text:
Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial
William B. Armstrong, Thomas H. Taylor, Ann R. Kennedy, Raymond J. Melrose, Diana V. Messadi, Mai Gu, Anh D. Le, Marjorie Perloff, Francisco Civantos, William Jarrard Goodwin, Lori J. Wirth, Alexander Ross Kerr and Frank L. Meyskens Jr
William B. Armstrong
Authors' Affiliations: Chao Family Comprehensive Cancer Center, Departments of Otolaryngology-Head and Neck Surgery, UC Irvine, Genetic Epidemiology Research Institute, Epidemiology, Departments of Radiation Oncology, University of Pennsylvania, Philadelphia; Department of Pathology, University of Southern California; School of Dentistry, University of California, Los Angeles; Department of Pathology and Laboratory Medicine, University of California, Irvine; Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, Philadelphia; Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland; Department of Otolaryngology-Head and Neck Surgery, University of Miami, Miami, Florida; Dana Farber Cancer Institute, Harvard University, Boston, Massachusetts; and College of Dentistry, New York University, New York, New York; Medicine, Biological Chemistry, and Public HealthAuthors' Affiliations: Chao Family Comprehensive Cancer Center, Departments of Otolaryngology-Head and Neck Surgery, UC Irvine, Genetic Epidemiology Research Institute, Epidemiology, Departments of Radiation Oncology, University of Pennsylvania, Philadelphia; Department of Pathology, University of Southern California; School of Dentistry, University of California, Los Angeles; Department of Pathology and Laboratory Medicine, University of California, Irvine; Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, Philadelphia; Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland; Department of Otolaryngology-Head and Neck Surgery, University of Miami, Miami, Florida; Dana Farber Cancer Institute, Harvard University, Boston, Massachusetts; and College of Dentistry, New York University, New York, New York; Medicine, Biological Chemistry, and Public Health
Thomas H. Taylor
Authors' Affiliations: Chao Family Comprehensive Cancer Center, Departments of Otolaryngology-Head and Neck Surgery, UC Irvine, Genetic Epidemiology Research Institute, Epidemiology, Departments of Radiation Oncology, University of Pennsylvania, Philadelphia; Department of Pathology, University of Southern California; School of Dentistry, University of California, Los Angeles; Department of Pathology and Laboratory Medicine, University of California, Irvine; Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, Philadelphia; Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland; Department of Otolaryngology-Head and Neck Surgery, University of Miami, Miami, Florida; Dana Farber Cancer Institute, Harvard University, Boston, Massachusetts; and College of Dentistry, New York University, New York, New York; Medicine, Biological Chemistry, and Public HealthAuthors' Affiliations: Chao Family Comprehensive Cancer Center, Departments of Otolaryngology-Head and Neck Surgery, UC Irvine, Genetic Epidemiology Research Institute, Epidemiology, Departments of Radiation Oncology, University of Pennsylvania, Philadelphia; Department of Pathology, University of Southern California; School of Dentistry, University of California, Los Angeles; Department of Pathology and Laboratory Medicine, University of California, Irvine; Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, Philadelphia; Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland; Department of Otolaryngology-Head and Neck Surgery, University of Miami, Miami, Florida; Dana Farber Cancer Institute, Harvard University, Boston, Massachusetts; and College of Dentistry, New York University, New York, New York; Medicine, Biological Chemistry, and Public HealthAuthors' Affiliations: Chao Family Comprehensive Cancer Center, Departments of Otolaryngology-Head and Neck Surgery, UC Irvine, Genetic Epidemiology Research Institute, Epidemiology, Departments of Radiation Oncology, University of Pennsylvania, Philadelphia; Department of Pathology, University of Southern California; School of Dentistry, University of California, Los Angeles; Department of Pathology and Laboratory Medicine, University of California, Irvine; Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, Philadelphia; Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland; Department of Otolaryngology-Head and Neck Surgery, University of Miami, Miami, Florida; Dana Farber Cancer Institute, Harvard University, Boston, Massachusetts; and College of Dentistry, New York University, New York, New York; Medicine, Biological Chemistry, and Public Health
Ann R. Kennedy
Authors' Affiliations: Chao Family Comprehensive Cancer Center, Departments of Otolaryngology-Head and Neck Surgery, UC Irvine, Genetic Epidemiology Research Institute, Epidemiology, Departments of Radiation Oncology, University of Pennsylvania, Philadelphia; Department of Pathology, University of Southern California; School of Dentistry, University of California, Los Angeles; Department of Pathology and Laboratory Medicine, University of California, Irvine; Oral and Maxillofacial Surgery/Pharmacology, University of Pennsylvania, Philadelphia; Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland; Department of Otolaryngology-Head and Neck Surgery, University of Miami, Miami, Florida; Dana Farber Cancer Institute, Harvard University, Boston, Massachusetts; and College of Dentistry, New York University, New York, New York; Medicine, Biological Chemistry, and Public Health
Raymond J. Melrose
Diana V. Messadi
Mai Gu
Anh D. Le
Francisco Civantos
William Jarrard Goodwin
Lori J. Wirth
Alexander Ross Kerr
Frank L. Meyskens
DOI: 10.1158/1940-6207.CAPR-13-0004 Published May 2013
Oral premalignancy serves as an ideal model for study of chemopreventive agents. Although 13-cis-retinoic acid showed reversal of oral premalignancy, toxicity, and reversal of clinical response after cessation of therapy obviated its widespread use. A search for nontoxic agents with cancer preventive activity led us to evaluate Bowman Birk Inhibitor (BBI) formulated as BBI Concentrate (BBIC). We previously reported encouraging results in a phase IIa trial of BBIC in patients with oral leukoplakia with measurable clinical responses and favorable biomarker changes. On the basis of these results, we undertook a randomized, placebo controlled phase IIb trial with patients receiving BBIC or placebo for 6 months, with assessment of clinical response and change in lesion area as primary end point and an intent-to-treat analysis. One hundred and thirty two subjects were randomized; and 89 subjects completed six months on study drug or placebo. Both placebo and BBIC showed a statistically significant decrease in mean lesion area of 17.1% and 20.6%, respectively, and partial or greater clinical responses of 30% and 28% respectively. No significant difference between placebo and study drug arms was observed. Histologic review, review of photographs of lesions, and comparison of serum neu protein and oral mucosal cell protease activity also did not show significant differences between study arms. Probable reasons for these negative results were considered, are discussed, and include a placebo with non-BBIC clinical activity and reduced pharmacokinetic availability of the second batch of BBIC. This experience should be a strong cautionary note to those considering "Green" chemoprevention. Cancer Prev Res; 6(5); 410–8. ©2013 AACR.
See related commentaries by Mulshine and Ondrey, p. 371
See related commentaries by William and Papadimitrakopoulou, p. 375
Considerable epidemiologic evidence links dietary habits and incidence of a variety of cancers. Consumption of high levels of soybeans has been associated with decreased incidence of cancer of the breast, colon, and prostate (1–4). Soybeans contain a number of compounds that have potential anticarcinogenic activity including isoflavones, phytic acid, saponins, and several protease inhibitors. Both epidemiologic and experimental data strongly suggest a broad role for protease inhibitors in providing a protective effect against cancer formation, and those with chymotrypsin inhibitory activity have been found to be the most potent (1–5).
The Bowman Birk Inhibitor (BBI) is a serine protease inhibitor isolated from soybeans possessing domains with trypsin and chymotrypsin inhibitory activity (6). In vitro and in vivo studies show anticarcinogenic activity in a number of animal model systems. BBI Concentrate (BBIC) has the same anticarcinogenic profile as purified BBI, and it has been developed for human trials (5). Both BBI and BBIC are nontoxic, and safety has been reported in a phase I trial of BBIC administered as an oral troche in patients with oral leukoplakia (4). BBIC safety has also been shown in numerous other human trials using BBIC (7).
It has been suggested previously that premalignant human tissues may have elevated levels of proteolytic activity for hydrolysis of the tripeptide fluorescence substrate, butoxycarbonyl-valine-proline-arginine-(7-amino-4-methylcoumarin), which can be used as a biomarker for human cancer prevention studies (8). This proteolytic activity can be inhibited by several anticarcinogenic serine protease inhibitors, including BBI (9). As the abilities of these protease inhibitors to inhibit proteolytic activity correlates with their abilities to suppress malignant transformation (9), the hydrolysis activity may be involved in the carcinogenic process, and therefore, could be a candidate biomarker for human cancer prevention studies. Another biomarker potentially useful for human cancer prevention studies is neu oncoprotein (10–13). Increased level of neu protein from tumor cells was shown to be correlated with the elevated concentration of neu protein in serum (14, 15). Increased levels of neu protein have been detected as well in patients with various cancers, including cancers of the breast, ovary, prostate, stomach, pancreas, colon, liver, and lung (10, 16, 17). In our phase IIa trial of BBIC modulation, neu protein levels were correlated with changes in protease activity in subjects receiving BBIC (4, 13, 18).
We have previously reported encouraging findings in a phase IIa trial of BBIC in patients with oral leukoplakia (4). Thirty one percent of 32 subjects receiving BBIC for one month showed clinical response. A dose–response relationship in decreased lesion size was observed, and blinded evaluation of lesion photographs confirmed this relationship. Protease activity was found to decrease in individuals with elevated activity at initiation of treatment. These encouraging results led us to proceed with a double-blind randomized placebo controlled trial of BBIC in patients with oral leukoplakia for 6 months. Clinical and histologic response, toxicity, and oral mucosal cell proteolytic activity and Neu levels and serum Neu were evaluated.
Design and patient characteristics
This was a 2-armed, double-blind, placebo-controlled, multicenter, phase II-B trial. There were 8 geographically separated performance centers (in California, Massachusetts, New York, and Florida). Subjects had an equal chance of being assigned to the drug or placebo arm. Independent randomization schedules were created for each performance center (so study-arm assignment would not be confounded with geography). For those centers expected to accrue at a faster rate, the randomization schedule incorporated a block size of 4. A block size of 2 was used for centers with lighter accrual goals.
The primary end point was relative percent change in total lesion area after 6 months on study, and the percent of subjects showing a clinical response on that measure. Other end points included change in clinical impression from photographs of lesions, a central pathology review, and changes in buccal-cell and serum Neu protein, and buccal cell protease activity. Early in the study, subjects on the drug arm who showed a partial or complete response at 6 months were allowed to continue treatment for an additional 12 months (total 18 months) with final follow up at 21 months. However, due to the limited supply of drug, the protocol was soon modified to limit treatment to 6 months.
Potential subjects were recruited through radio and print advertising and outreach to dental associations. Eligible participants had to be at least 18 years old and have histologically proven oral leukoplakia and/or erythroplakia capable of being measured bidimensionally (to enable estimates of lesion area). Initially, we required that total lesion area estimated at baseline be at least 100 mm2, but later this requirement was relaxed to facilitate accrual. Those otherwise meeting the inclusion criteria were excluded for any of the following reasons: (i) use of systemic or topical oral steroids within 3 months, (ii) currently pregnant or lactating, (iii) presence of head-and-neck cancer (including in situ disease), or history of such within 2 years, (iv) retinoid or beta-carotene therapy for any reason within 2 years, or beta-carotene capsules of any size within 6 months (patients were allowed up to 2 multivitamins per day), (v) participation in another randomized clinical trial within 6 months. Subjects had to be willing to have photographs taken of the lesion fields, and commit to serial appointments. Premenopausal and perimenopausal women were required to agree to use adequate birth-control methods and have a negative pregnancy test. At the completion of the 4-week run in phase of the study, 75% compliance with administration of drug measured by counting unused drug packets was required for continuation in the study. Written informed consent was obtained for all subjects at initial screening, and the study was approved by the Institutional review boards of the University of California, Irvine (Irvine, CA) and all other performance sites.
Study procedures
After consent and prescreening, potentially eligible subjects underwent a screening oral examination. Buccal mucosal cells were collected, urine specimen obtained, and approximately 15 mL fasting blood drawn at the initial visit. If recent (within 3 months) histologic analysis had not been documented with review of biopsy, 3 mm punch biopsy of representative lesions were conducted after measurement and photodocumentation of lesion(s).
Subjects meeting eligibility criteria underwent a one-month run-in period during which they self-administered the placebo compound. After the run-in period, if compliance with medication was adequate (see above), then baseline examinations were conducted and biospecimens collected. Similar examinations were conducted at 3 months and 6 months on treatment. Lesion biopsy and collection of blood and urine samples were repeated at the 6-month visit. At 3 months off treatment, subjects were evaluated for adverse events and lesion measurements. Subjects were questioned about palatability, side effects, and any adverse events at each visit while on the trial.
Study agent and treatment
For the run-in interval, all patients received placebo, which was Quaker Tortilla Mix–Masa Harina De Maiz. During the run-in period only, 40 mg of citric acid per 3 grams Masa Harina was added for taste. This product was tested for chymotrypsin inhibitory activity and none was measurable. The dose level for placebo was 6 grams per day. Study drug was Bowman-Birk Inhibitor Concentrate (initially produced and supplied by Central Soya Company, but later supplied by the NIH/National Cancer Institute/Division of Cancer Prevention pharmacy). Patients received daily doses of 600 chymotrypsin inhibitor units of BBIC, administered as 300 chymotrypsin inhibitor units twice a day as 3 grams of BBIC or 3 grams of placebo. Both placebo and drug were provided to subjects as powder in small, zippered, amber, plastic pouches each containing one day's dose. Participants were instructed to use half the material in the morning and the balance in the evening. Patients self-administered, by mixing the appropriate amount of powder with about 20 mL of water, swishing the mixture in the oral cavity for 60 seconds, then swallowing it. Treatment pouches were prepared centrally and sent to performance sites in lots of 100 pouches (3-month supply) per participant, renewed upon need.
Assessment of clinical response
The primary clinical response measure for each subject at each time point was estimated relative percent change in total lesion area, with primary interest being the comparison of baseline measures to those at 6 months on treatment. Clinical examiners recorded the estimated extent of the longest axis of each lesion and the extent perpendicular to the longest axis, in mm, at each time point for each subject. Clinicians made reference to previous exams to ensure all lesions were measured, recording values of zero for lesions that had resolved, and to document new lesions. After data entry, individual lesion areas were estimated by the product of length and width, and summed across lesions within each subject, by time point. Relative percent change in total lesion area was defined as 100 times (area posttreatment minus area pretreatment) all divided by pretreatment area. Category of clinical response was based on the magnitude of relative percent change in total lesion area. A complete response (CR) was declared if the relative percent change in total lesion area was minus 100 percent. A partial response (PR) was a relative percent decrease in total lesion area of 50% or more, without being a CR. Disease progression was a relative percent increase in total lesion area of at least 50%. Remaining cases were declared to be stable disease.
A secondary clinical response measure was based on blinded, comparative judgments of pairs of photographs of the same lesion at baseline and 6 months on study. Study staff assembled all available pictures of lesions from pretreatment (screening or randomization) and the 6 month time points, by subject and lesion. Pictures at randomization were preferred over those at screening, but the latter were used if the former were absent. Any picture from one time point without a mate at the other time point was set aside. (Note: lesions first appearing during the course of treatment had no mate from pretreatment exams.) If a subject had multiple picture pairs for the same lesion, then one pair was chosen at random and the others set aside. In case of multiple pictures for a lesion at one time point, then one was picked at random for use and the others set aside. If there were picture pairs for more than one lesion for a particular subject, then one pair was selected at random for use and the others set aside. Thus, each subject having photos of the same lesion (or appropriate anatomic area, if the lesion had resolved) contributed exactly one picture pair to the task materials.
Picture pairs were arranged into a photo album, with one pair per page, one photo above the other. Picture pairs were assigned to album page at random, such that, both study performance center and treatment arm were balanced across the presentation sequence, as was whether the pretreatment picture or the 6-month picture was in the superior position. Five physicians experienced with evaluation of oral mucosal tissue abnormalities, but blinded to study arm and time point, independently compared the pictures in each pair using a 7-point scale. The scale ranged from, "top photo shows a complete response relative to the bottom photo," through, "the same degree of disease is shown by top photo and bottom photo," to "bottom photo shows a complete response relative to the top photo." Raw scores were transformed to account for relative position of the earlier and later photo, and averaged across the 5 reviewers. Final scores ranged from one, denoting a CR at 6 months, to 4, which indicated no change, through 7, which indicated that the 6-month photo depicted a much worse situation than the pretreatment photo.
Pathologic assessment
A single, experienced pathologist reviewed pre- and posttreatment pairs of tissue specimens. The reviewer was blinded to study-arm assignment (drug or placebo), but not to time point of specimen. For each specimen, the reviewer marked a continuum to indicate degree of tissue abnormality. The continuum was 140 mm long, and anchored by the word 'Normal' on the left and 'Malignant' on the right. The distance from the left edge of the continuum to the reviewer's mark, in mm, was determined. For analyses, a score was formed by subtracting the pretreatment value from the 6-month value. Thus, a retreat from 'Malignancy' over time produces a negative score, a score of zero denotes no change, and a positive score denotes a worsening situation.
The central pathologist also made a direct comparison of pre- and posttreatment specimens, marking a 170 mm continuum anchored on the left by "Posttreatment shows no dysplasia in comparison with pretreatment," and on the right by, "Posttreatment shows greater dysplasia than pretreatment." The center of the continuum was labeled, "Pretreatment and posttreatment show no difference." The reviewer's mark was coded as the distance from the left edge, in millimeters. On this measure, low scores denote improvement over time, a score of 85 denotes no change, and a value higher than 85 indicates histologic worsening.
Intermediate marker endpoints
Titer information was developed for Buccal-Cell Neu protein (ng/mg), Serum Neu protein (ng/ml), and Protease Activity (delta RFU/min/μg). Laboratory and assay methods were the same as described by Wan and colleagues (13). Titer amounts by subject number and date were forwarded to the statistician, who consolidated the information. For all 3 intermediate marker endpoints (IME), multiple readings for the same subject at the same time point were averaged. IME data are reported as the relative percent change from pretreatment to 6 months (post minus pre, all divided by pre).
Statistical analyses and data management
Power estimates for our phase IIB study were informed by the dose response observed in our preceding, single-arm, phase IIA trial in which study response rate (PR+CR) at the lowest dose (200 CIU) was 12.5% (1/8 participants). We used this figure to anticipate response in the placebo arm of the phase IIB effort. Similarly, we used the phase IIA figure of 36.4% (4/11) responding (PR+CR) at the 533 CIU dose to anticipate the response rate of the treatment arm in the phase IIB effort. Thus, the phase IIB trial was powered to contrast response rates of about 12.5% and 36%. In both the phase IIA and IIB trials, our criterion for a partial response was a reduction of estimated lesion area of at least 50%.
Analyses were conducted using SAS/STAT software (19). Raw data were entered into a central database (Microsoft Access) by staff of the Biostatistics Shared Resource of the University of California Irvine Chao Family Comprehensive Cancer Center. Data on lesion size and judgments of photos and pathology specimens were formed into SAS data sets that were subject to 100% verification against the case-report forms by the study statistician. Results of IME assays were entered into spreadsheets by wet-lab staff, which the statistician converted to SAS data sets, which were then verified against the original spreadsheets. Data on host factors were extracted from the central database. Statistical tests of proportions were by Fisher's exact test (20). Because measures of relative percent change profoundly violate normality, as did estimates of total lesion area and the pathology judgments, comparisons of continuous measures between groups were by Wilcoxon 2 sample test (20). The signed-rank test was used to evaluate the null hypothesis that measures of change were centered on zero (20). Confidence intervals about medians are based on order statistics. Correlations among relative percent change scores were by Spearman rank correlation (21). No adjustment was made for multiple testing or for any correlation among the various dependent measures.
A total of 513 people were screened for participation across all 8 performance sites, of which 188 (37%) were ineligible and 325 were consented. The date of first randomization was May 1999 and the last in September 2009. Of those screened, 118 (23%) did not complete the run-in period. Of those consented, 157 (48%) completed the run-in period but 25 declined to continue, resulting in 132 randomized patients. Sixty-seven patients were randomized to the drug arm, whereas 65 were assigned to placebo. The difference in numbers assigned to the 2 arms did not exceed one at any performance site. Of the 132 randomized, 89 participants (67.4%) had lesion sizes recorded at both randomization and 6 months, and so were evaluable on the primary end points. Twenty-one participants had lesion sizes recorded at randomization, but not at 6 months. Furthermore, 22 had no lesion measurements recorded at randomization (the majority from a remote performance site, with high turnover in study personnel).
The 89 subjects who were evaluable on the primary end point at 6 months seem fairly representative of the 132 who were randomized (Table 1). Importantly, the proportion of those randomized who contributed data at 6 months did not differ between study arms [drug arm 64% (43/67), placebo arm 71% (46/65); P > 0.46] nor did that proportion differ by gender (P > 0.44) or major race/ethnic group (P > 0.57). About 36% (48/132) of those randomized reported use of beer, wine, or liquor, whereas 42% (56/132) did not answer questions on alcohol consumption. Proportions reporting, not reporting, or denying alcohol use did not differ between those who did and did not contribute data on the primary end point at 6 months (P > 0.39). About 21% of those randomized (28/132) reported using tobacco (viz., cigarettes, cigars, pipe, oral use), whereas 50% (66/132) did not answer questions on tobacco use. Proportions reporting, not reporting, or denying tobacco use did not differ between those who did and did not contribute data on the primary end point at 6 months (P > 0.25). Estimates of total lesion area at randomization did not differ between those with lesion measurements only at randomization (n = 21, mean 530.7 mm2, median 380 mm2, range 19–1976 mm2) and those evaluable on the primary end point at 6 months (n = 89, mean 502.6 mm2, median 310 mm2, range 48–3500 mm2; P > 0.70).
Patient characteristics by study arm (for those evaluable on relative percent change in total lesion area at six months)
Table 1 also summarizes measures describing the patients evaluable on the primary end point at 6 months, overall and by study arm. Fifty-seven men and 32 women contributed data on relative percent change in total lesion area (the primary end point) at 6 months. The proportion that were male did not differ across study arm (P > 0.99), nor did the distribution of age (P > 0.15). About 78% (69/89) were White, and the proportion of Whites did not differ across study arm (P > 0.99). The proportions reporting, not reporting, or denying alcohol or tobacco use, did not differ between study arms (alcohol P > 0.82; tobacco P > 0.29). Estimated total lesion area at randomization did not differ between study arms (P > 0.64).
Clinical response
Table 2 shows the number and proportion showing various degrees of clinical response, by study arm (degree of clinical response is defined in the Materials and Methods section above). Both the number and proportion of participants in each category of clinical response are similar across study arms (P > 0.94). About 28% of those in the drug arm achieved a partial response or better (12/43) while that figure for the placebo arm was 30% (14/46), which are not statistically different (P > 0.81). The 2 arms produced similar rates of disease progression: 9% in the drug arm (4/43) and 13% in the placebo arm (6/46; P > 0.74). Thus the data in Table 2 show no evidence that the treatment produced a shift in the distribution of clinical response, relative to the placebo arm.
Number and percent of subjects by category of clinical response at six months, by study arm
Figure 1 shows the distribution of relative percent change in total lesion area after 6 months on treatment, by study arm, and Table 3 gives corresponding summary measures of these distributions. As the figure shows, the bulk of scores, ignoring study arm, fall below zero (sign-rank P < 0.0002) implying that lesion area was reduced in both groups. Per Table 3, the median relative percent change across study arms was about a 26% reduction. The distributions by study arm seem reasonably coincident, with no sign of a difference in location (P > 0.75) or spread (F(45,42) = 1.60, P > 0.12).
Relative Percent Change in Total Lesion Area, by Study Arm: FINAL ANALYSIS (Note: BBIC-grey bars, Placebo-solid bars)
Summary of relative percent change in total lesion area from baseline to six months on study, by study arm
Clinical impression from photographs confirmed these assessments (Supplemental 1). No significant adverse events related to drug or placebo administration were observed during the trial (details in Supplemental 2). This assessment included the 10 patients treated with BBIC or placebo for up to 18 months in the trial. Medication was tolerated, with some subjects expressing palatability issues. The distribution of adverse events in the 2 arms was not different. Pre and post levels of cholesterol and tryglycerides was similar in the 2 groups (Supplemental 3).
Central pathologic review
The central pathologist reviewed 98 pairs of slides, a small percentage of which were re-cuts substituted for original material that could not be evaluated. Three subjects had materials for multiple lesions, but for analysis, we randomly selected just one lesion in each case. Each participant contributed just one lesion to the analysis. One subject was dropped because the only available postrandomization specimen was from the 3-month time point. The materials for an additional 4 subjects were deemed inadequate for review, and no re-cuts were available. Thus final analysis was based on 88 subjects, representing 67% of those randomized (88/132). This proportion did not differ statistically across study arm (drug: 41/67; placebo: 47/65; P > 0.19).
Table 4 summarizes the difference in rated degree of malignancy between randomization and 6-month specimen. Positive values indicate histologic worsening, whereas negative scores denote improvement over the 6-month study period. Across study arms, the location of these scores is not statistically different from zero (sign-rank, P > 0.46), and, consistent with inspection of the table, there is no difference between groups (P > 0.88). A similar result was obtained from the pathologist's direct comparison of the specimens. The median score overall and for each study arm was that point indicating no change, and of course there is no significant difference between the 2 arms (P > 0.68: data not shown).
Summary measures of the difference in rating of degree of malignancy of tissue from pretreatment to six months on study, by study arm
Intermediate markers
Table 5 shows relative percent change over 6 months on-study in buccal-cell Neu protein and protease activity, and serum-Neu protein, overall and for each study arm. Necessary specimens and evaluable results for these assays were available for 45, 45, and 41 subjects, respectively. Pooled across study arm, the relative percent change in protease activity was statistically elevated above zero (sign-rank, P < 0.05, n = 45). However, neither study arm showed this effect when considered separately (placebo: P > 0.07; drug: P > 0.30). Relative percent change in the remaining 2 markers was not statistically different from zero, either overall (ps > 0.18) or by study arm (ps > 0.30). None of the 3 measures showed a statistically significant difference between placebo and drug arms (ps > 0.32). When study arm was ignored, none of these 3 measures showed a significant correlation with relative percent change in total lesion area (buccal-cell Neu: rank correlation 0.11, P > 0.45, N = 45; protease activity: rank correlation 0.92, P > 0.88, N = 45; serum Neu: rank correlation 0.07, P > 0.66, N = 41).
Median relative percent change in biomarkers, by study arm
In this phase IIb clinical trial of BBIC, no significant difference between placebo and treatment arms was identified for clinical response, change in lesion area, histologic grade, or biomarkers studied. Interestingly, both the treatment and placebo group showed statistically significant decreases in total lesion area (Table 3), and the 2 groups showed PR + CR rates of 27.9% and 30.5%, respectively (Table 2). No significant difference in photographic review of lesions was identified between study groups, but the placebo group showed slight improvement following treatment. Oral leukoplakia has a waxing and waning clinical course, and spontaneous improvement or disappearance has been reported in more than 10% of cases (22, 23). However, the approximate 30% response rate raises the possibility that there was clinical activity in the placebo used in the trial.
In designing the study, considerable attention was directed at placebo selection. It was very difficult to identify a compound that would be inert, palatable, and have similar consistency and physical properties similar to those of BBIC. Ultimately, a corn-based product was selected, and Masa Harina was used. Although no chymotrypsin inhibitory activity was measurable, this product contains several vitamins, antioxidants, protease inhibitors, and supplemental nutrients, and is processed by lime cooking, which alters levels of phytochemicals and phenolic compounds, such as ferulic acid (24). The levels of calcium and ferulic acid were sufficiently high in the placebo that cancer preventive activity may have been present; in addition, several other nutrients were present in the placebo at micromolar concentrations that have been shown to have radioprotective or cancer preventive activity in other studies (as described in Supplemental 4). These properties raise the issue of the placebo having had an unexpected clinical effect. Similar concerns about a placebo effect have been raised in a trial of the COX inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia (25), suggesting that the placebo oral rinse, which contains alcohol, and improved oral hygiene may contribute to a beneficial overall effect on oral inflammatory processes. In studies of other oral inflammatory processes, higher than expected response rates were attributed to increased frequency of oral rinsing (26, 27). In total, this report indicates that future trials of chemoprevention agents in oral leukoplakia need to carefully consider whether a no treatment arm should be part of the trial and/or a much larger trial should be done. However, with a 30% placebo effect, trials become prohibitively large (see Supplemental 6 for discussion).
The potential activity of the placebo raises concerns about the overall result. A number of natural compounds have potential chemopreventive activity, and if these compounds are biologically active, they will mask effects of the study drug tested in placebo-controlled trials. Even limited activity could mask the clinical effect of the study drug, and require larger sample sizes to distinguish statistically significant differences in clinical effect. Given the difficulty of accruing subjects in chemoprevention studies, this will make these studies even more expensive and prolonged. This dilemma has raised the question of whether alternative study designs would be more effective. For example, a study design in which the patient serves as her/his own control with serial periods on or off study drug may eliminate issues related to placebo activity.
To further complicate the evaluation, there seems to have been a loss in drug potency over time. An interim analysis was conducted approximately half way through the study. Preliminary blinded analysis indicated a modest but promising difference in treatment response between the 2 study arms (Supplemental 5). On the basis of these encouraging results, the trial was continued and completed. Analysis of the subjects accrued during the second half of the trial showed no difference between the 2 arms of the study. These results suggest that patients treated with BBIC in the earlier years of the trial exhibited better responses, in terms of effects on size of the oral leukoplakia lesions as well as the intermediate marker end points evaluated, than those treated with BBIC in the later trial years, (as detailed in Supplemental 5). It is hypothesized that the apparent loss of potency could have been caused by the BBI storage conditions during this long time period. The directions that came with packages of BBIC initially prepared by Central Soya Company (and dispensed during the early years of the oral leukoplakia trial) indicated that BBIC should not be refrigerated or frozen, as it was known at an early stage of BBIC development that storage under refrigerated or frozen conditions greatly diminished the ability of BBIC to inhibit the malignant transformation of cells in vitro (28). Retrospectively, it was discovered that a different batch of BBIC (termed the new formulation of BBIC), maintained by the same pharmacy that dispensed BBIC during the later years of the oral leukoplakia trial, was kept at both refrigerated and frozen temperatures. Analysis of the bioavailability of the original and new formulations of BBIC in human subjects showed an approximately 60% reduction in bioavailability of the new formulation, compared with the original formulation, of BBIC (unpublished results, made available to the reviewers). As the new formulation of BBIC was maintained under both refrigerated and/or frozen conditions by the same pharmacy that provided the BBIC for the oral leukoplakia trial, it is conceivable that storage of BBIC in a refrigerated/frozen state could have decreased the clinical activity of the drug during the later years of the oral leukoplakia trial. The reduced bioavailability of the second BBIC product also raises concerns as our phase IIA trial showed a clear dose–response effect (4) and a 40% bioavailability would be below the effectiveness of the chosen dose in the current phase IIB trial. Another difficulty encountered was the long time duration between trial initiation and completion; patients with oral leukoplakia were actually treated with BBIC over a period of approximately 11 years (May 1999 to March, 2010).
In conclusion, this phase IIb randomized placebo-controlled trial did not show greater efficacy for the BBIC compared with placebo in patients with oral leukoplakia. This experience should be a strong cautionary note to those considering "Green" chemoprevention (29).
F.L. Meyskens has ownership interest (including patents) in Cancer Prevention pharmaceuticals. No potential conflicts of interest were disclosed by the other authors.
Conception and design: T.H. Taylor, A.R. Kennedy, F.L. Meyskens
Development of methodology: W.B. Armstrong, T.H. Taylor, F.L. Meyskens
Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): W.B. Armstrong, T.H. Taylor, D. Messadi, A.D. Le, F. Civantos, W.J. Goodwin, L.J. Wirth, A.R. Kerr, F.L. Meyskens
Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): T.H. Taylor, R.J. Melrose, A.R. Kennedy, L.J. Wirth, F.L. Meyskens
Writing, review, and/or revision of the manuscript: W.B. Armstrong, T.H. Taylor, A.R. Kennedy, M. Gu, M. Perloff, F. Civantos, W.J. Goodwin, L.J. Wirth, A.R. Kerr, F.L. Meyskens
Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): T.H. Taylor, D. Messadi, M. Gu, M. Perloff, F. Civantos, F.L. Meyskens
Study supervision: M. Perloff, F. Civantos, L.J. Wirth, T.H. Taylor, W.B. Armstrong, F.L. Meyskens
This work is supported by the NIH (U01-CA72294, P30-CA 62203; to F.L. Meyskens).
The authors thank Westley Lagerberg, Sharon Maxwell, Rachel Gonzalez, and Janis DeJohn for their work on this study. Thanks to Alisz M. Demecs for outstanding editorial support.
Received January 3, 2013.
Revision received February 28, 2013.
Accepted March 18, 2013.
Messina M,
Barnes S
. The role of soy products in reducing risk of cancer. J Natl Cancer Inst 1991;83:541–6.
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. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer 1994;21:113–31.
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. Soy, its components, and cancer prevention: a review of the in vitro, animal, and human data. Cancer Epidemiol Biomarkers Prev 1998;7:1055–65.
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Kennedy AR,
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Taylor TH,
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Clinical modulation of oral leukoplakia and protease activity by Bowman-Birk inhibitor concentrate in a phase IIa chemoprevention trial. Clin Cancer Res 2000;6:4684–91.
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. Chemopreventive agents: protease inhibitors. Pharmacol Ther 1998;78:167–209.
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. The Bowman-Birk inhibitor. Trypsin- and chymotrypsin-inhibitor from soybeans. Int J Pept Protein Res 1985;25:113–31.
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. The status of human trials utilizing Bowman-Birk Inhibitor concentrate from soybeans. In: Soy in Health and Disease Prevention, edited by Michichiro Sugano , Taylor & Francis, Boca Raton, FL:2005;207–33.
Manzone H,
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Levels of proteolytic activities as intermediate marker endpoints in oral carcinogenesis. Cancer Epidemiol Biomarkers Prev 1995;4:521–7.
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. New prognostic factors in resectable non-small cell lung cancer. Thorax 1996;51:638–46.
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. Relationship between protease activity and neu oncogene expression in patients with oral leukoplakia treated with the Bowman Birk Inhibitor. Cancer Epidemiol Biomarkers Prev 1999;8:601–8.
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. Measurement of c-erbB-2 proteins in sera from patients with carcinomas and in breast tumor tissue cytosols: correlation with serum tumor markers and membrane-bound oncoprotein. J Clin Lab Anal 1995;9:151–65.
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. The c-erbB-2 protein in oncogenesis: molecular structure to molecular epidemiology. Crit Rev Oncog 1994;5:313–29.
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. Development of the Bowman-Birk inhibitor for oral cancer chemoprevention and analysis of Neu immunohistochemical staining intensity with Bowman-Birk inhibitor concentrate treatment. Laryngoscope 2003;113:1687–702.
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You are going to email the following Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial
Cancer Prev Res May 1 2013 (6) (5) 410-418; DOI: 10.1158/1940-6207.CAPR-13-0004


Instead of being owned by shareholders like chartered banks, credit unions and caisses populaires are owned and controlled by their members. Their main purpose is providing financial services to members.
To become a customer of a credit union or caisse populaire, you must become a member. The cost of joining ranges from $5 to $125. This makes you a shareholder and gives you one vote, no matter how much money you have in your account. Members can vote for the board of directors, run for election, attend annual meetings and vote on motions. As shareholders, members also receive dividends and profit sharing.
Almost all credit unions (outside Quebec) are shareholders in one of the nine provincial "Credit Union Centrals", which provide wholesale lending and look after settlement of cheques and electronic payments for local credit unions. And all nine provincial centrals are the main shareholders of Credit Union Central of Canada (CUCC), which is responsible for making sure there is enough available cash at the national level. The CUCC is chartered and regulated by the federal government under the Cooperative Credit Associations Act and gives the credit union system a national voice on financial service issues.
Caisses populaires are more centralized than credit unions and operate under a single name. The Mouvement des caisses Desjardins consists of a network of caisses populaires in Quebec, Manitoba, New Brunswick and Ontario – as well as a holding company called the Desjardins-Laurentian Financial Corporation (DLFC). They are all members of the Fédération des caisses Desjardins du Québec. If you add together all their assets, the Mouvement des caisses Desjardins is the sixth largest deposit-taking institution in Canada (Dec. 31, 2001).
In addition to key service areas such as residential mortgage financing, consumer credit and deposit services, most credit unions offer term deposits, RRSPs, RRIFs and RESPs, business financial products and services, loans, financial counselling, trust and insurance services and more.
Credit unions tend to be very receptive to the special needs of members. During periods of economic difficulty in many parts of the country, for instance, some credit unions have developed innovative loan repayment options and adopted a sensitive approach to accommodate individual member needs.
There are more than 500 credit unions and caisses populaires in Canada with more than 4.5 million members and combined assets of almost 78.5 billion dollars. Canada has the world's highest per capita membership in the credit union movement, with over 10 million members, or about one-third of the Canadian population.
BC based Vancity Savings, which owns Citizens Bank of Canada, serving members across the country by telephone, ATM, and the Internet.
Coast Capital Savings is Canada's second largest credit union with $6.7 billion in assets and 44 branches across the Lower Mainland, Fraser Valley and Vancouver Island.
Meridian Credit Union, launched on April 1, 2005, the result of the merger of two of Ontario's largest credit unions, NIAGARA Credit Union and HEPCOE Credit Union. Meridian is now the largest credit union in Ontario and the third largest in Canada.
Alterna Savings, which was formed by the merger of Metro Credit Union and CS CO-OP, . With 24 branches, approximately $1.8 billion in assets and over 190,000 members, Alterna Savings is now the second largest credit union in Ontario and one of the five largest in Canada.
Edmonton based Capital City is the largest credit union in Alberta and the fifth largest in Canada.
Employment in the sector increased from almost 41,000 employees in 1991 to about 56,400 in 2000 and, as with other financial institutions, a large proportion of their employees are immigrants.


text:
Nick Redfern: The Martians: Evidence of Life on the Red Planet
"The Martians opens a door into a possibility that most would reject as impossible. But Nick Redfern in this provocative and exciting book makes a startling case for there being life on Mars—and, in fact, for the whole history of Mars being very, very different from what we have supposed. A wonderful adventure and a very exciting story!"—Whitley Strieber, #1 New York Times bestselling author, Communion
The Martians is an in-depth study of the theory that Mars was once a world that teemed with life. Perhaps, even, life not too dissimilar to ours. Incredibly, the Martians may still be there. Alive.
The questions that this book asks and answers include the following:
What kind of society did the Martians have?
What caused their world to become harsh and desertlike?
Did global warming or nuclear war ensure the extinction of the Martians?
Are Martian artifacts strewn about the surface, just waiting to be found by the likes of NASA?
Has NASA already found such evidence, but chosen to withhold such monumental finds from the public and the media?
Could some form of the Martians still exist, deeply below the surface of the planet, in secure installations that allow them to ensure their civilization continues?
What do we know about the Martian environment, its atmosphere, and its landscape?
The Martians explores the CIA's top-secret search for the Martians, multiple photos of strange anomalies, and the latest revelations about the environment and water on Mars. And most tantalizing of all: Did an ailing Martian race come to Earth in past eons and were they confused with gods? The questions concerning life on Mars—then and now—are many. The answers are astounding.
Nick Redfern is a full-time author and journalist specializing in a wide range of unsolved mysteries, including Bigfoot, the Loch Ness Monster, UFO sightings, government conspiracies, alien abductions and paranormal phenomena. He writes regularly for the London Daily Express newspaper, Fortean Times, Fate, and UFO Magazine. His previous books include Three Men Seeking Monsters, Strange Secrets, Cosmic Crashes, and The FBI Files. Among his many exploits, Redfern has investigated reports of lake monsters in Scotland, vampires in Puerto Rico, werewolves in England, aliens in Mexico, and sea serpents in the United States. Redfern travels and lectures extensively around the world. Originally from England, he currently lives in Dallas, Texas.
Hugh Newman & Jim Vieira: The Giants of Stonehenge and Ancient Britain
Mohamed Ibrahim: Science of the Gods in Ancient Egypt
Manu Seyfzadeh: Under the Sphinx
Lynn Picknett & Clive Prince: When God Had a Wife, The Fall and Rise of the Sacred Feminine

redpajama_set_name: RedPajamaCommonCrawl


Congratulations to our Client FlipBelt for their feature in PARENTGUIDE News!
With a dash of style and a ton of hidden storage space, it's no wonder the ingenious accessory known as the FlipBelt is going to be the must-have gear for fitness enthusiasts this year. From jangling keys to cell phones and mp3 players, everyone has certain necessities that have to come along for the ride regardless of the activity. With the FlipBelt, there is finally a hands-free and fashionable way to keep track of all those goods while hitting the gym, pounding the pavement, or biking the city.
Let the FlipBelt take care of that age old question: "Wherever will I store my stuff?" In a world where cubbies are questionable and fanny packs are passé, the FlipBelt offers folks a sleek and roomy solution to all their storage woes. With flattering contoured lines and a sleek, bulk-free build, it's designed to sit comfortably along the waistline blending in as if it were only a waistband. A clever opening on one side of the belt leads to plentiful space and is easily secured or accessed by flipping it to the desired side.


Stream Tab | Streaming Pulse Inc.
Specifies the title for the stream. This will be displayed by listeners' media players when they tune into the stream.
Specifies the E-mail of the person in charge of managing your stream. Centova Cast will automatically send notifications to this address when necessary.
Specifies your company/organization name. This may be used by the streaming server for various purposes.
Specifies the URL to the web site associated with this stream (if any). This may be published by the streaming server.
Specifies the password required by streaming sources to connect to this stream and begin broadcasting. This password must be provided to DJs who will be connecting to your server via a live source to perform live broadcasts.
Specifies the password required to login to your Centova Cast account or the streaming server's internal administrative interface. Some streaming servers require that this password must differ from the source password, so it is best to use a unique password here.
Specifies your time zone. The autoDJ's track scheduler uses this to ensure that the times configured for playlists (in the Playlist Manager) always reflect your local time zone.
Specifies your locale. This determines the language and the date and time formats used in the control panel.
Specifies your preferred character encoding for reading MP3 ID3 (metadata) tags. MP3 audio files do not contain any information about the language or "character set" in which they were encoded, so if your MP3s' artist, album or track names use a non-Latin character set (Cyrillic, Asian, etc.), you will need to set your character encoding appropriately to ensure that all of the letters in the alphabet of your language are interpreted correctly from your media.
Note that this feature is only used for the interpretation of MP3 ID3 tags. Centova Cast itself uses Unicode (UTF-8) character encoding internally which can represent characters from virtually any language.


text:
Sök pressrum
Tobacco Harm Reduction is critical if we are to reduce smoking related disease rates worldwide
5.11.2021 11:10:00 CET | IEVA - Independent European Vape Alliance
Brussels - Eight million smokers worldwide die from a smoking-related disease every year. [1] Tobacco Harm Reduction is a chance for smokers to switch from an extremely harmful to a significantly less harmful alternative. [2]
Unfortunately, the WHO has lost sight of this in recent years. But it is not too late to repent. It must focus on the future of millions of smokers worldwide – a future that is much brighter should they switch to vaping – rather than its own counter-productive "quit or die" dogma.
The ninth conference on tobacco control of the WHO (WHO FCTC COP9) starts in Geneva next week. [3] During this important conference, measures to reduce the global smoking rate will be debated.
The WHO wrote in a publication a year ago: "There is conclusive evidence that: completely substituting [vaping] for combustible tobacco cigarettes reduces users' exposure to numerous toxicants and carcinogens present in combustible tobacco cigarettes." [4]
Now it is important to put this correct assessment into practice.
100 health experts write to the WHO
Similar demands have been made by leading scientists in this field. On October 18, 100 international health experts sent a public letter to the parties to the WHO Conference on Tobacco Control (FCTC COP9). [5]
Their view was clear: "100 specialists in nicotine science, policy and practice have come together to call on the 182 parties (countries) to the Framework Convention on Tobacco Control to take a more positive stance on tobacco harm reduction."
IEVA assessment
"As a European association that is independent of the tobacco industry, we would like the WHO, together with other representatives from politics and science, to develop a targeted strategy for reducing the damage caused by smoking. Of course we as an industry are ready for this critical dialogue" said Dustin Dahlmann, President of IEVA.
[1] WHO 2021: Tobacco key facts, Link
[2] Public Health England 2018: E-cigarettes are 95 per cent less harmful than tobacco cigarettes, Link
[3] COP9/ FCTC Geneva 2021, Link
[4] WHO 2020: Electronic nicotine and non-nicotine delivery systems, Link
[5] 18 October 2021: Letter to the Parties to the Framework Convention on Tobacco Control
Ninth Conference of the Parties, 8-13 November 2021 Link
Independent European Vape Alliance (IEVA)
President: Dustin Dahlmann
Press coordinator: Philip Drögemüller
E-Mail: p.droegemueller@eurovape.eu
Web: www.eurovape.eu
About IEVA - Independent European Vape Alliance
IEVA - Independent European Vape Alliance
https://www.eurovape.eu/
The Independent European Vape Alliance (IEVA) is the only pan-European association aimed at uniting national associations, companies, manufacturers and wholesalers in the vaping industry and providing them with responsible representation at the European level.
IEVA's founding principle is to contribute to harm reduction and public health. E-cigarettes have a significant positive impact and should be recognized as a harm reduction tool because vaping is not smoking.
Subscribe to releases from IEVA - Independent European Vape Alliance
Subscribe to all the latest releases from IEVA - Independent European Vape Alliance by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from IEVA - Independent European Vape Alliance
Vaping industry underlines the importance of product choice10.12.2021 07:51:27 CET | Pressmeddelande
The Independent European Vape Alliance (IEVA) welcomed the decision of MEPs to recognize tobacco harm reduction as a tool in beating cancer; but remains concerned that the report approved today by the European Parliament leaves the door open to a flavour ban in the EU. The Special Committee on Beating Cancer (BECA) today voted on the amendments and the draft of the Beating Cancer report by Rapporteur Véronique Trillet-Lenoir.[1] The authors of the report identify smoking as one of the main causes of cancer and IEVA agrees that everything should be done to significantly reduce the smoking rate in Europe. There is little scientific doubt that tobacco harm reduction is a key tool in achieving this goal.[2] Even those skeptical of tobacco harm reduction concede that vaping is many orders of magnitude less harmful than continuing to smoke. According to Public Health England (PHE), e-cigarettes are 95 percent less harmful than tobacco and the risk of cancer drops by 99.6 percent.[3] The repo
EU scientific committee ignores the science on vaping29.4.2021 16:57:55 CEST | Pressmeddelande
Brussels - The European Commission has today missed an opportunity to bolster its Beating Cancer Plan and recognise the importance of vaping in reducing smoking-related diseases among Europeans.
Beating cancer with Harm Reduction4.2.2021 08:00:29 CET | Pressmeddelande
Bruxelles - The Independent European Vape Alliance (IEVA) welcomes and supports the "EU Beating Cancer Plan" presented today by the European Commission. The plan is extremely important in order to significantly reduce the number of cancer-related deaths. However, the new EU strategy neglects an important instrument for public health: Harm Reduction.
E-Cigarettes flavours ban in the Netherlands endangers Public Health14.1.2021 14:45:38 CET | Press release
Brussels - Around 65 percent of adult vapers in Europe use fruit or sweet liquids. [1] The variety of flavours is one of the most important reasons for smokers to switch to e-cigarettes and for vapers not to go back to smoking. Without paying attention to this fact, the Dutch State Secretary Paul Blokhuis has announced to ban all e-cigarette flavours except tobacco flavours in the Netherlands, as they are supposedly particularly attractive to young people. [2] This measure risks very negative consequences for Public Health and tobacco harm reduction: With only tobacco flavours left vaper's threshold to relapse on tobacco smoking dangerously lowers. A public consultation on the plan will run until January 19, 2021. The vast majority of the comments so far come from vapers and scientists who reject the government's plan. [3] The Dutch plan ignores important facts: The number of young people in the Netherlands who have ever tried e-cigarettes has decreased by a quarter in the past five ye
European survey: 80 percent of vapers stopped smoking completely. Flavors are extremely important to vapers30.10.2020 08:31:25 CET | Pressmeddelande
Brussels - More than 80 percent of smokers who switched to e-cigarettes have completely stopped smoking. Around 65 percent of vapers in Europe use fruit or sweet liquids. These are two important results of a survey carried out by the European Independent Vape Alliance (IEVA). More than 3,300 european e-cigarette users took part. The European survey shows: E-cigarettes are a widely used method in Europe to stop tobacco use. 81 percent of vapers have completely stopped using tobacco. Further twelve percent have reduced smoking with the help of e-cigarettes. 86 percent of the participants assume that e-cigarettes are less harmful for them than tobacco cigarettes. Only two percent think e-cigarettes are equal or more harmful compared to combustible cigarettes. The British government agency Public Health England estimates that e-cigarettes are 95 percent less harmful than tobacco cigarettes. [1] Importance of flavors The variety of flavors seems to be one of the most important reasons for v
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Phần mềm Maritime Software Suite bao gồm 3 chương trình con là Draft Survey, Lashing Calculations và Route Planning.
1. Draft Survey: lập bảng và biểu đồ mớn nước.
* Imperial measures and Metric unit system support.
* 2 modes of calculation - MANUAL or AUTO.
* Unique feature: to receive necessary accuracy of calculation it is necessary to enter only 35 lines of values into the Hydrostatic Table which correspond to various condition of a vessel. Intermediate values (corresponding to actual mean draft of a vessel) will be received by interpolation.
* Initial Survey, with calculation of constant and full report and saving to file.
* Final and/or Intermediate Survey with full report and saving to file.
* Easy hydrostatic tables interpolator; to reduce errors and provide very fast entry of data.
* Extensive help available throughout the program.
* Storage and automatic usage of hull hydrostatic data; especially useful for Surveyors who have regularly calling ships or Ship's officers assigned to one ship.
* During entry of the Survey you can go back and change any entered value at any time.
* Produce a one page Report.
* Entry of Ship Name, Voyage number etc at start of Survey for ease of use.
* Export to text file for later printing or editing in your Word processor or ransmission by e-mail.
2. Lashing Calculations: các tính toán chằng buộc hàng hóa.
* Lashing Calc is a calculation tool for evaluation of semi- and non-standardized securing arrangements.
* Lashing Calculations calculates accelerations and balance of forces in semi- and non-standardized lashing arrangements in accordance with annex 13 to the Code of Safe Practice for Cargo Stowage and Securing (the CSS code) from IMO.
3. Route Planning: lập kế hoạch chuyến đi.
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text:
The Effect Of Tillage On The Fate Of Hard Seeds ...
G. B. Taylor
Division of Land Resources Management. CSIRO, P.O., Wembley, W.A. 6014
Natural regeneration of annual legume pastures after a crop depends on the persistence of hard (ieimpermeable) seeds through the crop year and their subsequent softening prior to the break of season in the pasture year. Tillage in the crop year will result in burial of some of the clover seeds with a consequent effect on future pasture establishment. This experiment was aimed at determining the effect of several tillage systems on the depth distribution of clover seeds and the subsequent pattern of seedling emergence.
Subterranean clover (cv. Daliak) was sown on a sandy gravelly loam soil on a clover-free site at Bakers Hill. W.A. in 1976. Tillage treatments, which were imposed on replicated plots in May-June 1977 after the break of season, were as follows: no tillage; minimum tillage (scarified once); and conventional tillage (disc ploughed to 10 cm and scarified twice). No crop was actually sown. Regenerating clover plants were killed by spraying with a herbicide in August 1977 to prevent further seed set.
TABLE 1. Effect of tillage on depth distribution of seeds, seedling establishment and residual seed numbers (numbers/dm2)
There were clear effects of tillage treatments on the depth distribution of the clover seeds (Table 1). Tillage buried 44 and 55% of the seeds below 2 cm in the minimum and conventional treatments respectively. These treatment differences were reflected in the seedling densities obtained in 1978 with the no tillage treatment producing the highest density. On the other hand there were considerably more residual seeds in the tilled treatment.
Tillage affects the fate of seeds in at least two ways. Firstly it places some seeds below a depth from which they are able to emerge (= 3 cm). Secondly seed burial reduces the rate of softening by insulating the seeds from extremes of daily temperature fluctuations. Results from this experiment suggest that, at least in the early stages of a crop-pasture system, tillage will reduce pasture establishment in the following year. However, it is possible that in the longer term this effect may be offset by the build up of a reserve of seeds in the soil which can be brought to the soil surface by later tillage. The effect of a further series of tillages in the present experiment is being investigated.


text:
The View from My Window
Though he's not in a penthouse and the lake is nowhere in sight, "I wouldn't trade [the view] for the world," says Bobins.
By Nora O'Donnell
From his third-floor office in the LaSalle Bank Building (135 S. LaSalle St.), the bank's president and CEO, Norman Bobins, not only keeps watch over the heart of the city's financial district but has a front-row view of several gems of Chicago architecture. And though he's not in a penthouse and the lake is nowhere in sight, "I wouldn't trade [the view] for the world," says Bobins.
Photography: Nathan Kirkman
1. Built by the firm of Daniel Burnham and John Root in 1888, The Rookery (209 S. LaSalle St.) is named for where the birds-not to mention the politicians-roosted on what was once, briefly, City Hall. The construction of this Chicago landmark employed Root's innovative "floating foundations" system that interwove iron rails with concrete rafts, giving extra support on the city's then marshy surface. Burnham and Root kept their offices on the building's top floor.
2. Originally called the Continental Commercial National Bank, the building now simply called 208 South LaSalle Street broke records in 1911 as the city's most expensive proposed new development, exceeding $10 million. Three buildings, including the Rand-McNally Building that had served as the headquarters of the World's Columbian Exposition, were demolished for the new construction. Completed in 1914, the 20-story Burnham-designed building was also one of Chicago's tallest structures.
photography: Rob Goodwin
LaSalle Bank Building
Marshall Field IV kept his private apartments on the 43rd and 44th floors (now home to private dining areas and a grand ballroom) of what was then known as the Field Building (1934). The million-square-foot structure was the last major office building completed in Chicago before the Great Depression and World War II caused a two-decade delay in new construction.
3. The Greco-Roman columns of the Federal Reserve Bank (230 S. LaSalle) and 208 South LaSalle show the popularity of neoclassical architecture during the American Renaissance movement of the late 19th and early 20th centuries. This classical-inspired style was meant to impress and project a sense of financial security. The interior of the Fed, however, was state of the art when it was built in 1922-and included one of the first building-wide wired communication systems.
Photography: Bill Holmes
4. In 1930, the firm of Holabird & Root constructed the fourth and final Chicago Board of Trade building, home to the country's central grain exchange. Atop its 45 stories, a six-ton statue of Ceres (Roman goddess of agriculture) by the sculptor John Bradley Storrs stands 31 1/2 feet high. Far below at street level, the foot of LaSalle, crowds have a way of congregating: last October, nearly two million fans-the largest public gathering in Chicago history-watched the White Sox championship parade.
5. LaSalle from Adams Street to Jackson Boulevard became known as the "LaSalle Street canyon" in the 1920s and '30s, but even earlier the area produced some of the city's tallest structures, thanks to the nearby Board of Trade. The Home Insurance building (1885), shown below, which stood at LaSalle Bank's current location, used a steel-frame skeletal construction-a revolutionary idea that, according to some historians, made it the world's first true skyscraper.


text:
Home Lifestyle In many California communities with a historical "red line", the incidence and...
In many California communities with a historical "red line", the incidence and mortality from COVID-19 are higher
One of the legacies of the Red Line may be the higher incidence and mortality from COVID-19, which mainly affects minorities and the poor in these neighborhoods, according to a study published at the ATS 2022 international conference. The Red Line is a federal policy of the Great Depression , in which a quarter with large ethnic / racial minority groups was denied federal resources.
"Our research shows that where you live matters," said presentation author Ernesto Casillas, MD, researcher at the University of California, San Francisco (UCSF). "Previous studies have shown that the red line is associated with worse outcomes of asthma, fertility and cancer."
He added: "When the pandemic began, early epidemiological data showed that the most vulnerable groups in our society were affected by COVID-19 disproportionately. As far as we know, no previous study has attempted to assess the role of the red line on COVID-19 health outcomes. Our study has attempted to close this important gap. "
The sale of housing was a racist mortgage policy imposed by the Federal Homeowners' Loan Corporation (HOLC), which refused financial assistance to homeowners at risk of losing their homes due to the Great Depression. HOLC literally drew red lines around the neighborhoods and found them less desirable because of the racial and ethnic composition of those neighborhoods. These communities are now vulnerable to poverty, crime and disease. Examples of areas of California with a red line include South and East Los Angeles and areas surrounding San Francisco, Tenderloin County and Mission.
In this study, Dr. Casillas and his colleagues at UCSF examined census data on cases and deaths from COVID-19 reported to the California Department of Public Health from January 2020 to August 2021. San Francisco, Auckland, Los Angeles, San Jose, Sacramento, Stockton, Fresno and San Diego were included in the study. The researchers then used digital versions of the HOLC maps to assign to each census a risk class assigned to the HOLC (AD, with a "D" in the form of census plots in areas with a historic red line). They then conducted a statistical analysis to assess the relationship between HOLC risk and the number of COVID-19 cases and mortality adjusted for the percentage of women, age, comorbidities, and overpopulation. The Healthy Places Index (HPI), the Combined Society Welfare Index, and the Extreme Concentration Index (ICE), a measure of the social division of economically deprived and privileged social groups, were used in separate analyzes to adjust for a set of social conditions.
If the results were not adjusted by any of the methods described above, they showed that as the HOLC class deteriorated, the number of COVID-19 cases and deaths increased. For sites with the worst HOLC score, D (with a red line), the incidence rate (RR) was 3.34 (i.e., 3.34 times higher), compared to the best scores. RR to death was 2.27. In the adjusted models, the RR for COVID-19 cases was 1.28 and the RR for death was 1.62. When adjusted for HPI, the frequency of RR was 1.21 and RR for death was 1.56. Similarly, when adjusted for ICE, the RR for COVID-19 cases was 1.14 and the RR for deaths was 1.38.
"The legacy of red-line housing is still present in almost every major city in America," said Dr. Casillas. "While generalizing red-line areas outside of California is beyond our current study, other red-line states have similar problems, such as racial segregation, poor access to healthy food, higher poverty, and poor housing quality. These are just some of the factors that make the red line communities vulnerable to serious health outbreaks such as COVID-19. However, more research is needed to better address this issue. "
Historically, "red" urban areas have higher levels of air pollution
www.abstractsonline.com/pp8/#! … 76 / presentation / 5838
American Thoracic Society
Citation: Many California Red Line communities in California have higher rates of morbidity and mortality from COVID-19 (2022, May 17), obtained May 17, 2022 from https://medicalxpress.com/news/2022 -05-historially-redlined-california-higher-covid -.html
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text:
Q: How to find the a triplet in an array of numbers having maximum product? Today i got stuck on the following problem.Kindly provide some clues, the statement is following:
Given an array A[] of size n. Maximize A[i]*A[j]*A[k] under the following constraints:

*

*i < j < k

*A[i] < A[j] < A[k]

The code which i tried is as follow:
#include<iostream>
using namespace std;

int main(){
  int A[]={1,3,6,8,9};
  int max=0;
  int n=sizeof(A)/sizeof(A[0]);
  for(int i=0;i<n;i++)
      for(int j=i+1;j<n;j++)
        for(int k=j+1;k<n;k++)
        {
          if(A[i]<A[j]&&A[j]<A[k]&&max<A[i]*A[j]*A[k])
            max=A[i]*A[j]*A[k];
        }
        cout<<max;
   return 0;
}

A: Given i < j < k and you wanted to do something with 3 for loops, then you can obviously do
for(i = 0; i < n; ++i) {
    for(j = i + 1; j < n; ++j){
         if (A[i] < A[j]) {
             for(k = j + 1; k < n; ++k){
                 if(A[j] < A[k]) {
                 /*DoSomething with i,j,k*/
                 }
            }
         }
    }
}

This is mostly an indentation nightmare more than anything.

A: The following solution should be O(n^2)
#include <stack>
#include <iostream>
#include <stdexcept>

template <typename T>
std::stack<T> getStack (T const * a, std::size_t dimA)
 {
   if ( nullptr == a )
      throw std::runtime_error("nullptr in getStack()");

   if ( 0U == dimA )
      throw std::runtime_error("no values in getStack()");

   T              top;
   std::stack<T>  s;
   std::size_t    pos{ 0U };

   s.push(top = a[pos]);

   do
    {
      if ( top < a[pos] )
         s.push(top = a[pos]);
    }
   while ( ++pos < dimA );

   return s;
 }

int main()
 {
   int          a[] { 34, 12, 3, 7, 29, 45 };
   std::size_t  dimA { sizeof(a)/sizeof(a[0]) };
   std::size_t  numMult { 3U };

   std::stack<int> s;

   std::size_t     pos { 0U };

   do
    {
      s = getStack(a+pos, dimA - pos);
    }
   while ( (s.size() < numMult) && (numMult <= (dimA - ++pos)) );

   if ( s.size() < numMult )
      std::cout << "there is no solution" << std::endl;
   else
    {
      int res { s.top() };

      for ( auto ui = 1U ; ui < numMult ; ++ui )
       {
         s.pop();

         res *= s.top();
       }

      std::cout << "the solution is " << res << std::endl;
    }

   return 0;
 }

A: There is a simple O(N^2) algorithm. Here is the outline:

*

*For each element y

*Search maximum element x which is smaller than y and before y

*Search maximum element z which is larger than y and after y
Step 1 is O(N), Step 2 & 3 can be done in same loop which is O(N), in total it is O(N^2)

There is a O(N lg N) algorithm too, but it is more complicated:
We can precompute in O(N) and query in O(1) for finding maximum in range [l,r]. (Original thought is use segment tree or any RMQ structures, thanks for @PetarPetrovic pointing out)
Also we build a set (sorted list) on the fly while we iterate through each element in the array. The pseudo code is like:
Array A = []
Set S = {}
Ans = 0

For i = 0 to N // O(N)
  // A[i] is y
  x = binary search S, maximum element in S which is < A[i] //O(lg N)
  z = RMQ(i+1, N) // O(lg N), or O(1) if we precompute in O(N)
  if(x < A[i] && A[i] < z) Ans = Max(Ans, x*A[i]*z)
  Insert A[i] into S // O(lg N)
//Total is O(N lg N)

We try to see A[i] as the middle element y.
As we have a sorted set which contains all elements before i, we can binary search the maximum valid x using the set. We insert current element into this set afterwards.
We use O(N) to precompute an array and query in O(1) to find maximum in range [i+1, N-1]. The number found is z.
We update answer if (x,y,z) is valid tuple and greater than current answer.

redpajama_set_name: RedPajamaStackExchange


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This hand-built mahogany coloured bar unit will add a touch of class to any occassion.
4 Optic stand for your favourite spirits or shots.
Holds 4 bottles of various sizes up to 1 litre.


text:
Q: Upgrading MySQL Connector/Net I am trying to publish a website with our hosting provider.  I am getting error due to the fact that they only allow a medium trust and the MySQL Connector/Net that I am using requires reflection to work.  Unfortunately, reflection is not allowed in a medium trust.
After some research I found out that the newest version of the MySQL Connector/Net may solve this problem.  Connector/Net 6.6 includes enhancements to partial trust support to allow hosting services to deploy applications without installing the Connector/Net library in the GAC.  I am thinking that will solve my problem.
So, I unistalled MySQL Connector/Net 6.4.4 and I installed MySQL Connector/Net 6.6.4.
When I run the application in Visual Studio 2010 I get the error:
ProviderIncompatibleException was unhandled by user code

The message is
An error occurred while getting provider information from the database. This can be caused by Entity Framework using an incorrect connection string. Check the inner exceptions for details and ensure that the connection string is correct.
InnerException is
The provider did not return a ProviderManifestToken string.

Everything works fine when I have Connector/Net 6.4.4 installed.  I can access the database and perform Read/Write/Delete action against it.
I have a reference to the following in the project:

*

*MySql.Data

*MySql.Data.Entity

*MySql.Web

My connection string in Web.config
<connectionStrings>
  <add name="AESSmartEntities"
          connectionString="server=ec2-xxx-xx-xxx-xx.compute-1.amazonaws.com;
          user=root;
          database=nunya;
          port=3306;
          password=xxxxxxx;"
          providerName="MySql.Data.MySqlClient" />
</connectionStrings>

What might I be doing wrong?  Do I need any additional setting(s) to work with version 6.6.4 that wasn't required in the older version 6.4.4?

A: I also had this question posted on the MySQL forum.  Here is the response I received:
You're correct about that Connector/Net doesn't have to be in the GAC in order to work with Medium Trust, but this has some limitations. For the case of Entity Framework our driver needs Reflection, as you mention it, in order to be registered as a provider. Thus it can't be used without this permission. You need to add this reflection permission only for Member access to your policy or install the driver in the GAC.
We are looking for other ways to register the provider for Entity Framework. So far Connector can work with ADO.Net in Medium trust but not yet EF. We'll notify you as soon as we have this supported without the GAC for Medium Trust.


Is This the Guy That Broke Into Your Hamilton Township Home?
A break in an investigation has resulted in the arrest of an Atlantic City man for crimes committed in Hamilton Township over two years ago.
Hamilton Township Police say Gilbert Bonilla, 34, has been arrested an charged with a number of home burglaries from April and May of 2016. The burglaries had been reported from Anglesey, Brecknock, Bala, and Denbigh Courts.
Police say, "Detective VanGilder (who originally responded to these burglaries as a patrol officer) received a DNA hit from evidence collected at the scene of one of the burglaries and a suspect, Gilbert Bonilla."
Bonilla, who was being held in the county jail on another matter, has confessed to the crimes.
Source: Is This the Guy That Broke Into Your Hamilton Township Home?


text:
Who wins when you win?
Awards Services
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Awards Open in January 2021
by @donna-admin | Jan 13, 2021 | Blog, Business Awards
By Donna O'Toole
Welcome to our first monthly newsletter of 2021!
Every month we like to highlight a selection of awards open and waiting to receive your winning award entries.
Now the year hasn't begun quite how we had imagined with the pandemic still causing havoc across the world.
But we are pleased to report that awards are still going ahead this year, so you can still get the recognition you and your team deserve, and reap the benefits of winning awards.
Plus most awards are adding categories to reward business' resilience, ability to pivot and the employees and teams doing the most for their customers during the pandemic.
The companies and brands who are able to rise up during times of crisis and who strategically market and shout about their brand will be the ones who ultimately thrive. These are the brands who are continuing to strengthen their name, reward their people, and drive forward into the new year with renewed purpose.
So what are you going to do in 2021?
… are you going to sit and wait for all of this to be over?
…or are you going to stop waiting and start winning?
If you are ready to start winning here are just a few awards open right now!
Awards Open Now
UK Employee Experience Awards
The UK Employee Experience Awards organised by Awards International is a firm favourite of our clients. With categories available to recognise and celebrate all aspects of employee experience, including training and development, health and wellbeing, and use of digital technologies.
Plus the new Employee Experience in a Crisis category is open for the organisations who have continued to put their employees first even during the pandemic.
Earlybird deadline: 5th February 2021
Final Deadline: 5th March 2021
Global Social Media Awards
If you have a successful social media campaign that you are proud of then The Global Social Media Awards are a fantastic international award for you to enter! Get international recognition for your social team, with categories open for best use of Twitter, best integrated campaign, best agency of the year or best in-house team of the year, to name a few.
Plus they have introduced the category for best use of social media in a crisis to recognise the campaigns born from the pandemic.
Earlybird deadline: 29 January 20201
UK National Contact Centre Awards
Contact centres have been hugely impacted in the past 12 months with large teams condensed to abide by social distancing rules and whole teams adapting to working remotely from home, so winning a UK National Contact Centre Award could be a fantastic boost for morale.
There are categories open for individuals, including an unsung hero category for someone who has gone above and beyond for customers, colleagues or for the business, plus there are categories open for teams and organisations.
FS Tech Awards
The FS Tech Awards celebrate excellence and innovation in the UK and EMEA financial services and fintech industry. Choice of categories include best use of IT in consumer finance, best financial services IT team, digital transformation project of the year, technology provider of the year and more!
The awards are keeping entries open until they can confirm the timeline for this year's awards, giving additional entrants the opportunity to enter when they may have missed out.
The Princess Royal Training Awards
The Princess Royal Training Awards are organised by the City and Guilds Foundation with HRH The Princess Royal as the president. The awards are strong advocates of skills development in the workplace and are all about honouring the employers who have created outstanding training and skills development programmes resulting in exceptional commercial benefits.
There are two stages to the application process; the first comprises of completing the online entry form with successful entrants making it through to the assessment round where you will be visited by an official assessor.
Written entry deadline: 31 March 2021
Ready to win in 2021
As always we are here to support you with all your awards needs.
From choosing which awards to enter, writing winning entries and training you how to win awards just like we do, we have a solution for you.
So if you're ready to win in 2021 get in touch today!
Contact us now to find out which awards you could be winning.
With the latest news, I think we're all in the need of a bit of a boost right now! That's why we're sharing our ins… https://t.co/FX9I6spSut15 days ago
Welcome to our first monthly newsletter of 2021! Here are just some of the awards you could be entering right now in January 2021.
Does your business need a boost right now?
Does your business need a boost right now? We're sharing our insights to get your business through with the motivation & power you need to come out stronger
What does recognition really do? The New Year Honours List 2021
Find out the inspirational individuals who have made The New Year Honours List 2021 and what recognition actually does for people.
2020 has been one of the most difficult and tumultuous years, thankfully it hasn't all been so bad. Here is our 2020 year in review and our plans for 2021!
Awards Open in October 2020
by @donna-admin | Oct 1, 2020 | Blog, Business Awards
Hello and welcome to your monthly newsletter of awards open throughout October!
Now usually we'd all be donning our best black-tie outfits and heading to glamourous venues for awards ceremonies and celebrations, but with events still not able to go ahead, we've had to adjust to virtual ceremonies.
And what a fantastic job the award organisers have been doing!
We've had the pleasure of attending several virtual awards ceremonies this year, and for all the finalists the buzz of being up for an award is still there. And the excitement of hearing your name read out as the winner is still palpable, even on Zoom!
It's been fantastic to see teams and individuals getting the recognition they deserve for their work, especially for those winning specific COVID-19 crisis categories.
Winning awards has never been so important. Having a winners logo on your website, marketing and comms will play a huge part in building back better and ensuring your customers that you are the right choice.
Take a look at some awards you can enter right now!
AWARDS OPEN OCTOBER 2020
Think Global Awards
The Think Global Awards are open for entry from individuals, companies, and communities. The awards are a way of recognising achievements and promoting the awareness of thinking globally for individuals, communities, start-ups, small and medium-sized businesses, global brands, and large scale international organisations.
Deadline: 30 November 2020
Complaints Handling Awards
These are the only awards in the UK dedicated to recognising complaint handling excellence. Brought to you by Awards International, the UKCHA celebrates the incredible work done by complaint handling professionals – and gives you a chance for recognition!
Innovation in Talent Development Awards
The Innovation in Talent Development Awards are given in recognition of an innovation that has a measurable impact on an organisation or audience, moves the talent development industry forward, is sustainable, and is replicable. This award can be presented to an individual or a team.
STOP WAITING. START WINNING.
There are an abundance of awards around the world just waiting to recognise the best businesses in their industry, sector or country.
If you have good results, a good case study or project you are really proud of, the time to enter awards is NOW.
Because if you wait too long, your results will become old news and you'll miss out.
Take the first step today and complete the Win Business Award Test to find out if you are ready to enter and receive your invitation to our next Awards Strategy meeting!
2020 New Year Honours List
Happy New Year! And congratulations to the 1097 people who are starting 2020 with a huge accomplishment: receiving an honour from The Queen.
Personal Branding for Business Leaders and Entrepreneurs
August founder Donna O'Toole spoke to Business Leaders and Entrepreneurs about the importance of awards for personal branding and thought leadership.
Inspirational Individuals recognised in the Queen's Birthday Honours List 2019
The Queen's Birthday Honours List 2019 has seen 1073 individuals recognised for their fantastic personal achievements. Here is this year's roundup…
2019 New Year's Honours List
Congratulations to the 1148 who people have started the New Year with an incredible accolade; an honour from The Queen in the 2019 New Year's Honours List. The list features celebrities, sports professionals and extraordinary individuals, honouring them for their achievements, dedication to charity, and outstanding work in their chosen industries.
Awards Open in September 2020
by @donna-admin | Sep 1, 2020 | Blog, Business Awards
Hello and welcome to your monthly newsletter of awards open throughout September!
It's been 6 months since the pandemic rocked the world, and as we all adjust to a new way of living and working, award organisers around the world are adapting to ensure you can still get the recognition you and your teams deserve for all your hard work and accomplishments.
There are still so many awards open and accepting entries, with additional categories available to recognise businesses' Covid-19 response.
AWARDS OPEN SEPTEMBER 2020
FDM Everywoman in Technology Awards
The FDM Everywoman in Technology Awards shine a spotlight on the tech industry's most exceptional talent, from the UK and beyond, providing an opportunity for companies and individuals to put forward candidates for categories celebrating all stages of their career journey.
Deadline: 11 October 2020
Transform Awards Europe
The Transform Awards Europe 2021 will award excellence in rebranding and brand strategy. The awards will recognise best practice in corporate, product and global brand development work in the region, with categories that focus on strategy, execution, content and evaluation.
edie Sustainability Leaders Awards
The edie Sustainability Leaders Awards recognise excellence across the spectrum of green business; from the best efficiency programmes through to product innovations, from stakeholder engagement and social sustainability initiatives to the people on the ground who are making change happen.
Awards Open in August 2020
by @donna-admin | Aug 1, 2020 | Blog, Business Awards
Happy summer, and welcome to your monthly newsletter of awards open throughout August!
We may be having a slightly different summer this year as the world continues to handle the Coronavirus pandemic. But as we all take holidays and staycations to rest, recharge and enjoy the sun, there are still plenty of awards out there, ready and waiting for your entry.
September is a popular month for awards to deadline. So unless you want to submit a last-minute entry, now is the time to prepare and put together a strong, impactful entry!
AWARDS OPEN AUGUST 2020
Engage Awards
The Engage Awards are one of the only customer and employee engagement awards programmes, so if you've achieved great things with your engagement initiatives, then the Engage Awards could be perfect for you.
Deadline: 7 September 2020
International Business Excellence Awards
The IBXA recognise businesses achieving long-term sustainable profitability through the practice of excellence. There are 20 categories available and the 2020 awards finals will be a full-day experience, held fully online using the latest video conferencing software.
Deadline: 17 September 2020
The DMA (Data & Marketing Association) Awards celebrate and reward the campaigns with intelligent marketing at the heart. With 35 categories split across Industry Sector, Channels, Campaigns, Data and Craft.
Awards Open in July 2020
by @donna-admin | Jul 1, 2020 | Blog, Business Awards
Hello and welcome to your monthly round-up of awards open throughout July!
July is one of our busiest times of the year, we are super busy writing award entries, Queen's Award nominations, and implementing bespoke award strategies for our fantastic clients.
Lots of award programmes deadline in the summer, with their awards ceremonies scheduled for the winter, so there are still plenty of awards up for grabs in 2020.
Plus, many awards have added COVID-19 categories to recognise those businesses and individuals who have still managed to provide an excellent service, or gone above and beyond to support their community and customers, despite being hit by the pandemic.
So if you're ready to create some positivity in your business and win some business awards, take a look at just some of the awards open now!
AWARDS OPEN JULY 2020
Ethical Corporation Responsible Business Awards
The Ethical Corporation Responsible Business Awards are one of the world's leading Awards celebrating leadership in sustainable business.The Responsible Business Awards recognise those that are truly having an impact on business, society and the environment – delivering a new blueprint for business in the 21st Century.
Deadline: 14 August 2020
The Learning Awards
The Learning Awards are on the highest accolades you can win in learning and development. Whether you work as an individual learning professional or part of a wider team, for a commercial learning provider or within an internal learning department, you should be able to choose a suitable category to enter.
The Sunday Times Fast Track 100
The Sunday Times Virgin Atlantic Fast Track 100 league table ranks Britain's 100 private companies with the fastest-growing sales over their latest three years. It is compiled by Fast Track and published in The Sunday Times each December.
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