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Comparison of biomarkers between genotypes 1a and 3a in hepatitis C virus patients with control group
Sajjad Yazdansetad
Food and Mouth Disease Reference Laboratory, Razi Vaccine & Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
Hadi Razavi Nikoo
Infectious Disease Research Center, Golestan University of Medical Sciences, Gorgan, Iran; 3Department of Microbiology, School of Medicine, University of Medical Sciences, Gorgan, Iran
Seyed Mahmoud Azimi
Alireza Mohebbi
Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
Massumeh Niazi
Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
Mehdi Ajorloo
Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran; School of Allied Medical Sciences, Lorestan University of Medical Sciences, Khorramabad, Iran
kmehdiajorloo@gmail.com
Abstract Introduction Materials and Methods Results Discussion Conclusion Competing Interests References Comments
Submitted: May 1, 2019 | Published: Apr 30, 2019
Yazdansetad, S., Razavi Nikoo, H., Azimi, S. M., Mohebbi, A., Niazi, M., & Ajorloo, M. (2019). Comparison of biomarkers between genotypes 1a and 3a in hepatitis C virus patients with control group. Biomedical Research and Therapy, 6(4), 3121-3130. https://doi.org/10.15419/bmrat.v6i4.537
Copyrights: Sajjad Yazdansetad, Hadi Razavi Nikoo, Seyed Mahmoud Azimi, Alireza Mohebbi, Massumeh Niazi, Mehdi Ajorloo, 2019. License:
Introduction: Three percent of people worldwide are infected with Hepatitis C virus (HCV). A few studies have been performed to evaluate the biochemical markers of the disease. In the current study, biochemical markers were evaluated in HCV patients and the control group.
Methods: Two sex- and age-matched healthy individuals (n = 100) and HCV positive patients (n = 100) were included (mean age of 20-75, 26.0% females and 74.0% males). Biochemical markers, including liver enzymes (ALT, AST and ALP), lipid profiles (cholesterol, LDL, and HDL) and triglyceride (TG) were investigated in both groups. HCV genotyping was also performed by Polymerase Chain Reaction (PCR) and OHNO methods.
Results: The biochemical markers between HCV patients and controls were compared (cholesterol, ALP, AST, ALT, LDL: p = 0.0001, HDL: p = 0.002, TG: p = 0.003), and statistically significant difference was found between two groups. The biochemical markers between HCV patients and the control group in terms of age was compared and no differences was observed (p = 0.741), however, there was a significant difference in sex between HCV patients and control group (26.0% females, 74.0% males in control group, and x% females and y% males in HCV patients) (p = 0.032). The results of HCV genotyping showed that 39 patients were genotype 1a, and 43 patients were genotype 3a, and 1 patient was genotype 2a. Evaluation of biochemical markers in patients with genotype 1a and 3a showed that there were significant differences in cholesterol (p = 0.001), LDL (p = 0.001) and HDL (p= 0.003) levels, but there were no significant differences in liver enzymes and TG levels in both genotypes.
Conclusion: In the present study, we found significant difference in biochemical markers between HCV patients and controls. In HCV patients, the biochemical markers were dependent on HCV genotypes, and their levels in genotype 1a were higher than genotype 3a. In conclusion, biochemical markers are one of the most important factors for the identification of treatment.
Keywords: Biochemical markers Genotype 1a Genotype 3a Hepatitis C Virus Lipid profiles Liver enzymes Photometric method
Hepatitis C virus (HCV) is the major cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the world 1. This virus is a single positive-stranded RNA genome of 9.6 Kb and belongs to the Flaviviridae family. Hepacivirus genus contains one long open reading frame (ORF). This single ORF encodes a polyprotein of about 3000 amino acids that produces viral proteins after cleavage by the host and viral encoded proteases2. In addition, core-encoding region of this virus expresses a protein entitled alternative reading frameshift protein (ARFP) or frame-shift protein (F protein) 3,4. It has been shown that in chronic HCV patients, 82% were positive for anti-F antibodies, showing a significant difference from the healthy individuals5. This protein increases the frequency of CD4+CD25+ Treg cells, which may be associated with persistent and chronic infection through subversion of the host immune response6 F proteins could also enhance liver cell proliferation7, which is subsequently associated with the disease progression towards cirrhosis8. The protease function of HCV NS3 protein is also a crucial factor for the induction of liver fibrosis via interaction with cellular miRNAs and down-regulation of miRNA gene expressions9,10.
HCV is transmitted through several ways such as drug injection, blood transfusion and sexual exposure11. It is estimated that more than 170 million people worldwide are infected with hepatitis C virus12. In Iran, approximately 200,000 people are infected with this virus (less than 1%). Also, the prevalence of HCV infection is low among Iranian blood donors13,14. There are six genotypes and more than 70 subtypes of Hepatitis C virus in the world15,16. Epidemiological studies have shown the relationship between HCV genotypes and geographic regions. Predominate genotype in Europe and North America is 1b, in Asia and Mediterranean region is 2 and in Europe is 3, whereas genotype 4 is often found in the Middle East, genotype 5 is only in South Africa, and genotype 6 is dominant in Southeast Asia17,18. Studies have shown that predominate genotypes in Iran are 1a and 3a19.
Hepatitis C virus attachment to hepatocytes is mediated by LDLr, which describes the role of lipids in HCV pathogenesis12,20. Many studies have shown that there is a relationship between serum cholesterol and LDL levels with the development of liver damage and HCV associated-cirrhosis16,20,21. Also, other findings have shown that the association between hepatitis C virus and LDL can protect the virus against antibodies22,23. This approach leads to the design of new drugs for HCV patients. Ledipasvir and Sofosbuvir are used for chronic HCV treatment24,25,26,21.
Fewer studies have been performed to evaluate and compare biochemical markers in HCV patients and healthy individuals (or control group). In the current study, biochemical markers in HCV patients and control group were evaluated and compared. We measured 3 groups of biomarkers: lipid profiles (total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)), liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphate (ALP)), and triglyceride (TG). Our research objectives included the evaluation of biomarkers in HCV patients and control group, finding the relationship between biomarkers in HCV patients and control group, evaluation of biomarkers in HCV patients with genotypes 1a and 3a, and finding relationship between biomarkers in HCV patients with genotypes 1a and 3a.
In this study, information such as age, sex, marital status, HCV genotype, biochemical markers (ALP, AST, ALT, HDL, LDL, TG, and cholesterol), and transmission ways were collected. The information was recorded in a questionnaire.
Study area and subjects
200 volunteers of 100 healthy individuals (control group) and 100 HCV patients were included. The serum samples were collected in a period of 18 months from 2011 to 2013 from HCV patients referred to a special clinic of Digestive Disease Research Center of Ghaem hospital, Mashhad, Iran. Before sampling, all patients were informed and signed the consent form that was approved by Ethics Committee of Mashhad University of Medical Sciences. The serum samples were kept at -700C freezer until examination.
Isolation of HCV RNA, cDNA synthesis and genotyping
HCV RNA was isolated from each patient's serum using the total RNA extraction kit following instructions by the manufacturer (Pars Tous biotechnology, Mashhad, Iran). HCV RNA was then detected by nested reverse transcription PCR using 5' UTR primers, as previously described by Krekulova et al27. Briefly, 10μl extracted RNA were reverse-transcribed into cDNA, using Maloney murine leukemia virus reverse transcriptase (M-MLV RT, 100 units) (Thermo Fisher Scientific) and 1M of downstream primer (outer anti-sense). The products generated from each sample were subjected to two separate PCR amplifications, one with primer set A and the other with primer mix B, in a final 20μl reaction volume containing 4.0μL of 5x First Strand Buffer, 1.0μL, dNTPs (10mM), 3.0μL dH2O and Taq polymerase (Fermentas Life Sciences, USA). The resulting specific HCV bands were visualized by ethidium bromide following electrophoretic separation on 2% agarose gel. Primer set A included primers for genotypes 1a, 1b, 1c, 3a, 3c and 4, while set B included primers for genotypes 2a, 3c, 3b, 5a, and 6a. To determine the sensitivities of PCR assays, prepared plasmids were quantified by UV spectroscopy, and the viral copy number was calculated. The 10-fold serial dilutions of all HCV cDNA-containing plasmids were made. For sensitivity, PCR was performed on a 10-fold dilution of plasmids ranging from 101 to 108 copies/reaction. The specificity was tested by determining the ability of primers to discriminate plasmids with different genotypes of HCV types. There was no specific signal for the independent PCR assays (data not shown). The ability of all types of PCR primers to amplify HCV cDNA-containing plasmids was analysed by using a dilution series that started from 101 plasmid copies to 108 plasmid copies. This assay showed significant sensitivity of about 100 viral copies for all HCV genotypes.
The normal and non-normal percent of biomedical markers between HCV patients and control group
Control group HCV patients Total
Variables Groups subjects percent subjects percent subjects percent
Cholesterol Normal 62 62.00% 77 77.00% 139 69.50%
Non-normal 38 38.00% 23 23.00% 61 30.50%
Total 100 100.00% 100 100.00% 200 100.00%
Alanine Aminotransferase (ALT) Normal 99 99.00% 28 28.00% 29 14.50%
Non-normal 1 1.00% 72 72.00% 171 85.50%
Triglyceride (TG) Normal 83 83.00% 83 83.00% 166 83.00%
High-density lipoprotein Normal 86 86.00% 57 57.00% 143 71.50%
(HDL) Non-normal 14 14.00% 43 43.00% 57 28.50%
Low-density lipoprotein Normal 76 76.00% 82 82.00% 158 79.00%
(LDL) Non-normal 24 24.00% 18 18.00% 42 21.00%
Aspartate Aminotransferase (AST) Normal 98 98.00% 37 37.00% 135 67.50%
Non-normal 2 2.00% 63 63.00% 65 32.50%
Alkaline Phosphatase (ALP) Normal 99 99.00% 0 0.00% 1 0.50%
Non-normal 1 1.00% 100 100.00% 199 99.50%
Minimum, maximum, mean, SD and p-value amounts of biochemical markers between HCV patients and control group
Variable Groups Mínimum Máximum Mean SD P-Value
Cholesterol HCV patient 54 456 149.6 70.2 Mann-Whitney U=-6.01P-Value=0.0001**
control 118 310 193.3 41.2
total 54 456 171.6 61.4
ALT HCV patient 10 3502 205.4 545.2 Mann-Whitney U=-8.73P-Value=0.0001**
control 4 129 19 14.9
total 4 3502 111.8 394.9
TG HCV patient 30 541 125 97 Mann-Whitney U=-2.97P-Value=0.003**
control 45 503 144.1 84.7
HDL HCV patient 14 125 41.1 22.8 Mann-Whitney U=-3.17P-Value=0.002**
control 22 98 45 14.1
total 14 125 43 19
LDL HCV patient 22 945 101.6 110.2 Mann-Whitney U=-3.88P-Value=0.0001**
AST HCV patient 11 3158 209.3 454 Mann-Whitney U=-9.31P-Value=0.0001**
control 7 106 21.8 11.7
ALP HCV patient 55 2713 401.5 475 Mann-Whitney U=-6.25P-Value=0.0001**
total 34 2713 283.3 358.5
The normal and non-normal percentage of biomedical markers between genotypes 1a and 3a in HCV patients
Genotype 1a Genotype 3a Total
Variable Groups HCV patients percent HCV patients percent HCV patients percent
Cholesterol Normal 29 74.40% 38 88.40% 67 81.70%
Non-normal 10 25.60% 5 11.60% 15 18.30%
Total 39 100.00% 43 100.00% 82 100.00%
ALT Normal 11 28.20% 11 25.60% 22 26.80%
TG Normal 31 79.50% 40 93.00% 71 86.60%
Non-normal 8 20.50% 3 7.00% 11 13.40%
HDL Normal 25 64.10% 17 39.50% 42 51.20%
LDL Normal 29 74.40% 40 93.00% 69 84.10%
Non-normal 10 25.60% 3 7.00% 13 15.90%
AST Normal 12 30.80% 20 46.50% 32 39.00%
ALP Normal 0 0.00% 0 0.00% 0 0.00%
Non-normal 39 100.00% 43 100.00% 82 100.00%
Minimum, maximum, mean, SD and p-value amounts of biochemical markers between genotypes 1a and 3a in HCV patients
Variable Groups Minimum Maximum Mean SD P-Value
Cholesterol 1a 54 362 161.9 66.6 Mann-Whitney U=-3.19
3a 65 456 127.9 72.7 P-Value=0.001**
ALT 1a 11 3012 222.1 537 Mann-Whitney U=-0.757
3a 10 3502 183.5 551.2 P-Value=0.449
TG 1a 30 448 127.8 108.2 Mann-Whitney U=-0.306
3a 30 298 102.4 59.8 P-Value=0.759
HDL 1a 17 120 47.7 26.5 Mann-Whitney U=-2.926
3a 14 125 34.2 20.1 P-Value=0.003**
total 14 125 40.6 24.2
LDL 1a 31 945 122.3 143.3 Mann-Whitney U=-3.668
3a 22 625 78.9 91 P-Value=0.0001**
total 22 945 99.5 120
AST 1a 11 3158 259.1 555 Mann-Whitney U=-1.57
3a 12 2099 141.6 337 P-Value=0.115
ALP 1a 98 2713 441 582.5 Mann-Whitney U=-0.664
Comparison of biochemical marker levels between patient and healthy groups
Clinical chemistry kits (Human, Pars Azemoon Kit) and an automatic biochemistry analyzer (Micro Lab 300, Merck Germany) were used to analyze biochemical markers such as aspartate aminotransferase (AST), alanine transaminase (ALT), -glutamyl transferase (-GT), alkaline phosphatase (ALP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol and triglycerides (TG) in the serum samples. These biomarkers were evaluated and compared between HCV patients and control group, and between HCV patients with genotypes 1a and 3a.
All data were recorded in the previously designed form and analyzed by statistic software SPSS 20. For analysis of biochemical markers between HCV patients and control group, we used Kolmogorov-Smirnov, Asti dent, Man Whitney, Pearson Chi-Square, Fisher's Exact Test and Cochran. At first the Kolmogorov-Smirnov was used, if data were normal, the Student t-test was then used, but if data were not normal, the Man-Whitney test was used. Statistical significance was considered as p < 0.05.
The mean age was 47.3±10.2 for patients and 47.8±9.7 for control group. Information based on age between HCV patients and control group was compared and the difference in age distribution among patient groups was not significant. Figure 1 shows the percentage of HCV patients and control group in four age subgroups. In case of sex (26.0% females, 74.0% males), there was a significant difference between control group (75.0% married, 25.0% single), and HCV patients (81.0% married, 19.0% single) (p = 0.032).
In investigation for other diseases, 4.0% of patients had hemophilia and 1.0% had thalassemia, but there was no hemophilia or thalassemia in control group. Percentage of individuals with diabetes was 4.0% in control group and 5.0% in HCV patients. Percentage of people had other diseases were 6.0% in HCV patients and 3.0% in control group. Transmission ways among HCV patients were different. The most prevalent transmission way of HCV was observed among injective drug users (62%). Other forms of transmission included blood transfusion in patients with hemophilia, thalassemia, and surgery (11.0%), sexual transmission (3.0%), and 20% of the causes were unknown.
Figure 1 . Age distributions of HCV patients and control group . The age group analysis of HCV-positive cases revealed that the highest infection rate was among patients less than 40 years of age with 33.0% prevalence. Patient between 51-60 years of age were the most affected (31.0%), while those within the age bracket of more than 60 years were the least affected (16.0%).
HCV typing
In 83% (83/100 in patient group) of clinical specimens positive for HCV, genotype 3a was the most prevalent among the patients (52% or 43/83 patients), followed by genotype 1a and 2a (47% and 1.2%, respectively). No genotypes were obtained for 17% of the patients.
Evaluation of biomarkers in control group and HCV patients
Analysis of associations between HCV genotypes and bio-chemical markers showed that the levels of cholesterol, HDL and LDL significantly differed (p < 0.005) in patient group (cholesterol = 77.0%, LDL = 82.0%, HDL = 57.0%) compared to control group (cholesterol = 62.0%, LDL = 76.0%, HDL = 86.0%). However, no significant differences between two groups in other biomarkers were detected. The normal percentage of TG were identical in two groups (TG = 83.0%) (Table 1).
The mean levels of lipid profile in HCV patients were: cholesterol = 149.6, LDL = 101.6, HDL = 41.1, and in control group were: cholesterol = 193.3, LDL = 108.6, HDL = 45.0. Mean TG levels in HCV patients was 125.0 and in control group was 144.1. The mean levels of liver enzymes in HCV patients were: ALT = 205.4, AST = 209.3, ALP = 401.5, and in control group were: ALT = 19.0, AST = 21.8, ALP = 166.3 (Table 2). The levels of biochemical markers between HCV patients and control group were compared and there was a significant difference between two groups (cholesterol, ALP, AST, ALT, LDL: p = 0.0001, HDL: p = 0.002, TG: p = 0.003).
Evaluation of biomarkers in HCV patients with genotypes 1a and 3a
The evaluation between genotypes 1a and 3a in HCV patients showed that the normal percentage of lipid profiles in genotype 1a was: cholesterol = 74.4%, LDL = 74.4%, HDL = 64.1%, and in genotype 3a was: cholesterol = 88.4%, LDL = 93.0%, HDL = 39.5%. The normal percentage of liver enzymes in genotype 1a was: ALT = 28.2%, AST = 30.8%, ALP = 0.0%, and in genotype 3a was: ALT = 25.6%, AST = 46.5%, ALP = 0.0%. Also, the normal percentage of TG in genotype 1a was 79.5% and in genotype 3a was 93.0% (Table 3).
The mean levels of biomedical markers in HCV patients with genotype 1a was: cholesterol = 161.9, LDL = 122.3, ALT = 222.1, TG = 127.8, HDL = 47.7, AST = 259.1, ALP = 441.0, and in HCV patients with genotype 3a was: cholesterol = 127.9, LDL = 78.9, ALT = 183.5, TG = 102.4, HDL = 34.2, AST = 141.6, ALP = 385.4 (Table 4). There were significant differences in the levels of cholesterol (p-value = 0.001), LDL (p-value = 0.001) and HDL (p-value = 0.003) in genotypes 1a and 3a, but there were no significant differences in liver enzymes and TG in both of genotypes.
In this study, the samples were selected among patients referred to a special clinic of Digestive Disease Research Center of Ghaem hospital in Mashhad, Iran. One hundred HCV positive patients were collected and 82% of them had genotypes 1a and 3a, and 100 healthy individuals were collected as control group. Some factors influence on severity of HCV disease such as: sex, age, other diseases and increased levels of biomarkers. For example the risk of HCV increases with age28,29.
For the evaluation of demography results, we collected male patients three times more than female patients, due to a higher risk of HCV in males in comparison with females. Jamalidoust et al.30 and Alavian et al.20 showed similar results.
Sixty two percent of our cases were drug addicted. Jamalidoust and her colleagues had similar samples to the current study and 62.2% of their cases were drug addicted30. Education range was higher in the control group, which can influence on HCV infection, therefore, there is a relationship between education and lower rate of HCV infection. Detection and rapid assessment of chronic liver disease that lead to liver fibrosis is important for monitoring and evaluating the risk of liver cancer. The first step after detection of positive HCV is to measure the levels of liver enzymes. If these markers are higher than normal levels, the individual is infected with chronic liver disease.
Hepatitis C virus enters host cells via LDL and cholesterol receptors, thus, the levels of these biomarkers increase in HCV patients. Agnello31 and Jine32 researched about this topic. Results of our study were opposite to their findings. In the current study, the levels of cholesterol and LDL in HCV patient were lower than that of the control group due of drug consumption and the types of diet, which were given to patients.
The results of our study showed the percentage of normal cholesterol, LDL and HDL levels in patients, which were lower than the levels in control group, and percentage of normal TG was equal in two groups. Orangi et al. evaluated the percentage of normal LDL and HDL in patients and control groups and showed the same results33. However, in a study by Alavian et al., the percentage of normal cholesterol, LDL, HDL and TG levels was lower than those from our patients. One reason for these differences in the results may be due to thalassemia patients in their study. Also, in the current study, the levels of normal ALT, AST and ALP in control group were higher than HCV patients. Alavian et al. showed similar findings to our results in two groups, but Pontisso et al. findings were opposite. Their results showed that percentage of normal ALT was more than 50%34 compared to 28% of normal ALT in our study. This difference may be related to the reason that some of our patients were at the beginning of the treatment, and the medicine had not exerted a full impact. In a study, Peymani et al. used chloroquine drug in non-responder patients for antiviral treatment. They showed that HCV RNA loads and ALT levels were decreased and normalized during treatment35. In the other study, Peymani and his colleagues showed that the use of chloroquine drug could reduce AST, ALT, cholesterol, and triglyceride levels and help to normalize some biochemical markers36. Riaz et al. evaluated the association of HCV genotypes with biomarkers in HCV infected patients. They found that infection with genotype 1a was associated with significantly higher ALT, AST and ALP levels compared to genotype 3a37. Moallemi et al. determined serum levels of IP-10 (as a new biomarker) in HCV patient and control groups. They found that the levels of IP-10 in patient group was higher than control group, and the difference was statistically significant between two groups. They also checked the levels of this biomarker between HCV genotypes and revealed that the levels of IP-10 were higher in genotype 1a than 3a38. According to the results, we found that the mean levels of biochemical markers in genotype 1a were higher than genotype 3a, also, the percentage of normal biochemical markers were different in genotype 1a and 3a. In evaluation of biochemical markers in the patient group, we found their relationship with genotypes. The new studies have shown a relationship between genotypes and HCV severity. In a research, Jhaveri et al. showed similar results to our study39. There were differences in the levels of ALT, AST and ALP between two groups. One reason for our different was due to different demography features. In the current study, sampling was randomly performed within 18 months. Some patients had finished their treatments, but some were being treated and the others had not started treatment. We used 7 biomarkers (cholesterol, HDL, LDL, TG, ALT, AST, and ALP), and our patients had special diets and have used drugs. Thus, triglyceride, cholesterol, LDL and HDL levels in these patients were lower than the controls.
The present study assessed the correlation between HCV genotypes with lipid profiles in a small sample size. Thus, it is be important to continue the analysis of lipid profile and characterization of HCV genotypes in a larger population, and to follow their changes over time. Genotyping by PCR is highly specific and sensitive for the determination of HCV genotype, but it is a time-consuming and costly technique. On the other hand, in association with blood born viruses, we need a highly trained technician.
The results of this study showed that there is a significant relationship between biomarkers in both control and patient groups. In HCV patients, the biochemical markers were dependent on HCV genotypes, and their levels in genotype 1a were higher than genotype 3a. There was a significant correlation between cholesterol, HDL, and LDL in patients with genotype 1a and 3a. Biochemical markers may be one of the most important factors that will help in the formulation of treatment strategies. We examined all the demographic information of our patients and control group, however, we did not check the demographic information of other family members. Evaluations of all family members are useful to prevent disease transmission and to help families to improve the patient care.
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Orangi E., Rahimi A.O., Mahdavi R., Somi M., Tarzemani M., Oxidative Stress-related Parameters and Antioxidant Status in Non-alcoholic Fatty Liver Disease Patients. Iranian Journal of Endocrinology and Metabolism. 2011; 12 (5) : 558 .
Daryani E.B., Haghpanah B., Hashtroody A., Evaluation steam hepatitis non-alcoholic. J digestion. 2004; 9 : 110-21 .
Peymani P., B. Yeganeh, S. Sabour, B. Geramizadeh, M. Fattahi, H. Keyvani, New use of an old drug: chloroquine reduces viral and ALT levels in HCV non-responders (a randomized, triple-blind, placebo-controlled pilot trial). Can J Physiol Pharmacol. 2016; 94 (6) : 613-9 .
Peymani P., Ghavami S., B. Yeganeh, R. Tabrizi, S. Sabour, B. Geramizadeh, Effect of chloroquine on some clinical and biochemical parameters in non-response chronic hepatitis C virus infection patients: pilot clinical trial. Acta Biomed. 2016 ; 87 (1) : 46-53 .
Riaz S., Bashir M.F., Haider S., N Rahid, Association of genotypes with viral load and biochemical markers in HCV-infected Sindhi patients. brazilian journal of microbiology. 2016; 47 : 980-6 .
Moallemi Z., Ayatollahi J., Dosti M., Serum and Urine Level of IP-10 in Patients with HCV infection Based on Clinical and Virological Markers. Iranian Journal of Virology. 2015; 9 (4) : 1-8 .
Jhaveri R., McHutchison J., Patel K., G. Qiang, A.M. Diehl, Specific Polymorphisms in Hepatitis C Virus Genotype 3 Core Protein Associated with Intracellular Lipid Accumulation. J Infect Dis. 2008; 197 (2) : 283-91 .
Sajjad Yazdansetad, Hadi Razavi Nikoo, Seyed Mahmoud Azimi, Alireza Mohebbi, Massumeh Niazi, Mehdi Ajorloo, 2019.


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text:
Q: Facebook App Token - does it ever expiry? Facebook App Token -

*

*Do App Token ever expiry?

*Do App Token ever change?

*1 Facebook app will only have 1 App Token, or can 1 Facebook App
have multiple App Token?

A: A Facebook application can only have one application token, resetting the secret changes it and invalidates the previous version.
A Facebook application can have multiple user access tokens.
https://developers.facebook.com/docs/opengraph/howtos/publishing-with-app-token/

An App Access Token does not expire unless you refresh the application secret through your app settings.

redpajama_set_name: RedPajamaStackExchange


The Tri-Grip[TM] is the highest quality tufted nylon-on-rubber mat designed for high-traffic areas with heat-set, Ultra-Twist[TM], nylon-yarn construction that traps moisture and dirt before they're tracked on the floor or carpet.
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Continuing professional development is key to the growth of every firm.
From updates on the latest changes in your area of law; professional skills training and the latest in strategy and management thinking to essential networking with fellow members.
LawNet's Head of Learning, Quality & Development, Peter Riddleston, talks about LawNet's complete CPD solution for members.


We welcome all comments from our fans and customers; what we do right, and how we could improve.
Please feel free to say anything about our farm, lamb, or share your culinary experience with us by leaving a comment on this page.
Ca n't wait to eat this year's lamb. Last year's was fabulous. we are looking forward to having at least one every year if not more. We are great supporters of artisanal foods and your farm fits the bill nicely.
Lamb like Lamb should taste. Not since I have been a kid have I tasted the flavor and tenderness of Lamb like The Green Shepherd Farm Lamb. I figure it is the care of the flock, the feed, soil, water and grazing area of Bovina, NY. Now, I know why the first settlers of Bovina raised sheep in Bovina. Thay were Scotish, you know. I have ordered another for next year. Try tasting one for your self and you can enjoy the true flavor of The Green Shephard Farm Lamb.
We just got a 33 lb (hanging weight) lamb from the Green Shepherd Farm and roasted it whole under charcoal for 25 people. It was absolutely fabulous, juicy and succulent as can be. We look forward to receiving our autumn lamb at the end of the summer. It doesn't get any better than this.
Just want to let you know that we have been enjoying your lamb.
Today (maybe being snowed in made me more culinarily ambitious than usual!) I roasted the lamb shoulder ala Jamie Oliver (see recipe above) which meant slow cooking it for 4 hours, made a version of his smashed root vegetables, sauteed greens with garlic (he boiled his) and added peas with mint for good measure. Fabulous! And the lamb did almost melt off the bone as "advertised"– not hurt at all by the delicious sauce.
won't do better than contacting Green Shephard Farm.
Ask for Steve or Annette, shepherds extraordinaire!
Last year we shared a lamb from Green Shephard Farm with good friends. This year we are each ordering our own. Steve and Annette raise these animals with respect and great care. The result is the best lamb we've ever tasted. We're loving this farm to table experience.
I came from NYC to visit Green Shephard Farm on lovely sunny day. I was really impressed with the quality of the land and the care that Stephen has towards his lambs and sheeps. All the animals on the farm were very friendly, serene and healthy; all signs of a great quality product!
I ordered a sheepskin and received it Saturday. I'd been so excited and looking forward to getting it. It is beautiful and luxurious. Stephen was most patient with providing information via pictures and descriptions. This was a sentimental purchase for me. Purely nostalgic. As a child, our grandmother would place a sheepskin in a reading nook near the fireplace and we would curl up and read. Well, I'm an adult now, much larger, but it sure felt great to rest on the sheepskin last night. Since I'm larger, most likely will need another sheepskin. Thanks, again.


text:
Q: Laplace transform of $1/t$ Does the laplace transform of $1/t$ exist? If yes, how do we calculate it? Putting it in $$\int_0^\infty (e^{-st}/t) dt$$ won't solve.
Is there any other way? If not, why?
Thanks!

A: You can actually simplify it further by substituting $st = x$, so you'll get
$$L \left(\frac 1 t \right) = \int \limits _0 ^\infty \frac {\Bbb e ^{-x}} x \ \Bbb d x$$
which is a divergent integral. In other words, the transform doesn't converge for any value of $s$.

A: No, it doesn't exist. In general the Laplace transform of $t^n$ is $\frac{\Gamma(n+1)}{s^{n+1}}$, and $\Gamma(n)$ isn't defined on $0,-1,-2,-3...$ This integral is the definition of the Laplace transform, so the transform doesn't exist if the integral doesn't. While there are other integral transforms that could transform $\frac{1}{t}$ in a useful way, anything other than what you gave wouldn't be considered a Laplace transform anymore.

A: $L\left[\frac{f(t)}{t}\right](s)=\int_s^{+\infty}f(u)du$ so $L\left[\frac{1}{t}\right](s)=\int_s^{+\infty}\frac{du}{u}=\ln u|_s^{+\infty}=\ln(s)-\ln(+\infty)$ as $\ln(+\infty)$ is not defined, then $L\left[\frac{1}{t}\right]$ is also not defined but it can be solved when $L\left[\frac{1}{t}-\frac{\cos t}{t}\right]$ or more .


text:
Feds Order National Guard to Close I-495 to Derail Trucker Protest
If true, the following report from Paul Joseph Watson proves yet again that President Obama's promises of transparency and giving every American a voice were nothing but political rhetoric. One promise that he has made good on is that he would "fundamentally transform" America. If the Federal government, under the orders of the President, does, in fact, call on the National Guard to prevent these Americans from their right to peacefully "assemble and to petition the Government for a redress of grievances" then we have yet another Constitutional Amendment that has been supplanted by this administration.
A conservative group claims it has spoken to sources within the Department of Transportation who admitted plans by the feds to order armed National Guard troops to close Washington DC's Interstate Route 495 tomorrow in order to derail a mass protest and potential blockade being organized by a group called Truckers Ride for the Constitution.
The sensational claim is posted on the Freedom Leadership Conference website, as well as prominent conservative blog RedState.com. The annual Freedom Leadership Conference has previously been sponsored by the likes of Judicial Watch and Human Events.
According to Glenn Ryt, the plan to close the route that circles the nation's capital will be implemented on Friday morning with the aid of armed National Guard troops from Maryland, Pennsylvania and Virginia who will use trucks, jeeps and armored vehicles to block traffic entering the Beltway.
"These sources at the Department of Transportation have advised off the record that the DOT proposal included the confident belief that the Capitol Beltway shutdown will successfully achieve the twin goals of thwarting the trucker protest scheduled for a three day period starting on Friday, as well as deal another punishing blow to what they call "the crazy wing of the GOP" which refuses to capitulate to their demands to approve a budget that includes Obamacare funding," writes Ryt.
Demonstrators under the banner of Truckers Ride for the Constitution will arrive in DC tomorrow morning to snarl traffic as part of "a shot across the bow that will ripple across all branches of government." 10,000 truckers are expected to continually circle the Beltway for three days, taking up two lanes and keeping a third clear to allow access for emergency vehicles.
A separate Million Vet March will also take place in DC on Sunday morning at the site of the World War II memorial which was barricaded and wired shut by the feds earlier this week.
On Saturday, Honor Flight veterans plan to break through barricades that have been placed around the Iwo Jima Monument just outside Arlington National Cemetery, setting up a potential confrontation with National Park Service employees. North Country Honor Flight executive director Daniel Kaifetz has asked for assistance from the Million Vet March protesters in allowing vets to gain access to the Iwo Jima Monument.
"Since Interstate 495 is clearly a federal roadway," report our DOT sources, and "the federal government is now closed because of the crazy House of Representatives Republicans, it is within the purview of the federal government to add it to the list of government properties that are closed and may not be used by citizens," claims Ryt adding that the I-95 and I-66 in Northern Virginia could also be closed.
The report seems somewhat dubious given that using National Guard troops to close the Beltway merely to counter a protest in the midst of a government shutdown could not possibly be justified by the Obama administration.
Many have accused the White House of acting spitefully in closing down numerous national parks, roads, hiking trails and memorials, and one Park Ranger even told the Washington Times that an order has gone out "to make life as difficult for people as we can."
However, closing down a major highway surrounding the nation's capital seems a step too far even for the Obama administration, which many charge has acted vindictively by using the shutdown as an excuse to punish the people as part of a political ploy to demonize its political opposition.
Start now to make sure you are staying prepared.
Via: shtfplan
Economy, Prepper disaster planning , doomsday , economy , emergency planning , Preparedness , Prepper , survival planning
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redpajama_set_name: RedPajamaCommonCrawl


Did you know that the Bulletin Boards in Blackbaud K–12's learning management system are an effective way to improve information access and cut paper and printing costs? Bulletin Boards provide teachers with a convenient location for posting general course information, such as the syllabus or helpful resources. This type of information has historically been printed out—or worse, not shared at all because there wasn't an easy distribution method.
We understand that many students are visual learners, so it's important to note that a reduction in paper doesn't mean fewer visuals—in fact, it can mean more! Bulletin Boards are a great way to showcase class visuals, such as photos, videos, and slideshow presentations—further reducing the paper footprint.
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Kathleen is a Customer Success Manager for the K-12 School Solutions Team and is based in Charleston, SC. She has been at Blackbaud since 2002 and a member of the K-12 Team for over 14 years. Not only does Kathleen work daily with Independent schools, but she can also personally identify with our K-12 Community as an alumna, current parent, and school board president. Kathleen enjoys sharing her passion for education with our customers and loves having the opportunity to help them succeed at using our solutions to obtain their unique goals.


Stephen Wolfram in a "New Kind of Science" describes a special kind of cellular automata. The automata he describes are rather interesting. They consist of rows of blocks, where blocks are either filled or not filled depending on the previous row. To generate a new row of blocks, the automata looks at the preceding row and then follows a pre-set "rule" to either color or not color a square on the output row.
was generated by repeated application of "Rule 254". The automaton was initialized with an input line that consisted of a single black square. Repeated application of rule 254 to the ouput line from the preceding step generated the black triangle shown above.
For this rule, the top row in each box gives one of eight possible color combinations for a cell (the middle cell) and its two neighbors (the left and right neighbors of the cell). The bottom row in a box specifies the color that the center cell should have on the next step for each of the 8 possible cases.
Unlike the automata in "A New Kind of Science", the automata for this problem operate in a "bounded space". In other words, each line output by an automaton consists of exactly n squares, and, the first square, and the last square of the output from a bounded automaton are always white no matter what the rule for the automata. This means that while an automaton can examine the first and last square of its input line when computing the new second and second to last characters, it cannot change the first or last square when it outputs a line. Thus, the first and the last square on a line must always remain white.
Bounded automata will always start life on a line with an odd number of squares, and all of the squares (except the middle square) are white. The middle square for step 1 is always black.
For every line in the input, your program must determine which (if any) of the 255 possible automata could have generated that particular line when started from the standard starting state. If none of the automata generate the sequence by the given step number, output "NONE". If more than one automata generated that line, then, you must output all of the automata that generate the line as described below in the output section.
The first field on a line of input consists of a maximum step number (max_step) for the automata to run. This number can be up to 32 bits. Values are chosen such that the problem is solvable within the given time limits given the input specifications.
The second field on a line of input consists of an odd-length string of characters which represent the "squares" on the line. These will not be longer than 256 characters in length, and can be shorter. The size of the second field determines n -- the number of squares in a particular automata.
The character 'W' represents a white square and a 'B' represents a black square.
If an input string contains characters other than 'W' or 'B', or if the input string is an invalid string (not a properly bounded string as described previously), then obviously the string cannot be found by any of the automata, and the output will be LINE # NONE as illustrated in the sample output.
Each line in the input file will have a terminating newline character.
Input is terminated by a single line with the characters "END OF INPUT" as illustrated below. The END OF INPUT line should not be processed by your search algorithm.
number of the automata (0 through 255) that generated a particular output and step is the first step in the sequence of outputs (1, 2,..., max_step) at which the automata generated the desired output sequence.
If more than one rule generated the desired output sequence on or before the maximum step number, list a pair for each rule number that generated the desired output, in order, from lowest automata number to highest automata number with a space between each output pair.
If none of the automata generate the particular line from the input file before or on the maximum step number, output LINE # NONE (where # represents the number of the input line with the search string).


This is one of my favorite dresses; it's a really easy shape and it doesn't take much to put together a cute but comfortable summer outfit. I wore a navy and white graphic maxi dress with clear, spiked, jelly, gladiator sandals, a basic envelope clutch in bright poppy, and a geometric necklace which I wore backwards for the texture. Keep the hair simple and you are good to go.


text:
name             'redis'
maintainer       'Frank Woeckener'
maintainer_email 'fwoeck@gmail.com'
license          'All rights reserved'
description      'Installs/Configures the redis server'
long_description ''
version          '0.1.0'
depends          'etc'

redpajama_set_name: RedPajamaGithub


text:
Q: 4-20mA loop voltage to high I have a 0-16 bar pressure probe connected to a module called Adca UD-720. The probe works on a 4-20 mA loop and the readings are ok. This module also has a 4-20 mA output and I need to connect this output to a data acquisition module in order to get the readings remotely. But when I connect the output to the module, the module goes into protection mode. When I measured the output I couldn't read any current, but I got a 14.7 voltage, which is way too high. The module can only support an input up to 10 V.
So, how can I reduce the voltage below 10 V, and still be able to read the current?
i was thinking to use resistors, but i do not know what resistors to use.
thanks.

A:
So, how can i reduce the voltage below 10v, and still be able to read
  the current? i was thinking to use resistors, but i do not know what
  resistors to use.

The standard load resistor for a 4/20 mA loop is 250 ohms. This will give a peak voltage of 5 volts across the DAQ inputs for 20 mA. I'd use a quarter watt resistor to be safe on power.

Picture source

A: It may be that your initial voltage from the probe is triggering the module's protection before the internal resistor can pull it down to a "safe" level.  Try putting 120 ohms in series with the module; it will cut the initial voltage by half, but shouldn't affect the current significantly.

A: That universal indicator module is highly configurable, both as to input type and as to the display that results from the input when the latter is configured correctly.
Appears to me that you have not set it up correctly.
Replace the indicator with a multimeter on current range to confirm the transmitter is functioning correctly (add a resistor in series to protect the meter fuse if you like).
Then you can proceed to RTFM and set up the indicator, which might well take some time and effort.


text:
India committed to closer defence ties with Indonesia: Envoy
By IANS | Bharat Defence Kavach | Publish Date: 5/7/2014 12:00:00 AM
Jakarta : As the navies of India and Indonesia engaged in a joint exercise on the waters off Indonesia, India's Ambassador Gurjit Singh said the country is committed to furthering close defence ties with Indonesia.
Speaking at the closing ceremony of the 23rd edition of the joint naval exercise between the two countries, code-named INDINDO CORPAT, earlier this month, Ambassador Singh expressed his confidence that the contemporary strategic partnership between these two maritime neighbours would be strengthened in the future, according to an Indian embassy statement issued Wednesday.
Singh pointed out that the presence of the two commanders-in-chief of the two navies at both the opening and closing ceremonies made this the highest level of interaction during the INDINDO CORPAT between the two navies since its inception.
He added that the Indian embassy in Jakarta under his leadership was committed to furthering the close defence ties the two countries enjoy.
The 23rd edition of INDINDO CORPAT started at Port Blair in India's Andaman & Nicobar Islands April 14 and concluded in the port city Belwan-Medan, in Indonesia's Sumatra May 3.
Under the broad ambit of a bilateral strategic partnership, Indonesia's navy TNI AL and the Indian Navy carry out coordinated patrolling twice a year near the International Maritime Boundary Line to keep this vital part of the Indian Ocean region safe and secure for commercial shipping and international trade.
The Parchim Class Corvette KRI Imam Bonjol and the Indonesian navy's latest indigenously built maritime patrol aircraft CN 235 participated in the exercise.
Rear Admiral Arief Rudianto, the commander-in-chief of Indonesia's Western Fleet Command, and Air Marshal P.K. Roy, the commander-in-chief of India's Andaman Nicobar Command, were the two senior officers who attended the closing ceremony.
During his visit, Ambassador Singh also called on the governor of the Indonesian province of North Sumatra, Gatot Pujonogroho.
The ambassador said that the close geographical proximity between North Sumatra and India has always encouraged trade over the centuries. It now needs to be diversified towards new investment in infrastructure, tourism and healthcare.
The governor, on his part, promised that his administration would extend all assistance in this regard.
One year of abrogation of Article 370: Rs 1,700 cror..
Putin visiting India: Is it strategic balancing?
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text:
MattHubert.com
2015 Hubert Baby Name Bracket
2015 Hubert Baby Name Bracket Standings
2015 Hubert Baby Name Bracket Boy First Name Results
2015 Hubert Baby Name Bracket Girl First Name Results
2015 Hubert Baby Name Bracket Boy Middle Name Results
2015 Hubert Baby Name Bracket Girl Middle Name Results
A Statistical Analysis of the 2015 Hubert Baby Bracket Entries
9. Jason Mraz
January 31, 2015 Matt Hubert	Leave a comment
In honor of me turning 30, I made mix CDs of my favorite songs from each of my 30 favorite musical artists/groups. Read the introductory post for more background information on my 30 at 30 project. Reminder: there is no scientific rationale for this list. They're simply my personal favorites. Coming in at number 9 is Jason Mraz.
"Yeah the Mr. A to Z, they say I'm all about the wordplay," Mraz sings on the song "Wordplay," a self-aware song of saccharine pop music in which Mraz explains the twists and turns of his lyrical acrobatics. Although that song didn't make the cut for my ultimate compilation, Mraz's lyrics have left an indelible imprint on my life. Over the past decade or so, Mraz has combined cocky, clever wordplay with introspection and sentimentality in his songs. His ability to vacillate between ice cool confidence and heart-on-his-sleeve vulnerability—plus his ability to turn a phrase—is what makes Mraz a top-10 favorite of mine.
After one listen through his 2002 album, Waiting For My Rocket to Come, I was on board the Mraz bandwagon. Songs like "Curbside Prophet" demonstrated a hip hop influence in terms of the way he put words together, but Mraz would never be confused for Eminem. He's not a rapper, and unlike Eminem, the man can sing, too. Plus, in place of thumping bass beats, Mraz's music included everything from acoustic guitars to a brass section to banjo. And for every happy-go-lucky track like "The Remedy (I Won't Worry)" Mraz also had something like "You and I Both", a tender-hearted love song. Over time, Mraz's softer side would prove to be his most commercially successful avenue, but it's his combination of moods that kept him in my rotation.
Mraz's music has been a constant in my relationship with Jessie like mile markers on a highway. So it is ironic that it was actually an ex-girlfriend that first introduced me to Mraz's music back in the early 2000s. It was on an impromptu unofficial first date on April 15, 2005, that Mraz's music earned a place in Matt and Jessie history. She introduced me to a mix of Mraz acoustic tracks from the early 2000s, four of which made it onto this compilation. Among those four songs, "Little You & I" and "Sleep All Day" earned a special place on the soundtrack of my life as listening to them led into our first kiss. Mraz's lyrics set the scene. "Little You & I" includes the following:
It's something we already know so well
And it's right on, right on the tip of our tongue
Something big that has already begun
"Sleep All Day" played next, featuring the lines:
and we knew it was time to take a chance here
and time to compromise our lives just a little while
and it was time for all the wrong reasons
but time is often on my side and I give it to you tonight
The rest, as we say, is relationship history, but we owe a special debt of gratitude to Mr. Mraz for the instrumental (or should I say lyrical?) role he played in kickstarting our relationship. And, aside from the personal love story connection, the songs are quite lovable on their own merit.
Later that year, 2005, Mraz would release his second major album, Mr. A-Z. While some of the album felt a bit overproduced, especially in light of the acoustic sets Jessie had introduced me too, there were a few standout tracks. "Clockwatching" is a smooth-talking track that again put Mraz's lyrical dexterity on display. The words really hit home for two young people in love fighting the uphill battle against parent-imposed curfews. "The Forecast" boasts that "crazy is the forecast all week." In my experience, that is a fair enough summation of trying to maintain a long distance relationship in college. At 8:10 "Song For a Friend" is the longest Mraz to make the cut. Just when it seems like the song is over, the drums bring in a fantastic gospel-style chorus that is goosebump-inducing.
In 2008, Jessie and I hit a rough patch, and Mraz released another album, We Sing, We Dance, We Steal Things that included "A Beautiful Mess" and "Details in the Fabric", the two most beautifully sad songs I think he has ever written. I cannot tell you how many times I sang along with those tracks during my down days. I still love them today, as they serve as reminders of both the cathartic power of music and the fact that beautiful things can come out of sad or tragic times. On the positive side, the longest breakup of our relationship proved not to be an ending. On a trip to Virginia Beach with Jessie, I still remember listening to "I'm Yours" and "Lucky" and although it wouldn't be made official until some time later, I couldn't help but feel Mraz and Colbie Caillat were stand-ins for us as they sang on Lucky:
Do you hear me? I'm talking to you
Across the water across the deep blue ocean
Under the open sky, oh my, baby I'm trying
Boy, I hear you in my dreams
I feel your whisper across the sea
I keep you with me in my heart
You make it easier when life gets hard
Lucky I'm in love with my best friend
Lucky to have been where I have been
Lucky to be coming home again
In 2010, when Jessie and I got engaged, I proposed at sunrise, and of course I had a playlist to accompany the event. Mraz's "Conversations With Myself" from the aforementioned acoustic mix Jessie had introduced to me some five years earlier was the second song I played that day. I just of easily could have included the appropriately named "Sunshing Song" from Mraz's 2009 release Jason Mraz's Beautiful Mess – Live On Earth or "Hey Love" from his early career live and acoustic release.
Only one song made my compilaion from Mraz's 2012 release Love is a Four Letter Word, but "I Won't Give Up" is a gem with a lyrical maturity that mirrors the mature, married love I share with Jessie.
Well, I won't give up on us (no I'm not giving up)
God knows I'm tough enough (I am tough, I am loved)
We've got a lot to learn (we're alive, we are loved)
God knows we're worth it (and we're worth it)
Unfortunately Mraz's latest album, 2014's was released so close to the date of making this compilation that it did not land any tracks. However, since I'm writing this several months later, I have to mention that Mraz's music is still going strong as several of these songs have already landed on recent Matt's Mixes. Clearly Jason Mraz and his trademark Jason Mraz hats aren't going anywhere anytime soon.
MM 30 at 30: Jason Mraz tracklist (finalized July 15, 2014)
1. Details in the Fabric feat. James Morrison
2. A Beautiful Mess
3. Song For a Friend
4. I Won't Give Up
5. The Remedy (I Won't Worry)
6. Conversation With Myself (Acoustic)
7. Clockwatching
8. The Forecast
9. Hey Love
10. Little You & I
11. You and I Both
12. No Stopping Us
13. Lucky
14. I'm Yours
15. 1000 Things (Acoustic)
16. Sleep All Day (Acoustic)
17. Curbside Prophet
18. Sunshine Song (Live)
30 at 3030 at 30 musical artistsJason Mraz
Previous Post30 at 30 List #10: My Dad's Ceramic Christmas OrnamentsNext Post8. Wyclef Jean
The first key to writing is to write.
Thankful for Rosemary
30 at 30 Lists #27: Favorite People, Moments, and Memories from the NBA Bubble
March Sadness
30 at 30 Lists #26: Feelings About LeBron Joining the Lakers
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Hiking the Tahoe Rim Trail
STORY AND PHOTOS BY PETER MIRES
The author poses on the Tahoe Rim Trail.
This summer, I'm checking off a significant entry from my bucket list: I'm hiking the Tahoe Rim Trail (TRT). Although experiencing the entire 165-mile trail that circumscribes the mountainous perimeter of the Lake Tahoe Basin didn't make Patricia Schultz's popular book "1,000 Things to See Before You Die," it's been on my list for some time. I retired last December and knew the time had come for me to tackle the TRT. I look forward to joining a group of fellow hikers who have completed the entire trail—the 165 Mile Club.
It's a sign of a clearly marked trail.
The Tahoe Rim Trail Association (TRTA), with headquarters in Stateline, maintains the official list of 165 Mile Club members―nearly 2,000 people to date. The genesis of the Tahoe Rim Trail and the non-profit organization that protects and preserves it can be traced to the vision of a U.S. Forest Service employee and avid hiker, Glenn Hampton. Beginning in 1980, he generated interest in a trail that would loop around the lake at high elevation and ultimately join the existing Pacific Crest Trail (PCT), which traverses the mountains on the Tahoe Basin's west side.
Four years later, with initial funding and permits obtained, the TRT began to take shape. It was finished in 2001, thanks to the efforts of many people, mostly volunteers. But any hiking trail is never really finished; it needs constant maintenance after winter, windstorms and gully washers, along with the tread of boots, bicycle tires, and horseshoes. According to TRTA estimates, more than 100,000 people use the TRT every year.
Approximately 40 percent of the TRT is on Nevada's side of the Tahoe Basin. Living in Carson City, the trail is practically in my backyard; I can get from home to the trailhead on Highway 50 at Spooner Summit in 20 minutes. Actually, the TRT is accessible from many locations, and the TRTA offers a free map series that breaks the trail into eight convenient sections.
GETTING OUTSIDE THE COMFORT ZONE
One thing I like about the TRT is that, although challenging, it is doable for most people that are in reasonably good physical condition―even 60-somethings like me. Perhaps you've read Bill Bryson's "A Walk in the Woods" or Cheryl Strayed's "Wild," or seen the movies based on those books, and find the prospect of a long-distance hike more than a little intimidating. You'd be right; hiking the Appalachian Trail 2,200 miles from Georgia to Maine or trekking 2,600 miles from Mexico to Canada along the Pacific Crest Trail is no mean feat!
The closest I've come to this sort of outdoor adventure was in 1978 when I completed the 262-mile Long Trail, which runs along the spine of the Green Mountains in my natal state of Vermont. The Long Trail is kind of similar to the TRT insofar as you have amazing views of a large lake―Lake Champlain―for most of the hike. A huge difference between the two trails, however, is their respective elevations; most of the TRT is between 7,000 and 10,000 feet, whereas the highest peak in the Green Mountains, Mount Mansfield (4,393 feet), is lower in elevation than where I live in Carson City! I've learned from experience that hiking in the East is not like hiking in the West, where one can't help but notice the thin air in the mountains.
This brings up how I'm hiking the TRT. Those aspiring to complete the entire 165 miles of the trail can do so in a number of ways—thru-hiking or segment hiking are the most common. Thru-hiking means you make a backpacking trip start to finish; segment hiking means you do a series of day hikes. In fact, you can even ride your horse or mountain bike on significant stretches of the TRT, or, if you're so inclined, run. You can do the trail alone or in the company of others, and, if you're like me, you can take advantage of TRTA-sponsored programs.
I'm participating in the TRT Wednesday segment hike this summer, which means our group of 11 plus our guide hike a section of the trail every week, and by summer's end we expect to add our names to the membership roll of the 165 Mile Club. Every Wednesday until Aug. 31, we cover an average of 14 miles of the TRT. I registered for the Wednesday group—Friday segment hike is also available—back in January, paid the $600 fee (a large portion of which goes to support the mission of the TRTA), and passed a medical history review and a hiking experience survey. This is the eighth year the TRTA has offered its segment hiking program, and the preparation packet I received back in the spring reflects a collective wisdom of boots-on-the-ground experience—such as foot care, trail food suggestions—and recommended day-hiking gear. I'd also recommend Tim Hauserman's excellent book: "Tahoe Rim Trail."
For me, the segment hike option is perfect. I carry a daypack, my trekking poles, a hearty lunch, and plenty of water and sunscreen. The best part—besides the TRTA shuttle to the starting point of each segment—is the camaraderie, blisters and all. My new friends and I are in complete agreement with the slogan that this is "a trail like no other."
Tahoe Rim Trail Association
128 Market St., Ste. 3E
Stateline, NV 89449
tahoerimtrail.org, 775-298-4485
Peter Mires—a native of the Green Mountain State—first came out West in 1990 and has been fascinated with the region, especially the Sierra Nevada and Lake Tahoe, ever since. Dr. Mires is the author of the recently published book "Lake Tahoe's Rustic Architecture." He lives in Carson City.


The bar/restaurant l'Océan is an institution in Vannes. For a drink or a lunch, the establishment has a loyal clientele and is one of the essential places in the beautiful Breton city.
The restaurant is the ideal place to enjoy a croque-monsieur, meats & carpaccios, salads, hamburgers, starters, desserts, set meals and children's menus! We offer a complete and tasty menu that will surely satisfy you.
You can also come by for a drink with friends or family, accompanied by a cheese board or local products! In the dining room or outside, the dynamic and pleasant team of l'Océan will welcome and serve you.
A simple break? A lunch? Let us take care of you!
* Reception for groups: Please remember to book beforehand.


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Joint Statement by UN human rights experts for World Environment Day
Recognition of the right to a healthy environment key to address the environmental crisis and protect human rights
GENEVA (4 June 2020) – On the eve of World Environment Day, a group of more than fifty United Nations experts called on States to take urgent and timely action to recognize and implement the right to a safe, clean, healthy and sustainable environment as a vital response to the current multi-faceted environmental crisis.
The world is currently facing a climate emergency, pervasive toxic pollution, dramatic loss of biodiversity, and a surge in emerging infectious diseases of zoonotic origin, such as COVID-19. The environmental crisis has negative impacts on a wide range of human rights including the rights to life, health, water, sanitation, food, decent work, development, education, peaceful assembly and cultural rights, as well as the right to live in a healthy environment.
The adverse effects have a disproportionate impact on women and girls and the rights of billions of people, especially those who are already vulnerable to environmental harm including people living in poverty, minorities, older persons, LGBT persons, racially and ethnically marginalized groups, indigenous peoples, people of African descent, persons with disabilities, migrants, internally displaced persons, and children.1
Peoples and communities historically subject to exploitation, including people of African descent, continue to bear the brunt of pollution, environmental degradation and climate change, including in some actions ostensibly intended to protect the environment. In addition, environmental human rights defenders have been facing a shocking rate of killings, threats, arbitrary arrests, harassment and intimidation as a direct result of their legitimate work on human rights and the environment.
Transformative actions are urgently required, not only to address the COVID-19 pandemic but to protect the environment and human rights, and to address the drivers of climate disruption, toxic pollution, biodiversity loss, and zoonotic diseases, including by requiring businesses to respect the rights of affected communities and the environment.
As human rights experts of the United Nations system, we call for human rights, including the right to a healthy environment, to be placed at the heart of the required transformations related decision-making processes. We need to address the root causes of inter-related environmental disasters and seize this opportunity to 'build forward better' in order to achieve a just and sustainable future and leave no one behind.
Applying a rights-based approach to the environmental crisis not only clarifies what is at stake; it catalyzes ambitious action, emphasizes prevention, focuses on the needs of those most affected and increases accountability. The rights-based approach would help address inequality and ensure protection for all members of society, with a particular emphasis on people in vulnerable situations.
One of the key elements of guaranteeing a human rights-based response is through global recognition and implementation of the right to a clean, safe, healthy and sustainable environment. If such a right were to be respected, protected and fulfilled, it would provide an important safeguard for people and the planet.
Currently the right to a healthy environment has been legally recognised by 156 States (out of 193) in constitutions, legislation and regional treaties.2 However, the UN has not yet formally recognized this right.
The first step towards the recognition of the right to a healthy environment occurred almost 50 years ago, as UN member States met in Stockholm, Sweden, during the United Nations Conference on the Environment, and declared that: 'Man has the fundamental right to freedom, equality and adequate conditions of life, in an environment of a quality that permits a life of dignity and well-being.'3
Since then, UN member States have adopted a range of resolutions on the inter-linkages between the environment and the enjoyment of human rights. The Human Rights Council adopted its first resolution on human rights and the environment in 2011, and appointed an independent expert (Professor John H. Knox) to articulate the links between human rights and the environment.4
Decades of experience have clarified that the right to a healthy environment includes clean air, safe and sufficient water, sanitation, healthy and sustainable food, a toxic-free environment, a safe climate and healthy ecosystems and biodiversity. It also includes the rights to environmental information, participation in decision-making and access to justice with effective remedies.
The core group on human rights and the environment (Costa Rica, the Maldives, Morocco, Slovenia, and Switzerland) declared in September 2020 their intention to put forward a resolution on the recognition of the right to a healthy environment at the Human Rights Council.5 In a recent joint statement endorsed by 69 States during the 46th session of the Human Rights Council, the core group on human rights and the environment stated that: "It is our belief that a safe, clean, healthy and sustainable environment is integral to the full enjoyment of human rights. Therefore the possible recognition of the right at a global level would have numerous important implications on what we leave to our future generations."
Further, the UN Secretary-General, António Guterres, called for the promotion of the right to a safe, clean, healthy and sustainable environment as he launched a Call to Action for Human Rights.6
The High Commissioner on Human Rights, Michelle Bachelet, has said that: "It is time for global recognition of the human right to a healthy environment – recognition that can lead to stronger policies, at all levels, to protect our planet and our children. The right to a healthy environment is grounded in measures to ensure a safe and stable climate; a toxic-free environment; clean air and water; and safe and nutritious food. It encompasses the right to an education with respect for nature; to participation; to information; and to access to justice [...]."7
In a recent joint statement, 15 UN agencies stated that " We have come together under the UN Secretary-General's Call to Action for Human Rights, through the inspiration provided by the Council, and in response to the urgent call for action from all corners of the world to declare that the time for global recognition, implementation, and protection of the human right to a safe, clean, healthy and sustainable environment is now."8
More than 1,100 civil society, child, youth and indigenous peoples' organizations have united to call upon Member States to recognize the right to a healthy environment as soon as possible.9
We, as human rights experts, urge States to take this opportunity in the face of the global environmental crisis to support the adoption of key UN resolutions recognizing that everyone has the right to a safe, clean, healthy and sustainable environment both at the Human Rights Council and at the United Nations General Assembly.
Similar resolutions adopted by the UN in 2010 and in 2016 to recognize the rights to water and sanitation have served as a catalyst for constitutional recognition of these rights, stronger laws and increased resources to deliver these essential services. Recognition of the right to a healthy environment through UN resolutions is expected to produce similar benefits.
In a world where the global environmental crisis causes more than nine million premature deaths every year and threatens the health and dignity of billions of people, the UN can make a difference by recognizing that everyone, everywhere, has the right to live in a healthy environment. The time for the global recognition and action is now.
The following UN independent experts endorsed this statement:
Lead: David R. Boyd, Special Rapporteur on Human Rights and Environment;
E. Tendayi Achiume, Special Rapporteur on contemporary forms of racism, racial discrimination, xenophobia and related intolerance;
Saad Alfarargi, Special Rapporteur on the right to development;
Pedro Arrojo-Agudo, Special Rapporteur on the human rights to safe drinking water and sanitation;
Mohamed Abdelsalam Babiker, Special Rapporteur on the situation of human rights in Eritrea;
Karima Bennoune, Special Rapporteur in the field of cultural rights;
Koumbou Boly Barry, Special Rapporteur on the right to education;
Elizabeth Broderick (Chair), Melissa Upreti (Vice Chair), Dorothy Estrada-Tanck, Ivana Radačić, and Meskerem Geset Techane, Working Group on discrimination against women and girls;
Francisco Calí Tzay, Special Rapporteur on the rights of indigenous peoples;
Alice Cruz, Special Rapporteur on the elimination of discrimination against persons affected by leprosy and their family members;
Dominique Day (Chairperson), Ahmed Reid, Michal Balcerzak, Sabelo Gumedze, Ricardo A. Sunga III, Working Group of Experts of People of African Descent;
Olivier de Schutter, Special Rapporteur on extreme poverty and human rights;
Fernand de Varennes, Special Rapporteur on minority issues;
Isha Dyfan, Independent Expert on the situation of human rights in Somalia;
Michael Fakhri, Special Rapporteur on the right to food;
Felipe González Morales, Special Rapporteur on the human rights of migrants;
Cecilia Jimenez-Damary, Special Rapporteur on the human rights of internally displaced persons;
Irene Khan, Special Rapporteur on the promotion and protection of the right to freedom of opinion and expression;
Mary Lawlor, Special Rapporteur on the situation of Human Rights Defenders;
Yuefen Li, Independent expert on foreign debt and human rights;
Michael Lynk, Special Rapporteur on the situation of human rights in the Palestinian Territory occupied since 1967;
Victor Madrigal-Borloz, Independent Expert on protection against violence and discrimination based on sexual orientation and gender identity;
Claudia Mahler, Independent Expert on the enjoyment of all human rights by older persons;
Tlaleng Mofokeng, Special Rapporteur on the right of everyone to the enjoyment of the highest attainable standard of physical and mental health;
Siobhán Mullally, Special Rapporteur on trafficking in persons, especially women and children;
Tomoya Obokata, Special Rapporteur on contemporary forms of slavery;
Obiora Okafor, Independent Expert on human rights and international solidarity;
Marcos Orellana, Special Rapporteur on the implications for human rights of the environmentally sound management and disposal of hazardous substances and waste;
Dante Pesce (Chairperson), Surya Deva (Vice-chairperson), Elżbieta Karska, Githu Muigai, Anita Ramasastry, Working Group on the issue of human rights and transnational corporations and other business enterprises;
Balakrishnan Rajagopal, Special Rapporteur on adequate housing as a component of the right to an adequate standard of living, and on the right to non-discrimination in this context;
Javaid Rehman, Special Rapporteur on the situation of human rights in the Islamic Republic of Iran;
Livingstone Sewanyana, Independent Expert on the promotion of a democratic and equitable international order;
Ahmed Shaheed, Special Rapporteur on freedom of religion or belief;
Dubravka Šimonovic, Special Rapporteur on violence against women, its causes and consequences;
Leigh Toomey (Chair), Elina Steinerte (Vice-Chair), Mumba Malila, M. Miriam Estrada-Castillo and Priya Gopalan , Working Group on Arbitrary Detention;
Morris Tidball-Binz, Special Rapporteur on extrajudicial, summary or arbitrary executions;
Gerard Quinn, Special Rapporteur on the rights of persons with disabilities;
Clément Nyaletsossi Voule, Special Rapporteur on the rights to freedom of peaceful assembly and of association.
1/ See the thematic reports of the Special Rapporteur on human rights obligations relating to the enjoyment of a safe, clean, healthy and sustainable environment. https://www.ohchr.org/EN/Issues/Environment/SREnvironment/Pages/AnnualReports.aspx
2/ A/HRC/43/53.
3/United Nations Conference on the Environment, Stockholm 1972 | United Nations
4/ See Framework Principles on Human Rights and the Environment, A/HRC/37/59.
5/ StatementCoreGroupHRE_towardsGlobalRecognition.pdf (genevaenvironmentnetwork.org)
6/ See https://news.un.org/en/story/2020/02/1057961.
7/ During the 44th session of the Council in June/July 2020
8/ During the Human Rights Council, 46th Session in March 2021
9/ http://healthyenvironmentisaright.org
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With youthful style and stand out fashion in mind, Love Moschino bring collections that feature simple style whilst keeping your wardrobe up to date and looking as brand new as ever. They present these women's Logo Core Track Pants which come in a black colourway and feature glitter heart print to the back for the perfect addition to your off duty, premium wardrobe. Details; black colourway, cotton stretch construction, draw tie waist, two side pockets, back pockets, tonal stitching throughout, slim fit, ribbed cuffs and branding to the back to complete. Model is 5'9" and wears a size 8.


In 2016, female obesity prevalence in Burundi was 8.6 %. In the ranking by female obesity prevalence including 188 countries, Burundi has the 144th rank that is close to the positions of such countries as Angola and the Benin. Compared to Australia which at the top of the ranking with female obesity prevalence of 28.4 % in 2016, Burundi has 69.72 % percent lower female obesity prevalence.


DURHAM — It has been more than a year since President Donald Trump put into place the "global gag rule," that cuts funding to foreign health care providers in developing countries for suggesting abortion as a service, and activists and politicians are taking a stand.
Amy McCall is New Hampshire's campaign organizer for the #Fight4HER campaign, a national project that opposes the president's controversial gag rule. She believes the policy is an affront to women's healthcare rights.
According to documents on the #Fight4HER website, Trump's gag rule affects women's health care services in Kenya, Colombia, Niger and Nepal.
McCall said the U.S. funding for foreign women's health care providers is less that 1 percent of the spending budget.
Foster's Daily Democrat reached out to New Hampshire Republican Party Chairman Jeanie Forrester numerous times by email and by phone on Thursday and Friday seeking a comment on the GOP's views about the global gag rule, but received no response.
The #Fight4HER campaign will run until November's midterm elections. McCall is spending time at the University of New Hampshire teaching students how to lobby, speak publicly and reach out to elected officials to bring change.
"We're seeing people who care about what's happening to other people, they realize that this is not OK and they want to see change," she said. "We're saying to elected officials who support the gag rule, that 'we will not support you and we will not re-elect you,' and it's working," McCall said.
Jane Kayarian, a social work student at UNH is events coordinator for the #Fight4HER campaign on campus. She joined the campaign because she believes adequate, well-rounded family planning and reproductive health care saves lives and that every woman and girl should have the right to choose when and how they want to enter motherhood. She also believes no administration or political party should control or stifle life-saving conversations on bodily autonomy or necessary reproductive aid to people across the globe.
This past week, #Fight4HER activists went to Capitol Hill in Washington, D.C., to thank politicians who support their cause and demand answers from those who don't.
McCall said many elected officials support their campaign and those who don't are often Republicans who receive money from anti-abortion lobby groups.
From now until the midterms, the #Fight4HER campaign will host events at UNH to get students involved. There will be a benefit concert sponsored by #Fight4HER and Planned Parenthood in the Memorial Union Building's Strafford Room on Wednesday, April 18, from 7 to 10 p.m. There will also be a panel discussion in late April or early May to discuss the campaign as a whole.
To get involved in the #Fight4HER campaign, email McCall at amy.mccall@popconnection.org.


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Georgia Democratic Candidates Held to Different Standards in Race for Governor
Changa, Opinion,
by Anoa Changa March 21, 2018, 9:00 am
staceyabrams.com | staceyevans.com
Georgia Democratic candidates for Governor are making the rounds as the primary is in full swing. As things heat up, the candidates will keep getting asked tough questions about exactly how they would fix problems facing Georgians. While the two Democratic candidates for governor have the same name, they do not have the same experience, and they are not being scrutinized to the same degree.
Not All "Tough" Questions Are Equal
The Atlanta Journal-Constitution's Greg Bluestein recently described the candidates facing "tough" questions at the 2018 Young Democrats Convention. Bluestein insinuates that the candidates are being treated equally in similar spaces. Stacey Abrams faces a higher bar and expectations than Stacey Evans. The two questions Bluestein referenced were not similar in tone or "toughness."
Since the start of this election cycle, Abrams has been attacked over the Hope Scholarship, the centerpiece of her opponent's campaign. Opponents have said that Abrams is working with Republicans and Gov. Nathan Deal to screw over Georgia families. During the candidate Q&As, Abrams was challenged by a voter regarding the Hope Scholarship. The situation was tense and became aggressive.
Considering this framing, it is not surprising that the person asking the question was so upset. Despite being talked over and having her involvement in Hope mischaracterized, Abrams responded with reason and balance. Recently released emails show Evans recognizing Abrams' leadership on the issue even when they disagreed.
Evans' "tough" question was regarding her failure to accept responsibility for the since-deleted Martin Luther King video, which her campaign produced. Bridgemon H. Bogler, newly elected chair of the Georgia Young Democrats Black Caucus, asked Evans why she blamed the Abrams campaign for the now-deleted video. Evans blamed an Abrams supporter for sharing the deleted video and again failed to accept responsibility.
Evans downplayed the video as simply celebrating her appreciation of MLK, but other candidates made MLK appreciation videos that didn't simply show them being seen with Black people. These other videos celebrated MLK by tying his words and legacy into their own work. Evans' disconnect on the difference between her video and other efforts to commemorate MLK is disappointing. She infringed upon a sacred space that is Ebenezer Baptist Church and doesn't get how disrespectful having her social media team follow her and take videos and pictures without permission was a problem. She also didn't address her surrogates who were not given accurate information when asked for comment.
But this is a standard way to attack Black women. It doesn't matter that the allegations have no merit, the mere appearance of negative action undermines our work. We get silenced and attacked by people who call us angry or claim the concerns we're raising are a threat to "unity." In her response, Evans quickly tries to brush past this issue but her discomfort is apparent. If this is how she handles a "tough" question from a Democratic voter, how would she fare in the general against a Republican opponent?
Clickbait Titles and Misleading Tweets
The Atlanta Journal-Constitution has relied on clickbait headlines to draw attention to nonissues to attack Abrams' credibility. A 2016 study found that nearly 60% of all links shared on social media are not actually clicked on — that the headlines get read, but not the articles. In the past week, two stories regarding Abrams (read here and here) contain headlines distorting the issue giving a negative impression of Abrams.
Both pieces buried the most important facts for voters to consider: In the case of her debt, Abrams was caring for and financially supporting her parents after Hurricane Katrina hit. She is handling her debt responsibly. Regarding the state contracts that were awarded to a nonprofit, she helped start the Atlanta Journal-Constitution article makes a mountain out of a molehill. Despite the negative impression given off from the title, the author acknowledges there was no evidence of ethical issues or other impropriety.
Evans and her campaign chime in on these random accusations without any valid support for their statements and no pushback.
When asked for comment about the state contracts, which again, there is no allegation of impropriety or some error on Abrams' part, Evans misstates the issue and alleged nature of business by claiming Abrams had business dealings with Governor Deal. Evans undercuts her opponent's reputation and credibility for cheap political points. If Abrams' campaign were to give such a response, she would most likely be depicted as a bully and a liar. There is no indication that the state contracts impacted the way Abrams conducted herself as House Minority Leader or that she improperly influenced action to benefit herself financially. Candidates can get competitive and rough, but this type of fabricated logic should not be tolerated by those who claim to want "unity."
The most prominent example the past week of someone exploiting the clickbait headlines and extrapolating negative impressions of Abrams was a tweet from writer Lee Fang of The Intercept. Either Fang did not read the article in its entirety and simply shared it based on the title alone, or he intentionally sought to further the distortion perpetuated by the title. Fang's reputation through his work at The Intercept gives his words more weight even in something as simple as a tweet. His sharing a story and claiming that Abrams not only acted improperly but also misrepresented her actual record.
If this isn't the most misleading, clickbait BS tweet from Fang and article from AJC. Clearly they have it out for Stacey Abrams. pic.twitter.com/YMkHAOFQu6
— Benjamin Dixon (@BenjaminPDixon) March 16, 2018
Interestingly enough, Fang does not address Evans' record on education. He tried to defend her over the MLK video by claiming that she was being attacked because she was white (see also: reverse racism, and the fact that it doesn't exist). Sadly, he is colored by his own thoughtless disdain and doesn't listen to other perspectives.
As we look forward to the General Election, we need to have the strongest candidate possible to reclaim the Governor's Mansion from Republicans. Regardless of who people are supporting, both candidates should be challenged and held accountable for their votes and advocacy. But when one candidate is challenged and another isn't, it's a double standard. Whether they're asked questions about the issues or accountability, Stacey Abrams is held to a higher standard than Stacey Evans.
This article was originally published at PeachPerspective.com.
GeorgiaGeorgia Democratic PartymlkStacey AbramsStacey Evanstaxestough questions
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Written by Anoa Changa
Mom 1st, Lawyer 2nd. Anoa Changa is Director of Political Advocacy and a Managing Editor of Progressive Army, as well as a member of its Editorial Board. She hosts The Way with Anoa, Wednesdays at 9pm ET on YouTube . Follow her on Twitter @TheWayWithAnoa. "Never tell me the odds." - Han Solo
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