YouTube as a source of information on the COVID-19 pandemic.

Introduction: YouTube is a popular website where public can access and gain information from videos related to COVID-19. This paper seeks to assess the quality and validity of information available on YouTube, based on the current Center for Disease Control (CDC) and World Health Organization (WHO) guidelines. Methods: We identified the 250 most-viewed videos from 1 January 2020 to 12 May 2020 on YouTube using keyword 'COVID 19'. Two independent reviewers analyzed the English-language videos as useful, misleading, or news updates. Result: After excluding non-English and irrelevant videos, 100 videos were analyzed. Forty-four videos were classified as useful, 33 videos were classified as news updates, and 23 videos were classified as misleading. Independent users had five times increased odds of posting misleading videos (40% vs. 12%, OR = 5.05, 95% CI = 1.84-13.9, P = 0.001), whereas news agencies have 2.8 greater odds of posting useful or update videos (87% vs 44%, OR = 2.85, 95% CI = 0.959-8.45, P = 0.087). Conclusion: YouTube is an increasingly important source of medical information during the COVID-19 pandemic. Most of the videos were useful, however due to the public nature of the platform, misleading information may also be easily disseminated. Independent users are more likely to post-misleading videos.

Quality improvement education in surgical specialty training: A comparison of Vascular Surgery resident and Urology Resident experiences and attitudes.

BACKGROUND: Academic institutions have increasingly focused on educating physicians and surgeons in concepts of value-based care, including quality improvement (QI). The extent to which QI curricular competencies are addressed in specialty surgical residency training is unclear. METHODS: A survey instrument was developed by content experts and sent to Vascular Surgery and Urology residents electronically. Descriptive statistics and bivariate associations were calculated using StataMP 13.1. RESULTS: Vascular Surgery and Urology residents reported exposure to similar types of QI curriculum. Fewer than half of residents reported achieving targets for graduation (Vascular 31%, Urology 42%) related to QI, and few residents in either group felt very well-prepared to lead a QI initiative (Vascular 13%, Urology 8%). CONCLUSION: QI education in surgical specialty training amongst Vascular Surgery and Urology residencies is similar and insufficient. Surgical specialties may benefit from collaborative efforts to improve the quality of QI education.

Experiences With Quality Improvement in Training: A National Survey of Urology Residents.

OBJECTIVE: To determine the quality improvement (QI) experiences of urology residents in the United States. MATERIALS AND METHODS: An Institutional Review Board approved national survey of Urology residents was administered in June 2019. The survey instrument sought to understand QI curricular methods and experiences of urology residents as well as their knowledge of QI fundamentals. RESULTS: Of 465 invited residents, 159 (34%) responded. Respondents represented all 8 AUA sections. The majority of respondents self-identified as white (66%). Females made up 30% of respondents. Less than 1/3 of residents (32%) report use of online modules, whereas nearly 2/3 (63%) report lecture-based didactics. Fifteen percent of residents report no QI curriculum. While nearly 2/3 of residents report receiving training in QI principles (64%), far less report receiving training in how to apply QI methodology (44%). Only 29% of residents report being required to lead a QI project. No differences were seen by training level. Only 3 respondents had heard of the Institute of Medicine's aims for quality improvement. Respondents had better knowledge of process, balancing and outcome measures, but less than half of respondents (49%) were able to correctly identify all 3. Having any QI curriculum is associated with correctly answering knowledge questions (P = .03). CONCLUSION: From a resident perspective, urology residency programs currently provide QI curricula that are inadequate to ensure residents achieve Accreditation Council for Graduate Medical Education milestones. It is imperative the urology community as a whole address these curricular gaps to ensure graduates are prepared to deliver high-quality, cost-conscious care to their patients once in practice.

Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine.

The non-specific effects (NSEs) of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV) induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV). The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

Green Tea Catechin-Inactivated Viral Vaccine Platform.

Traditionally, chemical agents such as formalin (FA) and ß-propiolactone (BPL) have long been used for the preparation of inactivated vaccines or toxoids. It has been shown that FA extensively modifies vaccine antigens and thus affects immunogenicity profiles, sometimes compromising the protective efficacy of the vaccines or even exacerbating the disease upon infection. In this study, we show that natural catechins from green tea extracts (GT) can be used as an inactivating agent to prepare inactivated viral vaccines. GT treatment resulted in complete and irreversible inactivation of influenza virus as well as dengue virus. In contrast to FA that reacted extensively with multiple amino acids including lysine, a major anchor residue for epitope binding to MHC molecules, GT catechin epigallocatechin-3-gallate (EGCG) crosslinked primarily with cysteine residues and thus preserved the major epitopes of the influenza hemagglutinin. In a mouse model, vaccination with GT-inactivated influenza virus (GTi virus) elicited higher levels of viral neutralizing antibodies than FA-inactivated virus (FAi virus). The vaccination completely protected the mice from a lethal challenge and restricted the challenge viral replication in the lungs. Of note, the quality of antibody responses of GTi virus was superior to that with FAi virus, in terms of the magnitude of antibody titer, cross-reactivity to hetero-subtypes of influenza viruses, and the avidity to viral antigens. As the first report of using non-toxic natural compounds for the preparation of inactivated viral vaccines, the present results could be translated into a clinically relevant vaccine platform with improved efficacy, safety, productivity, and public acceptance.

Association of pain intensity, pain-related disability, and depression with hypothalamus-pituitary-adrenal axis function in female patients with chronic temporomandibular disorders.

Patients with temporomandibular disorders (TMD) commonly experience myofascial and joint pain, pain-related disability, and other pain conditions including depression. The present study was carried out to explore the function of the hypothalamus-pituitary-adrenal (HPA) axis in relation to variables of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis II and comorbid depression in female patients with TMD. Cortisol and dehydroepiandrosterone (DHEA) levels were determined in saliva samples that had been collected at various periods after waking (0, 30, and 60min) and at nighttime (2100-2200h) from 52 female patients with chronic TMD pain and age- and gender-matched controls (n=54, 20-40 years old). There were no significant differences in the levels and diurnal patterns of cortisol and DHEA secretion between groups of patients with TMD and controls. In patients, the cortisol awakening response (CAR) or diurnal cortisol rhythm were not associated with any variables of the RDC/TMD Axis II or the Beck Depression Inventory (BDI)-II total scores. However, the ratio of overall cortisol secretion within the first hour after waking (CARauc) to overall DHEA secretion during the post-waking period (Daucawk), defined as CARauc/Daucawk, was significantly associated with pain-related RDC/TMD variables (pain intensity and pain-related disability) and BDI-II total scores. Pain intensity and pain-related disability scores were also significantly associated with BDI-II total scores. These results indicated that an increase in molar cortisol/DHEA ratio due to the dissociation between cortisol and DHEA secretion was associated with pain intensity, pain-related disability, and depression in female patients with TMD.

Organochlorine pesticides and polychlorinated biphenyls in Korean human milk: contamination levels and infant risk assessment.

The levels of persistent organic pollutants (POPs) were determined in 50 samples of Korean human milk. POPs include organochlorine pesticides (OCPs) [aldrin, chlordanes, dieldrin, dichlorodiphenyltrichloroethanes (DDTs), endrins, heptachlors, hexachlorobenzene (HCB), hexachlorocyclohexanes (HCHs), mirex, and toxaphenes] and marker PCBs (PCB28, PCB52, PCB101, PCB138, PCB153 and PCB180). In all samples, p,p'-DDE were determined as 75.5-1115.3 ng/g fat. The compounds ß-HCH and p,p'-DDT were detected at 72% and 60% of the samples, respectively. Chlordanes (nd-84.9 ng/g fat) heptachlors (nd-40.1 ng/g fat), HCB (nd-42.9 ng/g fat) and PCBs (nd-38.3 ng/g fat) were detected in several samples. The ratio of dichlorodiphenyltrichloroethylene (DDE)/DDT was 6.8, which explained that exposure of volunteers to DDT did not occur recently. Compared with the previous monitoring data, the level of marker PCBs generally decreased in the milk samples. The levels of OCPs are significantly correlated to the residential periods of the mothers but not with their dietary habits. Considering the daily intake of each OCPs, 18% of infants would ingest the amount of heptachlor exceeding the acceptable daily intake (ADI) proposed by World Health Organization (WHO). There was no sample surpassing the WHO ADI for DDTs, HCB and chlordanes.

Short-term clinical outcomes for 100 consecutive cases of laparoscopic pylorus-preserving pancreatoduodenectomy: improvement with surgical experience.

BACKGROUND: Few reports describe the use of laparoscopic pylorus-preserving pancreaticoduodenectomy (LPPPD) in centers with experience using this technique. In addition, the clinical outcomes of this procedure remain undetermined. METHODS: In the current study, 100 patients with benign or malignant lesions in the pancreatic head underwent LPPPD between May 2007 and December 2011. The overall clinical outcomes and changes in these outcomes during the surgeon learning period were analyzed to assess the feasibility and safety of this procedure. RESULTS: Pathologic examination of the pancreas confirmed intraductal papillary mucinous neoplasms in 37 patients, solid pseudopapillary tumors in 17 patients, neuroendocrine tumors in 15 patients, serous cystic neoplasms in seven patients, pancreatic ductal adenocarcinomas in seven patients, ampulla of Vater tumors and duodenal gastrointestinal stromal tumors in five patients, and other disease in seven patients. The median operative time was 7.9 h, which decreased with accumulating experience of the surgeon using this procedure, from 9.8 h for the first 33 cases to 6.6 h for the last 34 cases. Complications developed in 25% of the patients, including six cases (6%) with significant pancreatic fistula [International Study Group on Pancreatic Fistula (ISGPF) grade B]. The complication rate decreased from 33.3% for the first 33 cases to 17.6% for the last 34 cases. The mean hospital stay was 14 days, which also decreased from 20.4 days for the first 33 cases to 11.5 days for the last 34 cases. For the 12 patients in the study cohort with invasive malignant disease, the median tumor size was 2.8 cm, and the median number of lymph nodes harvested was 13. All the patients had margin-negative R0 resections. CONCLUSION: The LPPPD procedure is technically safe and feasible, with an acceptable rate of morbidity and other clinical outcomes for benign and malignant diseases. Clinical outcomes can be improved once a learning curve has been overcome.

Tnk1/Kos1: a novel tumor suppressor.

Tnk1/Kos1 is a non-receptor protein tyrosine kinase implicated in negative regulation of cell growth by a mechanism involving inhibition of Ras activation and requiring Tnk1/Kos1's intrinsic catalytic activity. Tnk1/Kos1 null mice were created by homologous recombination by deleting the catalytic domain. Upon aging, both Tnk1+/- and Tnk1-/- mice develop spontaneous tumors, including lymphomas and carcinomas at high rates (i.e. 27%, and 43%, respectively), indicating that Tnk1/Kos1 is a tumor suppressor. Tissues from Tnk1/Kos1-null mice exhibit proportionally higher levels of basal and growth factor-stimulated Ras activation. Mechanistically, Tnk1/Kos1 requires either or both Y277 and Y287 sites to be intact for enzymatic activity and phosphorylation of its substrate, growth factor receptor binding protein 2 (Grb2). Data indicate that following tyrosine phosphorylation of Grb2 by Tnk1/Kos1, the Grb2-Sos1 guanine exchange factor (GEF) complex that mediates growth factor stimulated Ras activation becomes disrupted, resulting in the reversal of Ras activation. Conversely, the loss of Tnk1/Kos1 activity results in constitutive activation of Ras due to prolonged stabilization/activation of the Grb2-Sos1 GEF activity. Tnk1/Kos1 is the first tyrosine kinase discovered to have tumor suppressor activity, and the mechanism of spontaneous tumor formation involves constitutive, indirect activation of Ras. Thus, Ras may display "oncogenic activity" without undergoing "oncogenic" mutation. We now find that a cohort of patients with diffuse large B-cell lymphoma (DLBCL) display downregulation of Tnk1/Kos1 that may account for tumorigenesis in humans.

Characterization of antimicrobial resistance of recent Salmonella enterica serovar Gallinarum isolates from chickens in South Korea.

Salmonella enterica serovar Gallinarum isolates (n=105) from chickens in South Korea between 2002 and 2007 were tested for antimicrobial susceptibility by determining minimum inhibitory concentrations of 16 antimicrobials, and their predominant resistance profiles were genetically characterized. Most isolates (99/105; 94.3%) were resistant to nalidixic acid and resistant/intermediately resistant to fluoroquinolones, and 63.8% (67/105) of the isolates were resistant to three or more antimicrobials. Forty-two quinolone-resistant isolates, of which the quinolone resistance-determining regions of the gyrA genes were sequenced, contained a substitution of a Ser to a Phe or Tyr at position 83 (71.4%), or a substitution of an Asp to an Asn, Gly, or Tyr at position 87 (28.6%). Fifty-seven sulphamethoxazole-resistant isolates were tested for the presence of class 1 integrons by polymerase chain reaction, and their resistance gene cassettes were analysed by sequencing. Three different class 1 integrons containing the resistance-gene insert aadA (52.6%; n=30), aadB (12.3%; n=7), or aadB-aadA (12.3%; n=7) were identified. Most isolates harbouring the integron containing aadB-aadA displayed resistance to all three aminoglycosides tested and also showed increased resistance to fluoroquinolones. These findings suggest that fluoroquinolone resistance may be epidemiologically linked to multiple aminoglycoside resistance.

Institutional practices of withholding enteral feeding from intubated patients.

OBJECTIVE: This study compared the practices of anesthesia, anesthesia critical care, surgical critical care, and medical critical care departments that have training programs for the length of time they withhold enteral feeding from intubated patients before seven scheduled procedures: 1) extubation; 2) tracheostomy; 3) abdominal surgery; 4) nonabdominal surgery; 5) magnetic resonance imaging or computerized tomography; or placing the patient in the 6) Trendelenberg or 7) prone position. DESIGN: One-time survey of 297 anesthesia and critical care training programs in the United States. MEASUREMENTS AND MAIN RESULTS: Eighty programs responded (27%). We compared the median hours of withholding enteral feeding of intubated patients according to training program type for each of the procedures. None of the programs withheld enteral feeds from intubated patients scheduled for magnetic resonance imaging/computerized tomography scans, nor for the Trendelenberg position (median = 0 hour). A significant difference among program types was found for extubation, with anesthesia departments having significantly longer times (median = 6 hours) compared with anesthesia critical care (median = 4 hours), surgical critical care (median = 2 hours), and medical critical care (1.5 hours) departments (chi = 8.77, df = 3, p = 0.032). For scheduled tracheostomy, surgical critical care departments reported shorter times (median = 4 hours) than did all other surveyed departments (median = 6 hours) (chi = 7.28, df = 3, p = 0.063). CONCLUSIONS: Differences in opinion exist among specialty training programs about the length of time necessary for withholding enteral feeding from intubated patients before scheduled procedures, especially extubation and tracheostomy. To resolve physician conflicts and to best serve these patients, best practice guidelines for withholding enteral feeding from intubated patients before scheduled procedures need to be developed jointly by the critical care specialties.

Zinc incorporation into hydroxylapatite.

By theoretical modeling and X-ray absorption spectroscopy, the local coordination structure of Zn incorporated into hydroxylapatite was examined. Density function theory (DFT) calculations show that Zn favors the Ca2 site over the Ca1 site, and favors tetrahedral coordination. X-ray absorption near edge structure (XANES) spectroscopy results suggest one dominant coordination environment for the incorporated Zn, and no evidence was observed for other Zn-containing phases. Extended X-ray absorption fine structure (EXAFS) fitting of the synthetic samples confirms that Zn occurs in tetrahedral coordination, with two P shells at approximately 2.85-3.07A, and two higher Ca shells at approximately 3.71-4.02A. These fit results are consistent with the most favored DFT model for Zn substitution in the Ca2 site.

Tnk1/Kos1 knockout mice develop spontaneous tumors.

Tnk1/Kos1 is a non-receptor protein tyrosine kinase implicated in negatively regulating cell growth in a mechanism requiring its intrinsic catalytic activity. Tnk1/Kos1 null mice were created by homologous recombination by deleting the catalytic domain. Both Tnk1(+/-) and Tnk1(-/-) mice develop spontaneous tumors, including lymphomas and carcinomas, at high rates [27% (14 of 52) and 43% (12 of 28), respectively]. Tnk1/Kos1 expression is silenced in tumors that develop in Tnk1(+/-) mice but not in adjacent uninvolved tissue, and silencing occurs in association with Tnk1 promoter hypermethylation. Tissues and murine embryonic fibroblasts derived from Tnk1/Kos1-null mice exhibit proportionally higher levels of basal and epidermal growth factor-stimulated Ras activation that results from increased Ras-guanine exchange factor (GEF) activity. Mechanistically, Tnk1/Kos1 can directly tyrosine phosphorylate growth factor receptor binding protein 2 (Grb2), which promotes disruption of the Grb2-Sos1 complex that mediates growth factor-induced Ras activation, providing dynamic regulation of Ras GEF activity with suppression of Ras. Thus, Tnk1/Kos1 is a tumor suppressor that functions to down-regulate Ras activity.

RAX is required for fly neuronal development and mouse embryogenesis.

RAX was originally discovered as the unique cellular activator for the dsRNA-dependent, interferon-inducible protein kinase PKR. Recent findings indicate that RAX is also a critical component of the RNA-induced silencing complex and a regulator of transcription. Here we report novel phenotypes for both fruit flies carrying a transposon insertion in the 5' UTR of dRax (independently identified as loqs/R3D1) and mice with a deletion of the entire Rax gene. In Drosophila we observe a high level of dRax expression in the developing nerve cord. Mutant fly embryos homozygous for the insertion dRax[f00791] display highly abnormal commissural axon structure of the CNS and 70% of the flies homozygous for the mutant allele die prior to adulthood. Surviving male flies have reduced fertility and female flies are sterile. Furthermore, these flies appear to have a severe defect in nervous system coordination or neuromuscular function resulting in significantly reduced locomotion. Mice were also generated that are heterozygous for a deletion of the entire Rax gene (exons 1-8). While mice that are heterozygous for the mutant allele are viable and appear normal, we are unable to obtain mice homozygous for this mutant allele. Furthermore, we have not observed any embryo obtained by mating heterozygous mice at either E3.5, 7, or 14 that is nullizygous for the Rax gene. Since Rax is expressed in preimplantation blastocysts, these data indicate that deletion of the entire Rax gene is embryonic lethal in mice at a preimplantation stage of development. Collectively, these findings in two different species illustrate the importance of RAX for embryonic development.

Intraductal papillary mucinous neoplasm of the pancreas: clinical characteristics and treatment outcomes of 118 consecutive patients from a single center.

BACKGROUND/PURPOSE: Appropriate surgical treatment strategies based on clinicopathological findings are unavailable for intraductal papillary mucinous neoplasm (IPMN) of the pancreas. We investigated the clinical features of pancreatic IPMN in a single-center database in order to design an optimal surgical strategy. METHODS: The medical records of 118 consecutive patients who had undergone surgical resection between August 1994 and December 2004, in whom IPMN was histologically confirmed, were reviewed retrospectively for radiological and pathological findings. RESULTS: Most of the invasive carcinomas in these patients were detected as the main-duct type (88.5%). The type of tumor (main-duct type vs branched-duct type), the tumor size, and the dilated duct size were significant predictive factors associated with malignancy. The relative risk of malignancy was greatest at 13-mm or more ductal dilation in the main-duct type (Odds ratio, 4.1), at 35-mm or more tumor size (Odds ratio, 7.6), and for main-duct type (Odds ratio, 3.9). Major pancreatic resections such as total pancreatectomy and pancreatoduodenectomy were performed in 14.5% and 69% of the patients, respectively. There was a 19.5% rate of incomplete resection, with these patients having a positive resection margin. However, significant recurrence did not occur in patients with a benign IPMN lesion which remained at the resection margin. The overall postoperative survival rate at 5 years was 98.2% for benign IPMN and 65.3% for malignant IPMN. CONCLUSIONS: Function-preserving strategies, based on the clinical status of the patient, are necessary in order to avoid possible severe metabolic complications following extended pancreatectomy in patients with benign IPMN because of the low recurrence rate and good prognosis of this entity, irrespective of margin status.

NMR spectroscopy of citrate in solids: cross-polarization kinetics in weakly coupled systems.

Solid-state NMR spectroscopy is a potentially powerful method for obtaining molecular level structural information crucial for understanding the specific relationship between calcite crystals and occluded organic molecules that are important in biomineralization and biomimetic materials. In this work, a method is developed based on cross-polarization/magic angle spinning (CP/MAS) NMR to measure the heteronuclear distances and obtain structural information for large intracrystalline citrate defects in a synthetic calcite/citrate composite. Using compounds with well-characterized crystal structures, Mg(II) citrate and Sr(II) citrate, a correlation is established between T(IS), the CP time, and M(2) (IS), the van Vleck heteronuclear dipolar second moment, which contains distance and structural information. This correlation is supported by peak assignments obtained from calculations of the (13)C chemical shifts for crystalline Mg(II) citrate. On the basis of T(IS) (-1) versus M(2) (IS) correlation, measurement of T(IS) for carbonate ions associated with citrate defects in a calcite((13)C-enriched)/citrate coprecipitate yields an estimate for the distance between citrate and the nearest carbonate carbon that indicates close spatial proximity and provides useful constraints for future computational study. The applicability of T(IS) (-1) versus M(2) (IS) correlations to other weakly coupled spin-1/2 systems is discussed in terms of the effects of (1)H homonuclear dipolar coupling, using the CP kinetics of Zn(II) dihydroxybenzoate and kaolinite for comparison. The results suggest a limited range of correlation constants and indicate that quantitative information can be obtained from CP/MAS kinetics obtained under similar experimental conditions.

Protective efficacy of live Salmonella gallinarum 9R vaccine in commercial layer flocks.

Salmonella enterica serovar Gallinarum (S. Gallinarum) is the causative agent of fowl typhoid, a severe systemic disease of chickens that results in high mortality. In this study we re-evaluated the ability of live S. Gallinarum 9R vaccine to protect from wild-type S. Gallinarum challenge. In laboratory trials, there was a significant difference between the vaccinated and unvaccinated control groups in mortality and the re-isolation rate of the challenge strain from the tissues (P<0.05). In field trials, efficacy of the 9R vaccine by one inoculation at the age of 18 weeks and two inoculations at the age of 6 weeks and 18 weeks was persistent throughout the duration of the study from 21 weeks old to 61 weeks old. The results from this study indicate that the protection against mortality and organ invasion in highly susceptible chickens exposed to virulent strains of S. Gallinarum may be severely limited by 9R vaccine.

Slice-selected LED and BPPLED: application of slice selection to DOSY.

High-resolution DOSY (Diffusion-ordered spectroscopy) is a series of 2-dimensional and 3-dimensional NMR techniques based on the differing diffusivity of constituent molecules in the solution state, with which the individual NMR spectrum of each component in a chemical mixture can be observed. All of the DOSY pulse sequences are derived from the spin-echo or stimulated-echo techniques under the effect of PFG (pulsed field gradient). One of the requirements for successful DOSY experiments and data fitting is that PFG must be uniform across the active sample volume. However, PFG, in general, is not uniform across the active sample volume in commercial high-resolution NMR probes and this nonuniformity of PFG is known to produce systematic errors in DOSY experiments. In fact, a strong and uniform gradient field can be realized only in the central region of the gradient coil and the slice-selection technique, widely used in Magnetic Resonance (MR) imaging, can be employed in resolving problems associated with the nonuniformity of PFG. We have developed a slice-selection pulse block, which can be generally applied to any DOSY pulse sequence with proper care of the phase cycling and experimental parameters. We applied the slice-selection technique to LED and BPPLED pulse sequences, which are among the most popular DOSY pulse sequences, and obtained good experimental results for a chemical mixture.