Education Series - The Nurtured Heart Approach is a social emotional and relationship-focused methodology developed for building relationships in which students and adults/families are intrinsically motivated both academically and pro-socially. This presentation will teach you how to respond to challenging behaviors with intention and purpose and how to build stronger children from the inside/out. The focus of these workshops is to provide EGUSD parents and staff with mental health supports for their student's success within the school and the home setting. This workshop will be presented by licensed mental health therapists.


Rules in Time to Decorate? A Lie!
Mixing prints pollutes the look of a room? Dark colors diminish the environment? These and many other issues come to the fore when it comes to decorating. And building on the 1st of April, the date on which we celebrate the "April Fool's day," Bontempo demystifies some of the decorating rules used to date and that in some ways are quite obsolete. After all, a sophisticated and charming not only depends on patterns, and the personality and the good taste of its residents. In fact, creativity, customization and boldness are the big trends in decoration. And we support.
For those who wish to dare, the use of strong colors such as yellow, purple and Red are great choices and do not need to be restricted only to the decorative objects. Wallpapers, for example, are more than welcome in any room of the House. With living hues and easy application, become protagonists of the decoration and brighten and transform an environment.
When properly positioned, just a few spots of light are able to enhance the environment in ways surprising. Look great, for example, when placed on the wall paintings and props. Choose strategic points in the room and opt for lamps of different heights or even spots on the ceiling.
Monochrome spaces can be sophisticated and cosy, just use the creativity and beautiful decorative objects. Also serve as a basis for sudden changes of decoration, allowing the insertion of dots of color when it is in the interests of the resident. White, beige and grey are the colors that are ideal for those who don't want to risk it, but at the same time seeking an environment clean, versatile and look again.
In contemporary environments, you will see glass coffee tables, wooden side tables, aluminum chairs and armchairs with metal feet. The mixture promotes a more diverse and functional room.
The mixture of classical pieces with modern furniture as well as vintage pieces with rustic furniture, etc, also brings a nice dose of charm to a room. The contrast makes the room more interesting and Rico, showing your entire personality.


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Gianluigi Buffon: Biography, Football Career, and Life | Odds2win
Birthplace, first steps, teams, and transfers
When we talk about the longer age of footballers, we consider the age of 40 as a notable point that is rarely passed even by goalkeepers. However, Gianluigi Buffon laughs at such talks - he is 44 and continues playing at the professional level. The playing legend was born in 1978, in Carrara, on January 28. He joined the youth academy of Parma being already 13, which looks like quite a late ignition. However, he fastly became a member of the main team (in 1995) and was even called as part of the Italian national team for the World Cup 1998.
In the next year, Gianluigi played one of his best seasons, winning UEFA Cup, Italian Cup, and Supercup, playing for Parma. His talent was noted, so Juventus agreed to set a long-time record for goalkeeper transfer in 2001 - the Old Lady paid incredible 52 million euros for Buffon. None of the accurate football predictions for free could predict that the next break will be only in 2018, when Liverpool signed Alisson, paying 10 million euros more for the keeper. However, Juventus was absolutely right in getting the young talent, who served as their goalie for 17 consecutive years.
Buffon is often considered one of the best goalkeepers in the history of football. Thus, he was named UEFA's best player in club competitions in 2003, when the Old Lady made it to the finals of the Champions League but lost to Milan. He was also named multiple times in the symbolic squads of the top events he participated in - UCL, Serie A, Copa Italia, and even the World Cup. The participation and victory of the WC 2006 skyrocketed him to the runner-up position in Ballon d'Or voting that year. Nonetheless, he left Juventus in 2018 and joined PSG to win a few local trophies with a French club. But even being 41, he still returned to Juve in 2019 until rejoining with Parma in 2021, which now plays in Serie B. Interestingly, Gianluigi still has a stable place in the starting squad, being 44.
Stats, records, and jersey number
With such a long football life, Buffon is among the leaders in terms of matches played at the professional level. Thus, he played 956 games at the club level, conceding 801 and having 424 clean sheets. He also added 176 games for the Italian national team, being the long-standing captain of the team, which looked easy for him like the Melbet register in Bangladesh procedure. He also claims joint-first place (with Casillas and Neuer) as IFFHS's most valuable keeper of the season, winning this prize five times.
Personal life: girlfriend, net worth, and non-football activity
It's not surprising that during such a long career, Buffon had few long-lasting relations. Thus, his first wife was Alena Seredova, whom he met in 2005 and marrier in 2011. The couple born two sons (in 2007 and 2009) but finished their relations in 2014. In a year, Gianluigi was linked to Ilaria D'Amico. In 2016, they announced the birth of a son while married the next year. The net worth of the Italian football legend is about $20 and is now replenished mostly from endorsements but not salary.
Latest news and rumors
Online outlets are probably tired of creating the titles for Buffon's possible last year in football instead of explaining how to register in India at Betwinner. The latest news and rumors are totally about his potential career end, while Gianluigi still looks happy on the pitch and wants to continue playing.
Each betting bonus that is offered by online bookmakers can become a very lucrative business for both the casual and professional punter. Most…
Quincy Promes: Biography,…

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KGC gears pumps can be used in a wide variety of applications. These positive displacement low inertia pumps are excellent at pumping fluids at low to medium pressures. These pumps can be used to pump water and a large range of other non abrasive fluids including oils and molasses.
Very useful for pressure boosting, liquid transfer, factory process pumping and lubrication duties.


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Warfarin dose requirement in Turkish patients: the influences of patient characteristics and polymorphisms in CYP2C9, VKORC1 and factor VII
Hippokratia 2014, 18(4):319-327
Yildirim E1, Erol K1, Birdane A2
1Pharmacology Department, 2Cardiology Department Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey
Background: To determine the contribution of cytochrome P4502C9 (CYP2C9), vitamin K epoxide reductase (VKORC1) and factor VII genotypes, age, body mass index (BMI), international normalized ratio (INR) and other individual patient characteristics on warfarin dose requirements in an adult Turkish population.
Methods: Blood samples were collected from 101 Turkish patients. Genetic analyses for CYP2C9*2 and *3, VKORC1 -1639 G>A and factor VII -401 G>T polymorphisms were performed. Age, INR, BMI values and other individual patient characteristics were also recorded.
Results: The mean daily warfarin dosage was significantly higher in patients with the CYP2C9*1/*1 genotype than in the CYP2C9*2/*2 and CYP2C9*1/*3 groups (p ≤ 0.05). With respect to the VKORC1 -1639 G>A polymorphism, the mean warfarin daily dose requirement was higher in the wild type group compared to the heterozygous group (p≤0.001). The mean daily dose requirement for patients with the GG form of factor VII was significantly higher than that of patients with the TT genotype (p ≤ 0.05). Age, gender, BMI, INR had no statistically significant correlation with warfarin dose (p ≥ 0.05).
Conclusions: Polymorphisms in CYP2C9, VKORC1 and factor VIIdid partiallyaffectdaily warfarin dose requirements, while age, gender, BMI and INR do not. However, further case-control studies with a larger study size and different genetic loci are needed to confirm our study.
Key words: Warfarin, CYP2C9, VKORC1, factor VII, polymorphism
Corresponding author: Yildirim Engin, Department of Pharmacology, Medical Faculty, Eskisehir Osmangazi University, 26480, Eskisehir, Turkey, tel: +905055413876, fax: +902222393772, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
Vitamin K antagonists are effective at preventing cardioembolic stroke, myocardial infarction and venous thrombosis, but they double the incidence of hemorrhage. The hemorrhage risk is greatest during the first weeks to months of therapy1.
Oral administration of anticoagulants in the prevention and treatment of thromboembolic disorders is the most commonly used method of treatment in clinical practice. Population differences in drug-metabolizing enzymes are important for modifying therapeutic doses and safety profiles of drugs among populations. Pharmacogenetic differences are regarded as an important factor to consider in the treatment of diseases and conditions with personalized medicine. Warfarin is the most widely prescribed oral anticoagulant in the world1-7. Clinically available warfarin consists of a racemic mixture of two active optical isomers, the (R)- and (S)- isoforms. Their pharmacokinetic properties differ considerably because they are cleared via different pathways. (S)- warfarin has about a 1.5-fold greater systemic clearance and is 5-fold more potent than the (R)- isoform1,4,8,9.
However, warfarin has a narrow therapeutic range and a given dose may result in a large inter-individual variation. An insufficient dose may fail to prevent thromboembolism, while an overdose increases the risk of bleeding. The degree of anticoagulation achieved in each patient is measured by obtaining the prothrombin time (PT) and is expressed as the international normalized ratio (INR)10.
The relationship between the dose prescribed and the individual response is regulated by genetic and environmental factors. Warfarin dose requirements are affected by many factors, such as gender, age, diet, race, concomitant medication and genetic factors. Pharmacogenomics, the study of the interaction of an individual's genotype and drug response, can help to optimize drug efficacy while minimizing adverse drug reactions4,5,10.
In particular, molecular analysis of two genes that encode the enzyme responsible for the warfarin (S)-isoform catabolism (CYP2C9) and the target enzyme vitamin K epoxide reductase complex 1 (VKORC1) strongly suggests that their genetic variations greatly affect the individual response to oral anticoagulants. Genotype-based modeling explained a large portion of the dose variation3,4,6,10. Possession of the CYP2C9*2 or CYP2C9*3 allele variants, which result in decreased enzyme activity, is associated with a significant decrease in the mean warfarin dose. Several single nucleotide polymorphisms (SNPs) in VKORC1 are associated with warfarin dose across the normal dose range. Haplotypes based on these SNPs explain a large fraction of the inter-individual variation in the warfarin dose and VKORC1 variation has an approximately three-fold greater effect than CYP2C9. Additionally, polymorphisms within the genes encoding transporters, receptors and vitamin K-dependent clotting factors (II, VII, IX, X) and the anticoagulant proteins C and S have been suggested to predict sensitivity to warfarin therapy2,5,6,10,11. Factor VII (FVII) is a vitamin K-dependent inactive protease, which is converted to its active form on contact with the tissue factor and then activates factor X and factor IX. Functional genetic polymorphisms in the gene encoding FVII could modify the response to warfarin during the first days of treatment6,12.
Algorithms incorporating genetic (CYP2C9 and VKORC1), demographic and clinical factors to estimate the warfarin dosage, could potentially minimize the risk of over dose during warfarin induction10. Until now, there was no accurate way to estimate the dose to reduce the risk of hemorrhage1.
It appears that it would be useful to increase the number of candidate genes involved in the metabolism of oral anticoagulants; pharmacogenomic profiling according to these genes could be a powerful, easily adoptable tool to improve oral anticoagulant therapy management4.
In this study, we evaluated the effects of CYP2C9, VKORC1 and factor VII polymorphisms and other patient characteristics on the warfarin dose required to maintain a therapeutic INR (2.0-3.0) in Turkish patients.
The Human Research Committee at Eskisehir Osmangazi University approved this study (28.07.2009/309) and all participants provided written informed consent. Participants requiring warfarin therapy were recruited from the outpatient clinic of the Cardiology Department of Eskisehir Osmangazi University Faculty of Medicine. In total, 101 consecutive patients fulfilled the inclusion criteria for this study, which included 1) use of warfarin for at least one month and 2) a stable INR of 2.0-3.0 since joining the clinic. Patients were still eligible for this study if there were transient alterations in warfarin requirements attributable to acute illness or medication changes, provided that they returned to their usual warfarin dose when the illness had resolved or the medication was discontinued. Patients with higher warfarin target INRs were included if a stable dose of warfarin maintained their INR between 2.0 and 3.0 for at least one month. The results of standard biochemical tests, age, height, body weight, gender, body mass index (BMI), indication for warfarin use, daily prescribed warfarin dose, comorbidity and concomitant medications were recorded on the study form. All subjects participating in this study were Turkish.
The exclusion criteria included non-genetic explanations for altered warfarin requirements, such as hepatic dysfunction, cancer, liver disease, renal disease, advanced heart failure, hypothyroidism, hyperthyroidism, diseases with bleeding tendency, alcohol consumption (>7 drinks/week), underweight (BMI < 18 kg/m2), concurrent rifampin or herbal use, a diet rich in green leafy vegetables including broccoli, spinach, cauliflower (> 2 servings/day), age > 80 years and use of > 13 acetaminophen (325 mg) tablets/week.
Genotyping was performed by experimenters blinded to the associated clinical information. We collected 10 mL blood in EDTA from each participant. Genomic DNA was isolated from blood samples. Genotyping of CYP2C9*2 (rs1799853), (Arg144Cys), CYP2C9*3 (rs1057910) (Ile359Leu), VKORC1 -1639 G>A (rs9923231) and factor VII -401 G>T (rs3093229) alleles were performed according to previously described methods2,13,14.
Subjects with either of the two non-functional alleles (*2 and *3) of CYP2C9 were defined as poor metabolizers (PMs). Homozygotes for the *1 allele were defined as homozygous extensive metabolizers (hmEms) and heterozygotes for the mutant allele were defined as heterozygous extensive metabolizers (htEms). For VKORC1 -1639 G>A, subjects with GG, GA and AA alleles were defined as wild type, heterozygous and homozygous, respectively. For factor VII -401 G>T, subjects with GG, GT and TT alleles were defined as wild type, heterozygous and homozygous, respectively.
All data analyses were performed in IBM Statistical Package for the Social Sciences (SPSS) version 20 (SPSS Inc., Chicago, IL, USA). The properties of our data distribution were investigated using the Kolmogorov-Smirnov and Shapiro-Wilk tests. In each group, all continuous variables (age, BMI, dose and INR) were compared across genotypes using a one-way ANOVA for normally distributed variables and a Kruskal-Wallis test for non-normally distributed variables. A Kolmogorov-Smirnov normality test was used to determine the normally distributed variables. Chi-square analyses were used for nominal variables. The effects of the tested parameters on warfarin dose were assessed using simple and multiple linear regression analysis. The results were evaluated in 95 % confidence intervals and p ≤ 0.05 was accepted as statistically significant.
A total of 101 warfarin-treated patients, including 60 females (59.41%) and 41 males (40.59%), were accepted for the study. The age range was 26-80 years, with a mean age of 63.74 ± 11.43 years. The median maintenance daily dose of warfarin was 4.07 mg/day. Average warfarin dose requirements ranged from 1.13 to 7.86 mg/day. Characteristics of the study group are shown in Table 1a. Concomitant interacting medications and comorbidity are shown in Table 1b.
1. The mean daily warfarin dosage was significantly higher in patients with the CYP2C9*1/*1 genotype [median: 3.93 (2.5-5.36) mg] than in patients with the CYP2C9*2*2 genotype [median: 2.5 (1.88-3.12) mg] (p<0.05). There was no statistically significant difference between the CYP2C9*1/*1 group and the CYP2C9*1/*2 group [3.93 (3.21-5) mg]. Additionally, there was no statistically significant difference between the CYP2C9*1/*2 group and the CYP2C9*2*2 group (p > 0.05) (Table 2).
2. The mean daily warfarin dosage was significantly higher in patients with the CYP2C9*1/*1 genotype [5 (3.93-5.71) mg] than in patients with the CYP2C9*1/*3 genotype [3.21 (2.5-5) mg] (p<0.05). There was no statistically significant difference between the CYP2C9*1/*1 group and the CYP2C9*3/*3 group [3.93 (2.85-5) mg]. Additionally, there was no statistically significant difference between the CYP2C9*1/*3 group and the CYP2C9*3/*3 group (p > 0.05) (Table 3).
3. The mean daily dose of the patients with the VKORC1 -1639 GG genotype [5 (3.93-6.07) mg] was significantly higher than that of the patients with the VKORC1 -1639 GA [3.21 (2.5-4.82) mg] genotype (p<0.001). There was no statistically significant difference between the mean daily doses in patients with the VKORC1 -1639 GA genotype and patients with the VKORC1 -1639 AA genotype (p > 0.05) (Table 4).
4. The mean daily dose of the patients with the factor VII -401 GG genotype [5 (3.93-6.96) mg] was significantly higher than that of the patients with the factor VII -401 TT genotype [3.57 (2.5-5) mg] (p<0.05). There was no statistically significant difference between the mean daily doses in patients with the factor VII -401 GG genotype and patients with the factor VII -401 GT genotype (p > 0.05) (Table 5).
Age, gender, BMI and INR parameters showed no statistically significant difference (p>0.05) across the CYP2C9*2, CYP2C9*3, VKORC1 -1639 G>A and factor VII -401 G>T genotype groups (Tables 2-6). A multivariate regression model including age (R2= 1.4 %), BMI (R2= 1 %), INR (R2= 2 %), CYP2C9*2 (R2= 0.2 %), CYP2C9*3 (R2= 1.1 %), VKORC1 (R2= 14.9 %) and factor VII (R2= 2.2 %) and used to estimate warfarin dose (R2= 18.2 %) is shown in Table 7.
In the present study, we investigated genetic [CYP2C9*2, CYP2C9*3, VKORC1 -1639G>A and factor VII -401G>T polymorphisms] and non-genetic predictors of warfarin dose requirements in 101 patients from Turkey.
Warfarin is a commonly used drug, but it is difficult to manage clinically. Warfarin therapy, especially at initiation, is particularly problematic. There is greater than 10-fold inter-individual variability in the dose required to attain a therapeutic response. The inter-individual variability in response to this drug requires patients to routinely visit coagulation clinics and undergo repeated INR measurements4,7,10,15.
Genetic polymorphisms in the genes encoding for VKORC1 and CYP2C9 have been shown to correlate with the response to warfarin during both induction and maintenance6,16-19. Many large and retrospective clinical studies of various populations have found that the CYP2C9 (*2,*3), VKORC1 -1639 G>A and factor VII -401 G> T polymorphisms and their allelic variants are important in determining the warfarin dose requirement5,10,20-28. Recent genome-wide association studies have confirmed known polymorphisms in CYP2C9 and VKORC1 as the primary genetic determinants of the stabilized warfarin dose29.
On the other hand, numerous clinical factors, including age, race, weight, height, smoking status and medication use, have been associated with variability in maintenance warfarin dose requirements30-32.
Our study assessed the contributions of the CYP2C9, VKORC1 and factor VII genotypes to inter-individual variability in the Turkish population. Determinable demographic factors such as age, gender and BMI, which have been considered as contributing covariates, along with INR parameters, were found not to be associated with warfarin dose requirements in our study. Based on these results, we conclude that patient age, gender, BMI, INR and genetic polymorphism of CYP2C9, VKORC1 and factor VII account for approximately 18.2% of the variability in the daily warfarin dose requirement, though the contributions of age, gender, BMI and INR were not statistically significant.
Thus, our analysis revealed that despite the results of other studies20,22,27,28, genetic polymorphisms in the genes encoding CYP2C9, VKORC1 and factor VII were partially associated with warfarin dose requirement.
We confirmed that the presence of the CYP2C9*2 polymorphism can explain only approximately 0.2% of the inter-individual variability in the warfarin dose requirement in our model, while CYP2C9*3 explains only1.1%. Furthermore, we found that the daily warfarin doses of patients with the CYP2C9*1/*1 genotype were only significantly higher than those of patients with the CYP2C9*2/*2 or CYP2C9*1/*3 genotypes (p < 0.05).
Thus far, more than 50 variant alleles of CYP2C9 have been identified. R- and S-enantiomers of warfarin are metabolized via different pathways. While the S-isoform is mainly metabolized by CYP2C9, the R-isoform is metabolized by the CYP3A4, 1A2 and 1A1 enzymes. Genetic variations in these regions may lead to inter-individual differences in the effective warfarin dose4,10,21,28,33,34.
Our results are similar to those of Miao et al, who concluded that the CYP2C9*3 allele can only explain approximately 1.7% of the inter-individual variability and those of Suriapranata et al, who revealed that CYP2C9*3 was not significantly associated with warfarin dose requirement. Additionally, our study is similar to previous studies demonstrating that CYP2C9 allelic variants fail to account for changes in the dose-anticoagulant effect of warfarin and that other factors may be involved29,35-37.
We confirmed that the VKORC1-1639 G>A polymorphismcan only explain approximately 14.9% of the inter-individual variability in the warfarin dose requirement; as such, it made the largest contribution to estimations of warfarin dose in our study. The daily doses for patients with the VKORC1 -1639 GG genotype were only significantly higher than those of patients with the VKORC1 -1639 GA genotype.
VKORC1 is the target of coumarin anticoagulants. Various mutations in the VKORC1 gene have been found in warfarin-resistant patients22,38. Reieder et al, previously reported that VKORC1 haplotypes can be used to classify patients into low, medium and high warfarin dose groups and that differences in VKORC1 may explain the variation in warfarin dose requirements between the patients39. Although VKORC1 -1639 G>A explains the highest percentage of variation in the warfarin dose, other SNPs may have independent effects and may explain additional variation that is not attributed to -1639G>A. It is necessary to note that different VKORC1 genotypes in various populations result in different warfarin-dosing patterns in these populations. It has been previously reported that ethnic differences in the VKORC1 gene may play an important role in warfarin sensitivity 4,23,26,38. On the other hand, most polymorphisms in the VKORC1 gene have been found to be associated with a normal warfarin dose range10.
We confirmed that the factor VII -401 G>T polymorphism only explains approximately 2.2% of the inter-individual variability in the warfarin dose requirement. The daily warfarin doses of the patients with the factor VII -401 GG genotype were only significantly higher than those of the patients with the factor VII -401 TT genotype. The factor VII gene is located on chromosome 13 and five polymorphic sites have been identified to date12. It has been proposed that the circulating FVII plasma levels are genetically determined to 30 %. The promoter variant at nt -402 has been associated with elevated plasma FVII levels, whereas the R353Q (rs6046) and -323Ins10 (rs36208070) polymorphisms have been associated with a 20% to 25% reduction in FVII plasma levels. There are a number of other factors that influence FVIIc (coagulant activity) levels. Age, body mass index (BMI) and, in women, the use of oral contraceptives and onset of menopause are associated with higher levels. In the general population, some 47% of the total variance in FVIIc levels is attributable to the variability between individuals12,21,40-42. As reported previously, the relationship between INR and the plasma concentrations of the vitamin K-dependent factors II and VII may significantly differ during warfarin induction and maintenance. Thus, even when identical INR values are measured, the plasma concentration of these coagulation factors may greatly vary between induction and stable anticoagulation within the same patient. Thus, it is possible that variability in the FVII concentration, similar to what may be expected among different R353Q genotype carriers, is not a powerful determinant of INR variability during stable anticoagulation6. Our data confirm these earlier findings. In this study, we used patients with stable INR values.
Many other factors are important for determining a safe and effective dose of warfarin at the beginning of therapy10. Drugs, diet, various diseases, ethnicity and environmental factors can change the pharmacokinetics of warfarin. Certain drugs (e.g. phenylbutazone, sulfinpyrazone, metronidazole, trimethoprim sulfamethoxazole, and amiodarone) may affect the oxidative metabolism of warfarin4,31,32,43. Others decrease the plasma levels of warfarin by reducing its absorption (e.g., cholestyramine) or increasing its hepatic clearance (e.g. barbiturates, rifampicin and carbamazepine). As a rule, if a patient receives a large number of medications, it is difficult to control anticoagulation. Long-term alcohol intake may increase the clearance of warfarin. Dietary vitamin K decreases the anticoagulant effects of warfarin, as does consumption of a large amount of green vegetables. Often, various foods and herbal medications, such as avocado and gingko, affect the stability of warfarin and may reduce the need for the dose of warfarin4,10,43.
Increased patient age may lead to a higher sensitivity to warfarin because there is a negative correlation between age and warfarin clearance. At the same time, as a result of age-related decreases in liver mass, the liver content of vitamin K epoxide reductase is reduced, causing increased sensitivity to warfarin4,24,26. To minimize these problems, which are often observed in elderly patients with age-related liver and kidney dysfunction, we tried to enroll patients with normal liver and renal function.
According to Suriapranata et al (2011), age, body weight, height and genetic variants of CYP2C9 and VKORC1 can explain approximately 15.4% of the variability in the daily warfarin dose requirement28. Other studies have demonstrated that genetic polymorphisms lead to inter-individual differences in the effective warfarin dose; the data obtained to date show that CYP2C9 polymorphisms explain 5-22% and VKORC1 polymorphisms 6-37% of the warfarin dose variability4,42,44. When taken together with age, gender, body weight, height and clinical factors such as other drug treatments and therapeutic indications, 33-57% of the dose of warfarin can be estimated in advance4,10,31.
In addition, the contribution of ethnicity is an important factor in determining the effective maintenance dose of warfarin. For example, previous studies have demonstrated that in Asian patients, the maintenance dose of warfarin was approximately 30-40% less than in Caucasians; this difference has been found to be connected to genetic variants of CYP2C9 and VKORC19,32,35. Also previous Clarification of Optimal Anticoagulation through Genetics (COAG) trial study showed that among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group32. The comparison of the allelic frequencies of CYP2C9*2,*3 and VKORC1 -1639 G>A across four different populations (Turkish, Asian, African-American and Caucasian) revealed that the allelic frequencies of these two genes in Turkish populations are very different from those in African-Americans and Asians but relatively close to those reported for Caucasians11. Turkish society is composed of people of many different ethnic backgrounds. In our study, due to a lack of sufficient and satisfactory information, the genetic origins of our patients could not be determined.
Based on the currently available clinical and pharmacogenetic information concerning warfarin, the source(s) of 40% of the variation in the warfarin dose requirement is still unknown10. It is likely that the inter-individual variability in warfarin-dose requirements is due at least in part to additional genetic factors, including polymorphisms in genes encoding apolipoprotein E, multidrug resistance 1 (MDR1), vitamin K-dependent clotting factors and possibly additional components of the vitamin K epoxide reductase complex, such as gamma glutamyl carboxylase (GGCX), microsomal epoxide hydrolase1 (mEH1), and calumenin (CALU)4,10,24,38. Cytochrome P4504F2 (CYP4F2) activity was recently found to be associated with warfarin dose23,24. Thus, the inter-individual variability in warfarin dose requirements is due at least in part to additional genetic and non-genetic factors that need further investigation. For a more complete survey of the genetic background for enzymes affecting individual warfarin pharmacokinetics and/or pharmacodynamics, full genotyping of the current list of SNPs is required.
In summary, the results of the present study show that a warfarin dosing regimen formulated using clinical data (age, dose, BMI, and INR) and pharmacogenetic information concerning the CYP2C9, VKORC1 and factor VII genotypes could benefit patients treated with warfarin. It is important that prospective clinical studies assess dosing algorithms that incorporate the contributions of age, genotype and weight, to allow for the individualization of warfarin dose during both the initiation and maintenance stages of therapy. On the other hand, polymorphisms in other genes that may help determine the dose of warfarin should be investigated. Ethnic differences should also be considered. Treatment algorithms that incorporate pharmacogenomic data must be evaluated prospectively in a randomized controlled clinical trial before being integrated into routine clinical practice. These new algorithms could help physicians to determine more accurate dosages for the patients and reduce the chances of bleeding during warfarin treatment.
The authors report no conflict of interest.
This work was funded by the Eskisehir Osmangazi University Scientific Research Projects Commission (Project number: 200911013).
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11. Oner Ozgon, G, Langaee TY, Feng H, Buyru N, Ulutin T, Hatemi AC, et al. VKORC1 and CYP2C9 polymorphisms are associated with warfarin dose requirements in Turkish patients. Eur J Clin Pharmacol. 2008; 64: 889-894.
12. Greisenegger S, Weber M, Funk M, Endler G, Lang W, Ferrari J, et al. Polymorphisms in the coagulation factor VII gene and risk of primary intracerebral hemorrhage. Eur J Neurol. 2007; 14: 1098-1101.
13. van 't Hooft FM, Silveira A, Tornvall P, Iliadou A, Ehrenborg E, Eriksson P, et al. Two common functional polymorphisms in the promoter region of the coagulation factor VII gene determining plasma factor VII activity and mass concentration. Blood. 1999; 93: 3432-3441.
14. Joffe HV, Xu R, Johnson FB, Longtine J, Kucher N, Goldhaber SZ. Warfarin dosing and cytochrome P450 2C9 polymorphisms. Thromb Haemost. 2004; 91: 1123-1128.
15. Caldwell MD, Berg RL, Zhang KQ, Glurich I, Schmelzer JR, Yale SH, et al. Evaluation of genetic factors for warfarin dose prediction. Clin Med Res. 2007; 5: 8-16.
16. Li T, Lange LA, Li X, Susswein L, Bryant B, Malone R, et al. Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation. J Med Genet. 2006; 43: 740-744.
17. Schelleman H, Chen J, Chen Z, Christie J, Newcomb CW, Brensinger CM, et al. Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans. Clin Pharmacol Ther. 2008; 84: 332-339.
18. Schwarz UI, Ritchie MD, Bradford Y, Li C, Dudek SM, Frye-Anderson A, et al. Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med. 2008; 358: 999-1008.
19. Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, et al; EU-PACT Group. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013; 369: 2294-2303.
20. D'Ambrosio RL, D'Andrea G, Cappucci F, Chetta M Di Perna P, Brancaccio V, et al. Polymorphisms in factor II and factor VII genes modulate oral anticoagulation with warfarin. Haematologica. 2004; 89: 1510-1516.
21. Shikata E, Ieiri I, Ishiguro S, Aono H, Inoue K, Koide T, et al. Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gama-glutamyl carboxylase) gene variants with warfarin sensitivity. Blood. 2004; 103: 2630-2635.
22. Yuan HY, Chen JJ, Lee MT, Wung JC, Chen YF, Charng MJ, et al. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet. 2005; 14: 1745-1751.
23. Daly AK. Pharmacogenomics of anticoagulants: steps toward personal dosage. Genome Med. 2009; 1: 10.
24. Jonas DE, McLeod HL. Genetic and clinical factors relating to warfarin dosing. Trends Pharmacol Sci. 2009; 30: 375-386.
25. International Warfarin Pharmacogenetics Consortium, Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009; 360: 753-764.
26. Gu Q, Kong Y, Schneede J, Xiao YB, Chen L, Zhong QJ, et al. VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China. Eur J Clin Pharmacol. 2010; 66: 1217-1227.
27. Eroğlu A, Oztürk A, Akar N. Asssociation between the -402GA, -401GT, and -323ins10-bp polymorphisms of factor VII gene and breast cancer. Breast Cancer. 2011; 18: 282-285.
28. Tatarūnas V, Lesauskaitė V, Veikutienė A, Jakuška P, Benetis R. The influence of CYP2C9 and VKORC1 gene polymorphisms on optimal warfarin doses after heart valve replacement. Medicina (Kaunas). 2011; 47: 25-30.
29. Suriapranata IM, Tjong WY, Wang T, Utama A, Raharjo SB, Yuniadi Y, et al. Genetic factors associated with patient-specific warfarin dose in ethnic Indonesians. BMC Med Genet. 2011; 12: 80.
30. Gage BF, Eby C, Johnson JA, Deych E, Rieder MJ, Ridker PM, et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008; 84: 326-331.
31. Sinxadi P, Blockman M. Warfarin resistance. Cardiovasc J Afr. 2008; 19: 215-217.
32. Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, et al. A Pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013; 369: 2283-2293.
33. Lefferts JA, Schwab MC, Dandamudi UB, Lee HK, Lewis LD, Tsongalis GJ. Warfarin genotyping using three different platforms. Am J Transl Res. 2010; 2: 441-446.
34. Lenzini P, Wadelius M, Kimmel S, Anderson JL, Jorgensen AL, Pirmohamed M, et al. Integration of genetic, clinical, and INR data to refine warfarin dosing. Clin Pharmacol Ther. 2010; 87: 572-578.
35. Miao L, Yang J, Huang C, Shen Z. Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients. Eur J Clin Pharmacol. 2007; 63: 1135-1141.
36. Yang L, Ge W, Yu F, Zhu H. Impact of VKORC1 gene polymorphism on interindividual and interethnic warfarin dosage requirement--a systematic review and meta analysis. Thromb Res. 2010; 125: e159-e166.
37. Shahin MH, Khalifae SI, Gong Y, Hammad LN, Sallam MT, El Shafey M, et al. Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients. Pharmacogenet Genomics. 2011; 21: 130-135.
38. Wadelius M, Chen LY, Eriksson N, Bumpstead S, Ghori J, Wadelius C, et al. Association of warfarin dose with genes involved in its action and metabolism. Hum Genet. 2007; 121: 23-34.
39. Rieder MJ, Reiner AP, Gage BF, Nickerson DA, Eby CS, McLeod HL, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Eng J Med. 2005; 352: 2285-2293.
40. Green F, Kelleher C, Wilkes H, Temple A, Meade T, Humphries S. A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterioscler Thromb. 1991; 11: 540-546.
41. Fuchshuber-Moraes M, Perini JA, Rosskopf D, Suarez-Kurtz G. Exploring warfarin pharmacogenomics with the ex-treme-discordant-phenotype methodology: impact of FVII polymorphisms on stable anticoagulation with warfarin. Eur J Clin Pharmacol. 2009; 65: 789-793.
42. Mo X, Hao Y, Yang X, Chen S, Lu X, Gu D. Association between polymorphisms in the coagulation factor VII gene and coronary heart disease risk in different ethnicities: a meta-analysis. BMC Med Genet. 2011; 12: 107.
43. Nutescu E, Chuatrisorn I, Hellenbart E. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update. J Thromb Thrombolysis. 2011; 31: 326-343.
44. Lubitz SA, Scott SA, Rothlauf EB, Agarwal A, Peter I, Doheny D, et al. Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population. J Thromb Haemost. 2010; 8: 1018-1026.


text:
Q: How do I use homebrew less instead of system less? I've installed less via
homebrew install less

but less starts the system version of less, not the one installed via homebrew. which less shows:
$ which -a less
/usr/local/bin/less
/usr/bin/less

where /usr/local/bin/less is a symlink to ../Cellar/less/487/bin/less (homebrew less)
and /usr/bin/less  is the system less. echo $LESS returns nothing. How can I start homebrew less instead of system less by default?

A: If homebrew is correctly installed /usr/local/bin/ is checked before /usr/bin/. Check this with echo $PATH, this will show you the path's the OS is trying to find the command you entered and it is trying them in the order that is shown.
A little fancier
using the bash shell:
echo $PATH | awk '{ n = split($0, paths, ":"); for (i=0; ++i <= n;) print i, paths[i] }'

(using the fish shell):
echo $PATH | awk '{ n = split($0, paths, " "); for (i=0; ++i <= n;) print i, paths[i] }'

This will show an numbered list of the path's tried. Mine shows
1 /Users/peter/.gem/ruby/2.0.0/bin
2 /usr/local/sbin
3 /usr/local/bin
4 /usr/bin
5 /bin
6 /usr/sbin
7 /sbin
8 /Library/TeX/texbin

The system will traverse the directories in the above order looking for commands, in your case less. If it's not in the first one, it will try the next one until it runs out of options and throw up an error.
So if your echo $PATH shows similar results as mine you are using the homebrew version of less.

A: This might be due to bash's hash table of commands in PATH still using the old value. Remove the hash of less, or clear the hash, so that bash re-searches PATH:
hash -d less
# or, hash -r

You can also manually add a path to the table:
hash -p /usr/local/bin/less less

From the Bash manual (emphasis mine):

If the name is neither a shell function nor a builtin, and contains no
  slashes, Bash searches each element of $PATH for a directory
  containing an executable file by that name. Bash uses a hash table to
  remember the full pathnames of executable files to avoid multiple PATH
  searches (see the description of hash in Bourne Shell Builtins). A
  full search of the directories in $PATH is performed only if the
  command is not found in the hash table.

A: I restarted the shell, and this fixed the problem. Maybe a caching issue.
If this doesn't help, make sure that /opt/homebrew/bin appeares above /usr/bin when running
echo $PATH | tr ':' '\n' | nl`

redpajama_set_name: RedPajamaStackExchange


Do you remember how you used to shop? Going to the mall or grocery store to pick up a few items. Now, all that has changed. You probably think about going shopping in a whole new way.
The best way to understand the change in consumer behavior is to examine the ways in which marketers track these behaviors. There are several ways to gather this data and use it to better engage with your target audience. Examining your target customer's digital footprint will enable you to glean more information about who they are, what they like, and what challenges exist.
When consumers think of a digital footprint they often think about the things they put on social media and how that contributes to their perception. These things are the social media updates, the blogs we write, videos and streams we create. Every day, hundreds of millions of people take photos, make videos and send texts. As consumers create and engage with this content they create massive amounts of data that can be tracked.
Clickjacking – when an attacker uses multiple transparent or opaque layers to trick a user into clicking on a button or link on another page when they were intending to click on the top level page.
Flash cookies – Like regular cookies, Flash cookies contain information about when you visited the site and may contain tracking and settings information.
Web Cookies -small pieces of data sent from a website and stored on the user's computer by the user's web browser while the user is browsing.
Built Into Apps – These tracking technologies include location services, geofencing, etc.
This data allows brands to collect data on consumer preferences, purchases, and trends. Insurance companies may use a consumer's digital footprint to determine the level of risk when issuing an insurance policy.
Bottomline, a consumer's digital footprint can be used to determine the value that consumer brings to the brand.
Your brand's digital footprint is a visual map of how and where a brand lives online, where target groups spend time online, and how these properties are or are not connected via brand behavior and communication.
Similar to how we examine a consumer's digital footprint to determine the value they bring to us, consumers are looking at our brand's digital footprint to see what value we bring to them.
Our Hub – This is where consumers find your brand. It could be your website, microsite, or landing page. It is essentially a place in which all your marketing communications is connected.
Owned Platforms – This is where you have a strong position in the digital space that you can leverage for the advancement of your brand. These owned platforms will certainly shape consumer perception.
Paid Platforms – This is where you purchase impressions or interactions online. Consumers examine the type of paid engagements (e.g. digital ads) your brand has developed. Remember, it's not the message necessarily. Consumer perception is also shaped by the medium, context, and timing of your paid engagements.
Earned Media – This is where other consumers are talking about your brand. Earned media can come from current customers or influencers. This chatter can take place as status updates, blog posts, videos, shares or direct messages (think 'dark social').
Brand Health – This will give consumers an indication of how active your brand is in the digital space. Most consumers believe a healthy and thriving digital brand consists of one that is actively engaging with followers, publishing and sharing content, and not fully automating communication.
Overall, it is important to understand that consumers are becoming savvier. They are quick to decode our marketing messages. They understand the various tactics that are used to convert them. And they probably are more familiar with online marketing than ever before.
Which is why they examine our brand's digital footprint to determine the value we may bring before deciding to work with us. As digital branders, it is important to understand how our consumer's thoughts and perceptions have changed so we can adjust our tactics accordingly.
It starts with meeting the customer where they are instead of expecting this to be aligned with our marketing funnel and persona buckets.
If you're a marketer, this traditional marketing funnel may be a familiar sight. You may have set up a digital marketing campaign that addresses each phase of the funnel: awareness, consideration, decision, and retention.
However, you may have also noticed that this linear funnel is starting to lose effectiveness. As consumers become savvier they start to circumvent any funnel you may build.
For instance, a significant number of consumers understand that they will be put in a funnel after giving their contact information. This can happen when registering for an event, signing up for a service, or when a downloading a lead magnet. This is why it is critical to establish a strong digital brand.
Many consumers will get their information from sources outside of your pre-defined funnel. Which is why many of the traditional marketing funnels are broken.
The modern funnel resembles the chart below and accurately reflects the reality of your customer's path to purchase.
The first customer interaction may not be sparked by your awareness campaign. The first time they opt into your marketing communication may be when they are trying to decide to do business with you. You may even be on their 'short list' of solutions. It is difficult to know what previous experience these people have with your brand and what type of content is most relevant to their unique situation.
This is why your branding initiatives need to be more flexible today than in the past. As consumer behavior and technology change, so must your marketing initiatives. That's what this post is all about…finding your consumer's desired path to purchase. But, before we can begin, we must understand the role that digital branding plays in our customer's path to purchase.
You know that cliché saying, "We interrupt your programming to bring you a word from our sponsor?" Well, that's traditional marketing and advertising in a nutshell. It comes along and interrupts whatever you're doing – listening to a song on the radio, watching a T.V. show.
This is why you don't want to use traditional marketing tactics on a regular basis. You make your reader, customer, or client stop what they're doing and focus on your message. Let's put this in a different context: When you talk with people, do you interrupt them mid-sentence? Probably not (at least, you shouldn't). So why is it ok to do this to your potential customers when they're online? It's not.
DBI TIP: Instead of interrupting your customer's or reader's experience, try being part of their experience. Or better yet, create that experience yourself.
As I mentioned earlier, we use consumer data to create profiles of our target audience. Conversely, our consumers do the same with our brands.
There is no sophisticated technology needed to examine our digital brands. Consumers are referencing the multitude of marketing messages they receive throughout the day. That's it! They are becoming savvier by the minute.
That's why enhancing your digital brand should be a priority.
You probably are aware of various digital marketing tactics such as social media marketing, content marketing, and SEO but digital branding is the whole puzzle. You may read other blogs and receive information about tactics but knowing where to start can be overwhelming.
How can you put it all together? It's like assembling a big puzzle.
Each of the individual tactics is an important piece, but Digital branding is the WHOLE puzzle and it plays a significant role in your consumer's path to purchase.
As great digital branders know, until you truly understand your customers, you'll never be able to market to them effectively. Consumers are referencing the multitude of marketing messages they receive throughout the day and are becoming savvier by the minute.
Similar to how we examine a consumer's digital footprint to determine the value they bring to us, consumers are looking at our brand's digital footprint to see what value we bring to them. This means finding your consumer's desired path to purchase is critical when turning your audience into customers.


text:
<!doctype html>

    <meta charset="utf-8">
    <title>Redirecting to Land Grab...</title>
    <meta http-equiv="refresh" content="0; url=https://FlyingJester.github.io/LandGrab/play">

Redirecting to Land Grab...

redpajama_set_name: RedPajamaGithub


New Zealand's ice hockey team was on the receiving end of a world record 58-0 shellacking by Australia at the 1987 world championships in Perth. Sports reporter Robert van Royen talked to the former president of New Zealand ice hockey, Graham Glass, who played for the Ice Blacks on that infamous day, about the match and the changes it caused to the game, both in New Zealand and internationally.
The New Zealand Ice Hockey Federation (NZIHF) had only been established about seven months before the official national side travelled to Perth to play in group D of the the 1987 world championships.
Pitted against Australia, Hong Kong and South Korea, New Zealand was making its debut on the international ice hockey scene.
Before 1987, a team from Auckland, which ''thought they were the New Zealand team'', had gone to Australia a couple of times. But it was a club team.
Graham Glass (62), who was 35 and ''long in the tooth'' in 1987, was part of the New Zealand team coached by Bryan Lewthwaite, an expat Canadian and former Gore schoolteacher.
''The team wasn't selected on merit, it was selected regionally,'' Glass said.
''There were representatives from all of the clubs in the South. At the time, in Auckland, they weren't involved with the federation.
Despite no international experience, the team went to Perth full of confidence.
''We had come from the wilderness,'' Glass said.
promptly shot back down to Earth with a 35-2 hammering.
''The funny thing was ... our coach said to us before the game, `I want you guys to go out there and knock these Korean guys around. They are pretty small, knock them around a bit,'.
''So we get out on the ice and the Koreans are all military guys. They were fast and fit; we couldn't even catch them, let alone knock them around,'' Glass said.
The Australian team, if you could call it ''Australian'', was stacked with Canadians and Finnish, who were playing domestically across the ditch.
There ''might have been one or two'' Aussies in the team, but when it came to singing the national anthem, they did not have a clue, Glass said.
Before the puck dropped in the record-breaking game, the New Zealanders thought the Australians feared them.
''Someone had said to us, `The Australian guys were watching you guys practise and they were all standing there with their mouths wide open,','' Glass said.
After the so called ''Australians'' failed to sing their own national anthem, the puck dropped on March 14, 1987, and the New Zealanders had no idea what was about to hit them.
''It's all a bit of a blur, really,'' Glass said.
''I think they scored five or six goals in the first few minutes. Our goalie pulled himself off and another goalie came on. Of course, he had to put up with the rest of the onslaught.
Partway through the game, Australian management called the International Ice Hockey Federation (IIHF) to find out what the record (47 goals) was, then went all out to pursue it.
Glass, who grew up in Albury, South Canterbury, with an ice hockey rink on his family's farm, played on the right wing in the match and cannot remember what was said after the game.
By the time the game was over, New Zealand had conceded 95 goals in its first two games of the championships and was on the wrong side of a record that still stands today.
The next day, the Kiwis had something to smile about after thumping Hong Kong 19-0 to record their maiden win.
However, before the campaign ended five days later, New Zealand was again beaten by South Korea (21-2) and Australia (29-0).
New Zealand finished its campaign with another 19-0 win against Hong Kong to finish third in the group and 27th overall in the world.
It did not take long for the IIHF to change rules around eligibility, after the world championships concluded.
A quick look at Australia's goal tally through six games - 177 for and just six against - and it is pretty obvious something needed to be done.
New rules were introduced to stop players jumping from one country to the other.
Foreign-born players who wanted to represent another country had to officially transfer to their chosen country, and play ice hockey domestically for two years.
Glass gave up playing and moved into an administrative role with NZIHF.
He managed the national side that competed in the world championships in Belgium in 1989New Zealand lost all four of its games against Belgium, Romania, Great Britain and Spain, conceding 96 goals and managing just four of its own in the campaign.
Australia did not fare much better in group C, losing all seven of its games, albeit against some tough opposition like the Netherlands, Yugoslavia, China and Hungary.
After returning home, Glass knew changes needed to be made to make New Zealand more competitive.
''I came back and made a report to the federation and said, `Look, we have got some serious work to do. We need to start working hard on the coaching; we have got to teach kids all the basics from the get go, and in 10 years' time we may be competitive,'.
''And that sort of happened. Not because of my recommendation, but gradually over the years,'' he said.
Glass became president of NZIHF in 1999, a position he held for 10 years.
Shortly afterwards, the IIHF realised it needed to start promoting the game and boosting it in countries like New Zealand.
It set up a programme which saw coaching clinics set up around the world.
''The IIHF came up with a learn-to-play programme for kids and really started getting it going. We started pushing that side of it and it's started to pay off,'' Glass said.
The launch of the national league in 2005 was also an important step to improve ice hockey in the country.
''That was the next crucial step. Because that meant the top players were getting more competition at a higher level. Up until then, our national championship was a one-off thing over a weekend,'' Glass said.
Until the Dunedin Thunder formed in 2008 to make it a five-team league, there were two teams in Auckland, one in Christchurch and one in the Southern region.
While the league allows imports, league rules state teams can only dress four imports per game and two assimilated players who intend to play for New Zealand or live here long-term. However, there is no limit to how many imports a team can carry on its roster.
''What's happened over the years is the level has raised, and now the level of the import players is better and it's just bought the whole level up and made our [international] teams much more competitive.
The Ice Blacks beat Australia for the first time at the 2011 Winter Games in Dunedin at the 2011 Winter Games.
New Zealand's women's team, the Ice Fernz, recorded its first ever win against Australia in 2013 with a thrilling 4-3 win.
At the under-20 and under-16 levels, New Zealand has also recorded wins against Australia.
The Ice Blacks, coached by Dunedin Thunder coach Janos Kaszala, now play in division II B in the world championships, and head to South Africa in April for the 2015 campaign.
They finished third in its pool last year to finish 37th overall in the world.
Dunedin will host the world under-20 (division three) championships next week, a tournament New Zealand won in 2008 in Belgrade.
While the sport is well behind the majority of other team sports in the country in terms of playing numbers and world ranking, there is no doubt there has been significant development and improvements since that record-breaking day in 1987.


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League Two side Accrington Stanley have signed winger Brayden Shaw on a short-term deal after a one-month trial.
The 18-year-old signed a six-month professional contract with Bury but was let go after failing to make an appearance for the first team.
"Not breaking into the first team at Bury was disappointing and I am hoping to change that this time," he told the club website.
"Hopefully I can come in and when I get a chance it's up to me."


Plastic bags are harmful to our environment and they kill animals. You may not care about animals, but animals are involved in our ecosystems and when they are gone, we are in trouble. I want people to understand that dolphins, sharks, whales, birds, fish, turtles, etc can inhale or eat plastic bags. This can suffocate them and cause diseases, and we eat what's in the ocean.
A fee will get people to stop using them and therefore their careless acts of polluting will save not only our lives, but animals' lives. It would save us money as well. That's what really gets to people is money, selfish but true. I am hoping that this opens people's eyes to how pollution in our environment can make us sick and cause us harm later on in the future.


For immediate release – New York, NY – On Site Opera will present the World Premiere of Michi Wiancko and Deborah Brevoort's new opera, Murasaki's Moon on May 17, 2019 in The Metropolitan Museum of Art's Astor Court. Made possible by Opera America's 2018 Female Composer Grant, the work was commissioned by On Site Opera, MetLiveArts at The Metropolitan Museum of Art, and the American Lyric Theater.
Murasaki's Moon tells a dramatic tale inspired by the life and work of Lady Murasaki, a member of the Japanese Imperial Court in 11th century Japan. Granddaughter of a writer and daughter of a scholar, Lady Murasaki was well known in her time for her poetry and story-telling, and is historically famous for authoring what many scholars consider the world's first novel, The Tale of Genji.
Throughout the hour-long, one-act Murasaki's Moon, Lady Murasaki attempts to escape the boundaries of her sequestered life as a lady-in-waiting by writing an epic tale of love and freedom. Though her life in the palace helps to shape the world of her novel, the story she creates (and the perils of new found fame) will begin to shape her life in return. Murasaki must contend with a delicate balance between the relationships with the rest of the royal court, the characters she creates, and the far-reaching impact of her writing.
Produced by both On Site Opera and MetLiveArts, Murasaki's Moonwill feature mezzo soprano, Kristen Choi as Lady Murasaki and tenor Andrew Stenson as Genji. Geoffrey McDonald will conduct a unique orchestration of traditional Japanese instruments including koto, percussion, Japanese flutes, and taiko performed by Yoko Reikano Kimura, Satoshi Takeishi, Kaoru Watanabe, and the Aizuri Quartet, respectively. The production also features stage direction by Eric Einhorn, and costume design by Beth Goldenberg.
Murasaki's Moon will be presented in conjunction with The Metropolitan Museum of Art's exhibition, The Tale of Genji: A Japanese Classic Illuminated, with six performances across May 17, 18, and 19. Tickets will go on sale beginning Thursday, December 27. Murasaki's Moon will be performed in English and will be an engaging opera for audiences of all ages.
The commissioning of Michi Wianko for Murasaki's Moon received funding from OPERA America's Opera Grants for Female Composers program, supported by the Virginia B. Toulmin Foundation. Additional funding support is provided by Kara Unterberg.
Michi Wiancko is an internationally-acclaimed,multi-dimensional composer, violinist, and collaborator. Her works have been performed by orchestras, ensembles, and bands around the world. She has been commissioned by the Ecstatic Music Festival, The Saint Paul Chamber Orchestra, Enso Quartet, Sybarite5, String Orchestra of Brooklyn, East Coast Chamber Orchestra, Spokane Symphony, Harvard Chamber Orchestra, Boston Conservatory Orchestra, and The Royal Conservatory of Music in Toronto (among others). She also composes for films, commercials, and for her own band, Kono Michi. Michi has worked closely and performed with musicians across a vast musical spectrum including Missy Mazzoli, Steve Reich, Silk Road Ensemble, Yo-Yo Ma, Emily Wells, Laurie Anderson, Daniel Wohl, Vijay Iyer, International Contemporary Ensemble, and the East Coast Chamber Orchestra, to name a few. She holds a Bachelor of Music in performance from the Cleveland Institute of Music and a Master's degree from Juilliard.
Deborah Brevoort is a playwright and librettist from Alaska who now lives in the New York City area. She was a resident artist in the American Lyric Theater's Composer Librettist Development Program. She is also an alumna of New Dramatists, one of the original company members of Alaska's Perseverance Theatre and a co-founder of Theatre Without Borders. Deborah has written the libretti, books, and lyrics for numerous operas and musicals. She received the Paul Green Award from the National Theatre Conference for her musical book writing and a Performing Artist/Writer Research Fellowship at the American Antiquarian Society in 2012. She has received grants and commissions from the NEA, Rockefeller Foundation, NYFA, CEC Arts Link, New Jersey Arts Council, Alaska State Council on the Arts, Danish American Society, Ludwig Vogelstein Foundation, Brown University, The Harburg Foundation, Banff Playwright's Colony and others. She received the Joe Calloway Award and was a MacDowell Fellow.
On Site Opera produces site-specific operas in non-traditional venues throughout New York City (and beyond!). By staging each opera in an environment specific to the piece, OSO surrounds the audience and artists in the music and drama of the story, amplifying the connection between the world of the opera and the reality of the audience. To date, OSO has produced operas in more than a dozen unique venues, including Ricky Ian Gordon's Morning Star at the Eldridge Street Synagogue, Shostakovich's The Tale of The Silly Baby Mouse using large-scale puppets in performances for families at the Bronx Zoo; Gershwin's Blue Monday in the historic Cotton Club of Harlem; and Rameau's Pygmalion in Madame Tussaud's Wax Museum which explored new technology in opera through the use of Google Glass supertitles.
The groundbreaking live arts series at The Metropolitan Museum of Art explores contemporary performance through the lens of the Museum's exhibitions and unparalleled gallery spaces with singular performances. MetLiveArts invites artists, performers, curators, and thought leaders to explore and collaborate within The Met, leading with new commissions, world premieres, and site-specific durational performances that have been named some of the most "memorable" and "best of" performances in New York City by The New York Times, New Yorker, and Broadway World.
Great Operas Don't Just Happen. American Lyric Theater (ALT) was founded in 2005 by Lawrence Edelson to build a new body of operatic repertoire by nurturing composers and librettists, providing an incubator for their collaborations, and contributing new works to the national canon. Many opera companies commission and perform new works; but ALT is the only company in the United States that offers extensive, full-time mentorship for emerging operatic writers. While the traditional company model focuses on producing a season, ALT's focus is on serving the needs of composers and librettists, developing new works, and collaborating with producing companies to help usher those works into the repertoire. Works by ALT alumni have been produced by diverse companies across the country, including Houston Grand Opera, Opera Philadelphia, Lyric Opera of Chicago, Fort Worth Opera, Utah Opera, Pittsburgh Opera, Opera Saratoga, Prototype Festival, and The Industry LA. In 2012, ALT was the first company dedicated to artist mentorship rather than operatic production to be recognized by OPERA America as a Professional Company Member – a testament to ALT's service to the field. For more information about the Composer Librettist Development Program, Resident Artists, works by CLDP alumni, and upcoming public events at ALT, please visit www.altnyc.org.


text:
Libya And The Scramble For Africa
Christopher Black
North Africa is in turmoil again and the cause of it can be found in the plots of the Europeans and Americans to break nations states into pieces in order to control the oil and gas producing areas of the region and in the plots of against each other. In Libya the CIA trained General Haftar has begun yet another offensive against the weak UN imposed government based in Tripoli, the Government of National Accord, whose forces are weak, which has little support among the people and which has not succeeded in restoring any of the public services, from electric power and water supply to transportation to medical, education, or other administrative systems that existed under the government of the Jamarahiya Republic destroyed by the NATO aggression of 2011. Haftar, who was sent in to Libya in 2011 from Langley, Virginia to join in the US aggression against his own country, is backed by Egypt which wants stability on its border with Libya as well as France, Saudi Arabia and Russia which see him, connected to the CIA as he is, to be the only man with the ability to unite the country under one government, for ill or for good.
Hafttar's offensive against Tripoli which seems to have bogged down or slowed down in the past few days, it is difficult to determine which, also worries the Americans, or so they claim. They express fears that it could lead to a wider conflict, another civil war in Libya. Laughably, the Americans, who destroyed the country, claim that only they can stop the violence and bring heaven to the hell they have created.
The American intrigues are exposed by their official position opposing Haftar's offensive while US forces, whose presence was not widely known, made very public announcements that they were withdrawing in face of Haftar's attacks. This can only be understood as meaning they are getting out of his way so he can conduct his attack. Where they will withdraw to has not been revealed, nor the real reason for their presence in Libya in the first place. The American Africa Command stated,
"Due to increased unrest in Libya, a contingent of U.S. forces supporting U.S. Africa........
© New Eastern Outlook


Anyone in media planning knows Erwin Ephron – the "father of modern media planning." So it is my pleasure to present my video interview with him. An articulate contrarian in the Engagement debate, Erwin suggests hope for the advertising business if it can get back to basics and focus on actual measurements that predict response.
During my visit, Erwin gave me a copy of his book, "Media Planning: From Recency To Engagement." I'm very familiar with much of Erwin's thinking and writing, but I've not read his book. I promise to eventually read it and offer a critique in the next couple months.
Click on the play button below to view my interview with Erwin.


text:
Are Scottish Conservatives now supporting mad Covid science?
According to a reliable source, the above leaflet is being delivered this morning by local Tory Councillor Cameron Rose for Newington Southside Edinburgh.
The Great Barrington Declaration headed up by the most nutty of professors has been widely debunked. For example:
Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:
"The Barrington Declaration is based upon a false premise – that governments and the scientific community wish for extensive lockdowns to continue until a vaccine is available. Lockdowns are only ever used when transmission is high, and now that we have some knowledge about how best to handle new outbreaks, most national and subnational interventions are much 'lighter' than the full suppressions we have seen for example in the UK across the spring of 2020.
"Those behind the Barrington Declaration are advocates of herd immunity within a population. They state that "Those who are not vulnerable should immediately be allowed to resume life as normal", with the idea being that somehow the vulnerable of society will be protected from ensuing transmission of a dangerous virus. It is a very bad idea. We saw that even with intensive lockdowns in place, there was a huge excess death toll, with the elderly bearing the brunt of that, and 20-30% of the UK population would be classed as vulnerable to a severe COVID-19 infection. Around 8% of the UK population has some level of immunity to this novel coronavirus, and that immunity will likely wane over time and be insufficient to prevent a second infection. A strategy for herd immunity would also promote further inequalities across society, for example across the Black, Asian and minority ethnic communities. The declaration also ignores the emerging burdens of 'long COVID'. We know that many people, even younger populations who suffered from an initially mild illness, are suffering from longer-term consequences of a COVID-19 infection.
"Independent SAGE are among the many scientists who have eloquently pointed out1 the many reasons why these initiatives are ultimately harmful and misleading as to the scientific evidence base. There are countries who are managing the pandemic relatively well, including South Korea and New Zealand, and their strategies do not include simply letting the virus run wild whilst hoping that the asthmatic community and the elderly can find somewhere to hide for 12 months. They have a proactive approach to 'test and trace' to reduce the impact of new outbreaks, and good public health messaging from the government to their populations. Ultimately, the Barrington Declaration is based on principles that are dangerous to national and global public health.
1 Independent SAGE report – https://www.independentsage.org/a-deliberate-population-immunity-strategy-before-a-vaccine-why-it-wouldnt-work-and-why-it-shouldnt-be-tried/
For a fuller account of the nuttiness, see:
https://www.theguardian.com/world/2020/oct/09/herd-immunity-letter-signed-fake-experts-dr-johnny-bananas-covid
17 thoughts on "Are Scottish Conservatives now supporting mad Covid science?"
Alasdair Macdonald says:
I am sure that Mornings on Radio Scotland will devote a session to this, so that it gets publicity for the Tories.
gavinochiltree says:
Johnsons many Covid-19 mistakes are now perculating into the public domain. A clever trick by Boris, to slip this stuff out while his ratings in one-party State England are high.
But he still bears responsibility for a huge cost in lives and disruption to peoples lives. England has had three lockdowns because of this incompetent Boris regime: the highest per capita death toll: the worst economic hit—and all Starmer can say is "me too, me too"!
Mad science, graft, corruption and Tory hegemony in England (and therefore the rest of us.
"Where did you get the money, Boris"?
"Haw, hum, mumble and we'll just get it done, hoi, hah, vaccines, best in the world".
ArtyHetty says:
What a sinister leaflet, it's akin to something you'd expect the Nazi's to distribute.
Terrifying, let's hope people tear it up into tiny pieces and send it back to whence it came. Brrrrr, it's chilly…
The Barrington Declaration isn't scientific, it's part of the radical-right's war against the precautionary principle. So yes, Scottish Conservatives appear to be attacking a scientific world-view. Though this will come as no surprise if you understand how the right-wing mind function.
https://www.lse.ac.uk/granthaminstitute/news/organisers-of-anti-lockdown-declaration-have-track-record-of-promoting-denial-of-health-and-environmental-risks/
https://skepteco.wordpress.com/2020/10/11/the-great-barrington-declaration/
This came up in 'more on WP'. Three 'scientists', looks like some folks signed it with names like Bananas etc though. That a Tory Councillor is distributing this pap is extremely concerning, in fact, are they even allowed to?
All in your own mind
Substitute Barrington
Goebels
Now you will be thinking correctly
Reminds me of those well known tory MPs
Mr Selwyn Gummer
Mrs Edwina Curry
Both went on tv to tell us british beef was safe when people were dying from CJD mad cow disease
And eggs were safe when people were getting serious illness from several types of bacteria proliferating in British eggs
British business profit is most important to these people
Indeed, and as if any Tory, paid highly from the public purse, gives one hoot about the actual people. All the Tories care about is themselves, and money.
I'd be surprised if it's even appropriate, if these leaflets are being sent out by a Tory councillor, or legal.
The Barrington Declaration is also part of the radical-right's war against international human rights law. Most specifically relating to environmental protection and the right to health. That's how psychotic Torydum is.
Human Rights, Health & Environmental
Protection: Linkages in Law & Practice
http://www.who.int/hhr/Series_1%20%20Sheltonpaper_rev1.pdf?ua=1
What had been exposed this last year is just how easily the conservative government can persuade academics in british universities who are prepared to say publicy that black is white.
So many of them scraped off the bottom to support the conservatives idiocy by BBC , newspapers , radio .
Its the corruption that shocks at first glance but then you realise that we have all gained knowledge , we now know that many of the people in positions we previously trusted automatically, are actually thin on credibility trust and reliability they value career progression above all else including lives.
All you state is referred to as
The English Way
Alex Lee-MacDonald says:
Maybe not the worst thing about this poster but I can't believe they used Finland as a case study of no lockdowns/the Great Barrington Declaration.
Finland is much closer to a case study of ZeroCovid – they locked down hard and fast last spring and then kept cases low using border controls, good financial support for self-isolation (100% pay), good sick pay (which are all measures very limited in Scotland throughout the pandemic by being part of UK) and contact tracing (including a very successful app). As cases have started rising this month, they just locked down again last week!
stewartb says:
Moreover, the Covid death rates per 100k of population in Finland and Sweden are completely different according to this chart available from the FT. Very odd leaflet.
See: https://ig.ft.com/coronavirus-chart/?areas=s92000003&areas=e92000001&areas=fin&areas=swe&areasRegional=usny&areasRegional=usnj&areasRegional=usaz&areasRegional=usca&areasRegional=usnd&areasRegional=ussd&cumulative=0&logScale=0&per100K=1&startDate=2020-01-01&values=deaths
It's too complicated. It will just go in the bin. The Tory waste of time, paper and monies. It will cost the taxpayers. Bit late. Everybody likely to die has been vaccinated.
The Tories have killed enough people already. How many more do they want to die. Their average members, male and over seventy. Appalling pandemic mismanagement. Brexit looming. Austerity killing people,
DR £150,000 in expenses. Plus salary and perks. Just a total waste of space.
Perhaps Tory Councillor Cameron Rose might agree to explaining the finer elements of this to a few bereaved family members in a soundproof room with only an outside key…?
Ronnie says:
"nutty" is an absolutely extraordinary (and utterly unscientific) way to describe some very highly credentialed ppl – get a grip folks
Previous Previous post: Don't panic, it's only a 'vaccine bounce'
Next Next post: SNP accused of failing to get enough of us infected?


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Condolences after deadly Las Vegas shooting
President Jacob Zuma has extended his condolences to the government and the people of the United States following the mass shooting in Las Vegas, Nevada.
At least 58 people were killed and more than 500 others injured in the mass shooting at a concert held in Las Vegas, making the incident the deadliest in US history.
The Presidency said South Africa's consulate in Los Angeles is in contact with South Africans in Las Vegas.
"The mission has confirmed that there were no South African victims from the shooting."
Concerned families with relatives in the affected city are invited to call the Department of International Relations and Cooperation on 012 351 1000 for assistance. – SAnews.gov.za


The "survival horror" genre is a term attributed to a wide variety of games, yet also many titles that are outside the boundaries of the genre's original definition. What defines a survival horror game usually comes down to how the scales of combat even out. In action games, it's the hero who has the upper hand, making each scenario an exciting session of mowing down the competition. But in survival horror, the scales are tipped against you, giving players little to no method of defending themselves against an ominous looming threat, creating a tense atmosphere that makes gamers turn the lights back on. In recent years, games like Amnesia: Dark Descent and Outlast took character vulnerability one step further and forced players to hide in every closet and under every bed in a terrifying, but numbingly repetitive, game of hide-and-seek. Unfortunately, every positive quality of Remothered: Tormented Fathers is overshadowed by repetition and poor design choices that make this a disappointing start to a new trilogy.
Is that you Jodie Foster?
Remothered: Tormented Fathers opens with Rosemary "Rose" Reed arriving at the Felton estate in order to investigate the cold case disappearance of Celeste Felton, the daughter of the unwell owner of the estate, Richard Felton. With great hesitation, Ms. Reed is permitted to speak with Richard Felton by Gloria, Felton's nurse. But what begins as a friendly conversation quickly turns accusatory as the mysterious Rose Reed suspects that Richard was responsible for the disappearance of his adopted daughter and Gloria promptly tosses Rose out of the estate and bans her from returning. But of course, this wouldn't be much of a story, so Ms. Reed ignores the warning and sneaks back into the house where players resume control and uncover the Felton family secrets while avoiding the twisted characters who so desperately want to get rid of her.
As the story unfolds through the six hour story, players will encounter plenty of moments that were intended as plot twists but were easily predicted, with the exception of a single reveal that was just too bizarre to anticipate; possibly even too bizarre to accept. The quality of the story can be described at best as a b-grade Japanese horror movie that doesn't have an ending. Even knowing that this title was intended to open the door for two sequels, there just wasn't enough closure at the end (which I had to look up) to leave Remothered: Tormented Fathers feeling like a complete experience.
But I did get to appreciate the underside of mid-century furniture.
Who hasn't experienced a trilogy in some medium where an installment felt incomplete? It's never good for a creator to publish work in that state, but I suppose that I could forgive it as it has become such a common practice. That is to say, I could forgive it if the rest of the experience wasn't so rough.
Visually, Remothered: Tormented Fathers has an uncomfortable range of quality. There's a wonderful level of realistic detail work that went into the environmental designs. Every shelf is filled with a variety of books, their order varied, avoiding the cut and paste look that can occur during fast development processes. As I explored Richard Felton's manor, I truly got the sense that this was a wealthy man who had lived as a recluse for as long as he had. Papers were scattered about on desks in a manner that appeared well used and not disorganized, furniture was placed in a logical and functional way, and everything felt as grand as a manor should. Yet, in contrast with it's realistic environments, characters were colored with a slightly different color pallet that often made them appear further in the foreground than their relation to the environment should have; like a disquieting pop-up book. Likewise, Rose's hair moved and looked so stiff that it would have been better suited for Life Is Strange.
Worse yet, there's no excuse for Fatal Frame's running animation. Rosemary is portrayed as an intelligent woman, but she refuses to take off her heels and run like a normal person.
If you run fast enough like this, the air below your arms will lift you off into the sky.
Remothered: Tormented Fathers succeeds in making players feel helpless as they explore the mansion. Richard will follow players throughout the house donning only his gardening apron and his small scythe. There are other characters that will take his place for reasons I won't reveal here, but Richard is the one that sticks out the most to me. While he is indeed the least ominous of the three featured stalkers, it's hard to forget the sight of Richard.
Even though I wish I could.
As the naked landscaper chases players through the halls of his home, players are forced to hide in closets and underneath beds and couches as they solve puzzles that reward them with keys and open paths to new areas. But completing each task is a frustratingly tedious process of finding a hiding place, waiting eons for a clearing, and then running out of hiding and hoping that you aren't spotted again. Players are able to pick up two categories of household items that will help them avoid or escape detection. Breakable objects such as (the odd number of) snowglobes scattered around the manor can be used to throw and distract enemies, while sharp objects such as knives and needles can be used to break free from their grip when you get caught. Weapons can only be used a finite number of times before they break, but players will have the opportunity to upgrade them, gaining a few extra uses.
Players familiar with survival horror games might think of this as standard procedure for the genre, but a single design flaw negates players' skill and makes this cat-and-mouse chase one of pure luck. One aspect, if not the most important aspect, of designing a survival horror game such as this, is audio design. Audio clues are a crucial part of determining the location of your pursuer, but Remothered: Tormented Fathers lacks any semblance of directional audio design. Without being able to pinpoint what direction a threat is coming from, it's nigh impossible to avoid walking straight into danger. Thankfully, there are at least audio proximity clues suggesting how close or far something may be, but it's far from acceptable. As soon as players enter the manor for the first time, they'll hear music playing from a gramophone somewhere within the house. It's not clear at first, but players are expected to seek out the source and in doing so, they'll discover something horribly wrong. The gramophone is actually on the second floor, but it's possible to stand on the first floor, just beneath the record player, and it will sound as if you're standing immediately next to the source. It's an unbearable flaw that even further limits the clues that players have to make the right decisions.
Remothered: Tormented Fathers was a disappointing experience filled with long cutscenes, uninspired characters, and design oversights that over-complicate the game mechanics. In full disclosure, I was unable to finish it. I had progressed five of the six hours in when my save file was corrupted, forcing me to start from scratch. I survived for five hours, but eleven was simply out of the question. However, as the game isn't without its merits, I'm hoping that Darril Arts is able to make the necessary corrections for the future installments.
Visuals are well detailed but inconsistent and often too surreal for the world created by Darril Arts.
A repetitious slog through puzzles and clumsy movement makes this more of a chore than anything else.
The atmospheric soundtrack complements the game's environment, but the lack of directional audio design is a crippling oversight.
Glaring design flaws force players to make poor decisions that ruin the whole experience.
Remothered: Tormented Fathers is available now on PC and is scheduled to release on Playstation 4 and Xbox One later this year.
A copy of Remothered: Tormented Fathers was provided by the publisher.


The first thing that pops into people's minds when you mention Panama is its famous canal, one of the seven wonders of the modern world. However, with a diverse landscape Panama offers a wide array of adventures. Tourists have the opportunity to explore mountains and rainforests, experience both the Pacific Ocean and Caribbean Sea, and learn about the life of the indigenous population. It is a relatively Americanized country, making it one of the most safe and modern destinations in Latin America.
Bocas del Toro – One of Panama's top tourist attractions. It is an archipelago consisting of nine islands located in the Caribbean Sea. Bocas offers dense rain forests with a wide range of wildlife and beautiful white-sand and blue-water beaches. The main city Bocas Town, located on Isla Colon, offers a good variety of restaurants and nightlife spots, in a laid back, bohemian atmosphere. Although Bocas mostly appeals to backpackers, it has a wide range of accommodations, from simple hostels to luxury bungalows. Water taxis that run around the clock make it easy to commute between the islands. The most common way of reaching Bocas del Toro is by bus to Almirante followed by a short boat ride, or through flying into Bocas Town from Panama City.
Panama City – Often referred to as the Miami of Central America, Panama City is both a vibrant cosmopolitan city and a getaway to many tropical escapes. It is a modern capital with beautiful skyline, making you wonder if you are actually in Latin America. This doubt quickly fades by visiting Casco Viejo, the charming old town, where brick roads link antique buildings and underground bars. Casco (as locals call it) has even earned the UNESCO World Heritage Status. Panama City offers a variety of day trips, such as visiting the canal, exploring rain forests, or simply relaxing on sandy beaches.
San Blas Islands – Panama's pocket of paradise. The San Blas Islands comprise of 378 islands in the Caribbean Sea, of which only 49 are inhabited. This is the perfect place to unwind and view some of the most spectacular islands and beaches you will ever encounter. The indigenous own the islands, and you live in relatively primitive conditions, with all your meals freshly caught from the sea. Apart from some of the most popular islands, the majority are not crowded. That means that if you're looking to find your deserted paradise, visiting the San Blas Islands is a must.
Santa Catalina – A small fishing village located on the Pacific Ocean. Santa Catalina is known for fishing snorkeling, scuba diving and world-class surf. Gaining popularity by tourists the last years, Santa Catalina is quickly transforming from an unknown fishing village to one of the most recommended places to visit in Panama.
Boquete – A small town in the highlands of Panama and a top destination for outdoor lovers. Boquete is surrounded by mountains, gushing streams and abundant coffee farms. The mountain village offers plenty of activities such as hiking, climbing, white water rafting, zip lining, coffee farm tours and soaking in hot springs. Alternatively, you can just enjoy the breathtaking scenery and let your travel companions do all the adventuring.
Accommodation in Panama is generally priced higher than other Central American countries. In general, the cheapest hotel rooms with cable tv and air-condition cost about 30 USD a night, while the going rate for a hostel dorm is around 10-18 USD per night.
For popular hostels it is recommended to book in advance, especially during pubic holidays or during the high season of December to March.
Panama has a well-maintained road infrastructure compared to other Central American countries, making it relatively easy to get around. Traveling by bus is inexpensive, and bus routes are available between most of the major destinations. Although bus services can sometimes be difficult to figure out, Panamanians are usually friendly and will be able to tell you where to wait for a particular bus – although the bus drives usually only speak Spanish.
Panama City has a Metro system but with limited routes. Generally, it is recommended to use taxis or Uber as they are relatively cheap and can save you a lot of time and hassle.
When to go – Panama mainly has two seasons. The months from December to March is the dry season, while the wet season is from March to December. Dry season is the peak season, mainly due to all the Europeans and Americans trying to escape freezing temperatures in their home countries. Despite the wet season not being very popular among travelers, it can be a good time to visit Panama as the prices are cheaper, and the tropical rain usually is short and evaporates quickly.
Costs – Panama is one of the more expensive countries in Latin America. A low range budget starts around 35 USD, while a mid-range budget is approximately 70-150 USD. There is little visible corruption and you will get a receipt for everything you buy. You can find ATMs in all major cities and even though many places accept credit card, it is still recommended to carry cash. It is not usual to haggle at shops, but prices are often negotiable in markets, especially if you're buying several items.
Tipping – It is common to tip 10 % at restaurants. For guided tours, one would typically tip 7 – 10 USD for per person for a day tour. It is not necessary to tip taxi drivers.
Food – Panamanian cuisine is a mix of Spanish, African and indigenous dishes, and ingredients, reflecting its diverse population. Recommended dishes to try are Guacho de Mariscos (Seafood Guacho), Ceviche del Mercado de Mariscos (Ceviche from the Seafood Market), Ropa Vieja y Arroz con Coco (Shredded Beef and Coconut Rice), Arroz con Guandú y Pollo Guisado (Rice and Beans with Chicken), Pargo frito (Fried Red Snapper) and Carimañolas. Regarding drinks, Panama has a good selection of beer, the country's most popular drink. You will also find a limited selection of Chilean, U.S., and Spanish wines on most menus. Finally, make sure you try seco, a sugar-cane-distilled alcohol commonly served with milk and ice.
Culture – Panama is a large melting pot of races, but in a small space. It's common to greet in Panama with a handshake, hug, or kiss on the cheek. Panamanians are not especially touchy people, and a comfortable distance should be kept while conversing. Macho attitudes do sometimes prevail. For women travelling in Panama, whistles and catcalls are not uncommon, although easily ignored.
Language – The main and official language is Spanish. Although English is spoken fluently by around 14 % of the population, it can be difficult to communicate in English outside of the main tourist areas. So brush up on your Spanish (or at least download Google translate)!
Currency – Panama's official currency is the US dollar.
How did you organize your trip to San Blas Island? Did you do it ahead of your trip?
We booked it from our hostel in Panama City a couple of days before the actual trip. We paid 230 USD per person for 3 days and 2 nights. That included transportation (including pickup/drop-off from Panama City), accommodation, food (3 meals per day) and 1 day-trip to the other islands.
Regarding when to book I would recommend that you book in advance if you plan to do the trip to San Blas during high season. Also, if you wish to go Panama – San Blas – Cartagena then you should definitely book in advance, as it was full for the next 3-4 weeks when we were in Panama (during New Years 2016/2017).


'A Place to Belong' is a beautiful children story written and illustrated by Adelaide artist, Rebekah Rocca. It is written in rhyming verse and brought to life through eye-catching and elaborate illustrations. While this is a children's book, it is sure to charm readers of all ages and we believe both you and the little people in your life will love it!
Soft cover book, signed by the author.


text:
Moskovsky Uyezd (Московский уезд) was one of the subdivisions of the Moscow Governorate of the Russian Empire. It was situated in the central part of the governorate and existed until 1929. Its administrative centre was Moscow.

Demographics
At the time of the Russian Empire Census of 1897, Moskovsky Uyezd had a population of 1,203,926. Of these, 95.6% spoke Russian, 1.5% German, 0.8% Polish, 0.4% Yiddish, 0.4% Tatar, 0.4% Ukrainian, 0.2% French, 0.1% Armenian, 0.1% Belarusian, 0.1% English, 0.1% Latvian and 0.1% Czech as their native language.

References

Uezds of Moscow Governorate
Moscow Governorate

redpajama_set_name: RedPajamaWikipedia


If you're a frequent listener to the show, you know what fans we are of Rita's so it was a privilege to interview their CEO Jim Rudolph. Jim gives our listeners advice by suggesting to use the 5Cs of franchising. Find out what they are by listening to this podcast.