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Is There Cross-Reactivity Between Penicillins and Cephalosporins?
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1 The American Journal of Medicine (2006) 119, 354.e e20 CLINICAL RESEARCH STUDY Is There Cross-Reactivity Between Penicillins and Cephalosporins? Andrea J. Apter, MD, MSc, a,b,c Judith L. Kinman, MA, b Warren B. Bilker, PhD, b,d Maximilian Herlim, b David J. Margolis, MD, PhD, b,d,e Ebbing Lautenbach, MD, MPH, MSCE, b,d,f Sean Hennessy, PharmD, PhD, b,c,d Brian L. Strom, MD, MPH b,c,d a Division of Pulmonary, Allergy Critical Care Medicine, Department of Medicine; b Center for Clinical Epidemiology and Biostatistics and Center for Education and Research on Therapeutics; c Leonard Davis Institute of Health Economics; d Department of Biostatistics and Epidemiology; e Department of Dermatology; f Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, Pa. ABSTRACT BACKGROUND: We sought to determine the risk of an allergic reaction to a cephalosporin exposure in those with prior penicillin reactions. METHODS: We conducted a retrospective cohort study using the United Kingdom General Practice Research Database. We selected all patients receiving a prescription for penicillin followed by a prescription for a cephalosporin and identified allergic-like events within 30 days after each prescription. Allergic events were defined by 2 sets of codes: 1 more restrictive, 1 more inclusive. Comparison was made with a population of patients receiving a prescription for a penicillin followed by a prescription for a sulfonamide antibiotic. RESULTS: A total of patients received a penicillin; (15%) received a subsequent cephalosporin. Among patients receiving a penicillin followed by a cephalosporin, the unadjusted risk ratio of an allergic-like event for those who had a prior event, compared with those who had no such prior event, narrowly defined, was 10.1 (confidence interval ). The absolute risk of anaphylaxis after a cephalosporin was less than 0.001%. The unadjusted risk ratio for sulfonamide antibiotic, rather than cephalosporin after penicillin allergic-like events was 7.2 (confidence interval ). CONCLUSION: Patients with allergic-like events after penicillin had a markedly increased risk of events after either subsequent cephalosporins or sulfonamide antibiotics. Cross-reactivity is not an adequate explanation for this increased risk, and the risk of anaphylaxis is very low. Thus, our data indicate that cephalosporins can be considered for patients with penicillin allergy Elsevier Inc. All rights reserved. KEYWORDS: Antibiotic allergy; Adverse drug reaction; Drug hypersensitivity; Penicillin; Cephalosporin Support was provided by the Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics Cooperative Agreement (grant HS10399) and the National Heart, Lung, and Blood Institute (HL K , Dr. Apter). Requests for reprints should be addressed to Andrea J. Apter, MD, MSc, 829 Gates Building, Hospital of the University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA address: Whether patients allergic to penicillin are at increased risk for an allergic reaction to cephalosporins has remained unknown since the introduction of cephalosporins. 1-4 Spurring this question is the fact that antibiotics share a beta-lactam ring. Indeed, cross-reacting antibodies have been identified in the laboratory. 5 Hypersensitivity to cephalosporins also has been reported in patients with penicillin allergy with a prevalence ranging from 3% to 18%. 1,2,6-8 At least 1 reported fatality resulted from anaphylaxis attributed to a cephalosporin administered to a penicillin-allergic patient. 9 However, not all reports support the notion that patients allergic to penicillin are at increased risk for an allergic reaction to a cephalosporin. 10,11 No controlled epidemiologic studies address the /$ -see front matter 2006 Elsevier Inc. All rights reserved. doi: /j.amjmed
2 354.e12 The American Journal of Medicine, Vol 119, No 4, April 2006 question of clinical cross-reactivity. 1,2 Nevertheless, physicians are cautioned about prescribing cephalosporins for penicillin-sensitive patients because cross-sensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. 12 A national task force recently emphasized the importance of research to improve prevention and management of drug hypersensitivity reactions. 13 A major component of this research is understanding the risk of cephalosporin hypersensitivity in patients with penicillin allergy. With the increase in bacterial antimicrobial resistance, particularly multidrug resistance, therapeutic options are increasingly limited. Furthermore, avoidance of an antibiotic because of an allergy history may result in the selection of a less effective or more toxic antibiotic. To study the question of allergic cross-reactivity between penicillins and cephalosporins, we conducted a retrospective cohort study using the United Kingdom General Practice Research Database (GPRD), a database of electronic primary care medical records and prescriptions. To better understand etiology, we compared our results with analyses replacing cephalosporin with sulfonamide antibiotics because there is no known structural or immunologic cross-reactivity between penicillin and sulfonamide antibiotics. METHODS Data Source: General Practice Research Database GPRD contains the actual outpatient medical records from 687 general practitioner (GP) practices geographically representative of England and Wales, comprising 6% of this population. The database includes demographic information, prescription drug information, clinical events and diagnoses, and hospital admissions, as entered by the GP. Contributing GPs are required to meet specific recording standards to be considered Up to Standard (UTS) Prior studies suggest that the clinical information in GPRD is of high quality for epidemiologic studies The UTS data provide a window of observation for patients, that is, prescriptions written before or after the UTS dates were not considered in this study. CLINICAL SIGNIFICANCE Patients with allergic-like events following penicillin have a markedly increased risk of an allergic-like event following a subsequent cephalosporin. Such patients also have a similarly increased risk of an allergic-like event following a sulfonamide antibiotic. Crossreactivity is not an adequate explanation for this finding. Patients with allergic-like events following penicillin have a very low risk of anaphylaxis following a subsequent cephalosporin ( 0.001%). Our data indicate that cephalosporins can be considered for patients with penicillin allergy. Study Population We identified all patients in the GPRD UTS database from 1987 to September 2001 who received a prescription for penicillin (Figure 1). Within that population, we identified patients who also received a cephalosporin prescription at least 60 days after a penicillin prescription. The 60-day interval between the first penicillin and the subsequent cephalosporin prescription ensured that an event after the cephalosporin was not a late event associated with the earlier penicillin. This cohort was used for the primary analyses. Two subgroups were compared to calculate the risk of an allergiclike event after a cephalosporin. The study group consisted of patients who had an allergic-like event within 30 days after a penicillin prescription. The first penicillin prescription followed by an allergic-like event was called the index penicillin prescription. Comparison subjects never had an allergic-like event within 30 days after any penicillin prescription. For the comparison group, the index penicillin prescription was the first prescribed penicillin. Antibiotics Identification From the British National Formulary, we identified codes for cephalosporins (British National Formulary code 5.1.2) and classified them by generation (Appendix A). 28,29 We also identified codes for penicillin (British National Formulary code 5.1.1) 28 and sulfonamide antibiotics (Appendix A). Allergic-Like Events Identification There is no clinical gold standard for a drug hypersensitivity reaction. Thus, we constructed 2 sets of codes, 1 restrictive and 1 more inclusive, for an allergic-like event, recorded 1 to 30 days after an antibiotic prescription. Both sets included diagnoses like anaphylaxis, urticaria, angioedema, erythema multiforme, laryngeal spasm, drug-induced dermatitis, and toxic epidermal necrolysis (Appendix B). Because diagnostic codes like bronchospasm or asthma could represent an adverse drug reaction, but frequently refer to asthma independent of adverse drug reactions, we excluded such codes from the narrowly defined set. Bronchospasm, asthma, eczema, and adverse drug reactions were then included in the broadly defined set of codes. The results were comparable. Unless otherwise specified, the results presented are those using the narrow definition.
3 Apter et al Penicillin and Cephalosporin Allergy 354.e13 Figure 1 Study protocol. The narrow definition of allergic-like event (ALE) is used. Primary Analyses The cohort was defined using Knowledge Manager (IMS Health, Frankfurt, Germany), a patient-level data warehouse and analysis tool developed for accessing GPRD. Analyses were performed using SAS Version 8.1 (SAS Institute Inc., Cary, NC) and STATA, Release 7.0 (StataCorp, College Station, Tex). Analyses were performed among all patients receiving 1 or more prescriptions for penicillin, reviewing the occurrence of allergic-like events 1 to 30 days after a prescription for penicillin and the probability of receiving a subsequent cephalosporin prescription. The primary analyses focused on all patients who received penicillin followed at least 60 days later by a cephalosporin prescription. We excluded events occurring on the prescription day because it was impossible to discern whether a drug given on the day of an event was responsible for an event or prescribed afterward. However, we included the antibiotic prescription day in a sensitivity analysis. The risk ratio (RR) was computed for the risk of an allergic-like event after the cephalosporin prescription in patients experiencing an allergic-like event after a prior penicillin exposure, compared with those with no events after the penicillin exposure. For perspective, we computed the RR for an allergic-like event after a sulfonamide antibiotic prescription (rather than a cephalosporin) for patients experiencing an allergic-like event within 30 days after a penicillin prescription. All ratios were computed with 95% confidence intervals (CIs). Logistic regression, which yields an odds ratio (OR) rather than an RR, was used to evaluate variables as potential confounders, examining each (eg, prior urticaria) individually. Confounders changing the point estimate of the OR of interest by 15% or more were included in the final adjusted model. 30 Age, sex, and cephalosporin generation were tested as effect modifiers of the relationship between exposure (ie, reaction to a penicillin) and outcome (ie, reaction to a cephalosporin) using the Breslow-Day Test for OR homogeneity. 31 Age was considered a continuous and categorical variable to allow for a nonlinear effect. Other potential confounders were the occurrence, before the index penicillin, of acute processes with manifestations similar to an acute hypersensitivity reaction, including diseases associated with a rash resembling an adverse drug reaction such as Epstein- Barr virus or vasculitis (Appendix C). We also adjusted for prior history of allergic-like events that together constitute the events under study such as urticaria or asthma (broad
4 354.e14 The American Journal of Medicine, Vol 119, No 4, April 2006 Table 1 Demographics of Subjects by Study Group or Comparison Group* Study Group* N 3920 Comparison Group N Total N Age (y) N % N % N % Sex Male Female *Proportions for the broad dataset were similar. Age was missing for 252 subjects. event codes only), both singly and as a group, and current use (within 30 days before the index cephalosporin prescription) of drugs known or suspected to be indicators of hypersensitivity/allergic reactions, such as corticosteroids or antihistamines. Finally, we accounted for the nonindependent nature of multiple patients from the same GP practice (ie, clustering) using the Huber-White sandwich estimator 32,33 for the variance of the model parameter estimates. 34 Sensitivity Analyses Several sensitivity analyses were performed to support the validity of our primary analysis. We included the antibiotic prescription day in the time interval for allergic-like events. We computed the RR limiting the interval to 10 (rather than 30) days after the penicillin prescription, the cephalosporin prescription, and both prescriptions. We excluded patients without 30 days of follow-up after the cephalosporin. Finally, we excluded those with penicillin prescriptions on the same day or within 30 days of the cephalosporin. We received approval from the Scientific and Ethical Advisory Group of the GPRD. The University of Pennsylvania Institutional Review Board determined that the protocol warranted exempt status. RESULTS Subjects Of patients receiving at least 1 prescription for penicillin (Figure 1), patients (using a narrow definition; patients using a broad definition of allergiclike event) received prescriptions for a penicillin followed by a cephalosporin. The demographics of these patients are presented in Table 1. Of the prescribed cephalosporins, 64% were first-generation antibiotics. Using either the broad or narrow definitions, 22% of the patients who had an allergic-like event after a penicillin were given a subsequent prescription for cephalosporin, compared with 16% (broad definition, 14%) who had never had an allergic-like event after penicillin. Allergic-Like Events The absolute numbers of allergic-like events other than urticaria were very small (Table 2). Twenty-five patients experienced anaphylaxis after the penicillin, and of these, 1 subject experienced anaphylaxis after the cephalosporin. In all, anaphylaxis was reported for 13 subjects after the cephalosporin. In this analysis, 30 (70%) of 43 patients who Table 2 Description of Allergic-like Events after Penicillin and Cephalosporin Prescriptions* Reaction type Index penicillin N 3920 subjects N (% of reactions) Cephalosporin N 624 subjects N (% of reactions) Anaphylaxis 25 (0.64) 13 (2.08) 1 Angioedema 106 (2.70) 15 (2.40) 3 Laryngospasm 19 (0.48) 2 (0.32) 0 Urticaria 2904 (74.1) 461 (73.9) 30 Erythema multiforme 174 (4.44) 24 (3.85) 1 Toxic epidermal necrolysis 2 (0.05) 1 (0.16) 0 Dermatitis caused by an ingested drug 13 (0.33) 1 (0.16) 0 Adverse drug reaction attributed to an antibiotic 677 (17.3) 107 (17.2) 2 ALE allergic-like event. *Narrow definition: N Subjects with same ALE after both antibiotics
5 Apter et al Penicillin and Cephalosporin Allergy 354.e15 Table 3 Primary Results and Sensitivity Analyses Using Various Assumptions for the Risk of an Allergic-like Event after an Antibiotic* Primary analyses Penicillin followed by cephalosporin Penicillin followed by sulfonamide antibiotic Sensitivity analyses Including day of antibiotic prescription Limiting observation after penicillin to 1-10 d Limiting observation after cephalosporin to 1-10 d Limiting observation after both antibiotics to 1-10 d Removing patients who did not have 30 d of follow-up after cephalosporin prescription Removing patients with a penicillin prescription within 30 d of the cephalosporin prescription ALE after both penicillin and second antibiotic ALE allergic-like event; CI confidence interval. *Allergic-like events are narrowly defined. NO ALE after both penicillin and second antibiotic ALE after penicillin but not after second antibiotic ALE after second antibiotic but not after penicillin Unadjusted risk ratio (95% CI) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) experienced allergic-like events after both penicillin and cephalosporin had urticaria after both antibiotics. There was a substantial increase in risk of having an allergic-like event after cephalosporin in patients who had experienced an event after the earlier penicillin; 1.1% of the patients who had an event after penicillin also had an event after the cephalosporin, for an unadjusted RR of 10.0 (CI ) (Table 3). The unadjusted RR using the broad definition for events was 15.2 (CI ). Using the narrow definition, no potential confounders changed the OR of interest by 15% or more in the analysis of allergic-like events. For perspective, we also analyzed allergic-like events after prescriptions for a sulfonamide antibiotic rather than a cephalosporin (Table 3); 1.6% of the patients who had an event after penicillin also had an event after the sulfonamide. The unadjusted RR of an allergic-like event after a sulfonamide in patients who had an event after a preceding penicillin, compared with patients who had no such prior event, was 7.2 (CI ). The corresponding data using the broad codes were similar. Sensitivity Analyses The results of the sensitivity analysis are presented in Table 3. When the prescription day of the antibiotic is included or the time interval after the antibiotic prescription is varied, the RRs change numerically but are clinically similar to the primary unadjusted analyses. In summary, these analyses support our primary results. DISCUSSION We used a large electronic medical record database to measure the risk of an allergic-like event after a prescription for a cephalosporin in patients with a previous allergic-like event after penicillin. We found a substantially increased risk whether we used broad or narrow codes for allergic-like events. However, the risk was similar for those patients receiving a sulfonamide antibiotic after an earlier event following penicillin. These findings argue against specific immunologic cross-reactivity between penicillins and cephalosporins. Because there is no clinical gold standard for a drug hypersensitivity reaction, we conducted 2 analyses using both narrowly and broadly defined codes for allergic-like events. The narrowly defined set likely has fewer false-positive events but more false-negative events. The broader set has the opposite limitation: more false positives and fewer false negatives. Obtaining similar results from both analyses reduces the risk of an incorrect result because of misclassification of the allergic-like event. It is also noteworthy that both sets of codes are relevant to the clinician. That is, clinicians are often confronted with patients describing allergic events somewhat vaguely, reflecting the broader codes.
6 354.e16 The American Journal of Medicine, Vol 119, No 4, April 2006 The absolute risk of all events, after cephalosporin intake in patients who had had an event after penicillin, whether using broad or narrow datasets, was vanishingly small. The rate of anaphylaxis was less than 0.001% using either definition of allergic event. One patient experienced anaphylaxis after both antibiotics (Table 2). Thus, although there is a substantial relative increase in risk, the absolute risk suggests these events are rare. Recently, we performed a related study examining the risk of an allergic event after a subsequent antibiotic prescription in patients with an allergic-like event after the first antibiotic prescription. 24,25 A retrospective cohort of 969 patients was used to examine whether cross-reactivity existed between sulfonamide antibiotics and sulfonamide non-antibiotics (eg, furosemide, hydrochlorothiazide, glyburide). 24 We found an association between an allergic-like event after a sulfonamide antibiotic and an allergic-like event after a subsequent sulfonamide non-antibiotic. This OR (6.6 [CI ]) was comparable to that of an allergic-like event after a penicillin for patients who had had an earlier event following a sulfonamide antibiotic (unadjusted OR 7.8 [CI ]). As in our current study, these findings did not support allergic cross-reactivity of 2 medication classes with structural similarity. Thus, examining different antibiotic combinations, we have shown that patients who have 1 allergic-like event are at risk for a subsequent event. Allergic cross-reactivity does not explain these phenomena. Instead, another mechanism may better explain these events, such as genetic predisposition. This is a study of clinical events documented in the outpatient medical record, not of patient report of allergy. It is in the outpatient setting that patients are most likely to be labeled as having an antibiotic allergy. 35 Many studies of drug allergy focus on hospitalized patients, who may have a different reaction rate than outpatients. Also, our study attempts to consider all events consistent with a hypersensitivity reaction and is not limited to dermatologic reactions, although these are among the most identifiable. Thus, we are attempting to capture the more serious clinical events related to drug hypersensitivity occurring in the outpatient population. It is important to recognize that although these events may be coded as allergic, we have no way of verifying an immunologic etiology. What we describe are signs and symptoms as the practicing clinician perceives them and makes medical decisions. Surprisingly, a higher proportion of patients who experienced an allergic-like event after penicillin subsequently received cephalosporin, compared with patients who experienced no allergic-like event after a prior penicillin, suggesting that practitioners substituted cephalosporin for penicillin in patients with prior events. Nevertheless, we cannot exclude the possibility that patients who did not receive cephalosporin after the index penicillin originally had events more consistent with drug allergy. Our study has limitations. Misclassification of an allergic-like event is a possibility, but the similarity of results from both the narrow and broad analyses supports our result. A limitation is the difficulty in studying time from prescription to the clinical event consistent with a hypersensitivity reaction. Medical records note patient contacts with their physician; it is possible that events were not reported immediately and/or not diagnosed. Also, prescriptions may not have been filled, or filled promptly, or once filled, not taken. To validate our methods, we repeated analyses with a second time interval of 10 days, examining the effect of the shorter surveillance period after either, then both, the index and subsequent antibiotic prescriptions. The RRs were not substantively changed. It is possible that patients had medical events before entering or after leaving a GPRD-participating practice, before or after their physician s participation in GPRD was terminated, or after September Such events were not captured in this study. Undercounting may have occurred if patients had a very severe reaction to penicillin, such as toxic epidermal necrolysis or anaphylaxis, before entering the GPRD database and subsequently avoided future prescriptions. However, these events are so rare they are unlikely to influence our results. Finally, the generalizability of the GPRD to other countries is unclear, given differences in population demographics. In conclusion, for patients who had an allergic-like event after penicillin, the risk of an allergic-like event after a subsequent cephalosporin is markedly increased, but the risk is similarly elevated for those patients after a sulfonamide antibiotic. Thus, cross-reactivity of penicillin and cephalosporin does not fully explain this increased risk, and the risk of anaphylaxis and other very serious adverse events is very low. Thus, our data indicate that cephalosporins can be considered for patients with penicillin allergy. References 1. Saxon A, Beall GN, Rohr AS, Adelman DC. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med. 1987;107: Kelkar PS, Li JT. Cephalosporin allergy. N Engl J Med. 2001;345: Greenberger PA. Drug Allergy, Part B: Allergic Reactions to individual drugs: low molecular weight. In: Grammer LC, Greenberger PA, eds. Patterson s Allergic Diseases, 6th Edition. 1 vol. Philadelphia: Lippincott, Williams & Wilkins; 2002: Puchner TC Jr., Zacharisen MC. A survey of antibiotic prescribing and knowledge of penicillin allergy. Ann Allergy Asthma Immunol. 2002; 88: Zhao Z, Baldo BA, Rimmer J. Beta-lactam allergenic determinants: fine structural recognition of a cross-reacting determinant on benzylpenicillin and cephalothin. Clin Exp Allergy. 2002;32: Dash CH. Penicillin allergy and the cephalosporins. J Antimicrob Chemother. 1975;1: Girard JP. Common antigenic determinants of penicillin G, ampicillin and the cephalosporins demonstrated in men. Int Arch Allergy Appl Immunol. 1968;33: Thoburn R, Johnson JE 3rd, Cluff LE. Studies on the epidemiology of adverse drug reactions. IV. The relationship of cephalothin and penicillin allergy. JAMA. 1966;198: Pumphrey RS, Davis S. Under-reporting of antibiotic anaphylaxis may put patients at risk. Lancet. 1999;353:
7 Apter et al Penicillin and Cephalosporin Allergy 354.e Anne S, Reisman RE. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol. 1995;74: Macy E, Burchette RJ. Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up. Allergy. 2002;57: Anon. Physicians Desk Reference, 57th Edition. Montvale, NJ: Medical Economics Company; Adkinson NF Jr., Essayan D, Gruchalla R et al. Task force report: future research needs for the prevention and management of immunemediated drug hypersensitivity reactions. J Allergy Clin Immunol. 2002;109:S461-S Anon. Statistics of N. The General Practice Research Database: Information for Researchers. London: GPRD, Office for National Statistics, Department of Health; EPIC. The General Practice Research Database: A Guide for Researchers. London: EPIC; Lawson D, Sherman V, Hollowell J. The General Practice Research Database. Q J Med. 1998;91: Lewis JD, Brensinger C, Bilker WB, Strom BL. Validity and completeness of the General Practice Research Database for studies of inflammatory bowel disease. Pharmacoepidemiol Drug Saf. 2002;11: Jick H, Jick SS, Derby LE. Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. BMJ. 1991;302: Jick H, Terris BZ, Derby L, Jick S. Further validation of information recorded on a general practitioner based computerized data resource in the United Kingdom. Pharmacoepidemiol Drug Saf. 1992;1: McKeever TM, Lewis SA, Smith C, et al. Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database. J Allergy Clin Immunol. 2002;109: Margolis DJ, Bilker W, Knauss J, Baumgarten M, Strom BL. The incidence and prevalence of pressure ulcers among elderly patients in general medical practice. Ann Epidemiol. 2002;12: Margolis DJ, Bilker W, Santanna J, Baumgarten M. Venous leg ulcer: incidence and prevalence in the elderly. J Am Acad Dermatol. 2002; 46: Bashford JN, Norwood J, Chapman SR. Why are patients prescribed proton pump inhibitors? Retrospective analysis of link between morbidity and prescribing in the General Practice Research Database. BMJ. 1998;317: Strom BL, Schinnar R, Apter AJ, et al. Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med. 2003;349: Apter AJ, Kinman JL, Bilker W, et al. Re-prescription of penicillin following allergic-like events. J Allergy Clin Immunol. 2004;113; van Staa TP, Wegman S, de Vries F, Leufkens B, Cooper C. Use of statins and risk of fractures. JAMA. 2001;285: Hennessy S, Strom BL. Statins and fracture risk. JAMA. 2001;285: British National Formulary 43. March London: British Medical Association, Royal Pharmaceutical Society of Great Britain; Gilbert D, Moellering RJ, Sande M. The Sanford Guide to Antimicrobial Therapy, 30th Edition. Hyde Park, VT: Antimicrobial Therapy Inc.; Rothman K, Greenland S. Modern Epidemiology. Philadelphia: Lippincott Williams and Wilkins; Breslow NE, Day NE. Statistical Methods in Cancer Research. Volume II-The Design and Analysis of Cohort Studies. Lyon: International Agency for Research on Cancer; Huber PJ. The Behavior of Maximum Likelihood Estimates Under Non-standard Conditions. Berkeley, CA: University of California; White H. A heteroskedasticity-consistent covariance matrix estimator and a direct test for heteroskedasticity. Econometrika. 1980;48: StataCorp. STATA Statistical Software: Release 7.0. College Station, TX: Stata Press; Huovinen P, Cars O. Control of antimicrobial resistance: time for action. The essentials of control are already well known. BMJ. 1998; 317: Lis Y, Mann R. The VAMP Research multi-purpose database in the U.K. J Clin Epidemiol. 1995;48: Gelfand JM, Margolis DJ, Dattani H. The UK General Practice Research Database. In: Strom BL, ed. Pharmacoepidemiology, 4th Edition. Chichester: John Wiley & Sons, Ltd; 2005:
8 354.e18 The American Journal of Medicine, Vol 119, No 4, April 2006 Appendix A Penicillins, Cephalosporins, and Sulfonamide Antibiotics Selected from British National Formulary Groups 28 BNF Penicillins BNF Sulphonamides and trimethoprim BNF Benzyl and phenoxymethyl penicillins Benethamine penicillin BNF Antimalarials Benzathine penicillin Dapsone Benzylpenicillin Sulphadoxine Penicillin Sulphonamide antibiotic Penicillin G Sulfphaguanidine Penicillin V BNF Sulphonamide and trimethoprim BNF Penicillinase-resistant penicillin Sulphaloxate Cloxacillin Sulphamoxole Flucloxacillin Sulphadiazine Methicillin sodium Cotrimoxazole Teocillin Phthalylsulphathiazole Succinylsulphathiazole BNF Broad-spectrum penicillins Sulfametopyrazine Amoxicillin Sulfasuxidine Amoxicillin clavulanic acid Sulfphacetamide Amoxicillin Sulfphadiazine Sulphadimethoxine BNF Anti-pseudomonal penicillins Sulphadimidine Ticarcillin Sulphafurazole Piperacillin Sulphaguandidine Sulphamerazine BNF Mecillinam Sulphamethazine Pivmecillinam Sulphamethizole Sulphamethoxypyridazine BNF Cephalosporins and Cephalomycins 29 Sulphaphenazole 1st generation Sulphapyridine Cefadroxil Sulphathiazole Cephalexin Sulphaurea Cefazolin Cephradine BNF Antileprotics Cephalexin Dapsone 2nd generation Cefaclor BNF Cefamandole Sulphanilamide nasal preparation Cefoxitin Cefprozil Cefuroxime 3rd generation Cefixime Cefodizime Cefotaxime Cefpodoxime Cefsulodin Ceftazidime Ceftibuten Ceftizoxime Ceftriaxone BNF British National Formulary. *BNF5.1.2 includes monobactams and carbapenems, but the numbers are small and their exclusion does not change the result.
9 Apter et al Penicillin and Cephalosporin Allergy 354.e19 Appendix B Diagnoses Included in the Definition of Hypersensitivity/Allergic Reaction* Narrow definition Allergic urticaria Anaphylactic shock Angioedema Dermatitis caused by drugs Erythema multiforme Laryngeal spasm Shock unspecified Shock without mention of trauma Stevens-Johnson Syndrome Toxic epidermal necrolysis Upper respiratory tract hypersensitivity reactions Urticaria Urticaria unspecified Selected codes for adverse drug reactions: Drug allergy Allergy drug by mouth Allergic drug reaction not specified (NOS) Hypersensitivity NOS Drug hypersensitivity NOS Adverse reaction to eye anti-infectives and other eye drugs Adverse reaction to anti-infectives and other enteric drugs Additional diagnoses in the broad definition Asthma Eczema Unspecified adverse effect of a drug, medicinal, and biologic substance NOS not otherwise specified. *Diagnoses are recorded using OXMIS (Oxford Medical Indexing System) codes that are cross-referenced to Read diagnostic codes. 36,37 Prescriptions are recorded using 2 drug code schemes (Multilex and Prescription Prescribing Authority of the National Health Service). 36,37 OXMIS and READ diagnostic codes are available on request.
10 354.e20 The American Journal of Medicine, Vol 119, No 4, April 2006 Appendix C Potential Confounding Variables Demographic variables: Age Sex Preexisting hypersensitivity/adverse reactions: See Appendix B Potential confounding drugs: Antihistamines Systemic and topical corticosteroids Other drugs used for asthma HIV human immunodeficiency virus. Potential confounding diagnoses: Allergic rhinitis Amyloid disease Arteritis Behçet disease Churg-Strauss disease Collagen vascular disease Erythromelalgia Giant cell arteritis Hay fever Mixed connective tissue disease Polyarteritis nodosa Polychondritis Polymyalgia rheumatica Raynaud s syndrome Rheumatoid arthritis Scleroderma Spondyloarthritis Systemic lupus erythematosus Takayasu s arteritis Vasculitis Wegener s granulomatosis Cytomegalovirus HIV infection Epstein-Barr virus infection Cellulitis Asthma Eczema
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text:
- Victoria
- I. biographical name 1819-1901 Alexandrina Victoria queen of Great Britain (1837-1901) II. biographical name Tomás Luis de circa 1548-1611 Spanish composer III. geographical name 1. city SE Texas on Guadalupe River population 60,603 2. city Canada capital of British Columbia on SE Vancouver Island population 74,125 3. river 350 miles (563 kilometers) Australia in NW Northern Territory flowing N & NW to Timor Sea 4. state SE Australia capital Melbourne area 87,884 square miles (228,498 square kilometers), population 4,244,221 5. (or Hong Kong) city & port Hong Kong special administrative region, China on NW Hong Kong Island; served as capital of Hong Kong colony population 1,026,870 • Victorian adjective or noun
New Collegiate Dictionary. 2001.

subset: commoncrawl


text:
Consent and Confidentiality Laws for Minors in the Western United States
Neinstein, Lawrence S.
Bibliographic Citation
Western Journal of Medicine. 1987 Aug; 147(2): 218-224.
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Abortion; Adolescents; Age Factors; Blood; Blood Donation; Children; Confidentiality; Contraception; Consent; Drug Abuse; Emergency Care; Government; Health; Informed Consent; Legal Aspects; Legislation; Laws; Married Persons; Medical Records; Mental Health; Minors; Notification; Parental Consent; Patient Access to Records; Patient Care; Records; Sex Offenses; State Government;
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Consent and Confidentiality Laws for Minors in the Western United States Neinstein, Lawrence S. (1987-08)
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Robust Gaming Console Sales To Provide A Significant Boost For AMD
- Sony has reported robust PlayStation 4 sales over the recent holiday season.
- Both PS4 and Microsoft's Xbox One have continued to sell well and contain AMD's CPUs and GPUs.
- The healthy console sales by the two companies will help AMD avoid major revenue disappointments as investors wait for the company to launch its much-awaited Zen PC Processors during the second half of 2016.
PC gaming has overtaken console gaming over the last couple of years in a somewhat ironic reversal of trends given how weak the PC market has become lately. PC gaming software sales in 2015 totaled ~$23.5B compared to ~22.5B for console gaming software. On the hardware side of things, PC gaming hardware sales totaled $21.5B vs. 11B for console hardware sales.
Source: GamingBolt
Industry-wide console gaming seems to have hit a plateau and is currently growing at a rather anemic pace. But this is not something you can tell by looking at console sales by the industry leaders, Sony Corp (NYSE:SNE), with its PlayStation 4, and Microsoft (NASDAQ:MSFT), with Xbox One. Sony has just released its latest PS4 sales numbers, which are impressive by any count. Sony has been reporting cumulative PS4 sales since it launched the console in November 2013. The company says that it has sold 35.9M PS4 consoles since its launch, up from 30.2M units sold by late November. In other words, Sony sold a good 5.7M PS4 consoles during the holiday season alone. Sony also says that it managed to sell a staggering 35M+ games through its PlayStation stores and other brick-and-mortar stores during the holiday season. Meanwhile, PlayStation subscriptions grew 60% Y/Y (Sony does not divulge the numbers here).
Microsoft has remained mum ever since it revealed that it had managed to sell 10M Xbox One units by November 2014, about 18 months after the launch of the console. NPD tracks monthly sales for PS4 and Xbox One, and PS4 frequently outsells its rival more often than not. Nevertheless, Xbox One sales have been impressive as well. According to NPD data, combined sales of PS4 and Xbox One for 25 months up to November 2015 were 47% higher than those by their predecessors PS3 and Xbox 360, implying a 21.2% annual growth clip over the period. PS4 is expected to perform even better in 2016.
That's great news for AMD (NASDAQ:AMD), because both PS4 and Xbox One are powered by AMD processors and graphic cards. Even better is the fact that sluggish gaming software sales have little effect on AMD. Both PS4 and Xbox One are kitted with a 28nm TSCM APU by AMD that features an eight-core Jaguar CPU paired with AMD's Radeon 7000-series GPU. The two rival consoles are powered by a virtually identical AMD CPU, the only major difference being that PS4 is clocked at 1.6GHz while Xbox One does better with 1.75GHz.
When it comes to graphics, PS4 and Xbox One are again remarkably similar since they are both powered by an AMD APU with PS4's GPU being slightly larger while Xbox One sports a higher clock speed. PS4 and Xbox One innards are largely similar, with the major differences being the RAM and storage units which are supplied by a different company other than AMD
So how much money does AMD make from selling gaming CPUs and GPUs to both Sony and Microsoft? IHS, well known for its phone/tablet tear-downs, estimated that AMD was receiving $100/unit when the PS4 launched two years ago. Since processor prices typically decline over the lifetime of a console, it's likely that AMD now receives ~$80 for every PS4 unit sold. So for the fourth quarter, AMD probably realized $456M for PS4 CPUs and GPUs. Since the processors and graphic units for PS4 and Xbox One are quite similar, its likely that AMD receives roughly the same for every Xbox One sold as it does for PS4. Assuming Microsoft sold 50% as many Xbox One consoles as Sony PS4s over the holiday period, then AMD probably realized $228M for Xbox One CPUs and GPUs. That's $684M from consoles for AMD, or nearly two-thirds of its revenue.
Looking at AMD's Q4 2015 guidance, you suspect that most of that revenue was booked during the third quarter. AMD guided for a 10% Q/Q revenue drop during the fourth quarter of FY 2015. AMD reported revenue of $1.04B during the third quarter, which implies that it expects fourth quarter revenue of $954M. The huge drop is probably due to the fact that the company expects lower consoles sales during the first quarter of 2016.
Looking at those revenue figures, it becomes clear that AMD relies very heavily on PS4 and Xbox One console sales for its top line. With both consoles continuing to do well, AMD investors can rest assured that the company is not likely to spring any major revenue disappointments over the coming quarters. That's important to help stabilize AMD stock as investors wait for the launch of AMD X86 Zen Processors during the second half of 2016. Zen is expected to breath new life into AMD's battered PC processor business, and the fact that it will hit the market around the time when then PC market is expected to start rebounding bodes well for AMD.


text: Hey all, looking for this bit of information like the title says. Just trying to add up the pressure drop for my total loop. I've found the info for everything else I plan to put in my loop and have been looking long and hard to find this one, but cannot seem to locate this info anywhere! So if anyone knows this I would really appreciate the knowledge!


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Starting 4/15, Harris Teeter will be having Super Doubles and all coupons face value $2 or below will be doubled! You can grab FREE Pine Bros Softish Throat Drops and pay ONLY $.20 each for Herdez Cooking Sauce with the Super Doubles!! Check it out:
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-Use one $.75/1 Herdez Cooking Sauce printable coupon (preclipped)
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Apricot Pillow Cookies – traditional Danish recipe.
Foodgawker: Composition – too tight
Sous vide sea bass on stack of brown rice pilaf and seaweed with cilantro sauce
Foodgawker: Harsh lighting and/or overexposed tastespotting: lighting/exposure
These margaritas will certainly liven up your weekend, both refreshing and delicious.
Foodgawker: Low lighting and/or underexposed
Lighting/exposure issues
French cheesy potatoes made easy!
composition too tight
Sous Vide Chicken and Mushroom Roulade with a mushroom espuma sauce
foodgawker: dull/unsharp image
Low lighting and/or underexposed
Simple, delicious, tangy, sweet. Lemon curd is a perfect addition to any dessert…or on its own.
Foodgawker: overexposed
Rejected by Food gawker for photo composition
I've been given the "composition" reason many times by Food Gawker. I don't really understand this reason though… Is it because they would like more props in the photo??
Sorry, …
With a bit of attention to weights, measures, and ingredients, the next pot of mac and cheese you make for your kids might actually be one you won't mind eating either.
Pumpkin bars gets a whole grain upgrade, and a cream cheese frosting spiked with Bourbon and real vanilla bean.


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|Half Baths
|864 sq. ft.
|Property type
|Minimum Stay
|2 - 3 nights
Enjoy some Mountain Seclusion in this 2 bedroom, 1 1/2 bath chalet located just minutes from downtown Gatlinburg where you can enjoy dining, shopping and all the fun attractions that are offered in the Great Smoky Mountains. You can grill hamburgers and
hot dogs on the charcoal grill and enjoy a picnic in your very own wooded wonderland. Come home from a long day of shopping & hiking to relax in a 4-6 person hot tub. This chalet has plenty to offer: three flat screen TV's, three DVD players, gas fireplace,
full kitchen, washer/dryer, sleeper sofa and sleeper loveseat. Enjoy a break from it all and some much needed family time together in this Smoky Mountain Home!
We also now have a 3 bedroom, 3 bath unit available for guests. vrbo 592306
Mountain Seclusion
Gatlinburg, TN 37738
Dear Valued Guest,
Thank you so much for staying with us here at Mountain Seclusion. As many of our guests are aware we offer 10% off your next stay with us if you go online and leave a review, however we have also decided to start a referral program for our Guest. So effective immediately and back dating to our very first guest we are now going to send a $10 Wal-Mart gift card to any of our Guest that refer a guest to stay with us. This is just a small token of our appreciation for being a valued guest. So please refer your family and friends to stay with us and have them give us the name that the reservation was made in along with the mailing address and we will send you this gift for every Guest you send that reserves, no matter how many.
Valid only for the name reserved on the original reservation.
The Taylor Family
vrbo 491031
I am a widow with two children. One of which is handicap and there is now a ramp to make it easier to take him in his wheelchair. I lost my husband in 2012 to cancer that he had fought for 13 years.
Mountain Seclusion Staff purchased this chalet in 2013
I purchased this property so that it would be a vacation home close to home and possibly a second home for me and my family.
The unique design and the seclusion that came with this property where what drew me to this property. The views are amazing and just the sense of privacy and not the busyness of downtown, yet the closeness to all the area attractions.
My family and I enjoyed our stay at the house there in TN. The house was just as the pictures portrayed it to be: clean, cute and cozy for my family of 6. So happy we picked this place with easy access to Gatlinburg and homey atmosphere. In addition, the contact person for the property was very helpful when calling for details on our arrival and then again when we arrived trying to get in to the home. Overall, just a great experience.
Overall great experience! Very nice cabin with a homely feel. Will recommend others to stay here. The one and only complaint is it needed hand towels and a few other regular towels.
We enjoyed our time at Mountian Seclusion! It was very clean and a short driving distance to Gatlinburg. Owner was wonderful in helping with any problems we had(minor -logs needed blowing out ) it was fixed by the time we were home from Dollywood! We definitely recommend staying here.
The house is well maintained,comfortable and pri ate.
The cabin was very conveniently located to Gatlinburg downtown and to get to Pigeon Forge. We didn't spend a lot of time at the cabin except morning and night, but it was clean and well set up. We loved the Dixie Stampede show, Dollywood (for us was less crowded on Saturday, very busy on Sunday), Pancake Pantry, and MagiQuest (better for older kids--7 year old could've stayed all day, my 4 year old gave up after about 30 min and my 2 year old was afraid). Thanks for a great visit!
We spent 9 nights of our Spring Break at Mountain Seclusion. Love the setting, spring views of LeConte, and close access to Gatlinburg and the National Park. We were very happy with the condition of the unit. Owner was very attentive to our needs. Quick response and did everything possible to address our needs. We do a lot of hiking, so it was nice to come back to a comfortable setting. Beds were very comfy and kitchen supplies were great (except more teaspoons really needed). Like the open concept of kitchen/living area. Love having the washer/dryer unit. WiFi and cable TV worked great. Nice outdoor space for kids to play. Food City Grocery/Gas nearby. Very handy. Definitely hope to be back next year!
Mountain Seclusion observes the right to change the rate on stays during heavier traveled dates. Customer will be given most accurate rates by contacting the staff directly.
|Rate Period
|Weekend Night
Nightly Rate
Nov 19 2017 - Nov 25 2017
3 night minimum stay
My Standard Rate
2 night minimum stay
|$70 + Tax
|Refundable damage deposit
|Tax Rate
Rates are subject to change prior to reservation confirmation.


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HJ has just bought a new website Antibiotic-online dot com
HJ has just bought new website www.antibiotic-online.com , a website about tips for removing cellulite and losing weight while taking antibiotics.
HJ has just new website www.antibiotic-online.com , a website about tips for removing cellulite and losing weight while taking antibiotics.
HJ bought this domain, because she used to get asked very often about antibiotics and weight loss. In fact, one woman has recently emailed HJ. She has been struggling with cellulite for a few year and after having found HJ's website about how to get rid of cellulite naturally, she has finally seen her first progresses. But because she had a bad sore throat, her doctor prescribed antibiotics for her.
After 2 weeks of cellulite all her cellulite progress was gone and in fact her cellulite has gotten so bad that she was ashame to leave the house without pants on. So, she emailed HJ and asked her what to about her situation.
HJ has always been a women who was interested in natural ways to cure any health issues. In fact she has always felt that taking antibiotics was the worst things you can do for your body, no matter what sort of illness one person has.
When she was a child, she was so sick that her doctor recommended antibiotics for her. After 2 days they destroyed her stomach flora so bad that she almost diet, so she has never taken antibiotics ever again. She still thinks that unless one person has a huge case of infection, he/she should not take antibiotics.
So, after a few weeks of research about how antibiotics influence weight loss for women and any cellulite treatments, she has finally decided to sum up all her conclusions in her new website http://antibiotic-online.com/ . Her website not only that speaks about the dangers of taking antibiotics and how they make weight loss and cellulite reduction almost impossible, but it also speaks about a few measures people can take to lose weight and get rid of cellulite if they took antibiotics.
She has bought this new domain, because she knew that a lot of people will look for antibiotics online and she wanted to prevent them from going through the dangers of taking antibiotics.
For the people who already took antibiotics, and want to lose weight or reduce their cellulite, in thei article they can read a few easy measures to take http://antibiotic-online.com/how-to-get-rid-of-cellulite-naturally-and-lose-weight-fast-if-you-take-antibiotics
About us:
After 3 years experience in health and fitness for women, we are dedicated to help women all over the world get in shape and get rid of cellulite fast.
Contact: Heather Jameson
Company: Cellulitenomore
Address: 122 Main Street, 03262, N. Woodstock, NH
Telephone No.: 603-745-8971
Website: http://antibiotic-online.com
HJ has just bought new website www.antibiotic-online.com , a website about tips for removing cellulite and losing weight while taking antibiotics.
how to get rid of cellulite on thighs fast , get rid of cellulite fast , on thighs , cellulite treatment , cellulite removal , how to lose cellulite , cellulite tips , cellulite diet , exercises , natural cellulite remedies , weight loss , fat loss
Sep 21, 2014


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Posted by ESPN.com's Paul Kuharsky
Let's play some post-holiday weekend catch up...
Houston Texans
With Antonio Smith out with a hamstring issue, Tim Bulman manned right defensive end like he owned it last week, writes Megan Manfull.
Several former Texans remain unsigned free agents, writes Alan Burge. You can always take that as a sign -- the rest of the league didn't place much value on your guys.
What sort of impact can Brian Cushing have? Jim McCurdy wonders.
Rashad Butler needs to be ready to back up both offensive tackles, says Burge.
A look at Houston's late-round draft picks, from Jesse Rios.
Indianapolis Colts
Hard work and strict discipline paved the way for Donald Brown, writes Phil Richards.
Among the five topics John Oehser ponders is how the offensive line's embarrassment over last year's performance will spur a big comeback.
The top five issues still facing the Colts, from Oehser.
Jim Caldwell talked to Marc Correnti. We found the link via Indyfootballreport.com.
Jacksonville Jaguars
The offense got a makeover, the defense gets a do-over, writes Vito Stellino.
Fred Taylor is taking a different training approach as a Patriot, says Stellino.
A look at the charity Reggie Nelson set up to honor his mom, from Josh Salman.
Looking at the Jaguars' options behind Maurice Jones-Drew with Daniel Shanks.
Tennessee Titans
As he tries to regain his starting job, Ryan Fowler admits he became complacent when he lost it, writes Gary Estwick.
A status report on the rookies after their first three practices with the veterans, from Jim Wyatt.
Bud Adams talked about founding the Oilers and ultimately moving them to Tennessee in this piece by Joe Biddle.
Leroy Harris is stuck as a backup for now, says Estwick.
Jevon Kearse likes it when Chuck Cecil is loud, according to David Boclair.


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Vintage Industrial Adjustable Wall Light
Love the look of anything vintage industrial? Then we've got the perfect lamp for you!
The Vintage Industrial Adjustable Wall Light is a beautiful and unique piece of light that's perfect for any part of your home or establishment. It would make a great lamp inside a bar, restaurant or even coffee shop. At home, it can work for both traditional styled spaces or sleek industrial ones.
Height 30 cm
Width: 10 cm
Depth: 120 cm
Requirements: 1 piece of E27 max 60 watt bulb
*Note: Please allow up to 21 days for delivery since each light is crafted in Ireland.
Product information
- aandp18086
- Wall lights
Delivery and returns
This item is sold and dispatched directly by Alexander and Pearl.
|Delivery cost
|England & Wales - standard delivery
|Scotland - standard delivery
We offer a 14 day no-quibble money-back guarantee, so if you're not delighted with your purchase you can return it for a refund. Note that bespoke and made-to-order items are excluded.
About the seller
Alexander and Pearl are online retailers of exquisite chandeliers, lighting, furniture, mirrors and decorative accessories for the home and garden. More about Alexander and Pearl...
Guaranteed and secure
- 14 day no-quibble returns *
- 100% safe and secure payments


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The mid 1990's was a time of great opportunity! The Internet was relatively new and nobody could have dreamed it would become what it has today. Not knowing what was in store, thousands of entrepreneurs chased after dreams of IPO and millions of dollars from this upcoming technology. We were no different.
In 1995, one of the Five Technology partners was spending winter break from college working as a limo driver in Aspen, CO to make a few extra bucks. He ran into a few guys that were interested in funding an interactive kiosk guide in town, so the crew picked up and moved to Aspen to complete the project. In these days there was no mobile phone let alone mobile technology, only the recently upgraded, high flying 28.8 modem that connected to the Internet via a phone line. The kiosks were strategically placed and offered a comprehensive guide to those visiting Aspen looking for dining, entertainment, ski rentals, and more. Think Google Maps of today, but much slower and a whole lot less portable.
A programmer, a graphic designer, a database admin, a network specialist, and a business/sales guy started their quest for the next big thing. We would no doubt be millionaires by time we were in our 30's, but it was going to require 16 hour days working for a dream rather than a paycheck. A whole lot of dreams fell short as part of the infamous dot com bust, instead we ran into a kiosk patent that put Admartek (us) and everyone else out of the kiosk business. Down but not out, we salvaged a healthy start on a content management system (unheard of in those days) and a new project to rebuild Aspen.com.
Our core competency is utilizing Internet technology to build things, so we relied heavily on partners for marketing and new sales. The SMC, or Site Management Console, was one of the first content management systems available to SMB, and it turns out business owners were getting weary of paying their website company $100 every time they needed a simple update to their site.
In addition to word of mouth and referral sales, we were building great relationships with partners such as Blue Tent Marketing who were sales and marketing machines. We focused primarily on making the SMC better, and our partners helped to bring our SMC subscriptions to close to 400 websites.
At a similar point in time, we had started seeing a lot of demand for IT services. While most companies did realize they needed a website, it was not bringing in the revenue needed to fuel the fire. Networks were less complex at that time and most website design companies had a few network geeks for hosting anyway, so it was an easy way to make a few extra bucks. We soon learned that what was once just an additional revenue source was emerging as a must have skill set for any company looking to effectively do managed services.
Call it "the cloud" or whatever the buzz word of the time, but organizations are moving more and more business functions online and a merger of the IT and website worlds had started to unfold.
Our partners were still treating us well but the open source content management era was upon us and competition was introduced to the SMC license. Open source CMS was "free" to use and seemingly a logical move for any website development company of any substance (see more on The True Cost of Open Source CMS and Web Developers and Engineers are not the Same for more on open source CMS topics).
It was going to be tough to rely on our partners moving forward for the sort of revenue we needed, so the time had come to go after the market directly with our own sales and marketing team. Five Technology was now a conversation.
Aaron Weiche (now with Get Five Stars) had made a decision to move on from his previous endeavor and was actively courting bankers about a loan for his Deep Six Marketing business plan. Intrcomm Technology (us) was looking to hit the website design and development market with our direct sales and marketing initiatives.
We desperately needed each other so we partnered to form Five Technology, a technology company that builds business class websites and helps to market them online though search engine marketing services. Over the next couple years Five was able to build a fantastic portfolio, bringing our website design and Internet marketing services to a whole new level.
With our headquarters in a suburb west of Minneapolis / St Paul and remote offices in Vail and Aspen CO, we continually strive to stretch the limits of technology for ourselves as well as our clients. If the business of the future is a distributed model with a central headquarters and remote clients, staff, partners, etc., dispersed throughout, then we've got a jump on that trend. Through online software, incredible leaps in technology (bandwidth, storage, software, etc.), and a team knowledgeable in the entire spectrum, we are prepared for this "Internet thing" to evolve even further.
Five Technology is still working relentlessly to build relationships with organizations as well as businesses needing a partner in technology. We have not abandon nor serviced small clients that have been with us through the years any less. Our growth continues to increase moderately year after year, regardless of the market conditions.
Internet marketing is the cost effective alternative to traditional marketing with a measurable ROI, so down markets should essentially translate to increased business. Our objective continues to be to provide our existing clients a great return on the money they spend with us while seeking a healthy balance of new business each year.
My goal is to double revenue from the site in the next 2 years. Now that Five Technology has built me this powerful portal management web application, I am able to streamline the process of publishing content.Paul Taylor III, SurvivingMold.com
The staff at Five Technology has been wonderful to work with. They are receptive to the needs of the school district and willing to work within our budget. They have gone above and beyond to make sure we are satisfied with the product they are delivering.Traci Lawman, Delano Public Schools
Wow, the transition to the new system was seamless. Kudos to everyone that worked this out. Thank you very much!Vicki Adney, Reck Agri
We have had many comments from our community on the ease of use of navigation and they really have enjoyed the new look and layout. Our staff certainly has benefited as we have used the website more and more as a communication device to our school patrons. I look forward to taking full advantage of the student section for our classes, hopefully next year.Paul Ludwig, Delano Public Schools


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A new poster for Kingsman: The Golden Circle has been released, suggesting that we'll see the return of a familiar face.
If you want to avoid spoilers, though it'll be difficult to avoid this reveal given how upfront the marketing team has been about it, you shouldn't take a look at the poster.
Taron Egerton (Eggsy) and Mark Strong (Merlin) will reprise their roles, but the poster teases that Colin Firth (Harry Hart / Galahad) will be back. "Reports of my death have been greatly exaggerated," the poster says. Intriguing!
The Kingsman sequel sees Eggsy heading for America where he will link up with Ginger (Halle Berry) and going toe-to-toe with Poppy (Julianne Moore).
Kingsman: The Golden Circle will be released in cinemas in June 2017.


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Weird Al to Parody Iggy Azalea, Lorde + Robin Thicke on New Album
Weird Al is back with a brand-new album, and in true form, is set to parody a number of pop hits on his upcoming record. Get the details!
Weird Al is back with a brand-new album, and in true form, is set to parody a number of pop hits on his upcoming record. Get the details!
The 2014 MuchMusic Awards featured some of our favorite celebs rocking their best red carpet looks!
Lorde performs 'Tennis Court' and 'Team' at the 2014 MuchMusic Video Awards in Toronto, Canada.
Iggy Azalea slams Lorde for joining singing with Nirvana at the Rock and Roll Hall of Fame Induction Ceremony.
Lorde, one of the night's biggest winners, unleashed the very first primetime performance of her new single 'Tennis Court' at the 2014 Billboard Music Awards tonight. The 17-year-old singer brought her signature arm movements -- and trademark vocals -- to the number, donning a wide-brimmed black hat and all-black ensemble (sans feathers) for the performance.
You don't want to mess with Lily Allen. In her bold new music video for 'Sheezus,' the title track off of her upcoming album, the outspoken British singer gets a little psychedelic and freely shouts out -- and even throws a little shade -- at her fellow female pop stars.
Lorde was just about to hit the road on an Australian tour. But the singer, 17, has had to pull a Miley Cyrus and cancel because she is sick.


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UP Nagar Nigam Safai Karamchari Recruitment Result 2016
UP Nagar Nigam there will be soon after release its Safai Karamchari recruitment result and its final selection list online.
UP Nagar Nigam District Wise UP Nagar Palika Result 2016 for Safai Karamchari
Uttar Pradesh Nagar Nigam there is now providing news update for the number of candidates. As per this Uttar Pradesh Nagar Nigam here was several months back also invited its many number of vacancies application forms for lot of posts. As per this organization here are having need about 40000 candidates for the posts of Safai Karmi. For all these vacancies in this organization there was after release this recruitment notification here was many number of interested candidates want to get that job submit them application form in different zones of UP Nagar Nigam. To complete all these vacancies from this UP Nagar Nigam here will be held number of different selection process top get select all the well qualified and eligible candidates for these require posts.
UP Nagar Nigam Interview:
UP Nagar Nigam as per here was released its recruitment notification there will be get select all the eligible candidates for the posts of Safai Karmi. After that there was form this organization to complete its this recruitment process and make selection of all the required candidates from the applicant candidates here was before the several days back organize this recruitment Interview. In these interview here was all these applicant candidates was get attend this interview and present them for this posts of Safai Karmi. In these interviews here was asking some basic question related to the candidates profile and them working ability. For them answer there will be soon after make selection of all the eligible candidates for all these require posts.
UP Nagar Nigam Result 2016:
After completed the entire interview from this UP Nagar Nigam here will be also get selection all the eligible candidates for the posts of Safai Karamchari. In this interview here was all the applicants were getting appeared to get selection. After completed all these interviews from this UP Nagar Nigam here are now all the applicant candidates are start searching from looking this recruitment result and final selection list. After that from this organization as per need of this final selection list form all these candidates there will be also soon release online. After release this selection list here will be you all the candidates also can check them online from here its official website link at http://lmc.up.nic.in/. After release this result here will be also provide posting to all the candidates for all these require posts.
UP Nagar Nigam:
UP Nagar Nigam here are works as the Municipal Corporation of India. From thin UP Nagar Nigam here is also having to complete its many number of works for the public of different cities. In this UP Nagar Nigam here coming about 15 cities. For all these cities complete its number of Municipal works. For all these different works in this organization there are having to complete its number of different recruitment process for the various posts. For all these posts you candidates there will be also provide all detail online from here our website.
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Free Delivery - Free Exchanges -
0333 200 4606
The classic yet modern design of this solid oak range offers an affordable and stylish collection of dressers, tables and cabinets ideal for any living or dining space around the home. All pieces are finished with a resilient matt satin finish.
"Absolutely perfect, just what I was looking for. Excellent quality - very solid and well made. Will last a long time." - Sarah Webster, 12 June 2012
Save £50 when you spend £850 or more - Code: NIFTY50
With classic yet modern design the Rivermead Oak Furniture range is an affordable and stylish collection of dressers, tables and cabinets ideal for any living or dining space around the home. Crafted from solid light oak, the Rivermead oak furniture range employs traditional joinery techniques to create quality products that you can treasure in your home for many years to come. The high quality oak is showcased to its fullest with the resilient matt satin finish that emphasises the natural beauty of the fine oak grain whilst protecting your furniture from the rigours of everyday use.
With an extensive array of versatile furniture you are sure to find the perfect match for your home in the Rivermead Oak Furniture. All of this range comes fully assembled so when it arrives, all you have to do is decide where you want it to go. Buy online or order over the phone today and we will deliver direct to your door.
Popular categories:
Corona Furniture | Leather Dining Chairs
| Extending Dining Tables |
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Oak Desks | Oak Wardrobes | Vancouver
Oak Furniture


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Columbus originally reached the Chinese port of Fuzhou on his second voyage. However he had nothing with which to trade and after preliminary talks with the city officials, he returned to Spain to relay the news of his discoveries. The Spanish commissioned a textiles mission to Fuzhou in 1498, though this too met with little success when it tried to trade with the Chinese market. A religious mission was also arranged in 1499, and landed at Ningbo in August.
By 1500 the Portuguese also established trade relations with China, with Vasco Da Gama arriving at Ningbo and buying up some gunpowder and supplies for silver. However upon leaving the port, his fleet seized to merchant vessels just outside the harbour, and fled on before they were apprehended.
1501 saw Juan Ponce de Leon explore the Yellow sea and Bay of Bohai in April, trading what he could in Qingdao and Incheon.
1502 Jorge Alvares, sailing for the Portuguese crown, arrived in Guangzhou. Later that year the Spanish reached Beijing, with Juan Urraca Coruna leading an embassy with tribute to the court of Hongzhi. The emperor was very interested in the lands to the east, and accommodated the embassy for a few months. However news of the Portuguese attack upon the Sultanate of Malacca, strained relations between the emperor and his european guests, and the mission left soon after.
From 1504-1508 there were a few counts of piracy by both Spanish and Portuguese sailors on journeys to the Indies. Relations became ever more fraught, even as another five ambassadorial missions were organised, three Spanish missions in 1504, 1512 and 1519 and two by Portugal in 1506 and 1511.The 1510s saw an increase of trade between Europe and China, and with it came more counts of piracy and other crimes.
The two European powers were not always amicable with one another either, Spanish traders arresting and killing Portuguese explorers in Shanghai in 1512. After an attack by the Portuguese on their colony in Sri Lanka in 1516, the Spanish even encouraged the Chinese court to expel Portuguese traders.
In 1520 there was a Chinese decree limiting European trade in China to Zhoushan Island by Ningbo harbour. Later in 1524 this was changed, making the Portuguese trade via Macau in Guangzhou harbour.