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Enfermedades Infecciosas y Microbiología Clínica (English Edition)
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Inicio Enfermedades Infecciosas y Microbiología Clínica (English Edition) Rate of cardiovascular, renal and bone disease and their major risks factors in ...
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Vol. 37. Issue 6.
Pages 373-379 (June - July 2019)
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Rate and predictors of comorbidities
Prediction of cardiovascular disease
Prediction of renal insufficiency
Prediction of bone disease
Antiretroviral therapy
DOI: 10.1016/j.eimce.2018.09.005
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Rate of cardiovascular, renal and bone disease and their major risks factors in HIV-infected individuals on antiretroviral therapy in Spain
Prevalencia de enfermedad cardiovascular, renal y ósea, y sus principales factores de riesgo en personas infectadas por el VIH que reciben tratamiento antirretroviral en España
Hernando Knobela,
hknobel@telefonica.net
HKnobel@parcdesalutmar.cat
Corresponding author. Servicio Enfermedades Infecciosas, Hospital del Mar, Barcelona, Paseo Marítimo, 25-29, 08003 Barcelona, España
, Pere Domingob, Ignacio Suarez-Lozanoc, Félix Gutierrezd, Vicente Estradae, Rosario Palaciosf, Antonio Antelag, José-Ramón Blancoh, Xavier Fulladosai, Elena Refolloj, on behalf of the VACH Cohort
a Servicio Enfermedades Infecciosas, Hospital del Mar, Barcelona
b Unidad Enfermedades Infecciosas, Hospital de la Santa Creu I Sant Pau, Barcelona; Servicio Enfermedades Infecciosas
c Hospital Infanta Elena, Huelva
d Servicio Enfermedades Infecciosas, University General Hospital, Elche
e Servicio Enfermedades Infecciosas, Hospital Clinico San Carlos-IdiSSC, Madrid
f Servicio Enfermedades Infecciosas, Hospital Virgen de la Victoria, Malaga
g Servicio Enfermedades Infecciosas, Hospital Clínico Universitario, Santiago
h Servicio Enfermedades Infecciosas, Hospital de San Pedro, Logroño
i Servicio de Nefrología, Hospital Universitario de Bellvitge, Barcelona
j Servicio de Cardiología, Hospital Universitario La Paz, Madrid
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Table 1. Main characteristics of the study population.
Table 2. Antiretroviral therapy in the study population comparing two different periods.
Additional material (1)
The life expectancy of HIV-infected individuals has dramatically improved with potent antiretroviral therapies. However, organ-specific toxicities of some antiretrovirals and persistent inflammation and immune activation due to residual virus replication account for a high burden of age-associated comorbidities in the HIV population.
The prevalence of overt cardiovascular, renal and bone diseases as well as their major risk factors were cross-sectionally examined during the year 2014 in the VACH cohort, a large nationwide population of HIV-infected individuals in Spain.
A total of 10,897 HIV-infected patients were examined. Seventy-one point four percent were male and the mean age was 48 years. Mean time since HIV diagnosis was 15.8 years and mean time on antiretroviral therapy was 13.1 years. The proportion of patients with undetectable viral load was 87.1%, whereas 65.7% had CD4 counts>500 cells/mm3. Overall, cardiovascular, renal and bone disease were recorded in 4.7%, 5.9% and 2.8%, respectively. The prevalence of major risk factors was as follows: smoking 51.3%, alcohol abuse 7.8%, overweight/obesity 42.2%, diabetes 19.9%, dyslipidaemia 72.6%, hypertension 25.6%, and osteoporosis 11.1%. In the subset of patients older than 55 years-old (18%), all figures for overt disease and their major risk factors were significantly greater.
Major age-related medical conditions and most of their risk factors are highly prevalent in HIV-infected individuals on long-term antiretroviral therapy in Spain. Preventive actions, including careful selection of antiretroviral agents, should be prioritized in the ageing HIV population.
La esperanza de vida de las personas infectadas por el VIH ha mejorado con la terapia antirretroviral. Sin embargo, la toxicidad de algunos antirretrovirales, la inflamación persistente y la activación inmune explican la alta carga de comorbilidades asociadas con el envejecimiento en la población con VIH.
La prevalencia de enfermedad cardiovascular, renal y ósea, así como sus principales factores de riesgo, se analizó en una cohorte de individuos infectados por el VIH en un estudio realizado en España durante el año 2014.
Se examinaron un total de 10.897 pacientes infectados por VIH. Varones el 74,1%, edad media 48 años. El tiempo medio transcurrido desde el diagnóstico del VIH fue de 15,8 años y el tiempo medio de tratamiento antirretroviral fue de 13,1 años. La proporción de pacientes con carga viral indetectable fue del 87,1%, mientras que el 65,7% tenían recuentos de CD4>500 células/mm3. La enfermedad cardiovascular, renal y ósea se encontró en el 4,7, 5,9 y 2,8%, respectivamente. La prevalencia de los principales factores de riesgo fue: fumar 51,3%, abuso de alcohol 7,8%, sobrepeso/obesidad 42,2%, diabetes 19,9%, dislipidemia 72,6%, hipertensión 25,6% y osteoporosis 11,1%. En el grupo de pacientes mayores de 55 años (18%), la prevalencia de comorbilidades y sus principales factores de riesgo fue significativamente mayor.
Las principales comorbilidades relacionadas con la edad y la mayoría de los factores de riesgo asociados son muy prevalentes en las personas infectadas por el VIH que reciben tratamiento antirretroviral en España. Las acciones preventivas, incluida la selección cuidadosa de agentes antirretrovirales, deben ser priorizadas en la población con VIH que está envejeciendo.
Enfermedad renal crónica
Enfermedad cardiovascular
Significant improvements in HIV therapies and increased antiretroviral treatment access have shifted HIV disease from being considered a life-threatening condition to become a chronic illness.1,2 This new paradigm brings new challenges in the management of the HIV population, as patients are living longer at the cost of prolonged exposure to antiretroviral drugs along with the harmful effects of persistent immune activation and systemic inflammation driven by residual virus replication.3,4 Accordingly, long-term drug toxicities and high rates of age-associated comorbidities have become leading causes of non-AIDS morbidity and premature death in the HIV population.4,5 In the START trial, non-AIDS illnesses were more frequent in patients that deferred initiation of antiretroviral therapy than in those treated earlier, with most clinical events occurring in patients with CD4 counts above 500 cells/mm3.6 In this context, it is important to characterize the prevalence and risk factors for major age-associated comorbidities in the ageing HIV population.
Certain antiretrovirals are associated with organ-specific toxicities, adding harm on the top of common illnesses that are age-related, such as diabetes and hypertension.7 In this regard, cardiovascular and renal diseases have become leading causes of death among elderly HIV patients on long-term antiretroviral therapy.3,5 In the international D:A:D study, abacavir, and ritonavir-boosted atazanavir or lopinavir were independent predictors of cardiovascular events in HIV-positive persons.8 Likewise, in the EuroSIDA cohort that examined nearly 7000 HIV-positive individuals, exposure to abacavir and boosted indinavir were significantly associated with an increasing risk for developing cardiovascular disease.9 Moreover, in both cohorts exposure to tenofovir disoproxil fumarate (TDF) instead of abacavir was associated with development of chronic kidney disease.10–12 More recently, boosted darunavir exposure was also linked to increased cardiovascular disease risk.13 Only when a better management of risk factors is ensured, benefits on the incidence of cardiovascular and/or renal complications are attained.14
The aim of our study was to assess the rate and predictors of cardiovascular, renal and bone disease in a large cohort of HIV-infected individuals on antiretroviral therapy followed longitudinally in Spain.
The VACH study is an open, prospective, multicenter cohort of HIV-infected adults consecutively attended since year 1997 at 23 hospital-based HIV clinics distributed across Spain (http://vach.es/). Up to the end of year 2014, a total of 15,559 subjects had been recruited.
Patients were included in the cohort provided that they were at least 16 years-old and gave informed consent to participate in the study. All analyses conducted using the VACH cohort conformed to Spanish laws and regulations regarding confidentiality, patient autonomy, data protection and medical research. Despite absence of a centralized laboratory, all of the VACH-associated clinics used the same viral load assay and definition criteria for laboratory test abnormalities throughout the study period.
All patients having at least one visit during year 2014 were included in the current analysis. Secondarily, a comparative cross-sectional examination of the same individuals seen 4 years earlier (2010) was performed.
Information on major comorbidities and their risk factors were collected electronically. They included cardiovascular disease (CVD) events (myocardial infarction, invasive coronary procedures, stroke or death associated to CVD); chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) below 60mL/min/1.73m2 using the CKD-EPI formula;15 and documented bone fractures at any location.
Data on risk factors was recorded following definitions proposed by international guidelines,16–21 and included arterial hypertension (systolic blood pressure ≥140mm Hg and/or diastolic blood pressure ≥90mm Hg, or taking anti-hypertensive drugs).17 Overweight and obesity were defined for body mass indexes above 25 and 30, respectively. Diabetes was defined as fasting glucose>125mg/dL, or taking oral antidiabetic drugs or insulin.18 Dyslipidemia was defined as elevated fasting total cholesterol ≥240mg/dL and/or elevated triglycerides ≥200mg/dL.19 High alcohol consumption was considered for a daily intake above 3 units (42g). Osteoporosis was defined for bone mineral density loss above 2.5 in the T score using densitometry, regardless age.20
A history of prior CVD events included having had coronary heart episodes, stroke, or peripheral arterial ischemia. Globally, atherosclerotic CVD was defined grouping four syndromes: 1) coronary heart disease (myocardial infarction, angina pectoris, heart failure, and coronary death); 2) cerebrovascular disease (stroke and transient ischemic attack); 3) peripheral arterial disease (intermittent claudication and significant limb ischemia); and 4) aortic aneurysm (abdominal and/or thoracic).
The Framingham risk score was used to determine individual chances of developing CVD events within 10 years.21 It includes age, gender, LDL-cholesterol, HDL-cholesterol, blood pressure, diabetes, and smoking. Individuals were categorized as having low (<10%), moderate (10-20%) or high (>20%) risk of myocardial infarction or coronary death at 10 years.
Resembling the Framingham risk score for predicting future CVD events, the D.A.D. study group built a predictive model for developing renal impairment in HIV-infected individuals.22 Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and CVD were independent predictors of renal impairment. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create a risk score. The chance for developing CKD within the next 5 years was 1:393 (0.25%), 1:47(2.13%) and 1:6 (16.67%) in the low (score <1), medium (score 1-4) and high (score ≥5) risk groups, respectively.
Statistical analysis. A cross-sectional examination was made in year 2014, recording the number of patients/events. For qualitative data, absolute and relative frequencies were used. Percentages were obtained based on the total number of subjects with non-missing values unless specified otherwise. Significance was compared using the chi-square test. For quantitative data, we used means (+/- standard deviations) for normally distributed continuous variables, and median (with interquartile ranges) for continuous variables with a skewed distribution.
A total of 10,897 patients met the inclusion criteria and were included in the analysis. This was the population attending at least one visit during year 2014. The main epidemiological and clinical characteristics of these patients are recorded in Table 1. Overall, 74.1% were male, 86.4% native Spaniards, and 36.7% former injection drug users. The mean time since HIV diagnosis was 15.8 years. Overall, 87.1% of patients had plasma HIV-RNA below 50 copies/ml. The mean CD4 count was 652 cells/mm3. Nearly two thirds of patients had more than 500 cells/mm3. Figure 1 records the distribution of patients according to age. Of note, 18% of subjects in year 2014 were ≥55 years-old.
Main characteristics of the study population.
n=10,897
Male gender (%) 74.1
Mean age (years) 48 (9.1)
Native Spaniard (%) 86.4
Risk group (IDU/MSM/HTX) (%) 36.7/27.4/31.6
Mean time since HIV diagnosis (years) 15.8 (7.4)
Mean time on antiretroviral therapy (years) 13.1 (5.8)
AIDS (%) 28.5
Anti-HCV+(%) 47.4
HBsAg+(%) 6.2
Mean CD4 count (cells/mm3) 652 (305)
CD4 count distribution (cells/mm3) (<200/201-350/351-500/>500) (%) 5.6/10.7/17.9/65.7
Plasma HIV-RNA <50 copies/mL (%) 87.1
IDU, injection drug user; MSM, men having sex with men; Heterosex, heterosexuals
Distribution of patients according to age.
(0.05MB).
The rate of prior CVD events, CKD and fractures in the study population was 4.7%, 5.9% and 2.8%, respectively. Compared to 4 years earlier, significant increases were noticed (42%, 24% and 40%, respectively). As expected, incident and cumulative events were more frequent in older patients, with more pronounced rates occurring after 55 years-old (Figure 2).
Major co-morbidities in the study population. Effect of age.
The prevalence of major risk factors was as follows: alcohol abuse 7.8%, overweight/obesity 42.2%, diabetes 19.9%, dyslipidemia 72.6%, hypertension 25.6%, and osteoporosis 11.1% (Figure 3). Interestingly and compared to 4 years earlier, while smoking and alcohol abuse had declined, all age-related metabolic complications had increased, being changes of 13%, 29% and 45% for dyslipidemia, diabetes and hypertension. These trends were generally more pronounced in the subset of patients older than 55 years-old (Figure 1supplementary).
Major risk factors in the study population.
(0.1MB).
The proportion of patients with distinct Framingham risk scores is depicted in Figure 2supplementary. The estimated risk of coronary heart disease within 10 years was overall low, moderate or high in 56.9%, 31.1% and 12% of patients, respectively. Of note, roughly three quarters of patients older than 55-years-old depicted moderate-high Framingham risk scores.
The proportion of patients with high risk for progressing to CKD using the D:A:D risk score is shown in Figure 3supplementary. In the subset of patients older than 55 years-old, high risk for developing renal impairment within the next 5 years was 53.3%.
Interestingly, half of patients with moderate/high risk for progressing to CKD had also moderate/high risk of coronary heart events within the next 10 years. Globally, 37% of patients had simultaneously moderate/high risk of both CKD and CHD.
Overall, 2.8% of patients had had a fracture. However, it had occurred in 8.1% in the subset older than 55 years-old. Osteoporosis was globally recorded in 11.1% of patients, but was present in 18.6% in those older than 55 years-old. Information for DEXA was recorded for the last testing available, which on average was within two years.
All but 148 (1.4%) of patients were on antiretroviral therapy. The reasons for remaining drug-naïve were very low or undetectable viremia along with high CD4 counts (long-term non-progressors or elite controllers), and/or patient's decision to reject treatment. For treated patients, the mean time on antiretroviral therapy was of 13.1 years. The most common used antiretroviral agents were tenofovir (50.4%), abacavir (24.2%) and boosted protease inhibitors (44.5%).
Table 2 shows the proportion of patients on tenofovir, abacavir and boosted protease inhibitors at two different periods. It is noteworthy that tenofovir use had drop roughly from 60% in 2010 to 50% in 2014, whereas abacavir use increased from 19% to 24% during the same period. Boosted protease inhibitors were roughly taken by 48% of patients in 2010 and remained prescribed in 45% in 2014.
Antiretroviral therapy in the study population comparing two different periods.
2010(n=10,897)
No treatment, n (%) 316 (3.3) 148 (1.4) <0.001
Tenofovir, n (%) 5,778 (60.3) 5,331 (50.4) <0.001
Abacavir, n (%) 1,851 (19.3) 2,559 (24.2) <0.001
Protease inhibitors, n (%) 4,577 (47.8) 4,709 (44.5) <0.001
Missing data, n (%) 1,317 (12.1) 315 (2.9) <0.001
Given the association between the most frequently used nucleos(t)ide analogues and major comorbidities, the prescription of tenofovir and abacavir was examined in patients showing different risk scores for cardiovascular disease and renal insufficiency (Figure 4). It is interesting to note that abacavir was more frequently prescribed in the subset of patients with high compared to moderate or low Framingham risk scores, given that some studies had found an association between abacavir use and myocardial infarction. Moreover, less than 15% of patients with high CDV risk on abacavir had renal impairment, and therefore other reasons than avoiding nephrotoxicity guided antiretroviral choice in most patients.
Antiretroviral treatment modality and risk for cardiovascular or renal disease.
This study is the first epidemiological investigation about the rate of major comorbidities and their risk factors in a large population of adult HIV-infected patients on long-term antiretroviral therapy in Spain. Multiple clinics across the whole country contributed to this cohort, enrolling roughly 15% of the estimated 100,000 individuals diagnosed with HIV living in Spain at the time this cross-sectional study was conducted.
The overall rate of prior CVD was 4.7% whereas the prevalence of CKD was 5.9%. Fractures had occurred in 2.8%. Classical conditions associated with cardiovascular, renal or bone disease, such as hypertension, diabetes, and obesity were relatively frequent in the study population. However, it was aging, a non-modifiable risk factor, that played the most significant role, largely accounting for the high rate of non-infectious comorbidities. Indeed, roughly three quarters of patients older than 55-years-old depicted moderate-high Framingham risk scores. These figures are particularly worrisome taking into consideration that the mean age of the population enrolled in the VACH cohort was 48 years-old. Likewise, the risk for developing renal impairment within 5 years was above 50% in this oldest group. Of note, 37% of patients had simultaneously high risk for developing cardiovascular and kidney diseases. Thus, it seems worthy to reinforce preventive actions on modifiable risk factors, such as tobacco and overweight/obesity by promoting healthy life style, diet and exercise. Furthermore, earlier interventions should prioritize the management of dyslipidemia, hypertension and diabetes. The benefit of better management of risk factors for reducing the incidence of CVD events has recently been pointed out.14
While dramatic improvements in antiretroviral therapy have allowed for better virologic and immunologic outcomes, the high and increasing prevalence of common age-related comorbidities and their risk factors should require prompt attention, including adequate choice of safer antiretroviral agents, considering their long-term toxicity profile and the fact that treatment is currently recommended for everyone infected and as soon as possible.23
In our study population, tenofovir was more than two-fold more frequently prescribed than abacavir as nucleos(t)ide analogue. However, abacavir use significantly increased since year 2010 approaching its prescription to one quarter of patients by 2014. This was most likely explained by the fact that older patients had more often renal impairment and concerns on TDF-associated nephrotoxicity prompted clinicians to shift their therapy.
Around 45% of patients were treated with protease inhibitors. It is noteworthy the relatively high rate of patients that received abacavir and/or protease inhibitors, since their use has been associated with an increased rate of CVD events.24,25 Whereas abacavir may enhance vascular thrombosis through platelet activation,24 boosted protease inhibitors may increase CVD risk largely by producing metabolic abnormalities, including insulin resistance and dyslipidemia.25
Whereas 30% of HIV patients with high cardiovascular risk were on abacavir, roughly 44% of those with high risk for renal insufficiency were on TDF. Most antiretroviral treatment guidelines suggest that abacavir should be avoided or used with caution in patients with high cardiovascular risk whereas TDF is not recommended in patients with high risk of renal impairment.23 The involvement of abacavir in myocardial infarction, however, remains controversial. Moreover, we should keep in mind that our HIV patients started these treatments when guidelines were different from the current ones. Furthermore, treatment options some years ago were limited in comparison with the multiple drugs with improved safety profile that are currently available. Clearly, the choice of safer options for individuals with either heart or renal risk scores should be prioritized.
The recent advent of tenofovir alafenamide (TAF) represents an attractive alternative option,26 as replacement for those on TDF and potentially for switching from abacavir. Until recently, TDF was discouraged in older HIV patients given its toxicity on the kidneys and bone mineralization, both of which have ameliorated significantly with the new formulation that depicts less systemic drug exposure.26 With respect to boosted protease inhibitors, unboosted integrase inhibitors are recommended as preferred initial treatments, because their safer metabolic profile.26 This advise is particularly important for subjects with CVD risk factors and high CVD Framingham risk scores.
Along with preventive efforts on CVD events, caution is warranted when using drugs known to be potentially harmful for the kidneys, such as TDF and/or ritonavir-boosted protease inhibitors.11,27 The improved life expectancy of HIV-infected individuals is inexorably leading to a growing population of HIV-positive elderly patients 1 and therefore choosing antiretrovirals with a safer renal toxicity profile would represent an important advantage.27 In this regard, the advent of TAF is an important step forward that would reduce concerns on tubular damage and bone mineral loss linked to long-term TDF therapy.26 Other alternatives that would minimize kidney damage may include nucleos(t)ide-sparing regimens, such as the recently approved dual combination of dolutegravir-rilpivirine for virologic suppressed patients.23 Moreover, promising results have been reported with dolutegravir-lamivudine in drug-naive patients 28 as well as with long-acting intramuscular dual therapy.29
Our study has several limitations largely due to its observational and cross-sectional design, which makes it strictly descriptive. Firstly, pro-active interventions could not be tested, and selection biases could have occurred without noticing. Secondly, exposure to different antiretrovirals was more extensively examined for a few agents and prior exposure time lengths were not considered, being the relative contribution as time dependent not weighted. However, the sample size is large and many clinics contributed, so the data are very representative of the whole Spanish HIV population. Furthermore, the assessment of comorbidities and their risk factors was carried out using objective and widely used criteria, which makes the data reliable and the survey useful for examining time trends in Spain and making comparisons with HIV patients at other regions.
A third limitation of our study is that age strata were made empirically trying to balance the size of distinct groups. In this regard, a threshold in 55 years-old for considering people older could be considered as too premature. However, similar approaches have been taken by others testing HIV populations with an average age younger than 45 years-old, as it was in our cohort. Finally, although aging, a non-modifiable risk factor, played the most significant role, largely accounting for the high rate of non-infectious comorbidities in our study, the relative weight of different risk factors was not compared, and aging by itself is associated with a higher proportion of other risk factors for CVD, kidney and bone disease.
In summary, our results highlight that common age-related comorbidities and their risk factors are highly prevalent in HIV-infected patients on long-term antiretroviral therapy in Spain. Nevertheless, tobacco remained the number one cause of preventable death in our cohort. In other words, antiretroviral treatment has improved so much that HIV-infected persons that smoke cigarettes are at greater risk of dying of lung cancer than of AIDS.30 Therefore, at the top of our agenda must be helping our patients to stop smoking, an effort too often forgotten. Lastly, attention must be given to selection of the most convenient antiretroviral drugs, considering aging and comorbidities of individual patients.
El estudio fue financiado por Gilead España.
Los autores declaran no tener conflictos de intereses relacionados con la autoría y publicación del presente artículo.
Queremos agradecer a todos los participantes de la cohorteVACH, así como a Valeska Andreozzi (ExigoConsultores, Lisboa, Portugal) por su excelente asesoramiento científico.
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Declining relative risk for myocardial infarction among HIV-positive compared with HIV-negative individuals with access to care.
http://dx.doi.org/10.1093/cid/civ014 | Medline
F. Ibrahim, L. Hamzah, R. Jones, UK CHIC/CKD* Study Group, et al.
Comparison of CKD-EPI and MDRD to estimate baseline renal function in HIV-positive patients.
Nephrol Dial Transplant., 27 (2012), pp. 2291-2297
http://dx.doi.org/10.1093/ndt/gfr657 | Medline
National Kidney Foundation. K/DOQI Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39 (suppl): 1-266.
A. Chobanian, G. Bakris, H. Black, et al.
National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection.
Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA., 289 (2003), pp. 2560-2572
http://dx.doi.org/10.1001/jama.289.19.2560 | Medline
Anonymous. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2006; 26 (suppl 1): 43-48.
National Cholesterol Education Program. Third Report of the National Cholesterol Education Program on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106: 3143-421.
E. Lewiecki, C. Gordon, S. Baim, et al.
International Society for Clinical Densitometry: 2007 Adult and Pediatric Official Positions.
Bone, 43 (2008), pp. 1115-1121
http://dx.doi.org/10.1016/j.bone.2008.08.106 | Medline
R. D'Agostino, R. Vasan, M. Pencina, et al.
General cardiovascular risk profile for use in primary care: the Framingham Heart Study.
Circulation, 117 (2008), pp. 743-753
Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study.
PLoS Med, 12 (2015), pp. e1001809
DHHS. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. https://aidsinfo.nih.gov/guidelines.(accessed June 2018).
A. Alvarez, S. Orden, I. Andújar, et al.
Cardiovascular toxicity of abacavir: a clinical controversy in need of a pharmacological explanation.
http://dx.doi.org/10.1097/QAD.0000000000001547 | Medline
F. Islam, J. Wu, J. Jansson, D. Wilson.
Relative risk of cardiovascular disease among people living with HIV: a systematic review and meta-analysis.
HIV Med, 13 (2012), pp. 453-468
B. Aloy, I. Tazi, C. Bagnis, et al.
Is tenofovir alafenamide safer than tenofovir disoproxil fumarate for the kidneys?.
AIDS Rev, 18 (2016), pp. 184-192
S. Rodríguez-Nóvoa, P. Labarga, A. D'Avolio, et al.
Impairment in kidney tubular function in patients receiving tenofovir is associated with higher tenofovir plasma concentrations.
http://dx.doi.org/10.1097/QAD.0b013e32833202e2 | Medline
B. Taiwo, L. Zheng, A. Stefanescu, et al.
ACTG A5353: a pilot study of dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500,000 copies/mL.
D. Margolis, J. Gonzalez-Garcia, H. Stellbrink, et al.
Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial.
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Lung cancer mortality associated with smoking and smoking cessation among people living with HIV in the United States.
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Economy and Business P2P Business Models
Cooperatives as an alternative economic model
June 17, 2012 No Comment	Michel Bauwens read
Excerpted from Robin Murray in Red Pepper (UK):
"What part can co-operatives play in a 21st-century model of an alternative economy? Could co-operatives become the dominant form of enterprise just as joint stock companies were in the industrial era? Can the state – itself part of the social economy – find a way of working with them in new collaborative ways? Can it indeed internalise not only co-operation's values but its practices? Can we imagine a model of the co-operative economy that generates as much confidence as once did the various versions of Fordist socialism?
Let's start with finance. Instead of a financial system dominated by a few centralised global banks that have subordinated production to their logic, can we imagine one with a thousand local banks, owned either by their members or municipalities? They would be a repository of local savings and lend them to small enterprises and households in need, whom they would know as intimately as the English country banks knew their neighbourhoods in the early 19th century.
For larger investments and technical support the banks would form their own regional and national bodies. And for the major strategic tasks, there would be a national public bank that would provide funds and advice to the local ones.
These were the dreams of 19th-century co-operators throughout Europe and North America. Today in Britain they would be seen as green utopianism. Yet in Germany they are part of everyday life. There are more than 1,100 independent co?operative banks, with 13,000 branches and 16 million members. In almost every neighbourhood in Germany you will find a co-operative bank, and usually on the other side of the street in co-operative competition will be one of the 15,600 branches of the 430 municipal savings banks or Sparkassen. That is more than 1,500 independent local banks with almost 30,000 branches.
Both the mutual and municipal banks have their own regional and national clearing and specialist banks. Together they dominate retail banking, with the commercial banks confined to less than a third of banking business. The public development bank, the KfW, commits more than €20 million each year to finance the switch away from nuclear energy and to meet its climate change targets. They need a highly granular banking network to reach the households and small enterprises who are key to the new energy model. That is provided by the co-operative and Sparkassen banks. These two social pillars of Germany's 'three pillar' system have been a principal factor behind the economic success of the small and medium industrial enterprises of the German 'Mittelstand'.
This model of co-operative banking was developed in the mountainous rural areas in the 1850s to support the local farmers, small traders and artisans ignored by commercial banks, and later in the eastern cities to fund urban artisans and traders. It spread all over Germany and to much of the continent, where it still plays a major part in the national banking systems. In Holland, for example, the second-largest bank (one of the top 30 in the world) is the Rabobank, a confederation of 141 local credit unions. Like the German co?operative banks, and the similarly inspired networks in Canada, they are geared to the welfare of their local economies.
What about industry? Can we imagine a co-operative region that holds its own in a globalised economy? It might equip its farmers and artisans with the most modern equipment, and help them to form co-operatives to sell their products all over the world. Each town could focus on a particular product so that it developed the necessary specialisms. It could have its own college where the skills of one generation are passed on to the next. The finance would come from local co-operative or public banks, the loans guaranteed by other artisans in the town, and all the invoices and accounting would be handled by a dense network of joint bookkeepers and accountants.
This is a description of the region of Emilia Romagna in Italy. Many of the light industries there and in neighbouring regions have not just held their own but become leaders in their sector in Europe. In the ceramics town of Imola the main co?operative is now the largest ceramic producer in Europe. Carpi is one of the major clothing areas in the EU – a town of 60,000 people with 4,000 artisan firms. The Emilian farmers not only supply the local co-operative supermarkets that dominate retailing in the province but they have established their own co-operative processing and branding. Parmesan cheese is made by a co-operative of 550 milk producers, Parma ham by a co-operative of pig keepers on the banks of the Po.
This pattern of production is not confined to the so called 'third Italy'. There are similar industrial regions in Denmark, Germany and the Basque and Valencian regions of Spain.
Alternatives of this kind already exist in many of the core areas of today's economy. In the face of industrialised food, Japanese consumers (almost all women) in collaboration with local farmers have created a remarkable food box scheme. Once a week they put in their orders, gather to assemble the produce into boxes and deliver them through a network of their own local micro groups (known as Han). The consumer co-ops now have 12 million members and have started associated co-ops for food processing, packaging, design, printing and catering, and are currently extending into childcare, health and elder care.
Or take renewable energy. Denmark produces a quarter of its energy from windpower. This is largely generated from turbines owned by more than 2,000 local wind co-operatives. The UK has many fewer, but those that there are can now distribute their energy through the recently-formed Midcounties Co-operative Energy, which attracted 20,000 members in its first year. There are similar thriving co-operative networks in fields such as education, health, social care and sport."
P2P Theory
Emergence, Crisis, and Replacement of the Era of Decentralized Networks
June 17, 2012 2 Comments Michel Bauwens read
← Emergence, Crisis, and Replacement of the Era of Decentralized Networks
Video of the Day: CATASTROIKA, on global finance and the destruction of the nation state →


Dawes Devices Boost Controller Swtich | Dawes Devices by 3 Bar Racing Inc.
Home — Turbocharged Automobiles — New: Dawes Devices Boost Controller Switch!
1) Use stage 1 for on-road and stage 2 for racing (use this product with two Manual Boost Controllers).
2) Use stage 1 for launch and switch to the high boost mode (stage 2) once you have traction (use this product with two Manual Boost Controllers).
3) Use stage one for factory boost control and then switch over to your manual boost controller with stage 2 (use this product with one Manual Boost Controller).
Note: the Boost Controller Switch requires that you run 3 hoses through the firewall grommet. Please check clearances, prior to ordering. If you do not have room for the hoses, then you can still use our Multi-Boost Control System, which requires only one wire through the firewall.


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ACT-SO
ACT-SO STUDENT APPLICATION
Advocacy & Issues
Black Workers Forum
Political Action/Voting Rights
Forward Together Wisconsin-Moral Monday Movement
Legal Redress
"Injustice anywhere is a threat to justice everywhere"
-Dr. Martin Luther King, Jr.
NAACP Restructures to Advance Advocacy Strategy
New York —The nation's most prominent civil rights organization announced today during its annual national board meeting in New York, a strategic restructuring which better positions the organization to lead the critical policy advocacy and social justice work needed to ensure the rights of all people. The group also signed memorandum of understanding with several African American organizations designed to expand its capacity to engage Black voters nationally.
"The NAACP is a membership-based advocacy organization with 2,220 branches and a unique and incomparable ability to drive change at the local, regional, and national levels. The current political and policy climate demands an NAACP that is agile and responsive in the face of the serious challenges confronting communities of color, including the continued assault on voting rights and foundational threats to democracy," said Derrick Johnson, President of the NAACP.
This new structure will enable the Association to deploy resources efficiently as conditions on the ground dictate, to employ a research-based approach to civic engagement, and to ensure closer alignment between National Office staff and NAACP branches across the country.
For more information visit: https://www.naacp.org/latest/naacp-restructures-advance-advocacy-strategy/
We Must Override this Veto!
On 2-26-2019, the U.S. House of Representatives voted in favor of H. J. Res 46, a resolution to reject and nullify President Donald Trump's declaration of an emergency so he could shift as much as $6.7 billion of previously appropriated monies away from their intended recipients and used instead to build a wall along the southern border of the United States. The resolution passed by a margin of 245 yeas to 182 nays.
Then, on Thursday, 3-14-2019, the U.S. Senate passed the same resolution by a margin of 59 yeas to 41 nays. 25 hours after the Senate action, on 3-15-2019, President Trump vetoed the bill. The House will hold a vote on overriding the veto on March 26, 2019, and we need to work very hard between ow and then to see that this veto is overridden.
To review the concerns and actions of the NAACP on this matter, as well as to learn how you can advocate, please review the attached Action Alert and take Fast Action here.
NAACP DANE
NAACP Condemns Video Captured by DeForest Village Police Chief
DEFOREST-- The DeForest Village Board will file a complaint with the Police Commission regarding Chief Daniel Furseth.
The board voted 4-2 late Tuesday after a regularly-scheduled meeting where they heard concerns from some members of the community.
The village board decided to file a complaint with the DeForest Police Commission after hearing from three people who asked members to send a message of inclusion and respect to minorities.
One of those who spoke was Greg Jones, the President of Dane County's chapter of the NAACP. He is also the co-chair for the "Law Enforcement and Leaders of Color Collaboration." During the meeting, Jones addressed the board, saying "The actions that the chief demonstrated do not demonstrate who and what this community is. The only responsible measure to that damage is termination of his employment with this municipality."
Jones, along with the Dane County Chiefs of Police Association, denounced Furseth's actions earlier in the day. The police chiefs association issued a press release it said was in response to the Furseth situation on Tuesday.
Jones told 27 News in an interview, "When you think about a police chief, you think about a person who is a face of the criminal justice system at that level in that municipality. And for that person to feel comfortable enough to engage in that kind of behavior, use those words, and really do a caricature of African American men, it's highly disappointing."
"That behavior is certainly disturbing and disappointing and certainly appalling to a lot of members and that's why the NAACP will be at the meeting this evening to share our expectations of a chief in Dane County." (Reported by: WKOW-TV)
NAACP Dane County Responds to...
...the Alec Cook Sentence
Is the "justice" we have witnessed, truly equal justice? Members of the NAACP Dane County don't believe it to be. At the June 2018 general meeting, members expressed outrage over the sentence received by former UW-Madison Student, Alec Cook by Judge Stephen Ehlke.
Cook had been charged with 23 criminal counts involving 11 women, about half of which involved varying degrees of sexual assault. The prosecutors in the case sought the maximum allowable sentence of 19½ years in prison followed by 20 years of extended probation. Cook pleaded guilty to three counts of third-degree sexual assault, and one count each of strangulation and stalking. Instead, Judge Ehlke issued a sentence of just three years in prison followed by 8 years of probation.
For these reasons, NAACP Dane County joins with others in decrying Judge Ehlke's decision and calling for:
1. An appellate review of the case.
2. An immediate examination of Judge Ehlke's sentencing record by race and sentencing data; and for all other criminal judges broken down by race.
3. A meeting with Dane County criminal judges to discuss this and other community concerns.
Judges have broad discretion in the number of years of prison a defendant receives, and it is critical that more sunshine be shone on how the discretion is exercised.
Madison, WI (July 12, 2018)
Cook Sentence - Full Article
What actions can you take?
Text "NAACP" to 40649 or click on the link below to take the NAACP's PLEDGE TO VOTE!
NAACP PLEDGE TO VOTE
NAACP and the vacancy on the U.S. Supreme Court
After thorough research and evaluation the NAACP opposed Brett Kavanaugh's nomination to the Court of Appeals for the D.C. Circuit in 2005, and we oppose his nomination to the U.S. Supreme Court now. Although we are still in the process of closely updating and scrutinizing his record, even the most cursory of reviews demonstrates that Judge Brett Kavanaugh does not empathize with the very real needs of most working middle-class Americans or with the unique concerns of racial and ethnic minority Americans.
This nomination is too important to rush. This nomination should only be considered by the Senate elected by the American people in November, 2018, when they are fully aware of the stakes and after the 116th Congress is sworn in.
For more information on this legislation and how you can advocate for it, click the button below.
2019 COMMUNITY CONVERSATION
A very special thank you to Wisconsin State Rep. Shelia Stubbs, our program moderators: Molly McGrath, Dee J. Hall, John Bauman and Quinn T. Craugh, and to the NAACP Dane County Planning Committee, Members and the Dane County Community Members who participated in the 2019 Community Conversation.
2018 NAACP National
Convention Highlight
NAACP Board Chairman, Leon W. Russell, delivers the 2018 call to action...
"We Cannot Agonize, We Must Organize!"
How do we deal with the political realities of the assault on civil rights we currently face?
Disenfranchisement of voters of color;
Voter suppression by "lawfully" removing infrequent voters from voting rolls;
Rollback of voting rights enforcement;
Attempts to remove fair housing enforcement from the mission of the Department of Housing and Urban Development;
The virtual elimination of funding for environmental justice programs at the EPA;
Demeaning references to Muslims;
Inhumane treatment of immigrant families at our boarders;
Slurs directed at predominantly black countries and their citizens; and
Increases in hate crimes and racial division while hate groups gain momentum.
The NAACP has activated a 21st century Civic Engagement strategy ahead of the November mid-terms, vowing to:
DEFEAT HATE. VOTE!
We cannot agonize, we must organize!
"We owe it to ourselves and our children to elect officials who champion our values and uphold the dignity of our democracy." –Willie L. Brown, Jr., the first black speaker of the California Assembly, former San Francisco mayor and the 2018 NAACP Spingarn Medal recipient.
2018 ACT-SO NATIONAL COMPETITION
Dane County NAACP Team
Although Team Dane County didn't "strike gold" at the National NAACP ACT-SO Competition in San Antonio, they represented themselves, and our Branch well! We are very proud of them!
TAKE ACTION NOW!
FACING DANE COUNTY
Talk to Us...Your Opinion Matters
What are the most pressing social issues facing Dane County? *
Disporportionate Incarceration Rate Education Achievement Gap Food Deserts Housing Lack of Employment Opportunities Poverty Racism
Under 18 19-25 26-35 36-50 Over 50 Prefer not to say
News from Region III
Do Not Forget...
This Is Not Over Yet!
WCCF-Race to Equity Report
NAACP Dane County
Branch #36AB
More NAACP Information
NAACP Wisconsin State Conference of Branches National NAACP
NAACP Dane County Branch #36AB is a 501-C4 organization.


Dexter's THE 9 bowling shoes have a patented interchangeable sole design that requires specialized THE 9 Soles. THE 9 Soles feature HyperFlex Hinges to help align the sole to the shoe properly in the HyperFlex Channels. The Toehold Clip is comprised of an abrasion-resistant material that was created to resist toe drag damage. These soles are available in a variety of materials for different slide preferences.
Due to the time it takes to produce the Dexter THE 9 S4 Slide Sole ball it will ship in immediately. We cannot ship this ball outside the United States.


Terminator's Super Stainless Buzzbait gives you 47% more vibration than ordinary buzzbaits. The flat head design allows it to get up on top of the water quickly, much like a water ski, and stay on the surface even at a very slow retrieve. This Buzzbait's Super Stainless frame is 30% more than ordinary stainless-framed buzzbaits, offering topwater enthusiasts a tougher, more maintenance free buzzbait. Features Quickskirt changeable premium silicone skirt.


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7 Top Stocks See Multiple Analyst Price Hikes
By Chris Lange	December 20, 2017 12:45 pm EDT
While the major U.S. exchanges (S&P 500, Dow Jones Industrial Average and Nasdaq) have been somewhat mixed on Wednesday, the markets collectively have never been stronger. The Nasdaq is in striking range of 7,000, and the Dow is only a couple hundred points away from a record 25,000, not to mention the S&P 500 is less than 1% away from 2,700. So what has helped push these markets to all-time highs?
Earnings and a strong rally in the tech sector have been a big part of this push, not to mention the advancement of the recent tax bill in Congress has spurred some optimism among corporations. Along with these, analysts have helped to shape the outlook of the market and encourage more growth.
24/7 Wall St. has taken a look at some of the biggest analyst calls on Wednesday that are driving stocks, and we have included some of the biggest analyst highlights. It's worth pointing out that most of these calls are coming on the heels of earnings reports this week, and with Christmas and New Year's just around the corner this could be the last big push by analysts in 2017.
Carnival Corp. (NYSE: CCL) reported solid earnings on Tuesday and ultimately closed the day out higher, winning the admiration of a few analysts. Deutsche Bank raised its price target to $70 from $61. Stifel raised its price target slightly to $80 from $79, and SunTrust Robinson Humphrey raised its target to $84 from $72. Wedbush also raised its price target, to $71 from $65. Shares of Carnival traded on Wednesday at $68.22, with a consensus analyst price target of $74.08 and a 52-week trading range of $51.70 to $69.89.
Darden Restaurants Inc. (NYSE: DRI) had one of the stronger earnings reports on Tuesday, posting a gain of roughly 7%. In turn, Barclays raised its price target 8% to $100. BMO raised its price target to $101 from $80. Credit Suisse maintained a Neutral rating and raised its price target to $90 from $80. Deutsche Bank raised its price target to $92 from $88, Maxim raised its target to $103 from $93 and Morgan Stanley raised its target to $95 from $88. Also, SunTrust raised its price target to $95 from $94. Shares of Darden were down 1% at $95.61. The stock has a 52-week range of $71.02 to $98.29 and a consensus price target of $93.05.
FedEx Corp. (NYSE: FDX) shares hit an all-time high Wednesday after it reported a strong fiscal second quarter. Baird raised its price target to $268 from $265, while BMO raised its target to $270 from $265 and Citigroup raised its target to $280 from $275. Credit Suisse has an Outperform rating and raised its price target to $283 from $278. Raymond James raised its price target to $270 from $232, and Stifel raised its target to $272 from $221. Shares of FedEx were trading up nearly 3% at $249.32, with a 52-week range of $182.89 to $253.24 and a consensus price target of $245.42.
Micron Technology Inc. (NASDAQ: MU) was a big premarket mover on Wednesday after beating earnings and raising guidance. Mizuho reiterated it as Buy and the price target was raised to $50 from $45. Cowen reiterated its Outperform rating and raised the target to $53 from $50. Credit Suisse raised its target price to $60 from $50 with a reiterated Outperform rating. Other target price hikes: Citigroup to $55 from $51, Deutsche Bank to $60 from $55, Instinet to $55 from $50 and Stifel to $75 from $65. Shares of Micron were up over 4% at $45.99. The consensus price target is $54.29, and the 52-week range is $20.34 to $49.89.
Red Hat Inc. (NYSE: RHT) was lower after an earnings beat and guidance. While this might not have been enough for investors, analysts took the opportunity to hike their price targets: BMO to $142 from $128, Credit Suisse to $120 from $113, Deutsche Bank to $150 from $130, KeyBanc Capital Markets to $138 from $135, Morgan Stanley to $130 from $120, Raymond James to $139 from $118 and RBC Capital Markets to $135 from $134. Jefferies has a Hold rating and raised its target from $100 to $119. Shares of Red Hat traded down about 6%at $121.87, with a consensus price target of $127.21 and a 52-week range of $68.54 to $130.93.
9 Oil and Gas Stocks Analysts Want Their Clients to Own for 2018
Stitch Fix Inc. (NASDAQ: SFIX) may have drifted lower after its first earnings report as a public company, but on the positive side three firms raised their targets in response to the report: Barclays to $27 from $26, JPMorgan to $26 from $25 (while maintaining a Neutral rating) and Stifel to $23 from $22. Shares traded down over 10% at $22.15. The stock has a post-IPO range of $14.48 to $25.98 and a consensus price target of $25.67.
Tenet Healthcare Corp. (NYSE: THC) may be the oddball of the group seeing as it did not report earnings this week like the rest. However, this firm is exploring the sale of its Conifer business unit, as well as looking to expand cost-cutting measures within the company. Leerink raised its price target from $25 to $27. Mizuho has a Neutral rating and raised its price target to $15 from $13. Morgan Stanley downgraded it to Underweight from Equal Weight. Morgan Stanley raised its price target to $15 from $14, and SunTrust raised its target to $16 from $15. Shares of Tenet were down about 3% to $14.56 on Wednesday. The 52-week range is $12.25 to $22.72. The consensus price target is $17.64.
By Chris Lange
« 9 Oil and Gas Stocks Analysts Want Their Clients to Own for 2018
50 Worst Action Movies of All Time »
Read more: Investing, Analyst Upgrades, Earnings, featured, Carnival Corp (NYSE:CCL), Darden Restaurants, Inc. (NYSE:DRI), FedEx (NYSE:FDX), Micron Technology, Inc. (NASDAQ:MU), Red Hat, Inc. (NYSE:RHT), Tenet Healthcare Corp (NYSE:THC)


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MotoVue
Motorcycling/Motoring
The Rise Of Marc Marquez.
Two 20-year-old MotoGP winners. Marquez the youngest ever by 133 days.
The temptation to compare great Grand Prix motorcycle racers from different eras is almost impossible to resist for many MotoGP commentators. Admittedly, it does help generate increased interest from the media, the fans, and the general public, but grabs of history both past and present that align nicely do not necessarily make for a fair comparison or do justice to those involved.
Marc Marquez has already claimed the mantle of the youngest winner of a MotoGP at age 20 by 133 days from "fast" Freddie Spencer. In 1983 Spencer went on to win his first World Championship aged 21 years in the 500cc class (MotoGP) becoming the youngest person to win the title. Marquez appears to be on course to wrest that achievement away from Spencer as well, currently leading the MotoGP World Championship with six rounds to go as this is written. However in 1985 at the age of 24 Spencer won both the 250cc (Moto2) and 500cc (MotoGP) World Championships, something that no other rider has done, and is a feat that is unlikely to ever be repeated. It should also be noted that Marquez started racing in the 125cc World Championship in 2008 when he was 15 and has won both the 125cc (Moto3) World Championship and the Moto2 World Championship, although he was not the youngest champion of either of those two classes.
Freddie Spencer the youngest MotoGP World Champion at 21.
The same commentators are also espousing that rookie Marquez may win the MotoGP title in his first year. The last person to achieve this was Kenny Roberts 35 years ago in 1978. But here there is a rather significant difference in circumstance between Roberts achievement and that of Marquez should he attain the title.
Roberts World Championship effort was backed by Yamaha America, who only supplied his team with equipment. This consisted of three different GP racers for the three different classes Roberts was contesting. Formula 750, 500cc GP and 250cc GP – one machine for each class with no spare bikes. His crew chief was expatriate Australian, Kel Carruthers, a former 250cc World Champion and a mentor to Roberts, accompanied by mechanics Nobby Clark, Trevor Tilbury and a Yamaha technician. Roberts had helped develop Goodyear's racing tyres in the States, and it was the American company that put up the money that was needed to go racing in Europe. Goodyear naturally supplied the tyres.
The situation was not an ideal one as Roberts explains, "When we got to our first race it became crystal clear that, for sure, I wasn't a Yamaha factory rider. Venezuelan rider Johnny Cecotto was. It wasn't hard to tell; all we had to do was look at his equipment and then look at ours. We did have a Yamaha engineer by the name of Mikawa, and at some races, we also had a Goodyear technician. But it was us against the factory, really."
'78 World Champion Kenny Roberts at the '79 French G.P. at Le Mans,
"So '78 was a piece of work. I was riding 250 and 500 Grand Prix and Formula 750 as well. We had just one bike per class; no backup bikes. At practically every race it was my first look at the track. Usually, all I had was 30 minutes to figure it out. And not just the track, everything–the right lines, bike setup and tire selection, if there was any. There I was, aiming to beat reigning World Champion Barry Sheene, who'd usually seen the track a dozen times before. And we were on Goodyear tires. We were on our own there, too, because nearly everyone else was on Michelins. I swear, some things never change! To say the Goodyear guys had their hands full is to understate the problems we faced. Usually, the Goodyear guys would show up at a track they'd never seen before, which meant they didn't have the right tires. That's a nightmare you really don't want to deal with. But deal with it we did."
Roberts went on to win a hat-trick of 500cc World Championships.
Nonetheless, Goodyear eventually weighed in with more development tyres, and Yamaha finally supplied Roberts with a second bike for the 500cc GP class. Roberts dropped the 250cc title challenge after winning two races and at one stage leading the championship, finally finishing fourth in the standings. Roberts continued on with the Formula 750cc World Championship finishing second in the title five points behind Johnny Cecotto. But Roberts won the 500cc GP (MotoGP) World Championship by 10 points from Barry Sheene against a flotilla of factory Suzuki's and the works Yamaha of Johnny Cecotto. It was an outstanding achievement.
Marc Marquez in action. A future multi MotoGP World Champion?
By comparison, Marc Marquez has raced in the world championships for five years now. In MotoGP, there is only one track that was new to him, Laguna Seca (The Circuit of the Americas was new to everyone in MotoGP this year). As a World Championship prodigy in the smaller classes, he has been groomed by both Repsol and Honda to fit seamlessly into the retired Casey Stoner's seat at the team. With a dearth of experience from the team around him and mountain of electronic data to relate to and the use of control tyres, the only thing that can stop Marquez from claiming the title may be fate. He has proven he is fearless and usually comes out on top when pressured by his peers. Indeed if there is a similarity between Marc Marquez and Kenny Roberts championship campaign, it is the fact that they are both real racers in every sense of the word. And there is no doubt in anyone's mind that Marquez will continue to break records.
Words Geoff Dawes (c) 2013. Images courtesy http://www.motogp.com
Read more: http://www.motorcyclistonline.com/features/122_0503_kenny_roberts/#ixzz2dn69hATZ
This entry was posted in Motorcycle Racing and tagged Barry Sheene, Freddie Spencer, Grand Prix motorcycle racing, Johnny Cecotto, Kenny Roberts, Marc Márquez on 03/09/2013 by Geoff Dawes.
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PIXUS Portals
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Continuing to Serve You
By Peg Moertl
Continuing to Serve You!
It has now been twenty weeks and counting since our workplace disruption here at OCCH, and we see no end in sight to the COVID-19 pandemic. OCCH remains concerned about the safety and wellbeing of our staff, partners, and the residents and communities we serve, and our thoughts are with all who remain affected by COVID-19. During this time, OCCH has remained highly focused, productive, and ready to serve you. We are pleased to offer our latest update on a variety of important activities and developments here at OCCH at a time when it appears the cessation of federal expanded unemployment insurance payments and the eviction moratorium at the end of July make the future a little more uncertain.
OCCH Board Update
Recently, our OCCH family and the affordable housing industry lost a friend and housing advocate with the passing of Dan Slane, who served on the Board of OCCH for many years – 10 years as Board Chair. His vision and leadership helped define OCCH and without his commitment and contribution over such a long period of time, OCCH would not be the organization it is today. Dan's relationships with the development and economic communities and his passion for helping those with special needs, those at risk for homelessness, those with extremely low incomes, and those in rural communities has led to the creation of homes for thousands of families and individuals. OCCH was fortunate to benefit from his wisdom, business acumen and guidance and he will be missed.
We would like to announce the new OCCH Board officers, as follows: Susan E. Weaver, Board Chair; Angela Mingo, Vice-Chair; Thomas Loos, Treasurer; and Jeanne Golliher, Secretary.
Our Next Normal
To protect staff and prevent the spread of COVID-19, OCCH largely continues to work remotely. The property management staff at Community Properties of Ohio (CPO) have mostly returned to the work of operations, management and services, albeit with new no-contact protocols or group activities. Asset managers have begun windshield inspections of property exteriors without live contact with site staff or unit interiors. We have embraced new solutions and technology to ensure we stay engaged and connected across the enterprise. We are committed to supporting one another and in turn, providing quality and excellence to you, our partners.
Ohio Equity Fund XXX Is Closed!
We want to express our sincere gratitude to the investors in the recently closed Ohio Equity Fund XXX, which achieved two important milestones: $5B in total equity raised and 50,000 units of affordable housing either created or preserved. During this unprecedented pandemic and economic uncertainty, with the support of our investors, OCCH closed a $302M fund which will have a meaningful impact across our footprint during this critically important time. We are especially grateful for the 10 investors who opted to become 'impact investors', resulting in a $1M contribution to Ohio Capital Impact Corporation programs to benefit thousands of residents.
Development and Fund Management News
OCCH has closed 26 transactions for a total of $238.6M in total gross equity; we anticipate an additional 25 closings by year-end. The OCCH Development team continues to work collaboratively with our developer partners to review and work through each deal in our pipeline from pre-development to closing, and construction to lease-up. We are proactively working with our developer partners to assess each project's ability to proceed with closing by ensuring the construction and lease-up schedules are achievable, building in extra cushion as necessary and evaluating the impact of any delays. In rehab developments, we are reviewing all COVID-19 safety protocols established by the developer, management agent of record, and the general contractor to maintain safe space at occupied properties and the plans for safe resident relocations. We are tracking and encouraging each developer to request an extension for the Placed-In-Service deadline as appropriate. We continue to monitor and assess the strength and liquidity of our partners, track guarantees, and discuss strategies to support our partners and their respective portfolios. The development team provided advisory and application submission assistance on the Federal Home Loan Bank of Cincinnati Affordable Housing Program (AHP) applications due July 31st, the Kentucky Housing Corporation (KHC) 9% LIHTC application due August 20th, the Ohio Housing Finance Agency (OHFA) 4%/Bond Gap Financing applications due September 3rd and the OHFA 9% Final applications due September 25th.
With Fund XXX closed and fully subscribed, Fund Management is focused on closings and working with Development to secure a robust Fund XXXI pipeline. We are thrilled to welcome CVS-Aetna to our stable of proprietary investors. We are working to balance what the industry predicts are rising investor yield requirements and lower pricing in the future with developers who have expectations grounded in today's market.
OHIO CAPITAL FINANCE CORPORATION (OCFC)
OCFC remains a strong and needed resource for affordable housing developers. OCFC has closed over $13M in loans in six transactions in the second quarter and is on target to close another $30M in the third quarter. Our demand remains robust and is expected to increase with the recently announced 2020 Ohio 9% LIHTC awards and with developer partners looking for assistance financing predevelopment costs.
COMMUNITY PROPERTIES OF OHIO (CPO)
CPO continues to focus on operating safely and resourcefully, while serving residents and maintaining the assets. Our Resident Services team remains focused on assisting our families with access to food, PPE, and educational resources, and activities for our CPO children. Over 50 CPO children participated in 8 weeks of a virtual or in person summer camp. In addition, through support in part by a Franklin County Board of Commissioner's Grant, we are implementing a Stable Families Initiative that will include introducing more trauma-informed policies and practices to help CPO families, many of whom have an extensive history with trauma, be more successful maintaining their housing.
OHIO CAPITAL IMPACT CORPORATION (OCIC)
Our philanthropic subsidiary, the Ohio Capital Impact Corporation, has a variety of programs to help our partners and our residents through these uncertain times. OCIC, with the help of our impact investors, has raised critical funds to help residents experiencing hardship due to the pandemic and ensuing economic crisis.
Summer Camp: Even though many summer camp programs were cancelled as a result of the coronavirus pandemic, our partners found creative ways to engage our resident children. Virtual camps, carefully designed socially distanced camps on site, and other solutions provided opportunities for over 500 children.
Resident Impact Emergency Fund: OCIC set up a Resident Impact Emergency Fund with $1 million from OCCH and over $800,000 raised from our investors. The funds are used strategically to help provide rental assistance at the property level to help stabilize families impacted by the crisis and to support other programs designed to help our communities facing this crisis.
Huntington Digital Inclusion Fund: Huntington Bank Community Development Corporation committed $2.5 million in grants over the next five years for flexible dollars to support technology infrastructure and training to further economic mobility through digital access. In this time of virtual learning at home and social isolation, digital connection is more important than ever.
Resident Development Fund: Through a competitive process, OCIC is providing grants to partners for services, training or opportunities for the residents. Examples include job readiness and opportunities for workers, social connection and health opportunities for seniors, or engagement and learning opportunities for youth.
Training and Policy News
OCCH Training Academy
In response to the pandemic, OCCH's in-person training offerings were suspended early in 2020, and we have purposefully accelerated our efforts to increase our e-learning platform. OCCH is in the process of deploying a series of six new online courses to help management companies directly respond to the pandemic. For example, recently released COVID-related course offerings include the following topics:
• How to show units via a virtual tour;
• Conducting maintenance during a pandemic; and
• Delivering quality services while being socially distant.
OCCH remains highly engaged across the industry in our efforts to influence state and federal policy objectives that support the LIHTC industry. For example, the negotiations with the County Auditors Association of Ohio (CAAO) have continued in or efforts to reform the methodology of real estate tax valuations in Ohio. At the federal level, working with the Affordable Housing Tax Credit Coalition and the Ohio Housing Council, we were successful in getting most of the Ohio Congressional delegation to sign on in bi-partisan support of including LIHTC-related actions in an upcoming COVID-relief package.
We continue to work on relief related to emergency rental assistance, REACC inspections, credit delivery extensions and other circumstances made more difficult by the ongoing pandemic. In addition, we are participating in industry initiatives to better understand and address the intersectionality of housing and racial justice and equity.
The OCCH team has responded exceedingly well to the COVID-19 pandemic. We are eager to keep the critical work we do together moving forward, and we will continue to work tirelessly to meet these challenges with action and expertise.
Stay safe and be well,
©2021 Ohio Capital
Corporation for Housing
by Ibel Agency


Israel submitted accession papers to WIPO at the end of May, and from September 1, 2010, it will be possible to file trademarks in Israel using the Madrid Protocol.
Israel submitted accession papers to WIPO at the end of May, and from September 1, 2010, it will be possible to file trademarks in Israel using the Madrid Protocol. Additionally, multi-class trademark applications will be allowed.
Meanwhile, the Israel courts and the Patent and Trademark Office are busy issuing sometimes controversial trademark decisions.


Can it get more classic than this? I mean, this is it if you want to wear one shirt the rest of the season and never change. The classic lightweight brushed cotton flannel in medium grey, an easy match with your dark denim for the colder months.
The classic button down Oxfords are cut slim with a tailored fit through the body and sleeves. Unlined collars and cuffs and our pre-washing process creates a softer look and helps to minimize additional shrinkage. Made in the USA.


I love candles and wax luminous holders. There are so many different patterns for a candle holder; I am going to look at some of the basic models such as votive, wrought iron, hurricane and crystal holder. In the beginning candles were made of tallow, very smoky and burnt very quickly. Later polish was used, but was expensive. Candle holders came into being to hold the candle and protect the user's hand, but also to collect the wax and reuse it. Nowadays the easy candle holder has become an ornamental item and is made use of in interior design. They are available in many forms, styles and colors. There is something to appeal to everyone from prayer holders to ones produced from wrought iron, or flute and crystal.
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Alaskan writer Sara King will be a guest lecturer at this summer's Odyssey Writing Workshop. She is the bestselling author of The Legend of ZERO, Outer Bounds, Guardians of the First Realm, and her latest urban fantasy series, Sunny Day, Paranormal Badass, among others. She's an alumna of the 2008 Odyssey Writing Workshop and has spent the last six years forging a successful career in independent publishing in the sci-fi and fantasy genres. To her chagrin, she is owned by four 120-plus-pound Tibetan Mastiffs, cautiously maintains a flock of ninja chickens, and has so many literary irons in the fire that she's losing count. Thankfully, whenever she needs writing inspiration, she can step out her front door to go wandering in the Alaskan wilderness until she gets cold or almost dies—usually one or the other, but sometimes both—and then stumble home with fresh stories to tell and a new respect for falling, drowning, hypothermia, disorientation, and aggressive 1,500-pound wildlife.
Part 1 of this interview, posted last Sunday, is available here.
For the past four years, you have sponsored the Parasite Publications Character Awards, which provide scholarships to three character-based writers attending Odyssey. Thank you for your generosity! What draws you to character-driven fiction? What do you think plot-driven writers could learn from writers of character-driven fiction?


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FOUR RUNNERS FOR BALLYMORE ON FRIDAY
Runners at different courses on Friday with Zume Forward and Walton Hall at Bendigo followed by Top Of The Range and Pedro Ximenez in the same race at Moonee Valley.
Zume Forward is the first to go in the third race, the Fillies and Mares Maiden Plate over 1300m with Jake Noonan to ride.
The three-year-old had legitimate excuses for finishing eighth at Cranbourne over 1600m at her last start.
"I'm happy to run her as long as the forecast rain doesn't arrive as she's not at her best on wet ground," Mike Moroney said.
"It doesn't look the strongest race so I'd like to run - she's drawn out a little bit but I'm confident she has enough speed to get across.
"They don't tend to go too hard early at Bendigo and I'm particularly pleased with the way she is handling the preparation."
Walton Hall is in race four, the Maiden Plate over 1400m with Jason Benbow to ride from barrier three after missing a start earlier in the week due to the weather.
The Ad Valorem three-year-old pleased Moroney with his debut fourth over 1450m at Kyneton on January 16.
"His work has been really good although this does look a tougher race than the one he missed," Moroney said.
"I wanted to put Jason on for his left handed ride to counter his habit of laying in.
"It's a harder race but the horse is in good order and I'm expecting him to run well."
Pedro Ximenez and Top Of The Range are in race six at Moonee Valley, the Chinese New Year Cup over 2500m with Ben Melham aboard Top Of The Range and Michael Dee on Pedro Ximenez.
"We've put Michael on for his left handed ride to help him," Moroney said. "He's been up a while but is handling it well and he's had a bit of time between runs.
"He's going very well and it's a winnable race, the hardest to beat is probably Top Of The Range but if he produces his best then I expect him to be right in the finish."
Top Of The Range (pictured) will jump from barrier nine.
"He's in terrific order and if he puts his best foot forward then I'm expecting him to be hard to beat," Moroney said.
"He's got the blinkers back on and now with the experience around the track then it does look a winnable race for him."


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Characters, Female Characters, Minor Characters,
Who is Sienna Khan?
" I was one of the first to suggest violence where violence was necessary. Peace bred complacency and acceptance of our place in the world. I will not allow Humanity to push us down without pushing them back. "
—Sienna Khan, explaining to Adam how he took her policy too far
Overview Affiliation Image Gallery Quotes
Chain Whip
High Leader of the White Fang
Sienna Khan was a character mentioned in "The Next Step" and introduced in "Dread in the Air". She was the High Leader of the White Fang before being killed by Adam Taurus, who usurped her role after covering up her murder, claiming that a Human Huntsman broke in and killed her.
Sienna was a female, Bengal[1] tiger-based Faunus with orange eyes, dark complexion and wild black, chin-length hair with an asymmetrical bob style. Her Faunus trait manifested as an extra pair of ears, and her body was adorned with numerous tattoos resembling tiger stripes.[2] She wore four golden earrings on three of her ears, one each on her Human ears, and two on her left Faunus ear as well as a small jewel on her forehead.
She was seen wearing a form-fitting black dress with light green accents on the rims of the outfit; the dress left most of her back open, had two long splits on the side which revealed a pair of black shorts, a shorter split in the front and a small squared keyhole. Over the dress, she wore a back-revealing red cape with gold accents, as well as a green waist cincher with red rims that had a black belt over it, which fastened a green pouch on her right hip. Aside from that, she wore black stockings in conjunction with green sandals that had red laces which were tied to her calves, as well as a black elbow length fingerless glove on her right hand.
Sienna's previous attire was similar to her original except she wore white pants with black thigh length boots and she lacked her cape. She also wore a pair of matching metal wristbands and an orange string band on her right arm.
Sienna was one of the White Fang's first advocates for using fear and violence to overcome Human prejudice towards the Faunus. She initiated this method, believing it necessary to make mankind regard them with fear to demand respect. Having personally created this change and becoming the leader of the White Fang, she was strong and willing to be violent, but not to the extent of hurting her cause on a global scale, which she believed the Fall of Beacon had done. She, however, greatly underestimated the descent into violence and hatred towards Humanity that many members of the White Fang such as Adam, the Albain brothers and her own bodyguards were taking that caused them to turn on her as they deemed her too soft towards Humans.
She was easily in touch with her anger but did not let it overrule her judgment. She let herself listen to Hazel Rainart briefly and also did not outright punish Adam for his misdeeds, instead choosing to lecture him.
While not as prejudiced towards Humans as Adam and many other members of the White Fang, Sienna still had a degree of disdain towards Humanity as she was unconcerned about the Human lives taken by Adam. She encouraged him on his way after he accidentally killed one and only chastised Adam when he went too far. In this, however, she cared for the damage Adam's excess caused to her cause rather than the victims of his actions.
Her strength and independence were also notable after it became clear that Adam had committed a coup, intending to overthrow and replace her as High Leader. She stated quite clearly that she would not simply follow him, which was predictable enough in her character that Adam had already decided to kill her.
As former High Leader of the White Fang, Sienna had a great influence over the organization. She was also fairly agile in combat and was able to easily defeat AK-130s and Human guards alike.
In battle, Sienna was shown wielding a chain whip that had three blades attached to the end. The blades were sharp enough to cut apart AK-130s with ease and each had a Dust crystal of differing types, such as ice. The blades could also be detached from the chain to be used as projectiles.
Five years before Blake Belladonna became a student at Beacon Academy, Sienna was appointed High Leader of the White Fang after Ghira Belladonna stepped down. Sienna stated that she believed in violence for some time prior to radicalization.
During a meeting arranged by Adam, he is seen kneeling before Sienna and begging her to invade Haven Academy. Sienna states that he should be trying to beg for forgiveness, berating him over the ramifications the White Fang is faced with due to their part in the Fall of Beacon and for leaning on the support of Salem's group when their knowledge of them is very limited and the group is primarily comprised of humans. When Adam reveals that he brought Hazel as a representative to meet her, she is briefly livid before relenting. Unable to be persuaded by Hazel, Sienna asserts her decision to not invade Haven Academy and orders her guards to apprehend Hazel and Adam. But the guards do not comply, and Adam reveals that he has staged a coup against her, as more Faunus enter the room and train their weapons toward her.
Not backing down, Sienna told Adam that she would never follow him and was impaled mid-sentence in the abdomen with Wilt. Using the sword to lift and bring her closer, Adam thanked Sienna for her service to the White Fang and told her that he is the leader now. After her death, Adam then instructed the mutineers present that Sienna was to be considered a martyr and to inform the rest of the White Fang that a Human Huntsman assassinated her. This act earned Adam contempt from Hazel, due to Adam omitting that he plotted a coup and Hazel seeing Sienna's death as unnecessary. Adam paid no mind to this, eager to wage his war on Humanity which Sienna would have hindered.
"Sienna" refers to a reddish shade of brown, while Khan translates as "sovereign", "king", or "military leader", in a number of languages.
She may allude to Shere Khan from Rudyard Kipling's "The Jungle Book", which is all the more evident as the predecessor, Ghira, may allude to Bagheera from the same story.
Shere Khan is a tiger, and Sienna is a tiger Faunus as indicated by her ears and stripes.
↑ RWBY Rewind Episode 2 at 19:56
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Start a Discussion Discussions about Sienna Khan
V5 Ch 2: Dread Air
Sentry 616 wrote:73.Anon.52 wrote:MajoraSolaris wrote:MetallicArcher wrote:ChishioKunrin wrote:Sentry 616 wrote: .... Maybe remove her eyes ...	 2017-10-31T04:50:54Z
Only because they activated. They don't fear the eyes themselves, only the power they have, and there's nothing to say that the power w...	 2017-10-31T05:05:43Z
SPOILERS Volume 5 Episode 2
Weiss gave her a gun magazine loaded with vials of Dust. I think she used her Aura to activate the specific type she wanted to use while pull...	 2017-10-25T00:30:19Z
Knightmareace
They should definitely explain the relationship between Dust and Semblances in a world of Remnant. I never noticed that before.	 2017-10-25T00:33:20Z
Retrieved from "https://rwby.fandom.com/wiki/Sienna_Khan?oldid=976133"


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redpajama_set_name: RedPajamaGithub


Last week the Oakland Raiders defeated the Arizona Cardinals on the road for the team's first win away from the Oakland-Alameda County Coliseum all season.The Cardinals finished last in the NFL in rushing yards allowed per game.I'm not frustrated, Anthony Davis said.
The 1986 season had been Anderson's 16th as a Bengal, a term that stands through 2017 as the longest in franchise history.Seahawks , wild card The Seahawks clinched a playoff berth with their win over the Chiefs on Sunday night.The second period would put the Penguins up by three when Zach Aston-Reese found a rebound and hammered it home.
The Canadiens have a total of 11 points on the season.Played in 14 games during his rookie season.The Broncos take the AFC's top seed with a win and losses by the Chiefs and Patriots.He had 107 strikeouts over the 119 innings he pitched during which he gave up 106 hits.
Big left arrow icon Big right arrow icon Close icon Copy Url Three dots icon Down arrow icon Email icon Email icon Exit Fullscreen icon External link icon Facebook logo Facebook logo Instagram logo Snapchat logo YouTube logo Grid icon Key icon Left arrow icon Link icon Location icon Mail icon Menu icon Open icon Phone icon Play icon Radio icon Rewind icon Right arrow icon Search icon Select icon Selected icon TV icon Twitter logo Twitter logo Up arrow icon User icon Audio icon Tickets iconAdd to calendar iconNFC icon AFC icon NFL icon Football iconCarousel IconList ViewFootball iconCarousel IconList View.The Rays have 730 hits, including 126 doubles and 75 home runs.Nadal's absence, however, puts Murray in the equation.The Wizards haven't swept a season series vs.15 pick initially, so that shows how much they wanted his services in the desert.
How do you mentally overcome those challenging workouts?Their total rebound percentage is 53% while their offensive rebound percentage is 29%.I didn't understand the Hyde move in the first place.
Its S1000RR-derived engine is pure inline-four bliss , so it'll hang with anything.Buddy Hield averages 12 points per contest in 22 minutes per game this year."He's really, really good." Justin Simon and LJ Figueroa each scored 13 for the Red Storm.Sky Bet Championship.There are almost countless issues we could point to – and the moronic jettisoning of Edwin Encarnacion in the offseason is far from the least of them.
Given he already missed a bulk of the season, Parise is arguably less in need of a rest for the final week, even if the Wild's playoff position gets locked in.He went 26 for 42 on the game, good for a 62% completion percentage.Their defense allowed a 38% shooting percentage and a 31% average from 3-point range, ranking them 3rd and 9th in those defensive statistics.They have had 98 men left on base and have an OPS of .730.Fisette was dumbfounded, too, that one of his favorite collector cars, a 1954 Corvette-and a barn find at that-was a few miles from his shop.I'd be stunned if it isn't returning starter and junior Marquise Williams over redshirt freshman Mitch Trubisky, but Fedora has had those guys competing and sharing first-team reps all through fall camp.
The Flyers haven't provided fans much to cheer about at all this season, so Parkey was cheered Monday night.New York went 1 ATS after a week off in Tom Coughlin's last five years, and the Giants are a horrific 16 ATS in their last 51 games in November.Russia plays Slovakia, Canada takes on Finland, and Sweden opposes Switzerland.