutions using headspace and direct immersion SPME gas chromatography mass spectrometry (GC/MS). Compared to linear PIL-based sorbent coatings containing the same anions, the cross-linked PIL-based coatings exhibited higher thermal stability and lower bleed, making them ideal for GC/MS. Recovery experiments were performed in deionized, well, and river water. The structural integrity of the sorbent coatings, as well as their analytical precision, was not diminished after 90 extractions from complex samples using headspace and direct immersion SPME.

Use of higher thromboelastogram transfusion values is not associated with greater blood loss in liver transplant surgery.

Plasma-containing products are given during the pre-anhepatic stage of liver transplant surgery to correct abnormal thromboelastogram (TEG) values and prevent blood loss due to coagulation defects. However, evidence suggests that abnormal TEG results do not always predict bleeding. We questioned what effect using higher TEG values to initiate treatment would have on blood loss. A single transfusion protocol was used for all patients who underwent liver transplantation between 2007 and 2010. Thirty-eight patients received coagulation products when standard TEG cutoff values were exceeded, whereas another 39 patients received coagulation products when the TEG values were 35% greater than normal. The results of postoperative coagulation tests for total blood loss and the use of blood products were compared for the 2 groups. When the critical TEG values for transfusion were higher, significantly fewer units of fresh frozen plasma (5.58 ± 6.49 versus 11.53 ± 6.66 U) and pheresis platelets (1.84 ± 1.33 versus 3.55 ± 1.43 U) were used. There were no differences in blood loss or postoperative blood product use. In conclusion, the use of higher critical TEG values to initiate the transfusion of plasma-containing products is not associated with increased blood loss. Further testing is necessary to identify what TEG value predicts bleeding due to a deficit in coagulation factors.

Reading Attitudes in Vietnam: Initial Study of the Early School Years.

Whereas cognitive and linguistic factors for learning to read have been extensively studied, less is known about affective factors including children's attitudes toward reading. Studies primarily from English-speaking and Western countries show gradual declines in reading attitudes in elementary school (McKenna et al., 1995) and a positive association between reading attitudes and achievement (Petscher, 2010). Children from Asian and African countries are underrepresented in this literature; whether these patterns can be generalized across cultures needs further investigation. This longitudinal study examined the reading attitudes of 84 children in Vietnam from grades 1 to 2 and their relations to reading performance, as measured by translated and adapted versions of the Elementary Reading Attitude Survey and Early Grade Reading Assessment, respectively. This sample from Vietnam showed a small decline in reading attitudes over time, particularly in attitudes toward academic reading. However, children on average reported feeling happy about reading in both grades. Correlations revealed different patterns of association between reading attitudes and performance based on the reading measure employed, grade level, and type of reading in question (academic versus recreational). In grade 2, reading attitudes explained unique variance in reading comprehension even after text fluency and mother's education were considered. We present a margins plot to visualize the role of reading attitudes on reading comprehension. We discuss educational implications and future directions.

"Employability in context": graduate employability attributes expected by employers in regional Vietnam and implications for career guidance.

This article examines how graduate employability is viewed by employers in six economically disadvantaged mountainous provinces in Vietnam. The study reported in this article identified continuous self-learning, resilience, adaptability, devotion and empathy for the local people and local community to be among the main employability attributes expected of graduates in regional Vietnam. The findings of the study raise the importance of context situatedness in looking at employability and show how employability is characterised by the local structural conditions, demographic features and socio-cultural norms. The study provides significant implications for career guidance and graduate employability development, especially in relation to regional areas.

"L'employabilité dans son contexte ¼: Attributs attendus par les employeurs·euses dans la région du Vietnam et implications pour l'orientation professionnelle Cet article examine comment l'employabilité des diplômé·e·s est perçue par les employeurs·ses dans six provinces montagneuses économiquement défavorisées du Vietnam. L'étude rapportée dans cet article a identifié l'auto-apprentissage continu, la résilience, l'adaptabilité, le dévouement et l'empathie pour la population locale et la communauté locale comme étant parmi les principaux attributs d'employabilité attendus des diplômés dans le Vietnam régional. Les résultats de l'étude soulignent l'importance de la situation du contexte dans l'étude de l'employabilité et montrent comment l'employabilité est caractérisée par les conditions structurelles locales, les caractéristiques démographiques et les normes socioculturelles. L'étude fournit des implications significatives pour l'orientation professionnelle et le développement de l'employabilité, en particulier en ce qui concerne les zones régionales.

"Empleabilidad en contexto": Atributos esperados por los empleadores en Vietnam regional e implicaciones para la orientación profesional Este artículo examina cómo los empleadores ven la empleabilidad de los graduados en seis provincias montañosas económicamente desfavorecidas de Vietnam. El estudio reportado en este artículo identificó el autoaprendizaje continuo, la resiliencia, la adaptabilidad, la devoción y la empatía por la población local y la comunidad local como uno de los principales atributos de empleabilidad que se esperan de los graduados en la región de Vietnam. Los hallazgos del estudio plantean la importancia de la situación contextual para observar la empleabilidad y muestran cómo la empleabilidad se caracteriza por las condiciones estructurales locales, las características demográficas y las normas socioculturales. El estudio proporciona implicaciones significativas para la orientación profesional y el desarrollo de la empleabilidad, especialmente en relación con las áreas regionales.

A conceptual model for studying the immersive mobile augmented reality application-enhanced experience.

Purpose: This study aims to develop and propose an integrated conceptual framework that illustrates how emerging technologies such as mobile augmented reality applications (MAR apps) stimulate a user's immersive MAR app-enhanced experience-a human psychological state of being engaged and engrossed in a virtual environment-which in turn facilitates user responses. Design/methodology/approach: This study draws on a literature review of related fields to develop a theoretical model showing the centrality of the immersive MAR app-enhanced experience. Findings: A conceptual model that explicates the selected antecedents and outcomes of the AR-enhanced immersive experience is proposed. The findings suggest that the traits of both the user (mental imagery, personal innovativeness) and the device (simulated physical control, environmental embedding) facilitate the immersive MAR app-enhanced experience. Moreover, the immersive MAR app-enhanced experience is identified as a key driver of customer emotions, values and behavioral responses. Originality/value: The integrated conceptual model provides scholars and practitioners with a general picture of the main factors affecting the immersive AR-enhanced experience, as well as the benefits available to firms; thus, theoretical and practical implications are delineated. Paper type: Conceptual paper.

Sorbent coatings for solid-phase microextraction based on mixtures of polymeric ionic liquids.

Four polymeric ionic liquids based on two different cations, poly(1-vinyl-3-hexylimidazolium) and poly(1-vinyl-3-hexadecylimidazolium), combined with two different anions, bis[(trifluoromethyl)sulfonyl]imide (NTf 2-) and chloride (Cl(-)), were combined in various weight percentages and used as sorbent coatings for solid-phase microextraction gas chromatography (SPME-GC). The selectivity of the fiber coatings for 12 test analytes was examined. The extraction efficiency of n-alcohols increased with an increase in the weight percentage of chloride ion in the sorbent coating. The ability to tune the interactions between the coating material and the analytes was exploited and resulted in distinct changes in the limits of detection for hydrogen-bonding analytes with varying chloride ion content in the sorbent coating.

Combination of Porous Silk Fibroin Substrate and Gold Nanocracks as a Novel SERS Platform for a High-Sensitivity Biosensor.

Novel concepts for developing a surface-enhanced Raman scattering (SERS) sensor based on biocompatible materials offer great potential in versatile applications, including wearable and in vivo monitoring of target analytes. Here, we report a highly sensitive SERS sensor consisting of a biocompatible silk fibroin substrate with a high porosity and gold nanocracks. Our silk-based SERS detection takes advantage of strong local field enhancement in the nanoscale crack regions induced by gold nanostructures evaporated on a porous silk substrate. The SERS performance of the proposed sensor is evaluated in terms of detection limit, sensitivity, and linearity. Compared to the performance of a counterpart SERS sensor with a thin gold film, SERS results using 4-ABT analytes present that a significant improvement in the detection limit and sensitivity by more than 4 times, and a good linearity and a wide dynamic range is achieved. More interestingly, overlap is integral, and a quantitative measure of the local field enhancement is highly consistent with the experimental SERS enhancement.

Implementation and evaluation of a nursing process support system for long-term care: a Taiwanese study.

AIMS: To (1) develop and implement a Nursing Process Support System in Chinese (NPSSC) enabling computerised documentation for nursing home residents, (2) evaluate the efficiency of NPSSC, (3) assess obstacles to the use of the NPSSC and (4) assess nurse users' satisfaction with the NPSSC. BACKGROUND: Long-term care facilities in Taiwan have been slow to computerise resident's medical records. The development and implementation of a computerised documentation system provides a way to enhance nursing documentation in long-term care settings and can prevent hazards that result from documentation errors. DESIGN: Quasi-experimental. METHODS: This study used one group pre/post-test. Five nursing homes in Taiwan were included in the study. Twenty-seven nurses used the NPSSC to computerise 396 residents' medical records. Using the NPSSC allowed nurses to enter health assessment data into the computer system, which automatically triggered appropriate nursing diagnoses. The NPSSC included geriatric nursing interventions and the use of alternative Chinese therapies. RESULTS: Obstacles that hindered nurses' use of the NPSSC were identified and possible solutions to overcome these hindering factors were discussed. The use of the NPSSC significantly improved nursing documentation in that resident's records were organised and consistent and nurses were able to complete a comprehensive care plan within 48 hours. Nurses reported a higher satisfaction in nursing documentation after the implementation of the NPSSC than previously. CONCLUSIONS: This study suggested a pathway to develop and implement a computer-based, user-friendly nursing documentation system for nursing homes. This study may be used as a template for implementing computerised documentation worldwide. Relevance to clinical practice. Nursing home providers may consider implementing the NPSSC to replace the traditional hand-written documentation system. An effective use of in-service programs within the workplace helped ease the transition from hand-written documentation to the computer-based NPSSC.

Exploiting the tunable selectivity features of polymeric ionic liquid-based SPME sorbents in food analysis.

In this work, the performances of polymeric ionic liquid (PIL) based solid-phase microextraction (SPME) coatings were assessed for applications concerning food safety and quality. Two different polymeric ionic liquid coatings, namely poly(1-4-vinylbenzyl-3-hexadecylimidazolium) bis[(trifluoromethyl)sulfonyl] imide (poly([VBHDIM][NTf2]), PIL 1, and N,N-didecyl-N-methyl-d-glucaminium poly(2-methyl-acrylic acid 2-[1-(3-{2-[2-(3-trifluoromethanesulfonylamino-propoxy)-ethoxy]-ethoxy}-propylamino)-vinylamino]-ethyl ester) (poly([DDMGlu][MTFSI]), PIL 2, were evaluated. The PIL-based coatings were compared to commercially available SPME coatings in terms of their performance toward extraction of pesticides and fruit metabolites. The partition coefficients (Kfs) of the tested coatings were calculated, with PIL 1 demonstrating similar or better performance compared to the commercial coatings. Design of experiment (DoE) was applied to optimize the parameters that most influenced SPME extraction, and a quantitative method for determination of 5 organophosphorus pesticides was developed by using PIL-based coatings and commercial SPME fibers. Despite the thin layer of the sorbent coating, PIL 1 achieved limits of quantitation at the low part-per-billion level. Moreover, in a comparative investigation of analyte coverage carried out via HS-SPME-GCxGC-ToF/MS with grape homogenate as model matrix, excellent performances were observed for the PIL-based coatings toward the determination of fruit metabolites, demonstrating their capability towards broad extractive coverage of analytes characterized by various physicochemical properties.

Use of ionic liquids as headspace gas chromatography diluents for the analysis of residual solvents in pharmaceuticals.

In this study, two ionic liquids (ILs), 1-butyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([BMIM][NTf2]) and trihexyltetradecylphosphonium bis[(trifluoromethyl)sulfonyl]imide ([P66614][NTf2]) were examined as contemporary diluents for residual solvent analysis using static headspace gas chromatography (SHS-GC) coupled with flame ionization detection (FID). ILs are a class of non-molecular solvents featuring negligible vapor pressure and high thermal stabilities. Owing to these favorable properties, ILs have potential to enable superior sensitivity and reduced interference, compared to conventional organic diluents, at high headspace incubation temperatures. By employing the [BMIM][NTf2] IL as a diluent, a 25-fold improvement in limit of detection (LOD) was observed with respect to traditional HS-GC diluents, such as N-methylpyrrolidone (NMP). The established IL-based method demonstrated LODs ranging from 5.8 parts-per-million (ppm) to 20ppm of residual solvents in drug substances. The optimization of headspace extraction conditions was performed prior to method validation. An incubation temperature of 140°C and a 15min incubation time provided the best sensitivity for the analysis. Under optimized experimental conditions, the mass of residual solvents partitioned in the headspace was higher when using [BMIM][NTf2] than NMP as a diluent. The analytical performance was demonstrated by determining the repeatability, accuracy, and linearity of the method. Linear ranges of up to two orders of magnitude were obtained for class 3 solvents. Excellent analyte recoveries were obtained in the presence of three different active pharmaceutical ingredients. Owing to its robustness, high throughput, and superior sensitivity, the HS-GC IL-based method can be used as an alternative to existing residual solvent methods.

Determination of acrylamide in brewed coffee and coffee powder using polymeric ionic liquid-based sorbent coatings in solid-phase microextraction coupled to gas chromatography-mass spectrometry.

This study describes a simple and rapid sampling method employing a polymeric ionic liquid (PIL) sorbent coating in direct immersion solid-phase microextraction (SPME) for the trace-level analysis of acrylamide in brewed coffee and coffee powder. The crosslinked PIL sorbent coating demonstrated superior sensitivity in the extraction of acrylamide compared to all commercially available SPME coatings. A spin coating method was developed to evenly distribute the PIL coating on the SPME support and reproducibly produce fibers with a large film thickness. Ninhydrin was employed as a quenching reagent during extraction to inhibit the production of interfering acrylamide. The PIL fiber produced a limit of quantitation for acrylamide of 10µgL(-1) and achieved comparable results to the ISO method in the analysis of six coffee powder samples.

Improved Label and Liver Warning for Nonprescription Acetaminophen Products.

OBJECTIVE: To compare consumer preferences for a revised and current acetaminophen over-the-counter "Drug Facts" labels (ODFL) on warnings and self-reported correct intended action following signs of overdose. METHODS: Adults visiting a community center were randomly assigned to revised or current ODFLs using previously reported label comprehension methodology. RESULTS: Participant (N = 110) ratings for both ODFLs were comparable for ease of finding and understanding information. In response to an emergent overdose scenario, the proportion reporting the correct intended action using the revised ODFL was significantly greater than the proportion using the current ODFL (91% [97.5% CI, 0.82-0.99] vs. 76% [97.5% CI, 0.64-0.89]). In side-by-side comparisons, the revised ODFL was superior for overall consumer preference, usefulness for first-time use, and better overdose-related directions. A revised bottle cap statement also outperformed the current statement used on brand acetaminophen. CONCLUSION: Findings support revision of acetaminophen ODFLs to improve liver damage warnings and to optimize labeling likely to be useful in prevention of and response to overdose.