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Official websites use. Share sensitive information only on official, secure websites. Lai S, Gestenblith, Li, and Lai H designed the study and conducted the analyses and prepared a draft of the manuscript. Lai H undertook the statistical analyses. All 11 authors contributed to, and have approved the final manuscript. It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy ART ; however, factors associated with these conditions have not been thoroughly investigated. The goals of this study were 1 to identify the risk factors for myocardial and hepatic steatosis in HIV-infected African Americans AAs and explore whether ART use is independently associated with myocardial and hepatic steatosis, and 2 to examine whether and how cocaine use influences any associations of ART use with myocardial and hepatic steatosis. Proton magnetic resonance spectroscopy was performed to quantify myocardial and hepatic triglyceride contents. Sociodemographic, medical and laboratory data were also obtained. Robust regression model was employed to perform primary statistical analysis. Free fatty acids are well recognized as the major source of energy for the myocardium. Under normal conditions, the majority of free fatty acids in the myocardium undergo rapid oxidation and little is stored. But when fatty acids influx into myocardial cells exceeds the oxidative needs, the excess fatty acids may be stored as triglycerides, resulting in myocardial, or cardiac, steatosis Schaffer, As a new marker for LV dysfunction, myocardial steatosis is common in patients with diabetes or obesity, and is associated with lipoapoptosis Szczepaniak et al. Animal model studies suggest that myocardial steatosis may result in cardiac dysfunction and eventual cardiomyopathy Glenn et al. However, the mechanisms responsible for the development of myocardial steatosis and the factors associated with myocardial steatosis in humans are not fully understood. In addition to its association with metabolic syndrome and diabetes, antiretroviral therapy ART used in treating HIV infection may also be associated with myocardial steatosis in persons with HIV infection Holloway et al. Nevertheless, the risk factors for myocardial steatosis in those with HIV infection have not yet been thoroughly investigated. Also, since cocaine use is known to modify the association between body mass index and myocardial steatosis Lai et al. In addition to myocardial steatosis, ART may also be associated with hepatic steatosis, a condition that may lead to liver inflammation Moreno-Torres et al. This investigation had four objectives. The first was to examine whether ART use is independently associated with myocardial steatosis, the second to assess whether and how cocaine use influences any association between ART use and myocardial steatosis, the third to examine whether ART use is independently associated with hepatic steatosis, and the fourth to assess whether and how cocaine use influences any association between ART use and hepatic steatosis. Of these , were HIV-infected. Chronic cocaine users who also used other drugs such as opiates or alcohol were included. Non-cocaine use was defined as never having used cocaine or not having used in the past 5 years or longer; assessment of cocaine use was based on self-reported use; and 4 AA race self-designated. Exclusion criteria were 1 any evidence of clinical coronary artery disease CAD or any history of or current symptoms or diagnoses related to cardiovascular disease; 2 pregnancy; and 3 history of MRI-related claustrophobia. All procedures used in this study were in accordance with institutional guidelines. Although the overall investigation is a cohort study, the data presented herein are cross-sectional baseline only. During the baseline visit, study participants underwent a detailed interview to obtain information about sociodemographic characteristics, medical history, behaviors, including alcohol consumption, drug use, and cigarette smoking, and medications. A medical chart review was used to confirm the information on medical history and medications provided by the study participants. A physical examination was performed and vital signs were recorded. Routine clinical laboratory blood chemistry tests were conducted. The following laboratory tests were performed at baseline: total serum cholesterol, triglycerides, high-density lipoprotein HDL , low-density lipoprotein LDL , glucose, and inflammation markers, including high-sensitivity C-reactive protein hsCRP. All studies were performed on a 3. Participants were instructed to hold their breath at end expiration during imaging and to breathe normally during spectroscopy. To measure left ventricular LV function, the heart was imaged in both long and short-axis orientations, using retrospectively gated steady state free precession cine images. One grid tagged short-axis slice was obtained at the middle LV. Myocardial 1 H MRS spectra were obtained with electrocardiogram gating during early systole, with navigator gating to enable free-breathing using a single voxel point-resolved spectroscopy sequence. The spectroscopic volume 6- to 8-mL voxel was positioned within the interventricular septum. The navigator was placed across the liver-lung interface. For reliable measurement of the low-fat signals, one spectrum was recorded with water suppression 32 averages , and another spectrum eight averages was recorded without water suppression Venkatesh et al. Measurement of hepatic triglyceride content was performed using the same sequence with the MRS voxel placed in the right hepatic lobe. Eight averages of water suppressed as well as eight averages of no water suppressed spectrum were acquired with breath holding. The areas under the resonance frequency estimates of lipids at 0. Myocardial fat fraction was expressed as the ratio of fat to water and reported as a percentage, while hepatic fat fraction was expressed as the ratio of fat to water plus fat and also reported as a percentage. Pre-study sample size was calculated to test a hypothesis that ART use and cocaine use have a synergistic effect. According to the results of previous regression analyses, the R 2 for cocaine use and the R 2 for ART use were roughly identical 0. The alpha was set to 0. With a sample size of , the power to test the above-mentioned hypothesis would be 0. With at baseline, participants would remain in the study after adjusting for the dropouts. Therefore, with a sample size of , the power to test this hypothesis would be 0. All continuous parameters were summarized by medians with interquartile ranges IQRs , and all categorical parameters were summarized as proportions. To compare between-group differences in demographic and clinical characteristics, lipid profiles, and other factors, non-parametric ANOVA was used for continuous variables and the Chi-square test was employed for categorical variables. Since outliers can be masked and very hard to detect in multivariate or highly structured settings, and since conventional multiple linear regression models, based on ordinary least squares, could yield misleading results if assumption of the normal distribution is not true, robust regression model with the least trimmed squares LTS estimation method was used to provide robust results in the presence of outliers Rousseeuw and Leroy, In order to examine whether duration of each class of ART was independently associated with myocardial and hepatic triglyceride contents, the importance of each variable included in the multivariate model was evaluated with 1 an examination of the Wald statistic for each variable in the model and 2 a comparison of each estimated regression coefficient in the multivariate model with the regression coefficient from the corresponding univariate model. Those variables that ceased to make significant contributions to the models based on these two criteria were deleted in a stage wise manner, and a new model was refitted. This process of eliminating, refitting, and verifying continued until all of the variables included were statistically significant, yielding a final model. General characteristics of the study participants by cocaine use status are presented in Table 1. Of the participants in this study, 55 Their median age was 47 IQR: 42—51 years, and The median myocardial triglyceride content was 0. The final model showed that only BMI regression coefficient: 0. Associations of demographic, laboratory, and clinical factors with myocardial triglyceride in all study participants, robust regression analysis. The final model for cocaine never users showed that only BMI regression coefficient: 0. Associations of demographic, laboratory, and clinical factors with myocardial triglyceride by cocaine use status, robust regression analysis. The final model showed that BMI regression coefficient: 0. Associations of demographic laboratory, and clinical factors with hepatic triglyceride in all study participants, robust regression analysis. Associations of demographic, laboratory, and clinical factors with hepatic triglyceride by cocaine use status, robust regression analysis. However, the final model for cocaine users showed that BMI regression coefficient: 0. The effect of individual PI used by study participants on myocardial and hepatic triglyceride contents was examined by robust regression analyses. Since these PIs predominantly affect cocaine users, our analyses were performed in cocaine users only. According to robust regression analyses, the presence of HCV infection was independently associated with hepatic triglyceride content Table 4. In this study, we found that 1 duration of PI use was independently associated with both myocardial and hepatic steatosis, 2 chronic cocaine use modified the association of duration of PI use with both myocardial and hepatic triglyceride content. We found that among the factors investigated, BMI and duration of PI use were independently associated with myocardial triglyceride content. Cumulative evidence indicates that obesity is not only an established risk factor for type-2 diabetes and coronary artery disease, but also leads to the over-accumulation of lipids in non-adipose tissues, including the heart Schaffer ; Szczepaniak et al. Our findings support previous studies that suggested that obesity plays a critical role in myocardial steatosis. Our study suggested that duration of PI use was independently associated with myocardial steatosis, which has not been reported before. It is known that some of the PIs elevate blood triglyceride levels, probably due to increased hepatic synthesis of triglycerides, however, our study suggested that elevated blood triglyceride levels were not independently associated with myocardial steatosis, although some of these patients may have been on a statin or other medications that would decrease triglyceride levels. Our study did not find significant associations of HIV-related factors or conventional cardiovascular risk factors with myocardial triglyceride content. Further studies are needed to confirm our findings. The exact mechanisms by which myocardial steatosis develops are not fully understood and the mechanism of action of cocaine on the effect of the association between duration of PI use and myocardial steatosis remains unexplained. A hypothetical mechanism for cocaine as an effect modifier is that cocaine is a potent stimulant of the sympathetic nervous system, and the sympathetic effects of cocaine may inhibit the leptin system, leading to less leptin production Trayhurn et al. Leptin has been recognized as an antisteatotic hormone, preventing the deleterious consequences of ectopic fatty acids overload in nonadipose tissue, such as the myocardium Trayhurn et al. We previously reported that cocaine use may modify the association between obesity measures and myocardial triglyceride content Lai et al. The potential interaction between cocaine use and PI toxicity has also not been thoroughly investigated. We found that BMI and duration of PI use were independently associated with hepatic triglyceride content. Obesity is linked to the over-accumulation of lipids in non-adipose tissues, including the liver Schaffer ; Szczepaniak et al. Our study suggested that the duration of PI use is independently associated with hepatic steatosis, which has never been reported before. It is known that some of the PIs elevate blood triglyceride levels, probably due to increased hepatic synthesis of triglycerides; however, our results indicate that elevated blood triglyceride levels are not independently associated with hepatic steatosis. The exact mechanisms by which hepatic steatosis develops in HIV-infected persons on PI are not fully understood. Hepatic steatosis may lead to liver inflammation and chronic liver inflammation result in hepatic fibrosis Moreno-Torres et al. Our study did not find significant associations of HIV-related factors or conventional cardiovascular risk factors with hepatic triglyceride content. The effect of tipranavir use on myocardial triglyceride has not been reported. Despite being well tolerated, clinical hepatitis and hepatic decompensation, and intracranial hemorrhage have been associated with tipranavir Orman and Perry, Although liver enzyme elevation during darunavir-based antiretroviral treatment in HIVinfected patients with or without hepatitis C coinfection was reported Di Biagio et al. The use of ritonavir has been frequently implicated in hypertriglyceridemia and lipodystrophy, though the effect of ritonavir on hepatic steatosis has not been reported. Large longitudinal studies are needed to confirm these findings. The mechanisms responsible for how cocaine use modifies the relationships between duration of PI use and hepatic steatosis are unknown and further investigations are needed. Cocaine is highly addictive and cocaine use is still prevalent in those with HIV-infection. There are some potential major limitations of this study which merit discussion. We recognize that the cardiac, metabolic and other disease burdens are high among AAs; nevertheless, we have not conducted similar studies in other populations. Likewise, we may have also failed to identify the effect of cocaine use on cardiac and hepatic steatosis based on changes since that use. Third, due to the nature of the cross-sectional design, some hidden confounding factors, such as socioeconomic status, were not adjusted for. Fourth, the study sample may not be representative of the population from which it was selected. This study suggests that duration of PI use is associated with increased myocardial and hepatic triglyceride contents, although larger longitudinal studies are needed to confirm this finding. This results of this study also indicate that cocaine use could exacerbate ART-induced toxicity in HIV-infected cocaine users. We believe that these findings are sufficient to alert physicians and other health care providers to inform their patients with HIV infection of the dangers of cocaine use and, specifically, that it is associated with myocardial and hepatic steatosis, and the likely consequent organ dysfunction. Since cocaine use is prevalent in the U. The NIDA had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. As a library, NLM provides access to scientific literature. Drug Alcohol Depend. Published in final edited form as: Drug Alcohol Depend. Find articles by Shenghan Lai. Find articles by Gary Gerstenblith. Find articles by Richard D Moore. Find articles by David D Celentano. Find articles by David A Bluemke. Find articles by Glenn Treisman. Find articles by Chia-Ying Liu. Find articles by Ji Li. Find articles by Shaoguang Chen. Find articles by Thomas Kickler. Find articles by Hong Lai. Contributors Drs. Issue date Aug 1. PMC Copyright notice. The publisher's version of this article is available at Drug Alcohol Depend. Characteristics of study participants in Baltimore, Maryland. Open in a new tab. Variable Never use cocaine Chronic cocaine users Univariate model Final multivariate model Univariate model Final multivariate model regression estimate SE p-value regression estimate SE p-value regression estimate SE p-value regression estimate SE p-value Age year 0. Conflict of interest No conflict of interest declared. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

The many-headed monster of the cocaine trade

Sannes where can I buy cocaine

Drug trafficking-related violence is becoming more extreme and brutal, while simultaneously the consequences of criminal convictions remain minimal. Although the Marengo trial has led to justified convictions of guilty people, aggressive drug crime itself, the entire network on which that trade rests, is largely unaffected. In her lecture, she discusses three so-called agent-based models of cocaine networks, which are computer models in which each player, or each 'agent' in a cocaine network, is represented as a ball in a kind of three-dimensional cloud. Once each player has been assigned a place in that cloud, you can then see what the consequences of certain interventions could be. You then run simulations with the system and see what happens to the network if, for example, you arrest the collectors of cocaine in the port containers. Or if you remove the bribed customs officials. No, the wish is that a better understanding of the operation of the entire network of cocaine trafficking, the so-called 'value chain', can allow you to study how that chain can be effectively and permanently disrupted. In short: you are trying to overthrow the entire system. Oetker shows on her slides how all players are first given a place in the computer model she built. Just like in a normal company, there are different jobs. There are dealers, cutters, security guards, bribed customs officers, often young 'collectors' who remove the drugs from the port containers. There are drivers, coordinators, 'brokers' who arrange the elimination of enemies and, unfortunately, murderers. Collectors and dealers are common jobs, but the number of killers is limited. Oetker then does computer simulations in which players are removed from the networks each time. You can then see how the network reacts to this. How quickly will the radar be replaced by another? In police television series it always goes like this: the officers are after the boss of a criminal organization. The idea is that you must catch small fish to ultimately put that one big fish, the top executive, behind bars. Once that boss is arrested, the entire network will collapse, that is the idea behind it. However, this appears not to be the case. Twelve years ago, Peter Sloot, professor of complex systems at the University of Amsterdam and founder of the Institute for Advanced Study, questioned this assumption. At the request of the police, he made an agent-based model of illegal cannabis cultivation in the Netherlands. The aim was to find out how the network could be permanently brought out of balance. Mapping such a system is difficult because, with every disruption in the system, everyone responds to everyone else. So the systems are not only complex but also adaptive systems that respond immediately to their environment after every disruption. This can result in a disabled member of a criminal organization being replaced at breakneck speed. The police busted up thousands of weed farms every year, but the networks still existed. How could this be? According to Sloot, it had to do with an incorrect perception of the structure of such organizations. It was always thought that a criminal network was a top-down organization controlled by one big boss, the so-called kingpin. Think of the 'Godfather'. By removing the top executive, the rest of the network would collapse on its own. But that usually turned out not to be the case in practice. The structure of a hemp network turned out not to have a pyramid shape at all, but rather to have its own dynamics, with many freelancers and changes of positions, in short, a company that had to be decisive and efficient. In a system like this, if you remove someone high up in the tree, there is a good chance that another person in an adjacent subnetwork is ready to immediately take that one kingpin's place. In fact, this person is sometimes even more able to take on that role. In this way, removing a kingpin can even lead to the strengthening of a network rather than its destruction. In the VPRO program Labyrint , Sloot explained in that it would be smarter to arrest people who do specialist work; people who are difficult to find and replace. For example, someone who insulates the areas used for cannabis cultivation or someone who installs irrigation systems. Or the electrician. If those people are removed from the system, you will see the efficiency drop, according to Sloot. He is sceptical about such 'disruption research', research into the possibilities of network disruption. He knows about the example of the electrician from Sloot, but 'I have not been able to find the long-term effect of removing that electrician in the studies. If you remove one, another network will immediately take over,' says Van der Maas. He believes we can learn a lot from the network approach to cocaine networks, but that the most important lesson is 'how super robust they are'. They are so-called 'small world' networks, he explains: 'A type of company that employs an average of about fifty people. The earnings in this company are so high that any disruption is resolved very quickly. They are networks with a limited number of connections, but in those networks, everyone is indirectly connected to everyone. The consequence of this structure is that major drug seizures or arrests not only make no difference to the networks themselves, but that disruption of the networks can even increase the amount of cocaine on the market. It is reminiscent of the undefeatable Hydra, the many-headed monster from Greek mythology. Every time you cut off one of its heads, two new heads grow back in that spot. For this reason, Van der Maas thinks that the only way to really stop these types of networks is to legalize and regulate the cocaine trade. The Netherlands is not properly preparing for the expansion of the global drug trade, according to Halsema. She also advocates for regulation but with a focus on addiction care. In January she spoke about this during a conference of the municipality of Amsterdam. Van der Maas remembers an impressive speech by a former police officer from England. The entire operation managed to frustrate the cocaine trade on the streets for a total of two hours. After that, trade had already recovered to its previous level. Naturally, the great fear is that regulation will lead to an increase in drug use. Van der Maas thinks that the crucial factor here is whether you leave the cocaine trade to commercial parties. That is why you should not only legalize but also regulate. So have the trade controlled by the government. Van der Maas finds it frustrating that a lot of money goes to disruption research. But we've known that for a long time. This means that there are islands, but that there are connections everywhere. Such a huge network is actually impossible to disrupt. That might have worked in the past. But now there is so much money involved, and the players are therefore so easily replaceable that network research mainly shows that disruption does not work. The fact that there is money for disruption research and not for research into regulated legalization is also a political problem, Van der Maas thinks. Crime is a major problem, and the only solution seems to be more law and order. But at the other end of the spectrum, very little is happening in the meantime: 'The left is just sleeping a bit. Of course crime is traditionally not a left-wing subject. It amazes me how few people know anything about this. We often know a lot about the addiction side, from a public health perspective. But nearly all scientists who have studied these networks well argue for controlled regulation. Published in De Groene Amsterdammer on April 13, Translated by the Institute for Advanced Study. The UvA uses cookies to measure, optimise, and ensure the proper functioning of the website. Cookies are also placed in order to display third-party content and for marketing purposes. You can change your preferences at any time by clicking on 'Cookie settings' at the bottom of each page. Also read the UvA Privacy statement. Sanne Bloemink is this year's journalist-in-residence at the Institute for Advanced Study IAS at the University of Amsterdam, where scientists conduct interdisciplinary research on complex scientific and societal issues. In a blog, she writes about her findings. Part 3: A conversation with several IAS community members about the Netherlands being well on its way to becoming a narco-state. Cookie Consent The UvA uses cookies to measure, optimise, and ensure the proper functioning of the website. Decline Accept Information about cookies.

Sannes where can I buy cocaine