Total synthesis of (-)-cylindrocyclophanes A and F exploiting the reversible nature of the olefin cross metathesis reaction.

Efficient total syntheses of the C(2)-symmetric (-)-cylindrocyclophanes A and F (1a and 1f) have been achieved. The initial strategy featured the use of a common advanced intermediate to assemble in stepwise fashion the required macrocycle of 1f, exploiting in turn a Myers reductive coupling followed by ring-closing metathesis. In a second-generation strategy, a remarkable cross olefin metathesis dimerization cascade was discovered and exploited to assemble the requisite [7,7]-paracyclophane macrocycles of both 1a and 1f from dienyl monomers. The successful syntheses also featured the effective use of the Danheiser annulation to construct substrates for both the Myers reductive coupling and the metathesis dimerizations strategies. Finally, the Kowalski two-step chain homologation of esters to siloxyalkynes proved superior over the original one-step protocol.

Harm reduction - a historical view from the left.

The harm reduction movement formed during a period in which social movements of the working class and the excluded were weak, neo-liberalism ideologically triumphant, and potential opposition movements were viewed as offering "tinkering" with the system rather than a total social alternative. This climate shaped and limited the perspectives, strategies, and tactics of harm reductionists almost everywhere. In many countries, this period was also marked by a "political economy of scapegoating" that often targeted drug users as the cause of social woes. This scapegoating took the form of "divide and rule" political initiatives by business and political leaderships to prevent social unrest in a long period of worldwide economic trends toward lowered profit rates and toward increasing income inequality. However, times have changed. Mass strikes and other labor struggles, opposition to the World Trade Organisation and other agencies of neo-liberalism, community-based protests against belt-tightening, and other forms of social unrest have been increasing in many countries. This opens up the possibility of new allies for the harm reduction movement, but also poses difficult problems for which we need to develop answers. On-the-ground experience in alliance formation needs to be combined with careful discussion of and research about what approaches work to convince other movements to work for and with harm reduction, and which approaches do not. Class differences within the harm reduction movement are likely to become more salient in terms of (a) creating internal tensions, (b) increasingly, opening up new ways in which working class harm reductionists can organize within their own communities and workplaces, and (c) producing different strategic orientations that will need to be discussed and debated. As a movement, we will need to find ways to accommodate and discuss differing perspectives, needs, and assessments of opportunities and threats without paralyzing harm reduction activities.

Behavioral risk reduction in a declining HIV epidemic: injection drug users in New York City, 1990-1997.

OBJECTIVES: This study assessed trends in HIV risk behaviors among injection drug users in New York City from 1990 to 1997. METHODS: Injection drug users were recruited continuously from a large drug detoxification treatment program (N = 2588) and a research storefront located in a high-drug-use area (N = 2701). Informed consent was obtained, and a trained interviewer administered a structured interview covering sociodemographics, drug use history, HIV risk behavior, and participation in syringe exchange. RESULTS: Trends were assessed for 5 risk behaviors in the 6-month period before the interview. The 3 injection risk behaviors declined significantly over time at each site (all P < .01). When data were pooled across sites, all 5 risk behaviors declined significantly over time (all P < .01). Participation in syringe exchange programs and in HIV counseling and testing increased greatly from 1990 to 1997. CONCLUSIONS: The continuing risk reduction among injection drug users indicates a "declining phase" in the large HIV epidemic in New York City. HIV prevention programs appear to be making an important contribution to the declining phase.

Escape behavior during academic tasks: a preliminary analysis of idiosyncratic establishing operations.

The presence or absence of idiosyncratic stimuli has been demonstrated to predictably alter the occurrence of problem behavior. By specifying stimuli related to negatively reinforced behavior during academic tasks, it may be possible to identify methods of instruction that decrease the occurrence of problem behavior. The current study used a four-step procedure that involved a functional analysis, descriptive assessment, establishing operations (EO) analysis, and follow-up evaluation (a) to identify the operant function of destructive behavior and (b) to evaluate the effects of idiosyncratic features of academic task demands and related methods of instruction on the occurrence of negatively reinforced destructive behavior of 3 boys with developmental disabilities and autism in a classroom setting. The data suggest that the four-step procedure was effective in identifying methods of instruction that decreased the likelihood of destructive behavior without disrupting the maintaining contingencies for destructive behavior. Results are discussed in terms of establishing operations for negatively reinforced destructive behavior during academic tasks and related methods of instruction in classroom settings.

Similarities and differences by race/ethnicity in changes of HIV seroprevalence and related behaviors among drug injectors in New York City, 1991-1996.

OBJECTIVE: To measure differences and similarities in the prevalence of HIV infection and of related risk and protective behaviors among New York City black, white, and Hispanic drug injectors during a period of decreasing HIV prevalence. METHODS: Drug injectors were interviewed at a drug detoxification clinic and a research storefront in New York City from 1990 to 1996. All subjects had injected drugs within the last six months. Phlebotomy for HIV testing was conducted after pretest counseling. Analysis compares the first half (period) of this recruitment interval with the second half. RESULTS: HIV seroprevalence declined among each racial/ethnic group. In each period, white drug injectors were significantly less likely to be infected than either blacks or Hispanics. Similar declines were found in separate analyses by gender, length of time since first injection, and by recruitment site. After adjustment for changes in sample composition over time, blacks and Hispanics remained significantly more likely to be infected than whites. Interactions indicate that the decline may be greatest among Hispanics and slowest among blacks. A wide variety of risk behaviors declined in each racial/ethnic group; and syringe exchange use increased in each group. Few respondents reported injecting with members of a different racial group at their last injection event. CONCLUSIONS: HIV prevalence and risk behaviors seem to be falling among each racial/ethnic group of drug injectors. Black and Hispanic injectors continue to be more likely to be infected. Declining prevalence among whites poses some risk of politically based decisions to reduce prevention efforts. Overall, these results show that risk reduction can be successful among all racial/ethnic groups of drug injectors and suggest that continued risk reduction programs may be able to attain further declines in infection rates in each group.

Geographic proximity, policy and utilization of syringe exchange programmes.

The objective of the research was to assess the effects of geographic proximity on the utilization of syringe exchange among injection drug users (IDUs) in New York City. Between 1994 and 1996, 805 IDUs were interviewed with a structured questionnaire. Geographic proximity was defined as living within a ten-minute walk. Eighty-one per cent of IDUs who lived close typically used a syringe exchange compared to 59% of those who lived further away. In multiple logistic regression analysis, those who lived close remained (adjusted odds ratio of 2.89; 95% CI 2.06 to 4.06, p = 0.001) more likely to use syringe exchange. Those who lived close were less likely to have engaged in receptive syringe sharing at last injection (adjusted odds ratio = 0.45, 95% CI 0.24 to 0.86, p = 0.015). In conclusion, locating exchange services in areas convenient to large numbers of IDUs may be critical for prevention of HIV infection.

HIV risk behaviours of current sex workers attending syringe exchange: the experiences of women in five US cities.

Existing research indicates that sex workers who inject drugs are vulnerable to HIV infection through both risky sexual and drug use practices. This study is the first attempt to learn whether this increased risk persists among current sex workers who participate in syringe exchange programmes (SEPs). With data from interviews with randomly selected participants in five US cities, we compared the demographic characteristics, sexual risk behaviours, drug use practices, emotional and physical health, and SEP utilization patterns of currently active female sex workers who attend SEPs with female SEP participants who do not engage in sex work. Data indicate that women enrolled in SEPs who were currently trading sex typically reported greater HIV risk than women non-sex workers. Current sex workers reported higher levels of risk for every drug risk variable examined in bivariate analysis. They were more likely than other women to inject with a syringe previously used by someone else, to inject daily and to attend shooting galleries; they were less likely to use a condom with their primary partners and to report higher levels of psychological distress than their counterparts. The relationship between sex work status and risky injection practices persisted when potential confounders were controlled for in multivariate analysis. SEPs can serve a pivotal role in providing sex workers with services and referrals which would help them reduce risk behaviours.

Doing a shotgun: a drug use practice and its relationship to sexual behaviors and infection risk.

There has been a rise in the frequency with which inhalational routes such as smoking are used for illicit drug use. A growing population of new inhalational drug users augments the pool of individuals at risk for transition to injection drug use. Further, illicit drug smoking has been implicated in the transmission of a variety of pathogens by the respiratory route, and crack smoking has been associated with an increased risk of HIV infection, particularly through the exchange of high-risk sex for drugs. Shotguns are an illicit drug smoking practice in which smoked drugs are exhaled or blown by one user into the mouth of another user. We conducted a series of ethnographic observations to attempt to characterize more fully the practice of shotgunning, the range of associated behaviors, and the settings and contexts in which this practice occurs. Shotguns may be seen as a form of drug use which has close ties to sexual behaviors, and which has both pragmatic and interpersonal motivations, combining in a single phenomenon the potential direct and indirect risk of disease transmission by sexual, blood borne and respiratory routes. These data support the need to develop and evaluate comprehensive risk reduction interventions, which take into consideration the relationships between interpersonal and sexual behaviors and specific forms of drug use.

Audio-computer interviewing to measure risk behaviour for HIV among injecting drug users: a quasi-randomised trial.

BACKGROUND: We aimed to assess audio-computer-assisted self-interviewing (audio-CASI) as a method of reducing under-reporting of HIV risk behaviour among injecting drug users. METHODS: Injecting drug users were interviewed at syringe-exchange programmes in four US cities. Potential respondents were randomly selected from participants in the syringe exchanges, with weekly alternate assignment to either traditional face-to-face interviews or audio-CASI. The questionnaire included items on sociodemographic characteristics, drug use, and HIV risk behaviours for 30 days preceding the interview. We calculated odds ratios for the difference in reporting of HIV risk behaviours between interview methods. FINDINGS: 757 respondents were interviewed face-to-face, and 724 were interviewed by audio-CASI. More respondents reported HIV risk behaviours and other sensitive behaviours in audio-CASI than in face-to-face interviews (odds ratios for reporting of rented or bought used injection equipment in audio-CASI vs face-to-face interview 2.1 [95% CI 1.4-3.3] p=0.001; for injection with borrowed used injection equipment 1.5 [1.1-2.2] p=0.02; for renting or selling used equipment 2.3 [1.3-4.0] p=0.003). INTERPRETATION: Although validation of these self-reported behaviours was not possible, we propose that audio-CASI enables substantially more complete reporting of HIV risk behaviour. More complete reporting might increase understanding of the dynamics of HIV transmission and make the assessment of HIV-prevention efforts easier.

Knowledge of tuberculosis among drug users. Relationship to return rates for tuberculosis screening at a syringe exchange.

Tuberculosis is an important health issue among drug users. We sought to evaluate active drug users' (DUs) knowledge of tuberculosis (TB) and to assess the relationship between TB knowledge and attitudes and tuberculin skin test (TST) return rates at a syringe exchange program. DUs were recruited at a syringe exchange program in New York City, were interviewed and offered TSTs, and received $15.00 upon returning for TST reading. The questionnaire evaluated knowledge of TB transmission, prevention, and treatment. From March 13, 1995 to January 31, 1996, 610 of 650 (94%) of DUs approached agreed to participate. Of these, 80% had previous TSTs within the past 2 years and 20% were known to be HIV infected. Almost all knew that TB is contagious and more than two thirds knew that TB is treatable and that TB preventive therapy existed. However, fewer than half knew that HIV-related TB could be treated, 30% thought TB could be treated without a medical doctor, and the majority (70%) thought a reactive TST implied infectivity. The rate of return for TST reading was 93%. In multivariate analysis, those who knew that HIV-related TB was curable were more likely to return for TST reading (odds ratio 2.0; 95% confidence interval 1.04 to 3.95; p = .03). The high acceptance and return rates suggest that TB services can be incorporated into syringe exchange programs. However, several important gaps in TB knowledge existed in this population at high risk of TB, which may impact on adherence and which support the need for TB education for drug users.

Syringe exchange in the United States, 1996: a national profile.

OBJECTIVES: This paper provides 1996 information on the status of US syringe exchange programs and compares these findings with data from our 1994 survey. METHODS: In November 1996, questionnaires were mailed to 101 syringe exchange programs. Program directors were contacted to conduct telephone interviews based on the mailed questionnaires. Data collected included number of syringes exchanged, syringe exchange program operations, legal status, and services offered. RESULTS: Eighty-seven programs participated in the survey. A total of 46 (53%) were legal, 20 (23%) were illegal but tolerated, and 21 (24%) were illegal-underground. Since 1994, there has been a 54% increase in the number of cities and a 38% increase in the number of states with syringe exchange programs. Eighty-four programs reported exchanging approximately 14 million syringes, a 75% increase from 1994. Syringe exchange programs also provided a variety of other services and supplies, and legal programs were more likely than illegal ones to provide these services. CONCLUSION: Despite continued lack of federal funding, syringe exchange programs expanded in terms of the number of syringes exchanged, the geographic distribution of programs, and the range of services offered.

Risk behavior and HIV infection among new drug injectors in the era of AIDS in New York City.

OBJECTIVE: To examine HIV risk behavior and HIV infection among new initiates into illicit drug injection in New York City. DESIGN AND METHODS: Cross-sectional surveys of injecting drug users (IDUs) recruited from a large detoxification treatment program (n=2489) and a street store-front research site (n=2630) in New York City from 1990 through 1996. Interviews covering demographics, drug use history, and HIV risk behavior were administered; serum samples were collected for HIV testing. Subjects were categorized into two groups of newer injectors: very recent initiates (just began injecting through 3 years) and recent initiates (injecting 4-6 years); and long-term injectors (injecting > or = 7 years). RESULTS: 954 of 5119 (19%) of the study subjects were newer injectors, essentially all of whom had begun injecting after knowledge about AIDS was widespread among IDUs in the city. New injectors were more likely to be female and white than long-term injectors, and new injectors were more likely to have begun injecting at an older age (median age at first injection for very recent initiates, 27 years; median age at first injection for recent initiates, 25 years; compared with median age at first injection for long-term injectors, 17 years). The newer injectors generally matched the long-term injectors in frequencies of HIV risk behavior; no significant differences were found among these groups on four measures of injection risk behavior. HIV infection was substantial among the newer injectors: HIV prevalence was 11% among the very recent initiates and 18% among the recent initiates. Among the new injectors, African Americans, Hispanics, females, and men who engaged in male-male sex were more likely to be infected. CONCLUSIONS: The new injectors appear to have adopted the reduced risk injection practices of long-term injectors in the city. HIV infection among new injectors, however, must still be considered a considerable public health problem in New York City.

Declining seroprevalence in a very large HIV epidemic: injecting drug users in New York City, 1991 to 1996.

OBJECTIVES: This study assessed recent trends in HIV seroprevalence among injecting drug users in New York City. METHODS: We analyzed temporal trends in HIV seroprevalence from 1991 through 1996 in 5 studies of injecting drug users recruited from a detoxification program, a methadone maintenance program, research storefronts in the Lower East Side and Harlem areas, and a citywide network of sexually transmitted disease clinics. A total of 11,334 serum samples were tested. RESULTS: From 1991 through 1996, HIV seroprevalence declined substantially among subjects in all 5 studies: from 53% to 36% in the detoxification program, from 45% to 29% in the methadone program, from 44% to 22% at the Lower East Side storefront, from 48% to 21% at the Harlem storefront, and from 30% to 21% in the sexually transmitted disease clinics (all P < .002 by chi 2 tests for trend). CONCLUSIONS: The reductions in HIV seroprevalence seen among injecting drug users in New York City from 1991 through 1996 indicate a new phase in this large HIV epidemic. Potential explanatory factors include the loss of HIV-seropositive individuals through disability and death and lower rates of risk behavior leading to low HIV incidence.

Injection drug users as social actors: a stigmatized community's participation in the syringe exchange programmes of New York City.

In 1992, New York State Department of Health regulations provided for fully legal syringe exchange programmes in the state. The policies and procedures mandated that: 'Each program must seek to recruit ... for inclusion on its advisory board ... program participants ... Programs are also urged to establish other advisory bodies, such as Users' Advisory Boards made up of program participants, to provide input and guidance on program policies and operations.' The inclusion of drug users as official advisors to the legal programmes was seen as a method for incorporating the views of the consumers of the service in operational decisions. The 1992 regulations implied a new public image for users of illicit psychoactive drugs: active drug users were seen to be capable not only of self-protective actions (such as avoiding HIV infection), but also of serving as competent collaborators in programmes to preserve the public health. This development has important implications with regard to the evolution of official drug policy, since it will be difficult in future to treat IDUs simply as the passive objects of state intervention. Whether as individuals or representatives of a wider population of illicit drug users, they have acquired a legitimacy and sense of personal worth which would have been unthinkable in previous periods.

Social network characteristics as mediators in the relationship between sexual abuse and HIV risk.

Recent research suggests that sexual abuse may be a potent risk factor for engaging in HIV risk behaviors for women. This relationship is likely mediated by the long term sequelae of sexual abuse. One plausible causal pathway posits that specific social network characteristics increase HIV risk exposure opportunities. This is premised on the belief that previous sexual abuse predisposes some women to become members of risk networks characterized by deviant behaviors and that HIV risk occurs in the context of these networks. One hundred and thirty women opiate users were systematically recruited from methadone maintenance and syringe exchange programs in New York City. The women participated in a one hour interview and provided information on drug use and frequency, HIV drug and sex risk behaviors, social network characteristics, and sexual abuse histories. Univariate and logistic regression techniques were used to test the relationship between sexual abuse and increased HIV risk as mediated by social network characteristics. Previous sexual abuse was strongly related to all social network characteristics examined. Moreover, these network characteristics appeared to affect patterns of drug use in identifiable ways. Social isolation was the only network characteristic associated with both HIV drug and sex risk behaviors. However, although a history of sexual abuse was significantly associated with five of the seven specific HIV risk behaviors examined, the relationship between sexual abuse and HIV risk behaviors remained unchanged when social network characteristics were included in the statistical model. Overall, the results suggest that a sexual abuse experience or its aftermath influence behavior far into the future. However, the results of this study did not show social network characteristics mediating the relationship between sexual abuse and HIV risk. Rather, previous sexual abuse and social network characteristics appear to be independent contributors to HIV risk behaviors for women.

Organizational issues in conducting tuberculosis screening at a syringe exchange program.

There has been a rise in tuberculosis (TB) cases in the United States and there is a potent link between human immunodeficiency virus (HIV) and tuberculosis. In New City it is estimated that 40% of the 200,000 injecting drug users are infected with HIV. In addition, the tuberculosis case rate is approximately four times the national average, and one third of these cases occurred in those persons infected with HIV. Drug users have a high prevalence of latent tuberculous infection and are at high risk for progression to active tuberculosis. Drug users are at high risk for both HIV and TB. Although studies have shown the value of incorporating TB services into drug treatment programs, the majority of drug users in the United States are not in drug treatment. We have been evaluating the feasibility of conducting TB screening and directly observed TB preventive therapy for active injecting drug users at a syringe exchange program in New York City. This paper describes issues relating to the implementation of the TB screening program and discusses general and operational issues relevant to integrating medical and public health programs into existing programs serving drug using individuals.

From ideology to logistics: the organizational aspects of syringe exchange in a period of institutional consolidation.

The initial period in the establishment of syringe exchange projects is often characterized by overt conflict: between community AIDS activists, on the one hand, and public officials and political leaders who remain ideologically opposed to the introduction of measures perceived as condoning illicit drug use. In this context, professionals concerned with legitimating the new institutions of syringe exchange may sometimes neglect aspects of their everyday logistics and social organization, obscuring the important choices which have to be made to carry these initiatives forward. In particular, the contrast between formally-constituted institutions-the "storefront" or "community-based" syringe exchange programs (SEPs)-and the model of low-threshold syringe availability through pharmacies, vending machines, and user networks, is here presented not as an either/or choice but rather as a pair of complementary strategies which respond to diverse needs and target different populations. The advantages and disadvantages of each particular approach make it likely that maximum effectiveness will be achieved through a combination of every possible form of needle distribution, each tailored to specific and cultural circumstances. The case is here examined in the light of the experience of the SEPs in New York City, from their clandestine origins in 1990 through their first years of official functioning in 1992-1996.