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February 28, 2007
The sudden interest in the metabolic complications of HIV and its therapies is remarkable considering how not long ago this topic was the forgotten stepchild at the Conference on Retroviruses and Opportunistic Infections (CROI); symposia on metabolic issues at past CROIs were often relegated to small meeting rooms and too often scheduled opposite more popular sessions. It was enough to give metabolic-minded investigators a complex! But at this year's CROI, metabolic issues were front and center. A dedicated session on the first day of the conference was packed, as was the agenda. Some of the most exciting CROI presentations were those that focused on metabolic issues, including evaluations of changes in body fat and lipids during HIV therapy as well as therapeutic approaches to the treatment of dyslipidemia and osteopenia/osteoporosis.
What we learned is that metabolic complications are complicated. Just when we thought we were getting a handle on what causes those love handles and fat-free limbs, well-designed studies come along to burst our ill-informed bubbles. Below are the details of the major metabolic-related studies presented at this meeting and my attempts to reckon with what these results mean.
A5142: Making Sense When Everything Stops Making Sense
The most important clinical study examining the metabolic complications of HIV therapy is AIDS Clinical Trials Group (ACTG) study A5142.1 This was a large (n = 753), three-arm trial of initial HIV therapy in which patients were given one of the following regimens:
The clinician and patient chose the NRTIs in the first two study arms. Importantly, during the initial phase of the study, the only NRTI provided to participants by the study was extended-release stavudine (d4T, Zerit). Later, tenofovir (TDF, Viread) was also made available by the study at no cost to patients. As a result, 42% of participants took zidovudine (AZT, Retrovir), 34% tenofovir and 24% stavudine. There were no major differences in the proportion of participants on a particular NRTI across the study arms.
The study provided unique opportunities to rigorously examine the effect of the disparate study regimens on metabolic parameters. Previously, despite their popularity, no study had compared the metabolic impact of efavirenz and lopinavir/ritonavir. Likewise, the relative effects of different NRTIs on body fat have remarkably not been compared in large studies. The nuke-sparing arm also provided a chance to investigate whether this approach prevented the development of lipoatrophy. Fortunately, the study team and the ACTG sponsor recognized the potential to gain important insights into the relationship between specific HIV therapies and metabolic outcomes and incorporated evaluations such as fasting lipid levels and DEXA (dual energy X-ray absorptiometry) scans into the protocol.
The first data to emerge from this trial were presented at the XVI International AIDS Conference (AIDS 2006) in Toronto, Canada, last summer.2 At that time the relative parity of efavirenz and lopinavir/ritonavir as far as high-grade hypertriglyceridemia and elevated low-density lipoprotein (LDL) cholesterol -- not to mention the interesting virologic and immunologic results of the study -- suggested that long-held assumptions about these agents were about to crumble. At CROI 2007, those expecting the unexpected from an expanded report on body shape and lipids during A5142 were not disappointed.
At a session on metabolic complications that was held the first day of the meeting, the results were presented and the shocker was the finding that more patients who were receiving a regimen of two NRTIs + efavirenz experienced lipoatrophy than patients in the other study groups. After 96 weeks of therapy, limb fat had increased from baseline a median of 18% in the lopinavir/ritonavir + efavirenz group compared to a 9.8% median gain in the lopinavir/ritonavir + two NRTI group (P = .013). The efavirenz + two NRTI group experienced a median increase in limb fat at 48 weeks of over 8%, but by 96 weeks this was largely lost and the overall change from baseline was reduced to only 1.4% -- a result that was significantly less than that seen in the lopinavir/ritonavir + two NRTI group (P = .007).
When looking at the definition of extremity lipoatrophy chosen a priori by the study team (more than 20% loss of overall limb fat), a substantial proportion of patients who had been assigned to efavirenz + two NRTIs developed lipoatrophy; at 96 weeks, 32% of the participants in this group had lipoatrophy detected by DEXA versus 17% in the lopinavir/ritonavir + two NRTI group and only 9% in the nuke-sparing group. The difference in the incidence of lipoatrophy was statistically significant between the lopinavir/ritonavir + two NRTI arm and the efavirenz + two NRTI arm (P = .003), but was not significantly different between the nuke-sparing arm and the lopinavir/ritonavir + two NRTI arm.
Given the mix of NRTIs, it is essential that any analysis include the potential influence of these agents on the changes in limb fat observed. As expected, lipoatrophy was more common in those exposed to stavudine; however, fat wasting of the limb was even more likely when participants were also taking efavirenz compared to participants assigned to lopinavir/ritonavir + two NRTIs.
Among those combining efavirenz and stavudine, lipoatrophy was documented in 51%, compared to 33% among those combining lopinavir/ritonavir and stavudine. Approximately 40% of those pairing efavirenz with zidovudine experienced peripheral lipoatrophy, compared to 16% of those combining lopinavir/ritonavir and zidovudine. As a whole, patients in the lopinavir/ritonavir + NRTI and efavirenz + NRTI groups who used tenofovir were not statistically more likely to develop lipoatrophy. However, in the comparison between the two groups, lipoatrophy was seen in 12% of patients taking efavirenz plus tenofovir versus 6% of patients taking lopinavir/ritonavir plus tenofovir. In a logistic regression model, taking efavirenz along with the NRTIs increased the odds of developing study-defined limb lipoatrophy by 2.7 fold (95% CI: 1.5-4.6).
|Table 1. Percentage With Limb Lipoatrophy at 96 Weeks by Treatment Assignment
The study also supports an effect of zidovudine on fat wasting that falls between that of stavudine and tenofovir. Zidovudine treatment increased the odds of developing lipoatrophy by 1.9 fold (95% CI: 1.1-3.5). Tenofovir assignment reduced the odds of lipoatrophy compared to that of zidovudine.
Before moving on to the lipid data, let's look at the data on fat and their implications. Prior to the presentation of these results, the interpretation of the available in vitro and in vivo data was that certain NRTIs drive fat wasting. In several studies, the substitution of stavudine with abacavir (ABC, Ziagen) or tenofovir has led to increases in peripheral fat -- all but confirming a role for this NRTI in fat loss.3,4 The data have been a bit more mixed with zidovudine.
Zidovudine has been implicated in limb fat loss by Gilead 934, an ongoing study of zidovudine/lamivudine (AZT/3TC, Combivir) + efavirenz versus tenofovir/emtricitabine (TDF/FTC, Truvada) + efavirenz. In that study, DEXA scans detected losses of limb fat on the zidovudine/lamivudine + efavirenz regimen compared to gains in peripheral fat with the tenofovir/emtricitabine + efavirenz combination.5
In contrast, A5005s, a metabolic sub-study of an ACTG treatment trial (study 384) that had much fewer participants than A5142, observed no evidence of limb fat loss by DEXA at 144 weeks among study participants receiving zidovudine/lamivudine + efavirenz, but did see a drop from baseline limb fat among those taking zidovudine/lamivudine + nelfinavir (NFV, Viracept).6 However, A5142 has much greater power to detect meaningful differences in fat changes than either the Gilead 934 or A5005s studies and, as such, should be considered definitive in regards to the effect of zidovudine/lamivudine + efavirenz on fat wasting.
In summary, the study A5142 finds that:
No data on trunk fat were presented and only the foolish or extremely lucky would hazard a guess as to what these will show.
The lipid data were also fascinating. As suggested in Toronto,2the differences between efavirenz and lopinavir/ritonavir when either was combined with NRTIs were fairly minimal. The median change in non-high-density lipoprotein (HDL) cholesterol (total cholesterol minus HDL cholesterol) was 26 mg/dL in the patients taking lopinavir/ritonavir + two NRTIs versus 22 mg/dL in the group taking efavirenz + two NRTIs (P < .005).
HDL cholesterol increases were almost the same at 8 mg/dL and 9 mg/dL, respectively. These are incredible data given the perception that non-nucleoside reverse transcriptase inhibitors (NNRTIs) are great HDL cholesterol boosters. We now know that ritonavir (RTV, Norvir)-boosted PIs also raise HDL cholesterol and in the case of lopinavir/ritonavir, at least, to the same extent as efavirenz. The median change in triglyceride levels was modestly, but statistically significantly, higher at 96 weeks with lopinavir/ritonavir than efavirenz in the NRTI-receiving study arms, 46 mg/dL versus 19 mg/dL, respectively (P = .006).
The nuke-sparing regimen led to greater changes in lipids than the other two study arms, raising triglycerides by a median of 62 mg/dL and non-HDL cholesterol by 44 mg/dL, but HDL cholesterol by an impressive 16 mg/dL -- all were significantly higher than in the other study groups.
The Bottom Line
These results need to be added to the scale on which we balance efavirenz and lopinavir/ritonavir. Some of the findings will tip us one way and the others will lean us to the opposite side. The size and rigor of this study mean these results cannot be easily dismissed -- although it will be important to see on-treatment analyses of body shape and lipids. As opposed to the intent-to-treat approach presented, the on-treatment analysis will help us better understand the associations between these drugs and the changes observed.
Meanwhile, for patients extremely fearful of fat wasting, avoidance of zidovudine/lamivudine + efavirenz may make sense. It is more difficult to advocate for avoidance of efavirenz when combined with tenofovir given that 88% of patients on such a regimen did not develop major fat loss (compared to 60% on zidovudine/lamivudine + efavirenz).
Further, it must be remembered that the efavirenz + two NRTI group had better virologic results than the lopinavir/ritonavir + two NRTI arm during this study. Foregoing NRTIs altogether is currently impractical and, in this study, led to concerning increases in atherogenic lipoproteins.
In addition to influencing treatment initiation, this data may lead to interest among patients who have experienced peripheral fat loss on an efavirenz-containing regimen to switch from this NNRTI. It is not without some irony that we would now be tempted to change from an NNRTI to a PI to ameliorate a body shape change! It is premature to suggest this as a strategy, but HIV physicians are not typically inclined to wait the few years it takes for the definitive study to come along.
The lipid data are reassuring and prove once again the beauty of the head-to-head comparative trial.
The results raise many questions and have many an expert scratching their heads. The pieces of the puzzle may not all fit together yet, but the findings of A5142 are not completely incongruent with the overall understanding of fat depot change during HIV therapy. We have evolved from blaming antiretroviral therapy classes to pointing the finger at specific agents. We now see in this study, as well as A5005s, that particular combinations can exacerbate or attenuate the fat effects we ascribed to individual drugs.
It is traditional to end a study summary by indicating that further research is needed. However, in this case such a recommendation is not hollow. The ACTG is in the midst of recruiting for another large clinical trial comparing ritonavir-boosted atazanavir (ATV, Reyataz) versus efavirenz when each is combined with either abacavir/lamivudine (ABC/3TC, Epzicom, Kivexa) or tenofovir/emtricitabine (i.e., there are four study arms). This study, A5202, also collects DEXA and lipid data. Consider yourself warned.
The Other Lopinavir/Ritonavir Versus Efavirenz Study
While A5142 attracted almost as much attention as Beyoncé in her one-shouldered Armani Privé gown at the Academy Awards ceremonies in another part of Los Angeles, there was another interesting study comparing the metabolic effects of lopinavir/ritonavir and efavirenz at CROI 2007 that helps us wrap our brains around the A5142 results: M03-613.
M03-613 was one of a slew of lopinavir/ritonavir monotherapy studies that were presented at the AIDS 2006 meeting in Toronto last summer;7 the data on changes in fat were presented at CROI 2007 by W. Cameron et al. In this study, 155 treatment-naive patients were randomized 1:2 to either start zidovudine/lamivudine + efavirenz or begin an induction-maintenance strategy in which lopinavir/ritonavir + zidovudine/lamivudine would be taken until three consecutive viral load levels of less than 50 copies/mL were achieved, at which point the NRTIs would be discontinued.8 DEXA scans were performed every 24 weeks during the 96 weeks of study follow-up.
As in A5142, the efavirenz + two NRTI group experienced an early median increase in limb fat -- peaking at week 24. Then at week 48 these gains were largely lost. By week 96, this group had a median 9% loss in limb fat compared to baseline. These data alone are extremely helpful in understanding the effects of zidovudine/lamivudine + efavirenz and complement the data from A5142 nicely.
In contrast to the peripheral lipoatrophy seen with efavirenz, the lopinavir/ritonavir arm experienced a sustained gain in limb fat during the 96 weeks -- again, similar to the changes seen in the lopinavir/ritonavir + two NRTI group in A5142. Here, though, the NRTIs were cast off before week 48, which could have contributed to the further increases in median limb fat seen in this study arm from weeks 72 to 96. Thus, jettisoning the NRTIs led to further gains in peripheral fat while on this boosted PI.
As opposed to A5142, trunk fat data were presented. Again, the results were reaffirming, demonstrating the increase in abdominal fat that has been seen in every study of body shape in initial potent antiretroviral therapy. Increases in trunk fat were seen in both study arms and were not different.
Cleverly, the investigators looked at the correlation between limb and trunk fat changes, as well as the predictors of lipoatrophy and lipohypertrophy. The combination of limb fat loss and truncal fat gain was rare. Only 16% of the trial participants experienced this combination of changes -- all were receiving efavirenz.
This was illustrated gorgeously in one of the researcher's slides, which, as far as the correlation between changes in fat depots, looks remarkably similar to data generated from A5005s.9
A low CD4+ cell count at baseline was found to be associated with fat gain in both the limb and trunk regions.
The Bottom Line
These data should not be overshadowed by the results of A5142. The body fat data on efavirenz + zidovudine/lamivudine alone is of great interest and adds considerable heft to the argument that this combination causes peripheral fat loss over time. Certainly, the overall favorable body fat changes seen in the lopinavir/ritonavir group may be a consequence of an absence of an effect of this boosted PI on peripheral fat or the result of ditching the zidovudine/lamivudine. Probably it is both. The data on the correlation between changes in fat depots can be considered the gravy on top.
Anyone looking for answers to explain A5142 should look at this study. It does not explain everything, but it certainly does provide some help.
Growth Hormone Releasing Factor for Fat Accumulation
The body shape data from the M03-613 study described above demonstrated again what almost every HIV treatment trial that has bothered to evaluate fat changes has discovered: Regardless of regimen, truncal fat increases following the initiation of antiretroviral therapy. Much of this gain in fat is not completely undesirable and often represents a return to improved health and better appetite subsequent to control of HIV infection. For some patients, however, the increase in fat is too much of a good thing -- especially when it seems to be disproportionately centered deep in the abdomen. That some degree of abdominal fat gain is an expected consequence of antiretroviral therapy is now clear. Much more murky is what to do about it.
There are limited data regarding a beneficial effect of switching HIV treatment regimens to reduce visceral adipose tissue and this makes sense given both NNRTI- and PI-based regimens have been demonstrated to produce increases in abdominal fat.
The most consistently effective approach to truncal fat accumulation has been to use recombinant human growth hormone (rhGH). Reduced growth hormone secretion has been associated with fat redistribution.
In a study presented by Carl Grunfeld et al at AIDS 2006, rhGH was found to reduce visceral adipose tissue (VAT) mass following 12 weeks of induction therapy with 4 mg administered daily subcutaneously.10 However, 40% of the patients receiving rhGH had regained at least 50% of the VAT lost during maintenance therapy at a dose of 2 mg every other day. In addition, side effects including peripheral edema, myalgia, arthralgia and elevated blood glucose were fairly common during induction.
At CROI 2007 Steven Grinspoon presented the results of a large clinical trial of TH9507, a synthetic growth hormone releasing factor (GHRF) that is designed to elicit the release of growth hormone from the pituitary in a pulsatile manner, mimicking the physiologic secretion of the hormone and avoiding the high levels achieved with direct injection of rhGH.11
In the study, individuals with HIV and an increased waist circumference (> 95 cm for men and > 94 cm for women) and an elevated waist-to-hip ratio (> 0.94 for men and > 0.88 for women) while receiving antiretroviral therapy were assigned to inject 2 mg of TH9507 daily (n = 275) or to take a matching placebo (n = 137).
Change in VAT volume at six months, as assessed by computed tomography (CT) scan, was compared and there was a mean 15% decrease in VAT among patients who were taking the active drug versus a mean 5% increase in VAT among patients who were assigned to placebo (P < .001). The mean VAT mass lost with TH9507 was 1 kg in contrast to a 0.4 kg gain in the control group.
A concern with rhGH is that as a lipolytic agent, subcutaneous fat is also lost with therapy. In this study of TH9507, subcutaneous abdominal fat increased slightly in both study groups, tending to be a tad higher in the placebo study arm (P = .05).
Interestingly, lipid parameters improved with TH9507. Total cholesterol and triglycerides fell, while HDL cholesterol increased with active drug. In contrast, in the control group, triglycerides increased and HDL cholesterol decreased. There was no change seen in either glucose or insulin parameters.
There were more treatment-limiting adverse events in those taking TH9507; 12% on active drug compared to 3% in the placebo arm (P < .01). Myalgia and rash, in particular, were more common with TH9507. The rash, seen in 2% of treated participants, appears to be a hypersensitivity reaction that Dr. Grinspoon stated was not completely unfamiliar to endocrinologists prescribing injectable hormones.
The Bottom Line
This is an exciting compound that is undergoing continued study as a potential treatment of HIV-associated visceral fat accumulation, as well as conditions beyond HIV. This study will continue and will involve a cross-over design so that longer-term data will be available. If TH9507 is ultimately found to be efficacious, one can only hope that it will be more accessible and affordable than its predecessor rhGH.
Cardiovascular Disease and HIV Therapy
Deciphering the forces that influence cardiovascular risk during HIV infection is complicated. Findings from two important studies offer a hint of the complexity involved. The D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) study finds that the risk of myocardial infarction (MI) rises with each year of exposure to highly active antiretroviral therapy (HAART).12 The SMART (Strategies for Management of Anti-Retroviral Therapy) study discovers higher rates of cardiac events among HIV-infected patients who stop their antiretroviral therapy.13 Before launching into an attempt to make the results of these two impressive studies jive, it is worth looking at a few related presentations at CROI 2007.
Researchers from the SMART study provided details regarding the cardiovascular events that were recorded during the trial.14 SMART was a landmark clinical trial in which participants were randomized to:
The main results of the trial, stopped early due to excessive morbidity and mortality among those discontinuing HIV therapy, have recently been published.13 Interestingly, cardiovascular events were discovered to be more common among patients who had interrupted their antiretroviral treatment compared to those who were taking continuous treatment.
At baseline, the 5,472 SMART study participants had run-of-the-mill lipid levels for an HIV-infected cohort. Total cholesterol was 191 mg/dL, LDL cholesterol was 111 mg/dL, HDL cholesterol was 41 mg/dL and triglycerides were 164 mg/dL. Lipid-lowering drugs were used by 16% of the trial participants at study entry. Almost three quarters of the cohort were male and an astounding 40% were smokers.
As previously reported, there were 48 cardiovascular disease (CVD) events among patients interrupting HIV therapy compared to 31 among those who stayed on their meds. (The definition of cardiovascular disease events included clinical myocardial infarction, silent myocardial infarction, coronary artery disease [CAD] requiring an invasive procedure or death from cardiovascular disease.) The difference in cardiovascular disease rates between the study arms was marginal with a relative hazard of 1.57 (95% CI: 1.00, 2.46) -- a result that was just statistically significant with a P value of 0.05.
However, when the definition of cardiovascular disease was expanded to include peripheral vascular disease, congestive heart failure and coronary artery disease requiring drugs, the confidence intervals narrowed and the difference between the study groups favoring the continuous treatment arm became even more significant with a P value of 0.03.
Adding in unobserved death from an unknown cause increased significance even further (P = .009). Therefore, cardiovascular disease was more common among those interrupting HIV therapy and the differences between this group and the continuous therapy group only strengthened when cardiovascular disease was defined more broadly.
Interestingly, the investigators could find little to explain the excess cardiovascular disease events among patients discontinuing antiretroviral therapy. Neither HIV viral load nor CD4+ cell count -- whether on or off antiretroviral therapy -- during follow-up and cumulative years on antiretroviral therapy were associated with cardiovascular disease risk.
However, in general, lipid parameters among the participants stopping HIV therapy were not as favorable as those in the continuous treatment group -- largely a consequence of a drop in HDL cholesterol during treatment interruption. This may help to explain the slightly higher incidence of cardiovascular disease seen early in this study arm.
The association of HIV infection with cardiovascular disease (SMART) and with HIV therapy (D:A:D) has led many to consider HIV itself as a cardiovascular disease risk factor, to be included alongside traditional risks such as diabetes, smoking, strong family history of heart disease and hypertension.
Whether HIV-infected patients experience more cardiovascular disease than HIV-uninfected individuals has been difficult to determine since prospective studies such as D:A:D do not include a control group of HIV-uninfected persons.
However, in another CROI 2007 presentation, rates of coronary heart disease were found to be higher in HIV-infected men compared to HIV-uninfected men. Daniel Klein et al conducted a retrospective analysis of data from 1996 to 2006 from the Kaiser Permanente group in Northern California.15 They compared rates of coronary heart disease -- as determined by ICD-9 (International Classification of Diseases, 9th revision) coding -- among about 5,000 male HIV-infected members without known coronary heart disease and 43,000 age-matched uninfected controls. They found that rates of coronary heart disease were higher among HIV-infected men compared to HIV-uninfected men (6.1 versus 2.9, P < .0001). Among the HIV-infected men, PI treatment was associated with a higher coronary heart disease rate compared to those not on a PI (7.1 versus 4.5, P = .02). Further, the duration of PI therapy was associated with risk of myocardial infarction.
Looking at hospitalizations for myocardial infarction in a larger group of members followed over time, HIV-infected patients had higher rates of myocardial infarction-related admissions dating back to 1996-1997. However, the rate of hospitalization for myocardial infarction among the HIV-infected patients trended down from 1997 through 2000 and has since stabilized -- possibly due to less use of antiretroviral therapies linked to severe dyslipidemia and increases in the use of lipid-lowering therapy among HIV-infected patients.
Unfortunately, this study has limited ability to control for the traditional risk factors for coronary heart disease and myocardial infarction, such as smoking and family history of coronary heart disease, that may be unevenly distributed among HIV-infected and HIV-uninfected patients and confound the results.
The Bottom Line
So, how do we make sense of these data? Both D:A:D and the Kaiser study clearly indicate that exposure to HAART can increase the risk of cardiovascular disease. In both studies the relative risk of cardiovascular disease was higher with therapy; however, the absolute risk -- that is the number of events that occurred -- was pretty low, at least so far.
Yet, results from the SMART study informs us that not being on effective HIV therapy can also contribute to cardiovascular disease risk, perhaps by way of inducing inflammatory states during uncontrolled HIV. This suggests that the consequences of a treatment interruption may trump the risks of continuous HIV therapy.
Reassuringly, rates of myocardial infarction or cardiovascular disease are not increasing in D:A:D or the Kaiser study. Data from both studies and the HIV Outpatient Study (HOPS)16 actually find that rates of cardiovascular disease seem to be stable if not declining -- this is possibly due to better clinical lipid management.
If all this is confusing to you, imagine how our patients must feel. It is important that we help patients understand that, although HIV therapy can slightly raise the risk for cardiovascular disease, the consequence for not taking antiretroviral therapy is even worse.
The hallmarks of HIV-associated dyslipidemia are low HDL cholesterol and hypertriglyceridemia. However, some HIV-infected patients do have undesirable LDL cholesterol levels and the reduction of LDL cholesterol is central to cardiovascular disease risk reduction. As such, statins are the most popular family of lipid-lowering medicines prescribed to HIV-infected persons. Yet, statins can have clinically significant drug-drug interactions with antiretrovirals and may lead to treatment-limited adverse effects.
Ezetimibe (Vytorin, Zetia) is a novel agent that selectively blocks the absorption of cholesterol in the duodenum by approximately 50%. Further, the drug is not metabolized via the cytochrome P450 system used by many antiretrovirals. Compared to statins, ezetimibe is less potent in lowering LDL cholesterol and, therefore, is typically used in conjunction with these drugs.
The safety and efficacy of ezetimibe in HIV-infected patients has not been well studied. Two small studies of the drug in HIV-infected individuals with elevated LDL cholesterol have been published: One examined ezetimibe added to a statin in 19 patients and the other looked at ezetimibe alone versus fluvastatin (Lescol) in 20 patients.17,18 Both studies found a reduction in LDL cholesterol levels of 15% to 20%.
To better understand the effects and tolerability of ezetimibe in HIV-infected individuals, our group (which included this author) at the University of North Carolina, along with colleagues at the University of California, San Francisco, conducted a double-blind, cross-over study of ezetimibe in 48 HIV-infected patients who had an LDL cholesterol level of greater than 75 mg/dL and who were not receiving another lipid-lowering agent.19 Patients were randomized to six weeks of ezetimibe or placebo followed by a two-week washout period and another six weeks of the alternative assignment study medication.
After six weeks of treatment, there was a mean 12% reduction in LDL cholesterol among the patients while they were taking the ezetimibe compared to a 3% rise when they were receiving placebo. There was no change in HDL cholesterol or triglyceride levels with ezetimibe therapy and the drug was well tolerated.
The Bottom Line
Ezetimibe is an LDL-cholesterol-reducing agent that is free of many of the limitations of existing statins. The drug does not have pharmacological interactions with antiretrovirals and does not cause rhabdomyolysis. This study demonstrates that ezetimibe has moderate activity and, in addition to its use along side a statin, is a reasonable monotherapy option for patients who will not or cannot take a statin.
Alendronate Is Safe and Effective for Osteopenia in HIV-Infected Patients
Reduced bone mineral density (BMD) is common among HIV-infected patients. In one meta-analysis by Todd Brown et al, 67% of over 880 HIV-infected patients were found to have osteopenia and 15% osteoporosis -- rates that are several fold that of HIV-uninfected individuals.20
The cause of low bone mineral density among HIV-infected men and women is not entirely clear, but it appears to be largely a consequence of the same factors that promote bone loss in the HIV-uninfected and includes smoking, low body weight, sedentary life style and hypogonadism -- factors common among HIV-infected patients. Further, there may be HIV- and antiretroviral-related influences contributing to bone loss, although these remain poorly characterized.
Bisphosphonates are a mainstay of the treatment of osteoporosis; however, studies of the management of low bone mineral density in the setting of HIV infection have been limited to small trials. Two studies of the bisphosphonate alendronate (Fosamax) have been published and demonstrated improvements in bone mineral density during therapy.21,22
At CROI 2007, a larger trial of alendronate for low bone mineral density in HIV-infected patients was presented by Grace McComsey et al.23 ACTG study 5163 was a prospective, randomized, placebo-controlled multicenter trial attempting to evaluate the safety and effectiveness of calcium and vitamin D supplementation with or without once-weekly alendronate (70 mg) in improving bone mineral density in HIV-infected individuals.
A total of 82 patients on stable antiretroviral therapy with a DEXA-derived lumbar spine t-score worse than -1.5 were enrolled and randomized. At baseline, the median lumbar t-score was -2.15 in the alendronate arm and -1.95 in the calcium/vitamin D alone arm. Osteoporosis (t-score less than -2.5) was observed in 24% of the alendronate-assigned patients and 18% of the controls.
Seventy percent of each arm was male and, by design, a targeted number of women were enrolled. Importantly, there were a number of major exclusion criteria, including vitamin D deficiency (a 25-OH vitamin D level less than 15 ng/mL is rightly considered to be low, despite being within the stated normal range reported by many commercial laboratories), hyperthyroidism and untreated hypogonadism. Each are underlying conditions that when treated can improve bone mineral density.
Over 48 weeks, there were increases in lumbar spine (the primary outcome measure), total hip and trochanter bone mineral density. However, the median change from baseline was consistently greater in the alendronate arm. There was no difference between the arms at the femoral neck.
Click to enlarge
Grace A. McComsey, M.D.; reprinted with permission. Click here to download the complete slide presentation.
In terms of adverse effects, although alendronate is known to cause esophageal irritation, in this study there were no reports of this occurring. In fact, there were more moderate to severe clinical adverse events during the trial in the placebo arm than the alendronate arm. Laboratory abnormalities between the groups were indistinguishable.
The Bottom Line
This study should be the final word on the tolerability and efficacy of alendronate plus calcium/vitamin D in HIV-infected patients with reduced bone mineral density. The study's positive results raise three major issues. First, exactly who should be screened for reduced bone mineral density has not been clear. For A5163, participating sites were instructed to consider the following questions when considering obtaining a screening DEXA bone scan.
The more "yes" answers, the greater the likelihood that reduced bone mineral density would be present. These questions can be used clinically to identify patients for bone density screening. In addition, the guidelines for osteoporosis screening developed for the HIV-uninfected patient should also be followed.
The second issue is: At what level of reduced bone mineral density is pharmacological intervention warranted? There is little argument that patients with osteoporosis are candidates for treatment. Fuzzier is the use of alendronate at less severe t-scores (i.e., in cases of osteopenia). This study suggests that, at a minimum, patients with osteopenia (t-score -1.0 to -2.5) should take adequate doses of calcium and vitamin D twice daily as this intervention alone led to significant gains in bone mineral density.
For patients with worse scores within this range and/or multiple risk factors for osteoporosis, the addition of alendronate seems reasonable. (A note about calcium supplementation: Calcium carbonate is an antacid and it remains unclear if the effects of this formulation of calcium can interfere with atazanavir absorption. It still is unclear whether taking calcium carbonate and atazanavir apart from one another helps avoid this interaction. An alternative would be to use calcium citrate, which is not an antacid. However, using calcium citrate would require a higher dose to achieve the same level of elemental calcium and, therefore, require that a patient take more pills.)
Lastly, a legitimate question is whether improving bone mineral density will reduce fracture risk. Data from the HIV-uninfected has correlated bone mineral density to the risk of atraumatic bone fractures. There is no reason to think that among HIV-infected people this is not also the case -- especially as those living with HIV infection enjoy the prospects of decades of AIDS-free survival.
Reduced Bone Mineral Density Is More Common Among HIV-Infected Individuals
As mentioned above,20 there is considerable data indicating that patients with HIV infection have less dense bones than HIV-uninfected persons. In an analysis by Turner Overton et al of DEXA data from the SUN (Seguimiento Universidad de Navarra) Cohort, a prospective observational study of HIV-infected patients cared for at clinics in Denver, St. Louis, Providence and Minneapolis, the bone health of cohort participants were compared to those in the National Health and Nutrition Examination Survey III (NHANES III), a large sample of the general U.S. population.24 The HIV-infected SUN Cohort patients were matched according to age, sex, race, and BMI with NHANES III controls to identify the prevalence and predictors of osteopenia and osteoporosis among the HIV-infected participants.
The HIV-infected population included 22% women, was 60% white and 28% black and 75% of the participants were receiving antiretroviral therapy. Mean age was 41 years. Low bone mineral density was very common among the HIV-infected patients, with 51.7% meeting DEXA criteria for osteopenia and 9.8% for osteoporosis. Only 29.1% of the controls had osteopenia and 1.0% osteoporosis. Overall, the HIV-infected group had a significantly lower femoral neck t-score (-0.77) compared to the controls (-0.36) (P < .001).
Factors associated with low bone mineral density included male gender, a BMI less than 22.6 kg/m2, age greater than 46 years and being unemployed. Exercise was found to be protective. For osteoporosis, low BMI, older age, longer duration since HIV diagnosis and a CD4+ cell count less than 308 cells/mm3 was predictive.
Another study presented at CROI 2007, this one by Sara Dolan et al included only women and compared bone mineral density in HIV-infected (n = 152) and HIV-uninfected controls (n = 100) and examined the effects of androgen levels, weight, body composition and menstrual dysfunction on bone density.25 HIV-infected women had lower bone mineral density at the lumbar spine, total hip and femoral neck. Even HIV-infected women in the same weight range as the HIV-uninfected women had lower bone mineral density in these areas compared to the controls. Risk factors for reduced bone mineral density in the women with HIV infection included low free testosterone, low weight and oligomenorrhea.
Another analysis of total body bone mineral content data collected during A5005s also found that low testosterone levels were associated with reduce bone mineral density.26 Further, bone mineralization declined subsequent to treatment initiation regardless of treatment assignment (efavirenz or nelfinavir, zidovudine + lamivudine [3TC, Epivir] or didanosine [ddI, Videx] + stavudine). There was a median decline in total body bone density by 2.25% (IQR: 0.35% to 4.75%) by 96 weeks after the start of HIV therapy. It appeared that demineralization did not progress after week 96.
The Bottom Line
The results of these analyses help us better understand which patients should be screened for low bone mineral density and validate the list of screening questions above. The A5005s data further demonstrate that bone demineralization can be seen in patients receiving disparate HIV regimens and, as in most studies, seems to stabilize over time.
|Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.
The content on this page is free of advertiser influence and was produced by our editorial team. See our content and advertising policies.


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Information by Country
Iran (Islamic Republic of): Background
In 2001 Iran's Human Development Index remained classified as "medium" although it gained ground by moving from the 97th position in 2000 to the 90th rank in 2002. Iran continues to experience a transition from a traditional rural-based society to a semi-industrialized country and faces many challenges. These include: a) high unemployment (generally estimated to be above 25 per cent); b) a distorted distribution of income and; c) inequality of opportunity (although poverty is officially set at 18 per cent of the population, 16.5 million people can be considered as living under the relative poverty line).
The health status of Iranians has improved over the last two decades. Iran has been able to extend public health preventive services through the establishment of an extensive Primary Health Care network. As a result child and maternal mortality rates have fallen significantly, and life expectancy at birth has risen remarkably. Infant (IMR) and under-five (U5MR) mortality have decreased to 28.6 and 35.6 per 1,000 live births respectively in 2000, compared to an IMR of 122 per 1,000 and an U5MR of 191 per 1,000 in 1970.
Immunization coverage is over 90 per cent and polio is almost eliminated. Over 85 per cent of the population has access to health services and 90 per cent of births are attended by trained health personnel. The maternal mortality rate is reported at 37 per 100,000 live births. Tetanus Toxoid coverage of women stands at approximately 80 per cent. The prevalence of moderate to sever underweight, wasting and stunting are 11 per cent, five per cent and 15 per cent respectively. About 93 per cent and 73 per cent of households had access to safe drinking water and sanitary toilet in 2000 respectively. Malnutrition remains relatively high as a result of inadequate income distribution and poor caring practices, especially in rural areas.
Iran has one of the highest rates of drug usage in the region. In addition to its social and economic consequences, drug use is emerging as a major contributor to HIV infection and AIDS. Official figures show a total of 3,680 reported cases of HIV/AIDS but the Ministry of Health believes that the actual number of HIV infections is at least three times higher. Some 64.5 per cent of the cases were contaminated through intravenous drug use (IVDU), 8.9 per cent through sexual transmission, 5.1 per cent through blood and blood product transfusion, 0.4 per cent through mother-to-child transmission (MTCT). Some 21.0 per cent of the contaminations were of unknown origin.
Developments in education have also been positive. In 2001 the literacy rate of the population aged over six years of age has reached 80.4 per cent (85.1 per cent of men and 75.6 per cent of women). The urban-rural gap has also narrowed to about 14 per cent (86.25 per cent of urban population versus 72.4 per cent of the rural). There are, however, still noticeable differences among and within Iranian provinces. The net enrollment ratio is above 97 per cent and is almost equal among girls and boys.
However, national averages hide disparities related to gender and area. While the overall enrollment rate for boys is 98 per cent, it varies significantly between provinces. For girls, the range is between 99 per cent in Tehran and 84 per cent in Sistan and Baluchestan. The enormous gains in the educational status of the Iranian population can be attributed to massive governments investment in public education (on average 45 per cent of the governments social affairs budget since 1989). Unfortunately, with less than 15 per cent enrolment, Iran has a significantly low rate of pre-school attendance, with no significant difference between boys and girls. Hence efforts should be directed towards expanding opportunities for early learning of pre-school aged children.
Despite all the investment in womens education and health, womens employment, which had reached a high of 13.8 per cent of total persons employed just before the Revolution, has actually declined since (12 per cent in 1996). In December 2001 the Cabinet approved the submission of a bill to the Parliament on Irans accession to the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW) with a general reservation. The bill has however not yet been passed by Parliament.

subset: commoncrawl


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I hear a lot of parents talk about how their kids disagree all the time. Little disagreements burst into huge arguments that then become the bane of their parental existence. I have the opposite problem. The rough stuff around our house, the things that send everyone into nuclear explosion mode are the agreements. My problem is that the kids agree too much. My kids' biggest fights are caused by agreements included in but not limited to the following list:
1. The one true place to sit at the dinner table. The one true place changes from night to night but you can be certain that both kids will know exactly where it is and fight to the death to get it.
2. Which of the two remaining yogurt flavors is the best. Strawberry may have been the favorite yesterday but today there are two strawberries and only one peach. Suddenly peach finds its way into favor again. Today Magoo picked out the last remaining peach yogurt and brought Laylee a strawberry, the usual favorite. Chaos ensued as she tried to beg, bully and coerce him into giving her the new beloved variety. I went in to break it up and to tell her to deal with it but when I went back in a few minutes later they were happily munching and talking, Laylee with the prized peach.
"Give it back," I commanded, "You do not steal yogurt from your little brother."
"He gave it to me," she answered innocently, "He wanted me to have it." I stared at the two of them, my mom-dar fully active, my eyes squinting.
"Did you pay him?" I asked."Yeah," she conceded, a ball of defensiveness, "I gave him a dollar. I offered him five but he said one was enough."
They both grinned up at me. What do I do with that? They seemed to be in agreement so I went on my way, scheming about how I could get in on this action. It was only a fifty cent yogurt.
3. The precise moment when my lap is the most luscious and inviting. I could beg them to come snuggle me and all I get is a limp shoulder nuzzle and then moments later they come running into the room in attack mode, mauling me and yelling about whose idea it was to sit on my lap and be held like a baby first.
4. What to say. Sometimes they agree so much that they say the exact same things! Tonight I heard this conversation:
Laylee: It's my turn, I mean it.
Magoo: It's my turn, I mean it.
Laylee: Hey!
Magoo: Hey!
Laylee: Stop copycatting me.
Magoo: Stop copycatting me.
Laylee: I said STOP.
Magoo: I said STOP.Ahhhh, the dulcet tones of total vocal consent.
5. What Wanda needs. They may both ignore Wanda for huge portions of the day but when one of them decides she needs entertaining, they both get in on the action. Sometimes this is fine. Sometimes there's ample room for both of them to squeeze into her personal space, spitting and making faces and peek-a-booing their little brains out. Sometimes it's cute. But sometimes there's not enough room. At those times it is not cute. At those times, Wanda's not the only one who ends up screaming. Neither are the kids.
6. How mean I am.
Visit Daring Young Mom's personal blog.


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CHICAGO – Speaking publicly for the first time since announcing she wouldn't run for Illinois governor, Attorney General Lisa Madigan was tight-lipped Wednesday about what conversations – if any – she had with her politically powerful father before she made her decision.
Madigan ended months of speculation Monday when she said she wouldn't challenge Gov. Pat Quinn, a fellow Democrat, in 2014. In an emailed statement, she said she never planned to run if her father, longtime House Speaker Michael Madigan, remained in his job. The comment raised questions about whether the speaker — who has held his position for 28 of his 42 years in the Illinois House — had contemplated stepping down so his daughter could run.
Asked Wednesday whether they had discussed that possibility, Lisa Madigan wouldn't say.
"As you can imagine there's a process I went through in terms of evaluating how I could best continue to serve the people of the state of Illinois," she said during an unrelated event in Chicago. "Obviously that involved private conversations that I will not be going through with you publicly."
Steve Brown, spokesman for Michael Madigan, declined to comment when asked the same question.
Lisa Madigan's comments came on the same day the Regional Transportation Authority heard testimony from the former CEO of the Metra commuter rail service about his dealings with Illinois politicians, including Michael Madigan. Alex Clifford has said Michael Madigan asked Clifford's staffers to give a pay raise to a Metra employee who was a contributor to political campaigns benefiting the speaker. Clifford said the request — revealed late last week during an inquiry into Clifford's $718,000 severance — betrayed a "moral and ethical flaw," but Brown said Madigan did nothing improper.
Asked if her father had ever asked her to hire someone or give someone a raise, Lisa Madigan repeatedly said she doesn't deal with hiring.
She also said she didn't see a problem with the state having an attorney general and House speaker from the same family, even though she said Monday that "the state would not be well served" by such an arrangement if it involved a governor and the speaker.
"I don't think there's any question about the record that I've had serving as attorney general," Madigan said, noting she has collected billions of dollars for the state through legal actions, such as a national settlement with mortgage with the country's five largest bank mortgage servicers accused of fraudulent foreclosure proceedings.


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Moving into a new home in your golden years can be invigorating. Not only can you finally get that granite countertop and scrapbooking room, but you can also "buy" maintenance free living, energy-saving conveniences and even a sense of community. The good news is you have choices — and the even better news is the market is waiting to woo you.
Picking and choosing
Choice abounds at Del Webb's four active adult communities in Illinois: Sun City Huntley in Huntley, Edgewater in Elgin, Grand Dominion in Mundelein, and Shorewood Glen in Shorewood.
"All offer buyers the opportunity to purchase new construction, and we have homes that are finished that are ready for a quick move-in," says Maria Wilhelm, vice president of sales. "The buyer has a lot of opportunity to choose features, fixtures and materials if they buy a to-be-built home."
Del Webb offers ranches — one-story homes that range from approximately 1,190 to 3,000 square feet. "Depending on the community, we offer up to 16 floor plans that can fit any buyers budget and housing needs," Wilhelm adds.
Single story ranches are also popular at D.R. Horton's three active adult communities: Carillon Club in Naperville, Carillon at Stonegate in Aurora and Carillon at Cambridge Lakes in Pingree Grove.
"By designing the homes with all of the living space on one level, it creates more open living environments and a greater perception of space versus dividing up the living areas on two levels," says Chris Naatz, vice president of sales for D.R. Horton. "In addition, single level living is very adaptable to how people will live in the home over time."
However, the builder also accomodates buyers that want two-story living, as well as those who may want basements. "Overall, we offer a variety of home designs (including townhomes) so that people can choose a home that works well with their living style," he says.
For those whose choice is to forego single family living altogether and chores such as cooking and housekeeping, Mather LifeWays offers one and two bedroom independent living apartment homes in two of its Illinois communities: The Mather in Evanston, a continuing care community with 241 independent living apartments, and Mather Place of Wilmette, a smaller boutique setting with about 120 apartments, gardens and more intimate community spaces.
Gale Morgan, vice president of sales Mather LifeWays, says buyers interested in these two Mather properties are also looking to the amenities they offer.
"The community amenities are so rich and abundant with social and recreational opportunities," she says. "And while potential buyers are interested in downsizing their homes, they still want flexible design and use."
Must haves
So, just what are today's homebuyers looking for when they contemplate a move? A lot.
"Based on our experience, baby boomers want a large, open kitchen that connects seamlessly to the great room; a walk-in pantry and kitchen island; and they prefer a master bath with a walk-in shower," says Wilhelm. "They also prefer stainless steel appliances and hardwood floors."
Morgan says Mather residents are looking for more "function" rather than size in their kitchens. "However, they want quality in the finishes and appliances," she adds. "They are still looking for beautiful cabinetry, especially with the open-concept kitchens in view of the living areas."
Naatz agrees that the kitchen, no matter its size, still steals the heart of homeowners.
"Kitchens remain a hub of the home and our Carillon buyers look for convenient work spaces with islands and ample cabinet space with pantries," he says. "Often they will choose roll-out shelves and the convenience of the raised dishwasher option. Lever hardware is popular and makes it easy to open doors when your arms are full."
Flexibility, reflecting the way people live today, is a top trend.
"We design the homes to incorporate open spaces that are flexible and adapt to the way the owners live in the home," says Naatz. "For example, we create spaces that can be fully functional as either a formal dining room or an office. Sunrooms are popular and invite the outside in with light through large windows. Storage is always a forefront in our design criteria, which we accomplish through abundant closet space, extended garages, three car garages, attic storage and optional basements."
Morgan agrees that today's resident seems most interested in quality finishes, and design that offers flexible use and space.
"Second bedrooms generally become the den/office/hobby space with comfortable furniture that can accommodate guests on occasion,"she says. "The smaller dining table often is used as a card/game table and the open kitchen has a breakfast bar for serving or dining."
Wilhelm says flexibility is "an absolute. "
"They want a flex room that allows them to pursue their hobbies and interests like scrapbooking or photography, or to use the space for an office," she says, adding that more than 50 percent of Del Webb homeowners still work either full- or part-time.
When it comes to trends in material, Wilhelm points to the mixing of finishes of cabinets and countertops for different effect. For example, having the finishes on the kitchen island be different from the rest of the cabinets.
Naatz says one of the most important trends is energy efficiency. "Every Chicagoland D.R. Horton home that someone buys today will have the highly regarded Energy Star Certification," he says. "Ultimately owners can feel good about having an energy efficient home while also saving on their utility bills."
Naatz says on the top of Carillon buyers' list is desire for community.
"Ultimately, people are looking for more than a home," he says. "They are looking for fulfillment. They want to enjoy experiences and share interests with people that have common interests and goals."


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The Bisons took both games on Saturday against the Illinois State Redbirds to earn their first series sweep of the season.
Sophomore right-hander Davey Hackett received the start in game one at Dugan Field at Stephen Lee Marsh Stadium. Hackett pitched seven complete innings, giving up one earned run as the Bisons took an 8-1 decision. With the doubleheader sweep, Lipscomb improved to 10-18 on the year while Illinois State dropped to 12-13.
Bisons head coach Jeff Forehand said Hackett gave the team a confidence boost going into Saturday's double-header.
"We hadn't been able to find what's going to make Saturday click," Forehand said. "He was able to give us a good lift. He gave us the lift and the confidence that we could go into Saturday with a little bit of momentum and I think that was huge on the weekend."
Bisons junior right-handed pitcher Chad Fromm came in to close things out for the Bisons in the final two innings. Fromm did not give up a hit and struck out two batters.
The second of the two games on Saturday was not as easy for the Bisons. After three innings, Lipscomb jumped out to a 7-2 start. However, the Bisons watched the Redbirds score five unanswered runs over the next three innings to tie the game at seven. Both clubs scored a run in the seventh to remain tied at eight.
The game would stay tied until the bottom of the tenth inning when Bisons junior short stop Zach Messer singled to left field which brought in junior third baseman Cory Hale for the game-winning run. Messer leads the Bisons with 32 runs batted in on the season.
"Zach has come up in some situations all year long," Forehand said. "He has had opportunities to drive in a lot of runs, and he had a chance to get one there today. He has had some opportunities where he has had to learn and he hadn't gotten it done. He just had to stay positive, and tonight happened to be his night."
The Bisons used five pitchers in the second part of Saturday's double-header. Freshman left-handed pitcher Chris Nunn got the start for Lipscomb and went for three and one-third innings. He gave up seven hits and six earned runs while striking out five batters.
Junior right-handed pitcher Mike Grace came in to relieve Nunn and pitched for two innings. Grace gave up two hits and one earned run. Junior left-handed pitcher Alex Ross replaced Grace, and sophomore right-hander Josh Cotham came in after that. It was Bisons sophomore right-handed pitcher Dannie Strable who came in for the last two innings for Lipscomb and got credit for the win. Strable did not give up a hit and walked only one batter.
Forehand said it was great to close out the series with such an exciting finish.
"We have lost several of those this year," Forehand said. "You like to win them, and when you have an opportunity to win one in extra innings in a walk-off fashion it's great."
Seniors Ryan Wilkins and Tyler Wilson each had four hits on the day as well as junior catcher Matt Brewer who went four-for-four on Saturday. The only homerun on the afternoon was a solo shot by Hale over the left field wall in Saturday's first game. The homerun was Hale's sixth of the year.
Forehand said he hopes the sweep will give the Bisons some momentum as the season moves forward.
"I hope they realize that we started off slowly," Forehand said. "And I hope they realize that this team can accomplish a lot of things.
Inside our league it is really good and everybody knows it's good. The games will be just like that. They will be intense, and I am hoping this will be a spring board to next week's non-conference games but then also when Kennesaw State comes in next weekend."
The Bisons next action is on Tuesday night at home when Tennessee Tech comes to visit. The first pitch is scheduled for 6 p.m.
Written by Benjamin Seamon of the Lipscomb Athletic Media Relations Office


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If you've paid attention to Victor Pineda's story over the last year, you'll know that just making the U.S. U-20 roster was a challenge.
The Fire's original Homegrown player came close to making his competitive debut at the end of 2012 before a meniscus injury sidelined him through much of this year's preseason.
Ever resilient, Pineda recovered in time to join the U.S. U-20s and will hopefully take the field when Tab Ramos' side opens up the FIFA World Youth Championships Friday vs. Spain in Istanbul, Turkey (LIVE 1pm CT on ESPN2).
Yanks Abroad's Brian Sciaretta wrote this excellent piece on Pineda's road to Turkey.


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Paul Walker's daughter, Meadow Walker, has been awarded $10.1 million after a settlement with Roger Rodas' estate.
Rodas was killed along with Meadow's father in a 2013 car crash, and her lawyer Jeffrey Milam released a statement Thursday regarding the settlement decision:
"The amount paid by the estate of Roger Rodas into a trust for Meadow Walker only covers a fraction of what her father would have earned as an international movie star had his life not tragically been cut short."
The statement continues, "Through his estate, Mr. Rodas, the driver of the car, took partial responsibility for the crash. Meadow's lawsuit against Porsche AG – a $13 billion corporation – intends to hold the company responsibly for producing a vehicle that was defective and caused Paul Walker's death."
Probate papers filed in November 2014 state that while Rodas was "not directing the car through any particularly unsafe maneuvers when it went out of control," he was "nevertheless...responsible, in part, for the accident."
Milam further explained that after expenses and attorneys' fees, Meadow will receive about $7.2 million from the settlement.
Earlier this week, in an unrelated lawsuit, a judge shut down all four allegations made in a lawsuit filed by Rodas' widow including negligence, wrongful death and product liability.
"The issues in the cases are very different. The federal case was filed on behalf of Roger Rodas, who was the driver of the Porsche Carrera GT and was killed instantly upon impact," Milam told E! News in response to the judge's ruling. "Meadow's father, Paul Walker, was a passenger in the car. He survived the crash but was trapped and burned to death because of the vehicle's defects."
PHOTOS: Paul Walker's biggest roles
PHOTOS: Paul Walker's Life in Pictures


text: Don't think this will be sitting alongside Yakuza 0 as one of my (currently 3) GOTY runners but still, it's pretty damn good. Just gotta remember that whilst it is a remake, it's a remake of the first game and not a new entry in the series like 0 was, and 6 will be. Enjoying it a lot though


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BAGHDAD — The quarrel didn't last long.
BAGHDAD — The quarrel didn't last long.
Angry Sunni fighters temporarily abandoned their checkpoints in a western Baghdad neighborhood after Iraqi soldiers briefly detained some of their colleagues, whose U.S.-backed patrols have helped curb violence.
The dispute last weekend, although relatively minor, points to a deeper and more complex test next Wednesday as the Shiite-led government begins to assume authority over the Sunni fighters, also known as Sons of Iraq.
Many of the fighters are former insurgents and suspect their new masters want retaliation rather than reconciliation. Much of Iraq's ceaseless violence in 2006-2007 was sectarian-based, with Sunnis and Shiites launching horrific attacks on each other.
Prime Minister Nouri al-Maliki has vowed to reward those who joined in the fight against al-Qaida in Iraq, which lost most of its Sunni strongholds when local tribesmen turned against the extremist group and joined the U.S. payroll. The U.S. considers the initiative a test of the government's willingness to reconcile with Sunnis.
But tens of thousands of mostly Sunni neighborhood guards — a key element in the sharp drop in attacks in Iraq since last year — are deeply uneasy about the Iraqi government. Some Sons of Iraq groups, also labeled Awakening Councils, have complained about arrests and harassment by police and soldiers.
"They want to occupy checkpoints instead of us," said Wahab al-Zubaie, an Awakening Council spokesman in the western Baghdad district of Abu Ghraib, where the weekend dispute took place in the neighborhood of al-Hamdaniya.
Al-Zubaie warned that security could deteriorate if Sunni fighters are sidelined because they know "movements of al-Qaida members and their whereabouts" better than government forces do.
Last week, an angry Salah al-Ageidi, the Awakening Council leader in the primarily Sunni neighborhood of Dora in southern Baghdad, accused Iraqi police of detaining and beating up several of his 850 men before letting them go.
"We want to protect our area and we have succeeded in this so far," he said. "If we are disbanded, then chaos will prevail again in Dora."
Lt. Gen. Lloyd Austin, the No. 2 U.S. commander in Iraq, has said the Iraqi government will begin paying the salaries of about 54,000 mostly Sunni fighters in Baghdad province. Monthly income is expected to be about $300, the same amount that the Americans are paying. There are nearly 100,000 Awakening Council members altogether.
Iraq plans to merge 20 percent of the Awakening Council members into the security forces, while others could obtain jobs in civilian ministries or rebuilding and repairing damage from the war. The question is whether enough Awakening Council members will get the work and money to prevent them drifting into alienation, and even outright defiance toward the government.
"There are frictions in any transition. We should not expect this one to be any different," said U.S. Brig. Gen. Robin Swan, deputy commanding general of the 4th Infantry Division.
Swan spoke in an armored vehicle as it lumbered through Mansour, a mostly Sunni, western neighborhood of Baghdad that once hosted elite loyalists of Saddam Hussein and his Baath party.
The upscale area sank into chaos after the U.S.-led invasion in 2003, but Awakening Councils have helped restore some peace.
In some cases, the guards share checkpoint duty with Iraqi police and soldiers. U.S. Lt. Col. Monty Willoughby said tension at some checkpoints had erupted in "fisticuffs," though joint teams worked well in most cases.
On a recent afternoon, dozens of neighborhood guards filed into an U.S.-Iraqi combat outpost in Mansour to register for the Iraqi government payroll. They entered the cramped, high-walled compound by the back door, walking past latrines and stacks of plastic water bottles. A sign out front said in English: "Stay out. Coalition forces only. All others may be shot."
Many guards have died in attacks, payback from militants at war with U.S. and Iraqi forces. Last week, gunmen distributed leaflets in Tarmiyah, north of Baghdad, that demanded the disbandment of the Awakening Councils. "Otherwise, we will inflict painful and strong blows on you," they said.
A senior officer in the Interior Ministry, speaking on condition of anonymity because he is not authorized to speak to the media, hinted at the challenges of assimilating the Awakening Councils.
The Sunni fighters have to fill out a form, the officer said. "Then the security services will check the information to separate out the bad members whose hands are stained with the blood of Iraqis."


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|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|John Omernik <j...@omernik.com>
|Re: Large Scale Table Reprocess
|Fri, 26 Jul 2013 22:09:22 GMT
Can you give some examples of how to alter partitions for different input types? I'd appreciate it :) On Fri, Jul 26, 2013 at 3:29 PM, Alan Gates <email@example.com> wrote: > A table can definitely have partitions with different input > formats/serdes. We test this all the time. > > Assuming your old data doesn't stay for ever and most of your queries are > on more recent data (which is usually the case) I'd advise you to not > reprocess any data, just alter the table to store new partitions in ORC. > Then with time you'll slowly transition the table to ORC. This avoids all > the issues you noted. And since most queries probably only access recent > data you'll see speed ups soon after the switch. > > Alan. > > On Jul 25, 2013, at 4:45 PM, John Omernik wrote: > > > Just finishing up testing with Hive 11 and ORC. Thank you to Owen and > all those who have put hard work into this. Just ORC files, when compared > to RC files in Hive 9, 10, and 11 saw a huge increase in performance, it > was amazing. That said, now we gotta reprocess. > > > > > > We have a large table with lots of partitions. I'd love to be able to > reprocess into a new table, like table_orc, and then at the end of it all, > just drop the original table. That said, I see it being hard to do from a > space perspective. and I will have to do partition at a time. But then > theirs production issues, if I update a partition, insert overwrite int the > ORC table, then I have delete the original and production users will be > missing data.... decisions decisions. > > > > So any ideas? Can a table have some partitions in one file type and > other partitions in another? That sounds scary. Anywho, a good problem to > have... that performance will be worth it. > > > > > >
|View raw message


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10/3/00 Johnson City, Tenn.-- The East Tennessee State women's soccer team stepped out of conference action this afternoon and cruised to a 9-0 victory over South Carolina State at the Libety Bell Soccer Complex.
Freshman Melissa Wilder scored three times to record the second hat-trick in ETSU soccer history. The first hat trick in program history was recorded by Lisa Gallagher in a 3-0 win against Chattanooga during the 1998 season.
Her first goal came 22 seconds into the match as Rebekah Eisenberg and Elizabeth Smith threaded the ball through the Bulldog defense to a wide open Wilder. Wilder added her second goal of the afternoon after receiving a cross from Smith with 4:22 elapsed.
Lisa Gallagher also had a stellar performance as she scored twice with her first goal coming at the 12:25 mark when junior Lena Summers delivered a pass and Gallagher put it home from ten-yards out. Gallagher also added her second goal with an assist from Courtney Edde with 16:04 elapsed.
ETSU also received goals from freshman Shawn O'Donnell, freshman Andrea Brown, Summers and Redfern.
It was a good win and a great confidence builder for our team, said head coach Heather Henson. It gave us a chance to work on our attacking offense and to gain momentum going into our matches against Chattanooga and Western Carolina.
Freshman goalkeeper Heather Sanden notched one save and picked up her second win of the year.
The Bucs will return to action Friday, October 6 as they host in-state rival Chattanooga. Kick-off is set for 4 p.m. at the Liberty Bell Soccer Complex.


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A Dying Ember: Shades of Delusion
A Dying Ember: Shades of Delusion - Forum
Dungeons & Dragons 3.5e
An old, bloated sun turns in the sky. Its rays fall upon a world covered in thick, roiling clouds, making them glow a deep crimson with its wearied light. Continuous rain and snow fall from these clouds, like drops of blood from an unhealing wound...
The sky is your enemy, the clouds looked upon warily, and sleep is uneasy. This is the world within which you live. For several centuries the great overhead has been feared. Long ago a star fell screaming. There were no warnings. No prophesies. The gods themselves say nothing of it and many took it to mean they were also surprised and no longer worthy of worship. Since then others have streaked across the sky, sometimes several in a year, others separated by scores of years. No one knows when or where the next will fall, but when it does dreams sour and life palls. Many civilizations have fled from open areas to underground, in the deepwood, wherever they can hide from the vengeful gaze above.
Strangely, much good has come of it, like a fire cleansing the underbrush. As such, while there are a great many who now venerate the sky, others simply think it is punishment from the deities. Trade still exists, and fields are sewn, but merchants and farmers are often greatly revered as men of uncommon fiber. A small minority think them men of great vanity, strutting beneath the open sky without proper reverence. Wars are rarely fought as it would mean taking great resources from the safety of the covered cities into view. The common consensus is why war on another when all could be destroyed with but a thought from above.
The main outbreaks of violence come of those from the open moving in on the land of the hidden. Fey creatures have begun to retaliate as mortals push deeper into forbidden sylvan depths. As well, Priests of Ruin are known to mete out punishment to those who venture into the open. They perform raids as warnings or sew complete devastation as an example to others.
It was twenty six years since the last fall, and many had begun to dare hope it was the last. Then three months ago the peace was broken in the middle of the night. A great fireball fell along the coast, destroying the home of the Seven Sages, seers and watchmen for the world. Since this star fell, thousands across the distances have fallen into a sleep so deep that none reawaken. They continuously thrash and scream, as if held in the throes of a nightmare from which they cannot awake. Many have died, while the more hardy can only be nursed as they wither away. Many have begun to change in uncanny and inexplicable ways.
The cult of Ruin has grown bold, attacking even in broad daylight, and fields and villages burn through the land. Many have fought back, however, in particular the roaming merchant city called the Bazaar, or Banzar. Though they have been burnt, kidnapped and murdered, they still move beneath the open sky, trading with the farms turned forts and taking in refugees. They have settled, for one day only, to host a festival and wake for both the living and the dead. A celebration of those who have defied Ruin. A gesture to oppressors that there are still those who will walk where they wish.
These are the events that currently define your life.
I have been running this campaign for nearly a year, but am looking to bring in some new blood. This is an edited version of this original thread here that I am reusing.
Character Creation
Game Description:
This is to be a gritty, high RP epic. Not epically leveled per se, but a tale of scope and depth.
Last edited by Silkspinner; Jun 4 '12 at 10:05pm..
|Man this game must be awesome.


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|Glen Arm, MD
|High School:
|Loyola Blakefield
2012: Appeared in all 13 games. He scored three goals, including a goal in a 13-9 win over Quinnipiac on April 28th.
2011: Played in all 13 games and made one start for SHU...Scored seven goals and added four assists for 11 total points...Registered a goal and an assists in an 11-6 win over Manhattan (3/12)...Tallied two scores against Bryant (4/16).
2010: Appeared in eight games as a freshman...Dished out five assists...Assisted on a pair of goals vs. Marist (2/27).
Before SHU: Played volleyball, basketball, and lacrosse at Loyola Blakefield High School...Named to 2nd Team All-State for lacrosse as a senior... Towson Times Athlete of the Year for 2008-'09...captained volleyball team twice and selected All-League twice.
Personal: Trevor Van Dauses. Born: 2/22/91. Parents: Barbara and Wade. Siblings: Cory and Alec. Major: Accounting. Hobbies: Sports, guitar. Favorite Team: Baltimore Ravens. Favorite Athlete: Steve Nash. Favorite Book: No One Here Gets Out Alive. Favorite Movie: Lord of War. Favorite Music: Classic rock. Favorite Food: Steak. Role Model: Dad.


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Submitted by Tania Ganguli on October 12, 2011
The Florida Times-Union
Pittsburgh Steelers watches his team play against the Tennessee Titans during the game on October 9, 2011 at Heinz Field in Pittsburgh, Pennsylvania. (Photo by Jared Wickerham/Getty Images)
Caused a stir with a tweet earlier about Steelers head coach Mike Tomlin hanging up on us during the conference call, so here's a little context to it.
First, understand, the playoff game between the Steelers and the Jaguars that followed the 2007 season had big implications for this franchise.
The Jaguars 31-29 win was Jack Del Rio's only playoff win as a head coach and followed a season when the Jaguars went 11-5 and thought they had a defense that was just a few pieces away from winning a championship.
After the season, Del Rio got a four year, $21 million extension, David Garrard was awarded the richest contract in franchise history, a six-year extension worth $60 million and the Jaguars traded seven draft picks to move up in the first and second round to take Derrick Harvey and Quentin Groves, neither of whom are still on the team.
It was a season that heavily impacted the Jaguars future, and that game that had a lot to do with it.
You'll read that story in a few places this week. So, when the Steelers called in for Tomlin's conference call with Jacksonville beat writers, it came up.
Now, Tomlin has a testy history with us, specifically my colleague Vito Stellino. It's something we laugh about and something he's laughed about with us in the past. It all started back in 2007, during the regular season game, when Stellino asked Tomlin a question about the running game that Tomlin objected to. As Stellino recalls, he asked Tomlin something along the lines of "What's the problem with the running game? The Steelers have been running the ball for 50 years."
So today's conference call began with Tomlin being asked if he remembered Stellino and Tomlin replying that he "unfortunately" did.
Chuckles all around.
We asked about the Steelers run defense. We asked about Ben Roethlisberger, we asked if the age of his defense was a concern. Then, another reporter (it wasn't Stellino), the Associated Press's Mark Long, asked if he had any memories from the playoff game after the 2007 season.
"Not really," Tomlin said. "I remember David Garrard of course on the draw on fourth down. That's one of those plays you'll never forget. It was a big play."
It was a very big play, and one on which officials missed a holding call. In March at the league meetings Mike Pereira, then the league's vice president of officiating, said officials missed the holding call.
As a follow up, and here's where it got testy, Long asked if he sent the play to the league office.
"No," Tomlin said.
Why not?
"Why would I?"
Wasn't there a questionable non-call on that play? Holding?
"Guys, come on man. I'm not going to cry over four-year-old spilled milk. Anybody got any legitimate questions? Goll-lly," Tomlin said, clearly perturbed.
We chuckled, but Tomlin didn't. So Long tried to explain it was a big game from a Jacksonville standpoint and that's why he was asking.
"Guys, that was four years ago," Tomlin said. "I understand that might have been a big game in Jacksonville but that's old news. Many of those guys are no longer here and definitely many of the guys that were in Jacksonville are no longer there. Anybody got any questions relative to this week?"
Three seconds passed and Vito began to ask a question, but Tomlin jumped in before he could finish his question.
"Thank you, have a good one."


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The International Black Sheep Society of Genealogists (IBSSG) is an Association of Genealogists who have found "blacksheep ancestors" in their direct family lines, or under the "One Degree Rule" of the Society.
The One Degree Rule is: If a person lived in the family domicile of an ancestor, and the actions of that individual affected the family, as if they were a ancestor, or member of the immediate family, then that individual's acts can be used for membership qualification under this rule.
The Society was formed in late 1997.
The mailing list for the International Black Sheep Society of Genealogists (IBSSG) is firstname.lastname@example.com, a combined topic list, where most of the activity occurs. the Society list requires you to subscribe before posting, non-member posts are held for approval, and since answers will likely be posted ON the lists, you should consider joining to see them.
Subscribing to Blacksheep
Subscribe to Blacksheep by sending a NEW email from the address you wish subscribed to: firstname.lastname@example.com adding the word SUBSCRIBE as the subject or body. If you want a daily digest of the list instead of individual emails, contact: firstname.lastname@example.com
A note of caution, the list is a high traffic list, and the topics are NOT limited to genealogy, but should have a connection to genealogy. Being a society, we like to be friendly with each other, it is a club.
Qualification for the Society membership (and the right to use IBSSG after your signature in genealogy correspondence) is granted on the main list ( firstname.lastname@example.com) by posting the following:
To: firstname.lastname@example.com
Subject: Qualification request
Body should mention the following: Your relationship to the individual Why you think he or she is a Blacksheep of the Family Whether or not the acts were of a social or criminal nature, unless it is obvious.
IMPORTANT If the individual is living, or the acts are still having an immediate effect on your family, or disclosure may lead to danger to anyone, please do not submit the details publicly.
Our Tender Lambs Corner is set up for the PRIVATE submission of this type of qualification, please write our Tender Lambs Coordinator (TLC) Sue Bates (mailto:firstname.lastname@example.com) to submit directly to her confidentially. What you submit under the TLC program is entirely private. Only Sue will know, and will announce your membership without details.
Purpose and Goals
The purpose of the Society is to discuss family blacksheep in order to learn more about them and share information about your "Black Sheep" with other members of the IBSSG! Many times having a Black Sheep in the family leads to a family "wall of silence" and research into the family becomes very difficult. Our Goal is to help find alternate routes to information sources, and to "normalize" the view of the blacksheep as a person, who has a place in the FACTUAL history of the family, without regard to behaviors.
Remember, the acts may be embarrassing to others in your family, but within the Society, you are not alone! Many of us have similar situations, and can relate (actually many of us are related) to the problems in doing this research.
Jeff Scism, IBSSG
Sunday, June 7, 2009
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© 2006 http://www.vintagecrochet.co.uk
Lucky Star 7144 Tablecloth
New Ideas in Crochet-Table Topics
Book No. 123
The Spool Cotton Company - 1938
eBook is authored and published by
Goldsky Media
Smashwords Edition
Copyright 2006 All Rights Reserved
It is not for resale by any other party
Smashwords License Notes
This eBook is licensed for your personal enjoyment only. This eBook may not be re-sold or given away to other people. If you would like to share this book with another person, please purchase an additional copy for each recipient. If you're reading this book and did not purchase it, or it was not purchased for your use only, then please return to Smashwords.com and purchase your own copy. Thank you for respecting the hard work of this author
© 2006 http://www.vintagecrochet.co.uk
Table of Contents


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Mary Shelley's classic horror tale of science gone awry has given Hollywood shambling visions of cemetery horror for decades, among them Boris Karloff's iconic 1930s performances and Robert DeNiro's very different take in the 1994 Kenneth Branagh remake. Next up? Guillermo Del Toro says that after he finishes the two-film version of " The Hobbit" he will turn his attention to the gothic morality tale and that actor Doug Jones (Abe Sapien in "Hellboy") might play the patchwork man. This one is still a long way off; "The Hobbit" films are due in theaters in 2010 and 2011. Del Toro has also talked about making a "Slaughterhouse Five" remake.
Copyright © 2018, Sun Sentinel


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Netanyahu: Israel won't let Iran get nuclear arms
Israeli Prime Minister Benjamin Netanyahu played the spoiler Tuesday to Iran's attempts to ease relations with the West, calling the Iranian leader "a wolf in sheep's clothing" and declaring that Israel will do whatever it takes to prevent Tehran from developing nuclear weapons, even if it has to stand alone.
Speaking to world leaders at the U.N. General Assembly, Netanyahu gave a point-by-point rebuttal of President Hassan Rouhani's speech last week signaling a willingness to discuss Iran's disputed nuclear program.
Accusing Rouhani of a "charm offensive" aimed at getting the West to lift crippling sanctions, Netanyahu portrayed him as "a loyal servant of the regime" who has done nothing to stop his country's nuclear program since he took office in June.
Rouhani, he added, must have known about terrorist attacks carried out by Iranian agents in Argentina, Saudi Arabia and Berlin in the 1990s because he was national security adviser at the time.
Israel's hope for the future is challenged "by a nuclear-armed Iran that seeks our destruction," the Israeli leader said.
A year ago at the General Assembly, Netanyahu held up a drawing of a spherical bomb with a sputtering fuse, then pulled out a red marker and drew a line across what he said was the threshold Iran was fast approaching and which Israel would not tolerate — 90 percent of the uranium enrichment needed to make an atomic bomb.
"Iran has been very careful not to cross that line," Netanyahu said Tuesday. "But Iran is positioning itself to race across that line in the future at a time of its choosing."
"I wish I could believe Rouhani, but I don't because facts are stubborn things, and the facts are that Iran's savage record flatly contradicts Rouhani's soothing rhetoric."
He pointed to Iran's continuing enrichment of uranium to a 20-percent level, its addition of thousands of new centrifuges and its development of intercontinental ballistic missiles "whose sole purpose is to deliver nuclear warheads" that the U.S. says will be capable of reaching New York in three or four years.
"Israel will never acquiesce to nuclear arms in the hands of a rogue regime that repeatedly promises to wipe us off the map," Netanyahu declared. "I want there to be no confusion on this point: Israel will not allow Iran to get nuclear weapons. If Israel is forced to stand alone, Israel will stand alone."
After his address, Netanyahu, like Rouhani, received warm applause.
Iran exercised its right of reply, with Khodadad Seifi, a deputy ambassador to Iran's U.N. mission, accusing Netanyahu of "saber rattling" and warning that he should "avoid miscalculation."
"Iran's centuries-old policy of non-aggression must not be interpreted as its inability to defend itself," Seifi said. "The Israeli prime minister had better not even think about attacking Iran, let alone planning for that."
He reiterated Iran's readiness to engage in "meaningful, time-bound and result-oriented negotiations" and "to ensure that its nuclear program will continue to remain exclusively peaceful."
Earlier, Iran's foreign minister, Mohammad Javad Zarif, said Netanyahu's nature was "to lie."
"Over the past 22 years … Israel has been saying Iran will have nuclear arms in six months," said Zarif, speaking in New York in an interview broadcast on Iranian state TV. "The continuation of this game, in fact, is based on lying, deception, incitement and harassment."
At the White House, press secretary Jay Carney said Netanyahu's skepticism about Iran and its intentions is "entirely justifiable" because until recently Iran's leadership "was pledging to annihilate Israel."
The U.S. shares Israel's goal of keeping Iran from obtaining a nuclear weapon, Carney said. He stressed that President Barack Obama will be "very firm" on demanding verifiable, transparent action to ensure that Iran has given up its nuclear weapons ambitions.
Netanyahu warned that a nuclear-armed Iran would have a choke-hold on the world's main energy supplies.
"It would trigger nuclear proliferation throughout the Middle East, turning the most unstable part of the planet into a nuclear tinderbox. And for the first time in history, it would make the specter of nuclear terrorism a clear and present danger," the Israeli leader said.
Netanyahu said the greater the pressure, the greater the chance for diplomacy to succeed. The only diplomatic solution, he said, is one that requires Iran to completely dismantle its nuclear weapons program and prevents it from starting one in the future.
This would require a halt to all uranium enrichment, removing uranium stockpiles from Iran, dismantling the infrastructure for "nuclear breakout capability" — reaching the point where the country can make a quick dash to a nuclear weapon.
He also said it would require stopping all work at a heavy water reactor aimed at producing plutonium, which like uranium can be used to produce nuclear weapons, he said.
At the U.N. last week, Rouhani presented a more moderate face of the hard-line clerical regime in Tehran.
He agreed to the first nuclear talks with six world powers since April at a meeting Thursday on the sidelines of the General Assembly, where Zarif and U.S. Secretary of State John Kerry met privately. On Friday, Rouhani and Obama spoke on the phone for 15 minutes, the highest-level contact between the two countries in 34 years.
But Netanyahu said Rouhani's goal was the same as his hard-line predecessor, Mahmoud Ahmadinejad.
"Ahmadinejad was a wolf in wolf's clothing. Rouhani is a wolf in sheep's clothing, a wolf who thinks he can pull the wool over the eyes of the international community," Netanyahu said.
All Iranian presidents serve the same "unforgiving regime" where the supreme leader, Ayatollah Ali Khamenei, is a dictator and the real power, Netanyahu said.
Netanyahu asserted that Rouhani must have known about the murder of 85 people in a terror attack on the Jewish Community Center in Buenos Aires in 1992, as well as the killing of 19 American soldiers in Saudi Arabia in 1996 and the slaying of Iranian opposition leaders in Berlin in 1992 because he was head of Iran's Supreme National Security Council from 1989-2003.
The U.S. has also accused Iran of sponsoring acts of terrorism around the world throughout the 1990s, blaming Iran and its proxy Hezbollah for a 1992 attack on the Israeli Embassy in Buenos Aires that killed 29 people, as well as the community center attack two years later. Some analysts linked Iran's Quds Force to helping direct the 1996 bombings of the Khobar Towers in Saudi Arabia that killed 19 American military personnel.
Netanyahu said Rouhani condemned the "violent scourge" of terrorism. "Yet in the last three years alone, Iran has ordered, planned or perpetrated terrorist attacks in 25 countries on five continents," he charged, without providing any evidence.
He also accused Iran of lamenting the human tragedy in Syria, while at the same time directly participating in President Bashar Assad's murder and massacre of tens of thousands of innocent men, women and children. He said Iran is propping up a Syrian regime that just used chemical weapons against its own people.
He said Rouhani denounced attempts to change the regional balance in the Middle East through proxies. "Yet Iran is actively destabilizing Lebanon, Yemen, Bahrain and many other Middle Eastern countries," Netanyahu said.
He cited an attempt by Iranian agents to assassinate Saudi Arabia's ambassador to the United States in Washington two years ago, and the arrest of an Iranian agent three weeks ago trying to collect information "for possible attacks against the American Embassy in Tel Aviv."
Israel's Shin Bet security agency says Iran recruited the Belgian-Iranian national Ali Mansouri last year and sent him to Israel to spy. He was arrested on Sept. 11 at Israel's international airport.
A lawyer for Mansouri said the allegations are baseless.
Israel announced the arrest on Sunday as Netanyahu left for the U.S. Israeli media have speculated that the timing of the announcement was politically motivated.


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Definition of ogham
n. - A particular kind of writing practiced by the ancient Irish, and found in inscriptions on stones, metals, etc. 2
The word "ogham" uses 5 letters: A G H M O.
No direct anagrams for ogham found in this word list.
Words formed by adding one letter before or after ogham (in bold), or to aghmo in any order:
e - homage ohmage s - oghams
Shorter words found within ogham:
ag ago ah am gam go goa ha hag ham hao hm ho hog ma mag mho mo moa mog ogam oh ohm om
List shorter words within ogham, sorted by length
Words formed from any letters in ogham, plus an optional blank or existing letter
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Other words with the same letter pairs: og gh ha am
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Easy Egg Salad Recipes
Cauliflower Tomato Salad Recipe
We recently had guests for dinner and I made a cauliflower and tomato salad. I explained to our guests how this "salade de chou fleur et tomates" was made and the following day our guests emailed me back thanking me for this new recipe.
Inevitably, whenever we have guests over, my mother-in-law exclaims "Look what an amazing dish Jackie made today! Did you know Jackie has a food website? She posts daily recipes on PhamFatale.com and she's a soon-to-be published author." And whenever she goes anywhere, she talks about my cooking and about PhamFatale.com. And now that I have my first cookbook coming out soon ("Haute Potato" due on December 18th), she hands out cards to promote my book. She's my own one-woman PR firm!
Back to the dish...I boiled cauliflower very briefly then flavored it with champagne vinegar and a bit of honey. I mixed the cauliflower with beautiful heirloom tomatoes from our garden and shredded lettuce. For a nice contrast in texture, I added lightly toasted almond slices. If you want more crunch you could also top the salad with croutons.
Full Recipe...
French Cauliflower Salad Recipe (Salade de Chou Fleur)
Today's recipe is an easy and healthy salad called "chou-fleur vinaigrette". During my childhood in France, it was a dish that was served fairly frequently at the cafeteria of my elementary school (carottes Vichy too!). Cauliflower is boiled, then coated with vinegar and oil and sprinkled with flat-leaf parsley. That's it! Who says French cooking has to be complicated?
I've mentioned quite a few times lately that I've been trying to eat healthier. Cauliflower is a big part of that because it's packed with fiber and vitamin C. But cauliflower salad is not a full meal by itself, so I added hard-cooked quail eggs and a piece of bread on the side. It's a simple, quick and healthy summer meal. Rachael Ray would be proud!
Full Recipe...


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Oct. 19, 2008
NEW HAVEN, Conn. - The No. 1 Bulldog women's sailing team qualified for the Women's Atlantic Coast Championships by virtue of its fourth-place performance with 184 points at the Yale Women's Intersectional held Saturday and Sunday at the McNay Family Sailing Center. The fourth-place finish is an improvement over last year, when the team placed eighth. The regatta was won by No. 2 St. Mary's College of Maryland.
The Yale Women's Intersectional is the only women's sailing regatta the Bulldogs will host this season and the Bulldogs made it count by sailing relatively consistently in tough conditions. The wind came from the North, which at the McNay Family Sailing Center is a direction where the wind frequently shifts with large puffs that roll through the course. On Saturday, the wind started out breezy, before dying as the day went on, allowing six races to be sailed in each division. On Sunday, the wind ranged from five-to-18 knots from the North and again was very shifty. In shifty, puffy conditions, it is frequently tough to be consistent in finishes because wind shifts are many times tough to predict and they can drastically change the outcome of races.
Senior captain Kate Hagemann and sophomore Elizabeth Brim were not daunted by the tricky conditions, however, as they sailed to a fifth-place finish in A Division, only five points out of third place. The duo won two of the 12 races during the regatta and placed second in one more race.
In B Division, junior Rebecca Jackson and senior Adriane Levin placed sixth with 99 points, only nine points out of third place. Jackson and Levin won one race and placed in the top-five finishers in four of the 12 races.
"The breeze was very shifty and puffy, which made it tough to be consistent," Jackson said. "We started strong on both days and learned a lot about sailing in the conditions that we faced. It was nice to be able to sail at home and qualify for the Women's Atlantic Coast Championship."
The Bulldogs performance is an overall improvement over the 2007 result, when the Bulldogs finished eighth overall. Hagemann and Brim matched their fifth place finish from 2007 while Jackson improved on her 13th place finish.
By being the second best New England Intercollegiate Sailing Association school at the event, behind No. 5 Boston College, the Bulldogs qualified for the Women's Atlantic Coast Championships that will be held Nov. 15-16 at Georgetown. The Women's Atlantic Coast Championships will feature the top 18 schools from the NEISA, MAISA and SAISA districts of college sailing. These three districts historically have some of the most competitive teams in the country, with 14 of the 15 ranked teams in college sailing from these three districts. In effect, the regatta can end up being the most competitive regatta of the year, even more competitive than the national championship. The Bulldogs, who hosted the event last year, impressively won the Championship.
The Bulldogs are next in action at the ICSA Singlehanded National Championship at Cornell and the Stu Nelson Trophy at Connecticut College. The ICSA Singlehanded National Championship will feature senior Bulldog Jane Macky, with competition starting on Friday and continuing through Sunday while the Stu Nelson Trophy will take place on Saturday and Sunday.
Report filed by Caleb Dorfman '09, Yale Sports Publicity