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Biomedical subjects

B L Smith

Publications and source records attributed to B L Smith.

At least 55 records · Page 3Linked to original sources
PubMed1999

Births and deaths: preliminary data for 1998.

OBJECTIVES: This report presents preliminary data for 1998 on births and deaths in the United States. U.S. data on births are shown by age, race, and Hispanic origin of mother. Natality data on marital status, prenatal care, cesarean delivery, and low birthweight are also presented. Mortality data presented include life expectancy, leading causes of death, and infant mortality. METHODS: Data in this report are based on more than a 99-percent sample of births and on more than an 85-percent sample of deaths in the United States for 1998. The records are weighted to independent control counts of births, infant deaths, and deaths 1 year and over received in State vital statistics offices in 1998. Comparisons are made with 1997 final data. RESULTS: The birth rate for teenagers continued to decline, dropping another 2 percent for 1997-98. The rate for young teens aged 15-17 years fell 5 percent, and the rate for teens aged 18-19 years declined 2 percent. Since 1991 rates have fallen 21 percent for teens aged 15-17 years and 13 percent for teens aged 18-19 years. Birth rates for women aged 20-29 years rose slightly. Among women in their thirties, birth rates rose 3 to 4 percent to the highest levels observed in three decades. The birth rate for women aged 40-44 years was the highest level reported since 1970. The birth rate for unmarried women was 44.3 per 1,000, 1 percent higher than 1997, but below the peak level reported for 1994 (46.9). The rate of prenatal care utilization continued to improve. The total cesarean rate increased to 21.2 percent. The low birthweight rate rose from 7.5 to 7.6 percent. In 1998 the age-adjusted death rate reached a record low, 2 percent below the rate for 1997. Human immunodeficiency virus infection (HIV infection) moved off the list of the 15 leading causes of death for the first time since 1987. Declines in age-adjusted rates occurred for Homicide and legal intervention (homicide) (14 percent) and Atherosclerosis (10 percent), while rates for Septicemia and Pneumonia and influenza increased 5 percent. Mortality also decreased for drug-induced deaths, deaths from injury by firearms, and alcohol-induced deaths. The infant mortality rate was unchanged. Life expectancy reached a record high of 76.7 in 1998.

Adolescent↗
PubMed1999

Births and deaths: preliminary data for July 1997-June 1998.

OBJECTIVES: This report presents preliminary data on births and deaths in the United States from the National Center for Health Statistics (NCHS) for the 12 months ending June 1998. U.S. data on births are shown by age, race, and Hispanic origin of mother. Natality data on marital status, prenatal care, cesarean delivery, and low birthweight are also presented. Mortality data presented include leading causes of death and infant mortality. METHODS: Data in this report are based on more than a 99-percent sample of births and on more than an 89-percent sample of deaths in the United States for the 12 months ending June 1998. The records are weighted to independent control counts of births, infant deaths, and deaths 1 year and over received in State vital statistics offices from July 1997 to June 1998. Unless otherwise indicated, comparisons are made with final data for the 12-month period ending June 1997. RESULTS: For the period July 1997-June 1998, the birth rate for teenagers dropped 4 percent to 51.5 births per 1,000 women aged 15-19 years, the lowest level since 1987. Birth rates for teenagers have been declining since 1991. Birth rates for women aged 20-29 years changed very little, whereas rates for women in their thirties and forties rose 2 to 4 percent. The birth rate for unmarried women declined slightly, but the number of births to unmarried women was up about 1 percent because of an increase in the number of unmarried women. The rate of prenatal care utilization continued to improve. The percent of births delivered by cesarean section rose from 20.7 percent to 20.9 percent as the result of a slight increase in the primary cesarean rate and a substantial decline in the rate of vaginal births after previous cesarean (VBAC). The overall low birthweight rate was unchanged at 7.5 percent. Age-adjusted death rates reached a record low, 2 percent below the rate for the previous 12-month period. The largest declines in estimated age-adjusted death rates among the leading causes of death were for Human immunodeficiency virus (HIV) infection (37 percent) and homicide (9 percent). Smaller declines were noted for most of the other leading causes of death, but no increases occurred. Mortality also decreased for firearm injuries and alcohol-induced deaths. The infant mortality rates for all races and white and black infants were about the same as the corresponding rates for the previous 12-month period.

Adolescent↗
PubMed1999

Bracken carcinogens in the human diet.

The ubiquitous bracken fern (genus Pteridium) is the only higher plant known to cause cancer naturally in animals. In addition to the well-recognized syndromes of thiamine deficiency, acute haemorrhage associated with myeloid aplasia and blindness due to retinal degeneration, it causes neoplasia of the urinary bladder and in some circumstances, of the upper gut. In addition, it has been shown to cause neoplasia in a wide range of tissues in many experimental species. The major carcinogen (and the cause of the retinal degeneration and the myeloid aplasia) has been shown to be ptaquiloside (PT), a norsesquiterpene glucoside that can be present in bracken in extraordinary concentrations, up to 13 000 ppm. The highest concentrations were found in the crosiers and young unfolding fronds. The mutagenicity, clastogenicity, teratogenicity and carcinogenicity have been convincingly demonstrated. Under alkaline conditions the loss of the glucose gives rise to the formation of a dienone intermediate which possesses a highly reactive cyclopropyl ring capable of reacting with cellular macromolecules. PT has been shown to alkylate DNA at N3 of adenines in the minor groove, preferentially in 5'-TAG and 3'-A in 5'-AA-3' sequences. It also alkylates N7 guanines in the major groove occurring in 5'-TG sequences. It is believed that these alkylations lead to mismatch repair and subsequent mutations in particular proto-oncogenes. Recently a rat model of carcinogenesis has been established using intravenously (iv) administered PT. Some epidemiological evidence has indicated higher risk of cancer in people who consume bracken crosiers, people who consume milk of cows feeding on bracken and those who live in bracken-infested areas. PT has been found in the milk of cows fed on bracken fern experimentally and the milk of bracken-fed cows has been shown to cause cancer in rats. PT carcinogenesis presents an excellent model of environmental and experimental carcinogenesis.

Animals↗
PubMed1999

Characterization of the binding and phosphorylation of cardiac calsequestrin by epsilon protein kinase C.

In this study, we report the cloning of the rat cardiac isoform of calsequestrin on the basis of its interaction with an epsilonprotein kinase C-unique sequence (epsilonV1) derived form the epsilonprotein kinase C regulatory domain. Calsequestrin binds activated epsilonprotein kinase C holoenzyme better than the inactive enzyme and nearly three times better than other protein kinase C isozymes. The interaction between epsilonprotein kinase C and calsequestrin is mediated by sequences in both the regulatory and kinase domains of the epsilonprotein kinase C. Finally, we show that calsequestrin is an epsilonprotein kinase C substrate in vitro and protein kinase C phosphorylation of calsequestrin leads to a decreased binding of epsilonprotein kinase C to calsequestrin.

Amino Acid Sequence↗
PubMed1999

Effect of butylated hydroxyanisole on the toxicity of 2-hydroxy-1,4-naphthoquinone to rats.

It has previously been shown that rats pre-treated with butylated hydroxyanisole (BHA), a well-known inducer of the enzyme DT-diaphorase, are protected against the harmful effects of 2-methyl-1,4-naphthoquinone. This is consistent with a role for diaphorase in the detoxification of this quinone, but it is not known if increased tissue levels of this enzyme give protection against other naphthoquinone derivatives. In the present study, rats were dosed with BHA and then challenged with a toxic dose of 2-hydroxy-1,4-naphthoquinone, a substance that causes haemolytic anaemia and renal damage in vivo. Pre-treatment with BHA had no effect upon the nephrotoxicity of 2-hydroxy-1,4-naphthoquinone, but the severity of the haemolysis induced by this compound was increased in the animals given BHA. DT-Diaphorase is known to promote the redox cycling of 2-hydroxy-1,4-naphthoquinone in vitro, with concomitant formation of 'active oxygen' species. The results of the present experiment suggest that activation of 2-hydroxy-1,4-naphthoquinone by DT-diaphorase may also occur in vivo and show that increased tissue levels of DT-diaphorase are not always associated with naphthoquinone detoxification.

Anemia, Hemolytic↗
PubMed1999

Multimodality management of Merkel cell carcinoma.

HYPOTHESIS: Merkel cell carcinoma is a rare dermal neuroendocrine carcinoma whose optimal treatment and prognostic factors are poorly defined. We hypothesize that high-risk patients with Merkel cell carcinoma are best treated with multimodality therapy. DESIGN: A retrospective review of all patients (N = 33) with Merkel cell carcinoma treated at the Massachusetts General Hospital from January 1, 1980, to August 24,1997. Median follow-up time was 37 months (range, 6-157 months). PATIENTS: Adequate data for evaluation were available for 31 patients. Male to female distribution was 14 men and 17 women, with a median patient age of 68 years. MAIN OUTCOME MEASURE: Stage at presentation; factors associated with recurrence; and the effects of surgery, radiation therapy (XRT), and chemotherapy on recurrence, salvage, and survival rates. RESULTS: There were 12 extremity, 11 head and neck, and 8 truncal tumors. There were 22 isolated primary tumors, 8 with additional clinically positive lymph nodes, and 1 with distant disease. Therapy was local excision with or without XRT in 19 patients, local resection and lymphadenectomy with or without XRT in 8 patients, and XRT alone in 4 patients with head and neck tumors. Fifteen patients developed recurrences (7 local, 8 nodal, and 10 distant). Median time to recurrence was 8 months (range, 3-48 months). There were 7 tumor-related deaths, 6 of which were associated with truncal lesions (P<.001). No locoregional recurrences occurred in patients with margins of resection of 2 cm or greater or adequate XRT. A multivariate analysis selected truncal location (P = .005) and nodal disease (P = .05) as predictors of mortality. Remission was possible in 5 patients with locoregional and 2 patients with distant recurrences. CONCLUSIONS: Merkel cell carcinoma is an aggressive dermal cancer with frequent nodal metastases; truncal tumors have the worst prognosis. Locoregional recurrence correlates with inadequate margins and lack of XRT, but remission is possible with multimodality therapy.

Aged↗
PubMed1999

Surgical management of phyllodes tumors.

HYPOTHESIS: Although phyllodes tumors have minimal metastatic potential, we hypothesized that they have a proclivity for local recurrence and should be excised with a wide margin. We reviewed the clinical and radiological appearance of phyllodes tumors and analyzed the role of surgical treatment in their management. DESIGN: Medical records, imaging studies, pathology reports, and interventions were reviewed. SETTING: A large tertiary care teaching hospital. PATIENTS: Between 1980 and 1997, 40 patients with phyllodes tumors were identified through the tumor registry at the Massachusetts General Hospital, Boston. MAIN OUTCOME MEASURES: Surgical resection margins, rates of local recurrence, incidence of distant metastases, and survival. RESULTS: All 40 patients were female, with a mean age of 41 years. Each patient had a palpable mass or a mammographic finding that was indistinguishable from a fibroadenoma on examination. Tumor size ranged from 5 mm to 28 cm. Local recurrence correlated with excision margins (P<.05), but not with tumor grade or size. Local recurrence occurred in 5 patients, each of whom had positive margins or margins less than 1 cm after excision. After reexcision with a 1-cm margin, these individuals remained free of recurrence. One patient developed metastatic disease after total mastectomy and died after chemotherapy. CONCLUSIONS: Phyllodes tumors mimic fibroadenomas and are often excised with close margins. Primary excision or reexcision with a 1-cm margin is recommended. Mastectomy is indicated for patients with large lesions. Lymph node metastases are unusual and occur secondary to necrotic tumor. Chemotherapy is based on guidelines for the treatment of sarcomas, not breast adenocarcinoma.

Adolescent↗
PubMed1999

Oriented, active Escherichia coli RNA polymerase: an atomic force microscope study.

Combining a system for binding proteins to surfaces (Sigal, G. B., C. Bamdad, A. Barberis, J. Strominger, and G. M. Whitesides. 1996. Anal. Chem. 68:490-497) with a method for making ultraflat gold surfaces (Hegner, M., P. Wagner, and G. Semenza. 1993. Surface Sci. 291:39-46 1993) has enabled single, oriented, active Escherichia coli RNA polymerase (RNAP) molecules to be imaged under aqueous buffer using tapping-mode atomic force microscopy (AFM). Recombinant RNAP molecules containing histidine tags (hisRNAP) on the C-terminus were specifically immobilized on ultraflat gold via a mixed monolayer of two different omega-functionalized alkanethiols. One alkanethiol was terminated in an ethylene-glycol (EG) group, which resists protein adsorption, and the other was terminated in an N-nitrilotriacetic acid (NTA) group, which binds the histidine tag through two coordination sites with a nickel ion. AFM images showed that these two alkanethiols phase-segregate. Specific binding of the hisRNAP molecules was followed in situ by injecting proteins directly into the AFM fluid cell. The activity of the hisRNAP bound to the NTA groups was confirmed with a 42-base circular single-stranded DNA template (rolling circle), which the RNAP uses to produce huge RNA transcripts. These transcripts were imaged in air after the samples were rinsed and dried, since RNA also has low affinity for the EG-thiol and cannot be imaged under the buffers we used.

DNA, Single-Stranded↗
PubMed1999

Membrane dynamics of the water transport protein aquaporin-1 in intact human red cells.

Aquaporin-1 (AQP1) is the prototype integral membrane protein water channel. Although the three-dimensional structure and water transport function of the molecule have been described, the physical interactions between AQP1 and other membrane components have not been characterized. Using fluorescein isothiocyanate-anti-Co3 (FITC-anti-Co3), a reagent specific for an extracellular epitope on AQP1, the fluorescence photobleaching recovery (FPR) and fluorescence imaged microdeformation (FIMD) techniques were performed on intact human red cells. By FPR, the fractional mobility of fluorescently labeled AQP1 (F-alphaAQP1) in the undeformed red cell membrane is 66 +/- 10% and the average lateral diffusion coefficient is (3.1 +/- 0.5) x 10(-11) cm2/s. F-alphaAQP1 fractional mobility is not significantly affected by antibody-induced immobilization of the major integral proteins band 3 or glycophorin A, indicating that AQP1 does not exist as a complex with these proteins. FIMD uses pipette aspiration of individual red cells to create a constant but reversible skeletal density gradient. F-alphaAQP1 distribution, like that of lipid-anchored proteins, is not at equilibrium after microdeformation. Over time, approximately 50% of the aspirated F-alphaAQP1 molecules migrate toward the membrane portion that had been maximally dilated, the aspirated cap. Based on the kinetics of migration, the F-alphaAQP1 lateral diffusion coefficient in the membrane projection is estimated to be 6 x 10(-10) cm2/s. These results suggest that AQP1 lateral mobility is regulated in the unperturbed membrane by passive steric hindrance imposed by the spectrin-based membrane skeleton and/or by skeleton-linked membrane components, and that release of these constraints by dilatation of the skeleton allows AQP1 to diffuse much more rapidly in the plane of the membrane.

Actins↗
PubMed1999

Tremorgenic mycotoxins paxilline, penitrem and lolitrem B, the non-tremorgenic 31-epilolitrem B and electromyographic activity of the reticulum and rumen of sheep.

The mycotoxic tremorgens penitrem, paxilline and lolitrem B had profound effects on electromyographic (EMG) activity of smooth muscle of the reticulorumen in conscious sheep, with a similar time course of action to their respective characteristic effects on the induction (1 to 2, 15 to 20 and 20 to 30 minutes) and the duration (1 to 2, 1 to 2 and 8 to 12 hours) of tremoring. Responses to penitrem revealed a greater sensitivity of smooth muscle than skeletal muscle. Effects included an inhibition of the vagally-dependent cyclical A and B sequences of contraction of the reticulorumen, an increase in their amplitude and an excitation of local intrinsic activity contributing to elevated baselines and the occurrence of chaotic activity of the reticulum. The excitatory local effects were partially blocked by atropine, indicating that stimulation of muscarinic cholinoceptors was involved. Increased local activity may mediate a reflex inhibition of cyclical contractions. A non-tremorgenic isomer of lolitrem B (31-epilolitrem B) had no effect on the reticulorumen. The intensity and duration of the effects of lolitrem B, up to 12 hours, indicate that severe disruption of digestion may occur in animals grazing endophyte-infected pasture.

Animals↗
PubMed1999

Urinary excretion of immunoreactive sporidesmin metabolites in sheep in relation to factors influencing susceptibility to sporidesmin intoxication.

AIM: To study the urinary disposition of orally administered sporidesmins A and D in sheep and identify factors influencing their kinetics, particularly the influence of breeding for resistance and susceptibility to sporidesmin, the mycotoxin responsible for the hepatogenous photosensitisation, facial eczema. METHODS: A competitive ELISA was used to monitor urinary output of immunoreactive metabolites after the intraruminal administration, to female Romney sheep, of either sporidesmin A or sporidesmin D, the nontoxic analogue. Preliminary characterisation of metabolites was carried out using HPLC with fractions monitored by ELISA. RESULTS: Maximum urinary excretion rates of immunoreactive metabolites occurred 2-8 h after dosing with sporidesmin D and 15-30 h after dosing with sporidesmin A. Sporidesmin D caused no liver injury, as detected by changes in serum enzyme activity, while the liver injury caused by sporidesmin A was greatest for the sheep with the highest cumulative output of metabolite. When sporidesmin D was administered in two separate doses to sheep bred for either resistance or susceptibility to facial eczema, the variability of metabolic output between sheep within groups was much less after the second dose. The mean urinary metabolite excretion was greater for the susceptible than the resistant sheep but the difference was not significant. Potentiation (caused by pre-administration of small doses of sporidesmin A) resulted in a more severe reaction to the dosed sporidesmin A. Urinary output of metabolite was less in the potentiated than in the unpotentiated sheep. When resistant and susceptible sheep were dosed with sporidesmin A after potentiation there was no difference between them in their cumulative totals or excretion rates of immunoreactive metabolites. However, the volume of urine produced by the susceptible sheep was lower and less variable than the resistant sheep and consequently the concentration of their urinary metabolites was higher. Preliminary ELISA examination of HPLC-fractionated urine from a sheep dosed with sporidesmin A indicated the presence of several metabolites of sporidesmin. CONCLUSION: Sporidesmin A and metabolites are rapidly excreted in urine but not as rapidly as sporidesmin D and its metabolites. Only minor differences between sheep bred for resistance and susceptibility were seen. Potentiation caused a more severe reaction to sporidesmin A and less urinary excretion of the sporidesmin and its metabolites. CLINICAL RELEVANCE: This work is part of a programme with the aim of identifying FE-resistant animals without the need for sporidesmin dosing.

Journal Article↗
PubMed1999

Effect of prior sporidesmin intoxication on the pancreopathy associated with zinc oxide toxicity.

AIM: To demonstrate the effect of prior sporidesmin-induced liver injury on the pancreopathy of zinc-induced toxicity. METHODS: Four groups, each of 15 sheep, were given 2 x 2 treatments of sporidesmin (0.3 mg/kg bodyweight spread over 3 consecutive days prior to zinc) and zinc (200 mg Zn/kg bodyweight as ZnO spread over 24 days) starting 4 days after the end of sporidesmin dosing. Liver and pancreatic changes were assessed by serum enzyme changes (serum amylase and gamma glutamyltransferase) or scoring for injury at post-mortem examination (hepatopathy) or by histopathological examination (pancreopathy). RESULTS: Minor pancreatic injury was caused by the administration of zinc. The pancreopathy associated with zinc oxide toxicity was significantly greater in those sheep receiving zinc after the sporidesmin-induced injury. Pathological and body weight changes associated with sporidesmin toxicity also occurred in both groups dosed with sporidesmin. These were slightly less in the group of sheep receiving zinc after the sporidesmin challenge than in those receiving sporidesmin alone. CONCLUSIONS: Zinc-induced pancreatic injury is greater if the zinc is administered after liver injury has been caused by sporidesmin. Only minor protection is given by zinc if it is administered after the challenge with sporidesmin. CLINICAL SIGNIFICANCE: The safety margin for the use of zinc is reduced if zinc is administered after significant liver injury has been caused by prior exposure to high Pithomyces chartarum spore counts.

Journal Article↗
PubMed1999

Changes in left ventricular dynamics during graded exercise.

Three mature Thoroughbred horses were prepared surgically with ultrasonic sonomicrometer crystals affixed to their ventricular pericardia. Signals from crystals recorded dimensions of axes across the left ventricle. Cubic algorithms were fitted to dimensional data to generate volume estimates that matched stroke volumes simultaneously measured using the Fick principle. As horses stood at rest or exercised at various intensities (approx 7, 12, 24, 47 and 100% maximal rate of O2 consumption VO2max[), left ventricular dimensions were recorded and 20 consecutive diastolic and systolic volumes calculated. Although Fick estimates detected no difference in stroke volume at different exercise intensities, sonomicrometer measurements of stroke volume were significantly lower at rest and higher at VO2max. These differences mirrored changes in end-diastolic volume, although end-systolic volume did not change. At all exercise intensities, stroke volume was most variable and end-diastolic volume the least. The pattern conforms to the Frank-Starling mechanism, and indicates that at high exercise intensities ventricular myocytes generate high pressures with higher myocardial wall stress due to the increased size of the chamber.

Animals↗
PubMed1999

Evaluation of detection techniques and laboratory proficiency in testing for drugs of abuse in urine: an external quality assessment scheme using clinically realistic urine samples. Steering Committee for the United Kingdom National External Quality Assessment Scheme for Drugs of Abuse in Urine.

Techniques for the detection of drugs of abuse were compared using data from 43 urine samples distributed by the United Kingdom National External Quality Assessment Scheme. Drug mixtures simulated clinical specimens and contained drugs at the following median concentrations: amphetamine 1.6 mg/L (six samples), barbiturates 1.7 mg/L (six samples), benzoylecgonine 0.6 mg/L (eight samples), benzodiazepines 1.6 mg/L (four samples), cannabinoids 59 micrograms/L (four samples), methadone 1.7 mg/L (11 samples) and morphine 1.7 mg/L (seven samples). Significant lack of sensitivity was demonstrated for one or more analytes by all chromatographic techniques, including gas chromatography with mass spectrometry. Commercial immunoassay kits exhibited higher sensitivity, though some assays performed significantly less well than others. Significant non-specificity was also a greater problem for chromatographic techniques compared with immunoassays in samples containing therapeutic agents not structurally related to abused compounds. In the presence of therapeutic interferents structurally related to the test compounds, false positive reports for illicit materials increased from < 1% to > 6%. Use of confirmatory tests significantly reduced the incidence of both false negative and false positive reports.

Evaluation Studies as Topic↗
PubMed1999

Psychosocial factors associated with the use of breast cancer screening by women age 60 years or over.

This study examined psychosocial factors related to breast cancer screening among older women. Data for the study were obtained from interviews with 719 women age 60 years or over attending rural and urban primary care clinics in North Carolina. The results indicated that 50% of the women had mammograms in the past year, 65% reported clinical breast examinations in the past year, and 31% said they practiced breast self-examinations once a month. Several psychosocial factors were significant predictors of a lower likelihood of being screened. Multivariate analysis confirmed the importance of psychosocial factors as predictors of breast cancer screening. Educational intervention to increase screening for breast cancer in this population is needed, and the results provide specific suggestions regarding the content of effective educational materials and approaches for older women.

Aged↗
PubMed1999

Phase II trial of i.v. vinorelbine and cisplatin in inoperable locally advanced or disseminated non-small-cell lung cancer: the South African experience.

PURPOSE: This multicentre phase II trial was conducted in South Africa to evaluate the activity of a combination of vinorelbine, administered in a new schedule, and cisplatin, in chemonaive patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between September 1995 and December 1996, 35 patients were enrolled. All patients had at least one bidimensionally measurable lesion. Vinorelbine was administered intravenously on day 1 and day 8 at a dose of 30 mg/m2 and cisplatin was administered intravenously on day 1 at a dose of 100 mg/m2. The chemotherapy cycle was repeated every three weeks. RESULTS: Of 35 evaluable patients, 14 (40%) achieved a response (one complete response and 13 partial responses). The median time to progression was 6.4 months (range 12-572 days) and the median survival was 15.7 months (range 12-882+ days). One-year survival was 56%. Toxicity was manageable and consisted of nausea and vomiting (grade 3 in 45% of patients) and grade 3-4 neutropenia seen in 13 patients with three patients experiencing grade 3 infection. Other side-effects were mild, including constipation grade 3 in 9.1%. A total of 153 courses were administered with patients receiving a median dose intensity of 81.7% for vinorelbine, while that of cisplatin was 74.1%. CONCLUSION: The combination of vinorelbine and cisplatin demonstrated substantial activity in terms of objective response and survival with manageable side-effects in patients with advanced NSCLC. These findings confirm the data from previous randomised studies. Further studies are ongoing in order to evaluate the efficacy of this combination in the neoadjuvant and adjuvant setting.

Adult↗