text:
Baseline Elevated Serum Angiopoietin-2 Predicts Long-Term Non-Regression of Liver Fibrosis After Direct-Acting Antiviral Therapy for Hepatitis C
Goki Suda, Naoki Kawagishi, Megumi Kimura, Osamu Maehara, Ren Yamada, and 14 more
published 28 Apr, 2021
Read the published version in Scientific Reports →
posted 14 Jan, 2021
We previously revealed that Angiopoietin-2 (Ang2) predicts non-regression of liver fibrosis based on liver stiffness measurement (LSM) at 24 weeks after anti-hepatitis C virus (HCV) treatment. In this study, we extended the observational period to 96 weeks to investigate the factors associated with non-regression after treatment with direct-acting-antivirals (DAAs). Patients treated with DAAs who underwent transient elastography at baseline and 24 and 96 weeks after DAA therapy were included. Baseline and post-treatment serum Ang2 levels were measured. Liver fibrosis stages were defined based on LSM. Multivariate regression was used to evaluate factors associated with non-regression of liver fibrosis between various time points. In total, 110 patients were included. Of these, 11% showed non-regression of LSM-based fibrosis stage at 96 weeks after DAA therapy. In multivariate analysis, advanced liver fibrosis stage and high baseline Ang2 levels were significantly associated with non-regression at 96 weeks. In patients with advanced liver fibrosis (F3/4), baseline Ang2 levels were associated with non-regression of liver fibrosis stage. Between SVR24 and SVR96, post-treatment Ang2 levels and controlled attenuation parameter values at SVR24 were significantly associated with non-regression of liver fibrosis stage in patients with F3/4. Thus, serum Ang2 levels are an important target for monitoring and therapy.
direct-acting antiviral agent
angiopoietin-2
liver stiffness measurement
Direct-acting antiviral agents (DAAs) targeting hepatitis C virus (HCV) proteins, including HCV protease, HCV NS5A, and HCV polymerase, have revolutionized anti-HCV therapy. Various clinical trials and real-world clinical studies have shown that DAA therapy for patients with HCV infection, including those previously classified as difficult-to-treat in the interferon treatment era, could achieve a sustained viral response (SVR) rate exceeding 95%.1-10 Most patients who achieve SVR experience an improvement in liver fibrosis11,12 with a low rate of hepatocellular carcinoma (HCC) occurrence. However, even after successful HCV eradication by IFN or DAAs, some patients develop HCC and/or the deterioration of liver fibrosis.11-14 Importantly, Tachi et al. showed that the deterioration of liver fibrosis after HCV eradication is significantly associated with HCC occurrence.11 Thus, predicting changes in liver fibrosis after HCV eradication is a clinically important issue.
Angiopoietin-2 (Ang2) has an antagonistic effect on Tie2-mediated signalling, which is associated with vessel stabilization in some situations.15,16 We and other groups have shown that serum Ang2 levels are elevated in patients with advanced liver fibrosis and advanced HCC,13,17,18 and this increase is partially due to a portal hypertension-induced decrease in blood flow.19,20 Thus, we hypothesized that portal hypertension-induced increases in serum Ang2 cause vascular leakage and inflammation, resulting in the deterioration of liver fibrosis. Consistent with this hypothesis, Seko et al. recently reported that the presence of portal hypertension-induced varices is an independent predictor of the deterioration of liver fibrosis based on the Fibrosis-4 (FIB-4) index at 96 weeks after the end of DAA treatment.21 In addition, we recently reported the possibility that baseline serum Ang2 levels could predict non-regression of liver fibrosis stage based on liver stiffness measurement (LSM) at 24 weeks after DAA therapy with high accuracy (sensitivity 0.882, specificity 0.733).13 However, in this previous study, the observational period was relatively limited.
In this study, we aimed to investigate the factors associated with non-regression of liver fibrosis based on LSM at 96 weeks after DAA completion and to validate the predictive value of baseline Ang2 levels over a longer observational period.
Patients and study design
A total of 208 HCV-infected patients at Hokkaido University Hospital between October 2014 and July 2016 were screened. The following inclusion criteria were applied: treated with IFN-free DAAs between October 2014 and July 2016, achieved SVR at 24 weeks after treatment completion (SVR24), had complete clinical information, had preserved serum samples at baseline and post-treatment (end of treatment to SVR24), and had FibroScan data for LSM at baseline, SVR24, and SVR96. Patients were excluded if they could not achieve SVR, had missing clinical information or FibroScan examination at baseline, SVR24, and SVR96, had a lack of serum samples at baseline and/or at post-treatment, had another liver disease or were receiving haemodialysis, and/or had a history of HCC.
Included patients were typically evaluated by the attending physician every 2 weeks during the treatment period and every 3 months after treatment completion. Data were collected at baseline, SVR24, and SVR96, including clinical information (laboratory data, HCV data, and treatment history of hypertension, diabetes mellitus, and dyslipidaemia) and FibroScan examination.
Preserved serum samples were used to measure serum Ang2 levels by a commercial enzyme-linked immunosorbent assay according to the manufacturer's protocol (R&D Systems, Minneapolis, MN, USA).13
This study conformed to the ethical guidelines of the Declaration of Helsinki and was approved by the ethics committee of Hokkaido University Hospital (UMIN000031091).
All enrolled patients provided written informed consent to participate in this study.
Definition of liver fibrosis stage and regression after successful HCV eradication
FibroScan 502 (Echosens, Paris, France) was used for LSM and controlled attenuation parameter (CAP) evaluation with the M-probe and XL-probe. As described previously, patients were placed in the supine position with the right hand at the most abducted position during the FibroScan examination procedure.13,22 Similar to our previous report, at least 10 valid measurements were obtained, and effective measurements were defined as those with a success rate of >60% and an interquartile range of <30%.13,22
The fibrosis stage was defined according to transient elastography data (FibroScan; Echosens) as described previously, with cut-off values of 7.1 kPa for F ≥ 2, 9.5 kPa for F ≥ 3, and 12.5 kPa for F4.13,23 In addition, according to a previous report, regression of liver fibrosis was defined as follows: in patients with liver fibrosis stage F2 to F4, the liver fibrosis stage decreased by more than 1 stage after DAA therapy; in patients with liver fibrosis F0/1, the liver fibrosis stage did not deteriorate.13,23
Continuous variables were analysed by the paired Mann–Whitney U-test, and categorical data were analysed by the chi-squared test. A multivariate logistic regression analysis with stepwise forward selection was performed with variables identified as significant at P ≤ 0.005 in univariate analyses of the factors associated with non-regression of liver fibrosis between baseline and at SVR96 and identified as significant at P ≤ 0.001 in univariate analyses of the factors associated with non-regression of liver fibrosis between SVR24 and SVR96. All P-values were two-tailed, and P < 0.05 was defined as statistically significant. Statistical analyses were performed using SPSS version 24.0 (IBM Japan, Tokyo, Japan).
Baseline patient characteristics
A total of 208 patients with HCV infection who received IFN-free DAA therapy between October 2014 and July 2016 and were regularly followed-up at Hokkaido University Hospital were screened. Of these, 110 patients with all FibroScan examination data at baseline, SVR24, and SVR96, complete clinical information, and preserved serum samples obtained at baseline and after treatment were included in this study (Figure S1). Table 1 shows the baseline characteristics of these 110 patients and a comparison of LSM-based liver fibrosis stages F0–2 and F3–4. The median age of patients was 66 years (range, 22–87 years), and 69 patients (62.7%) were female. The baseline median aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were 39 IU/L (range, 16–180) and 38 IU/L (range, 6–273), respectively, and the median platelet count was 16.2 × 104/μL (range, 2.6–37.3 × 104/μL).
In total, 19, 47, 39, and 5 patients were treated with daclatasvir plus asunaprevir, sofosbuvir plus ledipasvir, sofosbuvir plus ribavirin, and ombitasvir plus paritaprevir, respectively. Additionally, 62, 19, 8, and 21 patients had liver fibrosis stages based on LSM of F0–1, F2, F3, and F4, respectively.
Rate of non-regression at 96 weeks after successful HCV eradication by DAA therapy and associated factors
Figure 1 summarizes the changes in LSM-based liver fibrosis stage at 96 weeks after successful HCV eradication by DAA therapy. As the baseline liver fibrosis stage increased, the rate of non-regression at 96 weeks after DAA therapy increased. Among patients with baseline F4 stage, 33% (7/21) showed non-regression based on LSM, whereas 11% of all patients (12/110) showed non-regression based on LSM at 96 weeks after DAA therapy.
We further analysed the baseline predictive factors associated with non-regression of liver fibrosis at 96 weeks after DAA initiation. Table 2 provides a comparison of various factors in patients with or without non-regression of liver fibrosis stage based on LSM at 96 weeks after DAA initiation. A univariate analysis revealed that baseline liver fibrosis stage (F0–2 vs. 3–4, P = 0.002), FIB-4 index (P = 0.005), angiopoietin-2 (P = 0.004), HCV-RNA (P = 0.025), and AST (P = 0.029) were significantly associated with non-regression at 96 weeks after DAA initiation. Subsequently, we included significant factors identified in the univariate analysis (P ≤ 0.005) in a multivariate logistic regression analysis (i.e., the liver fibrosis stage, FIB-4 index, and Ang2 levels). As shown in Table 2, the multivariate logistic regression analysis revealed that baseline fibrosis stage (odds ratio 4.56, 95% confidence interval, 1.13–18.3; P = 0.033) and Ang2 level (odds ratio 1.004, 95% confidence interval, 1.00–1.01; P = 0.039) were significantly associated with non-regression of liver fibrosis stage based on LSM at 96 weeks after DAA initiation.
Table 3 summarizes the results of a subgroup analysis of patients with baseline fibrosis stage of F3/4. In this group, high Ang2 at baseline was significantly associated with non-regression of liver fibrosis stage based on LSM at 96 weeks after DAA initiation (P = 0.024).
Rate of non-regression of LSM-based liver fibrosis stage between 24 and 96 weeks after successful HCV eradication and associated factors
Subsequently, we analysed the rate of non-regression between SVR24 and SVR96 and associated factors. As shown in Figure 2, as the fibrosis stage increased at SVR24, the rate of non-regression at 96 weeks after DAA therapy increased. Among patients with stage F4 at SVR24, 58% (7/12) showed non-regression of liver fibrosis stage based on LSM, compared with 15% (17/110) for all patients.
As shown in Table 4, subsequent univariate analyses revealed that liver fibrosis stage at SVR 24 (F0-2 vs. 3–4, P < 0.001), platelet count at SVR24 (P = 0.004), history of hypertension (P = 0.006), AST level at SVR24 (P = 0.003), γGTP level at SVR24 (P = 0.019), FIB-4 index at SVR24 (P < 0.001), and post-treatment Ang2 level (P = 0.001) were significantly associated with non-regression of liver fibrosis stage between SVR24 and SVR96. Subsequently, we conducted a multivariate logistic regression analysis using significant factors (P ≤ 0.001) in the univariate analysis (i.e., liver fibrosis stage, FIB-4 index, and Ang2 levels). As shown in Table 4, fibrosis stage at SVR24 (odds ratio 12.35, 95% confidence interval, 3.86–39.6; P < 0.001) alone was significantly associated with non-regression between SVR24 and SVR96.
Next, we conducted a subgroup analysis of patients with liver fibrosis stage F3/4 at SVR24 (Table 5). A high Ang2 level post-treatment and high CAP value at SVR24 were significantly associated with non-regression of liver fibrosis stage between SVR24 and SVR96.
DAAs are revolutionary anti-HCV drugs. Numerous patients have experienced successful HCV eradication in the past several years due to these novel DAAs. However, recent studies have revealed that even after successful HCV eradication by DAAs, the occurrence of HCC and deterioration of liver function are sometimes observed. The deterioration of liver fibrosis after HCV eradication is closely associated with HCC occurrence11 and causes the deterioration of liver function; thus, the regression of liver fibrosis after successful HCV eradication is a clinically important issue. Previously, we reported that 25% (29/116) of patients show non-regression of LSM-based liver fibrosis stage at 24 weeks after DAA completion.13 In this study, 11% of patients (12/110) showed non-regression of LSM-based fibrosis stage at 96 weeks after the completion of DAAs. Thus, over a longer observation period, more patients with successful HCV eradication by DAAs could experience regression of the LSM-based fibrosis stage. A multivariate regression analysis revealed that baseline fibrosis stage and Ang2 levels were significantly associated with non-regression at 96 weeks after the completion of DAAs. These results are consistent with those of our shorter observational study (spanning 24 weeks) showing that the baseline fibrosis stage and Ang2 levels are significantly determinants of non-regression after DAA therapy.13
In addition, the observed association between an advanced fibrosis stage (F3/4) at baseline and non-regression of liver fibrosis after anti-HCV therapy is consistent with the results of a previous study in the IFN era.11 In a subgroup analysis of patients with advanced fibrosis (F3/4) at baseline (Table 3), we further showed that a high Ang2 level at baseline is significantly associated with non-regression of liver fibrosis stage at 96 weeks after DAA completion. Thus, high baseline Ang2 levels might be an important predictive factor for non-regression, even for long time periods (96 weeks) after DAA completion.
Because LSM could be affected by liver inflammation due to HCV infection, we analysed the period between 24 and 96 weeks after DAA completion (Table 4). Although a multivariate analysis revealed that advanced liver fibrosis stage (F0–2 vs. F3/4) alone was associated with non-regression, a subgroup analysis of patients with F3/4 at SVR24 revealed that high CAP and Ang2 values post-treatment were significantly associated with non-regression of liver fibrosis stage (Table 5). CAP is a well-established surrogate marker of liver steatosis.24 Liver steatosis is a risk factor for the development of liver fibrosis.25 Thus, even after successful HCV eradication, patients with liver steatosis should be carefully followed up and should take measures to improve liver steatosis. Elevated post-treatment Ang2 levels were also significantly associated with non-regression between 24 weeks and 96 weeks after the completion of DAA therapy in patients with F3/4 at SVR24 points, similar to the results obtained for the comparison between baseline and SVR96. Thus, serum Ang2 levels are a potential predictive marker of non-regression of liver fibrosis, even long after the completion of DAAs.
The ANG–TIE2 pathway has a unique effect on vascular stability. Ang1 is mainly expressed in mesenchymal cells and has agonistic effects on Tie2-mediated signalling, resulting in vessel stabilization and endothelial barrier function.15,16 Ang2 is mainly expressed in endothelial cells and is increased by VEGF, TGF, and hypoxia.26 In addition, it has been reported that portal hypertension-induced slow blood flow causes increased Ang2 expression.19,20 Ang2 has an antagonistic effect on Tie2-mediated signalling, resulting in the inhibition of ANG1–TIE2-mediated signalling, causing vascular instability, leakage, and inflammation.26
Several studies have shown that elevated serum Ang2 is a candidate biomarker in various liver diseases. Increased Ang2 expression in liver tissues is associated with the occurrence and recurrence of HCC after DAA treatment for hepatitis C.20 In this previous study, importantly, serum Ang2 levels after DAA therapy were significantly associated with liver tissue Ang2 expression levels. In addition, Lefere et al. reported the possibility that serum Ang2 levels could distinguish patients with NASH from those with simple liver steatosis.27 Mauro et al. reported that elevated serum Ang2 is associated with mortality and kidney outcomes in patients with decompensated cirrhosis with acute kidney injury.17 In addition, we have previously shown that baseline elevated Ang2 levels could predict non-regression of liver fibrosis stage based on LSM at 24 weeks after DAA treatment in patients with HCV infection. In this study, we showed that this association persists over a longer period, even at 96 weeks after DAA treatment in patients with HCV infection. Thus, elevated Ang2 could persist for a long duration and might have a pathogenic effect on liver fibrosis. It has been reported that elevated Ang2 expression causes vascular leakage and inflammation and might promote the progression of liver fibrosis.28
Recently, Ang2 has been identified as a potential therapeutic target26 in cancer and ophthalmologic diseases.26 Recently, the effectiveness of the inhibition of both Ang2 and VEGF in diabetic macular oedema has been reported29. Similarly, in liver disease, anti-Ang2 therapy is a potential novel therapeutic option. Lefere et al. observed higher serum Ang2 levels in patients with NASH than in patients with simple liver steatosis,27 and the inhibition of Ang2 restored liver fibrosis in a NASH mouse model. In addition, Pauta et al. reported that in a liver fibrosis rat model induced by CCl4, liver fibrosis and liver inflammation were reduced by the administration of an anti-angiopoietin 2 antibody.28
Accordingly, there is substantial evidence that the inhibition of Ang2 could be a novel therapeutic strategy in liver disease. In the present study, patients with elevated serum Ang2 levels showed non-regression of liver fibrosis, suggesting that anti-Ang2 therapy might lead to regression.
This study had several limitations. It was a retrospective study, and the number of patients was relatively small. Thus, a prospective, large-scale, and multicentre study is required to validate the findings. In addition, we evaluated the liver fibrosis stage using LSM. The gold standard for staging is liver biopsy; however, this procedure is invasive and carries a risk of sampling error. Thus, we utilized the LSM-based liver fibrosis stage, and this should be considered when interpreting the study results.
In conclusion, an advanced liver fibrosis stage and baseline high serum Ang2 levels are associated with non-regression of liver fibrosis stage at 96 weeks after the completion of DAA therapy. Thus, careful monitoring is necessary in these patients, even after successful HCV eradication by DAAs.
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
We thank the patients who participated in this study and their families. This study was supported in part by grants from the Japan Agency for Medical Research and Development (AMED; grant nos. JP20fk0210072, JP20fk0210064, JP20fk0210056, JP20fk0310101, JP20fk0210047, JP20fk0210048, JP20fk0210058, JP20fk0210066, and JP20fk0210067) and SPS KAKENHI (grant number 19K08458).
N.K. and G.S. designed this study, performed the statistical analyses, and wrote the manuscript. M.K., O.M., Y.T., K.S., A.K., M.N., T.S., Y.K., R.Y., T.K., T.S., and M.N. collected the data. M. Natsuizaka, K.M., and K.O. provided hepatological advice and edited the manuscript. N.S. revised the manuscript for important intellectual content.
Competing interests: Professor Naoya Sakamoto received lecture fees from Bristol Myers Squibb and Pharmaceutical K. K, grants and endowments from MSD K. K and Chugai Pharmaceutical Co., Ltd, and a research grant from Gilead Sciences Inc. Dr. Goki Suda received research grants from Bristol Myers Squibb. The other authors declare no competing interests.
Clinical trial number: UMIN000031091
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Table 1. Baseline characteristics of patients
Age (years)a
Sex (male/female)
DCV/ASV, SOF/LDV, SOF/RBV, OBV/PTV/r
9/9/10/1
HCV-RNA (log IU/mL)a
BMI (kg/m2)a
22 (15.8–36.3)
21.8 (15.8–31)
F0-1/2/3/4
62/19/8/21
62/19/0/0
Platelet count (×104) a
16.2 (2.6–37.3)
*<0.001
AST (IU/L) a
39 (16–180)
ALT (IU/L) a
γGTP (IU/L)a
FIB-4 index a
2.79 (0.54–13.51)
5.41 (1.55–8.69)
Angiopoietin-2 (pg/mL) a
305.6 (131.9–899.9)
*0.01
CAP (dB/m) a
214 (100–386)
Diabetes mellitus (n, %)
High blood pressure (n, %)
*0.001
Dyslipidaemia (n, %)
Abbreviations: HCV, hepatitis C virus; BMI, body mass index; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γGTP, γ-glutamyl transpeptidase; FIB-4, fibrosis 4; CAP, Controlled Attenuation Parameter.
aData are shown as median (range) values.
*Statistically significant difference, P < 0.05
Table 2. Factors associated with non-regression of liver fibrosis stage based on LSM between baseline and SVR96 in HCV-infected patients treated with DAAs
Non-regression
Univariate analysis
3/4/4/1
F0-2/3-4
4.56 (1.13–18.3)
1.004 (1.0–1.01)
Abbreviations: HCV, hepatitis C virus; BMI, body mass index; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γGTP, γ-glutamyl transpeptidase; FIB-4, fibrosis 4; CAP, Controlled Attenuation Parameter
Table 3. Factors associated with non-regression of liver fibrosis stage based on LSM between baseline and SVR96 in HCV-infected patients with baseline advanced liver fibrosis, who were treated with DAAs
6 (4.7–7.1)
22.6 (20–31.2)
344.1 (155.5–848)
493 (395.9–899.9)
*P < 0.05
Table 4. Factors associated with non-regression of liver fibrosis stage based on LSM between SVR24 and SVR96 in HCV-infected patients treated with DAAs
67(23-84)
Baseline BMI (kg/m2)a
22(15.8-36.3)
22.5(15.8-31.2)
F0-2/3-4 at SVR24
12.35(3.86-39.6)
Platelet count (×104) a at SVR24
17.8(3.6-34.1)
AST (IU/L) a at SVR24
21(11-50
26(17-128)
ALT (IU/L) a at SVR24
14(5-50)
16(9-121)
γGTP (IU/L)a at SVR24
FIB-4 index a at SVR24
2.07(0.5-9.35)
3.32(1.92-9.01)
Post-treatment Angiopoietin-2 (pg/mL) a
266(60.2-774.4)
416.6(219.1-913)
CAP (dB/m) a at SVR24
219(122-385)
Abbreviations: HCV, hepatitis C virus; BMI, body mass index; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γGTP, γ-glutamyl transpeptidase; FIB-4, fibrosis 4; CAP, Controlled Attenuation Parameter. aData are shown as median (range) values. *Statistically significant difference, P <0.05
Table 5 . Factors associated with non-regression of liver fibrosis stage based on LSM between SVR24 and SVR96 in HCV infected patients with advanced liver fibrosis at SVR24, who were treated with DAAs
22.5(20-31.2)
*Statistically significant difference, P <0.05
supplementaryFig.docx
Editorial decision: Major revision
Reviewers agreed at journal


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If a complaint is resolved properly, and the company goes above and beyond what they need to then it's always good to give feedback to their head office too. A site such as Head Office Finder will give you contact details for numerous supermarkets such as the Asda Head Office contact number.
Putting your negative complaint between two positives often helps it become resolved and can let the person you are complaining to see where you are coming from. The sandwich is made of three main ingredients, the 'ear opener' to make the listener sympathetic to your cause, some 'meat' that includes your complaint and suggested solution, and finally a sweet-sounding 'digestive' to motivate the listener to advocate on your behalf.
Whilst you may be very cross, being calm and polite usually resolves things sooner in my experience. Social media complaints are often littered with posts full of CAPS Lock, excessive punctuation - and often, shockingly, foul language. At the end of the day, the person you are speaking to usually hasn't played any part in the situation you are complaining about and it isn't fair to talk to them like this. Remain polite and they will be sure to help you to the best of their ability. If you are rude and threatening, they may terminate communication which they are well within their rights to do.
You don't want your complaint to go on forever and you are entitled to an explanation, if not an apology, within a certain time period. When making your complaint, give them a deadline in which you want it to be resolved so they don't keep dragging it on. With a deadline in place, you'll often find things resolve in a satisfactory way.
Whilst us British people like to complain about the weather, sport and other things like that, it seems we are often reluctant to actually complain when receiving shoddy service. I hope these tips help you in the future when considering making a complaint.
I have to say, I don't mind complaining, but then I am Irish and we are pretty direct. As long as you are polite and factual without making it personal, most companies will listen to an honest complaint.
I never heard of a complaint sandwich but agree placing it with two positives would be a great idea!
Hope it works for you, next time you have to complain.


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Peanut Company Officers Case Emanating From Salmonella Outbreak - Affirmed
By Ellen Podgor
The 11th Circuit affirmed the convictions of three defendants coming from a 2009 investigation of a peanut production plant that was identified as the source of a nationwide salmonella outbreak. The court in United States v. Parnell stated in an unpublished opinion:
"The jury found Stewart and Michael guilty of several counts of fraudulently introducing misbranded food into interstate commerce, interstate shipment and wire fraud, and conspiring to commit these offenses. The jury also found Stewart guilty of fraudulently introducing adulterated food into interstate commerce. The jury found Stewart and Wilkerson guilty of obstruction of justice. The district court sentenced Stewart to 336 months [28 years] in prison, to be followed by three years of supervised release; sentenced Michael to 240 months [20 years] in prison, to be followed by three years of supervised release; and sentenced Wilkerson to 60 months [5 years] in prison, to be followed by two years of supervised release."
The convictions were based on conduct related to food safety and conduct during the investigation. The appellants were found to have "not [been] forthcoming with the FDA during its investigation."
"The court rejected arguments related to "juror exposure to extrinsic evidence." The court also rejected a discovery argument made by one of the defendants. This defendant objected to the government "producing a large hard drive of documents in late June 2014 when the trial was set to begin on July 14th." The defendant argued that this was "one of many untimely data dumps, where the Government produced hard drives containing hundreds of thousands of documents..." The court found that the district court had made a finding that the documents were searchable and that the government had provided a Bates index seven months prior to trial, and that "an IT consultant helped" the defendant and counsel "search and review the documents." The Court stated that "[g]iven that [the defendant] was able to search the documents, they were not suppressed for purposes of Brady."
See also opinion - here
R. Robin McDonald, 11th Circuit Upholds Convictions in One of Nation's Largest Criminal Food Safety Prosecutions, Daily Report, Jan. 26, 2018.
January 28, 2018 in Environment, Food and Drink, Judicial Opinions | Permalink | Comments (0)
Food for Thought re Last Week's Peanut Sentencing in Georgia
By Lucian E. Dervan
Just over a year ago, Stewart Parnell, the former CEO of Peanut Corporation of America (PCA), was convicted by a jury in the Middle District of Georgia of charges related to a deadly nationwide salmonella outbreak. The matter came to the government's attention in late 2008 when people began falling ill across the country. The illnesses were eventually linked back to PCA's peanut processing plant in Georgia. As investigators continued to examine the salmonella outbreak, they discovered that the case involved potential criminal misconduct by Parnell and others who allegedly knew about the contamination, attempted to cover it up, and continued to ship contaminated and potentially contaminated product. In one now infamous email from 2007, after being informed that batch test results were not back from the lab, Parnell wrote, "Just ship it." The outbreak killed nine people and injured thousands more. Eventually, Parnell and others were charged in a 76-count indictment that alleged mail and wire fraud, introducing adulterated and misbranded food into interstate commerce, conspiracy, and obstruction of justice. A jury found Parnell guilty of 67 of the 68 charges against him on September 19, 2014.
On Monday of last week, U.S. District Court Judge W. Louis Sands sentenced Parnell to 28 years in federal prison. One interesting aspect of the sentencing is that because authorities charged this case as a "white collar" matter involving fraud, rather than a homicide case, the most significant factor driving the guideline sentencing range was not the deaths of nine people, but the loss of over $100 million by the various food companies that were forced to recall their products because of Parnell's actions.
According to last week's DOJ press release:
Judge Sands took into account the fraud loss of PCA's corporate victims when imposing today's sentence. The court found that Stewart Parnell and Mary Wilkerson should be held accountable for more than $100 million but less than $200 million in losses, and Michael Parnell should be held accountable for more than $20 million but less than $50 million in losses. The court also found the government established evidence that Stewart Parnell and Mary Wilkerson should be accountable for harming more than 250 victims, and Michael Parnell should be accountable under federal sentencing guidelines for harming more than 50 victims. The court additionally found that the Parnells should have known that their actions presented a reckless risk of death or serious bodily injury.
Looking at the applicable 2009 Federal Sentencing Guidelines (the Guidelines in place at the time of the offense conduct), one finds the following point allocations:
Base Offense – 7 points
Loss of more than $100 million – 26 points
250 or more victims – 6 points
Risk of death – 2 points
TOTAL: 41 points
While there were likely other applicable sentencing points, such as obstruction of justice and role in the offense, the above point allocations alone result in 41 total points. This translates into a guideline sentencing range of 324-405 months (27.00 – 33.75 years) for a defendant with no criminal history. Steward received 336 months (28 years).
To highlight the importance of the loss amount in the Guideline's calculation, note that if this case had involved nine deaths, but no financial loss to food companies, the sentencing range under section 2B1.1 of the Federal Sentencing Guidelines would have dropped to 18-24 months in the above calculation. Obviously, this would have been a grossly unreasonable sentence given the devastating harm caused by Parnell.
I don't know why this case was charged as a fraud and not a homicide. Perhaps it was to send a clearer message about national food safety by bringing federal charges, including charges directly related to the introduction of adulterated and misbranded food into interstate commerce. One additional item to note, however, as we think about the way this case proceeded, is that federal white collar sentences in high loss cases can often dwarf sentences for other crimes, including homicide. Consider that involuntary manslaughter in Georgia carries a maximum sentence of ten years in prison. Georgia also has automatic parole eligibility for most inmates. By comparison, Parnell received 28 years in prison using federal fraud statutes and their applicable sentencing guidelines. Further, there is no parole in the federal system.
Federal fraud offenses are often attractive to prosecutors because they are broad enough to apply in all manner of situations and carry potentially significant sentences. It should be no surprise, therefore, that we continue to see these statutes used in many cases that do not fit neatly into our traditional definitions of "white collar crime." For a further discussion of the way "white collar offenses" are used in a vast array of cases, many of which do not involve traditional white collar criminal activity, see "White Collar Crime": Still Hazy After All These Years, 50 Georgia Law Review Issue 3 (Lead Article) (forthcoming).
(LED)
September 28, 2015 in Food and Drink, Fraud, Prosecutions, Sentencing | Permalink | Comments (0)
Wine Fraudster Gets Ten-Year Sentence
By Lawrence S. Goldman
Last month Prof. Douglas Berman reported in his indispensable Sentencing Law and Policy blog about a ten-year prison sentence imposed by SDNY judge Richard Berman upon defendant Rudy Kurniawan, who had sold counterfeit wine to the very rich, including billionaire William Koch (one of the less political Koch brothers), and allegedly profited by over $28 million (see here by scrolling down to August 10, "Can wine fraudster reasonably whine that his sentence was not reduced given wealth of victims?" See also here). Some of the ersatz wine sold for as much as $30,000 per bottle.
Having a somewhat perverse sense of humor, I found it somewhat amusing that the 1% paid astronomical sums for and presumably sometimes drank the same wine that the other 99% of us drink. However, neither the judge nor the prosecutor (nor certainly the defendant and his lawyer) viewed the sentencing proceeding as a laughing matter.
To be sure, a $28 million fraud is a serious matter deserving serious punishment. Additionally, the judge seemed to view the crime in part as a public safety violation, declaring "The public at large needs to know our food and drinks are safe, -- and not some potentially unsafe homemade witch's brew," even though this was hardly a contaminated baby food case.
At the sentencing hearing, Kurniawan's attorney argued, reasonably I believe, that his client should be treated somewhat less severely since the victims were exceedingly wealthy. That argument provoked the prosecutor to the Captain Renault-like response that it was "quite shocking" for a lawyer to argue for a different standard for theft from the rich than from the poor.
That retort reminded me of Anatole France's immortal line (although not directly on point), "The law, in its majestic equality, forbids rich and poor alike to sleep under bridges, beg in the streets or steal bread." In my view, a sentencing judge should certainly consider in sentencing the extent of damage to the victim(s). A fraudster who steals a million dollars from a billionaire, notwithstanding the Sentencing Guidelines' overemphasis on absolute figures, should (all things being equal) not deserve as harsh a sentence as one who steals the same amount if it were the entire life savings of a senior citizen.
Prosecutors, when fraud victims are pensioners and widows, argue, I believe reasonably, that the judge should consider the degree of suffering of the victims. Indeed, every seasoned white-collar trial lawyer knows that in a multi-victim fraud case the government is likely to call as "representative" witnesses those most sympathetic victims for whom the monetary loss was most damaging.
I assume that the prosecutor will get over his "shock" when he prosecutes a fraud case where a less than affluent victim's life savings are stolen. I further assume he will not argue that the judge should impose the same sentence she would if the victim were a billionaire for whom the loss figure might be pocket change.
(goldman)
September 3, 2014 in Defense Counsel, Food and Drink, Fraud, News, Prosecutors, Sentencing | Permalink | Comments (0) | TrackBack (0)
Eleventh Circuit Finds Violation of Customs Regulation Not Criminal
by: Lawrence S. Goldman
One of the several troubling aspects of the continuing overcriminalization of federal law is the frequent elevation of a violation of civil regulation to a crime. In United States v. Izurieta, 11th Cir., 11-13585 (February 22, 2013), the Eleventh Circuit addressed this issue.
The defendants in Izurieta were convicted after trial by jury of violating the general smuggling statute, 18 U.S.C. 545, importing goods "contrary to law," by violating a customs regulation, 19 C.F.R. 142.113(c), in failing to redeliver to Customs for exportation or destruction goods purportedly contaminated with E. coli, Staphylococcus aureus and/or Salmonella which had been conditionally released.
The defendants appealed on various grounds -- significantly not including whether the indictment sufficiently charged a crime by relying on the Customs regulation. At oral argument, however, the Court raised this issue sua sponte and ordered supplemental briefing.
Section 545, as pertinent here, reads:
Whoever fraudulently or knowingly imports or brings into the United States, any merchandise contrary to law, or in any manner facilitates the transportation, concealment, or sale of such merchandise after importation, knowing the same to have been imported or brought into the United States contrary to law . . . shall be fined . . . or imprisoned . . . .
Emphasis added.
The regulation or "law" upon the charges here were based covered the "failure to deliver, export, and destroy with FDA supervision" certain foods found to be adulterated. 19 C.F.R. 141.113(c).
The Court in its opinion recognized a split among circuits on when a regulation constitutes the "law" upon which a Section 545 indictment may be based. The Ninth Circuit in United States v. Alghazouli, 517 F.3d 1179, 1187 (9th Cir. 2008) took what the opinion called "a relatively narrow interpretation" of Section 545 that regulations are included in "law" only when "there is a statute (a 'law') that specifies that violation of that regulation is a crime." The Fourth Circuit in United States v. Mitchell, 39 F.3d 465, 470 (4th Cir. 1994), to the contrary, took what the opinion called a "more expansive" view, deciding that Section 545 criminalizes violations of any regulation "having the force and effect of law" based on a three-prong test.
The Court, while claiming its binding authority, Bobb v. United States, 252 F.2d 702, 707 (5th Cir. 1958) was consistent with the Fourth Circuit's "expansive" approach in Mitchell, applied the rule of lenity and held that the regulation in question did not qualify as a "law" for purposes of Section 545 liability. It found that the regulation in question was primarily to reflect contractual requirements between Customs and the importer and thus was "civil only."
The rule of lenity was premised, it said, on two ideas: first, that "a fair warning should be given . . . of what the law intends to do if a certain line is passed" and, second, that "legislators and not courts should define criminal activity."
This apparent case-by-case approach, of course, does not establish a "bright line" as to when violations of an administrative regulation become a crime. Citizens and attorneys will often have to guess whether a violation of a regulation is a crime; that is, "what the law intends to do if a certain line is passed." The case may, however, curb the government's increasing efforts to convert violations of ostensible civil regulations into crimes.
This case should remind lawyers that the uncertainties in this area require that they pay attention at both the trial and appellate levels to the issue of whether a violation of an administrative regulation is a crime.
(A hat tip to Paul Kish and the Federal Criminal Lawyer Blog)
March 5, 2013 in Food and Drink, Judicial Opinions, Prosecutions, Prosecutors, Statutes | Permalink | Comments (0) | TrackBack (0)
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Ken Levy on Materiality and the Flynn Prosecution
Harvey A. Silverglate on Obstruction of Justice Charge in ICE Related Case - Old News?
Jeff Weiner on Decision to Dismiss Case of Senator Robert Menendez
Donnie Dixon on McCabe & Mr. Mueller: Where Are We Now?
David Bukey on Point of Personal Privilege: Can the President Obstruct Justice? Yes and No.
Peter Henning RIP
Fifth Circuit Reverses Tax Counts
Briefs Filed in Ruan and Khan.
More on Elizabeth Holmes
Theranos Founder Elizabeth Holmes Convicted On 4 Of 11 Counts. And That Will Be Enough.
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Ellen S. Podgor
Gary R. Trombley Family White-Collar Crime Research Professor
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redpajama_set_name: RedPajamaCommonCrawl


Assignment 6 of the Society of Botanical Artist's Distance Learning Diploma involved painting a fruit of our choosing. I really struggled with my choice of fruit in my head, but as soon as I got out into the local farm shops I was instantly struck by these pomegranates.
I got out my kitchen knife and you can see the results below! Choosing the composition was quite difficult.
As I mentioned above, to say there was a pressure of time is a huge understatement, but it was entirely my own fault so I just had to plow on.
I did do one small study, but basically I just dove in, I had to… I started work first on the main bulk of the skin, using varying mixes of Quinacridone Rose (Daniel Smith), Alizarin Crimson, Cobalt Blue, Scarlet Lake (all Windsor & Newton). I laid down a number washes to build up the depth of colour using the wet-in-wet technique. I did try and give the impression of the textured skin even at this stage.
Next I went onto the seeds. These I did do some practicing, as it was really important to capture the highlights, the translucency with the inner seed inside, as well as the bright pink colour.
The next part I had to work on was the twirl of skin. The outer part was just a continuation of the process I had used for the main bulk of the skin, but the inner pith required a mix of a botanical grey, with some yellow ochre, really trying to demonstrate the texture inside where the seeds lie.
The feedback I received was generally good, which I was very surprised about but obviously very pleased. The main critique was that the way the skin fell to the left hand side of the fruit wasn't quite believable. This was in fact how it did fall, but I do agree that it would make more sense to the eye to have it coming from slightly higher up! Sometimes we should use our artistic licence to help the eye understand the image.
Thank you for reading - the next assignment is vegetables!


text:
Stygnoleptes gibber is een hooiwagen uit de familie Zalmoxioidae.

Zalmoxioidae

redpajama_set_name: RedPajamaWikipedia


text:
Operational safety study: vehicle operations on a taxiway
Cologne Bonn Airport tasked airsight to conduct an operational study on safe operations of ground vehicles crossing an operational taxiway.
Cologne Bonn Airport commissioned airsight to carry out a comprehensive exercise to develop an operational solution to allow safe operations of ground vehicles on the maneuvering area (i.e. live taxiway).
Ground service vehicles crossing an operational taxiway can be hazardous and can cause aircraft and vehicle delays as well as severe operational constraints.
At Cologne Bonn Airport an essential service road connecting two main parts of the airfield crosses one of the operational taxiways – TWY B. To ensure safe and efficient operations of ground vehicles and aircraft taxiing, a suitable operational solution needed to be developed to improve the current situation.
Aviation safety is one of airsight's core competencies, with expertise ranging from operational analyses to aeronautical studies and assessments on all kinds of safety matters that concern airport operators or air navigation service providers.
One particular challenge of this project became apparent when a benchmarking exercise showed that the layout and operational necessities in CGN are unique in Europe and no similar processes exist at other airports that fulfil the specific requirements of this particular situation. To account for the distinctive nature of the task, specific safety requirements were defined, serving later as key indicators for the realisation of an operational concept. Various options were developed and evaluated including operational regulations aided by gates or barrier mechanisms, re-routing of taxiflows and a complete re-design of the intersection. During the optioneering process comprehensive stakeholder consultations were carried out to reach consensus and agree a serviceable solution.
This study derived a solution that provides operational safety and is commercially viable, provided vital aid for the consultation process and achieved the necessary stakeholder consensus.


This is a placeholder page for Douglas Barrett, which means this person is not currently on this site. We do suggest using the tools below to find Douglas Barrett.
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Morning only: ?opportunity to hear our 3 speakers and the Panel Q & A with our 2013 Award winners ? includes 2 servings of tea/coffee & biscuits at ?30 + ?1.40 online booking fee.
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Click on this link to download the invitation ?Students 2014 WeDO Scotland Conference Invitation?and click HERE for the full itinerary for the event where you can also book your ticket.
We are very pro-active in terms of supporting our Young Members and are increasing our engagement with the ?next generation of potential entrepreneurs in the making coming through the further education system. ?We hope that by engaging with students at an early stage, we will encourage more innovation and drive to build their own businesses. ?Our Young Members Club which launched in October of last year has proved very popular with our members under the age of 35 where they have the opportunity to not only brainstorm with their peers but also to learn from and gain advice from more experienced members. ?In turn, the young members also have, in many cases, different skill sets to the more experienced ones which has proven to be a winning formula with the exchange of information and knowledge flowing both ways.


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Home / News Releases / 2016 / 1121 Common Probiotics Can Reduce Stress Levels Lessen Anxiety
Using a zebrafish model, Daniel Davis and a research team from the University of Missouri determined that a common probiotic sold in supplements and yogurt can decrease stress-related behavior and anxiety.
Photos (3):
Common Probiotics Can Reduce Stress Levels, Lessen Anxiety
VIDEO: Common Probiotics Can Reduce Stress Levels, Lessen Anxiety
COLUMBIA, Mo. – Probiotics, or beneficial live bacteria that are introduced into the body, have become increasingly popular as a way to improve health and well-being. Previous studies have shown a direct correlation between gut microbes and the central nervous system. Now, researchers at the University of Missouri, using a zebrafish model, determined that a common probiotic sold in supplements and yogurt can decrease stress-related behavior and anxiety. Studying how gut bacteria affect behavior in zebrafish could lead to a better understanding of how probiotics may affect the central nervous system in humans. Their results recently were published in Scientific Reports a journal of Nature.
"Zebrafish are an emerging model species for neurobehavioral studies and their use is well-established in drug-screening," said Aaron Ericsson, director of the MU Metagenomics Center and a research assistant professor in the Department of Veterinary Pathobiology. "Our study has shown that simple probiotics that we normally use to keep our digestive tract in sync, could be beneficial to reducing our stress levels as well."
In a series of studies, researchers tested how zebrafish behaved after doses of Lactobacillus plantarum, a common bacteria found in yogurt and probiotic supplements. In the first study, scientists added the bacteria to certain tanks housing zebrafish; other tanks of zebrafish received no probiotics. Then, the researchers introduced environmental stressors to both groups, such as draining small amounts of water from the tank and overcrowding.
"Each day we introduced a different stressor — tests that are validated by other researchers and cause higher anxiety among zebrafish," said Elizabeth Bryda, professor of veterinary pathobiology in the MU College of Veterinary Medicine. "These are common environmental stress patterns, such as isolation stress and temperature change, so it made the tests relevant to humans as well."
By analyzing the gene pathways of both groups of fish, the research team found that zebrafish that were given the supplements showed a reduction in the metabolic pathways associated with stress.
"By measuring the genes associated with stress and anxiety, our tests were able to predict how this common probiotic is able to benefit behavioral responses in these fish," said Daniel Davis, assistant director of the MU Animal Modeling Core. "Essentially, bacteria in the gut altered the gene expression associated with stress- and anxiety-related pathways in the fish allowing for increased signaling of particular neurotransmitters."
To test their theory further, the researchers measured the movements of fish in their tanks using sophisticated computer measuring and imaging tools. Previous studies of fish behavior have found that fish that are stressed tend to spend more time at the bottom of their tanks. Once the fish were administered probiotics, they tended to spend more time toward the top of the tanks — the change in behavior indicating they were less stressed or less anxious.
"Using zebrafish, we've developed a relatively inexpensive platform for testing of other species of bacteria and probiotics and their potential benefit on different systems of the body," Ericsson said.
The study, "Lactobacillus plantarum attenuates anxiety-related behavior and protects against stress-induced dysbiosis in adult zebrafish," was published in Scientific Reports. The work was funded by a faculty research grant from the College of Veterinary Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.


Cynosure, a leading developer and manufacturer of a broad array of light-based aesthetic and medical treatment systems, retained Visnick and Caulfield to design the total renovation, expansion and connection of two buildings by way of a ground level connector in a multi-phased endeavor which integrated all aspects of design and project planning. The expanding company desired a space to more accurately portray their culture and brand. VC worked with Cynosure to shed new light to the face and brand of the company by creating a contemporary environment that would attract and retain new employees. VC brought both buildings together by designing an enclosed connector leading to a "chill zone" filled with bright pops of color and diverse array of collaboration areas. The chill zone features an interconnected stair separated by bright orange glass panels to the cafe area. VC continues to work with Cynosure through other expansion opportunities.


This transitional chair brings a unique blend of classic style and contemporary design to your home. The English rolled track arms and two sets of accent pillows add elegance to this chair. Features such as the nail head trim accenting around the base and tapered wood legs update this piece for a modern look at home in every design style.
The 5970 Transitional Chair with Nail Head Trim by Fusion Furniture at Standard Furniture in the Birmingham, Huntsville, Hoover, Decatur, Alabaster, Bessemer, AL area. Product availability may vary. Contact us for the most current availability on this product.
Create an elegant yet modern look for your living room with this collection. Features such as English rolled arms and nail head trim accenting combine to make the collection's flawless transitional style.
The 5970 collection is a great option if you are looking for Transitional furniture in the Birmingham, Huntsville, Hoover, Decatur, Alabaster, Bessemer, AL area.
Browse other items in the 5970 collection from Standard Furniture in the Birmingham, Huntsville, Hoover, Decatur, Alabaster, Bessemer, AL area.


This is our 'bread and butter' at Treetops Cattery, something we have done for over 30 years now.
The indoor accommodation at Treetops is warm and friendly - providing the perfect home away from home. Boasting a range of family pens from our largest play-pen to smaller 'two-storey' apartments including Television and Radio to provide the complete home experience.
The outdoor accommodation is set amongst the trees and provides spacious apartments for single cats or larger apartments for cat families.
Each cat is allocated one day free run in the outdoor accommodation which features cat grasses, plants and a pond.
Individual diets tailored to each guest.
Medication Administration including injections for diabetic cats.
Vet Services on call 24 Hours 7 Days a Week.
Apartment cleaning every morning for all guests.
All guests fed twice daily.


Be sure to attend church on Sunday, November 13th. We will be taking a group picture for our Directory. If you absolutely cannot attend that day, please email/bring a photo of yourself to the church office.


TB: You've just launched Australia's first all female and LGBTQI+ inclusive booking agency which is an incredible step in the right direction for our local scene. So what inspired you to make this venture?
KG: Thank you! Alpha stemmed from my own personal experience as a female music industry worker combined with the hardships I've seen my female talent experience. Women in music need to be supported and empowered, as do the LGBTQIA+ community and people of colour. So my mission is to represent those who have to work twice as hard to do the same job because of their gender, sexuality or ethnicity.
TB: How are you planning on adding and monitoring your roster?
KG: I was lucky enough to launch the agency with some incredible female DJs, producers, singers and songwriters who I had worked with previously or was connected through the electronic music traps. I'm actively scouting talent from the LGBTQIA+ community and encouraging performers from all genres to reach out. It's a super exciting process developing the Alpha roster and I can't wait to see it come together in the coming months.
TB: You've mentioned that your goal for Alpha Booking Agency is to see social change, not only for women in music, but for women in Australia and globally. So who are some strong females in the music industry that constantly inspire you?
KG: I'm continuously inspired by my mother; She's the reason I'm a strong and resilient woman. Mum raised my as a single parent with no support but still managed to put herself through TAFE to complete her HSC, be accepted into uni and then build a career all while working random jobs to make ends meat and give me the best possible childhood I could've asked for. She still amazes me daily!
Women in music who inspire me are the women I work with or have worked with previously. It's them who I really lean on for support and who have kept me motivated when things seem hopeless.
TB: Over the last year we have seen a real magnifying glass being put on our local festival scene with gender ratios being notably unequal. There have been a lot of mixed arguments about why this is, but what is your opinion on the obvious discrepancy?
KG: Women and identifying talent definitely need to be showcased more fairly on festival lineups. I'm a believer in the best person for the job at all times, however festival lineups are generally curated by males so this often skews gender parity. Lineups should be 50:50 where possible and if the genre of music featured at the festival has more male talent than female in the scene, a representation of that ratio should be on the lineup.
TB: Are there any festivals you think that are modelling the way at the moment with the correct gender ratios domestically or internationally?
KG: Keychange is a global initiative which aims to bring 50:50 gender balance on festival lineups by 2022, with women, trans and non-binary musicians being empowered and encouraged through the initiative. So far the only Australian festival registered is Beyond The Valley, so hopefully the rest of Australia follows their wonderful lead!
TB: Recently we have seen a massive growth in the music industry embracing LGBTQI+ artists and allowing them to be more honest with their identities in music and live shows. I still think we have a long way to go but with some mainstream artists leading the way with neutral pro-nouns in songs and true creative expression do you think that we are growing and evolving as a society?
KG: I think we are headed in the right direction, at a pace that may be a little slower than we would like but nonetheless it's happening. Australia has embraced queer commercial talent like Troye Sivan and Sam Smith which is a great indication that the industry and the people consuming music is making a positive change.
TB: With BigSound just passing, one of the most exciting things I noted was how many incredibly talented female acts we have in the Australian scene. So who are some newcomers that you are personally loving at the moment that you think people should check out?
KG: There are so many astounding female acts in Australia, we really do grow raw, awe-inspiring talent here! Go and check out the incredible roster at alphabookingagency.com; that's a good start!
TB: BigSound was a big week for you as you introduced Alpha Booking Agency to some of the biggest and most passionate names in the industry. So how was the reaction to this new venture?
KG: The response has been wonderful so far. Everyone has been so encouraging and thankful that Alpha is coming into the Australian music industry at a time where it's really needed. We're incredibly grateful for all of the support from everyone, so thank you.
TB: Over the years you've worked for other agencies with some of the biggest names in the Australian music industry. Witnessing everything first hand, where do you think other booking agencies are going wrong? And why do you think we have such a gender gap in Australia?
KG: From my personal experience I've seen males in the industry not take female talent seriously and not respect the talent that they have because of the misconception that women in electronic music are just a pretty face pressing a button. Women are skilled DJs with technical minds who like cutting songs, creating atmospheres and curating truly badass set-lists too so they need to be praised for that by men and other women in the industry alike.
TB: This industry and world can be a little patronising at times so what would you like to stay to females who are scared to be themselves or confused with the current state of the world?
KG: Be true to who you are and don't be afraid to ruffle feathers and stand up for what you believe. There have been times where I've been influenced or squashed by the 'boys club' and it felt defeating at the time but added to the fire in my belly to make positive change for everyone in music. I'm sure a lot of males in music feel the same pressure and are too afraid to stand up against the boys club at times, but we really need you as our allies to fight the good fight and have a more inclusive industry which is a better place for everyone to be.


In many job settings, employees perform the same tasks day after day without worrying about eventual injury. Unfortunately, repetitive stress injuries are a real risk for many employees in Illinois, whether they perform manual labor or sedentary work from a desk. Fortunately, under the Illinois Workers' Compensation Act, these employees can seek workers' compensation benefits just like they would for sudden traumatic injuries.
An employee must clearly be able to show that an injury was caused by the specific demands of his or her job. Injuries arising from risks the general public faces may not be compensable. For instance, an employee who develops leg or back problems from walking on a hard floor every day will typically not win compensation. However, if an employee is required to carry heavy loads or stand stationary for hours, he or she may be able to win compensation.
Employees with pre-existing conditions may still be entitled to workers' compensation benefits. Even if the employee previously sought or received workers' compensation benefits for a work-related condition, a second claim might be approved if the condition worsened or if a new related injury arose. However, the employee would need to clearly prove the condition was exacerbated by his or her job.
Illinois law requires victims to notify their employers of a repetitive stress injury within 45 days of discovering the injury and realizing it was work-related. The statute of limitations for filing a workers' compensation claim in Illinois is three years from the date the injury occurred or was discovered.
Some repetitive stress injuries may be associated with certain types of work. For example, office employees who type all day are at risk of developing carpal tunnel syndrome. For these employees, connecting a diagnosis of carpal tunnel to job duties may be straightforward. For other stress injuries, a medical professional's opinion can help establish the origin of the injury. An injured employee should fully describe any symptoms and the nature of his or her job to a physician so the physician can evaluate how the job may have contributed to the injury.
If a claim is denied, an employee has the right to appeal the decision by submitting a claim to the Illinois Workers' Compensation Commission. Although any employee with a workplace injury can benefit from seeking legal guidance, employees who are appealing claims should especially consider speaking with an attorney to improve the likelihood of approval.


The over all population of Peralta is 938 persons, 400 of them are male and 538 of them are female.
The population of this place consists of 320 minors and 618 adults, with 164 of them being 60 years and older.
A legal claim on health care and social insurance benefits have 476 citizens of Peralta.
In Peralta exist about 242 households.
Of these households 238 are common houses or apartments, 29 are without floor and about 17 consist of one room only.
185 of the normal households have sanitary installations, 236 are connected to the public water supply, 237 have access to electricity.
The economic situation allows 6 households to own a computer, 125 own a washing machine and 223 households are equipped with one ore more televisions.
Besides the 164 analphabets aged 15 or older, about 9 minors between 6 and 14 are not visiting a school.
170 inhabitants of the population of 15 years and older did not visit a school and 358 persons did not finish the school. 91 visited only the 6 years lasting primary school, 54 visited and finished the college or similar scholar institutions.
Do You know the places close to Peralta ?


They've been dirt and for the most part they don't care. The newest offering from renowned odd ball filmmaker Jim Jarmusch is a semi stylized look into one of the most revered groups in history, The Stooges. Starting at the start, we are given insight into the minds and aspirations of a couple of no good kids looking to make a living out of having a good time. From the grinding club days supporting fellow counter-culturists The MC5, to visiting New York for the first time to record their eponymous self- titled debut, a plethora of inspiring and angst-ridden anecdotes are unearthed (it's a wonder they still remember half of it). However this is a story that isn't without it's troubles. A car crash, which destroyed all of the equipment, injured several crew members as well as drummer Scott Asheton put the band in a tight spot to say the least. The band also had to let their founding bass player Dave Alexander go due to his intoxication and inability to play for an import show. He would be succeeded by a couple of other players, notably Jimmy Recca who played with them until the first break up in 1971. All of this culminates to show that everyone has their very up ups and incredibly down downs. Despite this, The Stooges have made more than a lasting impression and shows that all one needs is the drive to accomplish what they want despite set backs. Not bad for a bunch of snot nosed kids from Michigan.
Gimme Danger, directed by Jim Jarmusch and featuring Jim Osterberg, Ron Asheton, Scott Asheton, James Williamson, Steve Mackay, Mike Watt, Kathy Asheton, and Danny Fields is in select theaters nationwide November 4th.


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Aviation & Transport
Dubai airport passenger traffic up 11.7%
Emirates airline is one of many to fly from Dubai International Airport. (File photo: Shutterstock)
The airport - one of the world's biggest – handled 5.68 million people in Feb.
Reuters, Dubai
Published: 25 March ,2014: 12:00 AM GST Updated: 20 May ,2020: 10:43 AM GST
Passenger traffic through Dubai's main airport - one of the world's biggest - rose 11.7 percent from a year earlier to 5.68 million people in February, the airport operator said on Tuesday.
Dubai Airports cited the expansion of the networks of home carriers flydubai and Emirates. In the first two months of this year, passenger traffic climbed 13.5 percent to 12.08 million people.
Freight volume rose 3.4 percent in February to 188,702 tonnes.
Dubai airport to challenge Heathrow as world's busiest hub
The airport is now the world's second busiest for international traffic, exceeding Paris's Charles de Gaulle and Frankfurt Airport Aviation & Transport
Dubai's Emirates to move to new airport after 2020, exec says
Carrier says only the government can make decision to shift operations to Al Maktoum International Airport Aviation & Transport
Hundreds more flights canceled because of staff shortages due to COVID-19
Abu Dhabi's Etihad Airways to divest several businesses


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North London News
London coronavirus: Couple married for 57 years beat Covid after hospital staff move beds side by side
Domenico and Concetta Scolaro have been married for 57 years after meeting in an Italian club in the 1960s
Hannah KaneDeputy Editor
Domenico and Concetta Scolaro fought coronavirus side by side at Barnet Hospital (Image: SWNS)
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A London couple married for 57 years beat Covid-19 after hospital intensive care staff moved their beds together so they could fight the virus side by side.
Domenico and Concetta Scolaro have barely spent a night apart since they were married in 1963 after meeting at a dance at an Italian club in the capital.
But, on June 22 this year, 73-year-old Concetta feared that she'd never see her family again after she was taken by ambulance to Barnet Hospital suffering from a high temperature, delirium and breathing difficulties.
Nine days later, on July 1, 79-year-old Domenico also contracted the virus and was taken by ambulance to the same hospital.
Hearing their pleas to be close to one another, intensive care unit staff took the decision to place the couple in beds side by side so they could support one another.
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Their daughter Sabrina Scolaro said: "Because ICU wasn't as busy as it had been the staff listened to my father's impassioned request that he should be reunited with his wife.
"Staff went above and beyond to make this happen as they knew just how much strength they would both gain from being able to fight this battle together."
Domenico and Concetta Scolaro on their wedding day in 1963 (Image: SWNS)
Sabrina said when she was unable to reduce her mother's temperature with paracetamol, she feared the worst.
She said: "My mother was ashen-faced and had become delirious.
"Her temperature was 39.5. I spoke to NHS 111 and they were so helpful, the ambulance was with us in 20 minutes and the paramedics were so kind and understanding.
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"I could see how upset my father was and I kissed her goodbye.
"It sounds ridiculous, but because my mother had had chest infections in the past and they had been so careful I still didn't think it was coronavirus. We were now well into June and I just thought 'it can't be the virus'."
It was quickly confirmed Concetta had coronavirus, and was placed on a breathing machine.
After ordering tests for her and her father, Domenico tested positive.
Sabrina said: "The paramedics came, took dad's oxygen levels and said, 'he's coming with us'.
"That was it, suddenly both my parents were in hospital with the virus and I was left to lock their front door behind me and drive back to my own home in tears."
'I feared the worst'
Domenico and Concetta Scolaro on their 50th wedding anniversary (Image: SWNS)
Concetta said: "When the nurse woke me up she said she had something to tell me about my husband. I feared the very worst but instead she told me he had the virus, had been admitted the previous night but now he was being put in the bed right next to me.
"I cried, but actually it was incredibly comforting to be together and just being able to watch him as he slept gave me strength.
"The staff were angels, they looked after me so well and never left my side. I remember one nurse in particular, Rachel, who stroked my hair. Our care was outstanding."
As the couple, who live in Cockfosters, began to recover they were taken from ICU on the same day to a ward where they were again put together side by side in their own bay.
After 16 days in hospital Concetta went home on July 8, and Domenico was discharged the following day.
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The grandparents of five, who have owned Italian restaurants, are hoping to recover well enough to see friends and family.
Concetta said: "I thought I was going to die, I honestly thought I'd never see my husband, my children or my grand-children again.
Now I'm looking forward to going dancing with my husband again – we met at a dance at an Italian club back in London in 1962 - and when we have our strength back we will visit Italy.
"Both of us have been given a second chance and that means everything."
Debbie Kirby, ICU matron at Barnet Hospital, said: "We knew that putting this couple together would mean everything to them. Both of them had such spirit and determination.
"Staff were absolutely thrilled to be able to bring people together when so much of what we have had to do means separating loved ones. We will never forget them."
Bryleen Sebastian, the sister on Palm ward, said: "All our patients are special to us but to be able to put this couple together was fantastic.
"We made sure their beds and chairs were next to each other and they had a good view of the TV and out of the window. We know it's all the little things that make a difference to our patients and being together really spurred them to get well as it was like a mini competition between them to achieve milestones like coming off oxygen.
Join the London Coronavirus Updates Facebook group
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Please join this group to share information, find out more and offer or get help in the local community if it's needed.
Join the London Coronavirus Updates group here.
"We knew they wanted to leave together but we had to explain that we still had to monitor Mr Scolaro for one more night.
"He used that time to practise his walking up and down the bay which reassured us he was ready to say goodbye to us."
She added: "He was absolutely determined to rejoin his wife at home and it was so wonderful to see that bond."
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Thursday night's episode was an extremely emotional watch
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Hannah Warren had left London and drove to Port Talbot Harbour in Wales where her body was found
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The law firm wants to represent UK citizens who have been affected by using Johnson & Johnson's talcum powder


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Mehrangarh Fort
Jodhpur, India
This stunning 15th-century royal hill fort preserves the age of chivalry in Rajasthan.
Mehrangarh Fort Ankit6k2/cc by-sa 3.0
Mehrangarh Fort. Monica Goel/cc by-sa 3.0
Mehrangarh Fort Mariahwikiphoto/cc by-sa 4.0
Mehrangarh Fort public domain
Mehrangarh Fort Icekrish/cc by-sa 3.0
Sunset at Mehrangarh fort Lucy DiSanto (Atlas Obscura User)
Looking up Mehrangarh fort Lucy DiSanto (Atlas Obscura User)
Glowing evening light Lucy DiSanto (Atlas Obscura User)
Top Places in Jodhpur
Sati handprints
The Blue City of Jodhpur
Rajaram Meghwal Burial Place
One of the best-preserved and largest forts in India, the Mehrangarh Fort towers 400 feet above the city of Jodhpur. Founded in 1459 by Rajput leader Rao Jodha of the Rathore clan, it is owned and managed by the Jodhpur royal family to this day.
You can see the palatial hill fort from just about everywhere in the city, its distinctive walls soaring above the rocky plateau from which they were carved. Mehrangarh means "fort of the sun," referring to the myth that the Jodhpur royal family descended from the sun god, Surya.
A visit to Mehrangarh Fort takes hours, and it's worth every minute. Here, you can experience the history of war, the culture of honor, and the life of extravagance that Rajput royals enjoyed.
After the long walk from the city up to the fort (you can also take a taxi or rickshaw), you enter through the main gate, and continue to walk up a ramp through a series of seven gates. At a gate called Loha Pol, iron spikes are embedded in the wood (to prevent an elephant attack) and a set of small red hand prints on the wall memorialize a horrifying historic event. These are the handprints of the wives of Maharaja Man Singh's widows, left there as they went to throw themselves on his funeral pyre in 1843.
Inside the fort, the royal palaces now serve as the Mehrangarh Museum. You can walk from one to another, through enclosed courtyards adorned with lattice work and charming balconies. The former palaces are filled with antiques, artifacts, and art works, and even complete rooms. You will find miniature paintings, palanquins, howdahs (elephant seats), textiles, weaponry, and household goods. One room houses a collection of elaborate royal cradles from the 17th century. In the former bedroom of Maharaja Takhat Singh, also known as the Sheesh Mahal (Hall of Mirrors), every inch covered in painted panels, carvings, tiles, and mirrors.
Open every day, 9 am to 5 pm. Foreign ticket price 600 rupees (with audio cassette), 400 rupees for students. Domestic ticket price 100 rupees, 50 rupees for seniors, students. The audio cassette, available when you buy your ticket, is highly recommended and includes a welcome and some family history from the current head of the Rathore clan, Maharaja Gaj Singh II.
Atlas Obscura Trips
India: Desert Festivals of Rajasthan
Experience the traditions and customs of desert culture in Northern India.
forts royalty history museums
mariellen
Lucy DiSanto, MrCarl, gw66
https://www.google.com/maps/place/Mehrangarh+Fort/@26.2977257,73.0167258,681m/data=!3m1!1e3!4m13!1m7!3m6!1s0x39418dca49a88b9f:0x8242e95370c6cfd9!2sFateh+Pol+Rd,+Sodagaran+Mohalla,+Jodhpur,+Rajasthan,+India!3b1!8m2!3d26.2937306!4d73.0131821!3m4!1s0x39418db7f5a4e8d5:0x91c3eb1d93338906!8m2!3d26.298074!4d73.018407
The Fort
Sodagaran Mohalla
Mahila Baag Jhalra
Legend has it a commoner volunteered to be buried alive in the foundation so that the great fortress could be built.
Hidden in the shadow of a rocky fortress is one concubine's long-forgotten legacy.
Fifteen Jodhpur queens left their handprints before going to their fiery death.
Once an indicator of social class, the color blue has come to define this city on the edge of the Thar Desert.
Fort of San José el Alto
Half-hidden by grassy slopes, this striking Spanish colonial fort is now a museum of underwater archaeology.
Hillerød, Denmark
Frederiksborg Castle
This striking royal residence is the largest Renaissance-style castle in Scandinavia.
Prilep, North Macedonia
Museum of Tobacco
Thousands of objects tell the story of a city famous for its tobacco.
Amer, India
This opulent 16th-century Maharaja's palace is a unique mix of Hindu and Muslim designs.


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Resources News/Blog Sesotec presents a virtual interpack exhibition stand
Mar 26, 2020 | Sesotec
Sesotec presents a virtual interpack exhibition stand
Highlight: "THiNK" AI-powered metal detection for greater food safety and reduced food waste
In light of the developing coronavirus situation, the 2020 interpack trade fair in Düsseldorf has been rescheduled for February 25 to March 3, 2021. Sesotec GmbH welcomes this postponement as a necessary measure to protect the health and safety of all interpack presenters and visitors.
In the meantime, in order to keep Sesotec customers up-to-date on company news, the manufacturer of contaminant detection and material sorting technologies is launching a virtual trade show experience. Starting May 7, 2020, interested parties can visit http://www.sesotec.com/en/interpack to learn about the exciting product developments Sesotec would have presented at the exhibition.
Under the slogan "Driving Impact – Safe food and saving food," Sesotec will present on a number of issues concerning food safety and the fight against food waste. The virtual exhibition will cover some of the most pressing challenges facing the food processing and manufacturing industries, from conserving resources, to production efficiency, to increasing profitability, to environmental protection.
Highlight: Metal Detection with Artificial Intelligence
The virtual trade show exhibit will also feature the debut of Sesotec's latest innovation: "THiNK," an AI-software for metal detection equipment. Other topics include food safety compliance and a lifetime warranty package for x-ray inspection systems.
"The interpack may have been rescheduled for next year," says Uli Hurzlmeier, Product Manager for Food at Sesotec, "but we will still take this opportunity to present our latest products and service innovations to our customers. We look forward to welcoming many visitors to our virtual exhibition stand."
What HACCP means and how to implement it
Using artificial intelligence for sustainably profitable food processing
Legal requirements and important standards in the food industry and their differences
How food safety standards impact production
How better food safety technology can help minimize waste


CONVERTING leads and inquiries into sales in an increasingly digital and competitive environment is a challenge.
Customers have often educated themselves online or made their purchase decision before engaging with a dealer, reducing the opportunities to influence decision making during the initial stages of the customer journey.
Dealers need to have a powerful Dealer Management System in place and make full use of its capabilities, to convert leads into sales. Many dealers still don't make use of the tools available to them which is a missed opportunity.
With a growing number of car buyers preferring to browse vehicle information online rather than in-store, it's vital to make sure website listings include lots of high quality photos, accurate vehicle specification and are up to date.
Dealers who provide more detailed and better quality website listings are more likely to gain leads.
Many dealers have the ability to update vehicle listings quickly from their DMS. Pinewood is focused on helping dealers achieve a customer-centric online experience, with system offering the ability to capture up to 40 vehicle images, which are immediately available to the dealers' website.
This provides the ideal tool to showcase vehicle stock, enhancing the online search phase and resulting in more enquiries.
Similarly, choosing a DMS with tools to improve a showroom management processes will positively impact on lead conversion. From managing new inquiries, to the first contact with a customer, to the vehicle handover.
The modern dealership is no longer an environment where a 'quick and hard sell' works – therefore converting leads relies upon the customer experience. This is an opportunity for dealers to impress.
Dealers must ensure follow-ups are dealt with effectively. Pinewood DMS can prompt sales users to schedule a future contact following every customer interaction – whether this is online, over the phone or in person.
It connects with Outlook, scheduling reminders for any future appointments or contacts, helping sales teams to never let a lead go cold. Every interaction is stored on the customer's CRM record.
Dealers can boost inbound inquiries by having a DMS with manufacturer integrations for their represented brands. For the systems which offer these integrations, inquiries submitted to manufacturers websites can automatically be sent to the DMS and flagged as opportunities for the sales team to action. Pinewood have close working relationships with manufacturers to help facilitate this.


The organizer must be a current member (for 2019) in good standing.
Invited speakers must register for the meeting but need not be members.
No speaker can participate in more than one symposium.
Speaker substitutions are not allowed.
If a symposium talk has more than one author, it must be presented by the first author.
Submitting a symposium proposal or speaking in a symposium does not prevent you from submitting an abstract for a talk or poster presentation at VSS.


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Q: How to show a dropdown selected value in the same page in laravel? I have a database table named country(id,country,capital).I have retried the country name through dropdwon selection list. I want that when I will select a option from the dropdown ,the capital name will be shown the the same view page .
Here my view page..

Country name

         <select class="form-control" name="country_id">
          <option>Select Country</option>

          @foreach ($countries as $key => $value)
            <option value="{{ $key }}">
                {{ $value->country }}
            </option>
          @endforeach
        </select>

Capital name

Capital name:

Here the controller ..
class CountryController extends Controller
{
public function index()
{

    $countries=Country::all();

   return view('country', compact('countries'));
}

}

My expected output will be:

Capital name:Istanbul

A: To achieve this you can use JavaScript.
Example:
First add onchange="displayCountryName(this.value)" on your select element.
Secondly,replace p element with a disabled input element add an id to your input element like so, id="countryName"

Country name

             <select class="form-control" onchange="displayCountryName(this.value)" name="country_id">
              <option>Select Country</option>

              @foreach ($countries as $key => $value)
                <option value="{{ $key }}">
                    {{ $value->country }}
                </option>
              @endforeach
            </select>

Capital name

              Capital name: <input disabled id="countryName">

for your JS
 function displayCountryName(value)
{
    document.getElementById('countryName').value = value
}

A: below is the HTML code..

Country name

         <select class="form-control" onchange="capitalName(this.value)" name="country_id">
          <option>Select Country</option>

          @foreach ($countries as $key => $value)
            <option value="{{ $key }}">
                {{ $value->country }}
            </option>
          @endforeach
        </select>

Capital name

          Capital name: <input disabled id="countryName">

this should b your javascript code...
function capitalName(cap){
  document.getElementById('countryName').value = cap;
}

here is the working code for referance

redpajama_set_name: RedPajamaStackExchange


Established in 1968, Emser Tile, headquartered in Los Angeles, is the leading designer, marketer and producer of the world's finest tile and natural stone. By offering unparalleled service and a dynamic selection of products, Emser is one of the most comprehensive sources for interior and exterior products. Emser products are designed for both residential and commercial projects. Emser is the fashion leader in glazed ceramic and porcelain tile, glass, metal and natural stone products. Emser offers the latest in fashion, colors, finishes, patterns and textures, accompanied by a broad assortment of coordinating trims and decorative accent pieces.