Ethical and practical issues involved in behavioral pharmacology research that administers drugs of abuse to human volunteers

Researchers carrying out non-therapeutic research that involves the administration of drugs of abuse to human volunteers can be faced with many ethical and practical questions. The history of this type of research is relatively brief, with little in the way of published information relevant to carrying out behavioral pharmacological research with human participants. The aim of this article is to raise issues that occur in most studies of this type and to provide solutions that we have found acceptable and which have been approved by a variety of institutions and regulatory agencies. Clearly, there are other approaches that would work equally as well, and we are not attempting to provide 'the' answer to many of the issues raised. We believe that raising these issues and providing our perspectives is important for stimulating others to discuss them and for all of us to strive, where possible, to reach a consensus concerning ethical practices and to become aware of gaps and pitfalls. The topics discussed range from the nuts and bolts of acquiring and keeping track of drugs, to selecting research participants and designing ethical studies that protect our volunteers while still collecting scientifically useful data.     

The Drug Evaluation Classification Program: using ocular and other signs to detect drug intoxication

BACKGROUND: A systematic approach to determining drug intoxication has been developed for use by police officers. By considering specific physiological signs, trained officers can detect the effects of seven major drug types. METHODS: Officers follow a 12-step testing sequence and evaluate signs such as pupil sizes and responses, eye movements, heart rate, body temperature, mental timing, and balance. A matrix is then used to compare that subject's signs to those that would be produced by the seven types of drugs. If a pattern match is found, the officer concludes that the subject is under the influence of a drug and specifies the drug type. RESULTS: Several field and laboratory validation studies have been conducted using these procedures. In general, officers were 70% to 90% accurate in determining intoxication status and drug classification, but poly-drug use and drug rebound effects can sometimes cause problems in interpretation. CONCLUSION: Ocular and other physiological signs can be used to detect drug intoxication and classify the type of drug taken. Knowledge of the procedures used in the Drug Recognition Program can enable optometrists to serve as consultants to the police and as expert witnesses in cases involving the use of ocular signs that indicate illicit drug use.     

Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues

A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.     

Recruitment strategies in the women's health trial: feasibility study in minority populations. WHT:FSMP Investigators Group. Women's Health Trial:Feasibility Study in Minority Populations

The Women's Health Trial:Feasibility Study in Minority Populations (WHT:FSMP) examined the feasibility of recruiting postmenopausal women from a broad range of racial and socioeconomic backgrounds into a primary prevention trial requiring marked reductions in dietary fat. Postmenopausal women aged 50-79 yr who had no history of cardiovascular disease or cancer and who consumed 36% or more total energy from fat qualified to participate. We randomized the women into dietary intervention (60%) or control (40%) groups; we aimed to randomize 750 women in 18 months in each of the three clinical centers. All centers achieved goals for randomization based on ethnicity, and two centers exceeded overall recruitment goals. The greatest source of randomized participants was mass mailing, followed by items in the media, referrals, and community outreach. Recruitment yields were generally similar for the ethnic groups but lower for less-educated participants. The experience of WHT:FSMP indicates that postmenopausal women from the African-American, Hispanic, and non-Hispanic white communities can be recruited into dietary intervention studies for the prevention of disease.     

Bureau of Commercial Fisheries Oil Research program

Summary The Bureau of Commercial Fisheries has had under way since 1955 an extensive research program to develop wider uses for fish oils. The program is carried out in the Bureau’s own laboratories, in university laboratories, and in other qualified laboratories. The initial effort has been concentrated largely on basic research in an effort to learn more about the chemistry of fish oils, a field heretofore incompletely explored. Some applied research projects also were begun concurrently. Basic studies are being carried out on the chemistry of the components of fish oils (for example, polyene fatty acids), on the extracted fish oils themselves, and onin situ fish oils of the fish tissue. Investigations of fish-oil fatty acids are being made on chemical structure, methods of separation, chemical reactions, oxidative deterioration, and nutritive value, with especial emphasis on possible therapeutic aspects for human beings. The applied research projects include investigation of fish oils and the chemically modified compounds thereof as fungicides, as leather lubricants, and as ore-flotation agents. The applied and basic programs are coordinated so that findings of the basic work can be put to use in the applied work as soon as available.     

Horizontal wells and steam-assisted gravity drainage

Petroleum can be produced more efficiently using horizontal wells instead of conventional wells. For a typical 16 hectare well spacing, the pressure drawdown is as small as one-fiftieth of that for conventional wells. In some cases, where coning is a problem in conventional production, horizontal wells allow operation with much less coproduction of the displacing fluid. In the thermal recovery of bitumen and heavy oils, the Steam-Assisted Gravity Drainage process with horizontal production wells allows the systematic sweeping of the reservoir with economic production rates and without steam bypass. This paper described and reviews the application of horizontal wells to the production of heavy crude oils and bitumen by both non-thermal and thermal methods.     

Evaluation of diamond films by nuclear magnetic resonance and Raman spectroscopy

The quality of chemically vapor deposited diamond films was assessed in terms of sp²/sp³ content as determined by solid-state nuclear magnetic resonance (NMR) and Raman spectroscopy. While the results of the two techniques are in qualitative agreement, only the NMR spectra yield quantitative values for the sp²/sp³ ratio. Only sp³ carbon was observed in the NMR spectra of very high quality hot-filament, microwave plasma, and d.c. arc-jet chemically vapor deposited films. As expected, Raman spectroscopy is extremely sensitive to sp² bonded carbon, identifying small amounts below the detection limit of the NMR spectrometer. Comparison of the two techniques, however, indicates that Raman spectroscopy may be so sensitive to sp² bonded carbon that sp³ bonded carbon in films containing as much as 90% sp³ bonded material may remain undetected. NMR linewidths indicate that the sp³ carbon in such material shows more disorder than that found in high-quality polycrystalline films.     

The mechanism of the poisoning of ammonia synthesis catalysts by oxygenates O2, CO and H2O: an in situ method for active surface determination

The effect of adding an oxygenated poison (O₂, CO or H₂O) to a hydrogen/nitrogen stream producing ammonia over a triply promoted (K₂O, CaO, Al₂O₃) commercial catalyst is not unsurprisingly rapidly to poison the catalyst. However, immediately the oxygenated poison reacts with the catalyst and before total poisoning has occurred, which in these experiments took 10 min, there was an explosive release of ammonia producing concentrations in the gas phase in excess of the equilibrium value. This is thought to be due to a convulsive reorganisation of the surface of the catalyst in forming regions of an oxide overlayer, resulting in the expulsion of the standing surface nitrogen atom coverage as ammonia. However, in contradistinction to the observation of complete poisoning of the triply promoted catalyst shortly after switching the water (2.9%) into the hydrogen/nitrogen stream, when polycrystalline iron was used as the catalyst, after the initial pulse of ammonia was observed, the small quantity of water (2.9%) in the hydrogen/nitrogen stream resulted in an increased rate ( ×3) of ammonia synthesis which declined only slightly over the twenty minute duration of the experiment. The difference in behaviour between the triply promoted catalyst and the polycrystalline iron is thought to be due to the relative ease of reduction of the latter, so that submonolayer quantities of oxide can be stabilised on the surface of the polycrystalline iron. The promoting effect of this oxide overlayer is either structural or electronic; no distinction can be made from these experiments. The technique of injecting either O₂ or CO into a hydrogen/nitrogen stream which is producing ammonia over promoted catalysts in quantities insufficient to cause complete poisoning and measuring the oxygen coverage of the catalyst to a measured decrease in the ammonia synthesis rate, appears to be a ready, in situ method for the determination of the active catalyst area.     

On detecting co-resident cloud instances using network flow watermarking techniques

Virtualization is the cornerstone of the developing third-party compute industry, allowing cloud providers to instantiate multiple virtual machines (VMs) on a single set of physical resources. Customers utilize cloud resources alongside unknown and untrusted parties, creating the co-resident threat—unless perfect isolation is provided by the virtual hypervisor, there exists the possibility for unauthorized access to sensitive customer information through the exploitation of covert side channels. This paper presents co-resident watermarking, a traffic analysis attack that allows a malicious co-resident VM to inject a watermark signature into the network flow of a target instance. This watermark can be used to exfiltrate and broadcast co-residency data from the physical machine, compromising isolation without reliance on internal side channels. As a result, our approach is difficult to defend against without costly underutilization of the physical machine. We evaluate co-resident watermarkingunder a large variety of conditions, system loads and hardware configurations, from a local laboratory environment to production cloud environments (Futuregrid and the University of Oregon’s ACISS). We demonstrate the ability to initiate a covert channel of 4 bits per second, and we can confirm co-residency with a target VM instance in $<$ 10 s. We also show that passive load measurement of the target and subsequent behavior profiling is possible with this attack. We go on to consider the detectability of co-resident watermarking, extending our scheme to create a subtler watermarking attack by imitating legitimate cloud customer behavior. Our investigation demonstrates the need for the careful design of hardware to be used in the cloud.