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1.
Int J Cosmet Sci ; 40(4): 367-376, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29876949

ABSTRACT

OBJECTIVES: Petrolatum and soybean oil are common ingredients incorporated in topical skin formulations for skin protection and moisturization. However, the stratum corneum (SC) penetration kinetics of these two cosmetic ingredients has not been systematically studied. Glyceryl monooleate (GlyMOle) has been shown to enhance skin penetration of various compounds. It was hypothesized that GlyMOle could enhance skin penetration of petrolatum and soybean oil. This study aimed to examine the in vitro skin penetration of petrolatum and soybean oil in the presence or absence of GlyMOle. METHODS: Skin permeation experiments were conducted using the in vitro Franz diffusion cell model with split-thickness human skin and human epidermal membrane (HEM). The effect of permeant dose and the kinetics of permeant penetration were examined with and without GlyMOle in vitro. RESULTS: Petrolatum and soybean oil were found to permeate across HEM, and no effect of GlyMOle on skin permeation into the receptor chamber was observed. GlyMOle enhanced the penetration of petrolatum into the split-thickness skin at 50 µg dose (petrolatum:GlyMOle, 49 : 1, w/w). However, no effect of GlyMOle on petrolatum penetration was observed at 200 µg dose (of the same petrolatum:GlyMOle ratio), indicating a dose-dependent effect. GlyMOle at the level used in the study did not enhance the penetration of soybean oil with 50 and 200 µg doses at any timepoints. CONCLUSION: GlyMOle was a skin penetration enhancer for petrolatum under the in vitro conditions identified in this study.


Subject(s)
Glycerides/pharmacology , Petrolatum/pharmacokinetics , Skin Absorption/drug effects , Soybean Oil/pharmacokinetics , Administration, Cutaneous , Humans , In Vitro Techniques
2.
Arch Dermatol ; 137(10): 1303-7, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11594853

ABSTRACT

BACKGROUND: The issue of workforce requirements in dermatology has come to attention in recent years because it affects the delivery of dermatologic care in the United States. OBJECTIVE: To determine the waiting times for appointments with dermatologists in order to assess the adequacy of the current level of dermatology workforce. METHODS: Waiting times were determined for new and return patient appointments by telephone survey of a random sample of American Academy of Dermatology members. Physicians' perception of the adequacy of the number of dermatologists in their area was used as a criterion standard to validate waiting times as a measure of workforce adequacy. Benchmark waiting times of 3 weeks for a new patient appointment and 2 weeks for a return appointment were established. RESULTS: Physicians' estimates of the waiting time for a new patient appointment and their perceptions of the adequacy of the number of practicing dermatologists in their area were closely correlated (r = -0.65; P<.001), validating the use of waiting times as a measure of workforce adequacy. More than 60% of the dermatologists surveyed exceeded the criterion cutoff waiting times, and more than 42% of the US population lives in areas underserved by dermatologists. Dermatologists practicing in areas of higher population density were more likely to have shorter waiting times for new patient appointments and were more likely to include cosmetic dermatology in their practices. CONCLUSION: The long waiting times for appointments suggests that the current supply of dermatologists is not adequate to meet the demand for dermatologists' services.


Subject(s)
Attitude of Health Personnel , Dermatology , Needs Assessment , Waiting Lists , Benchmarking , Humans , Internet , Surveys and Questionnaires , Time Factors , United States , Workforce
3.
Semin Oncol Nurs ; 17(3): 159-70, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11523482

ABSTRACT

OBJECTIVES: To highlight sociocultural factors reported to influence and strategies to promote breast and cervical cancer screening and early detection behaviors of racial and ethnic minority women. DATA SOURCES: Published articles, book chapters, and reports. CONCLUSIONS: The most successful strategies for promoting screening and early detection among racial and ethnic minority women are collaborative and include approaches that are culturally sensitive and appropriate. NURSING IMPLICATIONS: Intercultural and intracultural differences in racial and ethnic minority women challenge nurses to explore strategies that focus on the health care provider, the health care delivery system, and the individual woman within the context of the woman's culture.


Subject(s)
Breast Neoplasms/ethnology , Breast Neoplasms/prevention & control , Cultural Diversity , Mass Screening , Uterine Cervical Neoplasms/ethnology , Uterine Cervical Neoplasms/prevention & control , Breast Neoplasms/nursing , Delivery of Health Care , Female , Humans , Mass Screening/methods , Oncology Nursing , United States , Uterine Cervical Neoplasms/nursing , Women's Health
5.
Dermatol Surg ; 27(12): 1035-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11849266

ABSTRACT

BACKGROUND: Despite being the most prevalent form of cancer, the economic impact of nonmelanoma skin cancer (NMSC) in the United States has not been assessed. OBJECTIVE: To determine the overall cost and to estimate the cost per episode of NMSC care in the United States in physicians' offices, outpatient surgery centers, and inpatient settings. METHODS: Data from the Medicare Current Beneficiary Study 1992-1995 were analyzed to obtain the total cost of NMSC and the cost in different settings. To normalize these data on a per episode basis, the cost in each setting was divided by the number of procedures performed in each setting obtained from the National Hospital Discharge Survey (NHDS, 1992-1997), the National Survey of Ambulatory Surgery (NSAS, 1994-1996), and the National Ambulatory Medical Care Survey (NAMCS, 1995). RESULTS: The total cost of NMSC care in the United States in the Medicare population is $426 million/year. Physician office-based procedures for NMSC accounted for the greatest percentage of money spent to treat NMSC and the greatest percentage of procedures. The average cost per episode of NMSC when performed in a physician's office setting was found to be $492. The cost per episode of care in inpatient and outpatient settings were $5537 and $1043, respectively. CONCLUSION: Compared to other cancers, the relative magnitude of NMSC treatment costs is currently small because NMSC is managed efficiently and effectively, primarily in office-based settings. Legislative or regulatory measures that discourage office treatment of NMSC will lead to increased cost.


Subject(s)
Carcinoma, Basal Cell/economics , Carcinoma, Squamous Cell/economics , Skin Neoplasms/economics , Ambulatory Surgical Procedures , Biopsy/economics , Carcinoma, Basal Cell/surgery , Carcinoma, Squamous Cell/surgery , Hospital Costs , Hospitalization/economics , Humans , Office Visits/economics , Skin Neoplasms/surgery , United States
7.
Am J Hosp Palliat Care ; 17(2): 87-96, 2000.
Article in English | MEDLINE | ID: mdl-11406963

ABSTRACT

If institutional systems that provide end-of-life care are to survive the demands of managed care, they will need to tie together methods of assessing the needs of the dying, leading to a new understanding of the functioning of a patient's existing helping networks. This paper presents the preliminary findings of a research project conducted at a Midwest hospice. The study utilized a cross sectional correlational survey of patients' needs via the Early Risk and Resiliency Inventory (ERRI), while mapping their helping networks with a Circles of Care Ecomap. It addressed the question, "What is the relationship between the needs of the dying and the formal and informal support provided?" Study findings supported the contention that higher need patients utilized the more expensive institutional services rather than relying on available natural networks; and statistical analysis of the study instrument suggested the creation of a new conceptual domain of psychospiritual need.


Subject(s)
Community Networks , Hospice Care/psychology , Needs Assessment/organization & administration , Patient Care Planning/organization & administration , Social Support , Surveys and Questionnaires/standards , Aged , Aged, 80 and over , Attitude to Health , Caregivers/psychology , Cross-Sectional Studies , Family/psychology , Female , Humans , Iowa , Male , Middle Aged , Models, Organizational , Risk Assessment , Social Work Department, Hospital
8.
Int J Paediatr Dent ; 10(3): 206-12, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11310113

ABSTRACT

OBJECTIVES: To assess the demand for paediatric dental general anaesthetic services at a specialist paediatric dental unit in Australia and to evaluate the changing pattern of general anaesthetic use in children at this unit over the past decade. METHODS: A retrospective review of hospital records of a random sample of children receiving dental treatment under general anaesthesia during the years 1984 and 1996. Demographic and clinical data was collated and analysed using SPSS for Windows. RESULTS: The number of children managed under general anaesthesia increased from 189 in 1984 to 777 in 1996. This was accompanied by an increase in the time the patients waited for treatment. There was little difference in the mean age of the patients with over two-thirds of the children being under the age of 6 years. Whilst children of Anglo-Saxon origin accounted for the majority of patients across the 13-year period there was a significant increase in the number of children from Asian or Middle Eastern backgrounds. A disproportionate number of these children accessed the services as self-referrals. Caries remained the most common reason for referral, with trauma and dental anomalies accounting for less than 10%. CONCLUSIONS: Despite the general decline in dental caries there remain an important group of young children who have high treatment needs and for whom general anaesthesia provides a useful treatment option. Preventive strategies should be targeted towards these groups of children.


Subject(s)
Ambulatory Surgical Procedures/statistics & numerical data , Anesthesia, Dental/methods , Anesthesia, General/statistics & numerical data , Dental Care for Children/methods , Chi-Square Distribution , Child , Child, Preschool , Dental Caries/therapy , Ethnicity , Humans , Infant , New South Wales , Referral and Consultation/statistics & numerical data
9.
J Virol ; 74(1): 326-33, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10590121

ABSTRACT

We devised an experimental system to examine sequential events by which the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) interacts with CD4 and coreceptor to induce membrane fusion. Recombinant soluble CD4 (sCD4) activated fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) but lacking CD4. sCD4-activated fusion was dose dependent, occurred comparably with two- and four-domain proteins, and demonstrated Env-coreceptor specificities parallel to those reported in conventional fusion and infectivity systems. Fusion activation occurred upon sCD4 preincubation and washing of the Env-expressing effector cells but not the coreceptor-bearing target cells, thereby demonstrating that sCD4 exerts its effects by acting on Env. These findings provide direct functional evidence for a sequential two-step model of Env-receptor interactions, whereby gp120 binds first to CD4 and becomes activated for subsequent functional interaction with coreceptor, leading to membrane fusion. We used the sCD4-activated system to explore neutralization by the anti-gp120 human monoclonal antibodies 17b and 48d. These antibodies reportedly bind conserved CD4-induced epitopes involved in coreceptor interactions but neutralize HIV-1 infection only weakly. We found that 17b and 48d had minimal effects in the standard cell fusion system using target cells expressing both CD4 and coreceptor but potently blocked sCD4-activated fusion with target cells expressing coreceptor alone. Both antibodies strongly inhibited sCD4-activated fusion by Envs from genetically diverse HIV-1 isolates. Thus, the sCD4-activated system reveals conserved Env-blocking epitopes that are masked in native Env and hence not readily detected by conventional systems.


Subject(s)
CD4 Antigens/physiology , HIV Envelope Protein gp120/physiology , Membrane Fusion/physiology , 3T3 Cells , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Epitopes/immunology , HIV Envelope Protein gp120/immunology , HIV-1/genetics , HIV-1/immunology , HeLa Cells , Humans , Mice , Protein Binding
11.
J Biol Chem ; 274(21): 14942-7, 1999 May 21.
Article in English | MEDLINE | ID: mdl-10329695

ABSTRACT

Dynamin is a 100-kDa GTPase that assembles into multimeric spirals at the necks of budding clathrin-coated vesicles. We describe three different intramolecular binding interactions that may account for the process of dynamin self-assembly. The first binding interaction is the dimerization of a 100-amino acid segment in the C-terminal half of dynamin. We call this segment the assembly domain, because it appears to be critical for multimerization. The second binding interaction occurs between the assembly domain and the N-terminal GTPase domain. The strength of this interaction is controlled by the nucleotide-bound state of the GTPase domain, as shown with mutations in GTP binding motifs and in vitro binding experiments. The third binding interaction occurs between the assembly domain and a segment that we call the middle domain. This is the segment between the N-terminal GTPase domain and the pleckstrin homology domain. The three different binding interactions suggest a model in which dynamin molecules first dimerize. The dimers are then linked into a chain by a second binding reaction. The third binding interaction might connect adjacent rungs of the spiral.


Subject(s)
GTP Phosphohydrolases/chemistry , Dynamins , Models, Molecular , Protein Binding , Protein Structure, Tertiary , Yeasts/metabolism
12.
Cancer Pract ; 7(5): 233-9, 1999.
Article in English | MEDLINE | ID: mdl-10687592

ABSTRACT

OBJECTIVES: Grief is the expected reaction to the death of a family member or close friend and is accompanied by substantial distress for almost everyone who experiences it. For some the grief response becomes complicated. This pilot study sought to identify individuals at high risk for complicated grief, by 1) examining the relationships that exist between family functioning before the death, psychological distress, and the grief reaction of a family after the death, and 2) presenting the use of screening with standardized measures to identify those at risk. MATERIALS AND METHODS: This pilot study examined the relationships between family functioning, psychological distress, and grief reaction. A cross-sectional design was used and the instrument included the Family Adaptability and Cohesion Evaluation Scale (FACES III), the Brief Symptom Inventory (BSI), and the Texas Revised Inventory of Grief (TRIG). Significant relationships were identified between the level of family functioning, psychological distress and grief reaction. Depression, anxiety, and general distress were significantly correlated with the two subscales of the TRIG. CONCLUSIONS: The findings clearly illustrate the merit of psychosocial screening of spouses and suggest the possible benefits of screening before the patient's death, using FACES III and the BSI to identify which spouses are at risk for complicated grief reactions.


Subject(s)
Attitude to Death , Grief , Mass Screening/methods , Neoplasms/psychology , Psychiatric Status Rating Scales/standards , Spouses/psychology , Stress, Psychological/psychology , Aged , Analysis of Variance , Cross-Sectional Studies , Family/psychology , Female , Humans , Male , Middle Aged , Models, Psychological , Pilot Projects , Predictive Value of Tests , Risk Factors , Stress, Psychological/diagnosis
13.
Curr Opin Genet Dev ; 8(4): 472-80, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9729725

ABSTRACT

Maternal factors laid down in the oocyte regulate blastomere identities in the early Caenorhabditis elegans embryo by activating zygotic patterning genes and restricting their expression to the appropriate lineages. A number of early-acting zygotic genes that specify various cell fates have been identified recently and their temporal and spatial regulation by maternal factors has begun to be elucidated.


Subject(s)
Caenorhabditis elegans/embryology , Animals , Caenorhabditis elegans/genetics , Endoderm , Gene Expression Regulation, Developmental , Signal Transduction , Zygote
14.
J Biol Chem ; 273(37): 23799-804, 1998 Sep 11.
Article in English | MEDLINE | ID: mdl-9726990

ABSTRACT

Fractalkine is a multimodular human leukocyte chemoattractant protein and a member of the chemokine superfamily. Unlike other human chemokines, the chemokine domain of fractalkine has three amino acids between two conserved cysteines, referred to as the CX3C motif. Both plasma membrane-associated and shed forms of fractalkine have been identified. Here, we show that the recombinant 76-amino acid chemokine domain of fractalkine is a potent and highly specific chemotactic agonist at a human orphan receptor previously named V28 or alternatively CMKBRL1 (chemokine beta receptor-like 1), which was shown previously to be expressed in neutrophils, monocytes, T lymphocytes, and several solid organs, including brain. CMKBRL1/V28 also functioned with CD4 as a coreceptor for the envelope protein from a primary isolate of HIV-1 in a cell-cell fusion assay, and fusion was potently and specifically inhibited by fractalkine. Thus CMKBRL1/V28 is a specific receptor for fractalkine, and we propose to rename it CX3CR1 (CX3C chemokine receptor 1), according to an accepted nomenclature system.


Subject(s)
CD4 Antigens/physiology , Calcium/metabolism , Chemokines, CX3C , Chemokines, CXC/metabolism , Chemokines/pharmacology , HIV-1/physiology , Membrane Proteins/metabolism , Membrane Proteins/physiology , Receptors, Chemokine/physiology , Receptors, HIV/physiology , CD4 Antigens/genetics , CX3C Chemokine Receptor 1 , Cell Fusion , Cell Line , Cell Membrane/metabolism , Chemokine CX3CL1 , Chemokines/physiology , Chemokines, CXC/pharmacology , Cloning, Molecular , Humans , Kidney , Kinetics , Membrane Proteins/genetics , Membrane Proteins/pharmacology , Radioligand Assay , Receptors, Chemokine/genetics , Receptors, HIV/genetics , Recombinant Fusion Proteins/metabolism , Recombinant Proteins/pharmacology , Transfection
15.
Ethn Health ; 2(3): 243-53, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9426988

ABSTRACT

The goals of this education outreach demonstration study were to prepare a cadre of registered nurses (RN) as Church Health Educators (CHE), and to test the efficacy of a hypertension (HBP) education and support program in African American (AA) churches for persons with HBP in managing blood pressure (BP). In this two-phase study, RNs were prepared as CHEs in phase 1 and a convenience sample of 97 subjects with HBP was taught by the CHEs in phase 2. The intervention's content included the bases of HBP and HBP management strategies, and was taught in eight 1-hour sessions. Using a pre-test-post-test design, data on knowledge, social support and BP were collected at baseline (pre), post-intervention (post1) and 3 months post-intervention (post2). Major findings include: (1) there was a significant increase in knowledge scores from pre to post1 and post2 (P < or = 0.0001; F = 95.08; df = 1.79); (2) education, age and number of years with HBP explained 49% of the variance associated with HBP knowledge; (3) systolic BP (SBP) and mean arterial BP (MAP) significantly decreased from pre to post1 and post2 (SBP-p < or = 0.0001, F = 18.35, df = 1.91; MAP-p < or = 0.0001, F = 17.80, df = 1.86); (4) DBP significantly decreased from pre to post1 only (p < or = 0.008, F = 17.48, df = 1.91); and (5) relationships were found between social support and DBP, and social support and MAP. Issues that emerged from this study with implications for outreach programming include recruitment and retention, randomization, selective sampling, intervention design and use of volunteers.


Subject(s)
Black People , Christianity , Health Education/organization & administration , Hypertension/prevention & control , Adult , Black or African American , Analysis of Variance , Blood Pressure , Chicago , Female , Health Knowledge, Attitudes, Practice , Humans , Linear Models , Male , Middle Aged , Program Evaluation , Risk Factors
16.
Genomics ; 41(2): 286-9, 1997 Apr 15.
Article in English | MEDLINE | ID: mdl-9143509

ABSTRACT

The dynamins are recently discovered GTP-binding proteins postulated to mediate the scission of clathrin-coated vesicles at the plasma membrane. Of the three known mammalian dynamins, dynamin-1 (DNM1) appears to be particularly important for the formation of synaptic vesicles at presynaptic nerve termini. To investigate the possibility that mutations in the DNM1 gene cause a human disease, we determined the chromosomal localization of human DNM1. We conclude from fluorescence in situ hybridization and from the analysis of somatic cell hybrids that the map position in 9q34. This region has syntenic homology with mouse chromosome 2p, in agreement with the map position of the mouse DNM1 gene [see accompanying article by Klocke et al. (1997, Genomics 41:290-292)]. We discuss the potential relevance of the human DNM1 localization to diseases that were mapped genetically to the same chromosomal region.


Subject(s)
Chromosomes, Human, Pair 9 , GTP Phosphohydrolases/genetics , GTP-Binding Proteins/genetics , In Situ Hybridization, Fluorescence , Animals , CHO Cells , Cricetinae , Dynamin I , Dynamins , Humans , Hybrid Cells
17.
Pediatr Surg Int ; 12(2-3): 81-5, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9156878

ABSTRACT

The dictum, "There is nothing new in surgery not previously described", is particularly true of hypospadias. The major significance of chordee was fully appreciated by Galen in the second century A. D. and then almost forgotten until Mettauer in 1842, all previous surgeons overstressing the position of the orifice. Mettauer recognised skin shortening as a cause of chordee, a fact not re-discovered until 1967. Urethroplasty from penile skin in situ was well described by Thiersch in 1869 and Duplay in 1874; additional covering skin flaps were developed in 1892 by Lauenstein. The modern enthusiasm for pedicle tubes from prepuce was first employed by Van Hook in 1896, Rochet in 1899, Hamilton Russell in 1900, and Mayo in 1901; the "buried skin" technique of Denis Browne was described by Duplay in 1880, although attributed by Browne to Hamilton Russell in 1915. Even scrotal tissues were incorporated in repairs in 1860 (Bouisson). Beck, in 1898, practised a repair for balanitic hypospadias very similar to the modern MAGPI repair, and free grafts, so popularised in the last 20 years, were performed by Nové-Josserand in 1897. We have certainly advanced from the era of the first millenium A. D., in which the treatment was amputation beyond the orifice, but almost all present-day techniques are well-founded in ideas developed by enterprising surgeons of the last century.


Subject(s)
Hypospadias/history , Skin Transplantation/history , Surgical Flaps/history , History, 19th Century , History, 20th Century , History, Ancient , Humans , Hypospadias/surgery , Male
18.
Cryobiology ; 33(5): 487-501, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8893508

ABSTRACT

Intraembryonic freezing (IEF) in Anopheles mosquito embryos has been evaluated by differential scanning calorimetry with respect to embryo age, temperature, rate and duration of cooling, and absence or presence of extraembryonic ice. The initial temperatures for intraembryonic ice nucleation were -30.1 +/- 0.3, -28.4 +/- 0.4, and -29.1 +/- 0.2 degree C for embryos incubated for 15 h at 17 degrees C, 15 h at 26 degrees C, and 24 h at 26 degrees C, respectively, after oviposition. The first value is slightly but significantly lower than the latter two. These values were obtained on embryos in which the surface water was removed by brief drying; however, the values were nearly identical when external water and ice were present. Not only were the embryos of all three ages able to supercool at least transiently to -26 degrees C, but they could remain supercooled for up to 4 h at -20 degrees C after being cooled to -20 degrees C at 10 degrees C/min or (in the case of embryos incubated for 15 h at 26 degrees C) at 100 degrees C/min. The amount of freezable water in single embryos has been calculated from the differential scanning calorimetry measurements to be 3.45 +/- 0.08, and 3.53 +/- 0.06 microgram for embryos incubated for 15 h at 17 degrees C, 15 h at 26 degrees C, and 24 h at 26 degrees C, respectively. The differences are not significant. The corresponding values for the total water contents for embryos of the three ages were 4.04 +/- 0.20, 3.72 +/- 0.16, and 3.98 +/- 0.10 microgram, values that also did not differ significantly. Water thus makes up approximately 74% of the total weight of the embryo (approximately 5.3 micrograms) and about 91% of that water is freezable. Total water contents were determined gravimetrically after extensive air and vacuum drying. The kinetics of dehydration were determined during the air drying. They differed substantially among the three ages. The embryos incubated for 15 h at 17 degrees C lost water at about four times the rate of those incubated for 15 h at 26 degrees C and 10 times the rate of the embryos incubated for 24 h at 26 degrees C.


Subject(s)
Anopheles/embryology , Embryo, Nonmammalian/physiology , Animals , Anopheles/physiology , Freezing
20.
J Air Waste Manag Assoc ; 46(11): 1075-1080, 1996 Nov.
Article in English | MEDLINE | ID: mdl-28071519

ABSTRACT

Plasma processing has been identified as a useful tool for immobilizing heavy metal-contaminated wastes into safe, leach-resistant slag. Although much effort has gone into developing this technology on a pilot scale, not much information has been published on basic research topics. A laboratory-scale plasma arc furnace located at the University of Illinois was operated in cooperation with the U.S. Army Construction Engineering Research Laboratories in an effort to establish an understanding of the chemical and physical processes (such as metal volatilization and resultant gas evolution) that occur during thermal plasma treatment of metal-spiked samples. Experiments were conducted on nickel and chromium using a highly instrumented furnace equipped with a 75 kW transferred arc plasma torch. The volatility of nickel and chromium was examined as a function of varying oxygen partial pressures. Oxidizing conditions reduced the total dust gathered for both the nickel and chromium samples, although each dust sample was found to be metal-enriched. Plasma treating increased the leach-resistance of the slags by at least one order of magnitude when compared to unprocessed specimens. The leach- resistance of the nickel-containing slags increased in the presence of oxygen, whereas chromium samples remained relatively constant.

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