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The Journal of allergy and clinical immunology 05/2013; · 9.17 Impact Factor
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Stacy J Chin,
Brian P Vickery,
Michael D Kulis,
Edwin H Kim,
Pooja Varshney,
Pamela Steele,
Janet Kamilaris,
Anne M Hiegel,
Suzanna K Carlisle,
P Brian Smith,
Amy M Scurlock, Stacie M Jones,
A Wesley Burks
The Journal of allergy and clinical immunology 03/2013; · 9.17 Impact Factor
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ABSTRACT: The field of food allergy is continually changing, with advances in clinical care to better understand the mechanisms of disease and in possible new diagnostics and treatment models. The development of several new guidelines that focus on improving the standardization of the diagnosis and management of food allergy has helped to further guide clinicians in providing optimized care for children and adults with food allergy around the world. Much of this work has been made possible through the collaborative efforts of advocacy organizations, industry, and government with clinicians and researchers in the fields of allergy and immunology. We have been able to advance our understanding of disease mechanisms and to help close gaps in knowledge and resolve misconceptions in the treatment of food allergy. This review will focus on the concepts of a holistic approach to food allergy that is working to improve CARE for subjects with food allergy, including new advances in clinical care, advocacy, research, and education.
The Journal of allergy and clinical immunology 01/2013; 131(1):3-11. · 9.17 Impact Factor
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David M Fleischer,
A Wesley Burks,
Brian P Vickery,
Amy M Scurlock,
Robert A Wood, Stacie M Jones,
Scott H Sicherer,
Andrew H Liu,
Donald Stablein,
Alice K Henning,
Lloyd Mayer,
Robert Lindblad,
Marshall Plaut,
Hugh A Sampson
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ABSTRACT: There are presently no available therapeutic options for patients with peanut allergy.
We sought to investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT).
After a baseline oral food challenge (OFC) of up to 2 g of peanut powder (approximately 50% protein; median successfully consumed dose [SCD], 46 mg), 40 subjects, aged 12 to 37 years (median, 15 years), were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5-g OFC was performed after 44 weeks, followed by unblinding; placebo-treated subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5-g OFC. Week 44 OFCs from both groups were compared with baseline OFCs; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders.
After 44 weeks of SLIT, 14 (70%) of 20 subjects receiving peanut SLIT were responders compared with 3 (15%) of 20 subjects receiving placebo (P < .001). In peanut SLIT responders, median SCD increased from 3.5 to 496 mg. After 68 weeks of SLIT, median SCD significantly increased to 996 mg (compared with Week 44, P = .05). The median SCD at the Week 44 Crossover OFC was significantly higher than baseline (603 vs 71 mg, P = .02). Seven (44%) of 16 crossover subjects were responders; median SCD increased from 21 to 496 mg among responders. Of 10,855 peanut doses through the Week 44 OFCs, 63.1% were symptom free; excluding oral-pharyngeal symptoms, 95.2% were symptom free.
Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo. Longer duration of therapy showed statistically significant increases in the SCD.
The Journal of allergy and clinical immunology 01/2013; 131(1):119-127.e7. · 9.17 Impact Factor
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Robert A Wood,
Scott H Sicherer,
Brian P Vickery, Stacie M Jones,
Andrew H Liu,
David M Fleischer,
Alice K Henning,
Lloyd Mayer,
A Wesley Burks,
Alexander Grishin,
Donald Stablein,
Hugh A Sampson
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ABSTRACT: OBJECTIVE: There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes. METHODS: Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg. Children enrolled with a clinical history of milk allergy were followed longitudinally, and resolution was established by means of successful ingestion. RESULTS: The cohort consists of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Milk allergy has resolved in 154 (52.6%) subjects at a median age of 63 months and a median age at last follow-up of 66 months. Baseline characteristics that were most predictive of resolution included milk-specific IgE level, milk SPT wheal size, and AD severity (all P < .001). Baseline milk-specific IgG(4) level and milk IgE/IgG(4) ratio were not predictive of resolution and neither was expression of cytokine-inducible SH2-containing protein, forkhead box protein 3, GATA3, IL-10, IL-4, IFN-γ, or T-bet by using real-time PCR in CD25-selected, casein-stimulated mononuclear cells. A calculator to estimate resolution probabilities using baseline milk IgE level, SPT response, and AD severity was devised for use in the clinical setting. CONCLUSIONS: In this cohort of infants with milk allergy, approximately one half had resolved over 66 months of follow-up. Baseline milk-specific IgE level, SPT wheal size, and AD severity were all important predictors of the likelihood of resolution.
The Journal of allergy and clinical immunology 12/2012; · 9.17 Impact Factor
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Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 12/2012; 109(6):470-1. · 2.83 Impact Factor
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Brian P Vickery,
Jing Lin,
Michael Kulis,
Zhiyan Fu,
Pamela H Steele, Stacie M Jones,
Amy M Scurlock,
Gustavo Gimenez,
Ludmilla Bardina,
Hugh A Sampson,
A Wesley Burks
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ABSTRACT: BACKGROUND: Patients with peanut allergy have highly stable pathologic antibody repertoires to the immunodominant B-cell epitopes of the major peanut allergens Ara h 1 to 3. OBJECTIVE: We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires. METHODS: Measurements of total peanut-specific IgE (psIgE) and peanut-specific IgG(4) (psIgG(4)) were made with CAP-FEIA. We analyzed sera from 22 patients with OIT and 6 control subjects and measured serum specific IgE and IgG(4) binding to epitopes of Ara h 1 to 3 using a high-throughput peptide microarray technique. Antibody affinity was measured by using a competitive peptide microarray, as previously described. RESULTS: At baseline, psIgE and psIgG(4) diversity was similar between patients and control subjects, and there was broad variation in epitope recognition. After a median of 41 months of OIT, polyclonal psIgG(4) levels increased from a median of 0.3 μg/mL (interquartile range [25% to 75%], 0.1-0.43 μg/mL) at baseline to 10.5 μg/mL (interquartile range [25% to 75%], 3.95-45.48 μg/mL; P < .0001) and included de novo specificities. psIgE levels were reduced from a median baseline of 85.45 kU(A)/L (23.05-101.0 kU(A)/L) to 7.75 kU(A)/L (2.58-30.55 kU(A)/L, P < .0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated patients, several subjects generated new IgE specificities, even as the total psIgE level decreased. Global epitope-specific shifts from IgE to IgG(4) binding occurred, including at an informative epitope of Ara h 2. CONCLUSION: OIT differentially alters Ara h 1 to 3 binding patterns. These changes are variable between patients, are not observed in control subjects, and include a progressive polyclonal increase in IgG(4) levels, with concurrent reduction in IgE amount and diversity.
The Journal of allergy and clinical immunology 11/2012; · 9.17 Impact Factor
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ABSTRACT: The β2-adrenergic receptor (β2AR) is an important target for respiratory and cardiovascular disease medications. Clinical studies suggest that amino-terminal polymorphisms of the β2AR may act as disease modifiers. We hypothesized that polymorphisms at amino acids 16 and 27 result in differential trafficking and down-regulation of β2AR variants following β-agonist exposure. The functional consequences of the four possible combinations of these polymorphisms in the human β2AR (designated β2AR-RE, -GE, -RQ and -GQ) were studied using site-directed mutagenesis and recombinant expression in HEK 293 cells. Ligand binding assays demonstrated that after 24 h exposure to 1 µM isoproterenol, isoforms with Arg16 (β2AR-RE and β2AR-RQ) underwent increased down-regulation compared to isoforms with Gly16 (β2AR-GE and β2AR-GQ). Consistent with these differences in down-regulation between isoforms, prolonged isoproterenol treatment resulted in diminished cyclic AMP response to subsequent isoproterenol challenge in β2AR-RE relative to β2AR-GE. Confocal microscopy revealed that the receptor isoforms had similar co-localization with the early endosomal marker EEA1 following isoproterenol treatment, suggesting that they had similar patterns of internalization. None of the isoforms exhibited significant co-localization with the recycling endosome marker Rab11 in response to isoproterenol treatment. Furthermore, we found that prolonged isoproterenol treatment led to a higher degree of co-localization of β2AR-RE with the lysosomal marker Lamp1 compared to that of β2AR-GE. Taken together, these results indicate that a mechanism responsible for differential responses of these receptor isoforms to β-agonist involves differences in the efficiency with which agonist-activated receptors are trafficked to lysosomes for degradation, or differences in degradation in the lysosomes.
Cell Biology International 09/2012; · 1.48 Impact Factor
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A Wesley Burks, Stacie M Jones,
Robert A Wood,
David M Fleischer,
Scott H Sicherer,
Robert W Lindblad,
Donald Stablein,
Alice K Henning,
Brian P Vickery,
Andrew H Liu,
Amy M Scurlock,
Wayne G Shreffler,
Marshall Plaut,
Hugh A Sampson
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ABSTRACT: For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy.
In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months.
After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months.
These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.).
New England Journal of Medicine 07/2012; 367(3):233-43. · 53.30 Impact Factor
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ABSTRACT: To examine circumstances of allergic reactions to foods in a cohort of preschool-aged children.
We conducted a prospective, 5-site observational study of 512 infants aged 3 to 15 months with documented or likely allergy to milk or egg, and collected data prospectively examining allergic reactions.
Over a median follow-up of 36 months (range: 0-48.4), the annualized reaction rate was 0.81 per year (367/512 subjects reporting 1171 reactions [95% confidence interval: 0.76-0.85]). Overall, 269/512 (52.5%) reported >1 reaction. The majority of reactions (71.2%) were triggered by milk (495 [42.3%]), egg (246 [21.0%]), and peanut (93 [7.9%]), with accidental exposures attributed to unintentional ingestion, label-reading errors, and cross-contact. Foods were provided by persons other than parents in 50.6% of reactions. Of 834 reactions to milk, egg, or peanut, 93 (11.2%) were attributed to purposeful exposures to these avoided foods. A higher number of food allergies (P < .0001) and higher food-specific immunoglobulin E (P < .0001) were associated with reactions. Of the 11.4% of reactions (n = 134) that were severe, 29.9% were treated with epinephrine. Factors resulting in undertreatment included lack of recognition of severity, epinephrine being unavailable, and fears about epinephrine administration.
There was a high frequency of reactions caused by accidental and nonaccidental exposures. Undertreatment of severe reactions with epinephrine was a substantial problem. Areas for improved education include the need for constant vigilance, accurate label reading, avoidance of nonaccidental exposure, prevention of cross-contamination, appropriate epinephrine administration, and education of all caretakers.
PEDIATRICS 06/2012; 130(1):e25-32. · 4.47 Impact Factor
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ABSTRACT: Background. Secondary skin infection with Staphylococcus aureus is a significant problem in atopic dermatitis (AD) patients. Objective. This study evaluated antimicrobial resistance patterns of S aureus isolates from skin lesions in AD patients and empiric antimicrobial prescribing patterns. Methods. Resistance patterns from positive skin cultures obtained from AD patients in the Allergy/Immunology clinic from May 1, 2006, to December 31, 2008, were compared with all outpatient wound cultures over the same period. Results. Fifty-nine cultures were obtained from 38 AD patients. S aureus was the most common pathogen cultured from AD patients (53/59 cultures). S aureus resistance to clindamycin and methicillin differed significantly between the study group and the outpatient reference population (37.7% vs 9.4% and 45.3% vs 76.4%). Clindamycin was the most commonly prescribed antimicrobial (59%). Overall, 31.4% of organisms showed resistance to the antimicrobial prescribed. Conclusions. Susceptibility profiles of S aureus isolates from AD patients vary significantly from that of the general population.
Clinical Pediatrics 04/2012; · 1.15 Impact Factor
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ABSTRACT: Asthma disproportionately affects children living in impoverished communities; however, factors related to asthma morbidity among impoverished rural children have not been adequately described.
To examine factors associated with asthma morbidity among rural children living in the Arkansas Delta region.
We performed a cross-sectional investigation of 109 rural children with asthma enrolled in public schools in the Arkansas Delta region. A questionnaire format and home inspection were used to examine participant, caregiver, and home characteristics.
The median age of the study participants was 9 years, 83% were African American, and 71% had an annual household income of $20,000 or less. Ninety-eight percent of participants were insured, and most fit the criteria for uncontrolled asthma, yet only 23% reported taking inhaled corticosteroids. Transportation problems were cited by 20%. In the past 4 weeks, more than 50% reported rescue medication use or exercise limitations of 2 or more days per week or nocturnal symptoms of more than 2 nights per month. Emergency department visits in the past 6 months were reported by 28%, and 43% reported an unscheduled physician's visits for asthma in the past 3 months. Sixty-four percent had 1 or more positive allergen skin test results, and allergic sensitization was associated with exposure to dust mite, dog, mouse, and cockroach allergens in the home.
Asthma morbidity was high among this cohort of atopic asthmatic children in the Arkansas Delta. Overuse of rescue medications and underuse of inhaled corticosteroids were prevalent even though the population was highly insured and had frequent health care use. Future asthma health initiatives should focus on the unique challenges associated with translating national guidelines-based care to rural pediatric populations.
clinicaltrials.gov Identifier: NCT00590304.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 04/2012; 108(4):254-9. · 2.83 Impact Factor
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A Wesley Burks,
Mimi Tang,
Scott Sicherer,
Antonella Muraro,
Philippe A Eigenmann,
Motohiro Ebisawa,
Alessandro Fiocchi,
Wen Chiang,
Kirsten Beyer,
Robert Wood,
Jonathan Hourihane, Stacie M Jones,
Gideon Lack,
Hugh A Sampson
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ABSTRACT: Food allergies can result in life-threatening reactions and diminish quality of life. In the last several decades, the prevalence of food allergies has increased in several regions throughout the world. Although more than 170 foods have been identified as being potentially allergenic, a minority of these foods cause the majority of reactions, and common food allergens vary between geographic regions. Treatment of food allergy involves strict avoidance of the trigger food. Medications manage symptoms of disease, but currently, there is no cure for food allergy. In light of the increasing burden of allergic diseases, the American Academy of Allergy, Asthma & Immunology; European Academy of Allergy and Clinical Immunology; World Allergy Organization; and American College of Allergy, Asthma & Immunology have come together to increase the communication of information about allergies and asthma at a global level. Within the framework of this collaboration, termed the International Collaboration in Asthma, Allergy and Immunology, a series of consensus documents called International Consensus ON (ICON) are being developed to serve as an important resource and support physicians in managing different allergic diseases. An author group was formed to describe the natural history, prevalence, diagnosis, and treatment of food allergies in the context of the global community.
The Journal of allergy and clinical immunology 02/2012; 129(4):906-20. · 9.17 Impact Factor
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ABSTRACT: To develop and validate a food allergy educational program.
Materials developed through focus groups and parental and expert review were submitted to 60 parents of newly referred children with a prior food allergy diagnosis and an epinephrine autoinjector. The main outcome was correct demonstration of an autoinjector.
The correct number of autoinjector activation steps increased from 3.4 to 5.95 (of 6) after training (P < .001) and was 5.47 at 1 year (P < .05). The mean score for comfort with using the autoinjector (7-point Likert scale) before the curriculum was 4.63 (somewhat comfortable) and increased to 6.23 after the intervention (P < .05) and remained elevated at 1 year (6.03). Knowledge tests (maximum 15) increased from a mean score of 9.2 to 12.4 (P < .001) at the initial visit and remained at 12.7 at 1 year. The annualized rate of allergic reactions fell from 1.77 (historical) the year prior, to 0.42 (P < .001) after the program. On a 7-point Likert scale, all satisfaction categories remained above a favorable mean score of 6: straight-forward, organized, interesting, relevant, and recommend to others.
This food allergy educational curriculum for parents, now available online at no cost, showed high levels of satisfaction and efficacy.
The Journal of pediatrics 11/2011; 160(4):651-6. · 4.02 Impact Factor
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ABSTRACT: Data from many studies have suggested a rise in the prevalence of food allergies during the past 10 to 20 years. Currently, no curative treatments for food allergy exist, and there are no effective means of preventing the disease. Management of food allergy involves strict avoidance of the allergen in the patient's diet and treatment of symptoms as they arise. Because diagnosis and management of the disease can vary between clinical practice settings, the National Institute of Allergy and Infectious Diseases (NIAID) sponsored development of clinical guidelines for the diagnosis and management of food allergy. The guidelines establish consensus and consistency in definitions, diagnostic criteria, and management practices. They also provide concise recommendations on how to diagnose and manage food allergy and treat acute food allergy reactions. The original guidelines encompass practices relevant to patients of all ages, but food allergy presents unique and specific concerns for infants, children, and teenagers. To focus on those concerns, we describe here the guidelines most pertinent to the pediatric population.
PEDIATRICS 11/2011; 128(5):955-65. · 4.47 Impact Factor
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The Journal of the Arkansas Medical Society 11/2011; 108(6):103-4.
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The Journal of allergy and clinical immunology 05/2011; · 9.17 Impact Factor
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Pooja Varshney, Stacie M Jones,
Amy M Scurlock,
Tamara T Perry,
Alex Kemper,
Pamela Steele,
Anne Hiegel,
Janet Kamilaris,
Suzanne Carlisle,
Xiaohong Yue,
Mike Kulis,
Laurent Pons,
Brian Vickery,
A Wesley Burks
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ABSTRACT: Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials.
To investigate the safety and effectiveness of OIT for peanut allergy in a double-blind, placebo-controlled study.
In this multicenter study, children ages 1 to 16 years with peanut allergy received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge (OFC) at approximately 1 year. Titrated skin prick tests (SPTs) and laboratory studies were performed at regular intervals.
Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study because of allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (n = 16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), whereas placebo subjects (n = 9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg; P < .001). In contrast with the placebo group, the peanut OIT group showed reductions in SPT size (P < .001), IL-5 (P = .01), and IL-13 (P = .02) and increases in peanut-specific IgG(4) (P < .001). Peanut OIT subjects had initial increases in peanut-specific IgE (P < .01) but did not show significant change from baseline by the time of OFC. The ratio of forkhead box protein 3 (FoxP3)(hi): FoxP3(intermediate) CD4+ CD25+ T cells increased at the time of OFC (P = .04) in peanut OIT subjects.
These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The current study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance.
The Journal of allergy and clinical immunology 03/2011; 127(3):654-60. · 9.17 Impact Factor
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The Journal of allergy and clinical immunology 03/2011; 127(5):1309-10.e1. · 9.17 Impact Factor
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Joshua A Boyce,
Amal Assa'a,
A Wesley Burks, Stacie M Jones,
Hugh A Sampson,
Robert A Wood,
Marshall Plaut,
Susan F Cooper,
Matthew J Fenton,
S Hasan Arshad, [......],
Bruce D Levy,
Phil Lieberman,
Stefano Luccioli,
Kathleen M McCall,
Lynda C Schneider,
Ronald A Simon,
F Estelle R Simons,
Stephen J Teach,
Barbara P Yawn,
Julie M Schwaninger
Nutrition 02/2011; 27(2):253-67. · 3.03 Impact Factor