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PubMed2005

Introduction to theme section on geographies of intellectual disability: 'outside the participatory mainstream'?

This paper introduces the following theme section on Geographies of Intellectual Disability. It outlines the historiography of geographical work on intellectual disability, noting in particular the contributions of Wolpert (Transactions of the Institute of British Geographers 5 (1980) 391) and Hall and Kearns (Health and Place 7 (2001) 237), before tracing claims made about both the 'institutional' and 'deinstitutional' eras in the changing geographies confronting and experienced by intellectually disabled people. This account, highlighting the tendency for such people to remain 'outside the participatory mainstream' in almost all circumstances, offers along the way an introduction to the four contributions that follow.

Deinstitutionalization↗

PubMed2004

Quad quantum cascade laser spectrometer with dual gas cells for the simultaneous analysis of mainstream and sidestream cigarette smoke.

A compact, fast response, infrared spectrometer using four pulsed quantum cascade (QC) lasers has been applied to the analysis of gases in mainstream (MS) and sidestream (SS) cigarette smoke. QC lasers have many advantages over the traditional lead-salt tunable diode lasers, including near room temperature operation with thermoelectric cooling and single mode operation with improved long-term stability. The new instrument uses two 36 m, 0.3 l multiple pass absorption gas cells to obtain a time response of 0.1s for the MS smoke system and 0.4s for the SS smoke system. The concentrations of ammonia, ethylene, nitric oxide, and carbon dioxide for three different reference cigarettes were measured simultaneously in MS and SS smoke. A data rate of 20Hz provides sufficient resolution to determine the concentration profiles during each 2s puff in the MS smoke. Concentration profiles before, during and after the puffs also have been observed for these smoke constituents in SS smoke. Also, simultaneous measurements of CO(2) from a non-dispersive infrared (NDIR) analyzer are obtained for both MS and SS smoke. In addition, during this work, nitrous oxide was detected in both the MS and SS smoke for all reference cigarettes studied.

Ammonia↗

PubMed2006

A/T-targeted somatic hypermutation: critique of the mainstream model.

The "affinity maturation" of the humoral immune response is driven by antigen-activated somatic hypermutation (SHM) of the genes that encode antibody variable regions and the subsequent antigenic selection of mutant clones. The molecular mechanism of SHM is yet to be completely elucidated. SHM affects cytosine-guanine (C/G) and adenine-thymine (A/T) pairs with approximately equal frequency in vivo. The proposition that error-prone DNA-dependent DNA synthesis explains A/T-targeted hypermutagenesis seems to have mainstream support within the hypermutation research community at present. A major feature of SHM in vivo is that C/G hypermutation is strand unbiased, whereas A/T hypermutation is strand biased. We show that the "DNA-based polymerase error" model of A/T-targeted hypermutagenesis does not explain this important aspect of SHM.

Adenine↗

PubMed2005

CC16 as a marker of lung epithelial hyperpermeability in an acute model of rats exposed to mainstream cigarette smoke.

The Clara cell secretory protein (CC16), which is produced along the tracheal-bronchial tree, has been shown to be a sensitive marker for the detection of lung hyperpermeability. Cigarette smoke inhalation has been associated with increased lung epithelial permeability. In this study we investigated the changes in CC16 in serum and bronchoalveolar lavage fluid (BALF) from female Sprague Dawley rats after a single exposure (2 x 1 h) to diluted mainstream cigarette smoke (MS) from the Reference Cigarette 2R4F. Rats were nose-only exposed to MS at concentrations of 0 (sham exposure), 250, 500, 750, 1000 or 1250 microg total particulate matter per liter. At 2, 4, 15 and 24h after exposure, serum and BALF-samples were collected. CC16 was determined in BALF and serum. Albumin in BALF, another marker for lung permeability was also determined. A trend towards a lower CC16 recovery was observed in BALF from smoke-exposed rats. The CC16 concentration in serum showed a marked (up to five-fold) concentration- and time-dependent increase after MS exposure. The increase of CC16 in serum was most prominent at the early timepoints, i.e. 2 and 4 h after exposure, and a return to baseline concentrations was obvious at 24 h after exposure. The effect of MS exposure on the amount of albumin in BALF was limited (up to 60% increase). This study clearly showed that CC16 is a good marker for the assessment of the increased permeability of the lung/blood barrier after MS-exposure.

Albumins↗

PubMed1999

Has behavior therapy drifted from its experimental roots? A survey of publication trends in mainstream behavioral journals.

In recent years it has been suggested that behavior therapy, characterized in part by single-subject designs and an idiographic approach to addressing practical problems, is drifting from its experimental roots. To examine trends in behavior therapy, and to provide an objective index of drift, two archival studies were conducted to identify publication trends in the use of single-subject designs vs. group designs, as well as citations to select basic behavioral science journals. In Study 1, articles appearing in Behavior Therapy from 1970 through 1996 were reviewed and categorized in terms of type of article, design, and citations to experimental journals. Findings from Study 1 suggest declining publication trends in single-subject designs and citations to experimental journals in Behavior Therapy, with a modest increase in the use of group designs over the period. Study 2 was designed to replicate and extend our initial findings by surveying three behavioral journals in addition to Behavior Therapy using the PsychLit database and years covering 1974 through 1996: Behaviour Research and Therapy, Journal of Behavior Therapy and Experimental Psychiatry, and Behavior Modification. Consistent with Study 1, results of Study 2 showed declining trends in single-subject designs for all mainstream behavioral journals. The significance of these findings in light of the argument that behavior therapy has drifted from its experimental roots is discussed, with emphasis on contingencies that may be responsible for the trends observed.

Behavior Therapy↗

PubMed2001

Particulate and vapor phase constituents of cigarette mainstream smoke and risk of myocardial infarction.

On pharmacological and compositional grounds, cigarette mainstream smoke (MS) aerosol can be broadly categorized as consisting of the following constituents: carbon monoxide, other vapor phase components, particulate matter ('tar') and nicotine. The relative risk of coronary artery disease for smoking 20 cigarettes per day has been estimated by meta-analysis of five large prospective epidemiology studies to be 1.78. These four major smoke components are simultaneously delivered to the active smoker as a complex aerosol composed of several billion semi-liquid particles per cm(3) within the mixture of combustion gases. Fractional attribution of the 78% increase in reported risk to a given constituent is problematic because of the complex mixture. However, a significant literature exists which suggests that some general statements regarding smoke constituent-associated risks for development or exacerbation of myocardial infarction are supportable. First, the atherogenic potential of MS is associated with the particulate and vapor phases and not with CO. Nicotine might exert an indirect effect on atherosclerotic plaque development by increasing shear forces in main conduction arteries. Similarly, the thrombogenic potential is associated primarily with the particulate and vapor phases and also possibly with nicotine via platelet aggregation. Vasoconstriction probably results from the actions of nicotine and hypoxia from carbon monoxide. Finally, the arrhythmia-inducing potential may result from catecholamine release following nicotine exposure, with a questionable contribution from carbon monoxide.

Animals↗

PubMed1990

Isotope dilution gas chromatography-mass spectrometry in the determination of benzene, toluene, styrene and acrylonitrile in mainstream cigarette smoke.

A cryogenic trapping method with isotope dilution gas chromatography-mass spectrometry analysis has been developed for the determination of benzene, toluene, styrene and acrylonitrile in mainstream vapor phase cigarette smoke. The method is simple, direct, and quantitative. Vapor phase samples are collected cryogenically in a series of four traps following removal of the particulate phase with a Cambridge filter pad. For all four analytes, 75-85% of the total amounts recovered were found in the initial trap and less than 1% in the final trap. Assessment of instrumental precision by multiple injections of a sample gave relative standard deviations of less than 2%. Linear calibration for all analytes over the analysis range gave an r2 value greater than 0.99 with average relative standard deviations at the mean ranging from 1.4 to 8.2%. The cigarettes analyzed include a reference cigarette (Kentucky 1R4F), a commercial ultra-low "tar" mentholated cigarette, and two cigarettes that heat but do not burn tobacco. The values determined for the four analytes in the 1R4F samples are comparable to reported values of similar cigarettes. The cigarettes which heat rather than burn tobacco yield less of all four analytes compared to the other cigarettes in the study.

Acrylonitrile↗

PubMed1990

Separation and quantitation of phenolic compounds in mainstream cigarette smoke by capillary gas chromatography with mass spectrometry in the selected-ion mode.

Cigarette smoke condensate is a complex chemical matrix and determination of phenolic compounds in it frequently requires extensive and laborious sample preparation. By utilizing derivatization techniques and capillary column gas chromatography with mass spectrometry in the selected-ion mode, separation and quantitation of selected phenolic compounds found in mainstream cigarette smoke can be accomplished with minimal sample preparation. This method has been used to determine concentrations of phenol, o-cresol, m-cresol, p-cresol, catechol, resorcinol and hydroquinone in cigarette smoke condensate from a number of commercially available cigarettes and a new cigarette which heats, but does not burn, tobacco. Unlike tobacco-burning cigarettes, levels of the phenolic compounds in the new cigarette smoke are at or below the detection limits for most of the compounds. This result is attributed to the unique design of the new cigarette.

Chemical Phenomena↗

PubMed2003

Analysis of pyridines in mainstream cigarette smoke.

A new technique has been developed for the quantitative analysis of pyridines in mainstream cigarette smoke using a GC-MS technique. For analysis, 10 cigarettes are smoked using conditions based on US Federal Trade Commission recommendations. The smoke is collected in a water trap and analyzed using a GC-MS technique. A standard or a fast GC separation can be applied for the analysis. The standard separation was followed by MS detection using selected ion monitoring (SIM) acquisition on a quadrupole instrument. The fast GC was followed by MS detection with total ion acquisition on a time-of-flight instrument. The levels of pyridine depend on the type of cigarette: for a full flavor cigarette pyridine is as high as 18.0 microg/cigarette (cig.). and for an ultra light cigarette is about 3.0 microg/cig. Substituted pyridines vary between 5.0 microg/cig. to 0.1 microg/cig. for a full flavor cigarette, and between 0.2 microg/cig. and a few ng/cig. for an ultra light cigarette. The reproducibility of the technique is very good, with less than 7-8% RSD in both separation procedures for most of the analyzed compounds.

Gas Chromatography-Mass Spectrometry↗

PubMed2003

New technique using solid-phase extraction for the analysis of aromatic amines in mainstream cigarette smoke.

A new procedure has been developed for the quantitation of aromatic amines in mainstream cigarette smoke. Two solid-phase extraction (SPE) cleanup steps using different retention mechanisms are required to process the samples. The first step uses a cation-exchange cartridge, followed by a second step that uses a cartridge with a hydrophobic retention character. The aromatic amines eluted from the second SPE cartridge are derivatized with heptafluorobutyric anhydride and analyzed with GC-MS selected ion monitoring in the negative chemical ionization mode. This new method has several advantages over other reported techniques, being sensitive, robust, and easily automated. The detection limits ranged from 0.02 ng/cigarette for tolidine to 1.41 ng/cigarette for aniline and the recoveries were from 79 to 109%.

Amines↗

PubMed2000

Migration and mainstreaming: matching health services to immigrants' needs in Australia.

The provision of special services for people of non-English speaking background in Australia emerged in the context of the development of policies of multiculturalism. This article documents the trends in state and federal policy development and service provision in the 1990s, as influenced by the sometimes-competing forces of political will, financial resources and community demand. The sustainability of various programmes is examined in the context of the continuing need to provide for people whose access to mainstream health services remains problematic.

Australia↗

PubMed2001

Lack of correlation between cigarette mainstream smoke particulate phase radicals and hydroquinone yield.

Evidence suggests that when compared with non-smokers, cigarette smokers are exposed to an increased burden of free radicals from both the vapor phase and particulate phase of the cigarette smoke aerosol. In this study, primary emphasis was placed on the free radicals found in the particulate phase. Published reports hypothesize that the particulate phase free radicals of cigarette mainstream smoke (MS) condensate consist of a hydroquinone/semiquinone/quinone shuttle. However, our results do not suggest that there is a positive correlation between the smoke yield of hydroquinone and the presence of particulate phase free radicals. First, 10-fold reductions in MS hydroquinone yield were obtained when KNO3 was applied to the surface of tobacco of an American blended cigarette. Surprisingly, there was no significant corresponding change in the yield of particulate phase radicals. Second, in experiments testing MS from low and high hydroquinone-yielding tobaccos there was no consistent corresponding relationship between hydroquinone and particulate phase radical yields. In one series of blends there was at best an inverse relationship between hydroquinone and particulate phase radical yields. In contrast with the published literature, we conclude that the particular compound or compounds driving particulate phase free radical formation are currently unknown. An additional experiment reported here suggested that components of the water soluble extract of burley tobacco may be driving the formation of particulate phase free radicals.

Antioxidants↗

PubMed2002

Evaluation of the potential effects of ingredients added to cigarettes. Part 2: chemical composition of mainstream smoke.

Cigarette mainstream smoke from blended research cigarettes with and without the addition of ingredients was analyzed for its chemical composition. In total, 333 ingredients commonly used in cigarette manufacturing were assigned to three different groups. Each group of ingredients was introduced at a low and a high level to the test cigarettes. The list of the 51 smoke constituents determined is based on those analytes suggested for analysis in a US Consumer Product Safety Commission proposal for low ignition cigarettes and cigarette smoke constituents identified by the International Agency for Research on Cancer as worthy of concern and characterized as carcinogens. An increase in the yield of total particulate matter (TPM) in the range of 13 to 28% relative to the control cigarette without ingredients was observed for all test cigarettes. This was presumably caused by the higher transfer rates of the added ingredients to the smoke compared to the transfer from the tobacco part of the filler. When the yields of individual constituents were normalized to the TPM yields, a reduction in the majority of the constituents was observed when compared to the control. For one of the ingredient groups this reduction was especially high: for phenols a maximum of 70%, for polycyclic aromatic hydrocarbons 50%, and for N-nitrosamines 45%. An increase in the amount relative to TPM was observed for a few smoke constituents: hydrogen cyanide and cadmium (one ingredient group), formaldehyde (one ingredient group), and resorcinol and lead (two ingredient groups). These results are consistent with the lack of any increased activity in the in vitro and in vivo assays in this same series of studies (Food and Chemical Toxicology 2002, 40, 105-111; Food and Chemical Toxicology 2002, 40, 113-131). An overall assessment of our data suggests that these ingredients, when added to the tobacco, do not add to the toxicity of smoke, even at the elevated levels tested in this series of studies.

Cadmium↗

PubMed2003

IARC carcinogens reported in cigarette mainstream smoke and their calculated log P values.

Cigarette smoke is a complex aerosol of minute liquid droplets (termed the particulate phase) suspended within a mixture of gases (CO(2), CO, NO(x), etc.) and semi-volatile compounds. The International Agency for Research on Cancer (IARC) has classified a number of the chemical constituents reported in cigarette mainstream smoke (MS) as carcinogens. Previously, we published a series of historical reviews reporting that 11 IARC Group 1 (known human), nine Group 2A (probable human) and 48 Group 2B (possible human) carcinogens have been observed in MS. Here, we expand the list of IARC classified carcinogens from 68 to 81 compounds (11 Group 1, 14 Group 2A and 56 Group 2B) reported in MS. A number of the IARC compounds reported in MS are found in the vapor phase including three Group 1, eight Group 2A and 18 Group 2B constituents. Several IARC MS compounds are found in both the vapor and particulate phases including two in Group 1, one in Group 2A and one in Group 2B. Forty-eight IARC MS carcinogens are found in the particulate phase only. Lipophilicity, as determined by the base 10 logarithm of the calculated octanol-water partition coefficient and denoted as Clog P, is reported for each of the 71 non-metallic MS IARC carcinogens. Clog P correlates with a number of biological activities including in vitro mutagenicity and carcinogenicity in rodents, and in the absence of any additional toxicological or epidemiological data, a high log P compound is more likely to be carcinogenic than a low log P compound.

Animals↗

PubMed2004

Percutaneous penetration enhancers in cigarette mainstream smoke.

Percutaneous penetration enhancers (PPEs) are chemicals used to enhance the transdermal delivery of drugs. Fifty-eight of the approximately 150 PPEs used for the transdermal delivery of drugs have been reported in cigarette mainstream smoke (MS). MS is a complex aerosol of minute liquid droplets (termed the particulate phase) suspended within a mixture of gases (CO(2), CO, NO(x), etc.) and semi-volatile compounds. The gases and many of the semi-volatiles are termed the vapor phase. Twenty-nine of the 58 PPEs have been identified in MS vapor phase, 15 in the particulate phase and 14 in both the vapor and particulate phases. There is a tendency for MS PPEs to be hydrophobic, with 40 of the 58 compounds (69%) being either hydrophobic or strongly hydrophobic, and only 24% being hydrophilic. Many of the 4800 known constituents of MS are hydrophilic and would not be expected to readily cross cell membranes or penetrate tissue when delivered as single compounds. The in vivo effect on biological activity of the juxtaposition within the cigarette smoke aerosol of the large number of hydrophilic constituents with the 58 PPEs is currently unknown. As an initial step in understanding this potential complex interaction, the 58 PPEs in MS have been identified and a number of molecular parameters related to the ability to penetrate tissue have been calculated, including MS concentration, measured and calculated base ten logarithm of the octanol-water partition coefficient (Mlog P and Clog P), molecular volume (MgVol) and calculated molar refractivity (CMR).

Administration, Cutaneous↗

PubMed1998

Chemical and biological studies of a new cigarette that primarily heats tobacco. Part 2. In vitro toxicology of mainstream smoke condensate.

The genotoxic and cytotoxic potential of mainstream cigarette smoke condensate (CSC) from a new cigarette that primarily heats tobacco (TOB-HT) was compared with that of CSC from a Kentucky reference low "tar" cigarette (1R4F) representative of the current US cigarette market, and Kentucky Reference 1R5F, representative of ultra-low "tar" cigarettes on the US market. TOB-HT was evaluated at concentrations which induced concentration-dependent positive responses with 1R4F and 1R5F in an in vitro toxicology test battery which included sister chromatid exchange, chromosome aberration, and neutral red cytotoxicity assays in CHO cells, and the Ames bacterial mutagenicity assay. CSC from 1R4F and 1R5F was positive in the Ames assay with Salmonella typhimurium strains TA98, TA100, TA1538 and TA1537, and negative with TA1535, while CSC from TOB-HT was negative in all five strains. CSC from 1R4F and 1R5F cigarettes was positive in sister chromatid exchange (SCE), chromosome aberration (CA) and neutral red cytotoxicity assays, while CSC from the TOB-HT cigarette yielded negative results in all the above endpoints. These data indicate that in these assays the genotoxic and cytotoxic potential of CSC from the new cigarette that primarily heats tobacco is significantly less than CSC from Kentucky reference 1R4F and 1R5F cigarettes, which are representative of cigarettes currently sold in the US.

Animals↗

PubMed1998

Distribution of major and minor alkaloids in tobacco, mainstream and sidestream smoke of popular Indian smoking products.

Various Indian smoking products--cigarette, bidi, chutta and a brand of US cigarette--were analysed by gas chromatography-flame ionization detection (GC-FID) for the levels of nicotine and minor tobacco alkaloids in tobacco, mainstream smoke (MS) and sidestream smoke (SS) employing modified smoking standards, namely two puffs/min. The analysis clearly demonstrated relatively higher levels of nicotine and minor tobacco alkaloids in tobacco from bidi (37.7 mg/g) and chutta (34.5 mg/g) when compared with Indian and US cigarettes (14-16 mg/g) studied. Relatively lower levels (SS/MS) of nicotine in SS from bidi and chutta compared with Indian/US cigarettes, suggest that the contribution of nicotine in SS from a single bidi/chutta to environmental tobacco smoke (ETS) is very much less than that of a single Indian/US cigarette. Reduced levels of nicotine in SS of bidi/chutta result in relatively higher deliveries of nicotine in MS as reflected by higher MS/SS values. The observed differences are likely to be due to difference in tobacco processing, burning rate/temperature and design of the smoking product.

Alkaloids↗

PubMed2002

Gene quantification using real-time quantitative PCR: an emerging technology hits the mainstream.

The recent flood of reports using real-time Q-PCR testifies to the transformation of this technology from an experimental tool into the scientific mainstream. Many of the applications of real-time Q-PCR include measuring mRNA expression levels, DNA copy number, transgene copy number and expression analysis, allelic discrimination, and measuring viral titers. The range of applications of real-time Q-PCR is immense and has been fueled in part by the proliferation of lower-cost instrumentation and reagents. Successful application of real-time Q-PCR is not trivial. However, this review will help guide the reader through the variables that can limit the usefulness of this technology. Careful consideration of the assay design, template preparation, and analytical methods are essential for accurate gene quantification.

Biotechnology↗